Miracle-dz/UniFAR-FTUs huggingface dataset:
Local origins of some GABAergic projections to the paraventricular and supraoptic nuclei of the hypothalamus in the rat

Axonal transport and immunohistochemical methods were used to characterize the organization of glutamic acid decarboxylase‐immunoreactive (GAD‐ir) projections to the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus in the rat. In line with prior reports, GAD‐ir varicosities were found to be densely and quite uniformly distributed throughout the hypothalamus, including the PVH and the SO. Nonetheless, the periventricular part of the PVH was consistently found to contain a disproportionately high density of GAD‐ir elements. Small crystalline implants of the retrograde tracer, true blue, into the PVH labeled GAD‐ir cells in the anterior perifornical region, portions of the anterior hypothalamic area immediately ventral to the PVH, a region just dorsal to the rostral SO and extending caudomedially over the optic chiasm and tract, and within the anterior one‐third of the PVH itself. Because possible uptake of retrograde tracer by local dendritic processes might have yielded false positive filling of nearby GAD‐ir cells, anterograde transport, Phaseolus vulgaris‐leucoagglutinin, and combined anterograde transport‐immunohistochemical methods were used to attempt to confirm these four putative local sources of GAD‐ir inputs. Tracer injections in each of the above mentioned regions labeled sparse to moderate axonal projections to the PVH, which ramified preferentially in the parvicellular division of the nucleus. Projections to the magnocellular division of the PVH and the SO were generally sparse and inconsistently observed in this material. A variable, and generally small, proportion of anterogradely labeled axons and terminals in the PVH also displayed GAD‐ir. These results suggest that GABAergic projections to visceromotor cell types in the PVH and SO arise, at least in part, from several diffusely distributed local sources. The fact that these afferents were found to terminate preferentially in the parvicellular division of the PVH makes it likely that additional sources of GABAergic projections to the magnocellular neurosecretory system remain to be identified. Peri‐ and intranuclear GABAergic neurons could provide an intermediary by which documented (and generally inhibitory) limbic system influences on neuroendocrine function are exerted. © 1993 Wiley‐Liss, Inc.
Relaxin‐3 null mutation mice display a circadian hypoactivity phenotype

Characterizing the neurocircuits and neurotransmitters that underlie arousal and circadian sleep/wake patterns is an important goal of neuroscience research, with potential implications for understanding human mental illnesses, such as major depression. Recent anatomical and functional studies suggest that relaxin‐3 neurons and their ascending projections contribute to these functions via actions on key cortical, limbic and hypothalamic circuits. This study reports the behavioral phenotype of C57BL/6J backcrossed relaxin‐3 knockout (KO) mice. Cohorts of adult, male and female relaxin‐3 KO and wild‐type (WT) littermate mice were subjected to a battery of behavioral tests to assess sensorimotor function and complex behavior. No overt deficits were detected in motor‐coordination, spatial memory, sensorimotor gating, anxiety‐like behavior or locomotor behavior in novel environments; and no marked genotype differences were observed in response to a chronic stress protocol. Notably however, compared to WT mice, relaxin‐3 KO mice displayed robust hypoactivity during the dark/active phase when provided with free home‐cage access to voluntary running wheels. This circadian hypoactivity was reflected by reduced time spent and distance traveled on running wheels, coupled with an increase in the time spent immobile, possibly reflecting increased sleeping. Overall, these studies support a role for relaxin‐3 signaling in the control of arousal and sleep/wakefulness, and identify the relaxin‐3 KO mouse as a useful model to study this role further.
Solution conformations and thermodynamics of structured peptides: molecular dynamics simulation with an implicit solvation model.

Calculations of the ensemble of solution conformations and thermodynamics of an analogue of the C-terminal helix of ribonuclease A (RN24) and of a synthetic, beta-hairpin forming peptide (BH8) are presented. For efficient sampling of conformation space, molecular dynamics simulations with an implicit solvent potential and umbrella sampling of the potential energy are performed. Starting from the fully extended chains, the simulations yield several folding and unfolding transitions between disordered (coil) conformations of the peptides and the "native" state (RN24, helix; BH8, hairpin); the simulations also lead to the occurrence of "misfolded" conformations (RN24, hairpin; BH8, helix). In agreement with experiment, the calculations predict 58% helix for RN24 at 275 K and an antiparallel-beta content of 38% at 275 K for BH8; the calculated probabilities for the misfolded species are 2% or smaller at all temperatures considered (250-1100 K). Good agreement is also shown between the calculated 3JHNalpha spin-spin coupling constants of RN24 and BH8 at 275 K, and those obtained from NMR experiments at the same temperature. From the calculated probabilities of helix (h), beta-hairpin (b), and coil (c), the free energy differences between the structured substates are DeltaGch=Gc-Gh approximately 1 kcal/mol and DeltaGbh>/=1.8 kcal/mol for RN24, and DeltaGcb approximately 0.7 kcal/mol and DeltaGhb>/=2.7 kcal/mol for BH8. The free energy difference between "correctly" folded and misfolded secondary structures are of interest for understanding the alpha to beta transition that is thought to play a role in amyloid fibril formation.
Correcting aspect ratio distortion of natural images by convolutional neural network

We propose a method to correct the aspect ratio distortion of images using convolutional neural network (CNN). The “aspect ratio”, which is focused on this research, is defined as the relative “image aspect ratio” (i.e. ratio of width to height of image) from non-stretched image. And the aspect ratio can be distorted by vertical or horizontal stretching, which does not maintain the image aspect ratio. In the proposed method, we construct an aspect ratio estimator whose input is a (possibly distorted) image and output is a scalar value of aspect ratio. Since estimation of aspect ratio from image can be regarded as regression problem, we modeled the estimator by CNN. Once we have a reliable estimate of aspect ratio of an image, the correction can be done straightforwardly by inverse stretching. In the experiments, we evaluated performance of the model trained on Pascal VOC2012 natural image dataset. Our method can accurately correct the distortion within 7% of stretch from original images on average, which outperforms average human performance (i.e. about 13%). In terms of precision, 85% of distorted images are successfully corrected. We also experimented to confirm what information is used by trained CNN. As the result, we observed that the model uses the edge component of the image to estimate the aspect ratio.
Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2

Pituitary homeobox 2 (PITX2), a Paired-like homeodomain transcription factor and a downstream effector of β-catenin signaling, plays substantial roles in normal embryonic development but its possible involvement in tumorigenesis was unknown. In this study, we extend its function in human cancer. Remarkably, we found that PITX2 was frequently expressed in human follicular cell-derived (papillary, follicular, and anaplastic) thyroid cancer tissues but not in normal thyroids, indicating for the first time that overactivated PITX2 may contribute to thyroid cancer. Cell-based and biochemical studies were performed to uncover the molecular mechanism of PITX2 action in thyroid cancer. Knockdown of PITX2 gene expression in human thyroid cancer cells significantly reduced cell proliferation and soft-agar colony formation. Biochemical analysis of cell cycle regulators upon PITX2 knockdown revealed down-regulation of Cyclin D1, Cyclin D2, and dephosphorylation of Rb. Chromatin immunoprecipitation and promoter reporter assay indicated that Cyclin D2 was a direct target gene of PITX2. Consistently, we observed that high expression levels of Cyclin D2 were frequently associated with PITX2 expression in follicular cell-derived thyroid cancer tissues. To confirm our results in vivo, we took advantage of a mouse model of thyroid cancer (TRbetaPV/PV mouse). Consistently, the aberrant elevation of Pitx2 levels in the thyroid cancer of TRbetaPV/PV mice was accompanied by up-regulation of Cyclin D1, Cyclin D2, and increased phosphorylation of Rb. Collectively, our findings demonstrate that the overactivated PITX2-Cyclin D2 pathway promotes thyroid tumorigenesis, and they provide the first evidence implicating an oncogenic role of PITX2 in human cancer.
Muscle Gene Expression Is a Marker of Amyotrophic Lateral Sclerosis Severity

Background: Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset degenerative disease characterized by the loss of upper and lower motor neurons leading to progressive muscle atrophy and paralysis. The lack of molecular markers of the progression of disease is detrimental to clinical practice and therapeutic trials. Objective: This study was designed to identify gene expression changes in skeletal muscle that could reliably define the degree of disease severity. Methods: Gene expression profiles were obtained from the deltoid muscles of ALS patients and healthy subjects. Changes in differentially expressed genes were compared to the status of deltoid muscle disability, as determined by manual muscle testing, electrophysiology and the degree of myofiber atrophy. Functionally related genes were grouped by annotation analysis, and deltoid muscle injury was predicted using binary tree classifiers. Results: Two sets of 25 and 70 transcripts appeared differentially regulated exclusively in early and advanced states of deltoid muscle impairment, respectively. The expression of another set of 198 transcripts correlated with a composite score of muscle injury combining manual muscle testing and histological examination. From the totality of these expression changes, 155 transcripts distinguished advanced from early deltoid muscle impairment with 80% sensitivity and 100% specificity. Nine of these transcripts, known also to be regulated in ALS mouse and surgically denervated muscle, predicted the advanced disease status with 100% sensitivity and specificity. Conclusion: We provide robust gene expression changes that can be of practical use when monitoring ALS status and the effects of disease-modifying drugs.
Utility of Whole Blood Hemostatometry Using the Clot Signature Analyzer® for Assessment of Hemostasis in Cardiac Surgery

Background A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer® is a hemostatometer that measures global hemostasis in whole blood. The authors hypothesized that point-of-care hemostatometry could detect a clinical coagulopathic state in cardiac surgical patients. Methods Fifty-seven adult patients scheduled for a variety of elective cardiac surgical procedures were studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and transfusion for post-CPB bleeding were all managed by standardized protocol. Clinical coagulopathy was defined by the need for platelet or fresh frozen plasma transfusion. The Clot Signature Analyzer® collagen-induced thrombus formation (CITF) assay measured platelet-mediated hemostasis in vitro. The activated clotting time, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration were also measured. Results The postprotamine CITF was greater in patients who required hemostatic transfusion than in those who did not (17.6 ± 8.0 min vs. 10.5 ± 5.7 min, respectively;P < 0.01). Postprotamine CITF values were highly correlated with platelet and fresh frozen plasma transfusion (Spearman r = 0.50, P < 0.001 and r = 0.40, P < 0.005, respectively). Receiver operator characteristic curves showed a highly significant relation between the postprotamine CITF and intraoperative platelet and fresh frozen plasma transfusion (area under the curve, 0.78–0.81, P < 0.005) with 60–80% sensitivity, specificity, positive and negative predictive values at cutoffs of 12–14 min. Logistic regression demonstrated that the CITF was independently predictive of post-CPB hemostatic transfusion, but standard hemostatic assays were not. Conclusions The Clot Signature Analyzer® CITF detects a clinical coagulopathic state after CPB and is independently predictive of the need for hemostatic transfusion. Hemostatometry has potential utility for monitoring hemostasis in cardiac surgery.
Low‐density lipoprotein (LDL) particle size in healthy prepubertal children: The STRIP study

Background: Small, dense low‐density lipoprotein (LDL) particles (diameter<255Å) are highly atherogenic, and in adults they are associated with an elevated risk of coronary heart disease (CHD). Aim: To examine possible contributors to LDL particle size distribution in healthy prepubertal children. Methods: We determined LDL particle size in 176 7‐y‐old children by non‐denaturing polyacrylamide gel electrophoresis. Children were divided into two groups in two ways: by using the median of their average LDL particle diameter (261.2 Å) or by using the LDL peak particle diameter (255 Å) as the cut‐off point. Results: Children with smaller LDL particles did not significantly differ from children with larger LDL particles with respect to anthropometric variables, serum triglyceride concentration (in all children<1.7 mmol/L), apoE phenotype, amount and quality of dietary fat, or child's family history of CHD. Furthermore, LDL particle size did not correlate with any of the anthropometric, lipid or nutrient variables. Children with average LDL particle size below the median had higher serum insulin and lower high‐density lipoprotein (HDL) cholesterol and apoA‐1 concentrations than those with LDL particle size above the median.
Re-Examination of Training Effects by Electrostimulation in the Human Elbow Musculoskeletal System

This study examines the effects of a 7 weeks sub-maximal training period of electrostimulation on the maximal isometric, concentric, eccentric voluntary torque and muscle contractile properties of the elbow flexor muscles of nine subjects. The daily program consisted of five series of six 6-s isometric actions (60 to 70% of maximal isometric voluntary action) at an elbow angle of 90 . After training the maximal voluntary isometric flexion torque increased significantly whereas the maximal voluntary isometric extension torque decreased significantly. Increases in isometric flexion torque were linked to an increase of the myoelectrical activity of the biceps brachii muscle. Under dynamic conditions flexion torque was significantly increased throughout the whole spectrum of angular velocities. These changes were accompanied by an increase in the myoelectrical activity of the agonist muscle under eccentric conditions and at two fast concentric angular velocities, without modifications of the myoelectrical activity of the antagonist muscle. The analysis of the electrical and mechanical twitches indicated that modifications of the muscle membrane electrical activity were also present at the muscle level. These results indicate that torque gains were attributed to neural adaptations and/or to a modification of the relative part of agonist and antagonist muscles in elbow flexion torque production.
Enhancing Human Cognition with Cocoa Flavonoids

Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects.
Standing low-field magnetic resonance imaging in horses with chronic foot pain.

OBJECTIVE Conventional imaging modalities can diagnose the source of foot pain in most cases, but have limitations in some horses, which can be overcome by using magnetic resonance imaging (MRI). However, there are no reports of the MRI appearance and prevalence of foot lesions of a large series of horses with chronic foot lameness. METHODS In the present study, 79 horses with unilateral or bilateral forelimb lameness because of chronic foot pain underwent standing low-field MRI to make a definitive diagnosis. RESULTS Of the 79 horses, 74 (94%) had alterations in >1 structure in the lame or lamest foot. Navicular bone lesions occurred most frequently (78%) followed by navicular bursitis (57%), deep digital flexor tendonopathies (54%) and collateral desmopathy of the distal interphalangeal joint (39%). Effusion of the distal interphalangeal joint was also a frequent finding (53%). CONCLUSION Low-field MRI in a standing patient can detect many lesions of the equine foot associated with chronic lameness without the need for general anaesthesia.
Immune effect of heat‐killed multistrain of Lactobacillus acidophilus against Salmonella typhimurium invasion to mice

Aims: This study attempted to determine whether lactic acid bacteria (LAB) could have a better probiotic function when used as a multistrain mixture, i.e. Mix‐LAB, than when used as a monostrain. To this end, three strains of Lactobacillus acidophilus, specifically strain LAP5, LAF1 and LAH7, were heat‐killed and mixed. This heat‐killed Mix‐LAB was used to evaluate the effectiveness of multistrain in inhibiting Salmonella invasion into cultured cells and into organs (spleen and liver) of live mice.
Regression of electrocardiographic left ventricular hypertrophy and decreased incidence of new-onset atrial fibrillation in patients with hypertension.

CONTEXT Atrial fibrillation (AF) is associated with increased risk of mortality and cardiovascular events, particularly stroke, making prevention of new-onset AF a clinical priority. Although the presence and severity of electrocardiographic left ventricular hypertrophy (LVH) appear to predict development of AF, whether regression of electrocardiographic LVH is associated with a decreased incidence of AF is unclear. OBJECTIVE To test the hypothesis that in-treatment regression or continued absence of electrocardiographic LVH during antihypertensive therapy is associated with a decreased incidence of AF, independent of blood pressure and treatment modality. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, parallel-group study conducted in 1995-2001 among 8831 men and women with hypertension, aged 55-80 years (median, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage, with no history of AF, without AF on the baseline electrocardiogram, and enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension Study. INTERVENTIONS Losartan- or atenolol-based treatment regimens, with follow-up assessments at 6 months and then yearly until death or study end. MAIN OUTCOME MEASURE New-onset AF in relation to electrocardiographic LVH determined at baseline and subsequently. Electrocardiographic LVH was measured using sex-adjusted Cornell product criteria ({R(aVL) + S(V3) [+ 6 mm in women]} x QRS duration). RESULTS After a mean (SD) follow-up of 4.7 (1.1) years, new-onset AF occurred in 290 patients with in-treatment regression or continued absence of Cornell product LVH for a rate of 14.9 per 1000 patient-years and in 411 patients with in-treatment persistence or development of LVH by Cornell product criteria for a rate of 19.0 per 1000 patient-years. In time-dependent Cox analyses adjusted for treatment effects, baseline differences in risk factors for AF, baseline and in-treatment blood pressure, and baseline severity of electrocardiographic LVH, lower in-treatment Cornell product LVH treated as a time-varying covariate was associated with a 12.4% lower rate of new-onset AF (adjusted hazard ratio [HR], 0.88; 95% CI, 0.80-0.97; P = .007) for every 1050 mm x msec (per 1-SD) lower Cornell product, with persistence of the benefit of losartan vs atenolol therapy on developing AF (HR, 0.83; 95% CI, 0.71-0.97; P = .01). CONCLUSIONS Lower Cornell product electrocardiographic LVH during antihypertensive therapy is associated with a lower likelihood of new-onset AF, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may reduce the incidence of new-onset AF.
Adult attachment representations, parental responsiveness, and infant attachment: a meta-analysis on the predictive validity of the Adult Attachment Interview.

About a decade ago, the Adult Attachment Interview (AAI; C. George, N. Kaplan, & M. Main, 1985) was developed to explore parents' mental representations of attachment as manifested in language during discourse of childhood experiences. The AAI was intended to predict the quality of the infant-parent attachment relationship, as observed in the Ainsworth Strange Situation, and to predict parents' responsiveness to their infants' attachment signals. The current meta-analysis examined the available evidence with respect to these predictive validity issues. In regard to the 1st issue, the 18 available samples (N = 854) showed a combined effect size of 1.06 in the expected direction for the secure vs. insecure split. For a portion of the studies, the percentage of correspondence between parents' mental representation of attachment and infants' attachment security could be computed (the resulting percentage was 75%; kappa = .49, n = 661). Concerning the 2nd issue, the 10 samples (N = 389) that were retrieved showed a combined effect size of . 72 in the expected direction. According to conventional criteria, the effect sizes are large. It was concluded that although the predictive validity of the AAI is a replicated fact, there is only partial knowledge of how attachment representations are transmitted (the transmission gap).