Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Characterization of CD300H, a New Member of the Human CD300 Immunoreceptor Family*

Background: CD300 family molecules regulate innate immune responses. Results: We identified and characterized a novel immunoreceptor, CD300H. Conclusion: CD300H mediates neutrophil chemoattractant production. Significance: CD300H may play an important role in innate immunity. Recruitment of circulating monocytes and neutrophils to infection sites is essential for host defense against infections. Here, we identified a previously unannotated gene that encodes an immunoglobulin-like receptor, designated CD300H, which is located in the CD300 gene cluster. CD300H has a short cytoplasmic tail and associates with the signaling adaptor proteins, DAP12 and DAP10. CD300H is expressed on CD16+ monocytes and myeloid dendritic cells. Ligation of CD300H on CD16+ monocytes and myeloid dendritic cells with anti-CD300H monoclonal antibody induced the production of neutrophil chemoattractants. Interestingly, CD300H expression varied among healthy subjects, who could be classified into two groups according to “positive” and “negative” expression. Genomic sequence analysis revealed a single-nucleotide substitution (rs905709 (G→A)) at a splice donor site on intron 1 on either one or both alleles. The International HapMap Project database has demonstrated that homozygosity for the A allele of single nucleotide polymorphism (SNP) rs905709 (“negative” expression) is highly frequent in Han Chinese in Beijing, Japanese in Tokyo, and Europeans (A/A genotype frequencies 0.349, 0.167, and 0.138, respectively) but extremely rare in Sub-Saharan African populations. Together, these results suggest that CD300H may play an important role in innate immunity, at least in populations that carry the G/G or G/A genotype of CD300H.
Health-related quality of life among cognitively intact nursing home residents with and without cancer – a 6-year longitudinal study

Background Limited information exists regarding the natural development of health-related quality of life (HRQOL) and its determinants among mentally intact nursing home (NH) residents. We aimed to examine HRQOL over time during a 6-year period among residents of NHs, who are not cognitively impaired, and to examine whether sense of coherence and a diagnosis of cancer influence HRQOL. Methods The study was prospective and included baseline assessment and 6-year follow-up. After baseline assessment of 227 cognitively intact NH residents (Clinical Dementia Rating score ≤ 0.5), we interviewed 52 living respondents a second time at the 5-year follow-up and 18 respondents a third time at the 6-year follow-up. We recorded data from the interviews using the Short Form-36 (SF-36) Health Survey and the Sense of Coherence Scale. To study different developments over time for residents without and with cancer, we tested interactions between cancer and time. Results The subscores of physical functioning and role limitation–physical domains declined with time (P < 0.001 and P = 0.02, respectively). Having a diagnosis of cancer at baseline was negatively correlated with general health (P = 0.002). Sense of coherence at baseline was positively correlated with all the SF-36 subscores from baseline to follow-up (P < 0.001). Conclusion The study indicates that the HRQOL changed over time during the 6 years of follow-up, and the sense of coherence appeared to be an important component of the HRQOL. Finally, our results showed that having a diagnosis of cancer was associated with decline in the general health subdimension.
Coinfection with the Intestinal Nematode Heligmosomoides polygyrus Markedly Reduces Hepatic Egg-Induced Immunopathology and Proinflammatory Cytokines in Mouse Models of Severe Schistosomiasis

ABSTRACT Infection with the trematode helminth Schistosoma mansoni results in a parasite egg-induced, CD4 T-cell-mediated, hepatointestinal granulomatous and fibrosing inflammation that varies greatly in severity, with a higher frequency of milder forms typically occurring in regions where the disease is endemic. One possible explanation for this is that in these regions the degree of inflammation is lessened by widespread concurrent infection with gastrointestinal nematodes. We tested this hypothesis by establishing a murine coinfection model in which mice were infected with the intestinal nematode parasite Heligmosomoides polygyrus prior to infection with S. mansoni. In CBA mice that naturally display a severe form of schistosomiasis, preinfection with H. polygyrus resulted in a marked reduction in schistosome egg-induced hepatic immunopathology, which was associated with significant decreases in the levels of interleukin-17 (IL-17), gamma interferon, tumor necrosis factor alpha, IL-23, IL-6, and IL-1β and with increases in the levels of IL-4, IL-5, IL-10, and transforming growth factor β in mesenteric lymph node cells, purified CD4 T cells, and isolated liver granuloma cells. There also were increases in liver Ym1 and forkhead box P3 transcription factor expression. In another model of high-pathology schistosomiasis induced in C57BL/6 mice by immunization with schistosome egg antigens in complete Freund's adjuvant, coinfection with the nematodes also resulted in a marked inhibition of hepatic immunopathology accompanied by similar shifts in cytokine production. These findings demonstrate that intestinal nematodes prevent Th1- and Th17-cell-mediated inflammation by promoting a strong Th2-polarized environment associated with increases in the levels of alternatively activated macrophages and T regulatory cells, which result in significant amelioration of schistosome-induced immunopathology.
In silico optimization of phase-change materials for digital memories: a survey of first-row transition-metal dopants for Ge2Sb2Te5

Phase-change materials are the alloys at the heart of an emerging class of next-generation, non-volatile digital memory technologies. However, the widely studied Ge–Sb–Te system possesses several undesirable properties, and enhancing its properties, e.g. by doping, is an area of active research. Various first-row transition-metal dopants have been shown to impart useful property enhancements, but a systematic study of the entire period has yet to be undertaken, and little has been done to investigate their interaction with the host material at the atomic level. We have carried out first-principles computer simulations of the complete phase-change cycle in Ge2Sb2Te5 doped with each of the ten first-row transition metals. In this article, we present a comprehensive survey of the electronic, magnetic and optical properties of these doped materials. We discuss in detail their atomic-level structure, and relate the microscopic behaviours of the dopant atoms to their influence on the Ge2Sb2Te5 host. By considering an entire family of similar materials, we identify trends and patterns which might be used to predict suitable dopants for optimizing materials for specific phase-change applications. The computational method employed here is general, and this materials-discovery approach could be applied in the future to study other families of potential dopants for such materials.
Physical abuse among depressed women

AbstractOBJECTIVE: To provide estimates of physical abuse and use of health services among depressed women in order to inform efforts to increase detection and treatment of physical abuse. DESIGN: Retrospective assessment of abuse and health services use over 1 year in a cohort of depressed women. SETTING: Statewide community sample from Arkansas. PARTICIPANTS: We recruited 303 depressed women through random-digit-dial screening. MEASUREMENTS AND MAIN RESULTS: Exposure to physical abuse based on the Conflict Tactics Scale, multi-informant estimate of health and mental health services. Over half of the depressed women (55.2%) reported experiencing physical abuse as adults, with 14.5% reporting abuse during the study year. Women abused as adults had significantly more severe depressive symptoms, more psychiatric comorbidity, and more physical illnesses than nonabused women. After controlling for sociodemographic and severity-of-illness factors, recently abused, depressed women were much less likely to receive outpatient care for mental health problems as compared to other depressed women (odds ratio [OR] 0.3; p=.013), though they were more likely to receive health care for physical problems (OR 5.7, p=.021). CONCLUSIONS: Because nearly all depressed women experiencing abuse sought general medical rather than mental health care during the year of the study, primary care screening for physical abuse appears to be a critical link to professional help for abused, depressed women. Research is needed to inform primary care guidelines about methods for detecting abuse in depressed women.
Surfactant lavage decreases systemic interleukin‐1β production in meconium aspiration syndrome

Background: Surfactant lavage has been used to remove meconium debris in meconium aspiration syndrome (MAS), but the influence of surfactant lavage on pro‐inflammatory cytokines and cellular apoptosis is unclear. The aim of this study was to investigate the response of pro‐inflammatory cytokine and the influence on alveolar cellular apoptosis using therapeutic bronchoalveolar lavage with diluted surfactant to treat MAS.
Increased insulin resistance and fat cell lipolysis in obese but not lean women with a high waist/hip ratio

Abstract. Increased lipolysis in abdominal adipocytes has been suggested to be of importance for the insulin resistance typical for abdominal obesity. In order to differentiate between fat distribution, measured as waist/hip ratio (WHR), and amount of body fat, glucose disposal during a euglycaemic clamp as well as lipolysis in isolated cells from abdominal and gluteo‐femoral regions were studied in 20 obese and 20 lean postmenopausal women with a high (n= 10) and low (n= 10) WHR, respectively.
Performance Study of a Torsional Wave Sensor and Cervical Tissue Characterization

A novel torsional wave sensor designed to characterize mechanical properties of soft tissues is presented in this work. Elastography is a widely used technique since the 1990s to map tissue stiffness. Moreover, quantitative elastography uses the velocity of shear waves to achieve the shear stiffness. This technique exhibits significant limitations caused by the difficulty of the separation between longitudinal and shear waves and the pressure applied while measuring. To overcome these drawbacks, the proposed torsional wave sensor can isolate a pure shear wave, avoiding the possibility of multiple wave interference. It comprises a rotational actuator disk and a piezoceramic receiver ring circumferentially aligned. Both allow the transmission of shear waves that interact with the tissue before being received. Experimental tests are performed using tissue mimicking phantoms and cervical tissues. One contribution is a sensor sensitivity study that has been conducted to evaluate the robustness of the new proposed torsional wave elastography (TWE) technique. The variables object of the study are both the applied pressure and the angle of incidence sensor–phantom. The other contribution consists of a cervical tissue characterization. To this end, three rheological models have fit the experimental data and a static independent testing method has been performed. The proposed methodology permits the reconstruction of the mechanical constants from the propagated shear wave, providing a proof of principle and warranting further studies to confirm the validity of the results.
Viral IL-10 Gene Transfer Prolongs Rat Islet Allograft Survival

Islet transplantation is a potential cure for diabetes. However, allotransplant rejection severely limits its clinical application. In this study, we sought to transfect rat islets with an adenoviral vector containing the viral IL-10 (vIL-10) gene and examine its efficacy in preventing graft rejection. The immunosuppressive effect of vIL-10 is reported but its efficacy is somehow debatable in transplantation model. vIL-10 transfected islets were transplanted into streptozotocin-induced diabetic rats. Blood glucose, serum vIL-10 concentration, graft histology, and graft cytokine expression were used to monitor graft function up to day 21 after transplantation. Transfected islets released a large amount of vIL-10 protein without affecting their viability and functional integrity. When we transplanted the transfected islets into allogeneic hosts, the survival of grafted islets was not significantly increased. However, the combined use of vIL-10 and subtherapeutic doses of CsA (cyclosporine) significantly prolonged graft survival beyond that achieved with either agent alone (p < 0.001). vIL-10 and CsA-treated rats contain high level of vIL-10 in serum, which is evidenced by the inhibition of allogeneic mixed lymphocyte reaction (MLR). Histological analysis additionally revealed the presence of viable islets up to 21 days. IL-10 mRNA expression in grafted liver was higher and IFN-γ mRNA was lower in vIL-10 and CsA-treated animals, compared with other groups. The synergistic effect of this combination therapy is potentially correlated with the induction of inhibitory cytokine secretion and downregulation of proinflammatory cytokine secretion from host cells.
Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers

Two monoclonal antibodies, 3.14. A3 and 1.10. F3, raised against a delipidated preparation of the human milk fat globule and characterized as epithelium‐specific (Taylor‐Papadimitriou et al., 1981) were assayed histologically, by an indirect immunoperoxidase technique, against formalin‐fixed, paraffin‐embedded, normal and tumour tissue sections, in order to establish their in vivo specificity. Both antibodies bound to less than 10% of the alveoli and ducts in the resting breast, but bound to all areas of alveoli, ducts and secretion in the lactating breast. Binding was to the luminal surface of the alveolar and ductal epithelium. Antibody 3.14. A3 showed positive reactions with each of 20 primary breast carcinomas tested, and with metastatic lesions in lymph nodes from six of these. Antibody 1.10. F3 also reacted with most of the primary carcinomas but not with those of the mucoid type nor with metastatic lesions in lymph nodes. When tested against a variety of normal tissues, 1.10. F3 bound only to the luminal epithelial surface of classically defined exocrine glands, to their associated ducts and to the collecting tubules of kidney and bronchioles of the lung. 3.14. A3 showed a similar pattern of binding to 1.10. F3 but also bound to sweat glands, the alveolar epithelium of lung and the luminal epithelium of the ductuli efferentes of the epididymis. The only tumours, other than breast, showing a positive reaction with the antibodies were adenocarcinomas of the lung, uterus and ovary.
Functionally important correlated motions in the single-stranded DNA-binding protein encoded by filamentous phage Pf3.

To elucidate the interplay between different parts of dimeric single-stranded DNA-binding proteins we have studied the correlated motions in the protein encoded by filamentous phage Pf3 via the combined use of 15N-NMR relaxation experiments, molecular dynamics simulations and essential dynamics calculations. These studies provide insight into the mechanism underlying the protein-DNA binding reaction. The most important motions can be described by a few essential modes. Most outstanding is the correlated symmetric motion of the DNA-binding wings, which are far apart in the structure. This motion determines the access of DNA to the DNA-binding domain. A correlation between the motion of the DNA-binding wing and the complex loop is indicated to play a role in the cooperative binding of the protein to DNA. These motions are in the nanosecond regime in correspondence with the 15N-NMR relaxation experiments.
Whole‐Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights the Importance of Microhomology in the Mechanism of Formation

Most balanced translocations are thought to result mechanistically from nonhomologous end joining or, in rare cases of recurrent events, by nonallelic homologous recombination. Here, we use low‐coverage mate pair whole‐genome sequencing to fine map rearrangement breakpoint junctions in both phenotypically normal and affected translocation carriers. In total, 46 junctions from 22 carriers of balanced translocations were characterized. Genes were disrupted in 48% of the breakpoints; recessive genes in four normal carriers and known dominant intellectual disability genes in three affected carriers. Finally, seven candidate disease genes were disrupted in five carriers with neurocognitive disabilities (SVOPL, SUSD1, TOX, NCALD, SLC4A10) and one XX‐male carrier with Tourette syndrome (LYPD6, GPC5). Breakpoint junction analyses revealed microhomology and small templated insertions in a substantive fraction of the analyzed translocations (17.4%; n = 4); an observation that was substantiated by reanalysis of 37 previously published translocation junctions. Microhomology associated with templated insertions is a characteristic seen in the breakpoint junctions of rearrangements mediated by error‐prone replication‐based repair mechanisms. Our data implicate that a mechanism involving template switching might contribute to the formation of at least 15% of the interchromosomal translocation events.
Direct and indirect effects of early-life environment on lifetime fitness of bighorn ewes

Cohort effects, when a common environment affects long-term performance, can have a major impact on population dynamics. Very few studies of wild animals have obtained the necessary data to study the mechanisms leading to cohort effects. We exploited 42 years of individual-based data on bighorn sheep to test for causal links between birth density, body mass, age at first reproduction (AFR), longevity and lifetime reproductive success (LRS) using path analysis. Specifically, we investigated whether the effect of early-life environment on lifetime fitness was the result of indirect effects through body mass or direct effects of early-life environment on fitness. Additionally, we evaluated whether the effects of early-life environment were dependant on the environment experienced during adulthood. Contrary to expectation, the effect on LRS mediated through body mass was weak compared to the effects found via a delay in AFR, reduced longevity and the direct effect of birth density. Birth density also had an important indirect effect on LRS through reduced longevity, but only when adult density was high. Our results show that the potential long-term consequences of a harsh early-life environment on fitness are likely to be underestimated if investigations are limited to body mass instead of fitness at several life stages, or if the interactions between past and present environment are ignored.
Family physicians' roles in cancer care. Survey of patients on a provincial cancer registry.

OBJECTIVE To describe cancer patients' experience of the role of family physicians (FPs) in their care. DESIGN Mail survey of a random sample of patients from the Manitoba Cancer Registry. SETTING Manitoba. PARTICIPANTS Two hundred two adults, 6 to 12 months after diagnosis. MAIN OUTCOME MEASURES Proportion needing different kinds of help from FPs and their rating of FPs' response; FACT-G quality-of-life score. RESULTS Response rate was 56.6%; two thirds of the sample were in the follow-up phase. Most (91%) had an FP involved in their care, but FP involvement decreased after diagnosis. The most frequently needed kinds of help (with general medical problems, quick referrals, taking extra time, and quick office appointments) were well provided by FPs, but family support was not. Higher quality-of-life scores were associated with more help with general medical problems, more provision of cancer-related information, and more emotional support of patients and their families. CONCLUSION Family physicians respond well to the most common needs of cancer patients and should be proactive in offering their support to both patients and families.
Phospholipase A2 activity in three species of littoral freshwater rotifers exposed to several toxicants

We analyzed three species of Lecane, a littoral rotifer, for susceptibility to six metals and four organic toxicants using a fluorometric assay based on inhibition of activity of the enzyme phospholipase A2. The metallic toxicants that we tested included Cd, Cr, Cu, Pb, Hg (as HgCl2), and Ti; the organic toxicants included benzene, ethyl acetate, toluene, and vinyl acetate. The three species differed greatly with respect to their susceptibility to the various toxicants. Lecane quadridentata, for example, was particularly sensitive to the four organic compounds (median effective concentration values [EC50] ranged from 6.6 × 10−4–0.987 mg/L). Lecane luna, in contrast, seemed particularly sensitive to metals (EC50 values ranged from 2 × 10−6–1.92 mg/L). Lecane hamata was relatively insensitive to organic solvents (EC50 values ranged from 4.25–126.5 mg/L).
A survey of 460 supernumerary teeth in Brazilian children and adolescents.

OBJECTIVE This study aimed to survey the demographic profile of supernumerary teeth (ST) in Brazilian children and adolescents. METHODS A retrospective analysis was carried out of all nonsyndromic patients with ST attended at the Pediatric Oral Surgery Service of the Universidade Federal de Minas Gerais between 1995 and 2004. Diagnosis of ST was based on clinical and radiographic examination. Chi-squared test was used for statistical analysis. RESULTS This study included 460 ST found in 305 patients. Radiographic assessment (32.1%) was the main care-seeking reason and also the means through which most (97.6%) permanent ST were identified. Most cases were single (63.0%), conical (44.6%), and unerupted (76.8%) ST. Most teeth were fully developed (41.3%), normally orientated (78.9%), placed in a palatal/lingual-sagittal position (84.1%), adjacent to the crown of permanent teeth (50.2%) (P < 0.001). The most frequent clinical complication was permanent teeth displacement (36.0%). Treatment was surgical removal followed by orthodontics (61.6%). CONCLUSIONS The demographic profile of ST herein presented will be useful to provide additional epidemiological information. A wide range of factors should be considered when evaluating ST. In addition, it is essential to detect ST as early as possible to avoid complications and to assure successful management. Even after treatment, patients must be followed up.
VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells.

Apical proteins are sorted and delivered from the trans-Golgi network to the plasma membrane by a mechanism involving sphingolipid-cholesterol rafts. In this paper, we report the effects of changing the levels of VIP17/MAL, a tetraspan membrane protein localized to post-Golgi transport containers and the apical cell surface in MDCK cells. Overexpression of VIP17/MAL disturbed the morphology of the MDCK cell layers by increasing apical delivery and seemingly expanding the apical cell surface domains. On the other hand, expression of antisense RNA directed against VIP17/MAL caused accumulation in the Golgi and/or impaired apical transport of different apical protein markers, i.e., influenza virus hemagglutinin, the secretory protein clusterin (gp80), the transmembrane protein gp114, and a glycosylphosphatidylinositol-anchored protein. However, antisense RNA expression did not affect the distribution of E-cadherin to the basolateral surface. Because VIP17/MAL associates with sphingolipid-cholesterol rafts, these data provide functional evidence that this protein is involved in apical transport and might be a component of the machinery clustering lipid rafts with apical cargo to form apical transport carriers.