Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Localization and Stimulation‐Associated Distribution Dynamics of Syntaxin‐1 and Syntaxin‐3 in Gastric Parietal Cells

Syntaxins are differentially localized in polarized cells and play an important role in vesicle trafficking and membrane fusion. These soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) proteins are believed to be involved in tubulovesicle trafficking and membrane fusion during the secretory cycle of the gastric parietal cell. We examined the cellular localization and distribution of syntaxin‐1 and syntaxin‐3 in rabbit parietal cells. Fractionation of gastric epithelial cell membranes showed that syntaxin‐1 was more abundant in a fraction enriched in apical plasma membranes, whereas syntaxin‐3 was found predominantly in the H,K‐ATPase‐rich tubulovesicle fraction. We also examined the cellular localization of syntaxins in cultured parietal cells. Parietal cells were infected with CFP‐syntaxin‐1 and CFP‐syntaxin‐3 adenoviral constructs. Fluorescence microscopy of live and fixed cells demonstrated that syntaxin‐1 was primarily on the apical membrane vacuoles of infected cells, but there was also the expression of syntaxin‐1 in a subadjacent cytoplasmic compartment. In resting, non‐secreting parietal cells, syntaxin‐3 was distributed throughout the cytoplasmic compartment; after stimulation, syntaxin‐3 translocated to the apical membrane vacuoles, there co‐localizing with H,K‐ATPase, syntaxin‐1 and F‐actin. The differential location of these syntaxin isoforms in gastric parietal cells suggests that these proteins may be critical for maintaining membrane compartment identity and that they may play important, but somewhat different, roles in the membrane recruitment processes associated with secretory activation.
Single-pixel digital ghost holography

Since its discovery, the "ghost" diffraction phenomenon has emerged as an unconventional technique for optical imaging with very promising advantages. However, extracting the intensity and phase information of a structured and realistic object remains a challenge. Here we show that a ghost hologram can be recorded with a single-pixel configuration by adapting concepts from standard digital holography. The presented homodyne scheme enables phase imaging with nanometric depth resolution and three-dimensional focusing ability and shows a high signal-to-noise ratio.
Therapeutic innovations in inflammatory bowel diseases

Inflammatory bowel disease (IBD) is a spectrum of complex multifactorial immune disorders characterized by chronic inflammation of the gut. Significant advances have been made in unraveling the pathogenesis of this disease spectrum, which have spurred the discovery of new therapeutic targets and strategies. In this review, we highlight the emerging new classes of IBD therapeutics under clinical evaluation and their method of action, including JAK inhibitors, anti‐SMAD7 oligonucleotides, and cell‐based therapies. Moreover, we discuss how an approach based on unique molecular insights in a given patient will, in the future, lead to a truly individualized/tailored disease management, starting at diagnosis, aiding in prognosis, and resulting in a personalized therapeutic approach.
Sepsis Mortality in Critical Care and Prior Statin Therapy: A Retrospective Cohort Study in Central Argentina.

INTRODUCTION Sepsis is a major public health problem, frequent, costly, and often fatal. Despite of improvements in supportive treatments the incidence of sepsis and the number of deaths related to sepsis is increasing. Statins have been recently proposed as adjuvants in the treatment of sepsis, but its effects on mortality show conflicting results worldwide. AIM The purpose of this study was to describe the clinical outcome of patients diagnosed with sepsis in a university-affiliated hospital in central Argentina and to evaluate it in relation to a group of septic patients with previous use of statins before the onset of sepsis. MATERIALS AND METHODS The present study was conducted as an observational retrospective research from April 2010 to December 2014 with patients over 18 years of age which were assigned to statins or control groups. Out of 2906 patients, 231 matched study and diagnostic criteria for sepsis and among them 33 (14.3%) belonged to the group of statins. The mean age was 64.2 ± 14.3 years. RESULTS The severity of sepsis on admission was as follows: Sepsis, n=147 (63.6%), Severe sepsis, n=26 (11.3%) and Septic shock, n=58 (25.1%). The mean length of stay in Intensive Care Unit (ICU) was10.8 ± 9.6 days and 21.2 ± 17 days in general hospital ward settings, without differences between groups of statin users and controls, p=0.873 and p=0.766, respectively. The in-hospital mortality rate was 31.2% (n=72). Previous statin use did not affect in-hospital or 30-day mortality (OR 0.978; 95% CI 0.339 to 2.274; p=0.789). Creatinine levels on days 3 and 14 were substantially higher in statins group (1.80 ±1.39 vs. 1.45 ± 1.47 mg/dl) (p=0.010) and (1.42 ± 1.14 vs. 1.09 ± 1.05 mg/dl) (p=0.009), respectively. CONCLUSION Prior use of statins did not reduce in-hospital or 30-day mortality in septic patients and it may be associated with impaired renal function in this group of Argentinian participants.
Homology modeling and deletion mutants of human nicotinamide mononucleotide adenylyltransferase isozyme 2: New insights on structure and function relationship

Nicotinamide mononucleotide adenylyltransferase (NMNAT) catalyzes the formation of NAD by means of nucleophilic attack by 5′‐phosphoryl of NMN on the α‐phosphoryl group of ATP. Humans possess three NMNAT isozymes (NMNAT1, NMNAT2, and NMNAT3) that differ in size and sequence, gene expression pattern, subcellular localization, oligomeric state and catalytic properties. Of these, NMNAT2, the least abundant isozyme, is the only one whose much‐needed crystal structure has not been solved as yet. To fill this gap, we used the crystal structures of human NMNAT1 and NMNAT3 as templates for homology‐based structural modeling of NMNAT2, and the resulting raw structure was then refined by molecular dynamics simulations in a water box to obtain a model of the final folded structure. We investigated the importance of NMNAT2's central domain, which we postulated to be dispensable for catalytic activity, instead representing an isozyme‐specific control domain within the overall architecture of NMNAT2. Indeed, we experimentally confirmed that removal of different‐length fragments from this central domain did not compromise the enzyme's catalytic activity or the overall tridimensional structure of the active site.
Visualizing brine channel development and convective processes during artificial sea-ice growth using Schlieren optical methods

ABSTRACT Two non-invasive optical Schlieren methods have been adapted to visualize brine channel development and convective processes in experimentally grown sea ice obtained when a NaCl aqueous solution is cooled from above in a quasi-two-dimensional Hele–Shaw cell. The two different visualization methods, i.e. traditional and synthetic Schlieren optical imaging, produce high spatial resolution images of transport processes during ice growth, without any external perturbation. These images allow observations of the flow dynamics simultaneously within the ice layer, around the ice/water interface, and in the liquid water layer, revealing connections between the processes occurring within the two phases. Results from these methods show that desalination of the growing ice layer occurs by two concurrent, yet independent, mechanisms: (1) boundary layer convection persisting throughout the ice growth period, with short fingers present just below the ice/water interface, and (2) gravity-driven drainage from the brine channels producing deep penetrating convective streamers, which appear after a given time from the beginning of ice growth. The improved visualization and qualitative characterization of these processes show that Schlieren optical methods have exciting potential applications for future study of convective processes during sea-ice growth.
Surgical approach to malignant melanoma in the gastrointestinal tract

The gastrointestinal (GI) tract is a common site for malignant melanoma. Diagnosis of lesions in the GI tract is usually delayed until complications occur, such as obstruction, bleeding, or perforation of the GI tract. Of 348 patients with malignant melanoma treated during a 10‐year period, 11 had GI involvement either in a metastatic form or as a primary melanoma. Three of these patients were treated surgically for metastatic lesions in the small bowel causing intussusception, two for peritonitis secondary to perforation of the small bowel, and one for massive bleeding from metastatic melanoma in the stomach. Another patient had a primary melanoma in the esophagus and underwent esophagectomy. Three patients had primary melanomas of the anal canal and one of the rectum. Three of them underwent abdominoperineal resections, and two had bilateral groin dissection in addition. Six of the patients are alive 6 months to 4 years following diagnosis. The remaining five died of metastatic melanoma from 6 months to 4 years post‐surgery.
Doping-dependent nonlinear Meissner effect and spontaneous currents in high- T c superconductors

We measure the local harmonic generation from superconducting thin films at microwave frequencies to investigate the intrinsic nonlinear Meissner effect near ${T}_{c}$ in the zero magnetic field. Both second and third harmonic generation are measured to identify time-reversal symmetry breaking (TRSB) and time-reversal symmetric (TRS) nonlinearities. We perform a systematic doping-dependent study of the nonlinear response and find that the TRS characteristic nonlinearity current density scale follows the doping dependence of the depairing critical current density. We also extract a spontaneous TRSB characteristic current density scale that onsets at ${T}_{c}$, grows with decreasing temperature, and systematically decreases in magnitude (at fixed $T∕{T}_{c}$) with underdoping. The origin of this current scale could be Josephson circulating currents or the spontaneous magnetization associated with a TRSB order parameter.
Sydney Principles’ for reducing the commercial promotion of foods and beverages to children

Abstract A set of seven principles (the ‘Sydney Principles’) was developed by an International Obesity Taskforce (IOTF) Working Group to guide action on changing food and beverage marketing practices that target children. The aim of the present communication is to present the Sydney Principles and report on feedback received from a global consultation (November 2006 to April 2007) on the Principles. The Principles state that actions to reduce marketing to children should: (i) support the rights of children; (ii) afford substantial protection to children; (iii) be statutory in nature; (iv) take a wide definition of commercial promotions; (v) guarantee commercial-free childhood settings; (vi) include cross-border media; and (vii) be evaluated, monitored and enforced. The draft principles were widely disseminated and 220 responses were received from professional and scientific associations, consumer bodies, industry bodies, health professionals and others. There was virtually universal agreement on the need to have a set of principles to guide action in this contentious area of marketing to children. Apart from industry opposition to the third principle calling for a statutory approach and several comments about the implementation challenges, there was strong support for each of the Sydney Principles. Feedback on two specific issues of contention related to the age range to which restrictions should apply (most nominating age 16 or 18 years) and the types of products to be included (31 % nominating all products, 24 % all food and beverages, and 45 % energy-dense, nutrient-poor foods and beverages). The Sydney Principles, which took a children’s rights-based approach, should be used to benchmark action to reduce marketing to children. The age definition for a child and the types of products which should have marketing restrictions may better suit a risk-based approach at this stage. The Sydney Principles should guide the formation of an International Code on Food and Beverage Marketing to Children.
Leave-Cluster-Out Cross-Validation Is Appropriate for Scoring Functions Derived from Diverse Protein Data Sets

With the emergence of large collections of protein-ligand complexes complemented by binding data, as found in PDBbind or BindingMOAD, new opportunities for parametrizing and evaluating scoring functions have arisen. With huge data collections available, it becomes feasible to fit scoring functions in a QSAR style, i.e., by defining protein-ligand interaction descriptors and analyzing them with modern machine-learning methods. As in each data modeling ansatz, care has to be taken to validate the model carefully. Here, we show that there are large differences measured in R (0.77 vs 0.46) or R² (0.59 vs 0.21) for a relatively simple scoring function depending on whether it is validated against the PDBbind core set or validated in a leave-cluster-out cross-validation. If proteins from the same family are present in both the training and validation set, the estimated prediction quality from standard validation techniques looks too optimistic.
Sons, Daughters, and Family Processes: Does Gender of Children Matter?

In the United States, parents prefer a child of each gender, and on many dimensions parents tend to treat sons and daughters similarly. However, fathers' investments appear to be somewhat higher in families with sons. Fathers spend more time with sons than with daughters. Fathers more often marry and stay married and mothers report more marital happiness in families with sons—although associations are weakening and differentials are not large. Divorced fathers more often have custody of sons than of daughters. Daughters do more housework than sons, mirroring the gendered division of labor in adulthood. Parental support of educational activities varies, with some parental behaviors greater for sons but others higher for daughters. Whether parents encourage gender differences or whether children's gender-differentiated behaviors elicit differential parental treatment cannot be easily determined with studies to date, most of which are cross-sectional or limited in other ways that hamper conclusions about cau.
Identification of a membrane protein associated with expression of the surface exclusion region of the F transfer operon

Membrane preparations from radioactively labeled male and female strains of Escherichia coli K-12 were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. An intensely labeled band corresponding to a protein of molecular weight of 24,000 was readily apparent in preparations from Hfr and F-prime strains but not in those from female strains. When preparations from a series of Hfr strains containing transfer operon deletions were examined, presence of the band was found to be associated with retention of the region of the F transfer operon between ilzA and traD. Thus, the band ("protein S") appears to be the product of an F tra operon activity corresponding to traS (the gene for surface or entry exclusion), or an unknown gene in its vicinity. As predicted, protein S was subject to Fin+ control; only a faint band was detectable if the repressed plasmid R100 was also present in the F lac strain. A 24,000-dalton protein was also found in membrane preparations from strains carrying the derepressed plasmids R100-1 and R1-19 but not in those from strains carrying the repressed plasmids R100 or R1. Thus, the appearance of protein S in the membrane may be a general phenomenon resulting from transfer operon expression of F-like plasmids.
RAD26, the functional S. cerevisiae homolog of the Cockayne syndrome B gene ERCC6.

Transcription‐coupled repair (TCR) is a universal sub‐pathway of the nucleotide excision repair (NER) system that is limited to the transcribed strand of active structural genes. It accomplishes the preferential elimination of transcription‐blocking DNA lesions and permits rapid resumption of the vital process of transcription. A defect in TCR is responsible for the rare hereditary disorder Cockayne syndrome (CS). Recently we found that mutations in the ERCC6 repair gene, encoding a putative helicase, underly the repair defect of CS complementation group B. Here we report the cloning and characterization of the Saccharomyces cerevisiae homolog of CSB/ERCC6, which we designate RAD26. A rad26 disruption mutant appears viable and grows normally, indicating that the gene does not have an essential function. In analogy with CS, preferential repair of UV‐induced cyclobutane pyrimidine dimers in the transcribed strand of the active RBP2 gene is severely impaired. Surprisingly, in contrast to the human CS mutant, yeast RAD26 disruption does not induce any UV‐, cisPt‐ or X‐ray sensitivity, explaining why it was not isolated as a mutant before. Recovery of growth after UV exposure was somewhat delayed in rad26. These findings suggest that TCR in lower eukaryotes is not very important for cell survival and that the global genome repair pathway of NER is the major determinant of cellular resistance to genotoxicity.
Hemin Upregulates Egr-1 Expression in Vascular Smooth Muscle Cells via Reactive Oxygen Species ERK-1/2–Elk-1 and NF-&kgr;B

Reactive oxygen species (ROS) and oxidant stress are important mediators of cardiovascular pathologies including atherosclerosis. One source of ROS in the vasculature is free heme released from hemoglobin. Because Egr-1, the regulator of cell proliferation and apoptosis, is also induced by oxidant stress and is likewise implicated in atherosclerosis, we examined the regulation of Egr-1 by heme in vascular smooth muscle cells (SMCs). Hemin increased Egr-1 expression (mRNA, protein) within 30 minutes and ERK-1/2 phosphorylation and nuclear translocation within 5 minutes. Inhibiting hemin-induced ERK-1/2 activation by U0126 (MAPK-inhibitor), the antioxidant N-acetyl cysteine, the NADPH oxidase inhibitors apocynin and diphenyleneiodonium chloride, the superoxide scavenger tiron, or tricarbonyldichlororuthenium(II)-dimer (carbon-monoxide donor; CORM-2) blocked hemin-induced Egr-1 expression. Hemin activated Elk-1, SRF, and NF-&kgr;B and promoted their interaction with the Egr-1 promoter. Downregulating Elk-1 (via siRNA) or blocking NF-&kgr;B activation (via BAY-11-7082) abolished hemin induction of Egr-1. Finally, hemin-induced Egr-1 bound the promoters of tissue factor (TF), Plasminogen Activator Inhibitor (PAI)-1, and NGF-1A Binding (NAB)-2, upregulating their expression, and increased the biochemical activity of TF and PAI-1. Upregulation of Egr-1 and its target genes by heme-induced oxidant stress may be an important event in the initiation and progression of inflammatory vascular diseases such as atherosclerosis.
Methylphenidate improves fatigue scores in Parkinson disease: A randomized controlled trial

Fatigue is a common nonmotor symptom in idiopathic Parkinson disease (IPD) that can prominently affect everyday function. This study was a randomized, double‐blind, placebo‐controlled trial evaluating methylphenidate for the treatment of fatigue in patients with IPD maintained on their regular medications. Thirty‐six patients were randomized to receive either methylphenidate (10 mg three times per day; n = 17) or placebo (n = 19) for 6 weeks. Primary outcomes were the change from baseline on two separate self‐report fatigue questionnaires: the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI). Secondary outcomes included the Unified Parkinson Disease Rating Scale (UPDRS) motor score and the five individual domains of the MFI. Fourteen patients in the methylphenidate group and 16 patients in the control group remained on the intervention for the entire study period. In the treatment arm, mean FSS score was reduced by 6.5 points (from a baseline of 43.8) and mean MFI score was reduced by 8.4 points (from a baseline of 51.0). Both these reductions were significant (P < 0.04). Smaller reductions in the placebo group were nonsignificant. Mean UPDRS motor score did not change significantly in either group. Analysis of MFI subscores showed a significant reduction in General Fatigue in the methylphenidate group (P < 0.001). Overall, adverse effects of medication were more frequent in the placebo group. In conclusion, methylphenidate was effective in lowering fatigue scores in patients with IPD following a 6‐week treatment period. © 2007 Movement Disorder Society
Cestocidal activity of Acacia auriculiformis

Abstract The cestocidal activity of Acacia auriculiformis was evaluated using rats each harbouring a single adult worm of Hymenolepis diminuta. The ethanol extract (300 mg/kg/day) and the saponins (200 mg/kg/day) obtained from the funicles of A. auriculiformis, were administered orally to two groups each of 10 rats, respectively, on day 20 after oral inoculation with a single cysticercoid of H. diminuta. Adult worms were expelled within 5 days from rats treated with the ethanol extract and within 3 days from those treated with saponins. No appreciable side effects were observed in the treated rats.
Metaphyseal osteopathy in three Australian Kelpie siblings

Case report Metaphyseal osteopathy (MO) was diagnosed in three Australian Kelpie puppies that were presented for veterinary assessment of lameness. The three puppies were siblings. Each was from a different litter by the same breeding pair. The puppy in case one was seen by the authors, and the puppies in cases two and three were patients at other veterinary hospitals. However, the medical records and radiographs were examined and reviewed for this report. Radiographic investigation of the lameness revealed pathognomonic appearance of MO affecting the metaphyseal region of the long bones in all three puppies. The diagnosis was confirmed on histopathology in one patient. Conclusion MO is considered a disease of large and giant‐breed dogs, being rarely reported in non‐large‐breed dogs, and has not been reported in the Australian Kelpie, which is considered a medium‐breed dog. This case series suggests a previously unreported breed predisposition to MO in the Australian Kelpie.