PSD-95 Is Associated with the Postsynaptic Density and Not with the Presynaptic Membrane at Forebrain Synapses

PSD-95, a prominent protein component of the postsynaptic density (PSD) fraction from rat forebrain, has been localized by light microscopy to dendrites of hippocampal neurons (Cho et al., 1992) and to the presynaptic plexus of cerebellar basket cells (Kistner et al., 1993). Here we extend these studies to show that an affinity-purified antibody to PSD-95 labels the dendrites of most neurons in the forebrain and of a subset of neurons in the cerebellum. To confirm that PSD-95 is associated with the PSD at forebrain synapses and to clarify whether it is also associated with the presynaptic membrane, we employed immunogold electron microscopy of forebrain synaptosomes. Gold-labeled antibodies to PSD-95 labeled postsynaptic densities in both intact and lysed forebrain synaptosomes but did not label presynaptic terminals or the presynaptic membrane. The asymmetric distribution of PSD-95 at synapses contrasts with that of its homologs, disks-large and ZO-1, which are arranged symmetrically at septate and tight junctions, respectively

Identifying Client and Significant Other Characteristics for Determining Type of Continuing Care Services: A Tool for Health Care Practitioners

There is a need to develop and provide more effective tools for assessing continuing care needs for discharge healthcare. An increasing elderly population, scarce resources and limited reimbursement for health care, necessitate the development of a method to accurately identify those who will require discharge assistance for continuing care. It is becoming more important that clients be afforded the proper and appropriate type of care so as to utilize scarce and costly resources effectively. Among the scarce resources is the health care provider whose scope and extent of responsibilities will change as the agency’s ability to provide services changes. These changes are expected to occur as the Prospective Reimbursement System is initiated in the United States after October 1, 1983. This paper will address these and other issues and provide a literature search and professional practice experience in the development of a tool identifying client and "significant other" characteristics for determining the type of needed continuing care services in the community.Master of Public AdministrationPublic AdministrationUniversity of Michigan-Flinthttps://deepblue.lib.umich.edu/bitstream/2027.42/143452/1/HuntC.pd

Expansion of the HSFY gene family in pig lineages : HSFY expansion in suids.

BACKGROUND: Amplified gene families on sex chromosomes can harbour genes with important biological functions, especially relating to fertility. The Y-linked heat shock transcription factor (HSFY) family has become amplified on the Y chromosome of the domestic pig (Sus scrofa), in an apparently independent event to an HSFY expansion on the Y chromosome of cattle (Bos taurus). Although the biological functions of HSFY genes are poorly understood, they appear to be involved in gametogenesis in a number of mammalian species, and, in cattle, HSFY gene copy number may correlate with levels of fertility. RESULTS: We have investigated the HSFY family in domestic pig, and other suid species including warthog, bushpig, babirusa and peccaries. The domestic pig contains at least two amplified variants of HSFY, distinguished predominantly by presence or absence of a SINE within the intron. Both these variants are expressed in testis, and both are present in approximately 50 copies each in a single cluster on the short arm of the Y. The longer form has multiple nonsense mutations rendering it likely non-functional, but many of the shorter forms still have coding potential. Other suid species also have these two variants of HSFY, and estimates of copy number suggest the HSFY family may have amplified independently twice during suid evolution. CONCLUSIONS: The HSFY genes have become amplified in multiple species lineages independently. HSFY is predominantly expressed in testis in domestic pig, a pattern conserved with cattle, in which HSFY may play a role in fertility. Further investigation of the potential associations of HSFY with fertility and testis development may be of agricultural interest.We gratefully acknowledge the Wellcome Trust Sanger Institute core teams for fingerprinting, mapping, archiving, library construction, sequence improvement and sequencing and Genus for providing the Duroc boar samples. This work was funded by BBSRC grant BB/F021372/1. The Flow Cytometry and Cytogenetics Core Facilities at the Wellcome Trust Sanger Institute and Sanger investigators are funded by the Wellcome Trust (grant number WT098051)

Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain–Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12–1.71 at 15–21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain–Barré syndrome (IRR, 2.32; 95% CI: 1.08–5.02 at 1–28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18). Overall, we estimated 38 excess cases of Guillain–Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test

Nutrition Risk Classification: A Reproducible and Valid Tool for Nurses

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141661/1/ncp0020.pd

The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity

Although the murine immune response to Venezuelan equine encephalitis virus (VEEV) is well-characterized, little is known about the human antibody response to VEEV. In this study we used phage display technology to isolate a panel of 11 VEEV-specfic Fabs from two human donors. Seven E2-specific and four E1-specific Fabs were identified and mapped to five E2 epitopes and three E1 epitopes. Two neutralizing Fabs were isolated, E2-specific F5 and E1-specific L1A7, although the neutralizing capacity of L1A7 was 300-fold lower than F5. F5 Fab was expressed as a complete IgG1 molecule, F5 native (n) IgG. Neutralization-escape VEEV variants for F5 nIgG were isolated and their structural genes were sequenced to determine the theoretical binding site of F5. Based on this sequence analysis as well as the ability of F5 to neutralize four neutralization-escape variants of anti-VEEV murine monoclonal antibodies (mapped to E2 amino acids 182–207), a unique neutralization domain on E2 was identified and mapped to E2 amino acids 115–119

Exploring men's and women's experiences of depression and engagement with health professionals: more similarities than differences? A qualitative interview study

<p>Abstract</p> <p>Background</p> <p>It is argued that the ways in which women express emotional distress mean that they are more likely to be diagnosed with depression, while men's relative lack of articulacy means their depression is hidden. This may have consequences for communicating with health professionals. The purpose of this analysis was to explore how men and women with depression articulate their emotional distress, and examine whether there are gender differences or similarities in the strategies that respondents found useful when engaging with health professionals.</p> <p>Methods</p> <p>In-depth qualitative interviews with 22 women and 16 men in the UK who identified themselves as having had depression, recruited through general practitioners, psychiatrists and support groups.</p> <p>Results</p> <p>We found gender similarities and gender differences in our sample. Both men and women found it difficult to recognise and articulate mental health problems and this had consequences for their ability to communicate with health professionals. Key gender differences noted were that men tended to value skills which helped them to talk while women valued listening skills in health professionals, and that men emphasised the importance of getting practical results from talking therapies in their narratives, as opposed to other forms of therapy which they conceptualised as 'just talking'. We also found diversity among women and among men; some respondents valued a close personal relationship with health professionals, while others felt that this personal relationship was a barrier to communication and preferred 'talking to a stranger'.</p> <p>Conclusion</p> <p>Our findings suggest that there is not a straightforward relationship between gender and engagement with health professionals for people with depression. Health professionals need to be sensitive to patients who have difficulties in expressing emotional distress and critical of gender stereotypes which suggest that women invariably find it easy to express emotional distress and men invariably find it difficult. In addition it is important to recognise that, for a minority of patients, a personal relationship with health professionals can act as a barrier to the disclosure of emotional distress.</p

The pig X and Y Chromosomes: structure, sequence, and evolution.

We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution.This work was funded by BBSRC grant BB/F021372/1. The Flow Cytometry and Cytogenetics Core Facilities at the Wellcome Trust Sanger Institute and Sanger investigators are funded by the Wellcome Trust (grant number WT098051). K.B., D.C.-S., and J.H. acknowledge support from the Wellcome Trust (WT095908), the BBSRC (BB/I025506/1), and the European Molecular Biology Laboratory. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 222664 (“Quantomics”).This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via http://dx.doi.org/10.1101/gr.188839.11