Miracle-dz/UniFAR-FTUs huggingface dataset:
Non nucleoside reverse transcriptase inhibitors, molecular docking studies and antitubercular activity of thiazolidin-4-one derivatives.

BACKGROUND Management of Co-existence of Acquired immunodeficiency syndrome and Tuberculosis has become a global challenge due to emergence of resistant strains and pill burden. OBJECTIVE Hence aim of the present work was to design and evaluate compounds for their dual activity on HIV-1 and tuberculosis (TB). METHOD A series of seven, novel Thiazolidin-4-one derivatives were synthesized and evaluated for their anti-HIV and anti-tubercular activity alogwith Molecular docking studies. All the seven compounds displayed promising activity against the replication of HIV-1 in cell-based assays. The four most active compounds were further evaluated against X4 tropic HIV-1UG070 and R5 tropic HIV-1VB59 primary isolates. Binding affinity of all the designed compounds for HIV-RT and Mycobacterium tuberculosis Enol Reductase (MTB InhA) was gauged by molecular docking studies which revealed crucial thermodynamic interactions governing their binding. RESULT The CC50 values for the test compounds were in the range of, 15.08-34.9 µg/ml while the IC50 values were in the range of 16.1-27.13(UG070; X4) and 12.03-23.64 (VB59; R5) µg/ml. The control drug Nevirapine (NVP) exhibited CC50 value of 77.13 µg/ml and IC50 value of 0.03 µg/ml. Amongst all these compounds, compound number 3 showed significant activity with a TI value of 2.167 and 2.678 against the HIV-1 X4 and the R5 tropic virus respectively. In anti-mycobacterial screening compounds proved effective in inhibiting the growth of both log phase and starved MTB cultures. CONCLUSION Compound 3 has been found to be active against HIV-1 as well as MTB.
Ubiquitin-proteasome system participates in the de-aggregation of spermadhesin and DQH protein during boar sperm capacitation.

We studied the participation of the ubiquitin proteasome system (UPS) in spermadhesin release during in vitro capacitation (IVC) of domestic boar spermatozoa. At ejaculation, boar spermatozoa acquire low molecular weight (8-16 kDa) seminal plasma proteins, predominantly spermadhesins, aggregated on the sperm surface. Due to their arrangement, such aggregates are relatively inaccessible to antibody labeling. As a result of de-aggregation and release of the outer layers of spermadhesins from the sperm surface during IVC, antibody labeling becomes feasible in the capacitated spermatozoa. In vivo, the capacitation-induced shedding of spermadhesins from the sperm surface is associated with the release of spermatozoa from the oviductal sperm reservoir. We took advantage of this property to perform image-based flow cytometry to study de-aggregation and shedding of boar spermadhesins (AQN, AWN, PSP protein families) and boar DQH (BSP1) sperm surface protein which induces higher fluorescent intensity in capacitated vs. ejaculated spermatozoa. Addition of a proteasomal inhibitor (100 µM MG132) during IVC significantly reduced fluorescence intensity of all studied proteins (P<0.05) compared to vehicle control IVC. Western blot detection of spermadhesins did not support their retention during IVC with proteasomal inhibition (P>0.99) but showed the accumulation of DQH (P=0.03) during IVC, compared to vehicle control IVC. Our results thus demonstrate that UPS participates in the de-aggregation of spermadhesins and DQH protein from the sperm surface during capacitation, with a possible involvement in sperm detachment from the oviductal sperm reservoir and/or sperm-zona pellucida interactions.
Adverse Outcomes after Major Surgeries in Patients with Diabetes: A Multicenter Matched Study

The impact of diabetes on perioperative outcomes remains incompletely understood. Our purpose is to evaluate post-operative complications and mortality in patients with diabetes. Using the institutional and clinical databases of three university hospitals from 2009–2015, we conducted a matched study of 16,539 diabetes patients, aged >20 years, who underwent major surgery. Using a propensity score matching procedure, 16,539 surgical patients without diabetes who underwent surgery were also selected. Logistic regressions were used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) for post-operative complications and in-hospital mortality associated with diabetes. Patients with diabetes had a higher risk of postoperative septicemia (OR 1.33, 95% CI 1.01–1.74), necrotizing fasciitis (OR 3.98, 95% CI 1.12–14.2), cellulitis (OR 2.10, 95% CI 1.46–3.03), acute pyelonephritis (OR 1.86, 95% CI 1.01–3.41), infectious arthritis (OR 3.89, 95% CI 1.19–12.7), and in-hospital mortality (OR 1.51, 95% CI 1.07–2.13) compared to people without diabetes. Previous admission for diabetes (OR 2.33, 95% CI 1.85–2.93), HbA1c >8% (OR 1.96, 95% CI 1.64–2.33) and fasting glucose >180 mg/dL (OR 1.90, 95% CI 1.68–2.16) were predictors for post-operative adverse events. Diabetes patients who underwent surgery had higher risks of infectious complications and in-hospital mortality compared with patients without diabetes who underwent similar major surgeries.
Degenerative Expansion of a Young Supergene

Suppressed recombination ultimately leads to gene loss, as demonstrated by the depauperate Y chromosomes of long-established XY pairs. To understand the shorter term effects, we used high-resolution optical mapping and k-mer distribution analysis on a young non-recombining region of fire ant social chromosomes. Instead of shrinking, the region has increased in length by more than 30%. This demonstrates that degenerative expansion can occur during the early evolution of non-recombining regions.
Multidrug-resistant plasmids repress chromosomally encoded T6SS to enable their dissemination

Significance Ab has an alarming predisposition to attain multidrug resistance (MDR), and plasmids serve as vehicles for the spread of MDR among Ab clinical isolates. Most Ab strains harbor a constitutively active type VI secretion system (T6SS) that mediates indiscriminate, contact-dependent killing of neighboring, nonsister bacterial competitors. This poses a unique challenge to conjugative plasmids, as Ab plasmid “donors” presumptively kill potential “recipients” and vice versa. However, Acinetobacter plasmids are successfully spreading and acquiring additional antibiotic resistance cassettes, suggesting that they have evolved mechanisms to overcome the T6SS-mediated restriction on dissemination. Here, we show that silencing the T6SS is essential for plasmid conjugation. Our work provides new insights into the establishment and evolutionary dynamics of MDR dissemination among Acinetobacter. Acinetobacter baumannii (Ab) is a nosocomial pathogen with one of the highest rates of multidrug resistance (MDR). This is partially due to transmissible plasmids. Many Ab strains harbor a constitutively active type VI secretion system (T6SS) that is employed to kill nonkin bacteria. T6SS and plasmid conjugation both involve cell-to-cell contact. Paradoxically, successful conjugation requires the survival of the recipient, which is the target of the T6SS. Thus, an active T6SS in either the donor or the recipient poses a challenge to plasmid conjugation. Here, we show that large conjugative MDR plasmids heavily rely on their distinctive ability to repress the T6SS of their hosts to enable their own dissemination and the conjugation of other plasmids, contributing to the propagation of MDR among Acinetobacter isolates.
Successful Pacing Profiles of Olympic and IAAF World Championship Middle-Distance Runners Across Qualifying Rounds and Finals.

PURPOSE: This was the first study to analyze high-resolution pacing data from multiple global championships, allowing for deeper and rigorous analysis of pacing and tactical profiles in elite-standard middle-distance racing. The aim of this study was to analyze successful and unsuccessful middle-distance pacing profiles and variability across qualifying rounds and finals. METHODS: Finishing and 100-m split speeds and season's best times (SB) were collected for 265 men and 218 women competing in 800 m and 1500 m races, with pace variability expressed using coefficient of variation (CV). RESULTS: In both events, successful athletes generally separated themselves from slower athletes in the final 200 m, not by speeding up, but by avoiding slowing compared with competitors. This was despite different pacing profiles between events in the earlier part of the race preceding the endspurt. Approximately 10% of athletes ran SBs, showing a tactical approach to elite-standard middle-distance racing, and possible fatigue across rounds. Men's and women's pacing profiles were remarkably similar within each event, but the previously undescribed seahorse-shaped profile in the 800 m (predominantly positive pacing) differed from the J-shaped negative pacing of the 1500 m. Pacing variability was high compared with world records, especially in the finals (CV: 5.2 - 9.1%), showing that athletes need to be able to vary pace and cope with surges. CONCLUSIONS: Previous studies have focussed more on athletes in finals, but the present study showed that the best athletes had the physiological capacity to vary pace and respond to surges through successive competition rounds.
Epigenetic Modification Is Regulated by the Interaction of Influenza A Virus Nonstructural Protein 1 with the De Novo DNA Methyltransferase DNMT3B and Subsequent Transport to the Cytoplasm for K48-Linked Polyubiquitination

The nonstructural protein 1 (NS1) of the influenza A virus (IAV) is a multifunctional protein that counters cellular antiviral activities and is a virulence factor. However, the involvement of NS1 in DNA methylation during IAV infection has not been established. Here, we reveal that the NS1 protein binds the cellular DNMT3B DNA methyltransferase, thereby inhibiting the methylation of the promoters of genes encoding suppressors of JAK-STAT signaling. As a result, these suppressor genes are induced, and JAK-STAT signaling is inhibited. Furthermore, we demonstrate that the NS1 protein transports DNMT3B to the cytoplasm for ubiquitination and degradation. Thus, we identify the NS1 protein as a potential trigger of the epigenetic deregulation of JAK-STAT signaling suppressors and illustrate a novel mechanism underlying the regulation of host immunity during IAV infection. ABSTRACT The influenza virus nonstructural protein 1 (NS1) is a nonstructural protein that plays a major role in antagonizing host interferon responses during infection. However, a clear role for the NS1 protein in epigenetic modification has not been established. In this study, NS1 was found to regulate the expression of some key regulators of JAK-STAT signaling by inhibiting the DNA methylation of their promoters. Furthermore, DNA methyltransferase 3B (DNMT3B) is responsible for this process. Upon investigating the mechanisms underlying this event, NS1 was found to interact with DNMT3B but not DNMT3A, leading to the dissociation of DNMT3B from the promoters of the corresponding genes. In addition, the interaction between NS1 and DNMT3B changed the localization of DNMT3B from the nucleus to the cytosol, resulting in K48-linked ubiquitination and degradation of DNMT3B in the cytosol. We conclude that NS1 interacts with DNMT3B and changes its localization to mediate K48-linked polyubiquitination, subsequently contributing to the modulation of the expression of JAK-STAT signaling suppressors. IMPORTANCE The nonstructural protein 1 (NS1) of the influenza A virus (IAV) is a multifunctional protein that counters cellular antiviral activities and is a virulence factor. However, the involvement of NS1 in DNA methylation during IAV infection has not been established. Here, we reveal that the NS1 protein binds the cellular DNMT3B DNA methyltransferase, thereby inhibiting the methylation of the promoters of genes encoding suppressors of JAK-STAT signaling. As a result, these suppressor genes are induced, and JAK-STAT signaling is inhibited. Furthermore, we demonstrate that the NS1 protein transports DNMT3B to the cytoplasm for ubiquitination and degradation. Thus, we identify the NS1 protein as a potential trigger of the epigenetic deregulation of JAK-STAT signaling suppressors and illustrate a novel mechanism underlying the regulation of host immunity during IAV infection.
Bacteremia by Chryseobacterium oranimense, A Colistin-Resistant Gram-Negative Bacilli, in an Immunocompetent Pediatric Patient.

D Wald and DeMuri provide an excellent summary of the evolution of acute otitis media (AOM) pathogens since the introduction of the pneumococcal conjugate vaccine. However, predicting clinical treatment failure rates by in vitro susceptibilities alone has significant shortcomings, and we do not agree that these epidemiologic changes alone are sufficient to justify the recommendation to use amoxicillin-clavulanate as a first-line therapy for all patients. First, despite the changes in microbial epidemiology, the percentage of patients potentially benefitting from broad-spectrum antibiotic therapy is relatively small. For example, clinical outcomes vary substantially across pathogens; while only 19% of AOM cases caused by Streptococcus pneumoniae self-resolve, 48% of Haemophilus influenzae and 75% of Moraxella catarrhalis cases self-resolve. Thus, it is likely that fewer patients benefit from treatment as the proportion of patients with H. influenzae or M. catarrhalis increases. Based on the AOM pathogen distribution provided by Drs Wald and DeMuri, the spontaneous resolution rates previously mentioned and an assumption that 35% of H. influenzae produce β-lactamase, we estimate that at least 58% of patients will require no antibiotics, 29% will benefit from amoxicillin and only 13% will benefit from amoxicillin-clavulanate. Furthermore, serious complications from AOM are exceedingly rare and do not differ between patients who receive placebo versus antibiotics. A marginal benefit in symptom reduction is achieved with antibiotics; however, the number needed to treat for symptomatic benefit at days 2–3 is 20 patients. Second, recent data show that the clinical treatment failure for acute respiratory infections in children is low and does not differ between patients who receive narrowand broad-spectrum antibiotics (3.1% narrow
Creating custom Foldit puzzles for teaching biochemistry

The computer game Foldit is currently widely used as a biology and biochemistry teaching aid. Herein, we introduce a new feature of Foldit called “custom contests” that allows educators to create puzzles that fit their curriculum. The effectiveness of the custom contests is demonstrated by the use of five distinct custom contests in an upper‐level biochemistry class. The new custom contest feature can be implemented in classes ranging from middle school to graduate school to enable educators to best complement their current curriculum. © 2019 International Union of Biochemistry and Molecular Biology, 47(2): 133–139, 2019.
ANPELA: analysis and performance assessment of the label-free quantification workflow for metaproteomic studies

Abstract Label-free quantification (LFQ) with a specific and sequentially integrated workflow of acquisition technique, quantification tool and processing method has emerged as the popular technique employed in metaproteomic research to provide a comprehensive landscape of the adaptive response of microbes to external stimuli and their interactions with other organisms or host cells. The performance of a specific LFQ workflow is highly dependent on the studied data. Hence, it is essential to discover the most appropriate one for a specific data set. However, it is challenging to perform such discovery due to the large number of possible workflows and the multifaceted nature of the evaluation criteria. Herein, a web server ANPELA (https://idrblab.org/anpela/) was developed and validated as the first tool enabling performance assessment of whole LFQ workflow (collective assessment by five well-established criteria with distinct underlying theories), and it enabled the identification of the optimal LFQ workflow(s) by a comprehensive performance ranking. ANPELA not only automatically detects the diverse formats of data generated by all quantification tools but also provides the most complete set of processing methods among the available web servers and stand-alone tools. Systematic validation using metaproteomic benchmarks revealed ANPELA’s capabilities in 1 discovering well-performing workflow(s), (2) enabling assessment from multiple perspectives and (3) validating LFQ accuracy using spiked proteins. ANPELA has a unique ability to evaluate the performance of whole LFQ workflow and enables the discovery of the optimal LFQs by the comprehensive performance ranking of all 560 workflows. Therefore, it has great potential for applications in metaproteomic and other studies requiring LFQ techniques, as many features are shared among proteomic studies.
Bitkilerde Markör Destekli Seleksiyon

Gelecekte artacagi tahmin edilen nufusun besin ihtiyacini karsilamak icin temel besin maddelerinin uretimlerinin artirilmasi gerekmektedir. Bu durumda uretimi arttirmanin en iyi yolu bitki islahidir. Ancak bircok bitki turunde genetik varyasyonun daralmasi nedeniyle gerekli varyasyon tescilli cesitlerden, yerel cesitlerden ve yabani akrabalardan saglanarak, uygun genlerin gelistirilmis tekniklerle kultur cesitlerine aktarilmasi gerekmektedir. Belirlenen bu genlerin klasik bitki islahiyla aktarilmasinda bircok problemle karsilasilmaktadir. Markor destekli seleksiyon, klasik bitki islahinda karsilasilan bu sorunlara cozum bulmak amaciyla gelistirilen bir yaklasimdir. Bu teknikte, bircok avantaji nedeniyle molekuler markorler daha cok tercih edilmektedir. Molekuler markorler, farkliligi DNA duzeyinde olcen ve arastirilan genotiplerde istenen bir geni ya da ozelligi izlemek icin kullanilabilen markorlerdir. Markor destekli seleksiyon teknigi yabani gen kaynaklarindan gen transferleri, resesif allellerin yonlendirilmesi ve seleksiyonu, erken seleksiyon gibi kullaniminin yani sira; gen izolasyonu ve klonlanmasinda da kullanilabilir. Bu teknik oldukca hizli, etkin, dogru ve ekonomik oldugu icin klasik islaha yardimci bir seleksiyon teknigidir.
Prospects of targeted and immune therapies in SCLC

ABSTRACT Introduction: Small cell lung cancer (SCLC) is a tumor with a poor prognosis, often diagnosed in an advanced stage. Despite aggressive treatment of early and locally advanced disease, SCLC often relapses. First line chemotherapy provides good response rates in advanced disease, but progression free and overall survival are limited. New drugs such as some targeted therapies and immune therapies are promising in SCLC. Areas covered: In this review, we discuss the preclinical rationale and trial data for targeted therapies and immune therapies in SCLC, with a specific focus on clinical trials. Expert commentary: Lack of identification of clear prognostic and predictive biomarkers has limited the advances in treatment efficacy. This has most likely been the main cause of failure for compounds tested so far. Due to the highly mutational profile and the rapid growth pattern of SCLC, immunotherapy combined with chemotherapy seems the most promising treatment option. Concerning targeted agents, achievements made so far are small, but DLL3-antibodies or combinations of PARPi and immunotherapy could be very promising. These promising strategies also need testing in limited disease.
Platelet‐derived growth factor‐D expression mediates the effect of differentiated degree on prognosis in epithelial ovarian cancer

Platelet‐derived growth factor‐D (PDGF‐D) can enhance invasion and metastasis in several human malignancies. Although several studies have been performed to investigate the association between clinicopathological characteristics and prognosis in epithelial ovarian cancer (EOC), the mediation effect of PDGF‐D on above‐mentioned association have been seldom assessed. In this study, we detected the PDGF‐D expression from the tissues of patients with EOC and further collected clinicopathological characteristics and prognostic information to identify whether PDGF‐D mediated the effect of differentiated degree on prognosis in patients with EOC. A total of 190 paraffin‐embedded tissue samples from patients with EOC between July 2005 and December 2010 were collected. We performed a Kaplan‐Meier analysis for the association between differentiated degree and prognosis followed by a causal mediation analysis. The analysis results indicated that differentiated degree was associated with prognosis and PDGF‐D mediated the effect of differentiated degree on prognosis in patients with EOC, which might be a potential target for ovarian cancer treatment.
Association of Interleukin-6 and Interleukin-1 Family Gene Polymorphisms in Autoimmune Hepatitis.

INTRODUCTION AND AIM Autoimmune hepatitis (AIH) is an immune-mediated destruction of liver cells, in recognition of interface hepatitis, seropositivity for autoantibodies, and interface hepatitis in histology sections. Hepatocyte destruction in AIH is the direct result of CD4+ T-cell destruction. Yet, Th17 mediated immune attach and a diversity of cytokine networks, including pro-inflammatory cytokines such as Interleukin 1 (IL-1) and Interleukin 6 (IL-6), set the stage for the destructive liver damage. MATERIAL AND METHOD Peripheral blood samples from 57 patients, with AIH, recruited from referrals to the main pediatric hospital in Tehran. Single nucleotide polymorphisms for the following cytokines genes, were evaluated through, polymerase chain reaction with sequencespecific primers (PCR-SSP) assay: IL-1a (C/T -889), IL-1α (C/T -511), IL-1β (C/T +3962), IL-1 receptor (IL-1R; C/T Pst-I 1970), IL-1RA (C/T Mspa-I 11100), and IL-6 (C/G -174 and A/G nt565). RESULTS Significant higher frequency of genotype AA was detected in patients in IL-6 at position nt565 (15.8% in AIH patients vs. 2.9% in controls, p = 0.003). The haplotype GA of IL-6 at -174 and nt565, was significantly overrepresented in the AIH group, compared to (20.9% of AIH vs. 1.4% in controls p < 0.0001). CONCLUSION Results of our study, indicate significant deviation toward high yield IL-6 polymorphisms, in AIH patients. These data could bring new insights in pathophysiology of disease, which could contribute to developing novel treatments for AIH.
Research advances in traditional and modern use of Nelumbo nucifera: phytochemicals, health promoting activities and beyond

Abstract Nelumbo nucifera, or sacred lotus, has been valuable for us to use as vegetable, functional food, and herb medicine for over 2,000 years. The purpose of this article is to systematically review the traditional/modern uses, chemical compositions and pharmacological activities on different parts of N. nucifera. Traditionally, this plant has been used to treat chronic dyspepsia, hematuria, insomnia, nervous disorders, cardiovascular diseases, and hyperlipidemia. Now, phytochemical investigations on different parts of N. nucifera have indicated a wide spectrum of at least 255 constituents belonging to different chemical groups, including proteins, amino acids, polysaccharides, starch, flavonoids, alkaloids, essential oils, triterpenoids, steroids, and glycosides. Meanwhile, its pharmacological activities, including anti-obesity, antioxidant, anti-inflammatory, cardiovascular, hepatoprotective, hypoglycemic, hypolipidemic, antitumor, memory-improving and antiviral activities, have also been reviewed, together with its applications in health food industry and clinic uses of its single plant or herbal formulae. Herein, this review will provide state-of-the-art overview on its traditional and modern uses in food industry and medicines, together with the comprehensive profiles of phytochemicals, and health promoting bioactivities of this valuable plant. In addition, the new perspectives and future challenges in the research on lotus are also outlined.