Miracle-dz/UniFAR-FTUs huggingface dataset:
F-box protein-32 down-regulates small-conductance calcium-activated potassium channel 2 in diabetic mouse atria

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation, but the underlying ionic mechanism for this association remains unclear. We recently reported that expression of the small-conductance calcium-activated potassium channel 2 (SK2, encoded by KCCN2) in atria from diabetic mice is significantly down-regulated, resulting in reduced SK currents in atrial myocytes from these mice. We also reported that the level of SK2 mRNA expression is not reduced in DM atria but that the ubiquitin-proteasome system (UPS), a major mechanism of intracellular protein degradation, is activated in vascular smooth muscle cells in DM. This suggests a possible role of the UPS in reduced SK currents. To test this possibility, we examined the role of the UPS in atrial SK2 down-regulation in DM. We found that a muscle-specific E3 ligase, F-box protein 32 (FBXO-32, also called atrogin-1), was significantly up-regulated in diabetic mouse atria. Enhanced FBXO-32 expression in atrial cells significantly reduced SK2 protein expression, and siRNA-mediated FBXO-32 knockdown increased SK2 protein expression. Furthermore, co-transfection of SK2 with FBXO-32 complementary DNA in HEK293 cells significantly reduced SK2 expression, whereas co-transfection with atrogin-1ΔF complementary DNA (a nonfunctional FBXO-32 variant in which the F-box domain is deleted) did not have any effects on SK2. These results indicate that FBXO-32 contributes to SK2 down-regulation and that the F-box domain is essential for FBXO-32 function. In conclusion, DM-induced SK2 channel down-regulation appears to be due to an FBXO-32-dependent increase in UPS-mediated SK2 protein degradation.
Regional neutrality evolves through local adaptive niche evolution

Significance Coexistence of species depends on two very general mechanisms. In one, species differentiate in their niches and coexist by negative frequency dependence, in the other they have similar niches and cooccur for long periods of time due to (quasi-) equivalence. These explanations ignore the role of local adaptive evolution. We model how local evolution-mediated priority effects (where species that recolonize patches can adapt sufficiently well to resist being displaced by later colonists) affect coexistence in a landscape. We find that evolution often leads to a situation where local patches are strongly dominated by a single species even though all species can be found in any habitat type. This unsuspected result may explain why coexistence of species is often scale dependent. Biodiversity in natural systems can be maintained either because niche differentiation among competitors facilitates stable coexistence or because equal fitness among neutral species allows for their long-term cooccurrence despite a slow drift toward extinction. Whereas the relative importance of these two ecological mechanisms has been well-studied in the absence of evolution, the role of local adaptive evolution in maintaining biological diversity through these processes is less clear. Here we study the contribution of local adaptive evolution to coexistence in a landscape of interconnected patches subject to disturbance. Under these conditions, early colonists to empty patches may adapt to local conditions sufficiently fast to prevent successful colonization by other preadapted species. Over the long term, the iteration of these local-scale priority effects results in niche convergence of species at the regional scale even though species tend to monopolize local patches. Thus, the dynamics evolve from stable coexistence through niche differentiation to neutral cooccurrence at the landscape level while still maintaining strong local niche segregation. Our results show that neutrality can emerge at the regional scale from local, niche-based adaptive evolution, potentially resolving why ecologists often observe neutral distribution patterns at the landscape level despite strong niche divergence among local communities.
Tuberculosis in the 21th century: Current status of diagnostic methods

Abstract Tuberculosis is an infectious bacterial disease with a high mortality rate worldwide constituting a serious public health problem. The diagnostic methods commonly used by health professionals are slow and expensive and the results may take about sixty days which will cause a delay in administrating the most proper treatment to the patient, as well as increase health care costs and infection transmission possibility. Patients infected simultaneously with human immunodeficiency virus and Mycobacterium tuberculosis are a constant and worrying challenge for the scientific community which will research and develop new methods of diagnosis, new drugs and new therapies. Nowadays there are new tuberculosis diagnosis methods and some of which are already in clinical trial phases. These methods have high sensitivity, but do not replace the microbiological examination for isolation and culture of Mycobacterium spp. However, in clinical practice, microbiological, imaging, clinical and epidemiological data integration provide the best diagnosis and treatment possible. Consequently, throughout this paper, the different methods of diagnosis of human tuberculosis with its advantages and disadvantages will be covered, describing new omics and ultra-fast methods to increase knowledge and obtain a rapid diagnosis of tuberculosis.
Flexible thermoelectric generators with inkjet-printed bismuth telluride nanowires and liquid metal contacts.

Solution phase printing of nanomaterials is becoming increasingly important for the creation of scalable flexible electronics including those associated with biomedical and energy harvesting applications. However, the use of solution-phase printed thermoelectric energy generators (TEGs) has been minimally explored. Herein we report a highly flexible inkjet-printed TEG. Bismuth telluride (Bi2Te3) and bismuth antimony telluride (Bi0.5Sb1.5Te3) nanowires (NWs) are inkjet printed onto polyimide to form n-type and p-type legs for the TEGs. A post-print thermal annealing process is used to increase the thermoelectric performance of the printed NWs while eutectic gallium-indium (EGaIn) liquid metal contacts electrically connect the TEG legs in series. Annealing conditions for the combination of p/n legs are examined to maximize the thermoelectric efficiency of the TEG prototype. The maximum power factor was found to be 180 μW m-1 K-2 and 110 μW m-1 K-2 for the Bi2Te3 and Bi0.5Sb1. 5Te3 nanowires respectively. A maximum power for the fully printed TEG device measured 127 nW at a 32.5 K temperature difference. The performance of the TEG device does not diminish even after multiple bending experiments (up to 50 times) around a tight radius of curvature (rod-dia. 11 mm). Hence this inkjet-printed flexible TEG is a step towards a fully functional wearable TEG device.
Necl‐4/Cadm4 recruits Par‐3 to the Schwann cell adaxonal membrane

Interactions between axons and Schwann cells are essential for the acquisition of Schwann cell radial and longitudinal polarity and myelin sheath assembly. In the internode, the largest of these longitudinal domains, axon‐Schwann cell interactions are mediated by the Nectin‐like (Necl) cell adhesion proteins, also known as SynCAMs or Cadms. In particular, Necl‐1/Cadm3 expressed on the axon surface binds to Necl‐4/Cadm4 expressed along the adaxonal membrane of myelinating Schwann cells. Necl‐4 promotes myelination in vitro and is required for the timely onset of myelination and the fidelity of the organization of the myelin sheath and the internode in vivo. A key question is the identity of the downstream effectors of Necl‐4 that mediate its effects. The cytoplasmic terminal region (CTR) of Necl‐4 contains a PDZ‐domain binding motif. Accordingly, we used the CTR of Necl‐4 in an unbiased proteomic screen of PDZ‐domain proteins. We identify Par‐3, a multi‐PDZ domain containing protein of the Par‐aPKC polarity complex previously implicated in myelination, as an interacting protein. Necl‐4 and Par‐3 are colocalized along the inner Schwann cell membrane and coprecipitate from Schwann cell lysates. The CTR of Necl‐4 binds to the first PDZ domain of Par‐3 thereby recruiting Par‐3 to sites of Necl‐4/Necl‐1 interaction. Knockdown of Necl‐4 perturbs Par‐3 localization to the inner membrane of Schwann cells in myelinating co‐cultures. These findings implicate interactions of Necl‐1/Necl‐4 in the recruitment of Par‐3 to the Schwann cell adaxonal membrane and the establishment of Schwann cell radial polarity.
Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection

Objective Chronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence indicates that functional cure of HBV infection by the host immune response is feasible. Developing T cell-based therapies able to achieve functional cure will require identification of the requirements for a successful T cell response against HBV and the relative contribution of individual T cell specificities to HBV control. Design The phenotype and function of HBV-specific T cells were studied directly ex vivo using fluorochrome-labelled multimers. We studied multiple HBV-specific T cell specificities targeting different HBV proteins in individuals with either an acute self-limiting or chronic HBV infection. Results We detected strong T cell responses targeting multiple HBV viral proteins in acute self-limiting and low-frequency core and polymerase-specific T cells in chronic infection. Expression of the T cell inhibitory receptor PD-1, as well as T cell differentiation, T cell function and T cell regulation differed by stages and outcomes of infection. In addition, these features differed significantly between T cells targeting different HBV specificities. Conclusion HBV-specific T cells with different target specificities are characterised by distinct phenotypical and functional profiles. These results have direct implications for the design of immunological studies in HBV infection, and are potentially relevant for informing immunotherapeutic approaches to induce functional cure.
Motile cilia of the male reproductive system require miR-34/miR-449 for development and function to generate luminal turbulence

Significance Motile cilia are found lining the respiratory and reproductive systems, as well as the brain and spinal column, and the coordinated beat moves fluids over the luminal surfaces. Disruptions of ciliary structure or beat patterns have been shown to be involved in numerous diseases called ciliopathies. For many years, it has been proposed that the ciliary beat in the male reproductive system propels sperm from testis into the epididymis via tiny efferent ductules. Here, we show that motile cilia lining the efferent ductules do not directly propel sperm, but rather serve as agitators, generating vigorous fluidic turbulence, to maintain suspension of sperm within the intraluminal fluid, thus ensuring an equilibrium in fluid reabsorption by the nonciliated cells. Cilia are cell-surface, microtubule-based organelles that project into extracellular space. Motile cilia are conserved throughout eukaryotes, and their beat induces the flow of fluid, relative to cell surfaces. In mammals, the coordinated beat of motile cilia provides highly specialized functions associated with the movement of luminal contents, as seen with metachronal waves transporting mucus in the respiratory tract. Motile cilia are also present in the male and female reproductive tracts. In the female, wave-like motions of oviductal cilia transport oocytes and embryos toward the uterus. A similar function has been assumed for motile cilia in efferent ductules of the male—i.e., to transport immotile sperm from rete testis into the epididymis. However, we report here that efferent ductal cilia in the male do not display a uniform wave-like beat to transport sperm solely in one direction, but rather exert a centripetal force on luminal fluids through whip-like beating with continual changes in direction, generating turbulence, which maintains immotile spermatozoa in suspension within the lumen. Genetic ablation of two miRNA clusters (miR-34b/c and -449a/b/c) led to failure in multiciliogenesis in murine efferent ductules due to dysregulation of numerous genes, and this mouse model allowed us to demonstrate that loss of efferent duct motile cilia causes sperm aggregation and agglutination, luminal obstruction, and sperm granulomas, which, in turn, induce back-pressure atrophy of the testis and ultimately male infertility.
Combination of skin flap and silicone prosthesis for rehabilitation of a large orbital defect: A case report

Exenteration surgery greatly affects a person in terms of function, esthetics, and psychological trauma. In such cases, restoration by silicone orbital prosthesis is a well-accepted treatment option. However, this is a difficult task, necessitating personalized design of method for each patient. This case report describes the technique for fabrication of a silicone orbital prosthesis for a male patient with left orbital defect due to exenteration of a Grade 3 squamous cell carcinoma of the left eye and surrounding tissues. The patient was delivered with a satisfactory silicone orbital prosthesis having good retention and finish. Multidisciplinary management and team approach are crucial in providing precise and effective rehabilitation for improving the patient's quality of life and help them return to their normal social life.
Video QoE Models for the Compute Continuum

1. Introduction Video traffic is exponentially increasing over wireless networks due to proliferating video technology and the growing desire for anytime, anywhere access to video content. Cisco predicts that two-thirds of the world's mobile data traffic will be video by 2017 [1]. This imposes significant challenges for managing video traffic efficiently to ensure an acceptable quality of experience (QoE) for the end user. Since network throughput based video adaptation without considering user's QoE could lead to either a bad video service or unnecessary bandwidth waste, QoE management under cost constraints is the key to satisfying consumers and monetizing services [2].
A Method for High-Throughput Robotic Assembly of 3-Dimensional Vascular Tissue.

An essential step towards commercializing engineered tissues is to scale-up and automate their production. This presents a challenge for self-assembled tissues, which are fragile at early time points and difficult to handle using robotic systems. The goal of this study was to automate tissue engineered blood vessel (TEBV) fabrication by creating a custom cell seeding and self-assembly system that is conducive to robotic manipulation, coupled with a robotic system to assemble smooth muscle cell ring units into tissue tubes. To generate self-assembled tissue ring units manually, cells are seeded at a high density into custom agarose wells that have center posts (2 mm inner diameter), around which cells aggregate and contract to form rings. Agarose is well-suited for cell seeding and ring self-assembly because it is non-cell adhesive, can be autoclaved, and reproducibly cast to form wells using silicone templates. However, agarose gel is soft, which makes reliable robotic manipulation challenging. To solve this problem, we designed a custom ring self-assembly plate utilizing a polyetherimide (PEI) wells with MED610 3D-printed center posts and a MED610 well negative that allows the casting of individual, annular agarose cell-seeding troughs within the PEI plate. Rings cultured in the new plate system were morphologically similar to rings cultured in control agarose wells and had a slightly higher failure load. To automate tube assembly, we created a unique robotic punch system to push tissue rings out of the PEI-MED610 plate onto a stainless-steel mandrel to enable tube fusion. Tubes fabricated via manual or robotic ring removal and placement demonstrated similar morphology after tube fusion, and the automated system substantially reduced the time required to assemble tubes manually. In summary, we developed a novel robotic assembly system to precisely manipulate self-assembled tissue rings and enable scale-up and automation of TEBV biofabrication.
Validity and Reliability of the Turkish Version of the 8-Item Parkinson's Disease Questionnaire.

Introduction Symptomatic control and improvement of health-related quality of life (HRQoL) is a key feature of the management of patients with Parkinson's disease (PD). The 39-item Parkinson's Disease Questionnaire (PDQ) and its short version, PDQ-8, validated disease-specific patient-reported instruments, have been highly recommended to use for assessing HRQoL in patients with PD. The aim of this study was to assess the reliability and validity of the Turkish version of the PDQ-8. Methods Eighty-three patients with PD were recruited for this methodological and cross-sectional study. The PDQ-8 was repeated to assess the test-retest reliability after one-week interval. The participants completed the 36-Item Short Form Health Survey (SF-36) as a generic HRQoL previously validated in Turkey. The Hoehn & Yahr stages of the patients were also determined. The SF-36 and Hoehn & Yahr stages were used to assess the convergent validity of the PDQ-8. Results The Cronbach's alpha coefficient was 0.78 (95% CI: 0.70-0.84, p<0.001) for PDQ-8. The test-retest reliability was very high as the intra-class correlation coefficient was 0.97 (95% CI: 0.93-0.99, p<0.001). The PDQ-8 had significant correlations with the physical and mental component scores of SF-36 (ρ=-0.52, p<0.001 and ρ=-0.64, p<0.001, respectively) and Hoehn & Yahr stages (ρ=0.56, p<0.001). There was no evidence of floor or ceiling effects. Conclusion The results of this study suggest that the Turkish version of the PDQ-8 is a reliable, valid, less time-consuming, and brief disease-specific instrument to assess HRQoL in patients with Parkinson's disease.
Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy

Sphingolipid imbalance is the culprit in a variety of neurological diseases, some affecting the myelin sheath. We have used whole-exome sequencing in patients with undetermined leukoencephalopathies to uncover the endoplasmic reticulum lipid desaturase DEGS1 as the causative gene in 19 patients from 13 unrelated families. Shared features among the cases include severe motor arrest, early nystagmus, dystonia, spasticity, and profound failure to thrive. MRI showed hypomyelination, thinning of the corpus callosum, and progressive thalamic and cerebellar atrophy, suggesting a critical role of DEGS1 in myelin development and maintenance. This enzyme converts dihydroceramide (DhCer) into ceramide (Cer) in the final step of the de novo biosynthesis pathway. We detected a marked increase of the substrate DhCer and DhCer/Cer ratios in patients’ fibroblasts and muscle. Further, we used a knockdown approach for disease modeling in Danio rerio, followed by a preclinical test with the first-line treatment for multiple sclerosis, fingolimod (FTY720, Gilenya). The enzymatic inhibition of Cer synthase by fingolimod, 1 step prior to DEGS1 in the pathway, reduced the critical DhCer/Cer imbalance and the severe locomotor disability, increasing the number of myelinating oligodendrocytes in a zebrafish model. These proof-of-concept results pave the way to clinical translation.
Free and hidden fumonisins in raw maize and maize-based products from China

ABSTRACT The occurrence of free and hidden fumonisins in raw maize and maize-based products from China was investigated. A total of 58 samples were analyzed using high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Among all the samples, 66% were contaminated with free fumonisins above limits of quantitation, and a higher percentage of 86% was found for total fumonisins (free + hidden). The highest contamination levels were observed in dried maize kernels which appeared mouldy, with mean levels of 15,737 and 30,785 µg/kg for free and total fumonisins, respectively. Frozen maize kernels, fresh maize kernels, and maize starch samples exhibited the lowest contamination levels, with no more than 200 µg/kg of total fumonisins. Except for one sample, the concentrations of total fumonisins were greater than those of free fumonisins with all the samples, the ratios of total-to-free fumonisins varied between 1.1 and 5.2, with an average ratio of 2.0.
Relationship between social capital and happiness in a Japanese community: A cross-sectional study.

The influence of social capital on happiness is attracting attention around the world. Many studies that investigated the relationship between social capital and happiness suggest that happiness correlates to a positive social environment. The aim of this study was to examine the relationship between social capital and happiness in a community with the lowest National Health Insurance expenditures in Miyazaki Prefecture (Japan). This cross-sectional study targeted 2730 residents in the community aged 40-75 years who were covered by National Health Insurance in 2015. A self-administered questionnaire consisting of questions focusing on demographic characteristics, happiness, and social capital was sent to the residents, and 1106 of them (40.5%) returned the questionnaires by the deadline. The analysis of responses indicated a positive relationship between social capital and happiness with regard to all three factors of social capital (trust, connections and interaction, and social participation). Evaluating the relationship between social capital and health in terms of happiness is important to creating a lively society in which citizens support one another, in addition to promoting physical and mental well-being.
Supplemental feeding of phospholipid-enriched alkyl phospholipid from krill relieves spontaneous atopic dermatitis and strengthens skin intercellular lipid barriers in NC/Nga mice

ABSTRACT Plasmalogen (Pls) is a glycerophospholipid derived from alkyl phospholipid (Alk) with antioxidant functions in vivo. The present study investigated the effects of ether phospholipids, such as Pls and Alk, on intercellular lipid barriers in the skin of NC/Nga mice, a model of atopic dermatitis (AD). NC/Nga mice fed Alk showed increased plasma levels of Alk and Pls. The AD-related changes in ceramide composition in the skin were abrogated by oral administration of Alk. Moreover, Alk suppressed skin inflammation in AD mice. These results indicate that Alk partially fortifies the stratum corneum lipid barrier and may be an effective treatment for AD. Abbreviations: Pls: plasmalogen; PlsCho: choline plasmalogen; PlsEtn: ethanolamine plasmalogen; Alk: alkyl phospholipid; TJ: tight junction; FA: fatty acid; AD: atopic dermatitis; SO: soybean oil; FO: fish oil; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; TG: triglyceride; PL: phospholipid; RF: retention factor; AlkCho: choline-type alkyl phospholipid; AlkEtn: ethanolamine-type alkyl phospholipid; LC-MS/MS: liquid chromatography-tandem mass spectrometry; FAR1: fatty acyl-coenzyme (Co)A reductase 1 Graphical Abstract Feeding of phospholipid-enriched alkyl phospholipid from krill increases plasma ether phospholipid, and strengthens intercellular lipid barriers in NC/Nga mice.