Miracle-dz/UniFAR-FTUs huggingface dataset:
Human vascular smooth muscle cells contain functional estrogen receptor.

BACKGROUND The decreased incidence of coronary artery disease observed in postmenopausal women given estrogen (E2) replacement demonstrates an atheroprotective effect of E2 that is generally believed to be mediated by indirect, E2-induced changes in cardiovascular risk factor profiles. We hypothesized that the atheroprotective effect of E2 may be in part mediated by a direct effect of E2 on vascular smooth muscle cells (VSMCs). Therefore, a series of experiments was performed to determine whether human VSMCs contain a competent E2 receptor, a ligand-activated transcription factor known to mediate E2-induced effects in nonvascular cells. METHODS AND RESULTS Ribonuclease protection assays, with a probe derived from the human E2 receptor, were used to demonstrate E2-receptor mRNA in human saphenous vein VSMCs. To show that VSMCs contain E2-receptor protein as well as message, immunoblotting and immunofluorescence studies with a monoclonal anti-E2-receptor antibody were performed, and E2-receptor protein was detected by both methods. Transient transfection assays using a specific E2-responsive reporter system were used next to determine whether the VSMC E2 receptor is capable of E2-induced transcriptional transactivation. Initial studies using mammary artery-derived VSMCs resulted in a 2.4-fold increase in reporter activity in response to 10(-7) mol/L E2. Subsequent studies using saphenous vein VSMCs demonstrated increasing levels of reporter activation as the concentration of E2 was increased from 10(-9) mol/L (1.3-fold increase; SEM, 0.07; P = .05, n = 3) to 10(-7) mol/L (1.6-fold increase; SEM, 0.04; P = .002, n = 6). The specificity of the E2-induced transactivation of the reporter gene was shown by dose-dependent inhibition of transactivation by the pure E2 antagonist ICI 164,384 and by enhancement of the transactivation by simultaneous overexpression of the E2 receptor. CONCLUSIONS We have demonstrated for the first time that human VSMCs express E2-receptor mRNA and protein and that the E2 receptor in VSMCs is capable of estrogen-dependent gene activation. These data suggest a mechanism by which estrogen may directly alter VSMC function.
Loss of Igfbp7 Causes Precocious Involution in Lactating Mouse Mammary Gland

Background Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals. Results We report here that loss of Igfbp7 significantly retards mammary gland development in the virgin animals. More significantly, the pregnant Igfpb7-null glands contained fewer alveolar structures and that during lactation these glands exhibit the morphological changes that are associated with involution. The transcriptome profile of the Igfbp7-null glands on the lactation day 3 revealed a distinct involution-related gene signature compared to the lactating WT glands. Interestingly, we found that the lactating Igfbp7-null glands exhibit increased expression of Stat3 and enhanced activation of (phosphorylated) Stat3, combined with decreased expression of Stat5 suggesting that the absence of Igfbp7 accelerates the onset of involution. We also found that in absence of Igfpb7, the lactating glands contain increased Igfbp5 protein along with decreased expression of IGF-1 Receptor and Akt activation. Finally, we show that during the normal course of involution, Igfbp7 expression is significantly decreased in the mammary gland. Conclusion Our data suggest that loss of Igfbp7 induces precocious involution possibly through diminished cell survival signals. Our findings identify Igfbp7 as major regulator of involution in the mammary gland.
ClinVar: public archive of interpretations of clinically relevant variants

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) at the National Center for Biotechnology Information (NCBI) is a freely available archive for interpretations of clinical significance of variants for reported conditions. The database includes germline and somatic variants of any size, type or genomic location. Interpretations are submitted by clinical testing laboratories, research laboratories, locus-specific databases, OMIM®, GeneReviews™, UniProt, expert panels and practice guidelines. In NCBI's Variation submission portal, submitters upload batch submissions or use the Submission Wizard for single submissions. Each submitted interpretation is assigned an accession number prefixed with SCV. ClinVar staff review validation reports with data types such as HGVS (Human Genome Variation Society) expressions; however, clinical significance is reported directly from submitters. Interpretations are aggregated by variant-condition combination and assigned an accession number prefixed with RCV. Clinical significance is calculated for the aggregate record, indicating consensus or conflict in the submitted interpretations. ClinVar uses data standards, such as HGVS nomenclature for variants and MedGen identifiers for conditions. The data are available on the web as variant-specific views; the entire data set can be downloaded via ftp. Programmatic access for ClinVar records is available through NCBI's E-utilities. Future development includes providing a variant-centric XML archive and a web page for details of SCV submissions.
Long-term outcome of medically confirmed and self-reported early traumatic brain injury in two nationwide samples

Abstract Primary objectives: To assess long-term effects of early traumatic brain injury (TBI) on mental health, cognition, behaviour and adjustment and to identify prognostic factors. Methods and procedures: A 1-year nationwide cohort of all 0–19 year old Icelandic children and adolescents diagnosed with TBI in 1992–1993 (n = 550) received a questionnaire with clinical outcome scales and questions on TBI and socio-economic status (SES) by mail ∼16 years post-injury. A control group (n = 1232), newly selected from the National Registry, received the same questionnaire. Non-respondents answered a shorter version by telephone. Overall participation was 67%. Main outcomes and results: Medically confirmed and self-reported TBI was reflected in worse outcome. Force of impact, number and severity of TBIs predicted poorer results. Parental SES and demographic factors had limited effects. Not reporting early, medically confirmed TBI did not exclude cognitive sequelae. In self-reported disability, absence of evaluation for compensation was not linked to outcome. Conclusions: Clinical outcome was consistent with late complaints attributed to early TBI. TBI-related variables had greater prognostic value than other factors. Self-reporting of TBI sustained very early in life needs supplementary information from parents and medical records. More consistency in compensation evaluations following paediatric TBI is indicated.
PRDE-1 is a nuclear factor essential for the biogenesis of Ruby motif-dependent piRNAs in C. elegans

Piwi-interacting RNAs (piRNAs) are small regulatory RNAs with essential roles in genomic maintenance. Weick et al. identify prde-1 as a novel C. elegans piRNA biogenesis gene. PRDE-1 is required specifically for the production of piRNA precursors from genomic loci containing an upstream motif, the Ruby motif. Intriguingly, the expression of a second class of motif-independent piRNAs is unaffected in prde-1 mutants. This study defines a new paradigm for two distinct classes of piRNAs and provides insights into the biogenesis and function of piRNAs in gene regulation.
Live video adaptation: a context-aware approach

Nowadays, networks can be accessed by multiple devices with different characteristics. Some of these characteristics, such as low processing power and memory capability, restrict the access to multimedia content. Researchers have then focused on developing automatic content adaptations in order to present the data according to devices' capabilities. One method that can be used to achieve content adaptation is the transcoding model. This paper presents a method of exploring context-aware computing in order to adapt video content in a way to be successfully accessed by users with different devices capabilities. It also presents an implementation of the transcoding model using efficient open source tools available in the literature. Finally, the adaptation mechanism is applied in the iClass system, a capture & access application used in lectures.
A Study of the Characteristics and Assimilation of Retrieved MODIS Total Precipitable Water Data in Severe Weather Simulations

Abstract This study determined the accuracy and biases associated with retrieved Moderate Resolution Imaging Spectroradiometer (MODIS) total precipitable water (TPW) data, and it investigated the impact of these data on severe weather simulations using the Weather Research and Forecast (WRF) model. Comparisons of MODIS TPW with the global positioning system (GPS) TPW and radiosonde-derived TPW were carried out. The comparison with GPS TPW over the United States showed that the root-mean-square (RMS) differences between these two datasets were about 5.2 and 3.3 mm for infrared (IR) and near-infrared (nIR) TPW, respectively. MODIS IR TPW data were overestimated in a dry atmosphere but underestimated in a moist atmosphere, whereas the nIR values were slightly underestimated in a dry atmosphere but overestimated in a moist atmosphere. Two cases, a severe thunderstorm system (2004) over land and Hurricane Isidore (2002) over ocean, as well as conventional observations and Special Sensor Microwave Imager (SSM/I.
o-Phenylenediaminium chloride nitrate

In the title molecular salt, C6H10N2 2+·NO3 −·Cl−, the complete cation is generated by a crystallographic mirror plane. The complete nitrate ion is also generated by reflection, with the N atom and one O atom lying on the mirror plane; the chloride ion also lies on the reflection plane. In the crystal, the components are linked by N—H⋯Cl and N—H⋯(N,O) hydrogen bonds, forming (001) layers with the benzene rings projecting into the interlayer regions. The layers are linked by weak C—H⋯O hydrogen bonds, generating a three-dimensional network.
Hemicraniectomy for Massive Middle Cerebral Artery Territory Infarction: A Systematic Review

Background and Purpose— Hemicraniectomy and durotomy have been proposed in many small series to relieve intracranial hypertension and tissue shifts in patients with large hemispheric infarcts, thereby preventing death from herniation. Our objective was to review the literature to identify patients most likely to benefit from hemicraniectomy. Methods— All available individual cases from the English literature were reviewed and analyzed to determine whether age, vascular territory of infarction, side of infarction, reported time to surgery, and signs of herniation predict outcome in patients after hemicraniectomy. All studies included were retrospective and uncontrolled; there were no randomized controlled trials. Results— Of 15 studies screened, 12 studies describing 129 patients met the criteria for analysis; 9 patients treated at our institution were added, for a total of 138 patients. After a minimum follow-up of 4 months, 10 patients (7%) were functionally independent, 48 (35%) were mildly to moderately disabled, and 80 (58%) died or were severely disabled. Of 75 patients who were >50 years of age, 80% were dead or severely disabled compared with 32% of 63 patients ≤50 years of age (P <0.00001). The timing of surgery, hemisphere infarcted, presence of signs of herniation before surgery, and involvement of other vascular territories did not significantly affect outcome. Conclusions— Age may be a crucial factor in predicting functional outcome after hemicraniectomy in patients with large middle cerebral artery territory infarction.
Understanding and living with glaucoma and non-communicable diseases like hypertension and diabetes in the Jhaukhel-Duwakot Health Demographic Surveillance Site: a qualitative study from Nepal

Background Primary open-angle glaucoma (POAG) is one of the most common causes of irreversible blindness. A possible association between POAG and non-communicable diseases such as hypertension and diabetes suggests that the incidence of POAG may increase. People with POAG in Nepal usually present late to hospital and have poor knowledge of glaucoma. Objectives Anticipating a knowledge gap regarding these diseases, this study aimed to explore the knowledge of POAG, hypertension, and diabetes in the community and barriers to health care. Design We conducted this qualitative study in the Jhaukhel-Duwakot Health Demographic Surveillance Site (JD-HDSS), a peri-urban community near Kathmandu, a capital city of Nepal. To study how disease influences knowledge, we conducted focus group discussions separately for men and women with and without pre-existing POAG, hypertension, and diabetes. Data were analyzed using the framework analysis approach. Results Although people suffering from POAG, hypertension, and/or diabetes exhibited adequate knowledge of hypertension and diabetes, they lacked in-depth knowledge of POAG. People believed mostly in internal health locus of control. Perception of disease consequences and impact of disease on daily life was influenced by pre-existing POAG, hypertension, and/or diabetes but only in men. Gender disparity was observed regarding health literacy, health perception, and health barriers, which put women in a more difficult situation to tackle their health. We also revealed a gap between knowledge, attitude, and practice of health among women and healthy men. Conclusion Although people in JD-HDSS exhibited adequate knowledge regarding hypertension and diabetes, they lacked in-depth knowledge about POAG. This study demonstrated gender difference in health literacy and access to health care, making women more vulnerable towards disease. We also demonstrated a gap between knowledge, attitude, and practice of health. However, tailored health literacy programs may bring changes in the health status in the community.
The Roles of Pore Ring and Plug in the SecY Protein-conducting Channel

The protein-conducting channel, or translocon, is an evolutionarily conserved complex that allows nascent proteins to cross a cellular membrane or integrate into it. The crystal structure of an archaeal translocon, the SecY complex, revealed that two elements contribute to sealing the channel: a small “plug” domain blocking the periplasmic region of the channel, and a pore ring composed of six hydrophobic residues acting as a constriction point at the channel's center. To determine the independent functions of these two elements, we have performed molecular dynamics simulations of the native channel as well as of two recently structurally resolved mutants in which portions of their plugs were deleted. We find that in the mutants, the instability in the plug region leads to a concomitant increase in flexibility of the pore ring. The instability is quantified by the rate of water permeation in each system as well as by the force required for oligopeptide translocation. Through a novel simulation in which the interactions between the plug and water were independently controlled, we find that the role of the plug in stabilizing the pore ring is significantly more important than its role as a purely steric barrier.
Selective development of T helper (Th)2 cells induced by continuous administration of low dose soluble proteins to normal and beta(2)- microglobulin-deficient BALB/c mice

Continuous administration of soluble proteins, delivered over a 10-d period by a mini-osmotic pump implanted subcutaneously, induces a long- lasting inhibition of antigen-specific T cell proliferation in lymph node cells from BALB/c mice subsequently primed with antigen in adjuvant. The decreased T cell proliferative response is associated with a down-regulation of the T helper cell (Th)1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma and with a strong increase in the secretion of the Th2 cytokines IL-4 and IL-5 by antigen specific CD4+ T cells. This is accompanied by predominant inhibition of antigen- specific antibody production of IgG2a and IgG2b, rather than IgG1 isotype. Interestingly, inhibition of Th1 and priming of Th2 cells is also induced in beta(2) microglobulin-deficient BALB/c mice, indicating that neither CD8+ nor CD4+ NK1.1+ T cells, respectively, are required. The polarization in Th2 cells is stably maintained by T cell lines, all composed of CD4+/CD8- cells expressing T cell receptor for antigen (TCR) alpha/beta chains, derived from BALB/c mice treated with continuous antigen administration, indicating that they originate from Th2 cells fully differentiated in vivo. This polarization is induced in BALB/c mice by continuous administration of any protein antigen tested, including soluble extracts from pathogenic microorganisms. Priming of Th2 cells is dose dependent and it is optimal for low rather than high doses of protein. Blocking endogenous IL-4 in vivo inhibits expansion of antigen-specific Th2 cells, but does not restore IFN-gamma production by T cells from mice treated with soluble antigen-specific Th2 cells, but does not restore IFN-gamma production by T cells from mice treated with soluble antigen, indicating the involvement of two independent mechanisms. Consistent with this, Th2 cell development, but not inhibition of Th1 cells, depends on non-major histocompatibility complex genetic predisposition, since the Th2 response is amplified in BALB/c as compared to DBA/2, C3H, or C57BL/6 mice whereas tested. These findings support the hypothesis that continuous release of low amounts of protein antigens from pathogenic microorganisms may polarize the immune response toward a Th2 phenotype in susceptible mouse strains.
Prdm9 Controls Activation of Mammalian Recombination Hotspots

Homing in on Hotspots The clustering of recombination in the genome, around locations known as hotspots, is associated with specific DNA motifs. Now, using a variety of techniques, three studies implicate a chromatin-modifying protein, the histone-methyltransferase PRDM9, as a major factor involved in human hotspots (see the Perspective by Cheung et al.). Parvanov et al. (p. 835, published online 31 December) mapped the locus in mice, and analyzed allelic variation in mice and humans, whereas Myers et al. (p. 876, published online 31 December) used a comparative analysis between human and chimpanzees to show that the recombination process leads to a self-destructive drive in which the very motifs that recruit hotspots are eliminated from our genome. Baudat et al. (p. 836, published online 31 December) took this analysis a step further to identify human allelic variants within Prdm9 that differed in the frequency at which they used hotspots. Furthermore, differential binding of this protein to different human alleles suggests that this protein interacts with specific DNA sequences. Thus, PDRM9 functions in the determination of recombination loci within the genome and may be a significant factor in the genomic differences between closely related species. Genome recombination during meiosis is likely controlled by a chromatin-modifying enzyme. Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.
The Self-Defensive Cognition of Self-Defense

Why do certain self-defense cases - ones, e.g., involving battered women who kill their sleeping abusers, or beleaguered commuters who shoot panhandling minority teens - provoke intense political conflict? The conventional and seemingly obvious answer is that people judge such cases in a politically partisan fashion. This paper, however, suggests a subtler and more complex explanation. Social psychologists have shown that individuals resolve factual ambiguities in a manner supportive of their defining values, both to minimize dissonance and to protect their connection to others who share their commitments. This form of self-defensive cognition, it is submitted, shapes individuals' perceptions of violent interactions between parties seen to be complying with or defying contested social norms. As a result, even individuals who are trying to decide such cases based on honest and politically impartial assessments of the facts polarize along cultural lines. The paper presents the results of an original empirical study (N = 1,600) that supports this hypothesis. It also explores the normative significance of this account of the origins of political conflict over self-defense cases and how such conflict can be mitigated.
Effect of early transient adherent leukocytes on venular permeability and endothelial actin cytoskeleton.

In a time course study of the development and recovery of venular leaks, it was shown that, after as early as 3 min of histamine application, venular leak formation was identified [Baldwin, A. L. , and G. Thurston. Am. J. Physiol. 269 ( Heart Circ. Physiol. 38): H1528-H1537, 1995]. This was accompanied by changes in the endothelial actin cytoskeleton and the presence of adherent leukocytes. The venular leaks remained elevated for at least 30 min, whereas the adherent leukocytes were decreased by 20 min. The present study was performed to determine the role that 3 min (early), transient histamine-associated adherent leukocytes play in the formation of venular leaks and changes in the endothelial actin cytoskeleton. In anesthetized rats, the microvasculature of a mesenteric window was perfused with buffered saline or fucoidin. FITC-BSA or FITC-BSA and 10-4 M histamine was added to the perfusate for the last 3 min. The vasculature was perfusion fixed, stained for filamentous actin, and viewed microscopically. Fucoidin pretreatment significantly reduced the number of early, transient histamine-associated adherent leukocytes ( P < 0.01). The number of adherent leukocytes in leaky venules was significantly greater than that seen in nonleaky venules ( P < 0.01); however, the reduction in the number of histamine-associated adherent leukocytes with fucoidin pretreatment had no significant effect on the number ( P > 0.05) or area ( P > 0.05) of FITC-BSA leaks or on the endothelial actin cytoskeleton.