Miracle-dz/UniFAR-FTUs huggingface dataset:
Hydrogen peroxide is a neuronal alarmin that triggers specific RNAs, local translation of Annexin A2, and cytoskeletal remodeling in Schwann cells

Schwann cells are key players in neuro-regeneration: They sense “alarm” signals released by degenerating nerve terminals and differentiate toward a proregenerative phenotype, with phagocytosis of nerve debris and nerve guidance. At the murine neuromuscular junction, hydrogen peroxide (H2O2) is a key signal of Schwann cells’ activation in response to a variety of nerve injuries. Here we report that Schwann cells exposed to low doses of H2O2 rewire the expression of several RNAs at both transcriptional and translational levels. Among the genes positively regulated at both levels, we identified an enriched cluster involved in cytoskeleton remodeling and cell migration, with the Annexin (Anxa) proteins being the most represented family. We show that both Annexin A2 (Anxa2) transcript and protein accumulate at the tips of long pseudopods that Schwann cells extend upon H2O2 exposure. Interestingly, Schwann cells reply to this signal and to nerve injury by locally translating Anxa2 in pseudopods, and undergo an extensive cytoskeleton remodeling. Our results show that, similarly to neurons, Schwann cells take advantage of local protein synthesis to change shape and move toward damaged axonal terminals to facilitate axonal regeneration.
Effect of Probiotics on Metabolic Outcomes in Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The metabolic effects of probiotic administration in women with gestational diabetes mellitus (GDM) is unknown. The objective of this review was to investigate the effect of probiotics on fasting plasma glucose (FPG), insulin resistance (HOMA-IR) and LDL-cholesterol levels in pregnant women diagnosed with GDM. Seven electronic databases were searched for RCTs published in English between 2001 and 2017 investigating the metabolic effects of a 6–8 week dietary probiotic intervention in pregnant women following diagnosis with GDM. Eligible studies were assessed for risk of bias and subjected to qualitative and quantitative synthesis using a random effects model meta-analyses. Four high quality RCTs involving 288 participants were included in the review. Probiotic supplementation was not effective in decreasing FBG (Mean Difference = −0.13; 95% CI −0.32, 0.06, p = 0.18) or LDL-cholesterol (−0.16; 95% CI −0.45, 0.13, p = 0.67) in women with GDM. However, a significant reduction in HOMA-IR was observed following probiotic supplementation (−0.69; 95% CI −1.24, −0.14, p = 0.01). There were no significant differences in gestational weight gain, delivery method or neonatal outcomes between experimental and control groups, and no adverse effects of the probiotics were reported. Probiotic supplementation for 6–8 weeks resulted in a significant reduction in insulin resistance in pregnant women diagnosed with GDM. The use of probiotic supplementation is promising as a potential therapy to assist in the metabolic management of GDM. Further high quality studies of longer duration are required to determine the safety, optimal dose and ideal bacterial composition of probiotics before their routine use can be recommended in this patient group.
Toward an Understanding of the Poor Health Status of Indigenous Australian Men

The purpose of this study was to investigate perceptions of health and health behaviors among Indigenous Australian men. Using a participatory action research (PAR) framework, we conducted two focus groups and 40 individual semi-structured interviews with men between the ages of 18 and 35 years in each of three locations across Australia. We used the health beliefs model to provide a framework for the analyses. Participants recognized that their Indigenous status placed them in a vulnerable position with regard to health, and that there might be serious consequences of failing to follow a good diet and engage in appropriate exercise. However, they delineated a number of barriers to engaging in such health behaviors. These perceived barriers require addressing at a range of policy levels within government, with a focus on social structures and institutionalized discrimination, as well as unemployment, poverty, dispossession, and cultural oppression.
Moderate influenza vaccine effectiveness against influenza A(H1N1)pdm09 virus and low effectiveness against A(H3N2) virus among older adults during 2013–2014 influenza season in Beijing, China

ABSTRACT Background: Since 2007, trivalent inactivated influenza vaccine has been provided free-of-charge to older adults aged ≥60 years in Beijing, China, but the data regarding influenza vaccine effectiveness (VE) among these people are very limited so far. We sought to estimate influenza VE against medically-attended laboratory-confirmed influenza illness among older adults during the 2013–2014 season. Methods: The influenza-like illness (ILI) patients aged 60 years and older who participated in the influenza virological surveillance of Beijing during 2013–2014 influenza season were recruited in this study. A test-negative design was employed to estimate influenza VE among older adults by using logistic regression models. VE was estimated using logistic regression, adjusted for sex, age, interval (days) between illness onset and specimen collection, and week of illness onset. Results: Between 1 November, 2013 and 30 April, 2014, a total of 487 elderly ILI patients were enrolled in the study, including 133 influenza-positive cases (of whom 6.8% were vaccinated) and 354 influenza-negative controls (of whom 10.2% were vaccinated). Among 133 influenza-positive cases, 51 tested positive for A(H1N1)pdm09 virus, 22 positive for A(H3N2) virus, 52 tested positive for B/Yamagata-lineage virus, 2 positive for B/Victoria-lineage virus, 1 positive for both A(H1N1)pdm09 and A(H3N2) viruses, and 5 tested positive for viruses of unknown subtype or lineage. The adjusted overall VE was estimated as 32% (95% CI:-48-69), with 59% (95% CI: −79–90) against A(H1N1)pdm09, 22% (95% CI: −253-83) against A(H3N2) and −20% (95% CI: −239-58) against B/Yamagata-lineage viruses. Conclusions: These results suggested a modest protective effect of the 2013–2014 influenza vaccine among older adults in Beijing which was not statistically significant, with higher VE against the A(H1N1)pdm09 viruses compared to A(H3N2) and B viruses.
On a recent stickiness criterion using a very simple generalization of DMT theory of adhesion

In the contact of rough surfaces, contact occurs on smaller and smaller scales, the well-known Tabor adhesion parameter decreases and the so-called Derjaguin–Muller–Toporov (DMT) theory is the appropriate limit. Fuller and Tabor developed 40 years ago a model based on asperities and JKR theory, and more recently the author developed an asperity theory using asperities and DMT theory in the form given by Maugis. Both lead to adhesion parameters which do not depend on the range of attractive forces, in contrast to the parameter recently suggested by Pastewka and Robbins (PNAS, 111(9), 3298–3303, 2014). As it is well known from random process theory that contact of rough surfaces can be described reasonably well by asperity summits at least for low bandwidths, the Pastewka–Robbins DMT model and stickiness criterion should correspond in the limit case of a spherical contact. We therefore consider this limit case, and show that Pastewka–Robbins DMT model introduces a dependence on range of attractive forces, or on Tabor parameter, which is not correct for the sphere, and therefore may be incorrect also in general.
Eigen Frequency Analysis of a Capacitive Micro-Beam Resonator Considering Residual, Axial Stresses and Temperature Changes Effects

This paper deals with the analysis of eigen frequency in a fixed-fixed micro-beam resonator considering effects of the tensile or compressive residual stresses, axial stress and temperature changes. Non linear governing differential equations of static deflection of the micro-beam using Euler-Bernoulli beam theory has been derived, and linearized using a step by step linearization method. The obtained linearized differential equation has been discretized using a Galerkin weighted residual method. The equation of small oscillations about electrostatically deflected position has been derived and solved using a Galerkin based reduced order model. The results show that owing to different applied voltage, residual stress and axial stress and temperature changes, the resonance frequency of the resonator is changed. Obtained results show that negative temperature changes and tensile residual stresses increase the first natural frequency and compressive residual stresses and positive temperature changes vice versa. Axial stress increases the first resonant frequency and its effect is more considerable when the applied DC voltage is close to the pull-in voltage.
Box Constrained Low-rank Matrix Approximation with Missing Values

In this paper, we propose a new low-rank matrix approximation model for completing a matrix with missing values. Our proposed model contains a box constraint that arises from the context of collaborative filtering. Although it is unfortunately NP-hard to solve our model with high accuracy, we can construct a practical algorithm to obtain a stationary point. Our proposed algorithm is based on alternating minimization and converges to a stationary point under a mild assumption.
Effects of renal impairment on transporter‐mediated renal reabsorption of drugs and renal drug–drug interactions: A simulation‐based study

Renal impairment (RI) significantly impacts the clearance of drugs through changes in the glomerular filtration rate, protein binding and alterations in the expression of renal drug transport proteins and hepatic metabolizing enzymes. The objectives of this study were to evaluate quantitatively the effects of renal impairment on the pharmacokinetics of drugs undergoing renal transporter‐mediated reabsorption. A previously published semi‐mechanistic kidney model incorporating physiologically relevant fluid reabsorption and transporter‐mediated active renal reabsorption (PMID: 26341876) was utilized in this study. The probe drug/transporter pair utilized was γ‐hydroxybutyric acid (GHB) and monocarboxylate transporter 1 (SCL16A1, MCT1). γ‐Hydroxybutyric acid concentrations in the blood and amount excreted into urine were simulated using ADAPT 5 for the i.v. dose range of 200–1500 mg/kg in rats and the impact of renal impairment on CLR and AUC was evaluated. A 90% decrease in GFR resulted in a > 100‐fold decrease in GHB CLR. When expression of reabsorptive transporters was decreased and fu was increased, CLR approached GFR. The effect of renal impairment on CLR was reduced when the expression of drug metabolizing enzymes (DME) was increased as a result of increased metabolic clearance; the converse held true when the DME expression was decreased. In conclusion, this study quantitatively demonstrated that the effects of renal insufficiency on the clearance of drugs is modulated by transporter expression, contribution of renal clearance to overall clearance, expression of drug metabolizing enzymes, fraction unbound and drug–drug interactions with inhibitors of renal transporters that may be increased in the presence of renal impairment.
Real‐time observation of flexible domain movements in CRISPR–Cas9

The CRISPR‐associated protein Cas9 is widely used for genome editing because it cleaves target DNA through the assistance of a single‐guide RNA (sgRNA). Structural studies have revealed the multi‐domain architecture of Cas9 and suggested sequential domain movements of Cas9 upon binding to the sgRNA and the target DNA. These studies also hinted at the flexibility between domains; however, it remains unclear whether these flexible movements occur in solution. Here, we directly observed dynamic fluctuations of multiple Cas9 domains, using single‐molecule FRET. We found that the flexible domain movements allow Cas9 to adopt transient conformations beyond those captured in the crystal structures. Importantly, the HNH nuclease domain only accessed the DNA cleavage position during such flexible movements, suggesting the importance of this flexibility in the DNA cleavage process. Our FRET data also revealed the conformational flexibility of apo‐Cas9, which may play a role in the assembly with the sgRNA. Collectively, our results highlight the potential role of domain fluctuations in driving Cas9‐catalyzed DNA cleavage.
Drosophila RSK Influences the Pace of the Circadian Clock by Negative Regulation of Protein Kinase Shaggy Activity

Endogenous molecular circadian clocks drive daily rhythmic changes at the cellular, physiological, and behavioral level for adaptation to and anticipation of environmental signals. The core molecular system consists of autoregulatory feedback loops, where clock proteins inhibit their own transcription. A complex and not fully understood interplay of regulatory proteins influences activity, localization and stability of clock proteins to set the pace of the clock. This study focuses on the molecular function of Ribosomal S6 Kinase (RSK) in the Drosophila melanogaster circadian clock. Mutations in the human rsk2 gene cause Coffin–Lowry syndrome, which is associated with severe mental disabilities. Knock-out studies with Drosophila ortholog rsk uncovered functions in synaptic processes, axonal transport and adult behavior including associative learning and circadian activity. However, the molecular targets of RSK remain elusive. Our experiments provide evidence that RSK acts in the key pace maker neurons as a negative regulator of Shaggy (SGG) kinase activity, which in turn determines timely nuclear entry of the clock proteins Period and Timeless to close the negative feedback loop. Phosphorylation of serine 9 in SGG is mediated by the C-terminal kinase domain of RSK, which is in agreement with previous genetic studies of RSK in the circadian clock but argues against the prevailing view that only the N-terminal kinase domain of RSK proteins carries the effector function. Our data provide a mechanistic explanation how RSK influences the molecular clock and imply SGG S9 phosphorylation by RSK and other kinases as a convergence point for diverse cellular and external stimuli.
The Arabidopsis kinesin-4, FRA1, requires a high level of processive motility to function correctly

ABSTRACT Processivity is important for kinesins that mediate intracellular transport. Structure–function analyses of N-terminal kinesins (i.e. kinesins comprising their motor domains at the N-terminus) have identified several non-motor regions that affect processivity in vitro. However, whether these structural elements affect kinesin processivity and function in vivo is not known. Here, we used an Arabidopsis thaliana kinesin-4, called Fragile Fiber 1 (FRA1, also known as KIN4A), which is thought to mediate vesicle transport, to test whether mutations that alter processivity in vitro lead to similar changes in behavior in vivo and whether processivity is important for the function of FRA1. We generated several FRA1 mutants that differed in their ‘run lengths’ in vitro and then transformed them into the fra1-5 mutant for complementation and in vivo motility analyses. Our data show that the behavior of processivity mutants in vivo can differ dramatically from in vitro properties, underscoring the need to extend structure–function analyses of kinesins in vivo. In addition, we found that a high density of processive motility is necessary for the physiological function of FRA1. Summary: This study shows that the motility of kinesin mutants can differ significantly between in vitro and in vivo conditions and that abundant processive motility is important for the kinesin function of FRA1.
Can quantum mechanics explain " free will "

My paper: Funda-Mentality: Is the conscious mind subtly linked to a basic level of the universe? Trends in Cognitive Sciences 2(4):119-127 (1998), was followed by an exchange focusing on the problem of free will (and other issues) between me and two critics, Emmet Spier from the Centre for Computational Neuroscience and Robotics, University of Sussex, Falmer, Brighton, UK, and Adrian Thomas, Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. They get the last word in this exchange, but I’ll counter later.
Type-B ARRs Control Carpel Regeneration Through Mediating AGAMOUS Expression in Arabidopsis

Abstract Plants are known for their capacity to regenerate organs, such as shoot, root and floral organs. Recently, a number of studies contributed to understanding the mechanisms of shoot and root regeneration. However, the mechanisms underlying floral organ regeneration are largely unknown. In this study, we established a carpel regeneration system in which two types of carpels were induced by exogenous cytokinin. For type I, all the floral organs in the regenerated inflorescence were transformed into carpels. For type II, carpels were generated directly from callus. The transcript level of AGAMOUS (AG), the carpel identity gene, was up-regulated during carpel induction. The expression signals of AG were detected in the initiating carpel primordia and regenerating carpels, and co-localized with those of two Type-B ARABIDOPSIS RESPONSE REGULATORs (ARRs), ARR1 and ARR10. Repression of either AG or type-B ARRs reduced carpel regeneration. Binding analyses showed that ARR1 and ARR10 directly bound to transcriptional regulatory regions of AG and positively regulated its expression. In addition, the expression of type-B ARRs overlapped with that of AG in the floral primordia in planta. Defects in type-B ARRs reduced the number of carpels. The results indicate that type-B ARRs control carpel regeneration through activating AG expression. Our results provide new information for understanding the mechanism of carpel formation.
Dyadic flexibility and positive affect in parent–child coregulation and the development of child behavior problems

Abstract Parent–child dyadic rigidity and negative affect contribute to children's higher levels of externalizing problems. The present longitudinal study examined whether the opposite constructs of dyadic flexibility and positive affect predicted lower levels of externalizing behavior problems across the early childhood period. Mother–child (N = 163) and father–child (n = 94) dyads engaged in a challenging block design task at home when children were 3 years old. Dynamic systems methods were used to derive dyadic positive affect and three indicators of dyadic flexibility (range, dispersion, and transitions) from observational coding. We hypothesized that the interaction between dyadic flexibility and positive affect would predict lower levels of externalizing problems at age 5.5 years as rated by mothers and teachers, controlling for stability in externalizing problems, task time, child gender, and the child's effortful control. The hypothesis was supported in predicting teacher ratings of child externalizing from both mother–child and father–child interactions. There were also differential main effects for mothers and fathers: mother–child flexibility was detrimental and father–child flexibility was beneficial for child outcomes. Results support the inclusion of adaptive and dynamic parent–child coregulation processes in the study of children's early disruptive behavior.
The natural history of meningococcal carriage and disease

The prevalence of Neisseria meningitidis carriage is highest in teenagers and lowest in young children. In contrast, invasive meningococcal disease is most common in young children with a smaller secondary peak in teenagers. Data on carriage and disease were analysed to quantify the risks of infection and disease by age and serogroup. The forces of infection for serogroups B, C, other meningococci and Neisseria lactamica were modelled together with the risk of disease given infection for serogroups B and C, using maximum likelihood to fit the models to the available data. The risk of meningococcal disease given infection declines steeply through childhood and is higher for serogroup C than for serogroup B. The secondary peak in disease in teenagers appears to be explained mostly by increased transmission although there is a suggestion that other factors may also contribute. These analyses provide important insights and may be used to guide further data collection and modelling studies.
Geographical variation in sound production in the anemonefish Amphiprion akallopisos

Because of pelagic-larval dispersal, coral-reef fishes are distributed widely with minimal genetic differentiation between populations. Amphiprion akallopisos, a clownfish that uses sound production to defend its anemone territory, has a wide but disjunct distribution in the Indian Ocean. We compared sounds produced by these fishes from populations in Madagascar and Indonesia, a distance of 6500 km. Differentiation of agonistic calls into distinct types indicates a complexity not previously recorded in fishes' acoustic communication. Moreover, various acoustic parameters, including peak frequency, pulse duration, number of peaks per pulse, differed between the two populations. The geographic comparison is the first to demonstrate ‘dialects’ in a marine fish species, and these differences in sound parameters suggest genetic divergence between these two populations. These results highlight the possible approach for investigating the role of sounds in fish behaviour in reproductive divergence and speciation.
The Parahippocampal Region and Object Identification

Abstract: The hippocampus has long been thought to be critical for memory, including memory for objects. However, recent neuropsychological studies in nonhuman primates have indicated that other regions within the medial temporal lobe, specifically, structures in the parahippocampal region, are primarily responsible for object recognition and object identification. This article reviews the behavioral effects of removal of structures within the parahippocampal region in monkeys, and cites relevant work in rodents as well. It is argued that the perirhinal cortex, in particular, contributes to object identification in at least two ways: (i) by serving as the final stage in the ventral visual cortical pathway that represents stimulus features, and (ii) by operating as part of a network for associating together sensory inputs within and across sensory modalities.