Miracle-dz/UniFAR-FTUs huggingface dataset:
Forged by DXZ4, FIRRE, and ICCE: How Tandem Repeats Shape the Active and Inactive X Chromosome

Recent efforts in mapping spatial genome organization have revealed three evocative and conserved structural features of the inactive X in female mammals. First, the chromosomal conformation of the inactive X reveals a loss of topologically associated domains (TADs) present on the active X. Second, the macrosatellite DXZ4 emerges as a singular boundary that suppresses physical interactions between two large TAD-depleted “megadomains. ” Third, DXZ4 reaches across several megabases to form “superloops” with two other X-linked tandem repeats, FIRRE and ICCE, which also loop to each other. Although all three structural features are conserved across rodents and primates, deletion of mouse and human orthologs of DXZ4 and FIRRE from the inactive X have revealed limited impact on X chromosome inactivation (XCI) and escape in vitro. In contrast, loss of Xist or SMCHD1 have been shown to impair TAD erasure and gene silencing on the inactive X. In this perspective, we summarize these results in the context of new research describing disruption of X-linked tandem repeats in vivo, and discuss their possible molecular roles through the lens of evolutionary conservation and clinical genetics. As a null hypothesis, we consider whether the conservation of some structural features on the inactive X may reflect selection for X-linked tandem repeats on account of necessary cis- and trans-regulatory roles they may play on the active X, rather than the inactive X. Additional hypotheses invoking a role for X-linked tandem repeats on X reactivation, for example in the germline or totipotency, remain to be assessed in multiple developmental models spanning mammalian evolution.
Molecular Links Between Angiogenesis and Neuroendocrine Phenotypes in Prostate Cancer Progression

As a common therapy for prostate cancer, androgen deprivation therapy (ADT) is effective for the majority of patients. However, prolonged ADT promotes drug resistance and progression to an aggressive variant with reduced androgen receptor signaling, so called neuroendocrine prostate cancer (NEPC). Until present, NEPC is still poorly understood, and lethal with no effective treatments. Elevated expression of neuroendocrine related markers and increased angiogenesis are two prominent phenotypes of NEPC, and both of them are positively associated with cancers progression. However, direct molecular links between the two phenotypes in NEPC and their mechanisms remain largely unclear. Their elucidation should substantially expand our knowledge in NEPC. This knowledge, in turn, would facilitate the development of effective NEPC treatments. We recently showed that a single critical pathway regulates both ADT-enhanced angiogenesis and elevated expression of neuroendocrine markers. This pathway consists of CREB1, EZH2, and TSP1. Here, we seek new insights to identify molecules common to pathways promoting angiogenesis and neuroendocrine phenotypes in prostate cancer. To this end, our focus is to summarize the literature on proteins reported to regulate both neuroendocrine marker expression and angiogenesis as potential molecular links. These proteins, often described in separate biological contexts or diseases, include AURKA and AURKB, CHGA, CREB1, EZH2, FOXA2, GRK3, HIF1, IL-6, MYCN, ONECUT2, p53, RET, and RB1. We also present the current efforts in prostate cancer or other diseases to target some of these proteins, which warrants testing for NEPC, given the urgent unmet need in treating this aggressive variant of prostate cancer.
Art and Analogy Help Scientists "See" Big Biological Molecules in 3D

Our research laboratory at Duke (joint with my husband Dave Richardson) studies the 3-dimensional structures of biological molecules such as proteins, nucleic acids, and their functional associations with each other. Those are the tiny machines that do almost all the work in our bodies, and are the targets of most drugs. Because the molecules are very much smaller than the wavelength of visible light, this research requires model-building with the data from high-tech tools such as synchrotron x-ray sources, big computers, big data, and now cryo-electron microscopy. However, we have often made breakthroughs initiated by a concept from the humanities, especially the visual arts. This piece tells four short stories of how art has influenced our scientific research.
A CVP-BASED LATTICE SIGNATURE SCHEME FOR NETWORK CODING

Pollution attack is one of the main threats confronting network coding. The policy of detection and prevention of polluted messages is an important aspect of secure framework in a network based on network coding. Inspired by the idea of self/nonself discrimination in immune principle, signature is an effective approach to the discrimination of normal message and abnormal message. Most of the existent signature schemes cannot catch up with the rapid development of high-speed computers. To provide a high-security guarantee to network coding and lower the computing complexity induced by signature scheme, we introduce lattice theory to construct a secure signature scheme. Firstly, we propose a lattice-based signature scheme for network coding and its core algorithm SampleCVP which can ensure the randomness of output signature. Secondly, we stipulate its security to the hard problem CVP (Closest Vector Problem) on lattices. Security analyses show that the proposed scheme has a stronger unforgeability for the natural property of lattices than traditional signature schemes.
Preoperative neurological deficit in acute type A aortic dissection.

OBJECTIVES Our goal was to evaluate postoperative outcomes in patients with type A aortic dissection with preoperative neurological deficits independent of shock. METHODS Between 2002 and 2017, 150 of 1600 patients, operated on for aortic dissection type A in 3 centres, presented with preoperative new onset neurological deficits. Postoperative outcomes were classified using a modified Rankin Scale (mRS) as 'no to moderate disability' (mRS 0-3) or as 'poor clinical outcome' (mRS 4-6). Clinical and radiographic data were analysed. RESULTS Ninety-three patients (62%) had no to moderate disability and 57 (38%) had a poor clinical outcome. The in-hospital mortality rate was 18% (28 patients). Patients with poor clinical outcomes were significantly older (P = 0.01) and had a significantly higher incidence of hypertension (P = 0.04), history of stroke (P = 0.03) and common carotid artery occlusion (left common carotid artery: P = 0.01; right common carotid artery: P < 0.01). One-third of all patients developed haemodynamic instability (P = 0.27). Cardiopulmonary bypass (P < 0.01) and cross-clamp (P = 0.03) times were significantly longer in patients with poor clinical outcomes. Age (odds ratio 1.041; P = 0.02) and history of stroke (odds ratio 2.651; P = 0.03) were predictive of poor clinical outcome; coma was not. Haemorrhagic transformation occurred in 7 patients without any independent predictors. CONCLUSIONS Most patients with preoperative neurological deficit have no to moderate disability postoperatively but commonly develop preoperative haemodynamic instability. This study suggests that an immediate surgical approach may be reasonable in patients with preoperative neurological deficit or coma.
Bcl-3 promotes multi-modal tumour cell migration via NF-κB1 mediated regulation of Cdc42.

A key challenge in the implementation of anti-metastatics as cancer therapies is the multi-modal nature of cell migration, which allows tumour cells to evade the targeted inhibition of specific cell motility pathways. The NF-κB co-factor B-cell lymphoma 3 (Bcl-3) has been implicated in breast cancer cell migration and metastasis, yet it remains to be determined exactly which cell motility pathways are controlled by Bcl-3 and whether migrating tumour cells are able to evade Bcl-3 intervention. Addressing these questions and the mechanism underpinning Bcl-3's role in this process would help determine its potential as a therapeutic target. Here we identify Bcl-3 as an upstream regulator of the two principal forms of breast cancer cell motility, involving collective and single-cell migration. This was found to be mediated by the master regulator Cdc42 through binding of the NF-κB transcription factor p50 to the Cdc42 promoter. Notably, Bcl-3 depletion inhibited both stable and transitory motility phenotypes in breast cancer cells with no evidence of migratory adaptation. Overexpression of Bcl-3 enhanced migration and increased metastatic tumour burden of breast cancer cells in vivo, while overexpression of a mutant Bcl-3 protein, which is unable to bind p50, suppressed cell migration and metastatic tumour burden suggesting that disruption of Bcl-3/NF-κB complexes is sufficient to inhibit metastasis. These findings identify a novel role for Bcl-3 in intrinsic and adaptive multi-modal cell migration mediated by its direct regulation of the Rho GTPase Cdc42 and identifies the upstream Bcl-3:p50 transcription complex as a potential therapeutic target for metastatic disease.
An overview of hypertension and cardiac involvement in Asia: Focus on heart failure

Cardiovascular Disease (CVD) is the leading cause of deaths worldwide, contributing to about 30% of all deaths. Half of the cases of CVD are estimated in Asia, the world's most populous continent. Hypertension, a major modifiable risk factor for CVD, results in more deaths than any other CV risk factors in the Asian regions. The total number of patients with hypertension is likely to grow as the population ages. The proportion of the elderly population aged 65 years or more in Asia is expected to increase from 7.4% in 2015 to 10.9% in 2030. It is important to note that more than half (54%) of the world's population live in Asia. Aside of being the biggest single risk factor for global deaths, hypertension is also an important precursor and most common risk factor of heart failure (HF). An increase in HF prevalence is clearly related to the rapid epidemiological transition caused by changes in lifestyle in Asian countries. However, the availability of data on HF burden and health care delivery is limited in Asia compared with Europe and North America. This reality has driven the working group of Asian experts for example the HOPE Asia Network to concentrate on hypertension as risk factors for CVD, with the mission to improve the management of hypertension resulting in organ protection toward a goal of achieving “ZERO” CV event in Asia. This paper aims to give an overview regarding the heart problems caused by hypertension in Asia, focus on HF.
Tree of motility – A proposed history of motility systems in the tree of life

Motility often plays a decisive role in the survival of species. Five systems of motility have been studied in depth: those propelled by bacterial flagella, eukaryotic actin polymerization and the eukaryotic motor proteins myosin, kinesin and dynein. However, many organisms exhibit surprisingly diverse motilities, and advances in genomics, molecular biology and imaging have showed that those motilities have inherently independent mechanisms. This makes defining the breadth of motility nontrivial, because novel motilities may be driven by unknown mechanisms. Here, we classify the known motilities based on the unique classes of movement‐producing protein architectures. Based on this criterion, the current total of independent motility systems stands at 18 types. In this perspective, we discuss these modes of motility relative to the latest phylogenetic Tree of Life and propose a history of motility. During the ~4 billion years since the emergence of life, motility arose in Bacteria with flagella and pili, and in Archaea with archaella. Newer modes of motility became possible in Eukarya with changes to the cell envelope. Presence or absence of a peptidoglycan layer, the acquisition of robust membrane dynamics, the enlargement of cells and environmental opportunities likely provided the context for the (co)evolution of novel types of motility.
Educational Interventions Improved Knowledge, Attitude, and Practice to Prevent HIV Infection among HIV-Negative Heterosexual Partners of HIV-Infected Persons

A 1-year quasi-experimental study was conducted among HIV-noninfected heterosexual partners of HIV-infected patients cared at a Thai tertiary care hospital. The educational interventions comprised a 1-hour educational session, a condom use teaching session, focus group discussion, and free HIV testing. Of the 88 seronegative partners enrolled, 53 and 35 underwent the educational interventions once and twice, respectively. After the educational interventions, the median score for knowledge on HIV infection and transmission prevention significantly increased (28 versus 21; P < .001). After the interventions, higher proportions of the participants would use treatment of the HIV-infected partners (77% versus 58%) and preexposure prophylaxis (59% versus 38%) as methods to prevent HIV transmission and have a regular HIV blood test every 6 months (94% versus 81%). Among the 35 participants who participated in the educational interventions twice, most of the knowledge and positive attitudes were retained. The rates of regular HIV testing every 6 months had increased significantly from baseline to 1 year later (29% to 74%, respectively). None of the participants developed HIV infection. These findings suggest that the study interventions could improve knowledge about HIV infection and transmission prevention, attitude and practices toward prevention, and increase regular HIV testing among the seronegative partners.
Time-correlated Single Ion Counting Mass Spectrometer with Long and Short Time-of-Flight Tubes and an Evaluation of Its Performance for Use in Trace Analysis of Allergenic Substances

An analyte molecule was ionized using a femtosecond laser as the ionization source and was measured by a twin-type time-of-flight mass spectrometer with long (42 cm) and short (6.4 cm) flight tubes. The signal was measured using an analog signal digitizer and a time-correlated single ion counting system, and performance was evaluated by comparing data obtained from both instruments. The short mass spectrometer had a mass resolution of 450 and was used in the trace analysis of allergenic substances in a fragrance.
Hormone‐mediated modulation of the electromotor CPG in pulse‐type weakly electric fish. Commonalities and differences across species

Like stomatogastric activity in crustaceans, vocalization in teleosts and frogs, and locomotion in mammals, the electric organ discharge (EOD) of weakly electric fish is a rhythmic and stereotyped electromotor pattern. The EOD, which functions in both perception and communication, is controlled by a two‐layered central pattern generator (CPG), the electromotor CPG, which modifies its basal output in response to environmental and social challenges. Despite major anatomo‐functional commonalities in the electromotor CPG across electric fish species, we show that Gymnotus omarorum and Brachyhypopomus gauderio have evolved divergent neural processes to transiently modify the CPG outputs through descending fast neurotransmitter inputs to generate communication signals. We also present two examples of electric behavioral displays in which it is possible to separately analyze the effects of neuropeptides (mid‐term modulation) and gonadal steroid hormones (long‐term modulation) upon the CPG. First, the nonbreeding territorial aggression of G. omarorum has been an advantageous model to analyze the status‐dependent modulation of the excitability of CPG neuronal components by vasotocin. Second, the seasonal and sexually dimorphic courtship signals of B. gauderio have been useful to understand the effects of sex steroids on the responses to glutamatergic inputs in the CPG. Overall, the electromotor CPG functions in a regime that safeguards the EOD waveform. However, prepacemaker influences and hormonal modulation enable an enormous versatility and allows the EOD to adapt its functional state in a species‐, sex‐, and social context‐specific manners.
Energy values of triticale or sorghum distillers' dried grains with solubles and rye fed to broiler chickens.

The current experiments were conducted to determine ileal digestible energy (IDE), metabolizable energy (ME), and nitrogen-corrected ME (MEn) of triticale distillers' dried grains with solubles (TDDGS), sorghum distillers' dried grains with solubles (SDDGS), or rye for broiler chickens using the regression method. Five diets including a corn-soybean meal reference diet and 4 assay diets, prepared by adding TDDGS or SDDGS at 10 or 20% of diet to partly replace energy-yielding ingredients in the reference diet. Each of the 5 diets was fed to 8 replicate cages of 6 birds per replicate cage from d 14 to 21 post hatching. Similarly in Exp. 2, corn-soybean reference diet and 2 assay diets in which rye at 20 or 40% replaced energy yielding sources in the reference diet and each of the 3 diets was fed to 8 replicate cages of 8 birds per replicate cage from d 18 to 23 post hatching. Excreta samples were collected twice daily from d 18 to 20 in Exp. 1 or d 20 to 22 in Exp. 2, and ileal digesta were collected on d 21 (Exp. 1) or d 23 (Exp. 2). The IDE, ME, and MEn (kcal/kg DM) of TDDGS or SDDGS were derived from the regressions of TDDGS-, SDDGS-, or rye-associated, IDE, apparent ME, and apparent MEn intake in kcal against the intake of TDDGS, SDDGS or rye (X, kg DM), respectively. For diets with TDDGS substitution, regression equations were IDE = 12.3 + 3,288X, ME = -3.0 + 2,800X, and MEn = -0.4 + 2,647X. The equations for the SDDGS diets were IDE = -4.8 + 3,247X, ME = -7.6 + 3,210X, and MEn = -7.0 + 3,072X; and those for the rye diets were IDE = 9.5 + 3,002X, ME = 6.3 + 3,053X, and MEn = 4.8 + 2,928X. The IDE contents did not differ between TDDGS and SDDGS whereas the ME and MEn contents were greater (P < 0.05) in the SDDGS than in the TDDGS. In conclusion, the current study provided energy values of the DDGS sources and rye using the regression method. The regression-derived IDE for TDDGS, SDDGS, or rye were 3,288, 3,247, or 3,002 kcal/kg DM, respectively; corresponding ME were 2,800, 3,210, or 3,053 kcal/kg DM. The respective regression-derived MEn for TDDGS, SDDGS, or rye were 2,647, 3,072, or 2,928 kcal/kg DM for broiler chickens.
MiR-29b-3p promotes particulate matter-induced inflammatory responses by regulating the C1QTNF6/AMPK pathway

Inflammatory responses are considered to be the critical mechanism underlying particulate matter (PM)-induced development and exacerbation of chronic respiratory diseases. MiR-29b-3p has been found to participate in various biological processes, but its role in PM-induced inflammatory responses was previously unknown. Here, we constructed a miRNA PCR array to find that miR-29b-3p was the most highly expressed in human bronchial epithelial cells (HBECs) exposed to PM. MiR-29b-3p promoted PM-induced pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) expression via inhibiting the AMPK signaling pathway in HBECs. RNA sequencing and luciferase reporter assay identified that miR-29b-3p targeted complement C1q tumor necrosis factor-related protein 6 (C1QTNF6), a protein that protected from PM-induced inflammatory responses via activating the AMPK signaling pathway. In vivo, miR-29b-3p antagomirs delivered via the tail vein prior to PM exposure significantly counteracted PM-induced miR-29b-3p upregulation and C1QTNF6 downregulation in lung tissues. Furthermore, miR-29b-3p inhibition alleviated inflammatory cells infiltration and pro-inflammatory cytokines secretion in the lung of PM-exposed mice. These findings firstly revealed that miR-29b-3p acted as a novel modulator of PM-induced inflammatory responses by targeting the C1QTNF6/AMPK signaling pathway, which contributes to a better understanding of the biological mechanisms underlying adverse PM-induced respiratory health effects.
Biology, diagnosis and treatment of Malassezia dermatitis in dogs and cats Clinical Consensus Guidelines of the World Association for Veterinary Dermatology.

BACKGROUND The genus Malassezia is comprised of a group of lipophilic yeasts that have evolved as skin commensals and opportunistic cutaneous pathogens of a variety of mammals and birds. OBJECTIVES The objective of this document is to provide the veterinary community and other interested parties with current information on the ecology, pathophysiology, diagnosis, treatment and prevention of skin diseases associated with Malassezia yeasts in dogs and cats. METHODS AND MATERIAL The authors served as a Guideline Panel (GP) and reviewed the literature available prior to October 2018. The GP prepared a detailed literature review and made recommendations on selected topics. The World Association of Veterinary Dermatology (WAVD) Clinical Consensus Guideline committee provided guidance and oversight for this process. The document was presented at two international meetings of veterinary dermatology societies and one international mycology workshop; it was made available for comment on the WAVD website for a period of six months. Comments were shared with the GP electronically and responses incorporated into the final document. CONCLUSIONS AND CLINICAL IMPORTANCE There has been a remarkable expansion of knowledge on Malassezia yeasts and their role in animal disease, particularly since the early 1990's. Malassezia dermatitis in dogs and cats has evolved from a disease of obscurity and controversy on its existence, to now being a routine diagnosis in general veterinary practice. Clinical signs are well recognised and diagnostic approaches are well developed. A range of topical and systemic therapies is known to be effective, especially when predisposing factors are identified and corrected.
DNA methylation in Schwann cells and in oligodendrocytes

DNA methylation is one of many epigenetic marks, which directly modifies base residues, usually cytosines, in a multiple‐step cycle. It has been linked to the regulation of gene expression and alternative splicing in several cell types, including during cell lineage specification and differentiation processes. DNA methylation changes have also been observed during aging, and aberrant methylation patterns have been reported in several neurological diseases. We here review the role of DNA methylation in Schwann cells and oligodendrocytes, the myelin‐forming glia of the peripheral and central nervous systems, respectively. We first address how methylation and demethylation are regulating myelinating cells' differentiation during development and repair. We then mention how DNA methylation dysregulation in diseases and cancers could explain their pathogenesis by directly influencing myelinating cells' proliferation and differentiation capacities.
Northeast Passage PATH™ Program: A Strengths-Based and Recovery-Oriented Approach for Veterans Who Experience Mental Health Disorders

The recreation therapy profession stands in a position to be a powerful agent of change from a strengths-based perspective (Anderson & Heyne, 2012). This article merges ongoing discussions regarding the need for development of effective evidenced-based treatment options for Veterans with mental health disorders, current dialogue regarding the changing focus in healthcare, and the role of strengths-based approaches to healthcare. It also offers a detailed example of the Northeast Passage PATH™ program (Promoting Access, Transition, and Health) as a strengths-based, recovery-oriented recreation therapy program implemented in a home/community-based setting (Craig, Wilder, Sable, & Gravink, 2013). Case examples are interwoven within the article to accent the discussion regarding strengths-based practices and illustrate how the PATH™ program implements interventions with Veterans with mental health disorders through all phases of treatment including assessment, planning, intervention, and evaluation.