The small molecule, genistein, increases hepcidin expression in human hepatocytes

Hepcidin, a peptide hormone that decreases intestinal iron absorption and macrophage iron release, is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. Endogenous stimulants of Hepcidin transcription include bone morphogenic protein 6 (BMP6) and interleukin-6 (IL-6) by effects on mothers against decapentaplegic homolog (Smad)4 or signal transducer and activator of transcription (Stat)3, respectively. We conducted a small-scale chemical screen in zebrafish embryos to identify small molecules that modulate hepcidin expression. We found that treatment with the isoflavone, genistein, from 28-52 hours postfertilization in zebrafish embryos enhanced Hepcidin transcript levels, as assessed by whole-mount in situ hybridization and quantitative real-time reverse-transcriptase polymerase chain reaction. Genistein's stimulatory effect was conserved in human hepatocytes: Genistein treatment of HepG2 cells increased both Hepcidin transcript levels and promoter activity. We found that genistein's effect on Hepcidin expression did not depend on estrogen receptor signaling or increased cellular iron uptake, but was impaired by mutation of either BMP response elements or the Stat3-binding site in the Hepcidin promoter. RNA sequencing of transcripts from genistein-treated hepatocytes indicated that genistein up-regulated 68% of the transcripts that were up-regulated by BMP6; however, genistein raised levels of several transcripts involved in Stat3 signaling that were not up-regulated by BMP6. Chromatin immunoprecipitation and ELISA experiments revealed that genistein enhanced Stat3 binding to the Hepcidin promoter and increased phosphorylation of Stat3 in HepG2 cells. Conclusion: Genistein is the first small-molecule experimental drug that stimulates Hepcidin expression in vivo and in vitro. These experiments demonstrate the feasibility of identifying and characterizing small molecules that increase Hepcidin expression. Genistein and other candidate molecules may subsequently be developed into new therapies for iron overload syndromes.

Darwin after dark: illuminating suburban atmospheres

In Australian cities, culturally diverse suburban landscapes are often sensed as discomforting sites of fear and anxiety, particularly after dark. Imagined risks of encounters with bodies of colour easily policed during the day when vision is clear, but who escape biopolitical regimes of securitisation and surveillance at night contribute to such atmospheric qualities of place. These affective atmospheres of fear and anxiety that haunt bodies and limit their ability to inhabit public space, however, can provide a sense of freedom for bodies who claim suburban spaces of darkness through tactile and sonic senses. This paper draws on the contemporary literature on affective atmospheres to show how racialised Indigenous and asylum seeker bodies become present in different ways in suburban places in Darwin after dark. The paper focuses on two events – spontaneous dancing to Indigenous music at Mindil beach market and a Vigil commemorating asylum seeker lives in a suburban courtyard. Drawing on ethnographic research I explore these affective intervention that illuminate dark suburban atmospheres in Darwin. Such interventions that draw attention to the attunement of bodies to difference unsettle biopolitical regimes that victimise and patronise visible non-white bodies and contribute to rethinking racism and darkness in suburban Darwin and the Top End.

Fibre properties affecting the softness of wool and other keratins

The emerging market for next-to-skin knitwear requires wool to satisfy the consumer’s tactile requirements for softness. The role of the fibre’s surface and physical properties on fibre and fabric softness was examined. The fibre’s cuticle properties were found to have a greater influence on softness than the fibre’s mechanical properties.

Analyses and comparison of counter-movement jump performance and self-rated recovery in state under-18s Australian Rules Football players during a national championship

Recovery of team sport athletes during multiple competitive games is an important area for strength and conditioning coaches to monitor as it facilitates for athletes to be ready to perform (11,13). Utilising athletic performance data in conjunction with self-rated reporting measures can help determine if in fact a player or team has recovered sufficiently or shown a trend towards recovery prior to a competitive match (11). Positive improvement in recovery variables can provide confidence in the effectiveness of recovery methods used and assist in determining the training schedule in order to positively manipulate the fitness-fatigue relationship (3).

Various methods of analysing the recovery of athletes have been reported in the literature and are available to the strength and conditioning coach. These include subjective, self-rated scales and perceived level of recovery questionnaires (11,12,13). Athletic performance measures during exercises such as the counter movement jump (CMJ) have also been analysed, predominantly utilising force plates to obtain kinetic data. (5,13,14). However, such equipment can be difficult to transport, requires continual calibration and is costly to purchase. A linear transducer can provide important information on CMJ variables in the assessment of athletic movements and due to its size and portability could serve as a valuable tool to assist strength and conditioning coaches, (8,10), and potentially enable the monitoring of recovery.

Previous studies have investigated the fatigue effects of competitive games in various sports (11,13,14) including Australian Rules Football (AFL) at the senior elite league level (5, 6). To the authors’ knowledge, however, there is yet to be a study investigating the recovery response in AFL players, specifically in players 18 years and under competing in the National Under 18s Championships. Australian Rules football is an extremely physically demanding and fatiguing sport where players participate in games time exceeding 120 minutes duration, covering large distances (~12-18km, position dependent) with many high intensity efforts performed at random times throughout the game (2,6,16). Hence, it would seem pertinent to analyse the fatigue effects of competitive matches in an Australian Rules Under-18’s National Championship and the subsequent recovery from these games.

The aim of this study was to analyse and compare two self-rated subjective measures of recovery; they being muscle soreness (MS) of the lower body, overall perceived total recovery (TR), and the performance measure of peak velocity (PV) obtained from a CMJ analysed with a linear transducer. Data collection occurred between rounds four and five of the Australian Football League Under-18’s National Championship, representing a four-day recovery analysis period between matches.

A high performance position sensorless surface permanent magnet synchronous motor drive based on flux angle

A position sensorless Surface Permanent Magnet Synchronous Motor (SPMSM) drive based on flux angle is presented in this paper. The motor equations are written in rotor fixed d-q reference frame. A PID controller is used to process the speed error to generate the reference torque current keeping the magnetizing current fixed. The estimated stator flux using Recurrent Neural Network (RNN) is used to find out the rotor position. The flux angle and the reference current phasor angle are used in vector rotator to generate the reference phase currents. Hysteresis current controller block controls the switching of the 3-phase inverter to apply voltage to the motor stator. Simulation studies on different operating conditions indicate the acceptability of the drive system. The drive system only requires a speed transducer and is free from position sensor requirement. The proposed control scheme is robust under load torque disturbances and motor parameter variations. It is also simple and low cost to implement in a practical environment.

Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level.

The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These mice are hyperphagic and morbidly obese, but display only minimal changes in size and cellularity of the thymus, and cellular immune responses are unaffected. These animals also displayed liver damage in response to concavalin A comparable to wild-type and heterozygous littermates. Second, treatment of healthy mice with a neutralizing nanobody targeting IGD induced weight gain and hyperinsulinaemia, but completely failed to block development of experimentally induced autoimmune diseases. These data indicate that leptin receptor deficiency or antagonism profoundly affects metabolism, with little concomitant effects on immune functions.

Effects of variation in wool fiber curvature and yarn hairiness on sensorial assessment of knitted fabrics

Previous investigations have shown that prickle discomfort sensations of wool fabrics are primarily determined by the mean fiber diameter of the wool. It is also known that differences in wool fiber curvature (crimp) affect softness of handle of greasy wool and of wool textiles. In a replicated experiment, we investigated if wearers could detect the effect of using 17 µm superfine wool of low (74°/mm) or high (114°/mm) fiber curvature, and when the wools were blended with 17 µm cashmere (fiber curvature 49°/mm) in differing proportions, on four comfort sensations. Eight single jersey knitted fabrics were assessed under a controlled protocol using forearm sleeves made of the test fabric and a control fabric. Data (37 sensorial assessments of high curvature wool fabrics; 38 sensorial assessments of low curvature wool fabrics) were analyzed using linear mixed model analysis (restricted maximum likelihood), which included fixed effects for wool type and blend ratio and a random effect for participant. The use of a control sleeve fabric reduced variance due to participant effects by providing an anchor for each sensation over time. Wool fiber curvature affected participant assessment of breathability, comfort, feel after exercise (damp/dry) and skin feel (prickly/soft), with preferred values associated with high curvature (crimp) superfine wool. Increasing the proportion of cashmere in fabrics increased skin feel (better assessed softness). Skin feel was strongly associated with the evaluation of the fabrics by the Wool ComfortMeter and with increasing hairiness of yarns.

Short communication: bovine-derived proteins activate STAT3 in human skeletal muscle in vitro

Bovine milk contains biologically active peptides that may modulate growth and development within humans. In this study, targeted bovine-derived proteins were evaluated for their effects on signal transducer and activator of transcription-3 (STAT3) phosphorylation in human skeletal muscle cells. Following an acute exposure, bovine-derived acidic fibroblast growth factor-1 (FGF) and leukemia inhibitory factor (LIF) activated STAT3 in differentiating myotubes. Chronic exposure to FGF and LIF during the proliferative phase reduced myoblast proliferation and elevated MyoD and creatine kinase (CKM) mRNA expression without altering apoptotic genes. In mature myotubes, neither FGF nor LIF elicited any action. Together, these data indicate that a reduction in proliferation in the presence of bovine-derived FGF or LIF may stimulate early maturation of myoblasts.

Signaling via the CytoR/JAK/STAT/SOCS pathway: emergence during evolution

Cell-cell signaling represents an essential hallmark of multicellular organisms, which necessarily require a means of communicating between different cell populations, particularly immune cells. Cytokine receptor signaling through the Janus kinase/Signal Transducer and Activator of Transcription/Suppressor of Cytokine Signaling (CytoR/JAK/STAT/SOCS) pathway embodies one important paradigm by which this is achieved. This pathway has been extensively studied in vertebrates and protostomes and shown to play fundamental roles in development and function of immune and other cells. However, our understanding of the origins of the individual pathway components and their assembly into a functional pathway has remained limited. This study examined the origins of each component of this pathway through bioinformatics analysis of key extant species. This has revealed step-wise accretion of individual components over a large evolutionary time-frame, but only in bilateria did a series of innovations allow their final coalescence to form a complete pathway. Assembly of the CytoR/JAK/STAT pathway has followed the retrograde model of pathway evolution, whereas addition of the SOCS component has adhered to the patchwork model.