Miracle-dz/UniFAR-FTUs huggingface dataset:
Hammock: a hidden Markov model-based peptide clustering algorithm to identify protein-interaction consensus motifs in large datasets

Motivation: Proteins often recognize their interaction partners on the basis of short linear motifs located in disordered regions on proteins’ surface. Experimental techniques that study such motifs use short peptides to mimic the structural properties of interacting proteins. Continued development of these methods allows for large-scale screening, resulting in vast amounts of peptide sequences, potentially containing information on multiple protein-protein interactions. Processing of such datasets is a complex but essential task for large-scale studies investigating protein-protein interactions. Results: The software tool presented in this article is able to rapidly identify multiple clusters of sequences carrying shared specificity motifs in massive datasets from various sources and generate multiple sequence alignments of identified clusters. The method was applied on a previously published smaller dataset containing distinct classes of ligands for SH3 domains, as well as on a new, an order of magnitude larger dataset containing epitopes for several monoclonal antibodies. The software successfully identified clusters of sequences mimicking epitopes of antibody targets, as well as secondary clusters revealing that the antibodies accept some deviations from original epitope sequences. Another test indicates that processing of even much larger datasets is computationally feasible. Availability and implementation: Hammock is published under GNU GPL v. 3 license and is freely available as a standalone program (from http://www.recamo.cz/en/software/hammock-cluster-peptides/) or as a tool for the Galaxy toolbox (from https://toolshed.g2.bx.psu.edu/view/hammock/hammock). The source code can be downloaded from https://github.com/hammock-dev/hammock/releases. Contact: muller@mou.cz Supplementary information: Supplementary data are available at Bioinformatics online.
Bioinformatics Applications Note Sequence Analysis Ampa: an Automated Web Server for Prediction of Protein Antimicrobial Regions

AMPA is a web application for assessing the antimicrobial domains of proteins, with a focus on the design on new antimicrobial drugs. The application provides fast discovery of antimicrobial patterns in proteins that can be used to develop new peptide-based drugs against pathogens. Results are shown in a user-friendly graphical interface and can be downloaded as raw data for later examination.
Increased Maintenance of Obsessive-Compulsive Disorder Remission after Integrated Serotonergic Treatment and Cognitive Psychotherapy Compared with Medication Alone

Background: Both medication and psychotherapy are effective in obsessive-compulsive disorder (OCD). However, they both have disadvantages. We aimed at studying the long-term effectiveness of integrated treatment compared with medication alone. Methods: A private practice sample of 20 consecutive patients with OCD (DSM-III-R) who achieved remission or marked improvement [Yale-Brown Obsessive-Compulsive Scale (YBOCS) score ≤10 and Global Assessment of Functioning (GAF) scale score ≧70] after drug treatment (clomipramine or selective serotonin reuptake inhibitors for 12–24 months) with or without concurrent cognitive psychotherapy were followed up. In the integrated treatment group, psychotherapy was started on the second or third visit and was timed to end after medication. Efforts were applied to integrate treatments within a biopsychosocial theoretical framework. As randomisation was not feasible in the study setting, treatment allocation was based on patients’ preference. Patients were assessed before treatment, after treatment and at each follow-up contact with the YBOCS, the Hamilton Depression Rating Scale, and the GAF scale. Kaplan-Meier survival analysis was performed on the time to OCD relapse. Results: Of the factors studied (gender, age, duration of disorder, severity of OCD symptoms at baseline), only treatment was associated with outcome. Of 10 patients treated with medication alone, 8 relapsed. Of 10 patients who received integrated treatment, only 1 relapsed. The estimated mean survival time was significantly higher (p < 0.001) in the integrated treatment group (132 months, 95% CI 107–157) than in the medication group (25 months, 95% CI 12–38). Conclusions: Although our results need confirmation by further, more robust studies, the long-term superiority of integrated treatment over medication alone was large. Patients with OCD might have viable options other than long-term drug treatment.
Agouti signaling protein and other factors modulating differentiation and proliferation of immortal melanoblasts

The melanocyte lineage potentially forms an attractive model system for studies in cell differentiation, developmental genetics, cell signaling, and melanoma, because differentiated cells produce the visible pigment melanin. Immortal lines of murine melanoblasts (melanocyte precursors) have been described previously, but induction of differentiation involved a complex culture system with keratinocyte feeder cells. Here we describe conditions for both growth and induced differentiation of the melanoblast line melb‐a, without feeder cells, and analyze factors that directly control proliferation and differentiation of these pure melanoblasts. Several active factors are products of developmental and other coat color genes, including stem cell factor (SCF), melanocyte‐stimulating hormone (αMSH), and agouti signaling protein (ASP), a natural antagonist at the MSH receptor (melanocortin 1 receptor, MC1R) encoded by the agouti gene. A stable analog of αMSH (NDP‐MSH) stimulated differentiation and inhibited growth. ASP in excess inhibited both effects of NDP‐MSH, that is, ASP could inhibit pigmentation and stimulate growth. These effects provide an explanation for the interactions in mice of melanocyte developmental mutations with yellow agouti and Mc1r alleles, and a role for embryonic expression patterns of ASP. © 2001 Wiley‐Liss, Inc.
From Bag of Languages to Family Trees From Noisy Corpus

In this paper, we use corpus-based measures for constructing phylogenetic trees and try to address some questions about the validity of doing this and applicability to linguistic areas as against language families. We experiment with four corpus based distance measures for constructing phylogenetic trees. Three of these measures were earlier tried for estimating language distances. We use a fourth measure based on phonetic and orthographic feature n-grams. We compare the trees obtained using these measures and present our observations.
High vancomycin serum trough is not associated with reduction of mortality in methicillin-resistant Staphylococcus aureus bloodstream infections

The current Infectious Diseases Society of America (IDSA) and the American Society of Health-System Pharmacists (ASHP) guidelines recommend a vancomycin serum trough concentration of 15 to 20 mg/L in patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). The objective of this study was to evaluate the mortality difference in MRSA BSI pre and post hospital-wide implementation of higher serum trough concentration per IDSA/ ASHP guidelines. This was a retrospective cohort study performed in an integrated hospital health system (2238 beds) in Southeast Michigan. We evaluated 1173 consecutive individual patients with MRSA BSI over a 9-year period. The vancomycin minimum inhibitory concentrations (MICs) were determined by Etest method for all isolates. Attainment of vancomycin serum trough concentration per IDSA/ASHP guidelines was implemented in January 2010 by clinical pharmacist as part of the antimicrobial stewardship program. During the study period, the mean vancomycin MIC was 1.57 ± 0.26 mg/L, the percentage of MRSA isolates with vancomycin MIC ≥ 2 mg/L was 17.5%, and the 30-day all-cause mortality was 16.5%. There was no difference in mortality during the 9-year period (p=0.193). There was no change in all-cause mortality for MRSA BSI after the hospital-wide implementation of higher vancomycin dose and serum trough concentration per IDSA/ ASHP guidelines. Prospective multicenter, controlled studies evaluating optimal dosing strategies for vancomycin are warranted. Correspondence to: Marcus J. Zervos, Division Head, Infectious Diseases, Henry Ford Health System, Professor of Medicine, Wayne State University School of Medicine, Detroit, MI 48202, USA, Tel: +1-313-916-2573; Fax: +1-313-9162993; E-mail: mzervos1@hfhs.org
Update: A non‐parametric method for the measurement of size diversity, with emphasis on data standardization. The measurement of the size evenness

A method for the measurement of the size diversity based on the classical Shannon–Wiener expression was proposed as a proxy of the shape of the size distribution. The summatory of probabilities of a discrete variable (such as species relative abundances) in the original Shannon–Wiener expression was substituted by an integral of the probability density function of a continuous variable (such as body size). Here, we propose an update of this method by including the measurement of the size e‐evenness, just dividing the exponential of the size diversity by its possible maximum for a given size range. Assuming a domain of the size range of (0,∞), for a given logarithmic mean ( mln ) and a logarithmic standard deviation (σln) , the distribution with the highest diversity is the Log‐Normal. The size e‐evenness ranges between 0 and 1 because of the division by the maximum exponential diversity. Size e‐evenness is useful to discriminate whether variations in size diversity are due to changes in the shape of the size distribution or caused by differences in size dispersion.
Enhanced physician adherence to antibiotic use guidelines through increased availability of guidelines at the time of drug ordering in hospital setting

Some studies have shown that making practice guidelines accessible to physicians when they are making clinical decisions could improve prescribing practices. The aim of the study was to assess the benefit of impact on physician adherence of the intervention that consisted of embedding previously paper‐based antibiotic guidelines in the computerized physician drug order entry system of a teaching hospital in order to make these guidelines available to physician at the time of antibiotic ordering. Before the intervention, these guidelines were available in booklet form in all the wards of the hospital.
On the full trispectrum in multi-field DBI inflation

We compute the leading order connected four-point function of the primordial curvature perturbation in multi-field DBI inflation models. We confirm that the consistency relations in the squeezed limit and in the counter-collinear limit hold as in single field models thanks to special properties of the DBI action. We also study the momentum dependence of the trispectra coming from the adiabatic, mixed and purely entropic contributions separately and we find that they have different momentum dependence. This means that if the amount of the transfer from the entropy perturbations to the curvature perturbation is significantly large, the trispectrum can distinguish multi-field DBI inflation models from single field DBI inflation models. A large amount of transfer $T_{\mathcal{RS}} \gg 1 $ suppresses the tensor to scalar ratio $r \propto T_{\mathcal{RS}}^{-2}$ and the amplitude of the bispectrum $f_{NL}^{equi} \propto T_{\mathcal{RS}}^{-2}$ and so it can ease the severe observational constraints on the DBI inflation model based on string theory. On the other hand, it enhances the amplitude of the trispectrum $\tau_{NL}^{equi} \propto T_{\mathcal{RS}}^2 f_{NL}^{equi \;2}$ for a given amplitude of the bispectrum.
Deposition of ammonium and nitrate in the roots of maize seedlings supplied with different nitrogen salts

This study measured total osmolarity and concentrations of NH4+, NO3–, K+, soluble carbohydrates, and organic acids in maize seminal roots as a function of distance from the apex, and NH4+ and NO3– in xylem sap for plants receiving NH4+ or NO3– as a sole N-source, NH4+ plus NO3–, or no nitrogen at all. The disparity between net deposition rates and net exogenous influx of NH4+ indicated that growing cells imported NH4+ from more mature tissue, whereas more mature root tissues assimilated or translocated a portion of the NH4+ absorbed. Net root NO3– influx under Ca(NO3)2 nutrition was adequate to account for pools found in the growth zone and provided twice as much as was deposited locally throughout the non-growing tissue. In contrast, net root NO3– influx under NH4NO3 was less than the local deposition rate in the growth zone, indicating that additional NO3– was imported or metabolically produced. The profile of NO3– deposition rate in the growth zone, however, was similar for the plants receiving Ca(NO3)2 or NH4NO3. These results suggest that NO3– may serve a major role as an osmoticant for supporting root elongation in the basal part of the growth zone and maintaining root function in the young mature tissues.
Tumor suppressor cylindromatosis: expressed in IgA nephropathy and negatively associated with renal tubulo-interstitial lesion.

BACKGROUND IgA nephropathy is the major cause of end-stage renal failure in patients with primary glomerular diseases. Tumor suppressor cylindromatosis (CYLD), the recently identified member of the deubiquitinating enzymes, has been actively involved in regulation of inflammation. This study was undertaken to investigate the CYLD expression profile in IgA nephropathy and identify factors associated with CYLD expression. METHODS Forty-one cases of IgA nephropathy were selected. CYLD expression in the kidney biopsy tissue was measured by immunohistochemical staining. Relevant clinical and pathological data were analyzed, and Logistic regression analysis was carried out to identify factors associated with CYLD expression. RESULTS CYLD was specifically expressed in renal tubular epithelial cells in 70% of the studied patients with IgA nephropathy. All patients with positive CYLD staining had proteinuria, while only 72.7% of patients with negative CYLD had proteinuria (P = 0.003). Among studied proteinuric patients, those with positive CYLD had significantly less tubulo-interstitial lesions and higher estimated glomerular filtration rate (eGFR) levels when compared with those patients showed negative CYLD results. Logistic regression analysis indicated that the urinary protein excretion and eGFR were identified as predictors for the CYLD expression. CONCLUSION CYLD is expressed in renal tubular epithelial cells and appears to be associated negatively with tubulointerstitial lesions, however, its exact functional role remains to be clarified in further experiments.
Exposure to Ingested Airborne Pollutant Particulate Matter Increases Mucosal Exposure to Bacteria and Induces Early Onset of Inflammation in Neonatal IL-10–Deficient Mice

Background:Epidemiological associations between early-life air pollution exposure and increased risk of inflammatory bowel diseases have been shown. Our aim was to determine if exposure to airborne particulate matter (PM10) during the neonatal period would alter colitis in the interleukin (IL)-10−/− mouse model. Methods:IL-10−/− pregnant dams and pups were fed chow ± PM10 (9 &mgr;g/g) and pups were studied at 10, 14, and 20 weeks. Twenty-week-old mice were given 2% dextran sodium sulfate. Metagenomic analysis of stool was performed. Bacterial translocation was assessed by serum lipopolysaccharide and culturing bacteria from mesenteric lymph nodes and spleen. Cytokine expression was measured in gut homogenates using the MesoScale discovery platform. PM10 was applied to CMT93 cells ± J744 macrophages, and resistance and cytokine secretion were assessed. THP-1 macrophages were incubated with Escherichia coli HB101 ± PM10 for assessment of uptake and killing. Results:PM10 exposure increased colonic proinflammatory cytokines and bacterial translocation into mesenteric lymph nodes, whereas IL-17A levels were reduced in PM10-fed 10-week-old mice. Bifidobacterium was decreased in mice fed PM10, whereas serum lipopolysaccharide was increased. PM10 interfered with phagocytosis and killing in THP-1 cells. In coculture, PM10 increased tumor necrosis factor &agr; and fluorescein isothiocyanate–dextran flux. After dextran sodium sulfate treatment, PM10-fed mice responded with increased colonic tumor necrosis factor &agr; and IL-1&bgr; and a larger percentage of PM10-fed mice had live bacteria in the mesenteric lymph nodes. Conclusions:Our data suggest that early exposure to pollution particulates can result in an earlier onset of intestinal disease in genetically susceptible hosts and can alter responses to gut injury in later life.
Visual-cognitive processing deficits in pediatric multiple sclerosis

Background: Children with multiple sclerosis (MS) can suffer significant cognitive deficits. This study investigates the sensitivity and validity in pediatric MS of two visual processing tests borrowed from the adult literature, the Brief Visuospatial Memory Test-Revised (BVMTR) and the Symbol Digit Modalities Test (SDMT). Objective: To test the hypothesis that visual processing is disproportionately impacted in pediatric MS by comparing performance with that of healthy controls on the BVMTR and SDMT. Methods: We studied 88 participants (43 MS, 45 controls) using a neuropsychological assessment battery including measures of intelligence, language, visual memory, and processing speed. Patients and demographically matched controls were compared to determine which tests are most sensitive in pediatric MS. Results: Statistically significant differences were found between the MS and control groups on BVMTR Total Learning (t (84) = 4.04, p < 0.001, d = 0.87), BVMTR Delayed Recall (t (84) = 4.45, p < 0.001, d = 0.96), and SDMT (t (38) = 2.19, p = 0.035, d = 0.69). No significant differences were found between groups on confrontation naming or general intellectual ability. Validity coefficients exploring correlation between BVMTR, SDMT, and disease characteristics were consistent with the adult literature. Conclusions: This study found that BVMTR and SDMT may be useful in assessing children and adolescents with MS.
Adhesion of Composite Resin to Bleached and Unbleached Bovine Enamel

Cylinders of microfil and small-particle light-cured composite resin were bonded to the flattened labial enamel surface of young bovine incisor teeth which had previously been subjected to four different treatments: (1) teeth immersed in 35% hydrogen peroxide (HP) for 60 min and etched (E) with 37% phosphoric acid gel for 60 sec; (2) teeth immersed in saline (S) for 60 min and E for 60 sec; (3) teeth E for 60 sec and immersed in HP for 60 min; and (4) teeth E for 60 sec, immersed in S for 60 min. Specimens were stored in water at 37°C for one and seven days prior to tension- and shear-testing. A total of 256 teeth was tested— eight teeth in each group for each day, for each resin, and for each test. Statistical analysis of the results indicated that there was a highly significant reduction in adhesive bond strength of the resins when the enamel was exposed to HP as compared with S. SEM examination of randomly selected fractured test specimens indicated that this reduction in adhesive bond strength occurred primarily at the bonding resin-enamel interface. Less significant differences in bond strength were noted in the control specimens, with regard to resin type, time of storage, and the etching order.
Cardiac CaM Kinase II Genes &dgr; and &ggr; Contribute to Adverse Remodeling but Redundantly Inhibit Calcineurin-Induced Myocardial Hypertrophy

Background— Ca2+-dependent signaling through CaM Kinase II (CaMKII) and calcineurin was suggested to contribute to adverse cardiac remodeling. However, the relative importance of CaMKII versus calcineurin for adverse cardiac remodeling remained unclear. Methods and Results— We generated double-knockout mice (DKO) lacking the 2 cardiac CaMKII genes &dgr; and &ggr; specifically in cardiomyocytes. We show that both CaMKII isoforms contribute redundantly to phosphorylation not only of phospholamban, ryanodine receptor 2, and histone deacetylase 4, but also calcineurin. Under baseline conditions, DKO mice are viable and display neither abnormal Ca2+ handling nor functional and structural changes. On pathological pressure overload and &bgr;-adrenergic stimulation, DKO mice are protected against cardiac dysfunction and interstitial fibrosis. But surprisingly and paradoxically, DKO mice develop cardiac hypertrophy driven by excessive activation of endogenous calcineurin, which is associated with a lack of phosphorylation at the auto-inhibitory calcineurin A site Ser411. Likewise, calcineurin inhibition prevents cardiac hypertrophy in DKO. On exercise performance, DKO mice show an exaggeration of cardiac hypertrophy with increased expression of the calcineurin target gene RCAN1-4 but no signs of adverse cardiac remodeling. Conclusions— We established a mouse model in which CaMKII’s activity is specifically and completely abolished. By the use of this model we show that CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin-dependent hypertrophy. These data suggest inhibition of CaMKII but not calcineurin as a promising approach to attenuate the progression of heart failure.
Depressive-like behavioral profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

Background: To unravel the causes of major depressive disorder (MDD), the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament, or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored. Methods: Behavioral data (including body postures, orientations, gaze directions, inter-individual distances, and locations in the cage) were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys. Results: Consistent with our previous studies, we found depressive-like characteristics (e.g., inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall) among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles. Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a “spontaneous” model of depressive disorders.