Explore the vast range of titles available.

In plants and algae, light serves both as the energy source for photosynthesis and a biological signal that triggers cellular responses via specific sensory photoreceptors. Red light is perceived by bilin-containing phytochromes and blue light by the flavin-containing cryptochromes and/or phototropins (PHOTs), the latter containing two photosensory light, oxygen, or voltage (LOV) domains. Photoperception spans several orders of light intensity, ranging from far below the threshold for photosynthesis to values beyond the capacity of photosynthetic CO2 assimilation. Excess light may cause oxidative damage and cell death, processes prevented by enhanced thermal dissipation via high-energy quenching (qE), a key photoprotective response. Here we show the existence of a molecular link between photoreception, photosynthesis, and photoprotection in the green alga Chlamydomonas reinhardtii. We show that PHOT controls qE by inducing the expression of the qE effector protein LHCSR3 (light-harvesting complex stress-related protein 3) in high light intensities. This control requires blue-light perception by LOV domains on PHOT, LHCSR3 induction through PHOT kinase, and light dissipation in photosystem II via LHCSR3. Mutants deficient in the PHOT gene display severely reduced fitness under excessive light conditions, indicating that the sensing, utilization, and dissipation of light is a concerted process that plays a vital role in microalgal acclimation to environments of variable light intensities.

Background Anaplastic thyroid carcinoma (ATC) is one of the most aggressive tumours. We previously confirmed that apatinib has potential therapeutic effects on ATC via regulated cell death (RCD). As a newly identified RCD, pyroptosis demonstrates direct antitumour activity different from apoptosis or autophagy. Therefore, the clinical significance, regulatory role and underlying mechanisms of pyroptosis in ATC were focused on in this study. Methods In a phase II trial, patients with anaplastic or poorly differentiated thyroid carcinoma received apatinib 500 mg once daily. Multiple assays were implemented to evaluate the antitumour efficacy of apatinib and/or melittin in vitro and in vivo. High‐throughput sequencing was applied to analyse differential mRNAs expression in ATC cells treated by apatinib with or without melittin. In situ Hoechst 33342/PI double‐staining, LDH release assay and enzyme‐linked immunosorbent assay (ELISA) were employed to determine pyroptosis. In mechanism exploration, quantitative RT‐PCR, Western blotting and si‐RNA knocking down were executed. Results Seventeen patients were evaluable. Apatinib showed a promising therapeutic effect by a disease control rate (DCR) of 88.2%; however, treatment was terminated in 23.5% of patients due to intolerable toxicity. To reduce adverse events, a pyroptosis‐mediated synergistic antitumour effect of apatinib and melittin was identified in treatment of ATC in vitro and in vivo. The caspase‐1–gasdermin D (GSDMD) axis‐mediated pyroptosis was the key to extra antitumour effect of the combination of apatinib and melittin. Moreover, caspase‐3–gasdermin E (GSDME) pyroptosis pathway also functioned importantly in addition to caspase‐1–GSDMD pathway. Evidenced by in vitro and in vivo study, a two‐way positive feedback interaction was innovatively confirmed between caspase‐1–GSDMD and caspase‐3–GSDME axes. Conclusions Through pyroptosis mediated by caspase‐1–GSDMD and caspase‐3–GSDME axes synchronically, low‐dosage apatinib and melittin could synergistically achieve a comparable therapeutic potential with reduced AEs. More importantly, a two‐way positive feedback interaction is innovatively proposed between these two axes, which provide a new prospect of targeted therapy. Apatinib and melittin could synergistically achieve a comparable therapeutic potential, which could reduce adverse events. A novel antitumour effect of pyroptosis induced by combination of apatinib and melittin in anaplastic thyroid carcinoma (ATC) was identified. Both caspase‐1–GSDMD and caspase‐3–GSDME pyroptosis pathways were the key to this extra antitumour effect. A two‐way positive feedback regulation was innovatively proposed between caspase‐1–GSDMD and caspase‐3–GSDME axes.

Mitochondrial cytochrome c release and inositol (1,4,5) trisphosphate receptor (InsP 3 R)-mediated calcium release from the endoplasmic reticulum mediate apoptosis in response to specific stimuli. Here we show that cytochrome c binds to the InsP 3 R during apoptosis. Addition of 1 nM cytochrome c blocks calcium-dependent inhibition of InsP 3 R function. Early in apoptosis, cytochrome c translocates to the endoplasmic reticulum where it selectively binds InsP 3 R, resulting in sustained, oscillatory cytosolic calcium increases. These calcium events are linked to the coordinate release of cytochrome c from all mitochondria. Our findings identify a feed-forward mechanism whereby early cytochrome c release increases InsP 3 R function, resulting in augmented cytochrome c release that amplifies the apoptotic signal.

To promote motor learning, robotic devices have been used to improve subjects’ performance by guiding desired movements (haptic guidance—HG) or by artificially increasing movement errors to foster a more rapid learning (error amplification—EA). To better understand the neurophysiological basis of motor learning, a few studies have evaluated brain regions activated during EA/HG, but none has compared both approaches. The goal of this study was to investigate using fMRI which brain networks were activated during a single training session of HG/EA in healthy adults learning to play a computerized pinball-like timing task. Subjects had to trigger a robotic device by flexing their wrist at the correct timing to activate a virtual flipper and hit a falling ball towards randomly positioned targets. During training with HG/EA, subjects’ timing errors were decreased/increased, respectively, by the robotic device to delay or accelerate their wrist movement. The results showed that at the beginning of the training period with HG/EA, an error-detection network, including cerebellum and angular gyrus, was activated, consistent with subjects recognizing discrepancies between their intended actions and the actual movement timing. At the end of the training period, an error-detection network was still present for EA, while a memory consolidation/automatization network (caudate head and parahippocampal gyrus) was activated for HG. The results indicate that training movement with various kinds of robotic input relies on different brain networks. Better understanding the neurophysiological underpinnings of brain processes during HG/EA could prove useful for optimizing rehabilitative movement training for people with different patterns of brain damage.

We conducted behavioral and functional magnetic resonance imaging (fMRI) research to investigate the effects of two types of achievement goals--mastery goals and performance-approach goals--on challenge seeking and feedback processing. The results of the behavioral experiment indicated that mastery goals were associated with a tendency to seek challenge, both before and after experiencing difficulty during task performance, whereas performance-approach goals were related to a tendency to avoid challenge after encountering difficulty during task performance. The fMRI experiment uncovered a significant decrease in ventral striatal activity when participants received negative feedback for any task type and both forms of achievement goals. During the processing of negative feedback for the rule-finding task, performance-approach-oriented participants showed a substantial reduction in activity in the dorsolateral prefrontal cortex (DLPFC) and the frontopolar cortex, whereas mastery-oriented participants showed little change. These results suggest that performance-approach-oriented participants are less likely to either recruit control processes in response to negative feedback or focus on task-relevant information provided alongside the negative feedback. In contrast, mastery-oriented participants are more likely to modulate aversive valuations to negative feedback and focus on the constructive elements of feedback in order to attain their task goals. We conclude that performance-approach goals lead to a reluctant stance towards difficulty, while mastery goals encourage a proactive stance.

Damage to the superior and/or inferior parietal lobules (SPL, IPL) (Sirigu et al., 1996) or cerebellum (Grealy and Lee, 2011) can selectively disrupt motor imagery, motivating the hypothesis that these regions participate in predictive (i.e., feedforward) control. If so, then the SPL, IPL, and cerebellum should show greater activity as the demands on feedforward control increase from visually-guided execution (closed-loop) to execution without visual feedback (open-loop) to motor imagery. Using fMRI and a Fitts' reciprocal aiming task with tools directed at targets in far space, we found that the SPL and cerebellum exhibited greater activity during closed-loop control. Conversely, open-loop and imagery conditions were associated with increased activity within the IPL and prefrontal areas. These results are consistent with a superior-to-inferior gradient in the representation of feedback-to-feedforward control within the posterior parietal cortex. Additionally, the anterior SPL displayed greater activity when aiming movements were performed with a stick vs. laser pointer. This may suggest that it is involved in the remapping of far into near (reachable) space (Maravita and Iriki, 2004), or in distalization of the end-effector from hand to stick (Arbib et al., 2009). [Display omitted] •Closed-loop, open-loop, and imagined tool-use, in far space, obey Fitts' law.•Reduced influence of reciprocal aiming task difficulty during motor imagery•Superior-to-inferior gradient of feedback-to-feedforward control within the PPC•Mechanisms involved in motor imagery and open-loop control overlap substantially.•Anterior SPL supports dynamic representations of reachable as opposed to near space.

Systemic sclerosis (SSc) is characterized by excess collagen deposition in the skin, due to intrinsic transforming growth factor-β (TGF-β) activation. We tried to determine the expression and the role of discoidin domain receptor 2 (DDR2) in SSc. The expression of DDR2 mRNA and protein was significantly decreased in SSc dermal fibroblasts, which was recovered by knocking down TGF-β. The knockdown of DDR2 in normal fibroblasts induced microRNA-196a expression, which led to type I collagen downregulation, indicating that DDR2 itself has a negative effect on microRNA-196a expression and inducible effect on collagen expression. In SSc fibroblasts, however, the DDR2 knockdown did not affect TGF-β signaling and microRNA-196a expression. The microRNA-196a levels were significantly decreased in normal fibroblasts treated with TGF-β and in SSc fibroblasts. Taken together our data indicate that, in SSc fibroblasts, intrinsic TGF-β stimulation induces type I collagen expression, and also downregulates DDR2 expression. This probably acts as a negative feedback mechanism against excess collagen expression, as a decreased DDR2 expression is supposed to stimulate the microRNA-196a expression and further change the collagen expression. However, in SSc fibroblasts the microRNA-196a expression was downregulated by TGF-β signaling. DDR2–microRNA-196a pathway may be a previously unreported negative feedback system, and its impairment may be involved in the pathogenesis of SSc.

Hunger arouses sensory perception, eventually leading to an increase in food intake, but the underlying mechanisms remain poorly understood. We found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection. CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB). Local pharmacological and genetic manipulations revealed that endocannabinoids and exogenous cannabinoids increased odor detection and food intake in fasted mice by decreasing excitatory drive from olfactory cortex areas to the MOB. Consistently, cannabinoid agonists dampened in vivo optogenetically stimulated excitatory transmission in the same circuit. Our data indicate that cortical feedback projections to the MOB crucially regulate food intake via CB1 receptor signaling, linking the feeling of hunger to stronger odor processing. Thus, CB1 receptor-dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior.

Objective To determine whether the provision of comparative performance feedback during 4 km track cycling affects completion time. Design Five highly trained male cyclists first performed a baseline (BL) 4-km time trial (TT) on a velodrome track, followed by two further randomised 4-km TT, during which riders received either correct (COR) or non-contingent (FAL) feedback based on their BL performance. Results Participants completed the COR TT in a significantly faster time (t4=−3.10, p<0.05) than the FAL TT (341 (8) s vs 350 (12) s). Over the TT, a significant difference in mean speed was apparent between the two conditions (F15,60=1.95, p<0.05) on the second (t4=4.71, p<0.05), 15th (t4=3.45, p<0.05) and final lap (t4=3.30, p<0.05). Conclusion The significant difference in completion time and pacing strategy between the two conditions suggests that accurate, comparative performance feedback is beneficial to performance, especially during the start and end of an exercise bout. The results support the previously unfounded assumption that performance feedback is advantageous during exercise and highlights the importance of an athlete's support team during an event.

Rucci, JA and Tomporowski, PD. Three types of kinematic feedback and the execution of the hang power clean. J Strength Cond Res 24(3)771-778, 2010-The type and quality of feedback provided during instruction influences motor skill learning. The purpose of the study is to gain a better understanding of how altering feedback can impact discrete dynamic movements that are integral to strength training programs. The effects of 3 types of feedback on the execution hang power clean (4 sets of 4 repetitions at 75% of 1 repetition maximum) were evaluated over 6 training sessions. Nine different movement indices of the hang power clean were assessed using Dartfish video analysis software and comparisons among groups were made for each individually. Participantsʼ performance was predicted to benefit more from a combination of visual and verbal feedback cues than from visual feedback alone or verbal feedback alone. Results showed that 5 of the movement indices yielded a statistically significant interaction (p < 0.05). Analyses of movement form indicated that with training participants in both the video + cues group and the verbal-only group improved, whereas individuals in the video-only group did not. These results have implications for instructors seeking efficient methods of improving the way in which to teach female athletes to perform complex, dynamic, and technical movements through altering the type of feedback given.