Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypothalamic mTORC2 is essential for metabolic health and longevity

The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved protein kinase that regulates growth and metabolism. mTOR is found in two protein complexes, mTORC1 and mTORC2, that have distinct components and substrates and are both inhibited by rapamycin, a macrolide drug that robustly extends lifespan in multiple species including worms and mice. Although the beneficial effect of rapamycin on longevity is generally attributed to reduced mTORC1 signaling, disruption of mTORC2 signaling can also influence the longevity of worms, either positively or negatively depending on the temperature and food source. Here, we show that loss of hypothalamic mTORC2 signaling in mice decreases activity level, increases the set point for adiposity, and renders the animals susceptible to diet‐induced obesity. Hypothalamic mTORC2 signaling normally increases with age, and mice lacking this pathway display higher fat mass and impaired glucose homeostasis throughout life, become more frail with age, and have decreased overall survival. We conclude that hypothalamic mTORC2 is essential for the normal metabolic health, fitness, and lifespan of mice. Our results have implications for the use of mTORC2‐inhibiting pharmaceuticals in the treatment of brain cancer and diseases of aging.
Privacy-Preserving Multi-Receiver Certificateless Broadcast Encryption Scheme with De-Duplication

Nowadays, the widely deployed and high performance Internet of Things (IoT) facilitates the communication between its terminal nodes. To enhance data sharing among terminal devices and ensure the recipients’ privacy protection, a few anonymous multi-recipient broadcast encryption (AMBE) proposals are recently given. Nevertheless, the majority of these AMBE proposals are only proven be securely against adaptively chosen plain-text attack (CPA) or selectively chosen ciphertext attack (CCA). Furthermore, all AMBE proposals are subjected to key escrow issue due to inherent characteristics of the ID-based public cryptography (ID-PKC), and cannot furnish secure de-duplication detection. However, for cloud storage, it is very important for expurgating duplicate copies of the identical message since de-duplication can save the bandwidth of network and storage space. To address the above problems, in the work, we present a privacy-preserving multi-receiver certificateless broadcast encryption scheme with de-duplication (PMCBED) in the cloud-computing setting based on certificateless cryptography and anonymous broadcast encryption. In comparison with the prior AMBE proposals, our scheme has the following three characteristics. First, it can fulfill semantic security notions of data-confidentiality and receiver identity anonymity, whereas the existing proposals only accomplish them by formalizing the weaker security models. Second, it achieves duplication detection of the ciphertext for the identical message encrypted with our broadcast encryption. Finally, it also avoids the key escrow problem of the AMBE schemes.
Optical Tweezers: Phototoxicity and Thermal Stress in Cells and Biomolecules

For several decades optical tweezers have proven to be an invaluable tool in the study and analysis of myriad biological responses and applications. However, as with every tool, they can have undesirable or damaging effects upon the very sample they are helping to study. In this review the main negative effects of optical tweezers upon biostructures and living systems will be presented. There are three main areas on which the review will focus: linear optical excitation within the tweezers, non-linear photonic effects, and thermal load upon the sampled volume. Additional information is provided on negative mechanical effects of optical traps on biological structures. Strategies to avoid or, at least, minimize these negative effects will be introduced. Finally, all these effects, undesirable for the most, can have positive applications under the right conditions. Some hints in this direction will also be discussed.
Emergence of AnnexinVpos CD31neg CD42blow/neg extracellular vesicles in plasma of humans at extreme altitude

Background Hypobaric hypoxia has been reported to cause endothelial cell and platelet dysfunction implicated in the formation of microvascular lesions, and in its extremes may contribute to vascular leakage in high altitude pulmonary edema or blood brain barrier disruption leading to cerebral micro-hemorrhage (MH). Platelet function in the development of microvascular lesions remained ill defined, and is still incompletely understood. In this study platelet- and endothelial cell-derived extracellular vesicles (PEV and EEV, respectively) and cell adhesion molecules were characterized in plasma samples of members of a high altitude expedition to delineate the contribution of platelets and endothelial cells to hypobaric hypoxia-induced vascular dysfunction. Methods and findings In this observational study, platelet and endothelial cell-derived extracellular vesicles were analysed by flow-cytometry in plasma samples from 39 mountaineers participating in a medical research climbing expedition to Himlung Himal, Nepal, 7,050m asl. Megakaryocyte/platelet-derived AnnexinVpos, PECAM-1 (CD31) and glycoprotein-1b (GP1b, CD42b) positive extracellular vesicles (PEV) constituted the predominant fraction of EV in plasma samples up to 6,050m asl. Exposure to an altitude of 7,050m led to a marked decline of CD31pos CD42neg EEV as well as of CD31pos CD42bpos PEV at the same time giving rise to a quantitatively prevailing CD31neg CD42blow/neg subpopulation of AnnexinVpos EV. An almost hundredfold increase in the numbers of this previously unrecognized population of CD31neg CD42blow/neg EV was observed in all participants reaching 7,050m asl. Conclusions The emergence of CD31neg CD42blow/neg EV was observed in all participants and thus represents an early hypoxic marker at extreme altitude. Since CD31 and CD42b are required for platelet-endothelial cell interactions, these hypobaric hypoxia-dependent quantitative and phenotypic changes of AnnexinVpos EV subpopulations may serve as early and sensitive indicators of compromised vascular homeostasis.
Re-conceptualizing postural control assessment in sport-related concussion: Transitioning from the reflex/hierarchical model to the systems model

ABSTRACT Background: While postural control impairment is common following sport-related concussion, few investigations have studied the physiological basis for this impairment. Both the Reflex/Hierarchical Model and the Systems Model are commonly used to characterize the physiological basis of postural control. Purpose: To discuss the physiological basis of postural control impairment resulting from sport-related concussion based on these models and suggest directions for future research. Methods: Narrative literature review. Findings: Postural control impairment seen with sport-related concussion is a multifaceted construct that can result from deficits in numerous systems that underlie postural control as described by the Systems Model, rather than a unidimensional construct that stems from the central nervous systems’ inability to integrate sensory input to control posture as per the Reflex/Hierarchical Model. Conclusion: We recommend a transition away from the Hierarchical/Reflex Model of postural control towards the Systems Model in the conceptualization of sport-related concussion. Future research on postural control following sport-related concussion should account for the multifaceted nature of the resulting postural control impairment based on the Systems Model. Clinically, there is a need for a clinical postural control test that allows examination across the affected systems under single-task, dual-task, and sport-specific paradigms.
Lifelong exposure to dioxin-like PCBs alters paternal offspring care behavior and reduces male fish reproductive success.

Offspring survival, cohort performance, and ultimately population dynamics are strongly influenced by maternal characteristics (e.g., fecundity), whereas paternal contribution is often considered limited to genetic-driven fitness of males through sexual selection. However, male contribution to reproductive success can be particularly influential in species exhibiting paternal offspring care. Polychlorinated biphenyls (PCBs) are widespread, persistent contaminants that can disrupt maternal reproductive processes and negatively affect offspring. In contrast, how PCBs affect paternal reproductive success is largely unknown, but could ultimately affect population dynamics. We examined the effects of lifelong PCB exposure on the reproductive processes of male fathead minnows (Pimephales promelas), a species exhibiting sole paternal offspring care, by examining endocrine-associated gene expression, testes histology, secondary sexual characteristics, courtship ability, offspring care, and offspring survival. PCBs minimized male secondary sexual characteristics, but did not affect gonadal endpoints or inhibit ability to court females. Fathers exposed to high concentrations of dioxin-like PCBs had changes in gene expression, reduced offspring care behavior, and higher embryo mortality, possibly due to fathers spending less time within nests and less frequently tending to embryos. Through complex interactions among gene expression, physical characteristics, and behavior, PCBs inhibit paternal reproductive success and have the potential to suppress population size.
Spatio-temporal structure of single neuron subthalamic activity identifies DBS target for anesthetized Tourette syndrome patients

Objective. Deep brain stimulation (DBS) of basal ganglia effectively tackles motor symptoms of movement disorders such as Tourette syndrome (TS). The precise location of target stimulation site determines the range of clinical outcome in DBS patients, and the occurrence of side-effects of DBS. DBS implant procedures currently localize stimulation target relying on a combination of pre-surgical imaging, standardized brain atlases and on-the-spot clinical tests. Here we show that temporal structure of single unit activity in subthalamic nucleus (STN) of patients affected by pure TS can contribute to identify the optimal target location of DBS. Approach. Neural activity was recorded at different depths within STN with microelectrodes during DBS implant surgery. Depth specific neural features were extracted and correlated with the optimal depth for tic control. Main results. We describe for the first time temporal spike patterns of single neurons from sensorimotor STN of anesthetized TS patients. A large fraction of units (31.2%) displayed intense bursting in the delta band (<4 Hz). The highest firing irregularity and hence the higher density of bursting units (42%) were found at the optimal spot for tic control. Discharge patterns irregularity and dominant oscillations frequency (but not firing rate) carried significant information on optimal target. Significance. We found single unit activity features in the STN of TS patients reliably associated to optimal DBS target site for tic control. In future works measures of firing irregularity could be integrated with current target localization methods leading to a more effective and safer DBS for TS patients.
Anatomical analysis of periapical bone of maxillary posterior teeth: a cone beam computed tomography study

Objectives To investigate the periapical bone thicknesses of maxillary posterior teeth at the preferred level for root resection (3 mm apical to the root end) and to determine vertical distances from apex to maxillary sinus floor (MSF) using cone beam computed tomography (CBCT) scans. Methods CBCT scans were collected from 341 subjects (2389 teeth). Associations of bone thicknesses and vertical distances with age and sex were determined by one-way analysis of variance. Results At the level of root-end resection, buccal bone was the thickest over the mesiobuccal roots of second molars (mean, 2.99 mm) and thinnest over the double-root first premolars (mean, 0.29 mm). In maxillary posterior teeth, thicker buccal bone was found in men than in women. The mesiobuccal roots of second molars were nearest to the MSF (mean, 1.33 mm), and were also most frequently extended into the sinus cavity (15.81%). Subjects more than 40 years of age had larger vertical distances from root apices to MSF in the molar region, compared with younger subjects. Conclusions Generally, periapical bone was thicker in men, and root apices were located nearer to the MSF in younger subjects. Age and sex should be considered before endodontic microsurgery.
Necrotic Enteritis in Broiler Chickens: The Role of Tight Junctions and Mucosal Immune Responses in Alleviating the Effect of the Disease

Necrotic enteritis (NE) continues to present major challenges to the poultry industry, and the etiologic agent Clostridium perfringens is the fourth leading cause of bacterially-induced food- borne illnesses in the US. This study was designed to evaluate the effects of a probiotic during naturally occurring NE. On day of hatch, 1080 Cobb 500 male broilers were randomly allocated to three groups (12 replicate pens/treatment, 30 birds/pen) including (1) negative control (NC): corn-soybean meal diet; (2) positive control (PC): NC + 20 mg virginiamycin/kg diet (0.450 kg Stafac®20/ton); and (3) NC + PrimaLac (1.36 and 0.91 kg/ton from 1–21 and 22–42 days, respectively). One day (d) post placement, all birds were challenged by a commercial live oocyst coccidia vaccine as a predisposing factor to NE. Body weight and feed intake were measured at the onset of NE (d 8) and end of each feeding phase. On d 8, small intestines of two birds/pen were examined for NE lesions, and jejunum samples from one bird were collected for mRNA gene expression analysis of tight junction proteins, cytokines, and nutrient transporters. Data were analyzed using the JMP software and significance between treatments identified by LSD (p < 0.05). Compared to NC, supplementation of probiotic reduced d 1–42 mortality; however, PC was the only group with significantly lower mortality. Despite significantly improved feed conversion ratio (FCR) in PC and probiotic groups during d 1–42, average daily gain was only higher in PC (77.69 g/bird) compared with NC (74.99 g/bird). Furthermore, probiotic and PC groups had significantly reduced lesion scores in the duodenum and jejunum compared to NC. Expression of claudin-3 was higher, while expression of zonula occluden-2 tended (p = 0.06) to be higher in probiotic-supplemented birds compared to NC. Moreover, birds fed the probiotic diet had significantly higher expression of IL-10, IL-17, AMPK-α1, and SGLT1 mRNA compared to NC birds. The expression of PepT1 was higher for the probiotic-supplemented group compared to PC. IFN-γ expression was lower in PC compared to NC, while there was no difference between probiotic and NC. There were no differences in gene expression of sIgA, TNF-α, IL-1β, and IL-22 among treatments. Collectively, these data indicate that in a naturally occurring NE model, supplementation of a probiotic helps to improve FCR and reduce lesions, potentially due to the improvements in mRNA expression of tight junctions, cytokines, and nutrient transporters.
Genome‐wide investigation of intragenic DNA methylation identifies ZMIZ1 gene as a prognostic marker in glioblastoma and multiple cancer types

DNA methylation has long been recognized as a tumor‐promoting factor when aberrantly regulated in the promoter region of genes. However, the effect of intragenic DNA methylation remains poorly understood on the clinical aspects of cancer. Here, we first evaluated the significance of intragenic DNA methylation for survival outcomes of cancer patients in a genome‐wide manner. Glioblastoma patients with hypermethylated intragenic regions exhibited better survival than hypomethylated patients. Enrichment analyses of intragenic DNA methylation profiles with epigenetic signatures prioritized the intragenic DNA methylation of ZMIZ1 as a possible glioblastoma prognostic marker that is independent of MGMT methylation in IDH1 wild‐type patients. This intragenic region harbored molecular signatures of alternative transcription across many cell types. Furthermore, we found that the intragenic region of ZMIZ1 can serve as a molecular marker in multiple cancers including astrocytomas, bladder cancer and renal cell carcinoma according to DNA methylation status. Finally, in vitro and in vivo experiments uncovered the role of ZMIZ1 as a driver of tumor cell migration. Altogether, our results identify ZMIZ1 as a prognostic marker in cancer and highlight the clinical significance of intragenic methylation in cancer.
Raman spectroscopy of two-dimensional magnetic van der Waals materials

Two-dimensional magnetic van der Waals (vdW) materials have attracted much interest recently. Magnetism in two dimensions is one of the most fascinating topics in condensed matter physics whereas atomically thin magnetic materials present new opportunities for novel spintronic devices. Raman spectroscopy has been established as an invaluable tool in the studies of such magnetic vdW materials as it has been found that the magnetic ordering, which is often difficult to probe directly in atomically thin samples, can be reliably monitored by Raman spectroscopy. Here, we review recent progress in using Raman spectroscopy for the study of magnetic vdW materials with the examples of Ising-type ferromagnet CrI3, Ising-type antiferromagnet FePS3, and XY-type antiferromagnet NiPS3. By monitoring characteristic spectroscopic signatures of magnetic ordering, one can probe various aspects of magnetic ordering.
Silencing of the Chitin Synthase Gene Is Lethal to the Asian Citrus Psyllid, Diaphorina citri

Chitin synthase is a critical enzyme that catalyzes N-acetylglucosamine to form chitin, which plays an important role in the growth and development of insects. In this study, we identified a chitin synthase gene (CHS) with a complete open reading frame (ORF) of 3180 bp from the genome database of Diaphorina citri, encoding a protein of 1059 amino acid residues with the appropriate signature motifs (EDR and QRRRW). Reverse transcription-quantitative PCR (RT-qPCR) analysis suggested that D. citri CHS (DcCHS) was expressed throughout all developmental stages and all tissues. DcCHS had the highest expression level in the integument and fifth-instar nymph stage. Furthermore, the effects of diflubenzuron (DFB) on D. citri mortality and DcCHS expression level were investigated using fifth-instar nymph through leaf dip bioassay, and the results revealed that the nymph exposed to DFB had the highest mortality compared with control group (Triton-100). Silencing of DcCHS by RNA interference resulted in malformed phenotypes and increased mortality with decreased molting rate. In addition, transmission electron microscopy (TEM) and fluorescence in situ hybridization (FISH) also revealed corresponding ultrastructural defects. Our results suggest that DcCHS might play an important role in the development of D. citri and can be used as a potential target for psyllid control.
Proactive Telephone Smoking Cessation Counseling Tailored to Parents: Results of a Randomized Controlled Effectiveness Trial

A recent Dutch efficacy trial showed the efficacy of a telephone smoking cessation counseling tailored to smoking parents. Currently, it is unknown whether such telephone counseling would be effective under more real-world conditions. This study aimed to examine the effectiveness of parent-tailored telephone smoking cessation counseling in a two-arm randomized controlled effectiveness trial and whether the effectiveness depended on the recruitment approaches that were used to recruit parents (mass media vs. health care). In total, 87 parents received either telephone counseling (intervention) or a self-help brochure (control). Parents were asked to complete questionnaires at baseline and three months post-intervention. Results showed that the odds of reporting 7-day point-prevalence abstinence at three months post-intervention was 7.54 higher for parents who received telephone counseling than for parents in the control condition (53.3% vs. 13.2%, 95% CI = 2.49–22.84). Because inclusion was lower than anticipated, interaction-effects of condition and recruitment approach could not be interpreted. The present study demonstrates that the parent-tailored smoking cessation telephone counseling is effective in helping parents to quit smoking. Yet, before large-scale implementation, future research should focus on how recruitment of parents via the recruitment approaches could be improved.
Age-Associated Changes in Gut Microbiota and Dietary Components Related with the Immune System in Adulthood and Old Age: A Cross-Sectional Study

The fecal microbiota plays an important role in human health, and alterations in the microbiota–host interaction seem to be involved in the ageing process. Therefore, it is of interest to develop strategies for promoting a balanced microbiota in old age in order to prevent the physiological and immune decline associated with age. However, the specific microbiota changes in the transition from adulthood to senescence are not yet well understood. Here we assessed the levels of some intestinal microorganisms and short chain fatty acids (SCFAs) across different age-groups. In total, 153 adults from four age groups (<50, 50–65, 66–80, and >80 years-old) were recruited; the levels of different bacterial groups in fecal samples were determined by quantitative polymerase chain reaction (qPCR), and those of SCFA by gas chromatography. Dietary information was collected by using a Food Frequency Questionnaire. The presence of the Bifidobacterium, Faecalibacterium, Bacteroides group, and Clostridium cluster XIVa decreased with age up to 66–80 years of age, with differences reaching statistical significance for the latter group. Interestingly, the levels of some of these microorganisms recovered in the very old age group (>80 years), with these older individuals presenting significantly higher counts of Akkermansia and Lactobacillus group than adults and the younger elderly. In addition, ageing was associated with a progressively and statistically significant reduction in the fecal concentrations of SCFAs. Dietary intakes also showed some statistically significant differences among the groups for some macro- and micronutrients. Moreover, associations of some microorganisms with age and macronutrients were also evidenced. Considering the role that fecal microbiota alterations may have in terms of impairing homeostasis and resilience, our results underline the importance of understanding the ageing and immunosenescence processes by including the microbiota perspective.
Predicting respiratory failure in amyotrophic lateral sclerosis: still a long way to go

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease that affects the brain and spinal cord motor neurons leading to progressive muscle weakness, irreversible disability, respiratory failure and death within a time range of a few months to more than 10 years [1]. Although use of noninvasive ventilation (NIV) is standard of care in ALS and improves health-related quality of life and survival [2, 3], no accurate model to predict respiratory failure in ALS was available until the recently published work by Ackrivo et al. [4]. The authors should therefore be congratulated for this much awaited contribution to this field. Recently published model to predict respiratory failure in ALS may not perform well across different populations and in single individuals http://bit.ly/2XbI6Me