Iron homeostasis requires subtle control systems, as iron is both essential and toxic. In Aspergillus nidulans, iron represses iron acquisition via the GATA factor SreA, and induces iron-dependent pathways at the transcriptional level, by a so far unknown mechanism. Here, we demonstrate that iron-dependent pathways (e.g., heme biosynthesis) are repressed during iron-depleted conditions by physical interaction of HapX with the CCAAT-binding core complex (CBC). Proteome analysis identified putative HapX targets. Mutual transcriptional control between hapX and sreA and synthetic lethality resulting from deletion of both regulatory genes indicate a tight interplay of these control systems. Expression of genes encoding CBC subunits was not influenced by iron availability, and their deletion was deleterious during iron-depleted and iron-replete conditions. Expression of hapX was repressed by iron and its deletion was deleterious during irondepleted conditions only. These data indicate that the CBC has a general role and that HapX function is confined to iron-depleted conditions. Remarkably, CBC-mediated regulation has an inverse impact on the expression of the same gene set in A. nidulans, compared with Saccharomyces cerevisae.

We sought to determine if an in-field gait retraining program can reduce excessive impact forces and peak hip adduction without adverse changes in knee joint work during running. Thirty healthy at-risk runners who exhibited high-impact forces were randomized to retraining [21.1 (± 1.9) years, 22.1 (± 10.8) km/week] or control groups [21.0 (± 1.3) years, 23.2 (± 8.7) km/week]. Retrainers were cued, via a wireless accelerometer, to increase preferred step rate by 7.5% during eight training sessions performed in-field. Adherence with the prescribed step rate was assessed via mobile monitoring. Three-dimensional gait analysis was performed at baseline, after retraining, and at 1-month post-retraining. Retrainers increased step rate by 8.6% (P < 0.0001), reducing instantaneous vertical load rate (-17.9%, P = 0.003), average vertical load rate (-18.9%, P < 0.0001), peak hip adduction (2.9° ± 4.2 reduction, P = 0.005), eccentric knee joint work per stance phase (-26.9%, P < 0.0001), and per kilometer of running (-21.1%, P < 0.0001). Alterations in gait were maintained at 30 days. In the absence of any feedback, controls maintained their baseline gait parameters. The majority of retrainers were adherent with the prescribed step rate during in-field runs. Thus, in-field gait retraining, cueing a modest increase in step rate, was effective at reducing impact forces, peak hip adduction and eccentric knee joint work.

SUMMARY Arboreal locomotion has mainly been looked at to date in the context of investigations into the specialization of primates and other ‘arboreally adapted’ animals. The feat of moving on branches as small or smaller than the body's diameter was tested in rats (Rattus norvegicus) as they moved on horizontal poles of different diameters. The data were compared with data pertaining to terrestrial locomotion. We investigated three-dimensional kinematics and dynamics using biplanar cineradiography with simultaneous substrate reaction force (SRF) measurements. As predicted, rats flexed fore- and hindlimbs and reduced vertical forces during pole locomotion. In addition, the orientation of the mediolateral substrate reaction force resultant (SRR) and impulses switched from lateral to medial. In order to maintain stability during arboreal locomotion, lateral spine movements increased. We propose that the combination of lateral sequence gaits, similar travel speed of the animals and similar contact times, higher or similar peak vertical forces as well as similar mediolateral impulses in forelimbs and hindlimbs are typical of clawed mammals moving on thin supports. Clawed mammals and primates share the reduction of vertical oscillations and side-to-side fluctuations, a crouched posture as well as the increase in lateral spine movements. We conclude that these features are behavioral adaptations caused by the biomechanical constraints of small branch locomotion, regardless of the way they make contact with the substrate.