Miracle-dz/UniFAR-FTUs huggingface dataset:
Human sperm subpopulations: relationship between functional quality and protein tyrosine phosphorylation.

BACKGROUND Human semen is composed of a heterogeneous population of sperm with varying degrees of structural and functional differentiation and normality, which result in subpopulations of different quality. METHODS Using a discontinuous Percoll gradient, we separated three subsets of sperm [(45%; L45), (65%; L65) and (90%; L90) fractions] from normozoospermic human semen samples from healthy donors and proceeded to characterize their morphology, motility and hyperactivation, as well as their ability to undergo tyrosine phosphorylation under capacitating conditions. RESULTS As expected, sperm isolated from the lowest density layer (L45) showed the poorest quality, displaying the smallest percentage of morphologically normal and motile sperm. During a capacitating incubation, this subset of cells also showed deficient capacity to undergo hyperactivation and protein tyrosine phosphorylation. Conversely, sperm isolated from the other layers (L65 and L90) showed a time-dependent progressive increment in tyrosine phosphorylation, establishing statistically significant differences with sperm from L45. The tyrosine phosphorylation deficiency of L45 sperm could be overcome when sperm from that fraction were stimulated with activators of the cAMP-dependent kinase (PKA) pathway (dbcAMP + pentoxifylline), pointing to the sperm's plasma membrane as the main site of such deficiency. CONCLUSIONS Poor quality sperm isolated from a Percoll gradient display an intrinsic tyrosine phosphorylation deficiency, possibly caused by a plasma membrane defect, which is associated with their inability to undergo normal capacitation and, ultimately, acquire optimal fertilizing potential.
Cell Adhesion to Tropoelastin Is Mediated via the C-terminal GRKRK Motif and Integrin αVβ3*

Elastin fibers are predominantly composed of the secreted monomer tropoelastin. This protein assembly confers elasticity to all vertebrate elastic tissues including arteries, lung, skin, vocal folds, and elastic cartilage. In this study we examined the mechanism of cell interactions with recombinant human tropoelastin. Cell adhesion to human tropoelastin was divalent cation-dependent, and the inhibitory anti-integrin αVβ3 antibody LM609 inhibited cell spreading on tropoelastin, identifying integrin αVβ3 as the major fibroblast cell surface receptor for human tropoelastin. Cell adhesion was unaffected by lactose and heparin sulfate, indicating that the elastin-binding protein and cell surface glycosaminoglycans are not involved. The C-terminal GRKRK motif of tropoelastin can bind to cells in a divalent cation-dependent manner, identifying this as an integrin binding motif required for cell adhesion.
Does a Physician's Attitude toward a Patient with Mental Illness Affect Clinical Management of Diabetes? Results from a Mixed-Method Study.

OBJECTIVE To determine whether physician's attitudes toward patients with comorbid mental illness affect management of a chronic disease. DATA SOURCE A total of 256 primary care physicians interviewed in 2010. STUDY DESIGN This randomized factorial experiment entailed physicians observing video vignettes of patient-actors with poorly controlled diabetes. Patients were balanced across age, gender, race, and comorbidity (schizophrenia with bizarre or normal affect, depression, eczema). DATA COLLECTION Physicians completed structured and semistructured interviews plus chart notes about clinical management and attitudes. PRINCIPAL FINDINGS Physicians reported more negative attitudes for patients with schizophrenia with bizarre affect (SBA). There were few differences in clinical decisions measured quantitatively or in charting, but qualitative data revealed less trust of patients with SBA as reporters, with more reliance on sources other than engaging the patient in care. Physicians often alerted colleagues about SBA, thereby shaping expectations before interactions occurred. CONCLUSIONS Results are consistent with common stereotypes about people with serious mental illness. Vignettes did not include intentional indication of unreliable reporting or danger. Reducing health care disparities requires attention to subtle aspects of managing patients--particularly those with atypical affect--as seemingly slight differences could engender disparate patient experiences over time.
A pathway that links reproductive status to lifespan in Caenorhabditis elegans

In the nematode Caenorhabditis elegans and the fruit fly Drosophila, loss of the germline stem cells activates lifespan‐extending FOXO‐family transcription factors in somatic tissues and extends lifespan, suggesting the existence of an evolutionarily conserved pathway that links reproductive state and aging. Consistent with this idea, reproductive tissues have been shown to influence the lifespans of mice and humans as well. In C. elegans, loss of the germ cells activates a pathway that triggers nuclear localization of the FOXO transcription factor DAF‐16 in endodermal tissue. DAF‐16 then acts in the endoderm to activate downstream lifespan‐extending genes. DAF‐16 is also required for inhibition of insulin/insulin‐like growth factor 1 (IGF‐1) signaling to extend lifespan. However, the mechanisms by which inhibition of insulin/IGF‐1 signaling and germline loss activate DAF‐16/FOXO are distinct. As loss of the germ cells further doubles the already‐long lifespan of insulin/IGF‐1 pathway mutants, a better understanding of this reproductive longevity pathway could potentially suggest powerful ways to increase healthy lifespan in humans.
Anisotropic Covalency Contributions to Superexchange Pathways in Type One Copper Active Sites

Type one (T1) Cu sites deliver electrons to catalytic Cu active sites: the mononuclear type two (T2) Cu site in nitrite reductases (NiRs) and the trinuclear Cu cluster in the multicopper oxidases (MCOs). The T1 Cu and the remote catalytic sites are connected via a Cys-His intramolecular electron-transfer (ET) bridge, which contains two potential ET pathways: P1 through the protein backbone and P2 through the H-bond between the Cys and the His. The high covalency of the T1 Cu–S(Cys) bond is shown here to activate the T1 Cu site for hole superexchange via occupied valence orbitals of the bridge. This covalency-activated electronic coupling (HDA) facilitates long-range ET through both pathways. These pathways can be selectively activated depending on the geometric and electronic structure of the T1 Cu site and thus the anisotropic covalency of the T1 Cu–S(Cys) bond. In NiRs, blue (π-type) T1 sites utilize P1 and green (σ-type) T1 sites utilize P2, with P2 being more efficient. Comparing the MCOs to NiRs, the second-sphere environment changes the conformation of the Cys-His pathway, which selectively activates HDA for superexchange by blue π sites for efficient turnover in catalysis. These studies show that a given protein bridge, here Cys-His, provides different superexchange pathways and electronic couplings depending on the anisotropic covalencies of the donor and acceptor metal sites.
Intrinsic ruminal innervation in ruminants of different feeding types

According to their feeding habits, ruminants can be classified as grazers, concentrate selectors and those of intermediate type. The different feeding types are reflected in distinct anatomical properties of the forestomachs. The present study was designed to investigate whether the intrinsic innervation patterns of the rumen (the main part of the forestomach) differ between intermediate types and grazers. Myenteric plexus preparations from the rumen of goats (intermediate type), fallow deer (intermediate type), cattle (grazer) and sheep (grazer) were analysed by immunohistochemical detection of the following antigens: Hu‐protein (HuC/D), choline acetyltransferase (ChAT), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calbindin (CALB) and somatostatin (SOM). Myenteric ganglia of cattle contained 73 ± 6 neurons per ganglion, whereas the ganglia of sheep were significantly smaller (45 ± 18 neurons per ganglion). The ganglion density of the myenteric plexus was highest in fallow deer (15 ± 3 ganglia per cm2) and lowest in cattle (6 ± 1 ganglia per cm2). All myenteric neurons were either ChAT or NOS positive. The proportion of NOS‐positive neurons was significantly lower in sheep (29.5 ± 8.2% of all neurons) than in goats (44.2 ± 9.8%). In all species, additional analysis of the different neuropeptides revealed the following subpopulations in descending order of percentile appearance: ChAT/SP > NOS/VIP/NPY > ChAT/– > NOS/NPY. Expression of CALB was detected in a minority of the ChAT‐positive neurons in all species. Somatostatin immunoreactive somata were found only in preparations obtained from fallow deer and sheep. These data suggest that the rumen of grazers is under stronger cholinergic control than the rumen of species belonging to the intermediate type, although most subpopulations of neurons are present in all species. However, whether the strong mixing patterns of low quality roughage during digestion are enabled by the prominent excitatory input of the rumen of grazers requires elucidation in further studies.
Exogenous peptide ligand influences the expression and half‐life of free HLA class I heavy chains ubiquitously detected at the cell surface

A pool of free HLA class I chains has been detected at the plasma membrane of all cells concomitantly expressing folded and assembled class I molecules. To determine the origin of these free HLA heavy chains, we have examined the biosynthesis of a single HLA class I molecule, HLA‐B27, expressed by a murine cell line (L‐B27). In L‐B27 cells, as previously shown in Epstein‐Barr virus‐transformed lymphoblastoid cell lines, a precursor/product relationship exists, early in biosynthesis, between free (HC10‐reactive) and beta‐2‐microglobulin (β2m)‐associated (W6/32‐reactive) class I heavy chains as demonstrated by pulse/chase experiments. At later stages in class I biosynthesis, both HC10‐ and W6/32‐reactive heavy chains display complex oligosaccharides and accumulate at the cell surface. HC10‐ and W6/32‐reactive molecules are both very stable at the cell surface, with half‐lifes (t1/2) of > 7 h and ∼ 4 h, respectively. Interestingly, cell surface expression and turnover of HC10‐ and W6/32‐reactive molecules were affected by the addition of peptide ligands to the culture media. Culturing cells in the presence of HLA‐B27 ligands resulted in the increased expression of W6/32‐reactive molecules and the decreased expression of HC10‐reactive molecules. Moreover, addition of exogenous peptide extended the t1/2 of W6/32‐reactive molecules to > 7 h and reduced that of HC10‐reactive molecules to 4 h. These results indicate that surface HC10‐reactive molecules result largely from W6/32‐reactive molecules following peptide and β2m dissociation. Therefore, HC10‐reactive species are not only the precursors but also the end products in class I biosynthesis.
Prevalence of lower urinary tract symptoms and level of quality of life in men and women with chronic pelvic pain

Abstract Objectives. The aim of this study was to evaluate the prevalence of lower urinary tract symptoms and quality of life in patients with chronic pelvic pain syndrome (CPPS). Materials and methods. The McGill Pain Questionnaire, Dutch Leiden/Leuven Version (MPQ-DLV), Pain Disability Index (PDI), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Interstitial Cystitis Symptom Index (ICSI) and Pelvic Pain and Urinary/Frequency Symptom Scale (PUF) were used, based on their specific properties, to assess the symptoms and impact on the quality of life. Total scores and domains were compared for gender. Results. The studied group (N = 35; 18 male, 17 female) showed a good distribution in gender for age [Mann–Whitney U test (MW-U) p = 0.4] and body mass index (MW-U p = 0.2). The MPQ-DLV showed significantly higher scores for pain in women for Pain Rating Index – Affective (MW-U p = 0.030) and Total (MW-U p = 0.031), and Visual Analogue Scale for Pain – Most (MW-U p = 0.005). Women were less sexually active (PUF-SA) (chi-squared test p = 0.021) and had a significantly higher disability (PDI-T) (MW-U p = 0.005) and MPQ – Quality of Life (MW-U p = 0.003). The urinary symptoms showed similar results for gender (chi-squared test p > 0.05). Conclusions. A wide variety of symptoms and a negative impact on quality of life were shown. No differences in lower urinary tract symptoms were found between genders. Women were less sexually active than men. Chronic pelvic pain had a significantly higher negative impact on the level of quality of life in women than in men.
History of 7,093 Patients with Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia Treated with Alfuzosin in General Practice up to 3 Years

Objectives: As we have previously published 4 articles reporting the treatment of 7,093 clinical benign prostatic hyperplasia (BPH) patients treated with alfuzosin in a 3–month open–labelled study which was subsequently extended to 12, 24, and 36 months, the objective of this article is to provide additional data on dropouts, acute urinary retention (AUR), progression to surgery, and safety under the natural conditions of general practice, paying special attention to the predictive factors.Methods: 7,093 patients were initially enrolled by 1,812 centers for up to 3 months. Subsequently 1,508, 1,325, and 812 general practitioners agreed to extend the study up to 12, 24, and 36 months, respectively, which corresponds to 4 patient populations.Results: The baseline symptom profile of patients who completed the study was identical to that of patients who dropped out (because the center resigned or during treatment). In the 4 patient populations, the percentage of patients per month who dropped out, experienced adverse effects, AUR and surgery were 0.6–1.6, 0.1–0.5, 0.01–0.03, and 0.1–0.3%, respectively. The classes of symptom severity were not predictive for dropouts: 3.5, 12.6, 20, and 14.3% of the severe patients dropped out during treatment versus 4.2, 13.7, 22.9, and 14.0% of the moderate patients who dropped out up to 3, 12, 24, and 36 months, respectively. Safety was satisfactory regarding the number of adverse events and blood pressure measurement. No retrograde ejaculation was reported.Conclusion: Under the natural conditions of general practice the reasons for dropping out were not correlated with symptom severity.
Back to Work

This paper analyzes a puzzling aspect of retirement behavior known as “unretirement. ” Nearly 50 percent of retirees follow a nontraditional retirement path that involves partial retirement or unretirement, and at least 26 percent of retirees later unretire. I explore two possible explanations: (1) unretirement transitions result from failures in planning or financial shocks; and (2) unretirement transitions are anticipated prior to retirement, reflecting a more complex retirement process. I show that unretirement was anticipated for the vast majority of those returning to work, and is not a result of financial shocks, poor planning or low wealth accumulation.
Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells

A panning method has been developed to enrich Langerhans cells (LC) from murine epidermis. In standard culture media, the enriched populations progressively lose viability over a 3-d interval. When the cultures are supplemented with keratinocyte-conditioned medium, LC viability is improved and the cells increase in size and number of dendritic processes. Accessory function, as monitored by stimulating activity in the mixed lymphocyte reaction (MLR), increases at least 10- 20-fold. The conditioned media of stimulated macrophages and T cells also support the viability and maturation of cultured LC. A panel of purified cytokines has been tested, and only granulocyte/macrophage colony-stimulating factor (GM-CSF) substitutes for bulk-conditioned medium. The recombinant molecule exhibits half-maximal activity at 5 pM. Without activity are: IL-1-4; IFN-alpha/beta/gamma; cachectin/TNF; M- and G-CSF. A rabbit anti-GM-CSF specifically neutralizes the capacity of keratinocyte-conditioned medium to generate active LC. However, GM-CSF is not required for LC function during the MLR itself. We conclude that the development of immunologically active LC in culture is mediated by GM-CSF. The observation that these dendritic cells do not respond to lineage-specific G- and M-CSFs suggests that LC represent a distinct myeloid differentiation pathway. Because GM-CSF can be made by nonimmune cells and can mediate the production of active dendritic cells, this cytokine provides a T-independent mechanism for enhancing the sensitization phase of cell-mediated immunity.
Dynamic coronary MR angiography and first‐pass perfusion with intracoronary administration of contrast agent

To evaluate whether dynamic imaging of the coronary arteries can be performed with intracoronary infusion of low‐dose gadolinium (Gd)‐based contrast agent and assess the effect of long duration and multiple infusions on the image signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR).
Recommending Locations Based on Users' Periodic Behaviors

The research of location recommendation system is an important topic in the field of LBSN (Location-Based Social Network). Recently, more and more researchers began focusing on researching how to recommend locations based on user’s life behavior. In this paper, we proposed a new model recommending locations based on user’s periodic behaviors. In view of multiple periodic behaviors existing in time series, an algorithm which can mine all periods in time series is proposed in this paper. Based on the periodic behaviors, we recommend locations using item-based collaborative filtering algorithm. In this paper, we will also introduce our recommendation system which can collect users’ GPS trajectory, mine user’s multiple periods, and recommend locations based user’s periodic behavior.
Multimedia service creation platform for mobile experience sharing

The multimedia content created by users with their mobile phones is often shared with family and friends to recreate personal experiences. It is difficult for a single media sharing service to cover all variations on how people would like to present their experiences of different events; thus it is important to be able to easily create versions of these services. This paper presents in detail our platform implementation for enabling the creation of lightweight content- and context-aware mobile multimedia services. The platform supports state-of-the-art content management functionalities in order to enable easy creation of specialized multimedia services for various target groups and purposes. Our solution includes context metadata support for mobile multimedia content and creation of location-aware multimedia services. We have built example services on top of the platform using web-based technologies such as JavaScript, Media RSS feed and Java. The functionality of the platform has been tested in user evaluations with promising results.
Amyloid β-peptide stimulates nitric oxide production in astrocytes through an NFκB-dependent mechanism

The major pathological features of Alzheimer’s disease (AD) include amyloid plaques composed primarily of the β-amyloid (Aβ) peptide, degenerating neurons and neurofibrillary tangles, and the presence of numerous activated astrocytes and microglia. Although extensive genetic data implicate Aβ in the neurodegenerative cascade of AD, the molecular mechanisms underlying its effects on neurons and glia and the relationship between glial activation and neuronal death are not well defined. Aβ has been shown to induce glial activation, and a growing body of evidence suggests that activated glia contribute to neurotoxicity through generation of inflammatory cytokines and neurotoxic free radicals, such as nitric oxide (NO), potent sources of oxidative stress known to occur in AD. It is therefore crucial to identify specific Aβ-induced molecular pathways mediating these responses in activated glia. We report that Aβ stimulates the activation of the transcription factor NFκB in rat astrocytes, that NFκB activation occurs selectively from p65 transactivation domain 2, and that Aβ-induced NO synthase expression and NO production occur through an NFκB-dependent mechanism. This demonstration of how Aβ couples an intracellular signal transduction pathway involving NFκB to a potentially neurotoxic response provides a key mechanistic link between Aβ and the generation of oxidative damage. Our results also suggest possible molecular targets upon which to focus future drug discovery efforts for AD.
Immunotoxic Effects of cis‐Urocanic Acid Exposure in C57BL/6N and C3H/HeN Mice ¶

Exposure to ultraviolet radiation results in increased levels of intradermal cis‐urocanic acid (cUCA) and alters cutaneous immunity by interfering with processing and presentation of antigen by Langerhans cells. Reports on effects of systemic immunotoxicity with 30 day cUCA exposure in laboratory rodents include thymic atrophy, thymic hypocellularity and decreased T‐cell–mediated immunity; however, immune effects of single exposure or 5 day cUCA administration, which may better mimic human exposures, are poorly defined. The present study initially evaluated immune effects of single, 5 day, and 4 week cUCA exposure in C57BL/6N mice. Single administration of intradermal cUCA resulted in decreased splenocyte phagocytosis that persisted for 30 days after cUCA exposure. Five day consecutive cUCA exposure decreased numbers of phenotypically mature CD4+CD8− and CD4−CD8+ (single positive) thymocytes, increased CD4+CD8+ (double positive) immature thymocytes and increased splenocyte proliferation. Prolonged cUCA exposure (4 weeks) caused profound thymic hypocellularity and splenic hypercellularity and increased splenic macrophage chemiluminescence. Because of this apparent sensitivity of C57BL/6N mice to cUCA, thymic hypocellularity was compared between C57BL/6N and C3H/HeN mice dosed with cUCA, and was found to be more pronounced in the C57BL/6N strain. These results are an extension of previous conclusions on immune modulation caused by cUCA in the spleen and thymus. Further, the observed variation in sensitivity between the mouse strains is consistent with known genetic susceptibility of these strains to the immunomodulatory effects of exposure to sunlight.