Miracle-dz/UniFAR-FTUs huggingface dataset:
The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes

The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and influenced by the ILA subtype is not known. We evaluated the associations between the MUC5B genotype and ILA in cohorts with extensive imaging characterisation. We performed ILA phenotyping and MUC5B promoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively. We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although the MUC5B genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8–2.4, p=1×10−26), there was evidence of significant heterogeneity between cohorts (I2=81%). When narrowed to specific radiologic subtypes, (e.g. subpleural ILA), the MUC5B genotype remained strongly associated (OR 2.6, 95% CI 2.2–3.1, p=1×10−30) with minimal heterogeneity (I2=0%). Although there was no evidence that the MUC5B genotype influenced survival, there was evidence that MUC5B genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations. The MUC5B promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations. The MUC5B genotype is associated with specific subtypes of ILA, with varying heterogeneity in underlying populations http://ow.ly/pcmH30dRsZ7
Electron microscopic immunocytochemical study of the distribution of parvalbumin‐containing neurons and axon terminals in the primate dentate Gyrus and Ammon's horn

Five green monkeys were examined with light and electron microscopic preparations to explore the regional differences in the distribution of parvalbumin (PV)‐positive neurons and axon terminals in the primate hippocampus. PV‐positive neurons were mainly found in the hilus of the dentate gyrus and the strata oriens and pyramidale of Ammon's horn. In electron microscopic preparations, the PV‐positive cells displayed nuclear infoldings, intranuclear rods, a large rim of perikaryal cytoplasm with numerous organelles and both asymmetric and symmetric axosomatic synapses. One prominent PV‐positive cell type in CA1 was a large multipolar neuron that resembled the large basket cells of the neocortex. Although most PV‐positive dendrites were aspiny and postsynaptic to numerous axon terminals, some PV‐positive dendrites in the molecular layer of the dentate gyrus displayed filipodia‐like appendages with no synapses or spines that were postsynaptic to multiple axon terminals. The PV‐positive dendrites in the hilus and stratum oriens were apposed at specialized junctions that resembled gap junctions. PV‐positive axons were concentrated in the principal cell layers, and formed axosomatic, axodendritic, and axon initial segment synapses. In cases where these axons were observed to appose the surface of granule cells for a long length, only one axosomatic symmetric synapse per cell was found. In the hilus, PV‐positive axon terminals formed synapses onto thorny excrescences of spiny cells. Both semithin sections and electron microscopic preparations indicated that more PV‐positive axon terminals formed symmetric axosomatic synapses with pyramidal cells in CA2 than in CA1 and CA3. Also, CA2 displayed a unique plexus of PV‐positive axon terminals in stratum lacunosum moleculare.
The role of the Brambell receptor (FcRB) in liver: protection of endocytosed immunoglobulin G (IgG) from catabolism in hepatocytes rather than transport of IgG to bile

The Brambell receptor (FcRB) mediates functions of both immunoglobulin G (IgG) transport, transmitting immunity from mother to young, and IgG protection, making IgG the longest surviving of all plasma proteins. Reflecting its role as transport receptor (termed FcRn, for neonatal rat intestine, the tissue from which it was first cloned), FcRB is expressed antenatally in the rabbit, mouse and rat fetal yolk sac and in human placental syncytiotrophoblasts, and neonatally in the intestinal epithelium of mice and rats. Reflecting its role as protection receptor (FcRp), FcRB is expressed in the vascular endothelium throughout life, where it protects IgG from the on-going catabolic activities of this tissue. FcRB detected in hepatocytes was hypothesized to mediate transport of IgG from serum to bile, thus potentially extending the transport expression (FcRn) of this receptor beyond the perinatal period. Our results show serum-to-bile transport of IgG to be unaffected in mice functionally deleted for FcRB. Accordingly, the hypothesis is rejected that FcRB functions as transport receptor (FcRn) in liver. The default conclusion is that FcRB in hepatocytes functions as FcRp, serving to protect IgG from catabolism in hepatocytes that accompanies the endocytic activity of these cells. We conclude that there remains to date no evidence of an FcRn-like transport function of the Brambell receptor beyond the perinatal period, after which the FcRp function of the receptor predominates, paralleling the endocytic activities of the associated tissues.
Post-traumatic stress symptoms in pathological gambling: Potential evidence of anti-reward processes

Background Excessive gambling is considered to be a part of the addiction spectrum. Stress-like emotional states are a key feature both of pathological gambling (PG) and of substance addiction. In substance addiction, stress symptomatology has been attributed in part to “anti-reward” allostatic neuroadaptations, while a potential involvement of anti-reward processes in the course of PG has not yet been investigated. Methods To that end, individuals with PG (n = 22) and mentally healthy subjects (n = 13) were assessed for trauma exposure and post-traumatic stress symptomatology (PTSS) using the Life Events Checklist and the Civilian Mississippi Scale, respectively. Results In comparison with healthy subjects, individuals with PG had significantly greater PTSS scores including greater physiological arousal sub-scores. The number of traumatic events and their recency were not significantly different between the groups. In the PG group, greater gambling severity was associated with more PTSS, but neither with traumatic events exposure nor with their recency. Conclusions Our data replicate prior reports on the role of traumatic stress in the course of PG and extend those findings by suggesting that the link may be derived from the anti-reward-type neuroadaptation rather than from the traumatic stress exposure per se.
Correction of Thoracic Adolescent Idiopathic Scoliosis With Segmental Hooks, Rods, and Wisconsin Wires Posteriorly: It’s Bad and Obsolete, Correct?

Study Design. Forty-four consecutive thoracic idiopathic adolescent curves surgically treated between 1995 and 1999 at one institution were analyzed. All were thoracic curves; there were no lumbar curves, double major curves, or triple major curves. Objectives. To study the clinical and radiographic results for these 44 patients. Summary of Background Data. There is currently ongoing discussion regarding the “best treatment” for right thoracic idiopathic scoliosis. Methods. Patients were administered preoperative and postoperative Scoliosis Research Society questionnaires. Radiographs were studied for coronal correction, sagittal correction, junctional deformities two segments above/two segments below, fusion status, loss of correction status, complications, and imbalance of curves above and below. Radiographic analysis was by two independent observers. All patients were treated with bilateral 5.5-mm CD Horizon (M-10) instrumentation. Corrective forces were translational and in situ contouring. An average of 10 hooks and 4 Wisconsin wires were used for an average of 14 fixation points per 11 segments. Follow-up was minimum 2 years to maximum 5 years, with an average of 3-year, 10-month follow-up. Results. All were out of bed on postoperative day 1; none was braced after surgery. The average preoperative thoracic curve was 56°; the average ultimate postoperative curve was 31° (P = 0.0001). In the sagittal plane T5–T12 averaged 22° preoperation and 20° postoperation. For the complete study group (n = 44), the Cobb measurement (P = 0.001) and apical vertebral translation of the lumbar curve (P = 0.001) below improved. For the false double major curve (n = 11) patterns, the unfused lumbar curve averaged preoperation 46° and postoperation 27° (P = 0.0001). There were no neurologic deficits, no wound infections, and no respiratory complications. In regards to the Scoliosis Research Society questionnaires, significant (P < 0.05) changes preoperative to ultimate postoperative were found for questions 3, 5, 11, and 14. Conclusion. “Satisfactory” results were obtained in 44 patients treated with this technique. The complication rate was low and the fusion rate was high. Posterior treatment as described above produces reasonable and dependable results.
MgADP Antagonism to Mg2+-independent ATP Binding of the Sulfonylurea Receptor SUR1*

Pancreatic β-cell ATP-sensitive potassium (KATP) channels play an important role in the regulation of glucose-induced insulin secretion. The β-cell KATP channel comprises two subunits, the sulfonylurea receptor SUR1, a member of the ATP-binding cassette (ABC) superfamily, and Kir6.2, a member of the inward rectifier K+ channel family. The activity of the KATP channel is under complex regulation by the intracellular ATP and ADP. To understand the roles of the two nucleotide-binding folds (NBFs) of SUR1 in the regulation of KATP channel activity, we introduced point mutations into the core consensus sequence of the Walker A or B motif of each NBF of SUR1 and characterized ATP binding and ADP or MgADP antagonism to it. SUR1 was efficiently photolabeled with 8-azido-[α-32P]ATP and 8-azido-[γ-32P]ATP in the presence or absence of Mg2+ or vanadate. NBF1 mutations impaired ATP binding, but NBF2 mutations did not. MgADP strongly antagonized ATP binding, and the NBF2 mutation reduced MgADP antagonism. These results show that SUR1, unlike other ABC proteins, strongly binds ATP at NBF1 even in the absence of Mg2+ and that MgADP, through binding at NBF2, antagonizes the Mg2+-independent high affinity ATP binding at NBF1.
Lower prevalence of non-reproductive system cancers among female former college athletes.

Lower prevalence of non-reproductive system cancers among former college athletes. Med. Sci. Sports Exerc. , Vol. 21, No. 3, pp. 250-253, 1989. The prevalence (lifetime occurrence) rates of cancers of nonreproductive organs and tissues were determined for 5,398 living alumnae, 2,622 of whom were former college athletes and 2,776 who had been nonathletes, from data on medical history, reproductive history, athletic training, and diet. The non-reproductive system cancers were divided into two classes: class I, which included cancers of the digestive system, thyroid, bladder, lung, and other sites and hematopoietic cancers (lymphoma, leukemia, myeloma, and Hodgkin's disease), and class II, which included skin cancers and cutaneous melanoma. The former college athletes had a significantly lower prevalence of class I cancers compared to the nonathletes; the age-adjusted relative risk (RR) equals 3.34, 95% confidence limits (1.35, 8.33), P = 0.009. In contrast, the prevalence rates of malignant melanomas and skin cancers did not differ significantly between the former athletes and nonathletes. The age-adjusted RR did not differ from 1.0. The lower prevalence rate of class I cancers among the former athletes is in accord with previous findings of a significantly lower prevalence rate of breast cancer and cancers of the reproductive system among former college athletes compared to nonathletes.
Changes in the Expression of Apoptosis-Related Proteins in the Life Cycle of Human Villous Trophoblast

The outer layer of the human placenta is the multinucleated syncytiotrophoblast. The syncytiotrophoblast is formed by the fusion of mononuclear cytotrophoblasts, and aged syncytiotrophoblast nuclei are extruded into the maternal blood as membrane-enclosed “syncytial nuclear aggregates” that are then eliminated from the maternal circulation. Apoptosis proteins are hypothesized to be involved in both of these processes, but the mechanism of death in the syncytiotrophoblast is unclear and death processes in this multinucleated layer are likely to differ from related processes in mononuclear cells. We have used a combination of villous explant culture and immunohistochemical staining of semi-serial sections from the explants to study the changing expression of 4 proteins that are markers of apoptotic processes in first-trimester human placentae. These studies show that Bcl-2 expression is limited to the syncytiotrophoblast and syncytial nuclear aggregates, while conversely Bax is expressed in some cytotrophoblasts. Activated caspase 3 and the M30 cytokeratin neoepitope were localized to isolated regions of the syncytiotrophoblast and some syncytial nuclear aggregates but were never present in the same area. Combining our results with those of others, we suggest a refined scheme whereby proteins of the apoptosis cascade participate in both the processes of syncytial formation and death.
Cost Savings of Universal Decolonization to Prevent Intensive Care Unit Infection: Implications of the REDUCE MRSA Trial

Objective. To estimate and compare the impact on healthcare costs of 3 alternative strategies for reducing bloodstream infections in the intensive care unit (ICU): methicillin-resistant Staphylococcus aureus (MRSA) nares screening and isolation, targeted decolonization (ie, screening, isolation, and decolonization of MRSA carriers or infections), and universal decolonization (ie, no screening and decolonization of all ICU patients). Design. Cost analysis using decision modeling. Methods. We developed a decision-analysis model to estimate the health care costs of targeted decolonization and universal decolonization strategies compared with a strategy of MRSA nares screening and isolation. Effectiveness estimates were derived from a recent randomized trial of the 3 strategies, and cost estimates were derived from the literature. Results. In the base case, universal decolonization was the dominant strategy and was estimated to have both lower intervention costs and lower total ICU costs than either screening and isolation or targeted decolonization. Compared with screening and isolation, universal decolonization was estimated to save $171,000 and prevent 9 additional bloodstream infections for every 1,000 ICU admissions. The dominance of universal decolonization persisted under a wide range of cost and effectiveness assumptions. Conclusions. A strategy of universal decolonization for patients admitted to the ICU would both reduce bloodstream infections and likely reduce healthcare costs compared with strategies of MRSA nares screening and isolation or screening and isolation coupled with targeted decolonization.
Biochemical and electrophysiological characterization of N‐glycans on NMDA receptor subunits

In mammals, excitatory synapses contain two major types of ionotropic glutamate receptors: α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors and N‐methyl‐d‐aspartate receptors (NMDARs). Both receptor types are comprised of several subunits that are post‐translationally modified by N‐glycosylation. However, the precise N‐glycans that are attached to these receptor types are largely unknown. Here, we used biochemistry to confirm that native NMDARs are extensively N‐glycosylated; moreover, we found that the NMDAR GluN2B subunit differs from GluN1 subunits with respect to endoglycosidase H sensitivity. Next, we used a complete panel of lectins to determine the glycan composition of NMDARs in both cerebellar tissue and cultured cerebellar granule cells. Our experiments identified 23 lectins that pulled down both the GluN1 and GluN2B NMDAR subunits. We then performed an electrophysiological analysis using representative lectins and found that pre‐incubating cerebellar granule cells with the AAL, WGA, or ConA alters the receptor's biophysical properties; this lectin‐mediated effect was eliminated when the cells were deglycosylated with peptide‐N‐glycosidase F. Similar lectin‐mediated effects were observed using HEK293 cells that express recombinant GluN1/GluN2B receptors. Finally, using mutant recombinant GluN subunits expressed in HEK293 cells, we found that 11 out of 12 predicted N‐glycosylation sites in GluN1 and 7 out of 7 N‐glycosylation sites in GluN2B are occupied by N‐glycans. These data provide new insight into the role that N‐glycosylation plays in regulating the function of NMDA receptors in the central nervous system. All animal experiments were performed in accordance with relevant institutional ethics guidelines and regulations with respect to protecting animal welfare.
Design and implementation of an embedded system for real time analysis of speech from people with Parkinson's disease

Parkinsons disease (PD) is a neurodegenerative disorder that affects the coordination and regulation of muscles and limbs, including those responsible of speech production, resulting alterations in voice intelligibility. It is already demonstrated that the constant speech therapy can improve the communication skills of the patients; however, it is required the development of flexible tools able to assess and guide the speech therapy of the patients without the intervention of the experts. In this paper one embedded system for the real time analysis of speech from people with Parkinson's disease is presented. Two platforms are developed. First, a Matlab Graphical User Interface is presented; second, the application is deployed in a minicomputer that has an audio codec, storage capacity and a efficient processing unit. The device has been equipped with an LCD monitor to display the information on real time, and a mini keyboard for the interface with the user. Different measurements that are commonly used in the assessment of speech from people with PD are evaluated. In agreement with the state of the art, an increment of the pitch variation is showed for patients with PD, additionally, lower values of the vowel space area (VSA) are also shown for speech recordings uttered by people with PD.
Neonatal estrogen exposure induces lobe-specific alterations in adult rat prostate androgen receptor expression.

Brief administration of estrogen to newborn rats results in permanent suppression of prostate growth and reduced prostatic responsiveness to testosterone in adulthood. To determine whether this imprinting may be a result of alterations in androgen receptor (AR) expression, the separate adult prostate lobes of neonatally estrogenized rats were examined for AR concentration and distribution. Sprague-Dawley rat pups were given 25 micrograms estradiol benzoate or oil alone on days 1, 3, and 5 and were killed on day 90. Half of the animals received 2-cm testosterone implants 10 days before death to assess the activational response to androgen. In a separate series, neonatally estrogenized rats were given prepubertal dihydrotestosterone pellets for 3 weeks as well as testosterone implants in adulthood to determine if the observed effects of neonatal estrogen on the adult prostate were an indirect result of androgen deprivation during developmentally critical periods. The ventral, dorsal, and lateral prostate lobes were processed for nuclear AR quantitation by [3H]dihydrotestosterone exchange binding assay and for indirect immunocytochemical localization of AR. Weights and DNA contents of the three prostate lobes were significantly reduced in neonatally estrogenized rats, and this decrease was only partially reversed by prepubertal and/or adult androgen replacement. Histologically, the hypoplastic ventral and dorsal lobes exhibited a relative increase in interacinar stromal tissue, disorganized acini with epithelial hyperplasia, luminal sloughing, and an apparent lack of differentiation. The hypoplastic lateral lobe also showed a relative increase in the stromal fraction; however, the acinar epithelium appeared differentiated, with normal basal/apical orientation and luminal secretions. The AR concentration was significantly reduced in the ventral and dorsal prostates of estrogenized rats, but was unaltered in the lateral lobe. Immunocytochemistry revealed a marked reduction or absence of epithelial AR in ventral and dorsal lobes from estrogenized rats, whereas the lateral lobe epithelial cells expressed AR similarly to controls. The incidence of AR-positive fibroblastic stromal cells increased in lateral prostates from 5% in controls to approximately 25% in estrogenized rats. Neonatally estrogenized rats given testosterone for 10 days in adulthood showed increased levels of AR in the ventral and dorsal lobes compared to nonstimulated rats; however, these levels remained well below control values. Lateral lobe epithelial histology and AR expression appeared relatively unchanged in estrogenized rats given testosterone during adulthood, whereas an increased proportion of stromal cells (approximately 35%) were AR positive. In summary, neonatal estrogen administration permanently altered prostatic growth and produced lobe-specific changes in AR expression in the adult gland. (ABSTRACT TRUNCATED AT 400 WORDS)
Genetic analysis of the Legionella pneumophila DotB ATPase reveals a role in type IV secretion system protein export

The pulmonary pathogen Legionella pneumophila uses the Dot/Icm type IV secretion system (T4SS) to replicate inside host cells. This apparatus translocates proteins into macrophages to alter their endocytic pathway and enable bacterial growth. Although the secretion ATPase DotB is critical for T4SS function, its specific role in type IV secretion remains undefined. Due to similarity to the VirB11 and PilT ATPases, DotB has been proposed to play a role in assembly of the T4SS, retraction of pili and/or export of substrates. With the goal of understanding the protein's function(s), we isolated and characterized 30 dotB alleles using a variety of phenotypic and biochemical assays. Twenty‐four of these alleles possess several dot/icm mutant phenotypes, including a complete lack of intracellular replication, plasmid mobilization and contact‐dependent cytotoxicity. These 24 non‐functional alleles fall into three classes: those with a known biochemical defect, those with a predicted enzymatic defect and those with an unknown defect. Six other alleles display partial activity in dot/icm phenotypic assays, thus constituting a fourth class. Two mutants in this class are unable to export a subset of T4SS substrates, providing the first evidence for a DotB function in substrate export and suggesting a possible role in substrate selection.