The relationship of high-intensity cross-training with arterial stiffness

Background Central arterial stiffness is a cardiovascular risk factor that can be readily affected through engagement in physical exercise training, with resistance and aerobic exercise having disparate affects. Despite the growing popularity of high-intensity cross-training (HICT), little is currently known about the effects of this mixed modality exercise stimulus on arterial stiffness. Therefore, the purpose of this study was to characterize the arterial stiffness of habitual HICT participants vs. aerobically active and sedentary controls using a cross-sectional design. Methods A total of 30 participants were recruited: 10 middle-aged long-term participants of HICT (CrossFit) and 20 age, sex, and height matched controls (10 recreationally active, 10 sedentary). Central and peripheral pulse wave velocities were measured for the carotid-femoral and femoral-dorsalis pedis arterial segments. Aerobic fitness (maximal oxygen uptake, VO2max) was measured and typical exercise participation rates were self-reported for each group. Results HICT participants manifested central pulse wave velocity (PWV) (5.3 ± 1.0 m/s, mean ± SD) and VO2max (43 ± 6 mL/kg/min) values nearly identical to active controls. Both active groups had significantly better values than sedentary controls (7.1 ± 1.0 m/s, p ≤ 0.001; and 32 ± 7 mL/kg/min, p = 0.01). No differences were observed in peripheral PWV between groups. Conclusion Habitual participation in HICT exercise was not associated with increased central nor peripheral arterial stiffness. Long-term HICT participants presented with similar fitness and arterial stiffness as compared with participants who practiced traditional aerobic exercise. Compared to sedentary living, HICT may offer musculoskeletal and cardiovascular health benefits without negatively impacting arterial stiffness

Impact of boundaries on fully connected random geometric networks

Many complex networks exhibit a percolation transition involving a macroscopic connected component, with universal features largely independent of the microscopic model and the macroscopic domain geometry. In contrast, we show that the transition to full connectivity is strongly influenced by details of the boundary, but observe an alternative form of universality. Our approach correctly distinguishes connectivity properties of networks in domains with equal bulk contributions. It also facilitates system design to promote or avoid full connectivity for diverse geometries in arbitrary dimension.Comment: 6 pages, 3 figure

Dynamic Range Majority Data Structures

Given a set $P$ of coloured points on the real line, we study the problem of answering range $\alpha$-majority (or "heavy hitter") queries on $P$. More specifically, for a query range $Q$, we want to return each colour that is assigned to more than an $\alpha$-fraction of the points contained in $Q$. We present a new data structure for answering range $\alpha$-majority queries on a dynamic set of points, where $\alpha \in (0,1)$. Our data structure uses O(n) space, supports queries in $O((\lg n) / \alpha)$ time, and updates in $O((\lg n) / \alpha)$ amortized time. If the coordinates of the points are integers, then the query time can be improved to $O(\lg n / (\alpha \lg \lg n) + (\lg(1/\alpha))/\alpha))$. For constant values of $\alpha$, this improved query time matches an existing lower bound, for any data structure with polylogarithmic update time. We also generalize our data structure to handle sets of points in d-dimensions, for $d \ge 2$, as well as dynamic arrays, in which each entry is a colour.Comment: 16 pages, Preliminary version appeared in ISAAC 201

Possible common central pathway for resistin and insulin in regulating food intake.

Aim: Adipose tissue has been the object of intense research in the field of obesity and diabetes diseases in the last decade. Examination of adipocyte-secreted peptides led to the identification of a unique polypeptide, resistin (RSTN), which has been suggested as a link between obesity and diabetes. RSTN plays a clearly documented role in blocking insulin (INS)-induced hypoglycaemia. As brain injection of INS affects feeding behaviour, we studied the possible interaction between INS and RSTN in food-deprived rats, measuring effects on food intake. In addition, we examined how RSTN might affect neuropeptide Y (NPY)-induced feeding, as studies have shown that rat RSTN can interfere with the NPY system. Methods: Overnight food-deprived rats were injected into the third brain ventricle (3V) with either INS (10 or 20 mUI), RSTN (0.1–0.4 nmol/rat), or saline before access to food. Another group of rats was injected into the 3V with RSTN alone, NPY alone or RSTN plus NPY. Their food intake and body weight were measured. Results: Our results confirm the hypophagic effect of RSTN on food deprivation-induced food intake, and more importantly, show that RSTN neither potentiates nor blocks the effects of INS on food intake, but does reduce the hyperphagic effect of NPY. Conclusion:  The observation that RSTN does not modify feeding INS-induced hypophagia, but does influence NPY-induced feeding, points to the possibility that RSTN may be involved in control of food intake through an NPY-ergic mechanism as INS

Versatility in phospho-dependent molecular recognition of the XRCC1 and XRCC4 DNA-damage scaffolds by aprataxin-family FHA domains

Aprataxin, aprataxin and PNKP-like factor (APLF) and polynucleotide kinase phosphatase (PNKP) are key DNA-repair proteins with diverse functions but which all contain a homologous forkhead-associated (FHA) domain. Their primary binding targets are casein kinase 2-phosphorylated forms of the XRCC1 and XRCC4 scaffold molecules which respectively coordinate single-stranded and double-stranded DNA break repair pathways. Here, we present the high-resolution X-ray structure of a complex of phosphorylated XRCC4 with APLF, the most divergent of the three FHA domain family members. This, combined with NMR and biochemical analysis of aprataxin and APLF binding to singly and multiply-phosphorylated forms of XRCC1 and XRCC4, and comparison with PNKP reveals a pattern of distinct but overlapping binding specificities that are differentially modulated by multi-site phosphorylation. Together, our data illuminate important differences between activities of the three phospho-binding domains, in spite of a close evolutionary relationship between them

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

IgG light chain-independent secretion of heavy chain dimers: consequence for therapeutic antibody production and design

Rodent monoclonal antibodies with specificity towards important biological targets are developed for therapeutic use by a process of humanisation. This process involves the creation of molecules, which retain the specificity of the rodent antibody but contain predominantly human coding sequence. Here we show that some humanised heavy chains can fold, form dimers and be secreted even in the absence of light chain. Quality control of recombinant antibody assembly in vivo is thought to rely upon folding of the heavy chain CH1 domain. This domain acts as a switch for secretion, only folding upon interaction with the light chain CL domain. We show that the secreted heavy-chain dimers contain folded CH1 domains and contribute to the heterogeneity of antibody species secreted during the expression of therapeutic antibodies. This subversion of the normal quality control process is dependent upon the heavy chain variable domain, is prevalent with engineered antibodies and can occur when only the Fab fragments are expressed. This discovery will impact on the efficient production of both humanised antibodies as well as the design of novel antibody formats

Efficacy of coping mechanisms used during COVID-19 as reported by parents of children with autism

The COVID-19 pandemic’s alterations to daily life have been especially challenging for families with Autism Spectrum Disorder (ASD), worsening the core features of ASD and overall mental health. With the increased need for effective coping, the current retrospective study used data from a survey regarding parent reports of how often their child with ASD used certain coping strategies (frequency), as well as the extent to which they felt their child benefitted from their use (efficacy) in mitigating stress during the pandemic. This retrospective study Repeated measures ANOVAs were conducted to evaluate whether there were significant differences in both frequency and efficacy ratings for each coping strategy, for the entire sample as well as for three children’s age groups. Using Spearman’s rank-order correlations, correlation coefficients between the frequency and efficacy of each coping strategy were explored. Results revealed that maladaptive strategies were used more frequently than adaptive strategies, while parent routine as the most frequently used and efficacious for all age groups. Additionally, for adaptive strategies, humor and focusing on the positive had the strongest correlations between frequency and efficacy ratings amongst all age groups. Of the maladaptive strategies, repetitive behaviors, rumination, and isolation had the strongest correlations for the youngest, middle, and oldest age groups, respectively. Further, for each age group, the adaptive coping strategies had stronger correlations between frequency and efficacy than the maladaptive ones. It is our hope that the results of this study will lay the foundation for developing adaptive coping strategies to alleviate stress in children with ASD. Further investigations using a larger cohort are warranted to determine effective coping strategies for individuals with ASD across a range of situations, including acute stressors (such as future public health emergencies and natural disasters), as well as common daily stressors