Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-21 e Driven Neoplasms in SJL Mice Mimic Some Key Features of Human Angioimmunoblastic T-Cell Lymphoma

SJL/J mice exhibit a high incidence of mature B-cell lymphomas that require CD4 þ T cells for their development. We found that their spleens and lymph nodes contained increased numbers of germinal centers and T follicular helper (T FH ) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. We developed IL-21 receptor (IL21R) e de ﬁ cient Swiss Jim Lambart (SJL) mice to determine the role of IL-21 in disease. These mice had reduced numbers of T FH cells, lower serum levels of IL-21, and few germinal center B cells, and they did not develop B-cell tumors, suggesting IL-21 e dependent B-cell lymphomagenesis. We also noted a series of features common to SJL disease and human angioimmunoblastic T-cell lymphoma (AITL), a malignancy of T FH cells. Gene expression analyses of AITL showed that essentially all cases expressed elevated levels of transcripts for IL21 , IL21R , and a series of genes associated with T FH cell development and function. These results identify a mouse model with features of AITL and suggest that patients with the disease might bene ﬁ t from therapeutic interventions that interrupt IL-21 signaling. (Am J Pathol 2015, 185: 3102 e 3114; http://dx.doi.org/10.1016/j.ajpath.2015.07.021) in exon 5 of the R3ch1n gene. 15 Primers spanning exons 2 and 6 of the gene [exon 2, 5 0 -AATTTGCACTCAGACTTTCGAC-3 0 (forward); exon 6, 5 0 -TGAGACTGATCCCCATAAAGCA-3 0 (reverse)] were used in a 35-cycle PCR with melting at 95 (cid:4) for 30 seconds, annealing at 55 (cid:4) for 30 seconds, and extension at (cid:4) for 1 PCR genome browser.
Small Heat-Shock Proteins Select F508-CFTR for Endoplasmic Reticulum-associated Degradation□D

Secreted proteins that fail to achieve their native conformations, such as cystic fibrosis transmembrane conductance regulator (CFTR) and particularly the F508-CFTR variant can be selected for endoplasmic reticulum (ER)-associated degradation (ERAD) by molecular chaperones. Because the message corresponding to HSP26, which encodes a small heat-shock protein (sHsp) in yeast was up-regulated in response to CFTR expression, we examined the impact of sHsps on ERAD. First, we observed that CFTR was completely stabilized in cells lacking two partially redundant sHsps, Hsp26p and Hsp42p. Interestingly, the ERAD of a soluble and a related integral membrane protein were unaffected in yeast deleted for the genes encoding these sHsps, and CFTR polyubiquitination was also unaltered, suggesting that Hsp26p/ Hsp42p are not essential for polyubiquitination. Next, we discovered that F508-CFTR degradation was enhanced when a mammalian sHsp, A-crystallin, was overexpressed in human embryonic kidney 293 cells, but wild-type CFTR biogenesis was unchanged. Because A-crystallin interacted preferentially with F508-CFTR and because purified A-crystallin suppressed the aggregation of the first nucleotide-binding domain of CFTR, we suggest that sHsps maintain the solubility of F508-CFTR during the ERAD of this polypeptide.
Alcohol Involvement in Homicide Victimization in the U.S

, Abstract Background— Although the association between alcohol and homicide is well documented, there has been no recent study of alcohol involvement in homicide victimization in U.S. states. The objective of this paper was to determine the prevalence of alcohol involvement in homicide victimization and identify socio-demographic and other factors associated with alcohol involvement in homicide victimization. Methods— Data from homicide victims with a reported blood alcohol content (BAC) level were analyzed from 17 states from 2010–12 using the National Violent Death Reporting System. Logistic regression was used to investigate factors associated with the odds of homicide victims having a BAC ≥0.08%. Results— Among all homicide victims, 39.9% had a positive BAC including 13.7% with a BAC between 0.01%–0.79% and 26.2% of victims with a BAC ≥0.08%. Males were twice as likely as females to have a BAC ≥0.08% (29.1% vs. 15.2%; p < 0.001). Characteristics that were independent predictors of homicide victims having a BAC ≥0.08 included male sex, American Indian/Alaska Native race, Hispanic ethnicity, history of intimate partner violence, and non-firearm homicides. Future studies should explore the relationships between state-level alcohol policies and alcohol-involvement among perpetrators and victims of homicide.
T Cells Stimulated by an Analog Peptide of Type II Collagen Require FcR γ to Secrete IL-4 and Suppress Autoimmune Arthritis

Objective— Using the collagen-induced arthritis (CIA) model, we explored the characteristics of the T cell population which responds to an analog peptide (A9) of type II collagen (CII) and regulates autoimmunity. Methods— A9 is a 26 amino acid peptide analogous to the sequence of a segment of CII (CII 245-270) but with substitutions made at amino acid positions 260 (alanine for isoleucine), 261 (hydroxyproline for alanine), and 263 (asparagine for phenylalanine). We have previously shown that A9 profoundly suppresses immunity to CII and CIA. In order to determine the mechanism of suppression, we used a transgenic mouse whose T cells express a CII specific receptor (TCR) and performed passive cell transfer experiments. Results— The results demonstrate that suppression of CIA by the A9 is dependent upon T cells. Using multiparameter flow cytometry, we determined that the cells responsible for suppression were CD4+ and expressed high levels of Fc ε RI γ (FcR γ ). To establish the significance of this finding, we obtained mice genetically deficient in FcR γ to perform passive transfer experiments. The resulting FcR γ -/- CD4+ T cells when primed by culture with A9 could not transfer the suppression of arthritis nor secrete cytokines in response to A9. Conclusion— Taken together, these data suggest that the suppression of arthritis and the Th2 cytokine profile elicited by A9 is dependent upon the presence of FcR γ in the T cells. These findings are novel and may have therapeutic potential for patients with autoimmune arthritis.
IN VITRO PROPAGATION AND HOMING OF LIVER-DERIVED DENDRITIC CELL PROGENITORS TO LYMPHOID TISSUES OF ALLOGENEIC RECIPIENTS: Implications for the Establishment and Maintenance of Donor Cell Chimerism Following Liver Transplantation1,,2

Dendritic cell (DC) progenitors were propagated in liquid culture from nonparenchymal cells resident in normal mouse (B10.BR; H-2 k , I-E + ) liver in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The liver-derived DC progenitors were MHC class H − /dim and did not express counter receptors for CTLA-4, a structural homologue of the T cell activation molecule CD28. Following subcutaneous or intravenous injection, these liver-derived cells migrated to T cell-dependent areas of lymph nodes and spleen of unmodified, allogeneic (B10; H-2 b ; I-E − ) recipients, where they were identified 1-5 days, and 1 and 2 months after injection by their strong surface expression of donor MHC class II (I-E k ) and their dendritic morphology. Maximal numbers of liver-derived DC in the spleen were recorded 5 days after injection. Both clusters of strongly donor MHC class II + cells— and (more rarely) dividing cells—could also be identified, suggesting cell replication in situ. Using the same techniques employed to generate DC progenitors from normal liver, GM-CSF-stimulated cells were propagated for 10 days from the bone marrow and spleen of nonimmunosuppressed mice sacrificed 14 days after orthotopic liver transplantation (B10;H-2 b → C3H;H-2 k ). Immunocytochemical staining for recipient and donor MHC class II phenotype revealed the growth both of host cells with DC characteristics, and of cells expressing donor alloantigens (I-A b . These results are consistent with the growth, in response to GM-CSF, of donor-derived DC from progenitors seeded from the liver allograft to recipient lymphoid tissue. The functional activity of the progenitors of chimeric DC and the possible role of these cells in the establishment and maintenance of donor-specific tolerance following liver transplantation remain to be determined. Transplantation
Respiratory Sinus Arrhythmia Reactivity across Empirically-BasedStructural Categories of Psychopathology Among Adults: AMeta-Analysis

Low resting respiratory sinus arrhythmia (RSA) is observed in many mental health conditions, including anxiety disorders, mood disorders, schizophrenia spectrum disorders, disruptive behavior disorders, and nonsuicidal self-injury, among others. Findings for RSA reactivity are more mixed. We evaluate associations between RSA reactivity and empirically-derived structural categories of psychopathology—including internalizing, externalizing, and thought problems— among physically healthy adults. We searched multiple electronic databases for studies of RSA among participants who were assessed either dimensionally using well-validated measures or diagnostically using structured interviews. Strict inclusion criteria were used to screen 3,605 published reports, which yielded 37 studies including 2,347 participants and 76 effect sizes. We performed a meta-analysis, with meta-analytic regressions of potential moderators, including psychopathology subtypes. The sample-wide meta-analytic association between RSA reactivity and psychopathology was quite small, but heterogeneity was considerable. Moderation analyses revealed significant RSA reactivity (withdrawal) specifically in externalizing samples. Additional moderators included (a) stimulus conditions used to elicit RSA reactivity (only negative emotion inductions were effective), (b) sex (women showed greater RSA reactivity than men), and (c) adherence to established methodological guidelines (e.g., higher electrocardiographic sampling rates yielded greater RSA reactivity). These findings indicate that associations between RSA reactivity and psychopathology are complex, and suggest that future studies should include more standardized RSA assessments to increase external validity and decrease measurement error.
Derivatives of Procaspase-Activating Compound 1 (PAC-1) and Anticancer Activities

PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an in-depth discussion of four derivatives on which extensive studies have been performed.
Timing of first dental recall visits for newly Medicaid-enrolled children with an intellectual or developmental disability in Iowa

, Abstract This study compared the extent to which having an intellectual or developmental disability (IDD) is associated with the rates at which newly Iowa Medicaid-enrolled children ages 3–8 had a first dental recall visit. We used survival analytic techniques to test our hypothesis that children with an IDD would have later first dental recall visits than children without an IDD. Our results suggest no significant difference in the time to first dental recall for children by IDD status (p=.99). After adjusting for covariates, the only factor associated with earlier first dental recalls was the length of time from enrollment in Medicaid to the first comprehensive dental visit. Children for whom it took >13 months to see a dentist for their first comprehensive dental visit were 1.68 times as likely to have an earlier first dental recall as children who had their first comprehensive dental visit within 4 months of enrolling in Medicaid (p<.0001). We found that having an IDD was not associated with later first dental recall visits for newly Medicaid-enrolled children ages 3–8 in Iowa. Future work should identify other factors associated with poor oral health for Medicaid-enrolled children with an IDD.
THE HSV VECTOR Δ RR DELIVERS THE ANTI-APOPTOTIC PROTEIN ICP10PK AND PREVENTS APOPTOSIS AND LOSS OF FUNCTION IN KAINIC ACID TREATED ORGANOTYPIC HIPPOCAMPAL CULTURES THROUGH ERK AND AKT ACTIVATION

We have previously shown that the HSV-2 anti-apoptotic protein ICP10PK is delivered by the replication incompetent virus mutant Δ RR and prevents kainic acid (KA)-induced epileptiform seizures and neuronal cell loss in the mouse and rat models of temporal lobe epilepsy. The present studies used Δ RR and the ICP10PK deleted virus mutant Δ PK, to examine the mechanism of neuroprotection. Δ RR-infected neuronal cells expressed a chimeric protein in which ICP10PK was fused in frame to LacZ (p175) while retaining ICP10PK kinase activity. Δ PK-infected neuronal cells expressed a mutant ICP10 protein that is deleted in PK domain and is kinase negative (p95). p175 and p95 were expressed in CA3 (86±3%) and CA1 (69±7%) cells from Δ RR or Δ PK-infected organotypic hippocampal cultures (OHC) and 80–85% of the ICP10 positive cells co-stained with antibody to β III Tubulin (neuronal marker). Δ RR, but not Δ PK, inhibited KA-induced cell death and caspase-3 activation in CA3 neurons and inhibition was seen whether Δ RR was delivered 2 days before, or 2 days after KA administration (95 % neuroprotection). Neuroprotection was associated with ERK and Akt activation and was abrogated by simultaneous treatment with the MEK (U0126) and PI3-K (LY294002) inhibitors. Increased expression of the anti-apoptotic protein Bag-1 and the transcription factor CREB, and decreased expression of the pro-apoptotic protein Bad were associated with Δ RR-mediated neuroprotection and the surviving neurons retained normal synaptic function. The data indicate that Δ RR is a promising platform for neuroprotection from excitotoxic injury.
Major Technical Advances Longitudinal, Noninvasive Monitoring of Compensatory Lung Growth in Mice after Pneumonectomy via 3 He and 1 H Magnetic Resonance Imaging

Inrodentsandsomeothermammals,partialpneumonectomy(PNX) ofadultlungsresultsinrapidcompensatorylunggrowth.Inthepast,quantiﬁcationofcompensatorylunggrowthandrealveolarization could only be accomplished after killing the animal, removal of lungs, and histologic analysis of lungs at single time points. Hyperpolarized 3 He diffusion magnetic resonance imaging (MRI) allows in vivo morphometry of human lungs; our group has adapted this technique for application to mouse lungs. Through imaging, we can obtain maps of lung microstructural parameters that allow quantiﬁ- cation of morphometric and physiologic measurements. In this study, we employed our 3 He MRI technique to image in vivo morphometry at baseline and to serially assess compensatory growth afterleftPNXofmice. 1 Handhyperpolarized 3 HediffusionMRIwere performed at baseline (pre-PNX), 3-days, and 30-days after PNX. Compared with the individual mouse’s own baseline, MRI was able to detect and serially quantify changes in lung volume, alveolar sur-facearea,alveolarnumber,andregionalchangesinalveolarsizethatoccurredduringthecourseofpost-PNXlunggrowth.Theseresults are consistent with morphometry measurements reported in the literature for mouse post-PNX compensatory lung growth. In addi-tion, we were also able to serially assess and quantify changes in the physiologicparameteroflungcomplianceduringthecourseofcom-pensatorylunggrowth;thiswasconsistentwithﬂexiVentdata. With these techniques, we now have a noninvasive, in vivo method to serially assess the effectiveness of therapeutic interventions on post-PNX lung growth in the same mouse. technique to visualize and quantitate neoalveolarization in the mouse after pneumonectomy. This opens avenues of inquiry related to lung injury and repair, normal and compensatory lung growth, and alveolar simpliﬁcation during development.
Prevalence of Pragmatically-Defined High Cardiovascular Risk and Its Correlates in Ten Low- and Middle-Income Areas in Africa, Asia and South America

Background—Current available tools for assessing high cardiovascular risk (HCR) often require measurements not available in resource-limited settings in lowand middle-income countries (LMICs). There is a need to assess HCR using a pragmatic evidence-based approach. Carrillo-Larco et al. Page 2 Glob Heart. Author manuscript; available in PMC 2017 March 01. A uhor M anscript
FallSense: An Automatic Fall Detection and Alarm Generation System in IoT-Enabled Environment

In this paper, we elaborate the design, implementation, and testing of a system—FallSense, which is able to detect accidental falls of human beings in a precise way. The distinguishing feature of FallSense is its endeavors beyond the scope of accelerometer, which is a component of traditional body sensor network. Along with this acceleration measuring unit, FallSense uses the benefits of an Internet-of-Things-enabled environment, which consists of a number of infrared transmitter–receiver pairs and ultrasonic sensors. Employing a fuzzy inference system, FallSense fuses the data from multiple sensors and becomes over sure before inferring that a fall has occurred. Depending on the inputs from multiple sensors, FallSense generates a value between 0 and 1, which signifies the chance of fall. Results show that multi-sensor-based FallSense achieves overall 16% improvement in comparison with the existing approaches, on an average. Beyond the theoretical modeling, this paper also practically implemented the same with the help of the real-sensing units.
Acquired Chromosomal Anomalies in Chronic Lymphocytic Leukemia (CLL) Patients Compared to >50,000 Quasi-normal Subjects

and Abstract Pre-therapy CLL patients from US Intergroup trial E2997 were analyzed with single nucleotide polymorphism microarrays to detect acquired chromosomal anomalies. The four CLL-typical anomalies (11q-, +12, 13q- and 17p-) were found at expected frequencies. Acquired anomalies in other regions account for 70% of the total detected and their number per subject has a significant effect on progression-free survival after adjusting for the effects of 17p- (and other covariates). These results were compared with a previous study of >50,000 subjects from the GENEVA consortium of genome-wide association studies, which analyzed individuals with a variety of medical conditions and healthy controls. The percentage of individuals with acquired anomalies is vastly different between the two studies (GENEVA 0.8%; E2997 80%). The composition also differs, with GENEVA having a higher percentage of acquired uniparental disomies and a lower percentage of deletions. The four common CLL anomalies are among the most frequent in GENEVA subjects, some of whom may have CLL-precursor conditions or early stages of CLL. However, the patients from E2997 (and other studies of symptomatic CLL) have recurrent acquired anomalies that were not found in GENEVA subjects, thus identifying genomic changes that may be unique to symptomatic stages of CLL.
Age-Related Changes in Associative Memory for Emotional and Non-emotional Integrative Representations

Events often include novel combinations of items. Sometimes, through the process of integration, we experience and remember these items as parts of a whole rather than as separate entities. Recent research with younger adults has demonstrated that successfully integrating two nonemotional items at encoding, instead of imagining them separately, produces a disproportionately larger associative memory benefit than integrating an emotional and a non-emotional item (Murray & Kensinger, 2012). In the first study to examine whether age and emotion interact to influence integration, we use two measures of integrative success – the ability to successfully retrieve integrations, measured through associative cued recall, and the ability to successfully generate integrated representations at encoding, measured through self report. The cued recall results (Expt. 1 and 2) reveal that the emotional content of the word pairs interacts to influence the effect of integration on older adults’ associative memory, but in the opposite direction of younger adults: Older adults show no associative retrieval benefit of integration over non-integration for non-emotional pairs, but they show a significant integrative benefit for emotional pairs. We also demonstrate (Expt. 2) that encoding time interacts with emotion and integration in different ways for older and younger adults: Putting younger adults under time pressure reduces their success in generating integrated representations at encoding for non-emotional pairs, whereas for older adults it disrupts their ability to generate integrated representations for emotional pairs. We discuss possible age-related differences in the processes used to create emotional and non-emotional integrations.
Further adventures of a thermally pulsing star

Eight more thermal pulses have been calculated for a 7 M/sub sun/ model star with a carbon-oxygen core of mass 0.95--0.96 M/sub sun/. From the 10th to the 18th pulse, the maximum helium-burning luminosity, the maximum temperature at the base of the convective shell, and the amount of matter containing fresh carbon that is dredged up by the convective envelope increase, respectively, from 1.6 x 10/sup 6/ L/sub sun/, 286 x 10/sup 6/ K, and 3.5 x 10/sup -5/ M/sub sun/ to 5.5 x 10/sup 6/ L/sub sun/, 310 x 10/sup 6/ K, and approx.4. 0 x 10/sup -4/ M/sub sun/. The mass of carbon-rich matter dredged up near the end of the 18th pulse is over one-third of the mass through which the hydrogen-burning shell has advanced during the preceding interpulse phase.It is shown that the failure of the outer edge of the convective shell to reach the hydrogen-helium interface is a consequence of an ''entropy barrier'' set up through this interface during the interpulse phase and that radiation pressure is the dominant contributor to the magnitude of this barrier. Similarly, the dredging-up phenomenon can be understood in terms of widely different rates of entropy change on either side ofmore » the hydrogen-helium interface.Finally, it is shown that, during the dredging-up process, a discontinuity in the radiative gradient at the base of the envelope convective region may lead to overshoot, one consequence of which is the formation of /sup 22/Ne in a convective shell at an abundance exceeding the abundance of CNO elements at the surface. This has ramifications for the production of light s-process elements (/sup 23/Na.-->./sup 30/Si) in Population II stars of intermediate mass during the early history of the Galaxy. (AIP)« less
Soluble Amyloid b Peptide Concentration as a Predictor of Synaptic Change in Alzheimer’s Disease

We have characterized amyloid b peptide (A b ) concentration, A b deposition, paired helical filament formation, cerebrovascular amyloid angiopathy, apolipoprotein E (ApoE) allotype, and synaptophysin concentration in entorhinal cortex and superior frontal gyrus of normal elderly control (ND) patients, Alzheimer’s disease (AD) patients, and high pathology control (HPC) patients who meet pathological criteria for AD but show no synapse loss or overt antemortem symptoms of dementia. The measures of A b deposition, A b -immunoreactive plaques with and without cores, thioflavin histofluorescent plaques, and concentrations of insoluble A b , failed to distinguish HPC from AD patients and were poor correlates of synaptic change. By contrast, concentrations of soluble A b clearly distinguished HPC from AD patients and were a strong inverse correlate of synapse loss. Further investigation revealed that A b 40, whether in soluble or insoluble form, was a particularly useful measure for classifying ND, HPC, and AD patients compared with A b 42. A b 40 is known to be elevated in cerebrovascular amyloid deposits, and A b 40 (but not A b 42) levels, cerebrovascular amyloid angiopathy, and ApoE4 allele frequency were all highly correlated with each other. Although paired