14 Matching Annotations
  1. Jan 2025
    1. Disease for patient 1: Von Willebrand Disease Type1, transmitter VWD-type 3

      Disease for patient 2: Von Willebrand Disease Type 3

      Patient1: 90 YO female (Afro-Caribbean)

      Patient2: 40 YO female (Afro-Caribbean)

      Notes multiple variants in the VWF gene but have focused on variants in the D4 domain. However cannot discount the impact of some other variants.

      Variant 1: VWF NM_000552.5: c.6647del p.(Cys2216Phefs*9), results in VWF protein missing D4 domain and C-terminal end of molecule

      Phenotype patient 1: Reduced VWF levels in VWF:Ag, VWF:ristocetin cofactor, FVIII:C, FVIII(VWF:FVIIIB). Bleeding score 0, required Helixate treatment before and after receiving surgery.

      Variant 2: VWF NM_000552.5: c.6432dup p.(Pro2145Thrfs*5)

      Three sequence variations in family study showed other variants highlighted p.(Cys1149Arg) and p.(Pro2145Thrfs*5) are not on the same allele.

      Does have other variants in VWF but they are stated by authors to not be detrimental. p.(Val510=) is noted to be potentially deleterious.

      Phenotype patient 2: severely reduced VWF levels, absence of multimers, bleeding score 32, epistaxis, bruising, oral cavity bleeding, prolonged bleeding from minor wounds, menorrhagia, hemarthrosis, ankle arthropathy.

      Suggests premature termination codons in these variants may lead to NMD but that this mechanism was found to be PTC position-dependent. Degradation was not 100% and need to perform cellular experiments.

  2. Nov 2024
    1. Disorder studied: Type 1 von Willebrand disease (T1-VWD).

      Type of study: Translational

      Model organism: Mouse (inbred strains) Obtained from Jackson Laboratory

      Analyses:

      VWF plasma protein quantitation (ELISA)

      Hertiability calculations

      PCR genotyping

      QTL analysis

      Allele-specific primer extension analysis

      Results:

      Identified new modifier of VWF known as (Mvwf5). Also found two loci unliked to Vwf known as (Mvwf6-7)

      Mice with this variant displayed statistically significant decrease in VWF levels, recapitulating the decreasing patterns displayed in humans.

      However, another strain of inbred mice with a different mutation did not show an age-dependent decrease in VWF. Suggests strain-specific differences in regulation of VWF levels over time.

      Mvwf5 is a cis-regulatory variant altering Vwf mRNA expression.

      This is a natural variant of the Vwf allele among inbred strains of mice. Found this variant causes elevation in steady-state levels of Vwf mRNA.

      Authors state findings show equivalent of of type 1 VWD is remarkably common in mice and humans. ALso state the Mvwf1 analysis in wild mouse populations suggest this locus is under selective pressure.

      Of the 5 potential modifier loci identified, 3 display conservation of synteny with potential human modifier loci.

  3. Oct 2024
    1. Disease: Von Willebrand Disease (VWD) type 1

      Patient(s): 13 yo, female and 14 yo, female, both Italian

      Variant: VWF NM_000552.5: c.820A>C p. (Thr274Pro)

      Dominant negative effect

      Heterozygous carrier

      Variant located in the D1 domain on VWF

      Phenotypes:

      heterozygous carriers have no bleeding history

      reduced VWF levels compatible with diagnosis of VWD type 1

      increased FVIII:C/VWF:Ag ratio, suggests reduced VWF synthesis/secretion as possible phathophysiological mechanism

      Normal VWFpp/VWF:Ag ratio

      Modest alteration of multimeric pattern in plasma and platelet multimers

      plasma VWF showed slight increase of LMWM and decrease of IMWM and HMWM

      Platelet VWF showed quantitative decrease of IMWM, HMWM, and UL multimers

      In silico analysis:

      SIFT, ALIGN, GVD Polyphen 2.0, SNP&GO, Mutation Taster, Pmut all suggest damaging consequences.

      PROVEAN and Effect suggest neutral effect

      according to ACMG guidelines this variant was classified as pathogenic

    1. Disease: Von-willebrand Disorder, type 1

      Patient 1 Variant: VWF NM_000552.5: c.4135C>T p.(Arg1379Cys) Exon 28

      Family: History not mentioned

      Patient 1 phenotype: near normal VWF:Ag and WVF:RCo levels RIPA within normal range Platelet VWF levels were normal normal pattern for multimeric analysis of plasma Slightly reduced VWF levels

      In silico predictions available:

      I-Mutant 3.0 value = -1.36 PYMOL prediction = substitution of ARG 1379 with a cysteine results in the loss of hydrogen bonds with Lys1407 and Lys1408, predicted change in secondary structure of A1 domain

  4. Dec 2022
    1. educe animals to mere metaphors, similes, or symbolsdo not seem promising for theorizing ethical recognition of actual animals.Donna Haraway, for example, criticizes philosophical texts that show a “pro-found absence of curiosity about or respect for and with actual animals,even as innumerable references to diverse animals are invoked.” 15 SusanMcHugh, meanwhile, suggests that “the aesthetic structures of metaphor,though precariously supporting the human subject, seem unable to bearanimal agency.”16 An
    2. She maybelieve the comparison reveals the moral horror of industrial animal agri-culture, but, as Bénédicte Boisseron argues, such comparisons “instrumen-talize” Blackness in a “self-serving” way, ignoring the complex and ongoingBlack struggle against dehumanizing discourses and institutions in order toframe “the animal” as “the new black.
    3. remind us of the historical reduction of the human to the status of ananimal under transatlantic slavery, but also were used as a mode of resistancefor enslaved peoples

      first half is type 1, first half is type 2

    4. Paraphrasing Joel Chandler Harris, BryanWagner writes that animal stories were “political allegories in which therelative position of the weaker animals corresponded to the global per-spective of the race.”

      thow dean uses deer and how poe uses cat ... not how chris uses deer

    Tags

    Annotators

  5. Aug 2022
  6. Feb 2022
    1. Deepti Gurdasani. (2022, January 10). Lots of people dismissing links between COVID-19 and all-cause diabetes. An association that’s been shown in multiple studies- whether this increase is due to more diabetes or SARS2 precipitating diabetic keto-acidosis allowing these to be diagnosed is not known. A brief look👇 [Tweet]. @dgurdasani1. https://twitter.com/dgurdasani1/status/1480546865812840450

  7. Jan 2022
  8. May 2021
  9. Feb 2021
  10. Feb 2014
    1. Chapter 1, The Art of Community We begin the book with a bird’s-eye view of how communities function at a social science level. We cover the underlying nuts and bolts of how people form communities, what keeps them involved, and the basis and opportunities behind these interactions. Chapter 2, Planning Your Community Next we carve out and document a blueprint and strategy for your community and its future growth. Part of this strategy includes the target objectives and goals and how the community can be structured to achieve them. PREFACE xix Chapter 3, Communicating Clearly At the heart of community is communication, and great communicators can have a tremendously positive impact. Here we lay down the communications backbone and the best practices associated with using it

      Reading the first 3 chapters of AoC for discussion in #coasespenguin on 2013-02-11.