Miracle-dz/UniFAR-FTUs huggingface dataset:
Reproductive Aging is Associated With Altered Gene Expression in Human Luteinized Granulosa Cells

Declining reproductive success with aging is attributable to qualitative and quantitative deterioration in oocytes, which are nurtured by granulosa cells (GCs). This prospective study assesses whether reproductive aging is accompanied by differential gene expression in luteinized GCs from in vitro fertilization (IVF) patients. Women with nonovarian infertility etiologies were categorized as younger (≤30, n = 3) or older (≥40, n = 3). During oocyte retrieval, mural GCs were isolated; messenger RNA (mRNA) was extracted and transcribed for complementary DNA (cDNA) microarray analysis. Differential gene expression was confirmed by real-time polymerase chain reaction (PCR). Analysis revealed 120 genes were differentially expressed. Three genes were upregulated and 117 were downregulated (including interleukin [IL]-1β, IL-1R2, and IL-6R) in GCs of older versus younger patients. Our data provide evidence of downregulation in IL-1 and IL-6 gene families in luteinized GCs with advancing age. Given previously recognized roles for the IL gene family in folliculogenesis and ovulation, our findings may partly explain ovulatory and luteal dysfunctions associated with reproductive aging.
Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission

ABSTRACT Over the past 30 years, several cross-species transmission events, as well as changes in virus tropism, have mediated significant animal and human diseases. Most notable is severe acute respiratory syndrome (SARS), a lower respiratory tract disease of humans that was first reported in late 2002 in Guangdong Province, China. The disease, which quickly spread worldwide over a period of 4 months spanning late 2002 and early 2003, infected over 8,000 individuals and killed nearly 800 before it was successfully contained by aggressive public health intervention strategies. A coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and initial assessments determined that the virus crossed to human hosts from zoonotic reservoirs, including bats, Himalayan palm civets (Paguma larvata), and raccoon dogs (Nyctereutes procyonoides), sold in exotic animal markets in Guangdong Province. In this review, we discuss the molecular mechanisms that govern coronavirus cross-species transmission both in vitro and in vivo, using the emergence of SARS-CoV as a model. We pay particular attention to how changes in the Spike attachment protein, both within and outside of the receptor binding domain, mediate the emergence of coronaviruses in new host populations.
Repeated Intraplantar Injection of Low-pH Saline Produce Mechanical Hyperalgesia in Rat

Background: The purpose of this study was to characterize an animal model of persistent mechanical hyperalgesia induced by repeated intraplantar injection of low pH saline. Methods: Saline, at pHs of 4, 5, 7 and 7.4, was intraplantarily injected into the hind paw twice, 5 days apart. To quantify the hyperalgesia, the withdrawal threshold (WT) to mechanical stimuli was measured on the following schedule: before the first injection; 2 h and 4 h after the first injection; before the second injection and 4 h and weekly (6 weeks) after the second injection. The paw withdrawal latency to radiant heat was also measured with pH 4 saline. Mechanical hyperalgesia (MH) due to an intraplantar, subcutaneous injection was compared with that of a gastrocnemius muscle injection at pH 4. Results: Two unilateral injections of pH 4 and 5 saline solutions caused bilateral mechanical, but not heat hyperalgesia, which lasted 3 -4 weeks. An intraplantar injection of pH 4 saline showed a higher WT than the gastrocnemius muscle injection 4 hours after the second injection, but there was no significant difference between the two. Conclusions: Repeated intraplantar injections of low pH saline produced bilateral long-lasting MH in rats, but there was no significant difference in the WT between muscle and subcutaneous injections.
Atypical Antipsychotics: Impact on Overall Health and Quality of Life

The use of antipsychotic medications for the treatment of schizophrenia requires a detailed assessment of patient history, including comorbidities and concomitant medications. Because all antipsychotics may produce a complex array of adverse effects, the patient’s drug therapy may lead to exacerbation of pre-existent health problems and impaired quality of life. The occurrence of drug-related side effects such as cardiac disturbances, diabetes, and obesity is important to document for these patients, especially if they are already at increased risk because of underlying disease, substance abuse, or smoking. Antipsychotics may also cause anticholinergic effects, gait disturbances, and excessive sedation, which are particularly important reactions to monitor in elderly patients. Psychiatric nurses need to be aware of the risk for these side effects in relation to patients’ new or ongoing medication so that potentially serious events can be recognized and corrected. Appropriate patient education about medication is also an important component in helping patients to recognize and manage side effects and to gain the most from their drug therapy.
Ambulatory Monitoring of Oxygen Saturation in Chronic Lung Disease: Optimizing Long-Term Oxygen Therapy

The benefits of long-term oxygen therapy (LTOT) were defined in studies performed two decades ago that demonstrated a survival benefit in patients receiving LTOT. Optimal delivery of LTOT remains an essential management goal in patients with chronic obstructive pulmonary disease (COPD). Therefore, the method that clinicians use to initiate and monitor LTOT should provide an accurate assessment of a patient’s oxygen needs. Unfortunately, this may not always be true. Recommendations for prescribing LTOT suggest providing enough oxygen to correct hypoxemia at rest and during usual exercise. The standard approach for initiating LTOT uses a measurement at one point in time (either Pao2 per arterial sample or Sao2 by pulse oximetry) while the patient is at rest. This assessment is typically performed in the hospital or clinic setting. The assumption behind this approach is that patients will maintain a therapeutic oxygen saturation in the outpatient setting. The effectiveness of this approach has never been rigorously evaluated. Recent work has focused attention on the temporal pattern of oxygen saturation during activities of daily living in the outpatient setting in patients with chronic lung disease. Ambulatory oximetry monitoring (AOM) provides a way to accurately define oxygen needs in this setting. The information gained from this approach supports the view that oxygen prescriptions need to be individualized. We review the status of the work using AOM to monitor LTOT, the significance of the results, and how AOM can be used as a tool to improve delivery of LTOT in patients requiring oxygen supplementation in the outpatient setting.
A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection

ABSTRACT Neutralizing antibody protection against HIV-1 may require broad and potent antibodies targeting multiple epitopes. We tested 7 monoclonal antibodies (MAbs) against 45 viruses of diverse subtypes from early infection. The CD4 binding site MAb NIH45-46W was most broad and potent (91% coverage; geometric mean 50% inhibitory concentration [IC50], 0.09 μg/ml). Combining NIH45-46W and a V3-specific MAb, PGT128, neutralized 96% of viruses, while PGT121, another V3-specific MAb, neutralized the remainder. Thus, 2 or 3 antibody specificities may prevent infection by most HIV-1 variants.
Perceptive Evaluation of Prosthetic Foot and Ankle Systems

The availability of advanced prosthetic components may be beneficial to the amputee, but the great variety of available options may also cause confusion in selecting the proper prosthetic prescription. Ideally, the selection of components in a prosthetic prescription would be derived from published scientific outcomes and supported by the prosthetist’s successful clinical experience. However, clinical prescription is more often a result of anecdotal evidence and positive subjective feedback because objective amputee gait studies often fail to demonstrate significant differences among devices based on scientific measures. This void between anecdotal experience and scientific evidence is often acknowledged and even accepted in the literature, particularly in regards to prosthetic feet: “Most active patients subjectively prefer the dynamic response prosthetic foot to its predecessors although studies have yet to prove the dynamic response keel design to be significantly advantageous in improving ambulatory efficiency” (p. 69). Although scientific evidence does not significantly favor one prosthetic foot to another, there are alternative outcomes that can be used to assess prosthetic performance and amputee preference for prosthetic feet. If these perceptive measures are to be used to drive clinical decision making or prescriptions with respect to component selection, then these results must be presented in such a way as to convince clinicians that one type of prosthesis will offer an improved quality-of-life for their patients as compared with another. The purpose of this report is to summarize available outcomes measures used to assess prosthetic performance and preference and to review published outcomes that have been used to compare prosthetic feet.
Dengue Virus Infection Induces Upregulation of GRP78, Which Acts To Chaperone Viral Antigen Production

ABSTRACT Dengue virus (DENV) pathogenesis is related to the host responses to viral infection within target cells, and therefore, this study assessed intracellular changes in host proteins following DENV infection. Two-dimensional gel electrophoresis and mass spectrometry identified upregulation of the host endoplasmic reticulum (ER) chaperone GRP78 in K562 cells following DENV infection, in the absence of virus-induced cell death. Upregulation of GRP78 in DENV-infected cells was confirmed by immunostaining and confocal microscopy and by Western blot analysis and was also observed in DENV-infected primary monocyte-derived macrophages, a natural target cell type for DENV infection. GRP78 was upregulated in both DENV antigen-positive and -negative cells in the DENV-infected culture, suggesting a bystander effect, with the highest GRP78 levels coincident with high-level DENV antigen production and infectious-virus release. Transfection of target cells to express GRP78 prior to DENV challenge did not affect subsequent DENV infection, but cleavage of GRP78 with the SubAB toxin, during an established DENV infection, yielded a 10- to 100-fold decrease in infectious-virus release, loss of intracellular DENV particles, and a dramatic decrease in intracellular DENV antigen. However, DENV RNA levels were unchanged, indicating normal DENV RNA replication but altered DENV antigen levels in the absence of GRP78. Thus, GRP78 is upregulated by DENV infection and is necessary for DENV antigen production and/or accumulation. This may be a common requirement for viruses such as flaviviruses that depend heavily on the ER for coordinated protein production and processing.
Restarting Lytic Gene Transcription at the Onset of Herpes Simplex Virus Reactivation

ABSTRACT Herpes simplex virus (HSV) establishes a latent reservoir in neurons of human peripheral nerves. In this quiescent state, the viral genome persists as a circular, histone-associated episome, and transcription of viral lytic cycle genes is largely suppressed through epigenetic processes. Periodically, latent virus undergoes reactivation whereby lytic genes are activated and viral replication occurs. In this Gem, we review recent evidence that mechanisms governing the initial transcription of lytic genes are distinct from those of de novo infection and directly link reactivation to neuronal stress response pathways. We also discuss evidence that lytic cycle gene expression can be uncoupled from the full reactivation program, arguing for a less sharply bimodal definition of latency.
NASH

: Nonalcoholic steatohepatitis describes a hepatic disorder with the typical characteristics of an alcoholic pathogenesis without alcohol consumption. It was first described in 1962 and named NASH by Ludwig et al. 1980. Many researchers worked on this disease since this time. It represents the hepatic manifestation of the syndrome X. The pathogenesis is a two-hit phenomenon. The first hit leads to steatosis hepatis and makes the liver vulnerable to the second hit. Central factors of the second hit are oxygen-radicals, oxidative stress, lipid-peroxidation and cytokines. The exact pathogenic mechanisms are still unknown. NASH is a hepatic disease which can end up in liver cirrhosis and liver failure. Up to now a curative drug therapy does not exist. The poor prognosis in some cases, the increasing incidence in western populations and the lack of therapeutic options renders NASH to a serious problem. The aim of this article is to show the actual knowledge of this disease, especially focussed on the pathogenesis, by review of the literature from 1979 up to the present time.
Digital image compression based on non-stationary and inhomogeneous multiresolution analyses

Adaptive wavelet-based image compression methods are introduced. In contrast to the classical wavelet decomposition scheme one can use different wavelet and scaling functions at every scale-this leads to nonstationary multiresolution analysis. An inhomogeneous multiresolution analysis is obtained by using different functions for the two directions in the tensor product of the bidimensional multiresolution analysis, furthermore these two methods are combined. The freedom in using different functions is exploited for image compression in an adaptive way. Special non-stationary and/or inhomogeneous multiresolution analysis is built out of the functions in a given library that is best suited for compression of a given image. This is done by minimizing cost-functions at every scale-level. <<ETX>>
Witches, Westerners, and HIV: AIDS and Cultures of Blame in Africa. Alexander Rödlach

With over 40 million cases of HIV/AIDS worldwide, people who are infected, particularly the poor and underserved, seek to understand their illness better. In Witches, Westerners and HIV: AIDS and Cultures of Blame in Africa, Alexander Rodlach gives us a uniquely comprehensive perspective on how many people in Southern Africa and other developing areas explain the origin and spread of HIV/AIDS. While this work would stand alone as a significant contribution to anthropological theory and method, it is equally important for health (AIDS) education and treatment because illness beliefs influence prevention programs and help-seeking behavior, including anti-retroviral treatment. Further, through his richly detailed ethnography from Zimbabwe, Rodlach shows how the social and historical context fosters the development of sorcery beliefs and conspiracy theories that compete with scientifically-based information on the etiology of HIV/AIDS. Rodlach’s book is organized into four interrelated sections. The first addresses the cultural life of HIV/AIDS. The first chapter is devoted to a discussion of research methods. Rodlach explains the difficulty of gathering valid information through conventional quantitative social surveys on sorcery and conspiracy beliefs and practices. He outlines the participant observation case study method that he followed in Bulawayo and other communities in Zimbabwe. With local assistants, he conducted a series of in-depth qualitative interviews over time (approximately one year) detailing peoples’ personal and family experience with HIV/AIDS and how it related to themes of sorcery and conspiracy. Complementing the interviews with historical data, newspaper stories, film clips, and native art, Rodlach created a rich work of ethnography. Chapter 2 describes recent social, political, and economic events in Zimbabwe and how this situation of general decline and crisis was conducive to the emergence of sorcery and conspiracy beliefs about the HIV/AIDS epidemic. Using Social Representations Theory,1 the author explains how sorcery and conspiracy explanations become anchored and objectified in the minds of people struggling to understand their disease. For many Zimbabweans, the government is perceived as corrupt and exploitative, using the AIDS crisis to enrich itself. This is illustrated by a cartoon from the Harare Daily News, which suggests that officials have misappropriated a special AIDS levy earmarked for health services. International corporations and non-governmental organizations (NGOs) are also perceived as working against, not for, the common good. Drug companies aere criticized for profiteering on anti-retroviral therapies and NGOs for squandering on luxurious offices and generous administrative salaries donations meant to support victims of the epidemic.
Betaretroviral Envelope Subunits Are Noncovalently Associated and Restricted to the Mammalian Class

ABSTRACT The structure of the transmembrane subunit (TM) of the retroviral envelope glycoprotein (Env) is highly conserved among most retrovirus genera and includes a pair of cysteines that forms an intramolecular disulfide loop within the ectodomain. Alpha-, gamma-, and deltaretroviruses have a third cysteine, adjacent to the loop, which forms a disulfide bond between TM and the surface subunit (SU) of Env, while lentiviruses, which have noncovalently associated subunits, lack this third cysteine. The Betaretrovirus genus includes Jaagsiekte sheep retrovirus (JSRV) and mouse mammary tumor virus (MMTV), as well as many endogenous retroviruses. Envelope subunit association had not been characterized in the betaretroviruses, but lack of a third cysteine in the TM ectodomain suggested noncovalently associated subunits. We tested the Env proteins of JSRV and MMTV, as well as human endogenous retrovirus K (HERV-K)108—a betaretrovirus-like human endogenous retrovirus—for intersubunit bonding and found that, as in the lentiviruses, the Env subunits lack an intersubunit disulfide bond. Since these results suggest that the number of cysteines in the TM loop region readily distinguishes between covalent and noncovalent structure, we surveyed endogenous retroviral TM sequences in the genomes of vertebrates represented in public databases and found that (i) retroviruses with noncovalently associated subunits have been present during all of anthropoid evolution and (ii) the noncovalent env motif is limited to mammals, while the covalent type is found among five vertebrate classes. We discuss implications of these findings for retroviral evolution, cross-species transmissions, and recombination events involving the env gene.
Reality Orientation Thirty Years Later: Are We Still Confused?

Reality Orientation (RO) intervention represents the first significant attempt at rehabilitation programming for the disoriented, institutionalized elderly. Early anecdotal accounts reported sweeping positive effects. A first sign of hope for this severely disabled population, RO rapidly became widely implemented and continues to be a commonly accepted approach by numerous disciplines. However, careful examination of the research and clinical practice literature reveals many difficulties with the conventional RO classroom programme. Reliable research is limited and weakly supports a modest, temporary gain in verbal orientation after involvement in conventional classroom RO. The actual significance of these gains for these severely disabled elderly persons and their caregivers is doubtful. Although not yet clearly articulated, other approaches (eg. sensory stimulation, environmental manipulation) and a reformulation of RO itself are showing promise of effecting a broader range of functional behaviours (eg. self-feeding). Orientation information presented for reassurance, not re-articulation, is proving to be both more nurturing for clients and more clinically significant.
Development of a model for estimating the size and dynamics of the pet dog population

AbstractA conceptual model was developed to describe the dynamics of the pet dog population. The model synthesizes existing data collected for a variety of purposes to estimate the size of the various components of the pet dog population in Washington and Iowa during 1991. The total population mortality rate was estimated as 12.4% per year. Animal shelters in Washington and Iowa handled 7.6% and euthanized 4.0% of the dog population in those two states. When these estimates were extrapolated to the entire U.S. dog population, the model predicted that the total annual turnover in owned dogs was 14.7%, or 7.71 million dogs, that 4 million dogs were handled by animal shelters, and that 2.1 million were euthanized. It was also estimated that 79% of all female dogs were spayed, that household breeding could be attributed to less than one-fifth (18.7%) of the female dogs in the reproductive pool, and that the number of owners contributing to total dog population turnover through failure to retain their dog (103.
Intracellular Signaling Mechanisms and Activities of Human Herpesvirus 8 Interleukin-6

ABSTRACT Human herpesvirus 8 (HHV-8)-encoded viral interleukin-6 (vIL-6) has been implicated as a key factor in virus-associated neoplasia because of its proproliferative and survival effects and also in view of its angiogenic properties. A major difference between vIL-6 and human IL-6 (hIL-6) is that vIL-6, uniquely, is largely retained and can signal intracellularly. While vIL-6 is generally considered to be a lytic gene, several reports have noted its low-level expression in latently infected primary effusion lymphoma (PEL) cultures, in the absence of other lytic gene expression. Thus, intracellular autocrine signal transduction by the viral cytokine may be of particular relevance to the growth and survival of latently infected cells and to pathogenesis. Here we report that most intracellular vIL-6 is located in the endoplasmic reticulum (ER), signals via the gp130 signal transducer in this compartment, and does so independently of the gp80 α-subunit of the IL-6 receptor, required for hIL-6 signal transduction. Signaling and biological assays incorporating ER-retained vIL-6 and hIL-6 confirmed vIL-6 activity, specifically, in this compartment. Knockdown of vIL-6 expression in PEL cells led to markedly reduced cell growth in normal culture, independently of extracellular cytokines. This could be reversed by reintroduction via virus vector of exclusively ER-retained vIL-6. These data indicate that in virus biology vIL-6 may act to support the growth and survival of cells latently infected with HHV-8 in an autocrine manner via intracrine signaling and that these activities may contribute to the maintenance of latently infected cells and to virus-induced neoplasia.
Hepatitis C Virus RNA Replication Requires a Conserved Structural Motif within the Transmembrane Domain of the NS5B RNA-Dependent RNA Polymerase

ABSTRACT Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), the viral RNA-dependent RNA polymerase (RdRp), is a tail-anchored protein with a highly conserved C-terminal transmembrane domain (TMD) that is required for the assembly of a functional replication complex. Here, we report that the TMD of the HCV RdRp can be functionally replaced by a newly identified analogous membrane anchor of the GB virus B (GBV-B) NS5B RdRp. Replicons with a chimeric RdRp consisting of the HCV catalytic domain and the GBV-B membrane anchor replicated with reduced efficiency. Compensatory amino acid changes at defined positions within the TMD improved the replication efficiency of these chimeras. These observations highlight a conserved structural motif within the TMD of the HCV NS5B RdRp that is required for RNA replication.