In summary, we have developed a convenient and broadlyapplicable protocol for the synthesis of functionalized azulenederivatives via the regioselective ring opening of epoxides
This line clearly explains why the study was important. The researchers were able to show that the mechanism can be applied to many types of azulene derivatives since it proceeds through familiar Sn2 mechanisms.
Stereochemical studies support an SN2-type mechanism for the transformation.
This sentence further builds on the results of the experimental research. It also contributes as a semi-conclusion as it shows this reaction goes through a familiar Sn2 process and a mechanism can be deduced and interpreted.
5. Conclusion
While nature is known to improve health, this study shows that older students and environmental students experience stronger restorative benefits, emphasizing stress recovery depends on both personal background and environmental factors. Future research should explore how different settings can be used to enhance student well-being and campus designs.
carbocycles
Carbocycles underwent borylation at the most accessible bond which is the bond with least steric hindrance. The secondary C-H bond was found to undergo borylation.
Reactions that functionalize the C–H bonds
Borylations of heterocycles occured at C-H bonds closer to the heteroatom.
The origin of the accelerating effect of the 2-mphen ligand
Although several studies were carried out, the exact reason for the high reactivity of m-phen ligand is unclear. However, it can be concluded that the change in the methyl goup leads to the higher activity of the catalyst in borylation.
C–H bond functionalization process
Borylation of primary C-H bond is irreversible leading to exclusivity in the product formed.
This intermediate also underwent halogenation
Borylation enabled placement of bromine atom at the strogest C-H bond instead of the weaker C-H bond that is typically observed.
Saturated nitrogen heterocycles
Exclusive borylation occurred at the position beta to nitrogen.
3-substituted pivaloyl tetrahydropyran
Reaction preferentially occurred at the equatorial C-H over the axial C-H bond because reaction at the equatorial C-H bond is irreversible whereas the reaction at the axial C-H bond occurs but is reversible.
less-reactive carbocycles
Less reactive carbocycles also underwent borylation because of the high reactivity of mphen.
Primary, secondary, and tertiary alcohols
Primary, secondary and tertiary alcohols were borylated at primary C-H bonds. However, this occurred after initial borylation of the hydroxyl group.
borylation processes in good yield
Alkyl arenes underwent borylation forming a single product or a mixture of products depending on the substitution pattern, ortho, meta or para.
Neither substrate underwent
No borylation takes place at the hindered geminal dimethyl groups.
more hindered tert-butyl group
Monoborylation took place at the n-butyl group and not at the more hindered t-butyl group.
These reactions occurred without direction by the existing functional groups.
Several functional groups that containied methyl groups underwent borylation at the primary C-H bonds. Once again, the specificity of the C-H bonds was proven.
Likewise, the reaction of pentylcyclohexane,
When the borylation reaction was conducted with pentylcyclohexane with only one set of primary C-H bonds, only these bonds reacted. This shows the high specificity of the catalyst [Ir(OMe)(COD)]2 and 2-mphen for the primary C-H bonds.
Thus, the reactions in the remainder of the study were conducted in cyclooctane as solvent.
When reactions were performed in solvents such as cyclohexane and cyclooctane, it was found that borylation occurred on the substrate rather than on cyclohexane or cyclooctane. Between cyclohexane and cyclooctane, cyclooctane was more inert towards borylation. Therefore, all reactions were conducted in cyclooctane as the solvent.
The use of 2-methylphenanthroline (2-mphen) as ligand
When the ligand is 2-methylphenanthroline, the catalyst is way more reactive than when coordinated by other ligands and shows selectivity for primary C-H bonds.
Here, we report iridium-catalyzed borylations of primary C–H bonds
Borylations carried out in the presence of iridium catalysts are selective for primary C-H bonds in a wide range of substrates.
Top10F′ cells displayed none of the morphological responses to circuit regulation that were evident in MC4100Z1 cells; they always looked small and cylindrical, similar to circuit-OFF cells
Both cells are strains of E. Coli, but they responded differently to circuit regulation. A healthy cell is described as "small and cylindrical". The MC4100Z1 E. Coli cells used in figure 3's experiments underwent abnormal elongation (filamentation) from their exposure to the killer protein, which may explain the escape of culture 3 from the circuit. Top10F' cells were immune to this response, and therefore did not escape regulation.
circuit-ON cultures lost regulation within ∼70 hours for MC4100Z1 and 48 hours for Top10F′ cells
Macroscale experimentation not utilizing chemostat dilutions but still containing circuit regulation maintained their populations for approximately 2-3 days, but the microchemostat was able to maintain populations for upwards of 20 days.
By shrinking the volume of the bioreactor, the authors significantly reduced the mutation rate, allowing for observation of genetically similar populations for a longer time. This allowed for precise control of engineered bacterial populations over hundreds of hours without losing regulation control, which was not possible to achieve with larger reactors.
By this time, a fraction of cells had become filamented, showing the deleterious effect of LacZα-CcdB; due to a lag in the turnover of the signal (by dilution and degradation) and that of the killer protein (by cell division and degradation), cell death intensified (Fig. 3A, point d), leading to a sharp decrease in the cell density.
The killer protein took time to be diluted and degraded, so that it continued to filament and kill the cells. This "lag" in signaling is present in many biological systems and is why oscillations occur rather than population immediately reaching a steady-state.
Culture 3 escaped circuit regulation after 186 hours
As seen in cultures 1-3, the populations with the circuit showed a cyclic increase and decrease until they reached a concentration lower than that of unregulated circuits.
All three cultures eventually escaped the population control circuit, with Culture 3 exhibiting sustained oscillations for the longest duration, up to 186 hours.
Circuit-free and circuit-OFF cultures (4, 5, and 6) grew exponentially to a steady-state density of ∼3.5 cells/pL. In contrast, circuit-ON populations (1, 2, and 3) exhibited oscillatory dynamics before reaching a lower steady-state population density after ∼125 hours
Bacterial cultures lacking or with a disabled population-control circuit quickly reached and maintained a large population, whereas those with an active circuit showed unstable population dynamics before stabilizing at a lower level. As the population increased, more growth-limiting signals were released, causing a decline in population size and signal release. Subsequently, the population increased again, repeating the cyclic behavior until reaching an equilibrium between cell growth and death from the released signals.
The steady-state cell concentrations scaled with dilution rate and nutrient richness, decreasing with increasing dilution rates or decreasing bacto-tryptone concentration
As the dilution rate (how often cells are removed from the bioreactor) increases, the bacteria concentration decreases. Likewise, when the quantity of nutrients (bacto-tryptone) provided to the bacteria are reduced, their concentration also decreases.
Histologic analyses after 1, 2, 3, and 6 months indicate a close proximity of the cuff to the nerve and provide evidence of biocompatibility and bioresorption
Even after 6 months, the cooling cuff is still in contact with the nerve and demonstrate that it is compatible with the body's tissues and can gradually dissolve over time.
bioresorbable evaporative microfluidics provides for reversible elimination of local peripheral nerve activity.
The experiments and simulations presented in this paper demonstrate that microfluidic evaporative cooling is an effective approach for reversibly and precisely cooling nervous tissue to suppress pain signals. This method's success suggests its potential for providing pain relief without the side effects associated with traditional pain medications.
Acute animal trials demonstrate the capability of evaporative microfluidic coolers to reversibly eliminate evoked nerve signals.
The cooling cuff successfully blocked nerve signals in rat sciatic nerves, and this effect was reversible once the nerve tissue returned to normal temperature. This suggests that the device could potentially function in humans too, based on this early evidence on an animal model.
Localization of the cooling effect to a predefined site without the need for insulating layers represents a key capability of the evaporative microfluidic cooling approach introduced here.
The device in this paper can selectively cool a precise area of nervous tissue without affecting the surrounding tissue, ensuring that only the targeted area receives the cooling effect. This targeted cooling allows for localized pain relief without impacting neighboring tissue, which contrasts with the broader effects of opioid medication.
The perfusion of blood through the targeted nerve presents an additional source of heat flux.
When attempting to cool nervous tissue, the effect of blood circulation should be considered, as it can counteract the cooling process by bringing heat to the cooled area.
with effective moduli not substantially higher than those of peripheral nerves [rat sciatic nerve elastic modulus is 0.6 MPa
The rat sciatic nerve elastic modulus is 0.6 MPa, while the elastic modulus of the base material of the device, POC, is 2.8 MPa. This means that the device will deform and stretch even less than that of the present neural tissue in rats.
The elastic modulus of human neural tissue has been measured at 100 Pa to 10 kPa, meaning the device is vastly sufficient for human tissue as well.
Information about the human nerve tissue elastic modulus, as well as for other tissues, can be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519935/
Without active removal, biofilms invaded the fluidic channels within ∼48 hours
The nonadhesive coatings mentioned earlier slightly reduce bacteria adhesion and biofilm formation, but channels were still invaded within approximately two days.
The author's method of periodically closing off a section of the loop, cleaning it thoroughly, and reintroducing bacterial growth medium before resuming flow was effective for long-term experiments.
Studies using three additional animals that received both the SNI and the cooling cuff show that cooling of the SNI-treated nerve from 37° to 10°C after 3 weeks of implantation leads to a sevenfold increase in the mechanical sensitivity threshold (1.6 to 11.5 g), consistent with a significant cooling-induced analgesic effect (Fig. 5F)
The researchers conducted an experiment using three rats where they studied the impact of the cooling cuff on the pain associated with the spared nerve injury (SNI). They observed that the threshold at which the animal feels pain in response to a mechanical force increased as the temperature of the SNI-treated nerve decreased. This increase indicates a notable reduction in pain sensation due to cooling, suggesting that cooling has a significant analgesic (pain-relieving) effect.
Exactly how the cells lost regulation in the circuit-ON cultures (Fig. 3, culture 3, and Fig. 4, cultures 2, 3, 5, and 6) is unclear.
This aspect presents a significant knowledge gap for this research that remains elusive. As depicted in Figure 4, only one bacterial culture maintained a low concentration upon reactivation of the population-limiting circuit. The authors state that this behavior cannot simply be explained by mutation rate.
implantation of a bioresorbable cooler around the nerve that innervates damaged tissue enables reversible elimination of neural activity and pain signals through the focused application of cooling power
The authors envision clinical applications for addressing acute pain after surgery, particularly in cases where specific nerves causing pain are known and opioid therapy is necessary. This implantable device provides targeted cooling to nerves surrounding damaged tissues, thereby offering an alternative to addictive and risky pain medications. The neural activity is temporarily blocked by cooling, and can be reversed after the treatment. The device is biodegradable, eliminating the necessity for surgical removal post-healing.
Cooling from 33° to 4°C over a period of 15 min prompts a decrease in signal amplitude of 77% and increase in latency of 97% (Fig. 5B).
The temperature drop caused a reduction in nerve bundle electrical activity and a notable delay in neural signal propagation.
e hard scientist doesis to say that he "stipulates his usage"-that is, he informs youwhat terms are essential to his argument and how he is goingto use them. Such stipulations usually occur at the beginningof the book, in the form of definitions, postulates, axioms, andso forth. Since stipulation of usage is characteristic of thesefields, it has been said that they are like games or have a"game structure."
Depending on what level a writer stipulates their usage, they may come to some drastically bad conclusions. One should watch out for these sorts of biases.
Compare with the results of accepting certain axioms within mathematics and how that changes/shifts one's framework of truth.
Atg40-3xFLAG from both lysates bound to purified, bacterially produced glutathione S-transferase (GST)–Lst1, but not to GST-Sec13, GST-Sec24 (Fig. 3A and fig. S10, A and C), or GST-Sec23 (fig. S10B).
Only GST-Lst1 purified protein is able to bind with the Atg40 but not other subunits of COP11 coat proteins.
By contrast, Lst1 acted exclusively in ER-phagy.
A conclusion summarized by the authors based on experiments that have been done to distinguish the bulk autophagy and selective autophagy that happened in various organelles, and only ER-phagy is required by Lst1 coat protein.
To draw a conclusion which exclusively functional in one particular experiment, the designs of various experiments are needed in order to rule out other possibilities.
Thus, although Atg40 was not found to be a UPR target, the UPR responded to the loss of ER-phagy.
Lst1 and atg40 mutants have higher UPR response before and after DTT treatments, indicates that defeated in ER-phagy proteins will also induce the UPR.
These findings implied that Lst1 and Atg40 function in the same pathway.
No additive effect was observed when double mutant of lst1atg40 is investigated. This finding drawn another summary which LST1 and ATG40 function in the same pathway.
By contrast, Lst1 acted exclusively in ER-phagy.
A conclusion summarized by the authors based on experiments that have been done to distinguish the bulk autophagy and selective autophagy that happened in various organelles, and only ER-phagy is required by Lst1 coat protein.
To draw a conclusion which exclusively functional in one particular experiment, the designs of various experiments are needed in order to rule out other possibilities.
we found an unexpected role for Lst1-Sec23 in ER-phagy that was independent from its function in secretion.
Lst1-Sec23 is a coat adaptor protein that carry the cargo molecules form ER to Golgi, which mainly to help the secretory proteins transportation. The author discovered new function of the Lst1/Sec23 in self-eating and protein recycling process (autophagy), in which the Lst1-Sec23 functions together with the autophagy receptor, Atg40, to localize the ER domains for autophagic degradation.
Thus, although Atg40 was not found to be a UPR target, the UPR responded to the loss of ER-phagy.
Lst1 and atg40 mutants have higher UPR response before and after DTT treatments, indicates that defeated in ER-phagy proteins will also induce the UPR.
First, when Atg40 expression was up-regulated by the TOR inhibitor rapamycin, the Lst1-Sec23 complex associated with Atg40 puncta.
In response to stress caused by starvation or misfolded aggregate-prone secretory proteins, Lst1 acted to promote an additional function—ER-phagy. Together with autophagy receptors on the ER, Lst1 targeted ER domains for degradation to avert protein aggregation, thus preserving cellular health.
Our results clearly show that the epithelial cells not only remained viable but also increased their surfactant production, enhanced their structural integrity, and restored normal barrier permeability in this biomimetic microsystem.
This is confirming that the device's epithelial layer of cells was able to survive, create surfactants, become more structurally stable, and be selectively permeable much like those epithelial cells of the alveolar-capillary interfaces found in the human lung.
only exhibited low levels of nanoparticle translocation (Fig. 4G).
Transwell culture involves growing cells on a porous membrane to mimic the physiological environment of certain tissues and organs; the study found that static Transwell systems had fewer nanoparticles moving across the cell barrier, while the lung mimicking microdevice showed a larger number of nanoparticles crossing the barrier.
we found that nanoparticle transport from the alveoli into the microvasculature was significantly increased in the presence of cyclic breathing in vivo (Fig. 4I), just as we observed in the lung mimic device in vitro (Fig. 4G).
This is showing that the in vivo mouse model dosed with nanoparticles showed a higher number of nanoparticles moving across the alveolar-capillary interface, which is similar to the results obtained from the lung mimic device.
The level was similar to that measured with a static Transwell culture system containing a rigid, porous, ECM-coated membrane lined with opposing layers of alveolar epithelium and capillary endothelium (Fig. 4G). In contrast, there was an increase by more than a factor of 4 in nanoparticle transport into the vascular compartment when our microdevice experienced physiological breathing motions (10% strain at 0.2 Hz) (Fig. 4G). This was striking given that transport of fluorescent albumin remained unchanged under similar loading conditions (fig. S1). Thus, strain-induced increases in nanoparticle absorption across the alveolar-capillary barrier are not due to physical disruption of cell-cell junctions and simple convective transport. Instead, they more likely result from altered transcellular translocation or from a change in paracellular transport that somehow selectively permits passage of these nanoparticulates while restricting movement of small molecules, such as albumin.
These results state that physiological breathing motions caused an increase in nanoparticle transport across the alveolar-capillary barrier, which was not due to physical disruption of cell-cell junctions. The mechanism behind this phenomenon may help us gain a better understanding of how these nanoparticles translocate across tissues and cause toxicity.
Indeed, this mechanical strain–induced oxidative response appeared to be specific for the silica nanoparticles and carboxylated quantum dots, because it was not induced by treatment with various other nanomaterials, including single-walled carbon nanotubes, gold nanoparticles, polystyrene nanoparticles, or polyethylene glycol–coated quantum dots (fig. S8 and table S1). On the other hand, we found that longer exposure to silica nanoparticles alone for 24 hours induced similar high levels of ROS production even in the absence of mechanical strain (fig. S7), confirming findings of past pulmonary nanotoxicology studies that analyzed the effects of ultrafine silica nanoparticles in static cell cultures (34). Taken together, these data suggest that physiological mechanical stresses due to breathing might act in synergy with nanoparticles to exert early toxic effects or accelerate nanoparticle toxicity in the lung.
The findings indicated that although introducing simulated mechanical strain had no additional toxic effect for certain nanoparticles, others (specifically, silica nanoparticles and carboxylated quantum dots) demonstrated toxicity, especially at the early stages of exposure.
However, our results extend this observation by providing evidence to suggest that breathing motions might greatly accentuate the proinflammatory activities of silica nanoparticles and contribute substantially to the development of acute lung inflammation.
This is describing that the inflammatory response due to silica nanoparticles was significantly greater when strain simulating breathing was applied, meaning that the device can simulate the effects of nanoparticles much more accurately than any stagnant cell culture ever could.
These results show that this bioinspired microdevice can effectively recapitulate the normal integrated cellular immune response to microbial infection in human lung alveoli
Here the researchers are testing whether their microdevice can simulate the alveolar-capillary interface, by triggering a proper immune response to an infection. They observed that when they exposed the alveolar side to a bacterial pathogen (E. coli), neutrophils on the capillary side migrated across the membrane to render them ineffective. A similar immune response is observed in the human body, confirming that the microdevice emulates lung physiology properly.
To provide the proof of principle for a biomimetic microsystems approach, we developed a multifunctional microdevice that reproduces key structural, functional, and mechanical properties of the human alveolar-capillary interface, which is the fundamental functional unit of the living lung.
The human lung goes through a lot of changes over time! Not only must it handle breathing in and out every minute of every day, but the lungs have to deal with all sorts of infectious pathogens. If scientists are to make human-like 3D cell cultures for drug testing, they must be able to replicate the lungs' day-to-day functions. This work is very special because it represents the culmination of years of research into making a proper artificial lung-on-a-chip. The researchers report that their device not only inhales and exhales like a normal lung, but can also fight infections with an immune response! This means that any drug testing performed on this device has a higher potential to mimic the human lung response than a standard 2D cell culture
Lst1 interacts with Atg40,
Only GST-Lst1 purified protein is able to bind with the Atg40 but not other subunits of COP11 coat proteins.
This result demonstrates that soil compaction (and the associated increase in soil moisture due to decreased porosity) affects ethylene diffusion rates, consistent with our restricted gas diffusion model.
The authors found that ethylene diffused rapidly to the bottom chamber through empty column while diffused more slowly through uncompacted soil. However, ethylene was not able to diffuse through compacted soil even after 20 days of experiment. This suggests that soil compaction indeed affects the diffusion of ethylene.
slower outward ethylene diffusion rates under compacted soil conditions (Fig. 3H and fig. S25) due to the decreased volume of air-filled pores (1) (Fig. 1, A to D, and movies S1 and S2). This will result in a higher ethylene concentration close to roots (Fig. 3, F and G) and therefore in root cells, consistent with soil compaction triggering an ethylene response
The authors' mathematical model predicted that ethylene diffusion was slower in compacted soil when compared to that in uncompacted soil, resulting in a higher concentration of ethylene around roots.
when reporter lines were grown in compacted soil, both ethylene reporters were detected in root elongation zone cells
The authors observed increased intensity of GFP signals in roots grown in compacted soil. This suggests that soil compaction triggers ethylene response.
similar to roots exposed to soil compaction
The authors found that ethylene treatment alone induced increased root width and flattened cap shape, further supporting that ethylene is a critical controller of root growth in response to soil compaction.
Soil compaction caused wild-type rice roots to double in width and their root caps to develop a “flattened” shape (compare Fig. 2, H and I). Soil compaction–induced radial growth and root cap shape changes were blocked in osein2 (Fig. 2, J, K, and O). Hence, root tip shape changes induced by soil compaction appear to be controlled primarily by ethylene and not by mechanical impedance.
The authors observed induced radial growth and root cap shape changes in wild-type but not ein2 mutant grown in compacted soil when compared to plants grown in uncompacted soil. This suggests that ethylene but not mechanical impedance plays the primary role controlling root grwoth changes.
unlike the wild type (Fig. 2B), both osein2 and oseil1 roots were able to penetrate highly compacted soil (Fig. 2, D and F; quantified in Fig. 2G)
The authors found that wild-type plants had less root growth in compacted soil when compared to uncompacted soil. However, no difference was observed between uncompacted soil and compacted soil for plants defective in ethylene response. This indicates that ethylene is required to inhibit root growth in compacted soil.
Similarly, ethylene treatment reduced root length (fig. S8A) while increasing root width
The authors found that roots grown under high levels of ethylene or in compacted soil showed similar characteristics, reduced root length and increased root width, when compared to roots grown under low levels of ethylene or uncompacted soil.
Hypoxia reporters were not induced by the gas barrier but were induced by submergence (figs. S4 to S6). We conclude that EIN3-GFP induction results from restricted ethylene diffusion rather than from hypoxic conditions (11).
The authors found that the green signal indicating hypoxia response is not enhaced in roots with gas barrier when compared to roots without gas barrier. This suggests that the enhanced ethylene response is not due to hypoxia.
restricting gas diffusion from root tip tissues triggered a rapid and sustained increase in EIN3-GFP
The authors found enhanced ethylene-responsive green signals in roots with gas barrier when compared to roots without gas barrier. This result suggests that the inhibition of gas diffusion between roots and soil induces accumulation of ethylene and activation of ethylene response.
The permeability of the alveolar-capillary barrier to fluorescent albumin remained unchanged during cyclic stretching over 4 hours with physiological levels of strain (5 to ~15%) or after preconditioning with 10% strain for varying amounts of time (fig. S1).
This is confirming that there is no leakage of albumin, a globular protein found in serum, between the alveolar lung side of the chip and the capillary side during the chip's physiological simulation of breathing.
We found a defect in the degradation of the ER protein Sec61 in lst1Δ, but not in the sec24-3A iss1Δ and iss1Δ mutants
Sec61 as ER translocon protein marker and FM4-64 as vacuolar membrane marker. From the Fig 1 A, the overlapping green and red signals in the vacuolar membrane were decreased in the mutants lst1 and atg40 compared to WT, sec24-3A iss1 mutant and iss1 mutant, which were quantified in Fig 1 B, indicated that the Lst1 and ATG40 are required for degradation of ER in the vacuole .
Last, to define the relationship between the channel activity of RECS1 and the regulation of cell death induced under lysosomal stress, we generated a doxycycline-inducible MEF cell line expressing a single-point mutant version of RECS1 (Fig. 7H). When compared to WT RECS1, the overexpression of the D295Q mutant diminished cell death, behaving similarly to the mock conditions (Fig. 7H)
As opposed to normal RECS1, a high dose of non-functional RECS1 (D295Q) has no effect on cell viability/cell death, suggesting that the function of RECS1 as ion channel is linked to its role in cell death regulation
Mutation of the key Asp295 from the putative di-aspartyl sensor significantly reduced RECS1 opening probability at pH 7, while it only slightly affected the ability to respond to pH changes (Fig. 7D).
Asp295 is required as a pH sensor, because when cells with non-functional Asp295 are used, the probability of finding the channel in open state is significantly reduced at pH 7.
Lowering the pH to 6.5 caused a marked decrease in the number of current spikes in both channels (Fig. 7C), consistent with the hypothesis of RECS1 as a pH-regulated channel. Quantification of the total open probability (NPo) in addition to the probability for each independent opening state (NPo Ox) showed that the channel activity of RECS1 is heavily dependent on pH (Fig. 7D).
Lower amount of electricity is conducted at lower pH, suggesting that the ion channel function is regulated by pH.
interaction between Arg158 with the Asp268-Asp295 di-aspartyl sensor in the closed conformation (Fig. 7B, green)
The interaction of Arg158 with the Asp268-Asp295 maintains a closed state, leading to regulation of ion movements
BAX has been shown to translocate to lysosomes where it is suggested to trigger LMP and cell death under different pathophysiological conditions, including Parkinson’s disease, oxidative stress, and autophagic cell death (35–37). To assess BAX translocation to the lysosomal membrane and its colocalization with RECS1, we detected active BAX using the 6A7 conformational antibody. Analysis of RECS1 (using the Flag antibody) and the distribution of the lysosomal protein LAMP-2 in MEFs indicated that under basal conditions (no RECS1), BAX remained mainly cytosolic (fig. S4H). However, BAX colocalized with RECS1 in LAMP-2–positive vesicles following RECS1 induction (Fig. 3, E to G). After CQ treatment, BAX was redistributed into large LAMP-2–positive vesicles, an effect that was dependent on RECS1 expression (Fig. 3E). Active BAX was present preferentially in Flag-RECS1–positive lysosomes in cells treated with CQ (Fig. 3, F and G). Together, these results suggest that RECS1 induces cell death through LMP in response to lysosomal stress, correlating with the translocation of BAX to lysosomes
Overexpression of RECS1 in CQ-stressed cells causes LMP and translocation of BAX to the lysosome, which induces cell death. BAX is a proapoptotic protein.
An adviser should have their students explicitly practice decisions 25 and 26, test their solutions, and try to come up with the ways their decisions could fail, including alternative conclusions that are not the findings that they were hoping for. Thinking of such failure modes is something that even many experienced physicists are not very good at, but our research has shown that it can be readily learned with practice.
To help fight cognitive bias, one should actively think about potential failure modes of one's decisions and think about alternative conclusions which aren't part of the findings one might have hoped for. Watching out for these can dramatically help increase solution spaces and be on the watch out for innovative alternate or even better solutions.
Thus, our research contributes to aburgeoning literature on cross-group friendships by showingthat the positive effects of friendship can extend beyond inter-group attitudes per se to institutional attitudes, and by directlytesting causal links from cross-race friendships to positiveintergroup outcomes (cf. Pettigrew, 1998).
To the extent that a friend’s perceivedmembership in the university in-group is salient, cross-groupfriendship may increase the likelihood that minority-groupstudents will eventually incorporate a university identity as partof themselves.
Therefore, friendships with majority-group peers may be key in the development of dual identityamong minority-group students, and may provide a route towardrelational diversity within institutions of higher education.
Our research underscoresthe importance of the interpersonal climate for addressing issuesof access and diversity within such institutions, and shows thatthe development of affiliative ties across group boundariesprovides an important vehicle for achieving relational diversity.
Together, thefindings of these studies suggest that efforts to increase cross-group friendship are not incompatible with institutional effortsto clearly communicate acceptance of the minority group bysupporting organizations or activities centered on the ethnic orracial background of that group.
These findings provide experimental evidence that cross-group friendship is beneficial forpeople who are likely to experience anxiety in intergroup contexts.
Since facts and narratives live in different universes, we should avoid mixing them carelessly. Crossing the boundary between the two universes should always be explicit. A narrative should not include copies of pieces of facts, but references to locations in a fact universe. And facts should not refer to narratives at all.
C, Fortran, BLAS, and Unix
This polemic identifies CS as the culprit. That seems empirically wrong. As stated, it's "not a prerequisite for most programming" even in theory, and in practice, there are mountains of GitHub programmers, at least, who don't have CS backgrounds. Non-CS folks probably account for most of the "frontend"/"full stack" development today. This has exacerbated the Tower of Babel, not improved it.
HCI is CS—and that's what we should focus on. There's a fair bit of emphasis on engineering due, too. To be able to look at a problem and ask, "What should it take?" and ocnversely, "What isn't required here (contra cultural imperatives)?"
The PDMS ring and the free-standing membrane together formed an air gap structure that allowed the free-standing membrane to deform easily under an external force. The resulting devices are flexible and can have different sizes and geometries for different prosthetic applications
The authors determined the optimal PDMS thickness that would allow a sufficient air gap between the membrane and the sensor coil. In this case, the membrane could easily deform and its deflection was measured when an external force was applied.
not only perceived ultralow pressure but also had the ability to grasp heavy objects.
After the authors tested the ultralow pressure sensing ability of the sensor, they found that not only could the sensor detect ultralow pressures but that it could also detect pressures over 20 kPa. The means that sensor could also detect heavy objects as well as subtle sensations like wind blowing.
Therefore, a subtle force can be detected by the tactile sensor with high magnetic field sensitivity and a near-linear response to magnetic field.
The authors determined that a frequency of 250 kHz produced the largest percent change (500%) in magneto-impedance, thereby yielding the highest sensitivity. This meant that a small force could be detected by the sensor with a high magnetic field sensitivity.
Therefore, a minimum loading of 1.25 Pa (the contact area is about 4 × 10−5 m2 or 50 μN), beyond the sensing threshold value of humans (1 mN) (1), can be encoded as digital-frequency signals.
This result is valuable, because it proves the author's tactile sensor can detect pressure load smaller than the sensing threshold of a human. The tactile sensor is able to encode a digital-frequency signal of 0.7-Hz pulse waveform when a loading of 1.25 Pa (approximately 50 μN) was placed on the tactile sensor. This loading is much smaller than the sensing threshold value of humans, which is approximately 1 mN.
Therefore, a higher PDMS ring was required for the same sensitivity when the polymer magnet had a larger magnetization.
The authors conducted an experiment to optimize their tactile sensor. They found that a PDMS ring height of 1.3 mm allows the sensor to work in the most sensitive range.
The minimum loading of 50 micronewtons (or 1.25 pascals), which is less than the sensing threshold value of human skin, was also encoded into the frequency, similar to the pulse waveform of humans.
It takes less force to activate stimuli for the sensor than it would for human skin. This means the tactile sensor is more sensitive than human skin, which makes it an efficient replacement for those who suffer from limb loss.
The polymer magnet with a magnetization of 0.3 electromagnetic unit (emu) and the PDMS ring with a height of about 1.3 mm were chosen so that the tactile sensor would work at the most sensitive range.
The polymer magnet with a magnetization of 0.3 emu and PDMS ring height of 1.3 mm yields a sensor that works at the most sensitive range. This means that this device has been optimized for further testing and application.
(ii) after stepping on the robot with an adult human’s full body weight (59.5 kg, about 1 million times heavier than the robot), the robot could still move afterward, demonstrating exceptional robustness;
The authors prove the soft robot's robustness by highlighting its ability to remain functional after withstanding a significant weight. This achievement can be attributed to the prototype's deformable body.
The relatively fast locomotion and robustness are attributed to the curved unimorph piezoelectric structure with large amplitude vibration, which advances beyond other methods.
The authors determined that the rapid locomotion and robustness of the soft robot are due to the unique structure and materials used to construct it along with the large deformation that the robot undergoes upon actuation.
We found that the values of λ/L and β/π near 0.1 and 0.4, respectively, resulted in robots with the fastest running speeds.
The authors performed 25 tests to determine what combination of relative leg position and angle would offer the fastest running speeds of the soft robot. Given Fig. 3B, a position at 0.1 and angle of 0.4 was determined to result in the fastest speed.
(i) Under an alternating current (AC) driving power near the resonant frequency (850 Hz) of the structure, a prototype 10-mm-long robot (0.024 g) attained a relative speed of 20 BL/s
Here, the authors designed an insect-scale soft ground robot based on piezoelectric actuation that achieved the fastest speed (20 body lengths per second) reported up to date.
The climate change induced by anthropogenic release of CO2 is likely to be the most fascinating global geophysical experiment that man will ever conduct.
Climate simulations even today are subject to a high degree of uncertainty in the range of ecological and geological impacts. While warming is already ongoing and certain to continue for some time, there are likely to be several indirect effects which are difficult to predict before they begin.
A 2°C global warming is exceeded in the 21st century in all the CO2 scenarios we considered, except no growth and coal phaseout.
The estimate of greater than 2°C of warming by the end of the 21st century is consistent with current expectations.
We conclude that CO2 warming should rise above the noise level of natural climate variability in this century.
At the time of this paper's publication, there was too much year-to-year variability in temperature measurements to be certain that greenhouse effect warming was already occurring. The model predicts that the overall trend of increased temperatures would be clearer within the decade.
The observed warming since then has risen much further above the noise, and it is now clear that the earth is getting hotter due to the influence of greenhouse gases.
Thus CO2 growth as large as in the slow-growth scenario would overwhelm the effect of likely solar variability. The same is true of other radiative perturbations; for instance, volcanic aerosols may slow the rise in temperature, but even an optical thickness of 0.1 maintained for 120 years would reduce the warming by less than 1.0°C.
Carbon dioxide has such a great warming potential that increasing its concentration in the atmosphere will result in higher temperatures even if solar output and volcanic eruptions contribute substantially to cooling.
The general agreement between modeled and observed temperature trends strongly suggests that CO2 and volcanic aerosols are responsible for much of the global temperature variation in the past century.
A model that includes only carbon dioxide and volcanic aerosols as inputs produces predictions that agree well with observation. This indicates that these two factors are the primary drivers of the observed climate variation.
However, mixing of heat into the deeper ocean with k = 1 cm2 sec-1 brings both calculated trends into rough agreement with observations.
The ocean's ability to spread heat into deeper layers has a large impact on the greenhouse effect. By varying this mixing rate and observing how well the model agrees with real observations, the authors find an optimal value to use for further testing.
Surface warming of - 3°C for doubled CO2 is the status after energy balance has been restored.
The authors' atmospheric model is able to produce estimates of temperature change due to the greenhouse effect, which appear to be reliable for a period of several years after a major perturbation.
This large reduction of the climate response occurs for a perturbation that (unlike CO2) is present for a time shorter than the thermal response time of the ocean surface.
If the ocean were not able to buffer sudden impacts of atmospheric changes on the climate, volcanic eruptions would cause intense global cooling in the short term.
The time history of the warming obviously does not follow the course of the CO2 increase (Fig. 1), indicating that other factors must affect global mean temperature.
While the overall warming of the observed period is consistent with predictions, the year-to-year variability cannot be explained by carbon dioxide concentration alone.
A remarkable conclusion from Fig. 3 is that the global temperature is almost as high today as it was in 1940.
At the time of this paper's publication, many mistakenly believed that the earth's climate was cooling. This reconstruction of the global temperature record shows that, while the Northern Hemisphere cooled between 1940 and 1970, this trend did not persist at larger scales. Indeed, by 1981, this localized cooling had been almost entirely reversed.
We conclude that study of global climate change on time scales of decades and centuries must consider variability of stratospheric aerosols and solar luminosity, in addition to CO2 and trace gases.
This model predicts that the atmosphere will warm due to increasing carbon dioxide, but the change in surface temperature also depends strongly on the presence of other gases, suspended particles in air, and variations in solar light output. These factors must also be considered to ensure the accuracy of any predictions.
The full impact of the warming may be delayed several decades, but since man-made increases in atmospheric CO2 are expected to persist for centuries (1, 2, 6), the warming will eventually occur.
The predictions of global warming by this model are subject to uncertainty relating to the heat capacity of the ocean. However, even the lower estimate indicates substantial increases in surface temperature over the following decades.
Diffusion into the thermocline further reduces the warming to 0.25°C for k = 1 cm2 sec-1, an indirect effect of the mixed layer's 6-year e-folding time, which permits substantial exchange with the thermocline.
The ocean can only diffuse heat to deeper levels at a finite rate. If the ocean is able to vertically mix at a faster rate, more of the heat in the atmosphere can be absorbed into water rather than contribute to the surface temperature. This reduces the contribution of greenhouse gas concentration to warming in the short term.
The e-folding time for adjustment of mixed-layer temperature is therefore ~6 years for our best estimate of model sensitivity to doubled CO2.
Using the best model from the earlier comparisons (Model 4), the authors find that the climate reaches equilibrium in response to doubling carbon dioxide in about six years. This is an indicator of the time it takes for changes in greenhouse gas concentrations to have their full effect on global climate.
The sensitivity of surface temperature in 1-D RC models to changes in CO2 is similar to the sensitivity of mean surface temperature in global three-dimensional models (6-8).
Because the authors have developed a model which is simpler than other atmospheric simulations, its reliability must be verified. If it agrees with more complex models, this is a good sign that it captures the important factors.
We observed that a large percentage of aerial duty cycles were required to generate fast running speeds for the robot.
The authors used a high-speed camera to characterize the duty cycles of the soft robot. They concluded that the soft robot achieves the fastest speed when it spends most of its time in the air (maximizing the aerial duty cycle).
We plotted the results in Fig. 2F (shaded columns) for the trial with the fastest speed at 8.7 cm/s at 200 Hz (see fig. S6 for other frequencies with slower speeds).
The soft robot achieved its fastest speed of 8.7 cm/s when actuated at 200 Hz.
In general, robots with smaller lengths have higher resonant frequencies and faster relative speeds. The relationships between driving frequency and relative speed for robots with lengths of 10, 15, 20, 25, and 30 mm are shown in Fig. 3C driven by a peak-to-peak voltage of 200 V to achieve measured maximum speeds of 20 BL/s (20 cm/s), 8 BL/s (12 cm/s), 4.05 BL/s (8.1 cm/s), 2.4 BL/s (6 cm/s), and 1.33 BL/s (4 cm/s), respectively
The author concluded from the experimental data that there is a direct relationship between driving frequency, body length, and speed. Shorter bodies and greater frequency yields faster speeds while longer bodies and lesser frequency yields slower speeds.
We observed that if the applied load is below 100 g, then the robot can recover back to the original shape and maintain greater than 88% of its original speed. As the applied load increased, the moving speed decreased.
Here, the authors quantify the robustness of their device. The use of PVDF, PET, and silicon allows for the soft robot to maintain its shape. However, excess weight is shown to damage the structure of the device, resulting in decreased speed.
(iv) further enhancement of agility was demonstrated by designing the moving mechanism to emulate features of galloping-like gaits using a two-leg prototype robot.
The authors continue to demonstrate the soft robot's agility by applying a realistic insect movement pattern.
The reported tactile sensor exhibited a very high sensitivity of 4.4 kPa−1 and an ultralow detection limit of 0.3 Pa
The authors' found this information after their impedance and applied pressure experiment and ant experiment respectively. This showed the very high sensitivity of the sensor at an ultralow pressure range.
The tactile sensor could distinguish a weight of 10 μN. By taking the contact area as about equal to 4 × 10−5 m2, we calculated the corresponding pressure detection limit to be equal to 0.3 Pa.
After the authors' water drop experiment, they found that the impedance increased with increasing volumes of water. Therefore, the device was able to "sense" the weight of the different volumes of water. They found that the device's detection limit was 0.3 Pa.
The actions of the ant could be sensed. Figure 3C shows the moving trail of the ant, and Fig. 3D demonstrates the change of impedance of the tactile sensor with the moving ant. The impedance of the tactile sensor is about 38.57 ohms.
After the authors' ant experiment, they found that the sensor was able to detect the ant's movements across the sensor. This confirms the device's ability to detect changing tactile information.
(iii) the robot could move smoothly carrying a load weighing 0.406 g, which is six times heavier than that of the robot;
Despite bearing six times its weight, the prototype is able to maintain locomotion control, demonstrating its agility.
recovery of the ozone layer since the Montreal Protocol.
The Montreal Protocol was established to heal the hole in the ozone layer by phasing out the release of ozone-depleting substances. This paper concludes that the hole in the Antarctic ozone layer is starting to heal as a result of the reduction in ozone-depleting substances.
Our results underscore the combined value of balloon and satellite ozone data, volcanic aerosol measurements, and chemistry-climate models
This paper shows that in order to draw a conclusion about the healing of the Antarctic ozone hole, the following is required:
Gathering data on the amount of atmospheric ozone over time using balloons and satellites.
Since aerosols released by volcanic eruptions can deplete ozone, volcanic aerosols must be measured.
Ozone-depletion models which account for climate and chemistry must be used to interpret ozone-abundance data.
Further, the conclusion that the volcanic aerosols were the dominant cause of the record size of the October 2015 ozone hole
Since the ozone-depleting substances released by humans were not increasing, it was important to understand why the Antarctic ozone hole was so large in the year 2015.
The paper concludes that the unusually large hole was due to a volcanic eruption in Calbuco, Chile.
The sulfur-based aerosols released from volcanoes can also deplete the ozone layer, so they must be accounted for when tracking the hole over time.
ozone holes in 2011 and 2015 are estimated to have been, respectively, about 1.0 million and 4.4 million km2 larger because of volcanic eruptions (especially Puyehue-Cordón Caulle in 2011 and Calbuco in 2015) than they would otherwise have been, substantially offsetting the chemical healing in those years.
If the effects of the volcanic eruptions in 2011 and 2015 are removed, the chemically induced Antarctic ozone hole shows signs of healing.
Because the model reproduces much of the observed year-to-year variability in September total ozone from both the South Pole station and SBUV observations, confidence is increased that there is a significant chemical contribution to the trends
The model is accurately simulating the ozone trends, and it shows that the decline in ozone-depleting chemicals is driving the healing.
along with strong chemical recovery, make September the month when the Antarctic ozone layer has undergone the largest amount of healing since 2000
While October is the month when the Antarctic ozone hole was originally discovered, the smaller variations from non-chemical factors make it easier to observe healing in September.
These results indicate that Dmrt1functions downstream of Kdm6b to initiate the male pathway in T. scripta.
The authors demonstrate that Dmrt1 expression relies on Kdm6b function in male gonad development, and that Kdm6b targets Dmrt1 to activate male gonad development at MPT.
These data provide functional evidence that disruption of Kdm6b leads to female development at 26°C, indicating that high transcript levels of Kdm6b are critical to activate the male pathway in this temperature-dependent sex determination system.
The knock-down of Kdm6b caused female gonad development at MPT, which shows that Kdm6b is required for proper temperature-dependent male gonad development.
These expression profiles suggest that Kdm6b is an early responder to temperature or hormone treatments
The specific abundance of Kdm6b expression in developing gonads at MPT, FPT-to-MPT temperatures, and hormone treatment show that KDM6B likely functions in temperature-dependent sex determination.
implying that KDM6B functions in somatic cells to regulate the sexual development of T. scripta
The authors only detected KDM6B in the developing cells in the gonads at MPT, so they conclude that KDM6B may function in sex development.
The gene is not inherently responsive to temperature, as its male-specific expression was initiated at stage 13 in the gonad-mesonephros complexes but not in other embryonic tissues
The authors want to know how Kdm6b expression changes based on temperature specifically in the gonads instead of all developing tissues.
Although these findings suggest a reptile-wide role of Kdm6b in regulating temperature-dependent sex determination, they also suggest that both evolutionary recruitment to the pathway and the molecular mechanism of action differ across species.
It is important to note that the Kdm6b pathway is likely used by many reptiles to regulate temperature-dependent sex determination, but that the way each species has evolved to use it might be different.
These results strongly implicate KDM6B as the upstream regulator of the male pathway
KDM6B is required for Dmrt1 activation and specifically associates with the promoter of Dmrt1.
This shows that KDM6B orchestrates male sex development early in gonadal cells by directly removing H3K27me3 at the Dmrt1 promoter to activate Dmrt1 expression.
After ablation, we observed a 95% reduction in time spent exploring the open arm of the EPM and a 57% increase in duration of the immobility time in the FST
These findings validate the effectiveness of TH-IR ablation by 6-OHDA, as a decrease in time spent in the open arm of the EPM is associated with increased anxiety, and an increase in immobility time in the FST is associated with a depressed state. These results are not surprising as it is expected that a halt in the synthesis of dopamine (the feel-good transmitter) would increase anxiety and depression.
Long-day exposure produced the opposite effects
For rats, nocturnal mammals, increased photoperiod exposure is a stressor. Consequently, in both the EPM and FST, rats exhibit more depressive/anxious behaviors following long photoperiod exposure. In the EPM test, these rats spend less time in the open arm, and in the FST, they give up swimming and become almost immobile much sooner than the control group. For the short-day exposure group, the rats have more open arm activity, and in the FST persevere for longer, indicating reduced anxiety relative to the control group.
Assays of CRF in the CSF and corticosterone in the plasma confirmed this to be the case (Fig. 4D).
Panel D of Figure 4 shows that CSF levels of CRF and plasma levels of corticosterone significantly decrease following short photoperiod exposure. In panel B, short photoperiod exposure results in elevated coexpression of D2R and SST2/4R. These findings support the hypothesis that increased coexpression of D2R and SST2/4R has inhibitory effects on CRF neurons of the third ventricle.
These results demonstrate that transmitter respecification is not achieved by translation from preexisting transcripts and involves de novo induction of TH or SST mRNA
The experimenters' measurements of mRNA expression are used to determine whether transmitter respecification is resulting from new transcription or preexisting transcription. If transmitter respecification is resulting from preexisting transcripts, TH and SST mRNA would already be present in the cytosol and only following exposure to a certain photoperiod condition, translational machinery would translate that existing mRNA. Thus, if the source is preexisting mRNA, then we should not observe TH and SST mRNA counts follow numbers of TH and SST neurons, and instead mRNA levels should be unchanged. The fact that the experimenters are observing that mRNA levels follow TH and SST neuron count demonstrates that the photoperiod exposure condition is inducing de novo transcription, rather than direct translation of preexisting transcripts.
Newly expressing TH-IR neurons induced through short-day photoperiod exposure coexpressed additional dopaminergic markers (3), VMAT2 (fig. S6), and the dopamine transporter, DAT (fig. S7).
Because one role of VMAT2 is to package dopamine from the cytosol into synaptic vesicles for their release from the neuron, VMAT2 serves as a marker for the presence of dopamine. In addition to VMAT2 expression, the expression of the dopamine transporter, DAT, was also observed. Altogether, these findings serve as evidence that the newly expressed TH-IR neurons, induced by short-day photoperiod exposure, are indeed synthesizing dopamine.
The number of intracellular SST-IR storage vesicles depended on photoperiod light-cycle duration
Panel D is consistent with the findings in Panel B and Panel C, which also demonstrate an increase in SST expression following increase day exposure.
The 43% increase and 96% decrease in TH-IR/SST-IR coexpression after short- and long-day exposure, in contrast to the balanced photoperiod, suggest that TH-IR and SST-IR neurons are recruited from a reserve pool of cells (23) that are switching transmitters
In response to the photoperiod exposure condition, the circuit activity changes such that the neurons of the reserve pool are switching transmitters. The researchers believe that the TH-IR and SST-IR neurons are coming from this reserve pool of cells based on their finding that short-day exposure led to an increase in the recruitment of TH-IR neurons and diminishment of SST-IR neurons, while long-day exposure had the opposite effect.
Double immunofluorescence revealed that different photoperiods changed the balance of dopamine and SST coexpression in neurons in the PaVN and PeVN
The experimenters performed immunostaining for both dopamine and SST expression. Panel B depicts immunofluorescence of these transmitters in the PaVN. The first of the three images depicts the results from long day exposure; under this condition, there is an abundance of red representing an increase of SST expression and very little green indicating that there is a decrease in dopamine expression. Under short day exposure (third image), the opposite is true.
TH expression did not differ from controls exposed to the 12L:12D photoperiod for 2 weeks
Finding that the TH-IR neuron counts are reversible upon application of opposite photoperiod treatment is further evidence that sensory stimuli can induce neuroplastic changes in the already mature brain.
No significant BrdU labeling was detected in the LPO, PaVN, or PeVN
BrdU labeling did not result in significant amounts of active poliferating cells; this is an initial indication that inverse SST and dopamine expression is not due to neurogenesis.
Week-long exposure to each of the different photoperiods failed to produce changes in numbers of TH-IR neurons in an adjacent nucleus, A13 (Fig. 1E and fig. S2B), which does not receive retinal input via the SCN
In order for the dopamine alterations to be induced by changes in light exposure duration, the dopaminergic neurons must be able to receive retinal input, as is the case with the dopaminergic neurons in the hypothalmic nuclei, innervated by the retino-hypothalmic projection. If the neurotransmitter respecificaiton is indeed due to the photoperiod treatment, dopamine production at an adjacent dopamine source, which does not receive retinal input via the SCN, should be unaffected.
Circadian fluctuations do not account for changes produced by different photoperiods.
Within the three photoperiods, 19L:5D, 5L:19D, and 12L:12D, the number of TH-IR neurons are similar. Because there is a consensus within each photoperiod, this is indicating that circadian fluctuations are not contributing to neurotransmitter respecificaiton.
FFN511 generated fluorescent signals in hypothalamic slices from brains of animals exposed to each of the three photoperiods. Fluorescence decreased upon KCl depolarization
In panel C, before KCl depolarization, there is observable fluorescent signals from FFN511, indicating dopamine uptake. Upon KCl depolarization, the fluorescence is diminished; this is indicative of dopamine release. The results of panel C are consistent with panel A and B in that during the long day light condition (19 hours light, 5 hours darkness), the fluorescence signal is the lowest, which means less dopamine being taken up.
Dopamine is colocalized with TH in the PaVN after exposure to each of the photoperiods. n = 5 animals for each photoperiod.
Panel B: The fact that in all three photoperiod conditions, dopamine is colocalized with TH validates the use of TH as a marker of dopamine synthesis.
Natural stimulation of other sensory modalities may cause changes in transmitter expression that regulate different behaviors.
The researchers found that neurotransmitters are not actually fixed upon maturation, but are, in actuality, dynamic and can be affected by sensory stimuli such as longer or shorter photoperiods. Changes in transmitter expression result in behavioral changes as well. Thus, follow up research can explore what other sensory stimuli can change transmitter expression and also examine the corresponding behaviors that are regulated by those transmitters.
Induction of newly dopaminergic neurons through exposure to the short-day photoperiod rescued the behavioral consequences of lesions.
Shortening the length of daylight the rats are exposed to induced the formation of new dopaminergic neurons and thereby restored the rats' previous (normal) behaviors, i.e., the rats no longer displayed anxious and depressed behaviors.
Pharmacological blockade or ablation of these dopaminergic neurons led to anxious and depressed behavior, phenocopying performance after exposure to the long-day photoperiod
Using drugs to prevent dopamine production resulted in anxious and depressed behaviors by the rats; these same behaviors were also observed following extended day length exposure.
Changes in postsynaptic dopamine receptor expression matched changes in presynaptic dopamine, whereas somatostatin receptor expression remained constant.
When more of the neurotransmitter dopamine is produced, there is also an increase in the postsynaptic dopamine receptor. Likewise, when less dopamine is produced, it follows that there is a decreased expression of dopamine receptors. However, for somatostatin, this was not the case. Regardless of whether somatostatin production is increased or decreased, the somatostatin receptor expression is unchanged.
We found that specialization, modularity, nestedness, and the simulated robustness in all scenarios to species loss of the O‘ahu networks overlapped with the range of values observed in other networks.
The results from the simulated extinction, along with the measurement of network interaction patterns (modularity, nestedness, and specialization), were all similar between O'hau and other tropical or non-tropical locations.
Thus, plant-animal networks appear to have distinct links (high interaction rewiring) even when the same species are present in both sites, irrespective of whether networks are dominated by native or introduced species
The authors conclude that plants and animals at different sites across the island develop their own unique pattern of interactions, whether the sites are populated by mostly native or novel species.
Surprisingly, only 53% of the interaction dissimilarity was due to differences in species composition among sites (βST = 0.30 ± 0.09), whereas 47% was because pairs of species that interacted in one site did not interact in another site where they co-occurred (βOS = 0.27 ± 0.07; fig. S4
Referring to figure 3, the majority of dissimilarity across sites was due to linkage turnover, represented as the gray bars. This means that even though the sites shared similar species, the interactions were different.
[interaction dissimilarity (βWN) = 0.57 ± 0.11, mean ± SE; n = 21 pairwise sites; Fig. 3 and table S5], indicating that, on average, only 43% of interactions were shared between sites despite the most common bird and plant species occurring at all sites (tables S2 and S3)
The authors found that the majority of the sites in O'ahu had different sets of interactions between plant and bird species.
Here we show that the interaction patterns recurrently identified in native-dominated networks also emerge in novel mutualistic networks composed of species with little or no shared evolutionary history. This result indicates that prolonged shared evolutionary history is not necessary for the emergence of complex network structure
The authors concluded that introduced species do not necessarily have to be evolutionarily related to native species to form similar interaction networks. This conclusion was based on their results demonstrating that introduced species on the island successfully formed modular networks comparable to the networks that were formed between native species.
Furthermore, partner sharing (how distinct species share resources) in SDNs on Oʻahu is structured in a complementary way among bird and plant species, giving rise to distinct modules in which certain birds and plants interact preferentially. The emergence of such structures indicates that these novel SDNs largely reproduce the well-known patterns exhibited in mutualistic networks (18) and that SDN structure is highly conserved, regardless of variation in plant and bird communities.
The introduced birds and plants integrate successfully into the ecosystem of O'ahu because they follow the same strategies used by the native plants and birds: creating beneficial relationships with specific species and carefully sharing the resources of the island with other organisms.
We found that despite all interactions being novel and primarily involving introduced species, networks were structurally complex and notably similar between scales (local versus regional) and across sites.
The authors concluded that overall, the complex network structures of the island's ecosystem on both the local and regional scale remained the same, even though these networks were now infiltrated with invading plant and animal species.
At the local scale, networks had low to intermediate connectance and, unlike the regional network, were not nested. Similar to the regional network, six of seven local networks were specialized and modular, presenting three or four modules (Fig. 2, fig. S3, and table S4)
At individual sites, the authors again saw species mostly interact with only a subset of the total partners available.
Thus, although introduced birds are critical for seed dispersal in the ecosystem, they are primarily dispersing introduced plants (only 6.7% of interactions involved native plants).
The authors concluded that the majority of plants and animals involved in the seed dispersal networks of O'ahu are introduced species, and that the majority of seeds being dispersed by these birds are from introduced plant species.
Oʻahu’s SDN included 15 bird and 44 plant species connected by 112 distinct links (Fig. 1)
The authors identified 44 different plant species and 15 different birds in O'ahu. Figure 1 depicts each bird (left column) and each plant (right column) as rectangles. The lines connecting a bird to a plant represent a seed dispersal event.
Cities that implemented a Level 1 response (any combination of control measures) (figs. S2 and S4) pre-emptively, before discovering any COVID-19 cases, reported 33.3% (95%CI: 11.1-44.4%) fewer laboratory-confirmed cases
The result shows that early intervention can decelerate the spread of COVID-19.
To calculate the percentage used here, the authors first calculated the difference in the average numbers of laboratory-confirmed cases for two groups of cities. The difference was then divided by the number of cases for cities that introduced controls later.
The dispersal of COVID-19 from Wuhan was rapid
By referring to the cumulative number of cities that reported COVID-19 cases and comparing the spreading trend to that of the H1N1 pandemic, the authors concluded that the spread of COVID-19 was rapid.
Conclusions
when finishing a paper make sure to add transition phrases such as " finally" , " so", " in conclusion".
Indeed, when the same reactants were subjected to rhodium catalysis [1 mol % Rh2(OAc)4], O–H and N–H insertions were the predominant reaction pathways, and copper catalysis [10 mol % Cu(OTf)2] gave complex mixtures of products (table S7).
Reactions catalyzed by Rma cyt c have distinct advantages such as high chemoselectivity and enantiospecificity over reactions catalyzed by organometallic catalysts.
free alcohols and primary amines
Free alcohols and primary amines are reactive functional groups that do not interfere with this enzymatic carbene-transfer reaction.
chemoselectivity
Rma cyt c exhibits preference for carbon-silicon bond formation over other competing side reactions.
We thus chose Rmacyt c as the platform for evolving a carbon–silicon bond-forming enzyme.
The wild-type protein chosen must exhibit some degree of activity for the desired reaction. When compared to hemin, hemin with bovine serum, a range of cytochrome P450 and myoglobin variants, it was found that Rma cyt c showed 97% ee. This was chosen as the enzyme that would form the starting point for directed evolution.
We found that populations of interneurons in the adult rat hypothalamus switched between dopamine and somatostatin expression in response to exposure to short- and long-day photoperiods.
Altering the amount of time that a rat is exposed to light in a day leads to changes in the type of neurotransmitters being expressed by a set interneurons located in the hypothalamus. When the rat's daily light exposure is restricted to a shorter time frame, those interneurons favor dopamine expression. In contrast, longer daily periods of light exposure results in those same interneurons favoring somatostatin expression.
introduced plants accounted for 93.3% of dispersal events
Of all seeds found on bird poops, 93% are of introduced plant species
In summary, this analysis shows that
The authors summarized all major findings in this paragraph.
But together and interactively, these control measures offer an explanation of why the rise in incidence was halted and reversed
The simulated result agrees with the actual data, revealing that simultaneously taking both measures may be the reason for the reduction in the total case number.
Thus, neither of these interventions would, on their own, have reversed the rise in incidence by 19 February
The simulated patterns of transmission with single or no intervention taken are different from the actual scenario shown in Fig. 4A. The discrepancy means that neither of these interventions could overturn the spreading and growth of COVID-19 in China when implemented individually.
the case reproduction number declined to 0.97, 2.01 and 3.05 (estimated as C1R0) in three groups of provinces, depending on the rate of implementation in each group (Table 3 and table S4). Once the implementation of interventions was 95% complete everywhere (stage 2), the case reproduction number had fallen to 0.04 on average (C2R0)
The significant reductions in the case reproduction number due to the regional (stage 1) and massive (stage 2) implementation of transmission control measures point to the importance of intervention in stopping the epidemic.
suggest that transmission control measures were not only associated with a delay in the growth of the epidemic, but also with a marked reduction in the number of cases
The transmission control measures were also found effective in reducing the total number of cases.
Reaching the peak of the number of confirmed cases means that an epidemic stops growing and turns to an end. Thus, reaching the peak sooner is desired in this case.
cities that suspended intra-city public transport and/or closed entertainment venues and banned public gatherings, and did so sooner, had fewer cases during the first week of their outbreaks
The coefficients in Table 2 are statistically significant. This means that each coefficient is significantly different from the value under the null hypothesis of no correlation, indicated by the probability for the null hypothesis to be true, P, smaller than 0.01.
These results indicate correlations between the factors shown in the table and the number of laboratory-confirmed cases.
see also figs. S2 and S4
The authors summarized measures taken by different cities and the timing of responses.
The differences in the types of measures and the timings of their implementations offer directions for the correlational studies present in the later sections of this paper.
a delayed arrival time of COVID-19 in other cities by an estimated 2.91 days (95%CI: 2.54 to 3.29 days)
The Wuhan lockdown was found to effectively delay the spread of COVID-19 to other cities in China.
COVID-19 arrived sooner in those cities that had larger populations and had more travellers from Wuhan
Based on the statistically significant correlation shown in Figure 2C, the authors concluded that the outflow of people from Wuhan before the shutdown is positively associated with the spread of COVID-19.
This finding lays a foundation for the later examination of the effectiveness of the Wuhan shutdown in slowing the dispersal of COVID-19.
In 2020, the travel ban prevented almost all of that movement and markedly reduced the number of exportations of COVID-19 from Wuhan
A sharp drop in the number of movements from Wuhan confirmed the effectiveness of the travel ban.
During the following centuries, introduction of MeV into naive human populations and/or flare-ups of the disease might have caused some ancient epidemics whose etiology remains uncertain.
Because we do not have sequence data on all outbreaks occurring after measles emerged as a human virus, we cannot say if all outbreaks of similar diseases were caused by measles or a similar related virus that then died out.
Then, almost as soon as contiguous settlements reached sufficient sizes to maintain the virus’ continuous transmission (Fig. 3), it emerged as a human pathogen, the progenitor of modern-day MeV.
When human populations were large enough, this virus mutated again and kept spreading throughout human populations. This virus eventually became modern-day measles.
As a fast-evolving RNA virus, it may have produced variants that were able to cross the species barrier on several occasions, but small human populations could only serve as dead-end hosts.
Bovine virus mutates quickly because it is an RNA virus. It may have mutated so that it was able to infect humans on multiple occasions. However, human populations were not yet at the critical community size, so the virus died out.
Under this scenario, a bovine virus, the common ancestor of modern strains of RPV and MeV, circulated in large populations of cattle (and possibly wild ungulates) since its divergence from PPRV around the fourth millennium BCE [3199 BCE (95% HPD interval, 4632 to 1900 BCE)]
Before measles became a disease of humans, its predecessor, bovine virus, was common in cattle and possibly other hoofed mammals. This bovine virus was already distinct from peste des petits ruminants virus which is the virus most closely related to it.
We found a significantly negative coefficient for the time-dependent nonsynonymous/synonymous substitution rate ratio (ω) (11), indicating strong long-term purifying selection;
Nonsynonymous mutations change the sequence of a protein and are more likely to cause changes in function, while synonymous mutations don't change the protein and are silent in terms of function.
significant additional unexplained variation, as modeled by the random effects
a significantly positive coefficient for the fixed effect on the PPRV rate, indicating a faster evolutionary rate in this clade
The relatedness of the 1912 and 1960 genomes to now extinct MeV lineages is in line with a marked reduction of MeV genetic diversity during the 20th century as a product of massive vaccination efforts.
When vaccines for measles were introduced the number of people infected declined significantly this caused many strains to die out.
streamlined alternative to transition-metal catalysis
Although transition metal catalysis offers several advantages, the metals typically used are toxic. Removal of these metals after the synthetic process is time consuming and expensive. The process described in the research ensures sustainability and reduces cost.
functional-group protection and/or manipulation
Functional group protection and deprotection increases the number of steps and auxiliary agents during synthesis and is not considered green. The methodology described in this research obeys one of the principles of green chemistry: "Unnecessary derivatization (use of blocking groups, protection/deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste."
“Active site” structure of wild-type Rma cyt c showing a covalently bound heme cofactor ligated by axial ligands H49 and M100. Amino acid residues M100, V75, and M103 residing close to the heme iron were subjected to site-saturation mutagenesis.
Axial methionine in cyt c is known to be labile. The proposed model for the binding for the iron-silane complex is one where the complex forms such that the silane molecule takes the place of the axial methionine. The silane may approach from the more exposed side in the protein. This further explains the observed stereochemistry of the organosilicon product. The V75T, M100D, and M103E mutations are thought to improve reactivity by providing better access of the substrate to the iron center.
Synthetic methodologies such as carbene insertion into silanes can be rendered enantioselective using chiral transition metal complexes based on rhodium (11, 12), iridium (13), and copper (14, 15).
Certain iridium catalytic systems show 97% ee, while copper catalysts show 35% ee and rhodium has been shown to exhibit 77% ee.
The regional network had low connectance, moderate specialization, and nested and modular topologies, with three distinct modules (Fig. 1, fig. S2, and table S4).
When studying larger areas of the island, the authors observed that species engaged in only a small portion of the possible interactions available, with groups of species specifically interacting amongst each other.
Our findings suggest that shared evolutionary history is not a necessary process for the emergence of complex network structure, and interaction patterns may be highly conserved, regardless of species identity and environment.
Invasive species can maintain interactions and behaviors with their surroundings similar to the native species they replaced, even if both species are not related.
These in vitro and in vivo examples of carbon–silicon bond formation using an enzyme and Earth-abundant iron affirm the notion that nature’s protein repertoire is highly evolvable and poised for adaptation:
Rma cyt c V75T M100D M103E variant is not the most evolved protein. This is considered only as a starting point to future enzymes that will show greater selectivity.
Chemoselectivity and in vivo activity of evolved Rma cyt c.
With each mutation, the chemoselectivity of the enzyme is greatly enhanced. V75T M100D M103E favors the carbon-silicon bond 29 times more than the wild type. This is attributed to the improved binding and orientation of the silicon donor in the enzyme's active site.
No product formation was observed in the absence of heme,
Heme proteins are required for the reaction to occur.
only two mice treated with anti-CTLA-4 had tumors by day 30, and one additional mouse developed a tumor around day 40
By treating the mice with anti-CTLA-4, the authors were able to prevent tumor growth in two mice and delay it considerably in the other three.
These results demonstrate that tumor rejection mediated by CTLA-4 blockade results in immunologic memory
The mice described in this section rejected the tumors twice: the first time, they were being treated with anti-CTLA-4, and the second time, they were not. This means that their immune system was able to fight off the second tumor on its own, and much faster than the immune systems of mice which had not previously survived exposure to the tumor. These are hallmarks of immunologic memory, the same phenomenon that ensures you only get chicken pox once in your life.
Anti-CTLA-4 appeared to be less effective at a tumor dose of 1×1061×106<math xmlns="http://www.w3.org/1998/Math/MathML"><mn>1</mn><mo>×</mo><msup><mn>10</mn><mn>6</mn></msup></math> cells, where treatment resulted in significantly reduced tumor growth rates, but four of five mice developed progressively growing tumors
The authors repeated the experiment with an even lower tumor burden of 1x106 cells and found that the effectiveness of treatment was reduced at this dose. They do not propose a reason for this; perhaps you can think of one?
three of five mice treated with anti-CTLA-4 developed very small tumors, all of which regressed completely by day 17
The third group of mice was treated with antibodies targeting CTLA-4. Those mice were able to clear the tumors more quickly, by day 17, if they developed tumors at all.
We believe that the simple design, fabrication, and operation of these color-changing soft machines make these systems accessible and potentially useful to many different scientific fields.
The authors suggest that their devices can be used by other scientists to observe things such as how camouflage can affect predator/prey relationships. Because these devices are non-living things but have the same camouflaging capabilities of some living things, they can avoid using animals for testing and experiments; something that is unavoidable otherwise.
The ability of color layers simultaneously to change color in the visible and the IR is a capability not used by organisms and not easily replicated by using other technologies: Animals are limited in their ability to control their temperature; soft machines fabricated in silicone elastomers are not.
The authors show us here that their devices can camouflage in the visible light spectrum as well as the IR spectrum. This is something animals cannot do, and this shows that animals are limited in their camouflaging capabilities while their devices are not limited.
Both designs created large, disjointed patches of contrasting brightness similar to the environment but not to the shape of the robot; this disjuncture in shape [disruptive coloration (3)] helped conceal the robot.
This result sentence tells us that the robots have successfully camouflaged themselves because they have differences in brightness that mimicked the environment. Since the brightness patches did not outline the device structure, it blended right in.