Miracle-dz/UniFAR-FTUs huggingface dataset:
Significance of neutrophil microparticles in ischaemia‐reperfusion: Pro‐inflammatory effectors of endothelial senescence and vascular dysfunction

Endothelial senescence is an emerging cause of vascular dysfunction. Because microparticles are effectors of endothelial inflammation and vascular injury after ischaemia‐reperfusion, we examined leucocyte‐derived microparticles of spleen origin as possible contributors. Microparticles were generated from primary rat splenocytes by either lipopolysaccharide or phorbol‐myristate‐acetate/calcium ionophore, under conditions mimicking innate and adaptive immune responses. Incubation of primary porcine coronary endothelial cells with either type of microparticles, but not with those from unstimulated splenocytes, leads to a similar threefold raise in senescence‐associated β‐galactosidase activity within 48 hours, indicating accelerated senescence, to endothelial oxidative stress, and a fivefold and threefold increase in p21 and p16 senescence markers after 24 hours. After 12‐hour incubation, the endothelial‐dependent relaxation of coronary artery rings was reduced by 50%, at distinct optimal microparticle concentration. In vitro, microparticles were pro‐thrombotic by up‐regulating the local angiotensin system, by prompting tissue factor activity and a secondary generation of pro‐coagulant endothelial microparticles. They initiated an early pro‐inflammatory response by inducing phosphorylation of NF‐κB, MAP kinases and Akt after 1 hour, and up‐regulated VCAM‐1 and ICAM‐1 at 24 hours. Accordingly, VCAM‐1 and COX‐2 were also up‐regulated in the coronary artery endothelium and eNOS down‐regulated. Lipopolysaccharide specifically favoured the shedding of neutrophil‐ and monocyte‐derived microparticles. A 80% immuno‐depletion of neutrophil microparticles reduced endothelial senescence by 55%, indicating a key role. Altogether, data suggest that microparticles from activated splenocytes prompt early pro‐inflammatory, pro‐coagulant and pro‐senescent responses in endothelial cells through redox‐sensitive pathways. The control of neutrophil shedding could preserve the endothelium at site of ischaemia‐reperfusion–driven inflammation and delay its dysfunction.
PUBLIC SERVICE FOR SMART CITY THROUGH INTERNET MESSENGER: WHICH MESSENGER PERFORM BETTER IN TERMS OF ‘ANTI IDENTITY FRAUD’?

To deliver services to the public, the government needs to communicate with the resident. The easiest way to communicate without boundary is by using social media. This concept brings messenger applications such as Line, Whatsapp, and Telegram as a communication media for a smart city. However, of those three applications, which one is the safest to use? There are various threats such as cybercrime and identity fraud which make the government must choose the most appropriate application that can be applied as public service media. In this study the authors analyze that three application (Line, WhatsApp, and Telegram) in the most popular operating system, Android and iOS to assess which messenger application that has non repudiation characteristic – it means we should know the origin of data about who send the message to prevent an identity fraud in the development of e-government system in smart city. This research analyzed messenger storage location to get the desired data and perform further analysis into forensics analysis software. From this research WhatsApp messenger on every OS platform has the best performance. WhatsApp not only identifies user’s id but also their phone number like Telegram Messenger. Also, WhatsApp has no encryption on their conversation data that make the examiner easier to solve a case on WhatsApp than Telegram. WhatsApp also manages their media data well, all media have names registered in the database, have an extension and neatly organized in the media folder.
Identification of Regulatory SNPs Associated with Vicine and Convicine Content of Vicia faba Based on Genotyping by Sequencing Data Using Deep Learning

Faba bean (Vicia faba) is a grain legume, which is globally grown for both human consumption as well as feed for livestock. Despite its agro-ecological importance the usage of Vicia faba is severely hampered by its anti-nutritive seed-compounds vicine and convicine (V+C). The genes responsible for a low V+C content have not yet been identified. In this study, we aim to computationally identify regulatory SNPs (rSNPs), i.e., SNPs in promoter regions of genes that are deemed to govern the V+C content of Vicia faba. For this purpose we first trained a deep learning model with the gene annotations of seven related species of the Leguminosae family. Applying our model, we predicted putative promoters in a partial genome of Vicia faba that we assembled from genotyping-by-sequencing (GBS) data. Exploiting the synteny between Medicago truncatula and Vicia faba, we identified two rSNPs which are statistically significantly associated with V+C content. In particular, the allele substitutions regarding these rSNPs result in dramatic changes of the binding sites of the transcription factors (TFs) MYB4, MYB61, and SQUA. The knowledge about TFs and their rSNPs may enhance our understanding of the regulatory programs controlling V+C content of Vicia faba and could provide new hypotheses for future breeding programs.
Somatostatin Receptor-mediated Signaling in Smooth Muscle

In COS-7 cells, all five cloned somatostatin receptors are coupled via inhibitory G proteins to activation of an unidentified phospholipase C-β (PLC-β) isozyme and inhibition of adenylyl cyclase. In the present study, intestinal smooth muscle cells (SMC) that express only one receptor type, sstr3, and possess a full complement of G proteins and PLC-β isozymes were used to identify the PLC-β isozyme and the G proteins coupled to it and to adenylyl cyclase. Somatostatin-14 bound with high affinity to intestinal SMC; stimulated -myo-inositol-1,4,5-trisphosphate (IP3) formation, Ca2+ release, and contraction; and inhibited forskolin-stimulated cAMP formation in a pertussis toxin-sensitive fashion. Somatostatin also stimulated phosphoinositide hydrolysis in plasma membranes. Only those somatostatin analogs that shared a high affinity for sstr3 receptors elicited muscle contraction. IP3 formation, Ca2+ release, and contraction in permeabilized SMC and phosphoinositide hydrolysis in plasma membranes were inhibited (∼80%) by pretreatment with antibodies to PLC-β3 but not other PLC-β isozymes, and by antibodies to Gβ but not Gα. Inhibition of cAMP formation was partially blocked by antibody to Gαi1 or Gαo and additively blocked by a combination of both antibodies. Somatostatin-stimulated [35S]GTPγS-Gα complexes in plasma membranes were bound selectively by Gαi1 and Gαo antibodies. We conclude that in smooth muscle sstr3 is coupled to Gi1 and Go; the α subunits of both G proteins mediate inhibition of adenylyl cyclase, while the βγ subunits mediate activation of PLC-β3.
The Primacy of Gender: Gendered Cognition Underlies the Big Two Dimensions of Social Cognition

It is notable that across distinct, siloed, and disconnected areas of psychology (e.g., developmental, personality, social), there exist two dimensions (the “Big Two”) that capture the ways in which people process, perceive, and navigate their social worlds. Despite their subtle distinctions and nomenclature, each shares the same underlying content; one revolves around independence, goal pursuit, and achievement, and the other revolves around other-focus, social orientation, and desire for connection. Why have these two dimensions emerged across disciplines, domains, and decades? Our answer: gender. We argue that the characteristics of the Big Two (e.g., agency/competence, communion/warmth) are reflections of psychological notions of masculinity and femininity that render gender the basis of the fundamental lens through which one sees the social world. Thus, although past work has identified the Big Two as a model to understand social categories, we argue that gender itself is the social category that explains the nature of the Big Two. We outline support for this theory and suggest implications of a gendered cognition in which gender not only provides functional utility for cognitive processing but simultaneously enforces gender roles and limits men and women’s opportunities. Recognizing that the Big Two reflect masculinity and femininity does not confine people to act in accordance with their gender but rather allows for novel interventions to reduce gender-based inequities.
Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice.

The brain has evolved in an environment where food sources are scarce and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity/overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences of excessive energy intake are not well understood. Neurons expressing the neuropeptide hypocretin/orexin (Hcrt) in the lateral/perifonical hypothalamus (LH) are critical for homeostatic regulation, reward seeking, stress response, and cognitive functions. In this study, we examined adaptations in Hcrt cells regulating behavioral responses to salient stimuli in diet-induced obese mice. Our results demonstrated changes in primary cilia, synaptic transmission and plasticity, cellular responses to neurotransmitters necessary for reward seeking and stress responses in Hcrt neurons from obese mice. Activities of neuronal networks in the LH and hippocampus were impaired as a result of decreased hypocretinergic function. The weakened Hcrt system decreased reward seeking while altering responses to acute stress (stress coping strategy), which were reversed by selectively activating Hcrt cells with chemogenetics. Taken together, our data suggest that a deficiency in the Hcrt signaling may be a common cause of behavioral changes (such as lowered arousal, weakened reward seek and altered stress response) in obese animals.
Population characteristics of roe deer inhabiting a small forest

Studies were made over a period of several years of basic population processes in a group of roe deer inhabiting a small wood situated in fields. The purpose of this studies was to determine to what extent this community differs from roe deer living in fields surrounding the wood. It was found that the density of roe deer in the wood is several times greater than in the extensive area of fields surrounding it.
LMNA‐NTRK1 rearranged mesenchymal tumor (lipofibromatosis‐like neural tumor) mimicking pigmented dermatofibrosarcoma protuberans

We present the case of a 31‐year‐old female with a 1.5 cm pigmented nodule on the scalp. Histopathological examination revealed a proliferation of relatively bland spindle cells and pigmented dendritic cells, with interspersed lymphoid follicles diffusely infiltrating the adipose tissue. The microscopic differential diagnosis included pigmented dermatofibrosarcoma protuberans (DFSP). The spindle cells showed S‐100 and CD34 labeling but were negative for SOX‐10. Immunohistochemical stain for pan‐TRK was positive, while fluorescence in‐situ hybridization for PDGFB gene rearrangement was negative. Targeted RNA sequencing revealed an LMNA‐NTRK1 (exon2/exon10) fusion. This molecular result coupled with the histopathological findings and immunohistochemical profile supported the diagnosis of the recently characterized NTRK‐rearranged spindle cell neoplasm termed “lipofibromatosis‐like neural tumor (LPF‐NT). ” These neoplasms typically occur in superficial soft tissue and are characterized by a distinctive immunoprofile (CD34+, S‐100+, SOX10−). Histopathological differential diagnosis for LPF‐NT tumors includes lipofibromatosis, DFSP, low‐grade malignant peripheral nerve sheath tumor, and spindle cell/desmoplastic melanoma. The pigmented dendritic cells reminiscent of pigmented DFSP and lymphoid follicles noted in our case have not been previously reported in LPF‐NT, thus expanding the morphological spectrum of this entity. LMNA‐NTRK1 fusion serves both as a diagnostic and therapeutic biomarker, as cases with advanced disease may be amenable to targeted therapy using tyrosine kinase inhibitors.
Ras Suppressor-1 (RSU1) in Cancer Cell Metastasis: A Tale of a Tumor Suppressor

Cancer is a multifactorial disease responsible for millions of deaths worldwide. It has a strong genetic background, as mutations in oncogenes or tumor suppressor genes contribute to the initiation of cancer development. Integrin signaling as well as the signaling pathway of Ras oncogene, have been long implicated both in carcinogenesis and disease progression. Moreover, they have been involved in the promotion of metastasis, which accounts for the majority of cancer-related deaths. Ras Suppressor-1 (RSU1) was identified as a suppressor of Ras-induced transformation and was shown to localize to cell-extracellular matrix adhesions. Recent findings indicate that its expression is elevated in various cancer types, while its role in regulating metastasis-related cellular processes remains largely unknown. Interestingly, there is no in vivo work in the field to date, and thus, all relevant knowledge stems from in vitro studies. In this review, we summarize recent studies using breast, liver and brain cancer cell lines and highlight the role of RSU1 in regulating cancer cell invasion.
Global ocean spectrophotometric pH assessment: consistent inconsistencies.

Ocean Acidification (OA)-or the decrease in seawater pH resulting from ocean uptake of CO2 released by human activities-stresses ocean ecosystems and is recognized as a Climate and Sustainable Development Goal Indicator that needs to be evaluated and monitored. Monitoring OA related pH changes requires a high level of precision and accuracy. The two most common ways to quantify seawater pH are to measure it spectrophotometrically or to calculate it from Total Alkalinity (TA) and Dissolved Inorganic Carbon (DIC). However, despite decades of research, small but important inconsistencies remain between measured and calculated pH. To date, this issue has been circumvented by examining changes only in consistently-measured properties. Currently, the oceanographic community is defining new observational strategies for OA and other key aspects of the ocean carbon cycle based on novel sensors and technologies, that rely on validation against data records and/or synthesis products. Comparison of measured spectrophotometric pH to calculated pH from TA and DIC measured during the 2000s and 2010s eras, reveals that: 1) there is an evolution towards a better agreement between measured and calculated pH over time from 0.02 pH units in the 2000s to 0.01 pH units in the 2010s at pH>7.6; 2) a disagreement greater than 0.01 pH units persists in waters with pH<7.6, and 3) inconsistencies likely stem from variations in the spectrophotometric pH standard operating procedure (SOP). A reassessment of pH measurement and calculation SOPs and metrology is urgently needed.
Antibiotic Resistance Is Associated with Integrative and Conjugative Elements and Genomic Islands in Naturally Circulating Streptococcus pneumoniae Isolates from Adults in Liverpool, UK

Pneumonia is the sixth largest cause of death in the UK. It is usually caused by Streptococcus pneumoniae, which healthy individuals can carry in their nose without symptoms of disease. Antimicrobial resistance further increases mortality and morbidity associated with pneumococcal infection, although few studies have analysed resistance in naturally circulating pneumococcal isolates in adult populations. Here, we report on the resistome and associated mobile genetic elements within circulating pneumococcus isolated from adult volunteers enrolled in the experimental human pneumococcal colonisation (EHPC) research program at the Liverpool School of Tropical Medicine, UK. Pneumococcal isolates collected from 30 healthy asymptomatic adults who had volunteered to take part in clinical research were screened for antibiotic susceptibility to erythromycin and tetracycline, and whole-genome sequenced. The genetic context of resistance to one or both antibiotics in four isolates was characterised bioinformatically, and any association of the resistance genes with mobile genetic elements was determined. Tetracycline and macrolide resistance genes [tet(M), erm(B), mef(A), msr(D)] were detected on known Tn916-like integrative and conjugative elements, namely Tn6002 and Tn2010, and tet(32) was found for the first time in S. pneumoniae located on a novel 50 kb genomic island. The widespread use of pneumococcal conjugate vaccines impacts on serotype prevalence and transmission within the community. It is therefore important to continue to monitor antimicrobial resistance (AMR) genes present in both vaccine types and non-vaccine types in response to contemporary antimicrobial therapies and characterise the genetic context of acquired resistance genes to continually optimise antibiotic therapies.
Foraging Ecology and Energetics of the Frugivorous Bat Artibeus Jamaicensis

In Panama that bat Artibeus jamaicensis feeds primarily on figs (fruits of the genus Ficus). One hundred forty—two Ficus trees in 25 ha were mapped and their fruit production monitored for 2yr. Radio—tracking observations of foraging A. jamaicensis revealed that each bat carries away 9 ± 2 figs per night, enough to provide 40% more than the 43.9 kJ needed daily for basal metabolism and minimum maintenance flying. The estimated 6 ± 2 A. jamaicensis per ha carried away °7% of the 200, 000 figs (650kg) produced annually per hectare. Artibeus jamaicensis appears to be the most important dispersal agent for fig seeds in this area. See full-text article at JSTOR
Baloxavir Marboxil Single-dose Treatment in Influenza-infected Children

Background: Baloxavir marboxil (baloxavir) is a novel, cap-dependent endonuclease inhibitor that has previously demonstrated efficacy in the treatment of influenza in adults and adolescents. We assessed the safety and efficacy of baloxavir in otherwise healthy children with acute influenza. Methods: MiniSTONE-2 (Clinicaltrials.gov: NCT03629184) was a double-blind, randomized, active controlled trial enrolling children 1–<12 years old with a clinical diagnosis of influenza. Children were randomized 2:1 to receive either a single dose of oral baloxavir or oral oseltamivir twice daily for 5 days. The primary endpoint was incidence, severity and timing of adverse events (AEs); efficacy was a secondary endpoint. Results: In total, 173 children were randomized and dosed, 115 to the baloxavir group and 58 to the oseltamivir group. Characteristics of participants were similar between treatment groups. Overall, 122 AEs were reported in 84 (48.6%) children. Incidence of AEs was similar between baloxavir and oseltamivir groups (46.1% vs. 53.4%, respectively). The most common AEs were gastrointestinal (vomiting/diarrhea) in both groups [baloxavir: 12 children (10.4%); oseltamivir: 10 children (17.2%)]. No deaths, serious AEs or hospitalizations were reported. Median time (95% confidence interval) to alleviation of signs and symptoms of influenza was similar between groups: 138.1 (116.6–163.2) hours with baloxavir versus 150.0 (115.0–165.7) hours with oseltamivir. Conclusions: Oral baloxavir is well tolerated and effective at alleviating symptoms in otherwise healthy children with acute influenza. Baloxavir provides a new therapeutic option with a simple oral dosing regimen.
Context-sensitive cleavage of folded DNAs by loop-targeting bPNAs.

Herein, we demonstrate context-dependent molecular recognition of DNA by synthetic bPNA iron and copper complexes, using oxidative backbone cleavage as a chemical readout for binding. Oligoethyleneimine bPNAs displaying iron-EDTA or copper-phenanthroline sites were found to be efficient chemical nucleases for designed and native structured DNAs with T-rich single-stranded domains. Cleavage reactivity depends strongly on structural context, as strikingly demonstrated with DNA substrates of the form (GGGTTA)n. This repeat sequence from the human telomere is known to switch between parallel and antiparallel G-quadruplex (G4) topologies upon changing from potassium to sodium buffer: notably, bPNA-copper complexes efficiently cleave long repeat sequences into ~22 nt portions in sodium-but not potassium buffer. We hypothesize preferential cleavage of the antiparallel topology (Na+) over the parallel (K+) due to greater accessibility of the TTA loop to bPNA in the antiparallel (Na+) form. Similar ion-sensitive telomere shortening upon treatment with bPNA nucleases can be observed in both isolated and intracellular DNA from PC3 cells by qPCR. Live cell treatment was accompanied by accelerated cellular senescence, as expected for significant telomere shortening. Taken together, the loop-targeting approach of bPNA chemical nucleases complements prior intercalation strategies targeting duplex and quadruplex DNA. Structurally-sensitive loop-targeting enables discrimination between similar target sequences, thus expanding bPNA targeting beyond simple oligo-T sequences. Further, bPNA nucleases are cell membrane permeable, and therefore may be used to target native intracellular substrates. In addition, these data indicate that bPNA scaffolds can be a platform for new synthetic binders to particular nucleic acid structural motifs.
Interleukin‐1β but not tumor necrosis factor‐α potentiates neuronal damage by quinolinic acid: Protection by an adenosine A2A receptor antagonist

Quinolinic acid is an agonist at glutamate receptors sensitive to N‐methyl‐D‐aspartate (NMDA). It has been implicated in neural dysfunction associated with infections, trauma, and ischemia, although its neurotoxic potency is relatively low. This study was designed to examine the effects of a combination of quinolinic acid and the proinflammatory cytokines interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α). Compounds were administered to the hippocampus of anesthetized male rats, animals being allowed to recover for 7 days before histological analysis of the hippocampus for neuronal damage estimated by counting of intact, healthy neurons. A low dose of quinolinic acid or IL‐1β produced no damage by itself, but the two together induced a significant loss of pyramidal neurons in the hippocampus. Higher doses produced almost total loss of pyramidal cells. Intrahippocampal TNF‐α produced no effect alone but significantly reduced the neuronal loss produced by quinolinic acid. The adenosine A2A receptor antagonist ZM241385 reduced neuronal loss produced by the combinations of quinolinic acid and IL‐1β. The results suggest that simultaneous quinolinic acid and IL‐1β, both being induced by cerebral infection or injury, are synergistic in the production of neuronal damage and could together contribute substantially to traumatic, infective, or ischemic cerebral damage. Antagonism of adenosine A2A receptors protects neurons against the combination of quinolinic acid and IL‐1β. © 2007 Wiley‐Liss, Inc.