Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Neutral Sphingomyelinase-2 (NSM 2) in the Control of T Cell Plasma Membrane Lipid Composition and Cholesterol Homeostasis

The activity of neutral sphingomyelinase-2 (NSM2) to catalyze the conversion of sphingomyelin (SM) to ceramide and phosphocholine at the cytosolic leaflet of plasma membrane (PM) is important in T cell receptor (TCR) signaling. We recently identified PKCζ as a major NSM2 downstream effector which regulates microtubular polarization. It remained, however, unclear to what extent NSM2 activity affected overall composition of PM lipids and downstream effector lipids in antigen stimulated T cells. Here, we provide a detailed lipidomics analyses on PM fractions isolated from TCR stimulated wild type and NSM2 deficient (ΔNSM) Jurkat T cells. This revealed that in addition to that of sphingolipids, NSM2 depletion also affected concentrations of many other lipids. In particular, NSM2 ablation resulted in increase of lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) which both govern PM biophysical properties. Crucially, TCR dependent upregulation of the important T cell signaling lipid diacylglycerol (DAG), which is fundamental for activation of conventional and novel PKCs, was abolished in ΔNSM cells. Moreover, NSM2 activity was found to play an important role in PM cholesterol transport to the endoplasmic reticulum (ER) and production of cholesteryl esters (CE) there. Most importantly, CE accumulation was essential to sustain human T cell proliferation. Accordingly, inhibition of CE generating enzymes, the cholesterol acetyltransferases ACAT1/SOAT1 and ACAT2/SOAT2, impaired TCR driven expansion of both CD4+ and CD8+ T cells. In summary, our study reveals an important role of NSM2 in regulating T cell functions by its multiple effects on PM lipids and cholesterol homeostasis.
Differential effects of luteolin and its glycosides on invasion and apoptosis in MDA-MB-231 triple-negative breast cancer cells

Luteolin is known to have anticancer activity in various cancers. Recent studies have shown that luteolin glycosides, such as luteolin-8-C-β-fucopyranoside, 7-methoxy-luteolin-8-C-β-(6- deoxyxylopyranos-3-uloside) and luteolin-8-C-β-d-glucopyranoside, flavonoids that are present in Arthraxon hispidus, exert antimigratory and anti-invasive effects, but no cytotoxic effect in estrogen receptor-positive MCF7 breast cancer cells. In the present study, we further investigated and compared differential effects of luteolin and its glycosides in MDA-MB-231 triple-negative breast cancer cells. Luteolin suppressed the expression of matrix metalloproteinase-9 and inhibited migration and invasion in MDA-MB-231 cells treated with the tumor promotor 12-O-tetradecanoylphorbol-13-acetate at non-cytotoxic concentrations (0, 5, and 10 μM). Furthermore, at cytotoxic concentrations (20 and 40 μM), luteolin induced apoptosis via extrinsic and intrinsic pathways in MDA-MB-231 cells. However, luteolin glycosides did not exert any cytotoxic, antimigratory, or anti-invasive effect in MDA-MB-231 cells. In brief, luteolin had both antimetastatic and cytotoxic effects on MDA-MB-231 cells, whereas luteolin glycosides had no effect on this cell line. Taking together the present results and our previous findings on the differential effects of luteolin and its glycosides on MDA-MB-231 and MCF-7 breast cancer cells, luteolin and its glycosides can be suggested as a potential candidate for breast cancer therapy.
Detrimental Effects of a Retrieval-Extinction Procedure on Nicotine Seeking, but Not Cocaine Seeking

Retrieval-extinction memory reactivation procedures have been used to prevent the return of learned fear and drug seeking in preclinical models. These procedures first reactivate the original memory with a brief cue exposure (i.e., retrieval) session, and then disrupt memory reconsolidation by conducting extinction training within the reconsolidation window. The original memory is thought to be updated with the new information conveyed by extinction learning, resulting in a persistent therapeutic effect beyond that observed with extinction training alone (i.e., no retrieval). Here, we attempted to replicate the therapeutic effects on cocaine seeking reported by Xue et al. (2012), and extend these findings to nicotine seeking. Rats self-administered either cocaine or nicotine with contingent cues for weeks, and were then divided into two groups. The retrieval group underwent a 10-min retrieval session wherein drug cues were available, but drug was not. Ten minutes later, they were allowed to continue cue extinction training for an additional 60 min. The no retrieval group underwent a contiguous 70-min cue extinction session. These procedures continued for weeks, followed by a test for spontaneous recovery of drug seeking. No group differences were observed on any measure of cocaine seeking, although both groups exhibited extinction and spontaneous recovery. By contrast, for nicotine seeking, the retrieval group exhibited resistance to extinction, an effect that persisted on the spontaneous recovery test. These findings underscore the importance of drug type in the outcome of retrieval-extinction procedures and moreover indicate that retrieval-extinction procedures can be detrimental to nicotine seeking.
Synthesis and cytotoxic evaluation of some quinazolinone- 5-(4-chlorophenyl) 1, 3, 4-oxadiazole conjugates

1, 3, 4- Oxadiazoles and quinazolinones are privileged structures with extensive biological activities. On account of reported anticancer activity of them, in this study, a multi-step reaction procedure has been developed for the synthesis of some quinazolinone-1, 3, 4-oxadiazole derivatives. Reaction of the synthesized 3-amino-4(3H) quinazolinone derivatives with chloroacetyl chloride in the presence of dichloromethane/triethylamine yielded 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives as intermediate. Treatment of the resultants with 5- (4-chlorophenyl) 1, 3, 4-oxadiazole-2-thiol in dry acetone and potassium carbonate gave coupled derivatives of quinazolinone-1, 3, 4-oxadiazole. The cytotoxic effect of final compounds was tested against MCF-7 and HeLa cell lines using MTT assay. Compound 2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio) N-(4-oxo-2-propylquinazolin)3(4H)acatamide 6a exhibited remarkable cytotoxic activity at 10 and 100 μM against HeLa cell line. The alteration of substituents on C2 of quinazolinone ring revealed that the introduction of propyl moeity improved cytotoxic activity against HeLa cell line.
What Is Meditation? Proposing an Empirically Derived Classification System

Meditation is an umbrella term, which subsumes a huge number of diverse practices. It is still unclear how these practices can be classified in a reasonable way. Earlier proposals have struggled to do justice to the diversity of meditation techniques. To help in solving this issue, we used a novel bottom-up procedure to develop a comprehensive classification system for meditation techniques. In previous studies, we reduced 309 initially identified techniques to the 20 most popular ones. In the present study, 100 experienced meditators were asked to rate the similarity of the selected 20 techniques. Using multidimensional scaling, we found two orthogonal dimensions along which meditation techniques could be classified: activation and amount of body orientation. These dimensions emphasize the role of embodied cognition in meditation. Within these two dimensions, seven main clusters emerged: mindful observation, body-centered meditation, visual concentration, contemplation, affect-centered meditation, mantra meditation, and meditation with movement. We conclude there is no “meditation” as such, but there are rather different groups of techniques that might exert diverse effects. These groups call into question the common division into “focused attention” and “open-monitoring” practices. We propose a new embodied classification system and encourage researchers to evaluate this classification system through comparative studies.
Stress response associated with elective cesarean delivery: A comparison of the effect of general versus subarachnoid anesthesia

Context: Pregnancy, surgery, and anesthesia are identified forms of stress to the body. Sustained response to stress has been associated with increased morbidity and mortality. Aim: The aim of the study is to determine the effect of anesthetic techniques on the response to the stress of surgery and anesthesia. Study Design: This was a prospective, randomized, double-blind study. Subjects and Methods: One hundred and forty patients scheduled for elective cesarean section were recruited and randomized into two groups: general anesthesia and subarachnoid anesthesia. Heart rate (HR), blood glucose, and cortisol levels were used to evaluate the body response to stress. Blood samples to estimate glucose and cortisol levels were taken the night of the day before surgery, just before induction, 30 min after induction, 60 min after induction, and 24-h postsurgery. The Statistical Package for the Social Sciences Version 23 was used for analysis to find the mean and standard deviation of both categorical and noncategorical variables. The Independent t-test and two-tailed test were used to show the differences in the HR, blood glucose, and cortisol levels within and between the general anesthesia and subarachnoid anesthesia groups. Results: The two groups were comparable in terms of age, height, weight, and American Society of Anesthesiologists status. The changes in HR and blood glucose were similar in both groups. However, a statistically significant difference was noted in the level of cortisol between the two groups at 60-min postskin incision with 494 ± 161 nmol/L in the general anesthesia group as opposed to 347 ± 161 nmol/L in the subarachnoid anesthesia group with a P = 0.01. Conclusions: The study demonstrated that subarachnoid anesthesia offers an advantage over general anesthesia in terms of the reduction to stress response to surgery and anesthesia. However, patient's choice and the urgency in the delivery of the fetus should be considered in choosing a mode of anesthesia.
Evaluation of apamin effects on myelination process in C57BL/6 mice model of multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease that causes chronic inflammation in the central nervous system. The aim of this study was to investigate the effects of apamin administration on myelination process. MS was induced by feeding cuprizone pellets (0.2%) for 6 weeks (demyelination phase) followed by normal feeding for additional 2 weeks (remyelination phase). Briefly, C57BL/6 male mice were randomly divided into six groups. Group 1, received the regular food pellets. Group 2 contained two subgroups of 6 animals each (n = 2 × 6). First group received cuprizone for 6 weeks and the sacrificed while the second group after 6 weeks of cuprizone, received no treatment for additional 2 weeks. Group 3 (co-treatment group) was composed of two subgroups of 6 animals each (n = 2 × 6). Both subgroups received apamin (100 μ/kg) intraperitoneally twice a week for 6 weeks. First subgroup terminated at this time and the second subgroup was fed normal diet for two additional weeks. Group 4 (post-treatment, n = 6) received apamin (100 μ/kg) intraperitoneally twice a week for 2 weeks after cuprizone secession. Groups 5 and 6 (vehicle, n = 6 in each group) received phosphate buffered saline as the vehicle of apamin during demyelination and remyelination phase. At the end of each phase, mice were deeply anesthetized and perfused. Groups 5 and 6 (vehicle) received PBS as the vehicle during both phases. Mice were anesthetized, perfused with PBS through their heart, and their brains were removed. Brain sections stained with luxol fast blue and the images were analyzed. Apamin co-treatment significantly increased the myelin content as compared to the cuprizone group. Also, mild elevation in the myelinated areas was observed with apamin post-treatment in comparison with remyelination phase. Our results revealed that apamin prevents myelin destruction more significantly as compared to remyelination process. This observation explains the possible role of apamin in inhibiting the activation of the microglia cells than stimulation of the oligodendrocytic precursor cells.
Racing Fast and Slow: Defining the Tactical Behavior That Differentiates Medalists in Elite Men's 1,500 m Championship Racing

Background: 1,500 m running has long been a blue ribbon event of track championship racing. The eventual medalists employ common tactical behaviors such as a fast sustained pace from the start (gun-to-tape), or, slow initial laps that precede a precisely timed race kick. Before the kick, there are positional changes caused by surging, that can go uncharacterized. The inter-relationship of surge events, tactical positioning, and kick execution may have important implications for eventual medal winning outcomes and require further definition. Methods: In a randomized order, three middle-distance running experts were provided publically available video (YouTube) of 16 men's 1,500 m championship races across, European, World and Olympic championships. Each expert determined the occurrence of surges (defined as any point in the 1,500 m after the first 300 m where an athlete repositions by ≥3 places; or noticeably dictates a raise in the pace from the front) and the race kick. Following a second level verification of expert observations, tactical behaviors (quantity and distance marker within each race) mean distance from the finish were compared between fast (≤3:34.00, n = 5), medium (>3:34.00– ≤3:41.99, n = 7) and slow (≥3:42.00, n = 4) race categories. Results: Before the race kick, there were more surges in slow (5 ± 1.7, mean ±90% confidence limits) vs. fast races (1 ± 0.4, very large difference, very likely). The final surge before the race kick occurred earlier in fast (704 ± 133 m from the finish) vs. medium (427 ± 83 m, large difference, most likely), and slow races (370 ± 137 m, large difference, most likely). At initiation of the race kick in fast races, large positional differences were found between eventual gold (2 ± 1.2; likely) and silver (2.2 ± 1.6; likely) vs. bronze medalists (4.4 ± 1.2). In slow races, positional differences were unclear between eventual gold (4.3 ± 4.7), silver (4.8 ± 4.8) and bronze medalists (5.3 ± 1.5). Regardless of category, the race kick occurred on the last lap, with unclear differences between fast 244 ± 92 m medium 243 ± 56 m and slow 236 ± 142 m races. Conclusions: Presenting tactical behaviors by race categorization (slow, medium, fast race times), provides a novel understanding of the nuance of racing tactics. The present findings highlight the importance of considering within race athlete decision making across multiple-race scenarios during championship preparation.
Vertebral Artery Compression Syndrome

Objective: We aim to propose the term “vertebral artery compression syndrome” to describe a group of patients with a variety of clinical symptoms caused by vertebral artery compression of the medulla or spinal cord. Methods: We conducted the prospective case study in a university teaching hospital. Eleven patients who fulfilled the diagnostic criteria of vertebral artery compression syndrome and 22 age- and sex- matched controls were recruited. Clinical presentation and radiological findings of patients with vertebral artery compression syndrome were assessed and recorded. The basilar artery diameter was measured at the midpons level on T2 weighted MR images and compared between both groups. Results: Medullary compression was observed in 10 of 11 patients. The most common clinical presentation is dizziness, vertigo, imbalance, or ataxia followed by limb weakness. Cervical spinal cord compression was observed in one patient who presented with neck pain and left leg weakness. The mean basilar artery diameter was similar between patients and controls (3.95 ± 0.41 vs. 3.81 ± 0.43 mm). Conclusions: Vertebral artery compression of medulla and spinal cord may cause various clinical symptoms. Future studies are needed to further clarify the prevalence, natural history and treatment of this condition.
Transplanting Fecal Virus-Like Particles Reduces High-Fat Diet-Induced Small Intestinal Bacterial Overgrowth in Mice

Fecal microbiota transplantation (FMT) is an effective tool for treating Clostridium difficile infection in the setting of dysbiosis of the intestinal microbiome. FMT for other forms of human disorders linked to dysbiosis have been less effective. The fecal microbiota contains a high density of virus-like particles (VLP), up to 90% of which are bacteriophages, thought to have a role in regulating gut bacterial populations. We hypothesized that transplantation of the phage-containing fecal VLP fraction may reduce bacterial density in the dysbiotic setting of small intestinal bacterial overgrowth (SIBO). In an experiment using fecal transplantation, we compared the effect of the fecal VLP fraction (bacteria removed) against “Whole” FMT (bacteria intact) on the ileal microbiome. Recipients were either treated with a 30-day high-fat diet (HFD) as a model of dysbiosis to induce SIBO or were on a standard diet (SD). We observed that transplantation of fecal VLPs from donors on a HFD was sufficient to alter the ileal microbiota, but the effect was dependent on diet of the recipient. In recipients on a HFD, ileal bacterial density was reduced. In recipients on a SD, the ileal microbiome transitioned toward the composition associated with a HFD. In both recipient groups, transplantation of fecal VLP fraction alone produced the same outcome as whole FMT. Neither treatment altered expression of antimicrobial peptides. These findings demonstrated a potential role of VLPs, likely phages, for modifying the gut microbiome during dysbiosis.
Positive Selection in Bifidobacterium Genes Drives Species-Specific Host–Bacteria Communication

Bifidobacteria are commensal microorganisms that inhabit a wide range of hosts, including insects, birds and mammals. The mechanisms responsible for the adaptation of bifidobacteria to various hosts during the evolutionary process remain poorly understood. Previously, we reported that the species-specific PFNA gene cluster is present in the genomes of various species of the Bifidobacterium genus. The cluster contains signal transduction and adhesion genes that are presumably involved in the communication between bifidobacteria and their hosts. The genes in the PFNA cluster show high sequence divergence between bifidobacterial species, which may be indicative of rapid evolution that drives species-specific adaptation to the host organism. We used the maximum likelihood approach to detect positive selection in the PFNA genes. We tested for both pervasive and episodic positive selection to identify codons that experienced adaptive evolution in all and individual branches of the Bifidobacterium phylogenetic tree, respectively. Our results provide evidence that episodic positive selection has played an important role in the divergence process and molecular evolution of sequences of the species-specific PFNA genes in most bifidobacterial species. Moreover, we found the signatures of pervasive positive selection in the molecular evolution of the tgm gene in all branches of the Bifidobacterium phylogenetic tree. These results are consistent with the suggested role of PFNA gene cluster in the process of specific adaptation of bifidobacterial species to various hosts.
Progress Toward a Gonococcal Vaccine: The Way Forward

The concept of immunizing against gonorrhea has received renewed interest because of the recent emergence of strains of Neisseria gonorrhoeae that are resistant to most currently available antibiotics, an occurrence that threatens to render gonorrhea untreatable. However, despite efforts over many decades, no vaccine has yet been successfully developed for human use, leading to pessimism over whether this goal was actually attainable. Several factors have contributed to this situation, including extensive variation of the expression and specificity of many of the gonococcal surface antigens, and the ability of N. gonorrhoeae to resist destruction by complement and other innate immune defense mechanisms. The natural host restriction of N. gonorrhoeae for humans, coupled with the absence of any definable state of immunity arising from an episode of gonorrhea, have also complicated efforts to study gonococcal pathogenesis and the host's immune responses. However, recent findings have elucidated how the gonococcus exploits and manipulates the host's immune system for its own benefit, utilizing human-specific receptors for attachment to and invasion of tissues, and subverting adaptive immune responses that might otherwise be capable of eliminating it. While no single experimental model is capable of providing all the answers, experiments utilizing human cells and tissues in vitro, various in vivo animal models, including genetically modified strains of mice, and both experimental and observational human clinical studies, have combined to yield important new insight into the immuno-pathogenesis of gonococcal infection. In turn, these have now led to novel approaches for the development of a gonococcal vaccine. Ongoing investigations utilizing all available tools are now poised to make the development of an effective human vaccine against gonorrhea an achievable goal within a foreseeable time-frame.
Light Regulation of Carotenoid Biosynthesis in the Peel of Mandarin and Sweet Orange Fruits

Carotenoids are the pigments responsible for the coloration of the peel and pulp of Citrus fruits. Light is one of the major environmental factors influencing coloration and carotenoid content and composition of fleshy fruits and therefore their commercial and nutritional quality. Agronomical observations indicate that citrus fruits exposed to sunlight develop a brighter peel coloration than shaded fruit inside the tree canopy. In the present study, the effect of light deprivation on carotenoid profile, and in the expression of genes of carotenoid metabolism and their precursors have been analyzed in fruits of Clemenules mandarin (Citrus clementine) and Navelina orange (Citrus sinensis). Fruit shading accelerated peel degreening, chlorophyll degradation, and reduced chloroplastic-type carotenoids. Time-course shading experiments revealed that the stage of fruit ripening appears to be determinant for the effect of darkness in carotenoid biosynthesis. Fruit shading produced a down-regulation of the expression of key carotenoids biosynthetic genes (PSY, PDS, ZDS1, LCY2a, LCY2b, and CHX). However, expression of MEP pathway genes (DXS, HDR1, and GGPPS1) and the carotenoid cleavage dioxygenase, CCD4b1, responsible of the formation of the apocarotenoid β-citraurin, were not substantially affected by dark-grown conditions. The content of abscisic acid (ABA), an end product of the carotenoid pathway, was not affected by the light regime, suggesting that effect of shading on the precursor’s pool is not sufficient to impair ABA synthesis. A moderate increase in total carotenoid and in the expression of biosynthetic genes was observed in mature dark-grown mandarin and orange fruits. Collectively, results suggest that light stimulates carotenoid biosynthesis in the peel of citrus fruits but a light-independent regulation may also operate.