Here, the authors estimated how much a decrease of one standard deviation on the percentile score affected the number of publications and citations of a grant recipient.

Regression is a measure of the relation between the mean value of one variable and corresponding values of other variables. There are different types of regression, all of which are used to identify trends in data.

A Poisson regression is a form of regression analysis where we have a random variable, which is equal to the number of events over a period of time if these events are independent and occur at a constant speed.

The authors found that there is a lot of variation in the research output of projects that receive grants. They conclude that it would be useful to find a way to accurately screen applications to determine their potential.

An applicant's institutional affiliation is the organization that has agreed to be the legal recipient of the grant. This organization can be a nonprofit, a university, or an employer.

The authors studied some characteristics such as the grant history or the institutional affiliation to see if the previous work of the applicant has an impact on the result of the grant application.

The last measure is the number of patents that cite those publications from (i), or acknowledge support from the grant.

The second measure is the total number of citations the publications from (i) received through 2013.

The first measure of success is the number of papers a team published during the 5 years after they received the grant.

The authors considered grants which were already funded and competing for renewal. This makes it easier to attribute differences in research productivity to the peer review process, rather than the amount of funding the project has.

Standard deviation is a statistical measure that is used to describe how much variation there is in a data set. A high standard deviation means that the data is very spread out.

The percentile score is assigned by the peer review committee. It ranks all authors to determine which was the most favored by the committee. A lower score means the committee liked the application more.

Based on an analysis conducted by the authors, biomedical research is valued highly by individuals, governments, foundations, and corporations. Research is seen as a source of more effective treatments and preventive measures and as a route to policy, new commercial products, and economic development.

As a result, investments in biomedical research are the highest of all sectors.

One critique about peer reviewing is that peer review may not identify pioneering research.

This report highlights the possible disadvantages of peer review:

http://www.theepochtimes.com/n3/1334826-does-peer-review-pick-the-best-science/

If the evaluation by the peer review committee is correlated with the quality of work put out by the research group, then peer review has high value-added (meaning, it is useful for choosing research groups with the highest potential).

The outcome of this study could have important implications for how the NIH evaluates and chooses who it gives money to.

These articles show that receiving a grant for postdoctoral research leads to an increase in productivity.

Value-added is the amount by which the value of the product is increased. Here, it means by how much peer review increases new insights about the quality of grant applications.

In these articles, the authors found out that there was no link between higher ratings from the peer-review committee and the number of citations the article eventually got.

In this article, the authors showed that getting a research grant partially depends on chance. They reviewed the same proposals with different committees, who each gave different results.

The aim of the peer-review committees is to ensure research is high-quality and to encourage innovation. However, it has been shown that peer review committees can be undermined by various factors.

In 2016, the combined budgets totaled $41.7 billion. The following resources indicate that the research budget continues to increase (as of December 2016).

https://www.nih.gov/about-nih/what-we-do/budget http://www.nsf.gov/about/budget/fy2016/ https://erc.europa.eu/about-erc/facts-and-figures

A grant is a money given to enterprises, organizations, and individuals for research, development, and education. Grants do not have to be returned, but most granting organizations require a report about the progress of the outcome.

Peer-review is the review process for scientific articles, research, or ideas by scientific experts in the same field.

In addition to the observations and findings of this study, the physical instruments and experimental protocols that were developed will likely be very useful for further research and development of diagnostics, therapies, rehabilitation strategies, and preventative measures.

The work here will help military service personnel and others at risk for developing neurotrauma-related disease.

All of these are known to affect how susceptible a patient is to mild forms of neurotrauma and related effects. They can also affect how these are expressed.

The authors suggest that blast exposure may be more damaging than sports-related impact because they were able to observe substantial neural abnormalities after a single blast exposure.

In the case of impact-induced head injury, mild cases typically require repetitive impacts to cause neural abnormalities.

Holbourn compared the head to a jar containing gelatin, hypothesizing that if the jar was shaken or violently rotated it would cause a shearing effect. He believed this shearing may be the culprit behind TBI.

Mott's investigation of "shell shock" in WWI veterans was the first human clinicopathological analysis of the physical effects of blast exposure on the brain.

The idea that an explosion could cause damage to the brain, and therefore potentially be responsible for mental deficits, led to a controversial national inquiry into blast exposure and veterans' health.

U.S. Department of Defense study that focused on blast-related lung injury and influenced thought behind blast-related injury for nearly half a century.

One of the first uses of a compressed gas shock tube to study blast exposure in an animal model.

A report of the long-term effects of repetitive head injury linked to American football.

An influential paper that drew national attention to mild TBI in military veterans.

A possible alternative hypothesis is that the structure of the head and the brain would cause the blast wave to bounce around inside the brain, causing damage.

The authors' observations of roughly equal pressures both inside and outside the skull suggest that this is not a likely cause of injury. Furthermore, the magnitude of the pressure wave is far below the threshold that causes damage to tissues.

The results of this study suggest that pressure from the blast wave is not enough to cause brain injury. The data and calculations show that the brain rapidly adapts to the changing pressure, and that the pressure inside and outside the skull during the blast wave is comparable.

Thus, blast wave pressure alone is not responsible for TBI.

Although the wild-type mouse model has limitations (as do all experimental models), using laboratory animals allows researchers to test things that can't be directly tested in humans.

For example, mouse models are useful tools to study the effects of different genes. Biological research has generated thousands of genetically modified mouse strains that allow researchers to test hypotheses regarding specific genes and how these genes influence human diseases.

An atypical or less severe form of a disease.

Here, the authors use the term to mean that although their mouse model replicates most of the major signs of CTE, it is limited in not developing the mature NFTs seen in human cases.

Occurred at the same time.

This statement is based on the authors' human findings from the human case studies. They observed identical paterns in head-injured athletes and blast-exposed military veterans, which has important implications for our undersetanding of traumatic brain injury and CTE.

To test the "bobblehead effect," the authors performed the same experiments on mice whose heads had been held still during blast exposure and mice whose heads were allowed to move freely.

Mice whose heads were allowed to move freely were exposed to both the blast wave (the pressure of the blast) and the blast wind (the wind following a blast wave). Mice whose heads were restrained were only exposed to the blast wave.

The authors hypothesized that blast neurotrauma and the resulting cognitive deficits were the result of the acceleration of the head during a blast (i.e., the blast wind), meaning that mice whose heads were restrained would not show any abnormalities.

The results reported here support the authors' hypothesis that head acceleration is a major contributor to traumatic brain injury following blast exposure.

The length of time it takes to escape the maze.

A tool used to study spatial learning and memory. The fact that blast-exposed mice took longer to escape and had poorer memories of the maze suggests a cognitive deficit due to blast exposure.

It was important to assess locomotion (movement) because the behavioral cognition test used relies on locomotion for its results.

If locomotion were impaired, then the results of the behavioral test could not be linked to cognition alone.

The authors did not detect any abnormalities in locomotion in either the control or experimental group, meaning that any cognitive abnormalities they observed were not due to locomotor defects. This strengthens the argument that any of the abnormalities they saw were due to blast-related interference with brain functions affecting learning and memory.

Although we understand a lot about the hippocampus and its function, there is still a lot of active research into the exact way that learning and memory work. Because of this, the word "candidate" is used to qualify this statement.

As above, the authors found impairments in a neuronal process thought to be involved in memory storage.

Following blast exposure, the authors observed a slowing of axonal conduction in structures of the hippocampus that are important for long-term potentiation (LTP).

Long-term potentiation (LTP) is a measure of synaptic plasticity, or the ability of synapses to adapt and change. LTP is important to learning and memory. If it is impaired, it can cause cognitive deficits, specifically in processes important to memory.

The movement of electrophysiological signals along the axon. Slowed (or prolonged) conduction is a sign of a defect in the relaying of signals between different parts of the brain.

On both sides of the brain.

Clumps of stable molecules found in the nuclei and cytoplasm of cells. They are usually a sign of viral infection and are the site of viral multiplication, but they can also indicate neurological disease.

Some axons are surrounded by a layer of myelin, a fatty, white substance that helps regulate signal transmission.

Astrocytes support blood vessels and interact with other types of brain cells to control the blood-brain barrier (BBB), a membrane that protects the brain from disruptive changes in the blood.

Using the electorn microscopic images in Figure 4 and Supplementary Figures 11 to 16, the authors saw that a single blast exposure can damage not only are the smallest blood vessels but the astrocytic "feet" that wrap around and encase these blood vessels.

Because these blood vessels are critical for gas and fluid exchange, damage to them can disrupt many metabolic processes.

A region of the hippocampus.

Scarcity.

A region of the hippocampus.

Abnormalities.

Refers to a scale that is beyond detection by light microscopy, requiring a magnification that can only be achieved by electron microscope.

Choline acetyltransferase (ChAT) is an enzyme that produces the neurotransmitter acetylcholine.

Reduced ChAT concentrations are associated with Alzheimer's disease and amyotrophic lateral sclerosis (ALS).

Decreased ChAT following blast TBI suggests similarities between Alzheimer's, ALS, and TBI.

Cells that help regulate nerve impulses.

The authors also observed other key signs of CTE, such as the presence of activated microglia near small blood vessels (perivascular microgliosis).

This finding is consistent with traumatic microvascular injury and reactive microgliosis, which are signs of chronic inflammation in the brain.

Axons that are wasting away.

Neurons whose nuclear chromatin has condensed and gathered within the nucleus. This is a step that cells undergo during apoptosis or necrosis, two methods of cell death. Pyknotic neurons are either dead or dying.

Dead or dying neurons. These neurons have suffered a breakdown of Nissl bodies, large granular bodies that are the site of protein synthesis.

In this section, the authors sought to find out if their mouse model of blast neurotrauma caused similar brain abnormalities as those observed in human CTE cases.

If so, it would mean there is a causal linkage between blast exposure and development of CTE later in life.

The authors used high-speed video cameras (which capture 100,000 frames per second) to record mouse head movements during blast exposure.

The videos showed violent winds pushing and pulling on the head during the blast, which the authors measured as the kinematics (motions over time) of the head.

These pushing and pulling forces during blast exposure were similar to sport-related impacts leading to injury.

After investigating the effects of blast waves on the skull and brain, the authors turned their attention to the effects of blast wind.

See the following video for a look at the destructive nature of these blast winds during a 1955 atomic weapons test:

https://www.youtube.com/watch?v=ztJXZjIp8OA

"Parenchyma" refers to the bulk component of a tissue. The brain parenchyma includes the dense network of brain cells and their processes, but does not include membranes, vascular elements, etc.

The authors also calculated how the blast pressure wave would travel through the brain tissue. They found that, as with the skull, the pressure wave moved too quickly through the brain to cause injury.

The authors conclude that the head may be treated as a "lumped element," meaning that the blast pressure wave travels through it as if it were a single body.

The authors next investigated how the blast pressure wave interacted with the mice's skulls. They calculated the speed of the shockwave by taking pressure measurements with multiple sensors at different locations and measuring the time delay between recordings. Using the distance between sensors and the time delay, they were able to record the "speed" of the wave as it traveled down the shock tube.

By comparing the wave speed with the width of the mice's heads, the authors concluded that the wave traveled too quickly to create a pressure gradient large enough to cause injury. Based on these results, they were able to rule out skull compression as a cause of TBI.

Dynamic pressure is more complex than static pressure. It includes not only the pressure that results from particles in natural, random motion, but collisions of particles that result from movement in the flow direction.

A common hypothesis for the way blast waves cause traumatic brain injury is that the pressure from the blast compresses the thorax (chest region) and part of the circulatory system. It is thought that this creates vascular pressure, which forces blood into the brain and increases intracranial pressure. This is known as the "water hammer effect."

The first potential injury source the authors investigated was the interaction of the blast wave with the brain. The authors tested whether this interaction was destructive to the brain. To do this, they measured the pressure of the brain in living mice using a small needle hydrophone (a microphone used to detect sound waves underwater).

Like all moving fluids, blast shockwaves have two different pressure measures: static and dynamic. Static pressure is the pressure exerted on one particle of the fluid when it is at rest. Dynamic pressure incorporates the movement of the fluid (or gas), and is a measure of the kinetic energy of the fluid.

Static pressure can be measured with a "side-on" sensor.

The majority of previous studies did not allow free movement of the head during blast exposure in shock tubes. Because of this, these studies showed minimal or no brain injury from blast exposure, contributing to the long-held belief that blast exposure is not linked to brain injury.

By allowing free movement of the head, the authors obtained results that proved otherwise, i.e., blast exposure can cause brain injury and have long-term neurological consequences.

Mouse.

A type of fiber that connects different gyri (ridges) in the brain.

Damage to axons in multiple locations.

An increase in the number of astrocytes that is due to damage to the nervous system and a sign of neurodegenerative disease.

In areas of the cortex where the authors saw irregular tau proteins, they saw damage to the axons in the white matter beneath.

An irregular heartbeat (too fast, too slow, or the wrong rhythm).

An opioid pain medication with a high risk of addiction. If too high of a dose is taken, it can be fatal.

Worsening.

Reduced reaction time in movements related to mental processes.

A disorder that develops in some people who have a terrifying or dangerous experience. There are many symptoms, but the major signs are increased anxiety, flashbacks, nightmares, and uncontrollable thoughts about the event.

Pain relievers.

An infection that occurs after inhaling food, liquid, or vomit into the lungs.

Although not shown in the figure below, the authors also examined the brains of healthy controls that matched the age and sex of the experimental subjects. They used the same IHC technique.

No abnormalities were observed in the control cases.

The abnormalities seen in the brains of head-injured athletes and blast-exposed military veterans were similar, so the authors hypothesized that the cause of CTE in these two groups must also be similar. However, it is currently not possible to diagnose CTE until after a patient has died and their brain can be autopsied.

The authors identified a correlation between neurotrauma and CTE, but in order to test their hypothesis and prove a causal connection, they had to perform controlled experiments. They used a mouse model for this.

Microglia are immune cells in the brain that are related to the cells in our peripheral immune system. Cells from our peripheral immune system cannot enter the brain, so the brain has to develop its own innate immune system. Microglia are a key component of this.

Monoclonal antibodies are used in immunohistochemical staining to detect abnormal phosphorylated tau proteins. In this study, several different antibodies were used to detect various forms of tau proteins in different places in the brain.

If the specific set of abnormalities is detected in the postmortem brain of someone who had a history of neurotrauma, the diagnosis is CTE.

Spaces around blood vessels.

The unique neuropathological lesion of CTE is an irregular accumulation of NFTs and glial tangles around the small blood vessels deep in the sulci (grooves) of the cortex.

Similar to NFTs but in glial cells instead of neurons. These tangles are also associated with abnormal tau protein accumulation and, when they are observed in the brain, are an indicator of disease.

Bleeding in the brain.

An intracerebral hemorrhage can disrupt blood flow and deprive the brain of oxygen, put pressure on brain tissue around the hemorrhage, and introduce toxins into the brain.

Intracerebral hemorrhage can be fatal.

Weakness in the walls of the basilar artery at the base of the brain, resulting in ballooning. Rupture of this blood vessel can cause sudden onset of neurological symptoms and is often lethal.

Repetitive concussive injury means that the athlete had multiple reported concussions. Recent research suggests that repeated impacts to the head (but not necessarily concussions) are related to an increased risk of developing neurodegenerative diseases including CTE.

Thus, the number of head impacts, regardless of how many resulted in concussion, is a more accurate measure of risk of long-term neurological consequences, including CTE.

A control is a group or individual that is used as a standard of comparison in experiments.

The authors used neuropathological analysis to compare the brains of military veterans who were exposed to blasts with young American football players, a professional wrestler, and normal controls.

The relationship between the sequence of events that led up to the death of the patient or subject and the findings from an autopsy.

Recently, scientists have recognized that blast-related traumatic brain injury suffered during military service can have a negative impact on veterans' lives. It has been shown to impair many brain functions (concentration, memory, cognition) and negatively affect mood (irritability, suicidal ideation).

In 2012, President Barack Obama signed an Executive Order to improve access to mental health care for veterans: https://www.whitehouse.gov/the-press-office/2012/08/31/executive-order-improving-access-mental-health-services-veterans-service

If a mouse's head was prevented from moving when it was exposed to a blast, the learning and memory deficits described above did not occur.

Back and forth movement.

Mice that were exposed to blasts had memory and learning problems. Additionally, axons in their brain showed reduced function and they had defective activity-dependent long-term potentiation, which is thought to be important to learning and memory.

In this case, these defects were all correlated but not necessarily caused by one another.

Occurs when blood vessels are punctured and blood begins to flow out of them.

A group of psychiatric disorders with underlying neurological causes.

A common format of experimental design in medical research is to formulate a hypothesis based on findings in human patients and test the hypothesis in an animal model.

How exposure to blasts injures the brain.

Connects to Next Generation Science Standards Science and Engineering Practice 6: Constructing explanations (for science) and designing solutions (for engineering).

Nerves do not very often just hang out by themselves; they usually are part of a nerve sheath, a collection of nerves bundled together.

A major type of cell responsible for "bundling" or ensheathing these cells are Schwann cells. These cells are discussed below.

You can think of these as the cords connecting to your computer, most of you likely have all of your cords nicely wrapped and bound together. You don't have single cords going everywhere.

http://www.highlands.edu/academics/divisions/scipe/biology/faculty/harnden/2121/images/neurium.jpg

The "fingerlike" extensions from the body of a nerve cell. For a diagram of a nerve cell, see:

http://www.bbc.co.uk/staticarchive/5d3d66ef622165ae607b3c02f6e603c524eececf.gif

Nerves of the peripheral nervous system that innervate the limb. Does not include nerves found solely in the spinal cord or brain.

You have very likely heard of transmembrane proteins, proteins that integrate into the plasma membrane of a cell. A glycosylphosphatidylinosotol (GPI)-anchored protein is a very similar idea.

In the case of GPI-anchored protein, GPI is what actually integrates into the plasma membrane as opposed to the protein itself as in in a transmembrane protein. Because GPI is bonded to the protein it becomes anchored along with GPI. Now, a protein that was once free-floating and cytoplasmic is now bound to the plasma membrane.

Although it does have the same structure as GPI, the following diagram does show conceptually what is happening:

http://www.sigmaaldrich.com/content/dam/sigma-aldrich/articles/biology/Glycobiology/structure-of-gpi-anchored-proteins.jpg

Retinoic acid (a major component of vitamin A) and derived compounds are often used to treat acne. Many of these drugs, however, are known to cause major birth defects at the dosages effective for treating acne. The drug isotretnoin (brand name Accutane®) is in particular known to cause severe birth defects.

As a result, there is heavy regulation of this drug including mandatory birth control. This, unfortunately, was not always the case and resulted in many children born with birth defects. See this article in The New York Times for more:

http://www.nytimes.com/1984/10/11/us/acne-drug-accutane-linked-to-severe-birth-deformities.html

Although development is not regeneration, retinoic acid's role in causing defects in both these processes does highlight shared similarities. Retinoic acid does not disrupt every biology process, you need vitamin A to live of course!

Because retinoic acid is capable of disrupting both these processes this does suggest some link between the two.

The limb blastema is the site of regeneration. It is the region where the salamander's limb has been damaged and/or removed and the limb will regrow.

The limb blastema is composed of mesenchymal progenitor cells. These cells are able to become mesenchymal tissue such as cartilage, muscle, and connective tissue.

The blastema is formed after "healing," which ensures there isn't serious blood loss. For a picture, see:

http://openi.nlm.nih.gov/imgs/512/397/2656220/2656220_jbiol105-1.png

Connects to AP Science Practice 1:

The student can use representations and models to communicate scientific phenomena and solve scientific problems.

A method for making cells permeable to macromolecules by passing electric current though them.

Removal of the limb nerve supply.

Away from the point of attachment. For example, your fingers are distal to your shoulder.

For a picture, see:

https://www.geol.umd.edu/~jmerck/geol431/images/directions.jpg

The limb blastema is the site of regeneration. It is the region where the salamander's limb has been damaged and/or removed and the limb will regrow. The limb blastema cells are composed of specialized cells that are able to regenerate structures of the limb.

The blastema is formed after "healing," which ensures there isn't serious blood loss. For a picture see:

[http://openi.nlm.nih.gov/imgs/512/397/2656220/2656220_jbiol105-1.png] (http://openi.nlm.nih.gov/imgs/512/397/2656220/2656220_jbiol105-1.png)

This is a test annotation for view only test role

This is the second gap phase of the cell cycle, between DNA replication (S phase) and mitosis (M phase). During G2, the cell prepares to divide.

To move on to the next phase (the M phase), a checkpoint ensures that all chromosomes are fully replicated and have no other types of damage.

The number of full chromosome sets in a cell is indicated as a multiple of n. A eukaryotic cell with two complete sets of chromosomes is therefore described as being "2n" (or "diploid").

After DNA replication in the S phase, the cell's DNA content doubles, and it now contains four complete copies of the genome, making it "4n." Then, after the cell divides in the M phase, there are two daughter cells, each with two complete sets of chromosomes (2 x 2n cells).

Most cells cycle between being 2n and 4n. Sperm and egg cells (gametes), however, are special cases: They are "haploid" and contain only one set of chromosomes, making them 1n or simply n. Gametes therefore cycle between being 1n and 2n.

Each time the cell divides into two, it goes through a sequence of events that may include growth, DNA replication, preparation to divide, and finally division. We collectively refer to these events as the "cell cycle," and to the four major events as "phases" (G1, S, G2, and M phase).

Specialized proteins called "cell cycle regulators" or "checkpoint proteins" regulate the progression from one phase to the next. The progression through these checkpoints is a strictly regulated process that usually works without errors. When errors do occur, they can have catastrophic consequences, including the development of cancer.

Use this interactive tutorial to learn more: http://www.hhmi.org/biointeractive/eukaryotic-cell-cycle-and-cancer

A technique used to determine how a trait is inherited, and if it is inherited in a standard (Mendelian) way.

Refers to the autosomes, or the 22 numbered chromosomes (which do not include the sex chromosomes).

Studies have shown that there are many unique combinations of mutations that can cause autism, similar to the case of mental retardation and epilepsy. Unfortunately, given that there are so many ways for autism to occur, it is difficult to track which changes can lead to symptoms.

Here, "syndromic" means common varities of autism.

Disorders caused by a single gene.

A mental disorder that is caused by the nervous system.

A method for mapping genes that are involved in rare, recessive disorders. It is used in inbred populations (populations where many individuals are related to each other). Because these populations are very highly related, individuals will share large areas of their chromosomes surrounding target genes.

Autism-spectrum disorders (ASD), sometimes referred to collectively as "autism," are a family of developmental disorders that have different symptoms and intensities.

This 2007 paper from Chiang et al. presented a new method for looking at the recruitment of different types of white blood cells to the site of an injury, while simultaneously identifying clusters of ligand-receptor couplings.

All of this can be visualized in live mice!

From this initial study, PSGL-1 was identified as a promising neutrophil ligand protein.

P-selectin glycoprotein ligand 1 interacts with the P-selectin found on platelets.

For reference, P-selectin functions as a cell adhesion molecule on activated platelets. Ligands are molecules that produce a signal by binding to a site on a target protein (in this case, the P-selectin on platelets).

Previous research presented a new method for looking at the recruitment of different types of white blood cells to the site of an injury, while simultaneously identifying clusters of ligand-receptor couplings. This can be done in live mice.

From this initial study, PSGL-1 was identified as a promising neutrophil ligand protein.

Can you, based on the procedure described in the text, explain how the different microlattices are manufactured?

The Common Core English and Language Arts Standards

• 11-12.3: Follow precisely a complex multistep procedure when carrying out experiments, taking measurements, or performing technical tasks; analyze the specific results based on explanations in the text.

Nanoscale relates to objects whose characteristic dimensions lie between 1 and 999 nm (=10^-9 m). It is the scale below the microscopic scale.

Any animal that is not a member of the group of animals that includes human beings, apes, and monkeys.

Eudaimonic well-being, as compared with hedonic well-being, relates more to the achievement/fulfillment of meaning in life.

It relates to happiness/well-being that is achieved through a virtuous or transcendent life.

You can browse through daily issues of the Congressional Record here.

This study measured sunlight driven conversion of DOC to CO₂ in a lake in southern Finland. They measured lower quantum yields than the authors found in the paper you just read.

Organisms such as plants and algae that use sunlight to produce their own energy source. They do not need to eat.

The carbon dioxide (CO₂) released from surface water as calculated in this paper only accounts for 20% to 40% of the estimated CO₂ release from all arctic freshwater.

Other possible sources of CO₂ include CO₂ released directly from water in the ground and CO₂ produced by organisms living in the sediment at the bottom of lakes, rivers, and streams.

Sections of a molecule

How high in the sky the sun will get during the day

Measurement methods are summarized here and provided in detail in the supplemental information.

Photomineralization and partial photo-oxidation were measured for each water sample by first filtering the bacteria out of the samples and then putting them in ultraclean, air-tight, transparent vials.

Vials were exposed to sunlight for 12 hours. Control vials were wrapped in foil, and placed alongside the sunlight-exposed vials.

After the sunlight exposure, carbon dioxide (CO₂) production and oxygen (O₂) consumption were measured for each sample, as in the dark bacterial respiration experiment.

The amount of complete and partial oxidation that occurred were calculated based on the ratio of O₂ use to CO₂ production. This is possible because complete oxidation uses one molecule of O₂ for every CO₂ produced, whereas partial oxidation uses O₂ but does not produce any CO₂.

The details of how this was done are in the supplemental information. The method is summarized below:

The authors measured dark bacterial respiration by putting unfiltered water samples in extremely clean, air-tight vials and allowing them to sit for 5–7 days at 6°C to 7°C (the average temperature of nonfrozen water at the sampling sites).

As a control, the authors used water samples where all of the bacteria had been killed using mercury.

At the end of the 5–7 days, the authors measured how much carbon dioxide (CO₂) had been produced in each sample. In some samples, the amount of oxygen (O₂) decrease was also measured as a way of validating the results. Bacterial respiration uses one molecule of O₂ for each molecule of CO₂ produced. The two methods returned the same results, indicating high-quality data.

Breakdown of organic carbon to carbon dioxide driven by sunlight

Measured at the same time

From the surface of the water to the bottom

Breakdown by sunlight

Light-absorbing (yes, this word is redundant)

Sunlight-driven

This link discusses some possible implications of thawing permafrost.

Carbon "cycling" happens when carbon changes forms in the environment, for example, when dissolved organic carbon oxidizes to form carbon dioxide (CO₂), or when plants use CO₂ for photosynthesis. Carbon is not destroyed in the environment, but it frequently changes forms.

Image from globecarboncycle.unh.edu

Amount transfered

Clumped together in particles

The carbon budget is the amount of carbon dioxide that can be emitted before the earth starts to experience the most dangerous impacts of climate change.

Partial oxidation is when organic carbon is broken down, but not all the way. Partially oxidized carbon is not released into the atmosphere. Partial oxidation still requires oxygen (not as much as complete oxidation), though no carbon dioxide is produced.

An example would be "fading" of a colored fabric that you leave out in the sun, like a favorite blue hat that you wear all the time. The dye (which is made of organic carbon) gets broken down by light and fades in color, but it isn't converted into CO₂.

Carbon dioxide (CO₂), is the main form of carbon in the atmosphere.

CO₂ is a “greenhouse gas,” which means that extra CO₂ in Earth’s atmosphere contributes to global warming.

It is made when other forms of carbon are completely oxidized.

Complete oxidation is when organic carbon is broken down as much as possible to form inorganic carbon in the form of carbon dioxide (CO₂).

Oxidation of organic carbon to CO₂ requires oxygen (O₂) and is an important piece of the carbon cycle, that is, the cycling of carbon between its organic forms (organic carbon, DOC), and inorganic carbon (CO₂).

One molecule of oxygen (O₂) is required for each molecule of CO₂ that is produced from the oxidation of organic carbon.

Carbon is an element that is found in all living things and in many other substances in the environment, such as carbon dioxide (CO₂). It can also be found in soil and can be dissolved in lakes, rivers, and oceans.

Peer-review is the review process for scientific articles, research, or ideas by scientific experts in the same field.

This review was written by members of the same lab in which Dr. Roberson did the work described in this paper.

It outlines how the symptoms experienced by Alzheimer's patients seem to fluctuate constantly, suggesting that these symptoms cannot just be caused by dying neurons (which would result in symptoms that would get progressively worse).

The authors discuss known changes in other proteins in the brains of Alzheimer’s patients and how these protein networks might work together to mediate symptoms of Alzheimer’s disease in the brain.

Santa Cruz and colleagues studied genetically modified mice that had a mutation in the human version of the tau gene, which caused those mice to get tau tangles like those seen in Alzheimer’s disease.

Knocking out this tau gene allowed the mice to avoid memory and cognitive problems, although the tangles still formed.

Myers and colleagues examined patients that had died of progressive supranuclear palsy, a disease caused by a mutation in the tau gene.

They found that these patients also had an increased risk for Alzheimer’s disease, pointing to an important connection between tau and Alzheimer’s.

Lewis and colleagues made a genetically modified mouse with a mutated APP gene and a mutated tau gene.

These double mutants had plaques like other hAPP mice, but they also had tangles that were more severe than in other mice, showing that problems with amyloid and tau can interact and cause symptoms of Alzheimer’s disease.

Tanzi and Bertram review the "amyloid hypothesis," which is the idea that a build-up of amyloid-β into plaques causes problems in tau, which then form tangles, causing the symptoms of Alzheimer’s disease.

This work started as a side project and eventually became a pillar of Dr. Roberson’s later work on mouse models of Alzheimer’s disease. It has been credited with "sparking the research community’s interest in the role of tau in the pathogenesis of Alzheimer’s disease.”

Read more in Neurology Today:

http://journals.lww.com/neurotodayonline/_layouts/15/oaks.journals.mobile/post.aspx?blogId=1&postId=520

It might be difficult to recreate this mouse model in humans because previous research has shown that removing the gene that encodes tau in humans leads to serious learning impairments.

This work was covered by AlzForum, a leading advocacy group for Alzheimer’s research and patients.

Read more at AlzForum:

http://www.alzforum.org/news/research-news/app-mice-losing-tau-solves-their-memory-problems

Lowering tau even in normal mice (those without the hAPP gene, who would not get Alzheimer’s disease) was beneficial in making mice less prone to seizures when injected with an seizure-inducing drug.

This means that in healthy mice, normal tau may be involved in modulating excitation in neurons, reducing the overall risk of seizures.

(Seizures are a result of abnormally high electrical activity in the brain that occurs when certain neurons are excessively excited.)

An injection into the belly of a mouse that avoids hitting any internal organs.

Mice that do not have the hAPP gene (normal mice).

Like humans with Alzheimer’s disease, many mice used as models of the disease have a tendency to get seizures, including the hAPP mice used in this study.

However, hAPP mice without tau or with reduced tau had fewer seizures than those with the normal amount of tau.

During the course of Alzheimer’s disease, excess stimulation can occur in neurons, causing problems in the brain (including seizures).

http://www.medscape.com/viewarticle/813029

Wrong or deviating from the norm.

Eliminating tau in hAPP mice prevented memory and cognitive problems, but it didn’t prevent the neurons from becoming damaged and impaired.

The removal of tau must therefore work in an unrelated way to improve cognition in these mice.

All hAPP mice, independent of the amount of tau, had neurons whose axons and dendrites were withering away in regions near amyloid plaques.

These results show that this type of damage in Alzheimer’s disease can happen even without tau being present.

Any extension of a neuron, like an axon or a dendrite.

Wasting away.

Dots or points.

Reducing tau in hAPP mice protected those mice against the cognitive impairments seen in Alzheimer’s disease.

The authors looked at hAPP mice with normal amounts of tau to see how the tau became abnormal later in life. They compared these changes with abnormal tau measured in other mouse models of Alzheimer’s disease.

The connection between tau and amyloid-β in this model isn’t clear and may involve multiple types of tau or tau stored in various locations (or pools) within the cell.

The breakdown of a protein by enzymes.

Previous research has shown that fragments of abnormal tau are toxic and may also play a role in how toxic amyloid-β is to neurons. In fact, neurons lacking tau seem immune to damage by amyloid-β.

This may be the reason why, in this study, the researchers found that the reduction of tau had improved memory, even though amyloid-β or plaque levels remained unchanged.

http://www.ncbi.nlm.nih.gov/pubmed/15930385

Ground up or processed tissue.

Phosphorylation adds a phosphate group to a molecule. When proteins (like enzymes) are phophorylated, their function and activity changes.

Abnormal tau that is more phosphorylated than normal is a hallmark of Alzheimer’s disease.

In mice, tau is phosphorylated similarly to tau in humans, which makes comparisons feasible and simple.

A molecule that binds to a protein and changes its function.

The authors examined the brains of hAPP mice with different levels of tau. They found that, at all levels of tau, the amount of amyloid plaques and the amount of floating amyloid-β were the same in all hAPP mice.

Thus, the reduction of tau, which had improved memory, didn’t alter the amyloid-β or plaque levels, suggesting that amyloid-β or plaque levels alone are not responsible for memory loss.

hAPP mice are known to die young, as a result of the induced Alzheimer’s disease. But if hAPP mice had a reduced amount of tau, they lived much longer.

Additionally, hAPP mice with normal levels of tau were hyperactive even into middle age, whereas hAPP mice with no tau were not.

Cause or origin.

By examining older hAPP mice with and without tau, the authors could test how tau causes Alzheimer’s disease to progress as an animal ages.

Previous research has shown that damaging an area of the brain (the entorhinal cortex) that sits next to the hippocampus can make an animal hyperactive.

Damage to the entorhinal cortex is common in Alzheimer’s disease. Using the same methodology as in previous studies, the authors therefore tested their mice for increased hyperactivity to see whether there was any evidence of damage to this brain area.

Mice with the hAPP gene usually do poorly in the water maze because of their impaired memory. However, hAPP mice that have only half the amount of normal tau did remember where the platform was after additional training.

hAPP mice with no tau performed similar to normal, healthy mice, showing good memory on this test.

Thus, removal of all the normal tau seems to prevent memory problems. Even removing just half the normal tau already has some memory benefits.

After the researchers trained all mice to swim to a platform hidden under the water surface, the authors removed the platform to see how much time they spent in the area where the platform used to be. This way the researchers were able to test the memory of the mice.

Learning (and remembering) where something is in 3D space.

In this case, the mouse cannot see the platform hidden under the surface of the water. It has to remember from previous trials where it's located.

Alzheimer’s mice (with hAPP) that had normal amounts of tau (Tau+/+) took longer to learn to swim to a visible platform than the other five types of mice.

A maze in which mice learn the location of a platform. The platform is visible at first and then hidden under the water surface once the mice learn its location.

This type of maze requires the hippocampus, one of the first parts of the brain to become damaged in Alzheimer’s disease.

See a video about the Morris Water maze here:

http://www.jove.com/video/897/morris-water-maze-experiment

https://youtu.be/leHLL4vcbCc

Next Generation Science Standards: Connects to Practice 2: Developing and using models

The authors developed and used an animal model to study how different levels of tau might interact with amyloid-β to cause the symptoms of Alzheimer’s disease.

www.nap.edu/openbook.php?record_id=13165&page=42A

The authors used mice that were genetically engineered to express a human copy of the amyloid precursor protein (called hAPP mice). hAPP mice are a common animal model of Alzheimer’s disease. They develop amyloid plaques and severe memory and cognitive problems later in life, just like humans with the disease.

The authors bred these hAPP mice with other mice that were missing both their genes for the tau protein (called Tau-/- mice). From this breeding plan, the authors produced hAPP mice with normal amounts of tau (hAPP/Tau+/+), with half the normal amount of tau (hAPP/Tau+/-), and with no tau (hAPP/Tau-/-).

They also produced mice without the human APP gene that had normal, half, and no tau.

Specific genetic mutations that cause Alzheimer’s disease.

These mutations are very rare and only account for about 2% of all cases of Alzheimer’s disease. If an individual has one of these rare mutations s/he is destined to get Alzheimer’s disease (100% chance of developing Alzheimer's).