Miracle-dz/UniFAR-FTUs huggingface dataset:
The origins and evolution of chromosomes, dosage compensation, and mechanisms underlying venom regulation in snakes

Here we use a chromosome-level genome assembly of a prairie rattlesnake (Crotalus viridis), together with Hi-C, RNA-seq, and whole-genome resequencing data, to study key features of genome biology and evolution in reptiles. We identify the rattlesnake Z Chromosome, including the recombining pseudoautosomal region, and find evidence for partial dosage compensation driven by an evolutionary accumulation of a female-biased up-regulation mechanism. Comparative analyses with other amniotes provide new insight into the origins, structure, and function of reptile microchromosomes, which we demonstrate have markedly different structure and function compared to macrochromosomes. Snake microchromosomes are also enriched for venom genes, which we show have evolved through multiple tandem duplication events in multiple gene families. By overlaying chromatin structure information and gene expression data, we find evidence for venom gene-specific chromatin contact domains and identify how chromatin structure guides precise expression of multiple venom gene families. Further, we find evidence for venom gland-specific transcription factor activity and characterize a complement of mechanisms underlying venom production and regulation. Our findings reveal novel and fundamental features of reptile genome biology, provide insight into the regulation of snake venom, and broadly highlight the biological insight enabled by chromosome-level genome assemblies.
Influence of Matrigel on Single- and Multiple-Spheroid Cultures in Breast Cancer Research

This study aimed to develop and compare single and multiple 3D models such as multicellular tumor spheroids and to investigate the influence of Matrigel on their morphological and functional behavior. MDA-MB-231 3D models were generated in the presence and absence of Matrigel and their key biological properties within 6 days of culture were monitored. Our results revealed the formation of well-defined 3D models in the presence of Matrigel, with a uniform morphology, increased diameter, good circularity, and increased expression of a proliferation marker (PCNA). In comparison, 3D models generated without Matrigel were characterized by an irregular border, reduced dimensions and circularity, and a decrease of PCNA expression. Similarities between the single and multiple 3D cultures were found in their viability, Nrf2 expression, and glutathione (GSH) content. The influence of Matrigel on MDA-MB-231 spheroids metabolism under hypoxic conditions was highlighted by released lactate dehydrogenase and nitric oxide, GSH levels and expression of Nrf2 and Hsp70 proteins. Based on the increased expression of PCNA and the development of the hypoxia process in the presence of extracellular matrix, our study showed that the addition of Matrigel improves the growing environment of tumor spheroids, making it closer to that of in vivo tumor conditions.
Geminate Attrition in the Speech of Arabic–English Bilinguals Living in Canada

This study has three goals. First, it examines phonological attrition of the Arabic geminate (i.e., long sound)-singleton contrast in the speech of native speakers of Arabic who acquired English after puberty. Second, it compares geminate production in late bilinguals to early bilinguals. Third, it investigates whether universal phonetic/acoustic factors have an effect on the degree of attrition across generations. Participants performed a delayed word repetition task, where mean consonant duration was measured and compared across the two bilingual groups and compared with native speakers of Arabic. Results show that a geminate-singleton duration ratio continuum across groups was formed, where monolingual speakers of Arabic had the highest values, followed by late bilinguals, and then early bilinguals. These results are interpreted as evidence that language remains malleable across the lifespan. Moreover, whereas there was no effect of manner of articulation, voiced geminates showed a significantly higher degree of attrition across both bilingual groups. In addition, inherently longer geminates attrited at a significantly higher rate. Implications for models of phonological attrition are discussed.
Career Patterns in Administrations

Administrative careers are careers of civil servants, who are the individuals working in public administration institutions at different levels (central, state or regional, local) of government. Characteristics of a country’s civil service system determine what administrative career patterns typically look like. In the literature, two ideal-types of civil service systems are distinguished: the career-based system and the position-based system. In countries with a position-based civil service system, administrative careers usually are more diverse than in countries with a career-based civil service system. In most countries, however, intersectoral career mobility of civil servants is rather low. In democratic systems, recruitment and promotion in the civil service is formally based on merit and (with decreasing significance) seniority, while in practice political criteria and representativeness can be important selection criteria, especially for promotion to senior-level positions. As a consequence of their influential role in policy-making in many countries, research on careers in public administrations is mainly focusing on top-level positions: by analyzing the career background of top officials, public administration scholarship aims to understand the determinants of career success in public administrations as well as processes of administrative elite (re-)production and politicization. Findings from empirical studies suggest that political criteria do not crowd out meritocratic criteria in recruitment in most established democracies but that politicization can have severe negative impacts on administrative outcomes in young democracies and developing countries. Comparative empirical studies on administrative careers based on common datasets are largely lacking so far. More systematic comparative studies (across countries and over time) on administrative careers would not only make it possible to understand how larger systemic developments (e.g., administrative reform movements, democratic backsliding) affect mechanisms of recruitment and promotion in the civil service, but also help to better understand the inner mechanisms in bureaucratic organizations (e.g., by identifying organizational patterns of inequality).
Risk Factors for Sexual Violence Among College Students in Dating Relationships: An Ecological Approach

College students in dating relationships are vulnerable to sexual violence given that nine out of 10 acts of sexual violence are perpetrated by acquaintances, friends, or dating partners. Although past research has explored the risk factors for sexual violence, few studies have considered multileveled factors associated with sexual violence. This study uses the ecological model to investigate the risk factors for sexual violence among college students in dating relationships. Domains of individual, interpersonal, community, and societal levels were examined for their associations with sexual victimization. A prevalidated survey was conducted among 361 undergraduates in dating relationships from a public university in the south central United States. Chi-square tests and negative binomial regression analysis were conducted. Approximately 35% of the college students reported experiencing some form of sexual violence perpetrated by their dating partner including attempted and completed rapes. College women reported having experienced significantly higher rates of sexual violence in comparison with college men. On the contrary, this study documents the significant higher prevalence of sexual violence among heterosexual students than among lesbian, gay, bisexual, transgender, queer college students for experiencing at least one type of sexual violence or unwanted sexual contacts in a dating relationship. Sexual victimization is associated with gender, sexual assertiveness, the frequency of hookups, peer deviance, parental involvement, and perceived discrimination. Participants’ gender, frequent hookups, and lower sexual assertiveness are positively associated with risk of sexual victimization across all types of sexual violence. Multilevel prevention programs and strategies are needed on campuses to reduce sexual victimization among college students in dating relationships.
Stiripentol for the treatment of seizures associated with Dravet syndrome

ABSTRACT Introduction: Stiripentol is an orphan drug approved for the treatment of seizures associated with Dravet syndrome (since 2007 in Europe). Therapeutic options recently grew in this rare and severe early-onset epilepsy with the approval of stiripentol and cannabidiol in 2018 in the US and the positive trials just completed with fenfluramine. Areas covered: First, the short-term efficacy of stiripentol as adjunctive therapy to clobazam and valproate, which was discovered by serendipity thanks to a basket study and then confirmed in 1998 despite the small number of samples in phase III trials. Second, the further observational series worldwide, which showed sustained efficacy and satisfactory tolerability for up to 20 year exposure. Third, why it took more than 20 years for stiripentol be approved in a number of countries despite these extensive data: drug-drug interactions between stiripentol and comedication will be addressed, as well as the experimental and pharmacogenetic data which support the anticonvulsant effect of stiripentol per se. Expert opinion: Considering current and future competitors (cannabidiol and fenfluramine), efficacy seems lower for cannabidiol and seizure freedom seems occasionally be obtained with fenfluramine. Additionally, stiripentol could be especially useful in two critical conditions of the disease, very young age (<2 years) and convulsive status epilepticus.
Solid Lipid Nanoparticles Surface Modification Modulates Cell Internalization and Improves Chemotoxic Treatment in an Oral Carcinoma Cell Line

Solid lipid nanoparticles (SLN) present low toxicity, versatility to incorporate both lipophilic and hydrophilic drugs, controlled drug release and they are easy to scale-up. It is well known that the endocytosis pathway by which SLN are taken up and the subsequent subcellular distribution are crucial for the biological effect of the incorporated drug. In addition, interactions between SLN and cells depend on many factors, such as, the composition of nanoparticle surface. In this work different amounts of phosphatidylethanolamine polyethylene glycol (PE–PEG) were added to SLN composed of stearic acid, Epikuron 200 and sodium taurodeoxycholate. Characterization of obtained nanoparticle suspensions were performed by the analysis of particle size, polydispersity index, ζ-potential, cell toxicity and cell internalization pathway. We have observed that the presence of PE–PEG improves active cell internalization of the nanoparticles in an oral adenocarcinoma cell line, reducing non-specific internalization mechanisms. Finally, we have tested the effect of surface coating on the efficiency of incorporated drugs using all-trans retinoic acid as a model drug. We have observed that delivery of this drug into PE–PEG coated SLN increases its chemotoxic effect compared to non-coated SLN. Therefore, it can be concluded that surface modification with PE–PEG improves the efficiency and the specificity of the SLN-loaded drug.
Empirical and Computational Comparison of Alternative Therapeutic Exon Skip Repairs for Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is a common and devastating genetic disease that is primarily caused by exon deletions that create a genetic frameshift in dystrophin. Exon skipping therapy seeks to correct this by masking an exon during the mRNA maturation process, which restores dystrophin expression, but creates an edited protein missing both the original defect and the therapeutically skipped region. Crucially, it is possible to correct many defects in alternative ways, by skipping an exon either before, or after the patient’s defect. This results in alternatively edited, hybrid proteins, of possibly different properties and therapeutic consequences. Here, we examined three such dystrophin exon skipped edits, comprising two pairs of alternative repairs of the same underlying DMD defect. We found that in both cases, one member of each alternative repair was more stable than the other by a variety of thermodynamic and biochemical measures. We also examined the origin of these differences by molecular dynamics simulations, which showed that these stability differences were the result of different types of structural perturbations. For example, in one edit there was partial unfolding at the edit site which caused domain-localized perturbations, while in another there was unfolding at the protein domain junctions distal to the edit site which increased molecular flexibility. These results demonstrate that alternative exon skip repairs of the same underlying defect can have very different consequences at the level of protein structure and stability, and furthermore that these can arise by different mechanisms, either locally, or by more subtle long-range perturbations.
Clinical practice guidelines for the provision of renal service in Hong Kong: Peritoneal Dialysis

Clinical practice guidelines for the provision of renal service in Hong Kong: Peritoneal Dialysis CHEUK CHUN SZETO, WAI KEI LO and PHILIP KAM-TAO LI Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Department of Medicine, Tung Wah Hospital, and Dialysis Centre, Gleneagles Hospital, Hong Kong SAR, China
Preparation, characterization, and in vivo evaluation of cyclosporine cationic liposomes for the treatment of psoriasis

Abstract Cyclosporine (CYC), a calcineurin inhibitor acts specifically on T-cells and is one of the most effective treatment options for psoriasis. Systemic administration of the drug has been associated with dose-dependent toxic effects, while its topical delivery is a challenging task due to unfavourable physicochemical properties of drug. The aim of the present study is to develop and evaluate the efficacy of topical liposomal gel containing CYC loaded cationic liposomal nanocarriers in imiquimod induced psoriatic plaque model. Liposomes composed of DOTAP and cholesterol was formulated by different liposomal preparation techniques. Optimized liposomal carriers prepared by ethanol injection method were characterized with respect to size, zeta potential, entrapment efficiency, stability, in vitro drug release and in vivo studies. Cationic liposomes with particle size of 111 ± 1.62 nm, PDI of 0.27 ± 0.08, entrapment efficiency of 93 ± 2.12%, and zeta potential of 41.12 ± 3.56 mV were obtained. Drug loaded liposomal gels showed shear thinning behaviour, which is suitable for topical application. Topical application of CYC liposomal gels on imiquimod induced psoriatic plaque model reduced the symptoms of psoriasis and levels of key psoriatic cytokines such as tumour necrosis factor-α, IL-17, and IL-22. In conclusion, the developed liposomal carrier of CYC was found to be effective and can find application in treatment of psoriasis.
Extratemporal abnormalities in adults with unilateral temporal lobe epilepsy: A diffusion tensor imaging study

Aims & objectives: To analyse the fractional anisotropy (FA) and mean diffusivity (ADC) of various white matter tracts and the deep grey matter of unilateral temporal lobe epilepsy patients with age matched controls. Materials and methods: The study was conducted in the department of Radiology, Government Mohan Kumaramangalam Medical College, Salem. This study was done as an analytic, prospective case control study for a period of 2 years from September 2017 to August 2019. Patients with a clinical picture of temporal lobe epilepsy, with either structural abnormalities in temporal lobe on MR imaging or EEG consistent with temporal lobe epilepsy were included. Our control group consisted of 30 adults. Imaging protocol: The examinations were performed in 1.5T Philips MRI system. Results: Abnormalities are seen extensively bilaterally in the extra temporal grey and white matter, both ipsilateral and contralateral to the seizure origin. Conclusion: The findings strongly suggest that microstructural abnormalities are not only restricted to the seizure focus, but also involve ipsilateral and contralateral grey and white matter extensively.
Franchising—Paradigm of the Enterprise in the 21st Century

Franchising as a specific form of business is one of most interesting and perspective forms of doing business in the 21st century. The present circumstances on the market touched by the crisis require (expected in 2021) the permanent looking for the certainty for the enterprises. One of it is franchising. It concerned the classical closed vertical distribution system, which is managed on contractual basis and one of the system members, named franchisor, connects some levels in the production-distribution chain. His partner is a franchisee. Both partners are searching for the optimal level of correlative relationship. It is a dynamic commercial system, which represents a modern form of cooperation between the enterprises. Franchising is regarded as a progressive marketing strategy. It is one of few forms of entrepreneurship without stagnation in the crisis period, as well.
Cell surface α2,3-linked sialic acid facilitates Zika virus internalization

ABSTRACT The emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon antagonist rather than an entry receptor, the exact entry mechanism remains unresolved. Here we report that cell surface sialic acid plays an important role in ZIKV infection. Removal of cell surface sialic acid by neuraminidase significantly abolished ZIKV infection in Vero cells and human induced-pluripotent stem cells-derived neural progenitor cells. Furthermore, knockout of the sialic acid biosynthesis gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase resulted in significantly less ZIKV infection of both African and Asian lineages. Huh7 cells deficient in α2,3-linked sialic acid through knockout of ST3 β-galactoside-α2,3-sialyltransferase 4 had significantly reduced ZIKV infection. Removal of membrane-bound, un-internalized virus with pronase treatment revealed the role of sialic acid in ZIKV internalization but not attachment. Sialyllactose inhibition studies showed that there is no direct interaction between sialic acid and ZIKV, implying that sialic acid could be mediating ZIKV-receptor complex internalization. Identification of α2,3-linked sialic acid as an important host factor for ZIKV internalization provides new insight into ZIKV infection and pathogenesis.
A STUDY OF CRIMINAL BEHAVIOUR (CAUSALITY & PREVENTION OF CRIME)

This research is set out to carefully analyze the psyche of the criminals and to identify commonality in their behavior irrespective of the demographic aspect. The research aims at analyzing criminal law theories and their practical usage in modern scenario. Crime is defined as an act of deviance from socially accepted norms translated as criminal code. Countries all around the world have a definite set of criminal code compromising principles of morality and ethics as per their unique culture and society. But in practicality, these principles have failed to culminate the desired result of prevention of crime upon implementation by the traditional methods of enforcement. Deviance relates to the subjectivity of society. Considering morality as a subjective aspect would propagate deviance among individuals formed out of different circumstances than the majority. Hence, crime is often committed by the minority upon the majority in a society. The ultimate aim of the research is to identify the principle of causality in relation to crime and eventually portraying an effective approach for the prevention of crime.
The age‐related reduction in cerebral blood flow affects vertebral artery more than internal carotid artery blood flow

Ageing reduces cerebral blood flow (CBF), while mean arterial pressure (MAP) becomes elevated. According to ‘the selfish brain’ hypothesis of hypertension, a reduction in vertebral artery blood flow (VA) leads to increased sympathetic activity and thus increases MAP. In twenty‐two young (24 ± 3 years; mean ± SD) and eleven elderly (70 ± 5 years) normotensive men, duplex ultrasound evaluated whether the age‐related reduction in CBF affects VA more than internal carotid artery (ICA) blood flow. Pulse‐contour analysis evaluated MAP while near‐infrared spectroscopy determined frontal lobe oxygenation and transcranial Doppler middle cerebral artery mean blood velocity (MCA Vmean). During supine rest, MAP (90 ± 13 versus 78 ± 9 mmHg; P<0·001) was elevated in the older subjects while their frontal lobe oxygenation (68 ± 7% versus 77 ± 7%; P<0·001), MCA Vmean (49 ± 9 versus 60 ± 12 cm s−1; P = 0·016) and CBF (754 ± 112 versus 900 ± 144 ml min−1; P = 0·004) were low reflected in VA (138 ± 48 versus 219 ± 50 ml min−1; P<0·001) rather than in ICA flow (616 ± 96 versus 680 ± 120 ml min−1; P = 0·099). In conclusion, blood supply to the brain and its oxygenation are affected by ageing and the age‐related decline in VA flow appears to be four times as large as that in ICA and could be important for the age‐related increase in MAP.
Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli

Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli infection mounts for activation of MMP-9 and TACE in monocytes and whether this process regulates PICD. Results: The surface expression of TACE was most prominent on infected adult monocytes. In contrast, surface presentation of MMP-9 was highest on infected neonatal monocytes. Selective blocking of MMP-9 decreased CD95L secretion, while inhibition of TACE left CD95L secretion unaltered. Blocking of MMP-9 increased surface CD95L (memCD95L) expression on infected neonatal monocytes to levels comparable to infected adult monocytes. Moreover, MMP-9 inhibition raised PICD of infected neonatal monocytes to levels observed for infected adult monocytes. In contrast, TACE inhibition decreased PICD in infected monocytes. Addition of extracellular TNF effectively induced memCD95L presentation and PICD of adult monocytes and less of neonatal monocytes. Conclusion: MMP-9 activity is crucial for downregulating cell-contact dependent PICD in E. coli infected neonatal monocytes. By this mechanism, MMP-9 could contribute to reducing sustained inflammation in neonates.