bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-Paced Team-Sport Match Simulation Results in Reductions in Voluntary Activation and Modifications to Biological, Perceptual, and Performance Measures at Halftime and for up to 96 Hours Postmatch
Authors: Tofari Paul J. , Kemp Justin G. , Cormack Stuart J. 
Published: February 2017

Abstract
Tofari, PJ, Kemp, JG, and Cormack, SJ. Self-paced team-sport match-simulation results in reductions in voluntary activation and modifications to biological, perceptual, and performance measures at halftime and for up to 96 hours postmatch. J Strength Cond Res 32(12): 3561–3572, 2018—Assessing responses to soccer match play is limited by match variability or unrealistic simulations. To address this, the biological, perceptual, and performance responses were assessed using a self-paced, simulated soccer match protocol using a nonmotorized treadmill. Twelve male team-sport athletes performed the 90-minute simulation. Match activity, quadriceps twitch interpolation (voluntary activation [%VA] and potentiated twitch [POT]), biochemical markers, strength and power performance, rating of perceived exertion (RPE), and self-report wellness were collected prematch, halftime, postmatch, and 2, 24, 48, 72, and 96-hour postmatch. Change compared with prematch was calculated using effect size ±90% confidence limit, and relationships were assessed using regression analysis. Subjects covered 12,445.8 ± 768.7 m at 87.1 ± 3.2% maximal heart rate (mean ± SD). Reductions in %VA and POT was present at halftime (−0.38 ± 0.46 and −0.79 ± 0.30, respectively) and persisted postmatch. Squat jump height decreased at halftime (−0.42 ± 0.31) and was decreased until Post96. Perceptual fatigue, soreness (−0.92 ± 0.88 and −1.49 ± 0.76, respectively), and creatine kinase (CK) (1.11 ± 0.43) peaked at Post24. Pretest strength (N·kg−1) correlated with changes in CK (r = −0.58 to −0.81), peak oxygen consumption (

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peak) correlated with reduced perceived wellness at Post24 (r = 0.44–0.58) and RPE post (r = −0.71 ± 0.28). High-speed running correlated with soreness (r
2 = 0.42) and very high-speed running with reduced POT (r
2 = 0.61). Previously, unreported half-time reductions in %VA and POT plateaued by postmatch, suggesting a role in regulating second-half performance. Perceptual and neuromuscular responses seem related to running intensity. Greater lower-body strength and

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peak were associated with less CK (i.e., muscle damage) and perceptual responses postmatch, respectively, suggesting a training focus should be placed on these capacities.
Cycling Power Profile Characteristics of National-Level Junior Triathletes
Authors: Stevens Christopher J. , Bennett Kyle J.M. , Novak Andrew R. , Kittel Aden B. , Dascombe Ben J. 
Published: February 2017

Abstract
Stevens, CJ, Bennett, KJM, Novak, AR, Kittel, AB, and Dascombe, BJ. Cycling power profile characteristics of national-level junior triathletes. J Strength Cond Res 33(1): 197–202, 2019—With the draft-legal rule recently introduced to junior triathlon competition, it has become difficult to assess cycling performance through race results. Therefore, this study assessed the cycling power profile characteristics of national-level junior triathletes to assist with physical assessment and program design. Thirteen male (17.0 ± 1.0 years) and 11 female (17.2 ± 1.3 years) national-level junior triathletes completed a cycling power profile that consisted of maximal intervals that lasted 6, 15, 30, 60, 240, and 600 seconds in duration. Each power profile was completed on a LeMond ergometer using the subject's own bicycle, with power output and cadence recorded for all intervals. Mean power output values for males (783 ± 134, 768 ± 118, 609 ± 101, 470 ± 65, 323 ± 38, and 287 ± 34 W) were significantly (p ≤ 0.05) higher than those for females (554 ± 92, 510 ± 89, 437 ± 75, 349 ± 56, 248 ± 39, and 214 ± 37 W) across all intervals, respectively. Peak power output values for males across the 6- and 15-second intervals (1,011 ± 178 and 962 ± 170 W) were also significantly higher than those for females (674 ± 116 and 624 ± 114 W), respectively (p ≤ 0.05). Developing junior triathletes should aim to increase their capacity across the power profile above the mean values listed. Athletes should further aim to have power outputs equal to that of the best performers and beyond to ensure that they can meet the demands of any competition situation.
Recurring Functional Interactions Predict Network Architecture of Interictal and Ictal States in Neocortical Epilepsy
Authors: Khambhati Ankit N. , Bassett Danielle S. , Oommen Brian S. , Chen Stephanie H. , Lucas Timothy H. , Davis Kathryn A. , Litt Brian 
Published: February 2017

AbstractHuman epilepsy patients suffer from spontaneous seizures, which originate in brain regions that also subserve normal function. Prior studies demonstrate focal, neocortical epilepsy is associated with dysfunction, several hours before seizures. How does the epileptic network perpetuate dysfunction during baseline periods? To address this question, we developed an unsupervised machine learning technique to disentangle patterns of functional interactions between brain regions, or subgraphs, from dynamic functional networks constructed from approximately 100 h of intracranial recordings in each of 22 neocortical epilepsy patients. Using this approach, we found: (1) subgraphs from ictal (seizure) and interictal (baseline) epochs are topologically similar, (2) interictal subgraph topology and dynamics can predict brain regions that generate seizures, and (3) subgraphs undergo slower and more coordinated fluctuations during ictal epochs compared to interictal epochs. Our observations suggest that seizures mark a critical shift away from interictal states that is driven by changes in the dynamical expression of strongly interacting components of the epileptic network.
Single Neurons in the Avian Auditory Cortex Encode Individual Identity and Propagation Distance in Naturally Degraded Communication Calls
Authors: Mouterde Solveig C. , Elie Julie E. , Mathevon Nicolas , Theunissen Frédéric E. 
Published: February 2017

One of the most complex tasks performed by sensory systems is “scene analysis”: the interpretation of complex signals as behaviorally relevant objects. The study of this problem, universal to species and sensory modalities, is particularly challenging in audition, where sounds from various sources and localizations, degraded by propagation through the environment, sum to form a single acoustical signal. Here we investigated in a songbird model, the zebra finch, the neural substrate for ranging and identifying a single source. We relied on ecologically and behaviorally relevant stimuli, contact calls, to investigate the neural discrimination of individual vocal signature as well as sound source distance when calls have been degraded through propagation in a natural environment. Performing electrophysiological recordings in anesthetized birds, we found neurons in the auditory forebrain that discriminate individual vocal signatures despite long-range degradation, as well as neurons discriminating propagation distance, with varying degrees of multiplexing between both information types. Moreover, the neural discrimination performance of individual identity was not affected by propagation-induced degradation beyond what was induced by the decreased intensity. For the first time, neurons with distance-invariant identity discrimination properties as well as distance-discriminant neurons are revealed in the avian auditory cortex. Because these neurons were recorded in animals that had prior experience neither with the vocalizers of the stimuli nor with long-range propagation of calls, we suggest that this neural population is part of a general-purpose system for vocalizer discrimination and ranging.SIGNIFICANCE STATEMENTUnderstanding how the brain makes sense of the multitude of stimuli that it continually receives in natural conditions is a challenge for scientists. Here we provide a new understanding of how the auditory system extracts behaviorally relevant information, the vocalizer identity and its distance to the listener, from acoustic signals that have been degraded by long-range propagation in natural conditions. We show, for the first time, that single neurons, in the auditory cortex of zebra finches, are capable of discriminating the individual identity and sound source distance in conspecific communication calls. The discrimination of identity in propagated calls relies on a neural coding that is robust to intensity changes, signals' quality, and decreases in the signal-to-noise ratio.
Tamoxifen Provides Structural and Functional Rescue in Murine Models of Photoreceptor Degeneration
Authors: Wang Xu , Zhao Lian , Zhang Yikui , Ma Wenxin , Gonzalez Shaimar R. , Fan Jianguo , Kretschmer Friedrich , Badea Tudor C. , Qian Hao-hua , Wong Wai T. 
Published: February 2017

Photoreceptor degeneration is a cause of irreversible vision loss in incurable blinding retinal diseases including retinitis pigmentosa (RP) and atrophic age-related macular degeneration. We found in two separate mouse models of photoreceptor degeneration that tamoxifen, a selective estrogen receptor modulator and a drug previously linked with retinal toxicity, paradoxically provided potent neuroprotective effects. In a light-induced degeneration model, tamoxifen prevented onset of photoreceptor apoptosis and atrophy and maintained near-normal levels of electroretinographic responses. Rescue effects were correlated with decreased microglial activation and inflammatory cytokine production in the retinain vivoand a reduction of microglia-mediated toxicity to photoreceptorsin vitro, indicating a microglia-mediated mechanism of rescue. Tamoxifen also rescued degeneration in a genetic (Pde6brd10) model of RP, significantly improving retinal structure, electrophysiological responses, and visual behavior. These prominent neuroprotective effects warrant the consideration of tamoxifen as a drug suitable for being repurposed to treat photoreceptor degenerative disease.SIGNIFICANCE STATEMENTPhotoreceptor degeneration is a cause of irreversible blindness in a number of retinal diseases such as retinitis pigmentosa (RP) and atrophic age-related macular degeneration. Tamoxifen, a selective estrogen receptor modulator approved for the treatment of breast cancer and previously linked to a low incidence of retinal toxicity, was unexpectedly found to exert marked protective effects against photoreceptor degeneration. Structural and functional protective effects were found for an acute model of light-induced photoreceptor injury and for a genetic model for RP. The mechanism of protection involved the modulation of microglial activation and the production of inflammatory cytokines, highlighting the role of inflammatory mechanisms in photoreceptor degeneration. Tamoxifen may be suitable for clinical study as a potential treatment for diseases involving photoreceptor degeneration.
Pathogenic Huntington Alters BMP Signaling and Synaptic Growth through Local Disruptions of Endosomal Compartments
Authors: Akbergenova Yulia , Littleton J. Troy 
Published: February 2017

Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) stretch within the Huntingtin (Htt) protein. Pathogenic Htt disrupts multiple neuronal processes, including gene expression, axonal trafficking, proteasome and mitochondrial activity, and intracellular vesicle trafficking. However, the primary pathogenic mechanism and subcellular site of action for mutant Htt are still unclear. Using aDrosophilaHD model, we found that pathogenic Htt expression leads to a profound overgrowth of synaptic connections that correlates directly with the levels of Htt at nerve terminals. Branches of the same nerve containing different levels of Htt show distinct phenotypes, indicating that Htt acts locally to disrupt synaptic growth. The effects of pathogenic Htt on synaptic growth arise from defective synaptic endosomal trafficking, leading to expansion of a recycling endosomal signaling compartment containing Sorting Nexin 16 and a reduction in late endosomes containing Rab11. The disruption of endosomal compartments leads to elevated BMP signaling within nerve terminals, driving excessive synaptic growth. Blocking aberrant signaling from endosomes or reducing BMP activity ameliorates the severity of HD pathology and improves viability. Pathogenic Htt is present largely in a nonaggregated form at synapses, indicating that cytosolic forms of the protein are likely to be the toxic species that disrupt endosomal signaling. Our data indicate that pathogenic Htt acts locally at nerve terminals to alter trafficking between endosomal compartments, leading to defects in synaptic structure that correlate with pathogenesis and lethality in theDrosophilaHD model.SIGNIFICANCE STATEMENTHuntington's disease (HD) is the most commonly inherited polyglutamine expansion disorder, but how mutant Huntingtin (Htt) disrupts neuronal function is unclear. In particular, it is unknown within what subcellular compartment pathogenic Htt acts and whether the pathogenesis is associated with aggregated or more soluble forms of the protein. Using aDrosophilaHD model, we find that nonaggregated pathogenic Htt acts locally at synaptic terminals to disrupt endosomal compartments, leading to aberrant wiring defects. Genetic manipulations to increase endosomal trafficking of synaptic growth receptors from signaling endosomes or to reduce BMP signaling reduce pathology in this HD model. These data indicate that pathogenic Htt can act locally within nerve terminals to disrupt synaptic endosomal signaling and induce neuropathology.
Spike and Neuropeptide-Dependent Mechanisms Control GnRH Neuron Nerve Terminal Ca2+over Diverse Time Scales
Authors: Iremonger Karl J. , Porteous Robert , Herbison Allan E. 
Published: February 2017

Fast cell-to-cell communication in the brain is achieved by action potential-dependent synaptic release of neurotransmitters. The fast kinetics of transmitter release are determined by transient Ca2+elevations in presynaptic nerve terminals. Neuromodulators have previously been shown to regulate transmitter release by inhibiting presynaptic Ca2+influx. Few studies to date have demonstrated the opposite, that is, neuromodulators directly driving presynaptic Ca2+rises and increases in nerve terminal excitability. Here we use GCaMP Ca2+imaging in brain slices from mice to address how nerve terminal Ca2+is controlled in gonadotropin-releasing hormone (GnRH) neurons via action potentials and neuromodulators. Single spikes and bursts of action potentials evoked fast, voltage-gated Ca2+channel-dependent Ca2+elevations. In contrast, brief exposure to the neuropeptide kisspeptin-evoked long-lasting Ca2+plateaus that persisted for tens of minutes. Neuropeptide-mediated Ca2+elevations were independent of action potentials, requiring Ca2+entry via voltage-gated Ca2+channels and transient receptor potential channels in addition to release from intracellular store mechanisms. Together, these data reveal that neuromodulators can exert powerful and long-lasting regulation of nerve terminal Ca2+independently from actions at the soma. Thus, GnRH nerve terminal function is controlled over disparate timescales via both classical spike-dependent and nonclassical neuropeptide-dependent mechanisms.SIGNIFICANCE STATEMENTNerve terminals are highly specialized regions of a neuron where neurotransmitters and neurohormones are released. Many neuroendocrine neurons release neurohormones in long-duration bursts of secretion. To understand how this is achieved, we have performed live Ca2+imaging in the nerve terminals of gonadotropin-releasing hormone neurons. We find that bursts of action potentials and local neuropeptide signals are both capable of evoking large increases in nerve terminal Ca2+. Increases in Ca2+driven by spike bursts last seconds; however, the increases in nerve terminal Ca2+driven by neuropeptides can persist for tens of minutes. These findings reveal new mechanisms by which neuroendocrine nerve terminal Ca2+can be controlled in the brain.
Neto2 Assembles with Kainate Receptors in DRG Neurons during Development and Modulates Neurite Outgrowth in Adult Sensory Neurons
Authors: Vernon Claire G. , Swanson Geoffrey T. 
Published: February 2017

Peripheral sensory neurons in the dorsal root ganglia (DRG) are the initial transducers of sensory stimuli, including painful stimuli, from the periphery to central sensory and pain-processing centers. Small- to medium-diameter non-peptidergic neurons in the neonatal DRG express functional kainate receptors (KARs), one of three subfamilies of ionotropic glutamate receptors, as well as the putative KAR auxiliary subunit Neuropilin- and tolloid-like 2 (Neto2). Neto2 alters recombinant KAR function markedly but has yet to be confirmed as an auxiliary subunit that assembles with and alters the function of endogenous KARs. KARs in neonatal DRG require the GluK1 subunit as a necessary constituent, but it is unclear to what extent other KAR subunits contribute to the function and proposed roles of KARs in sensory ganglia, which include promotion of neurite outgrowth and modulation of glutamate release at the DRG–dorsal horn synapse. In addition, KARs containing the GluK1 subunit are implicated in modes of persistent but not acute pain signaling. We show here that the Neto2 protein is highly expressed in neonatal DRG and modifies KAR gating in DRG neurons in a developmentally regulated fashion in mice. Although normally at very low levels in adult DRG neurons, Neto2 protein expression can be upregulated via MEK/ERK signaling and after sciatic nerve crush and Neto2−/−neurons from adult mice have stunted neurite outgrowth. These data confirm that Neto2 is a bona fide KAR auxiliary subunit that is an important constituent of KARs early in sensory neuron development and suggest that Neto2 assembly is critical to KAR modulation of DRG neuron process outgrowth.SIGNIFICANCE STATEMENTPain-transducing peripheral sensory neurons of the dorsal root ganglia (DRG) express kainate receptors (KARs), a subfamily of glutamate receptors that modulate neurite outgrowth and regulate glutamate release at the DRG–dorsal horn synapse. The putative KAR auxiliary subunit Neuropilin- and tolloid-like 2 (Neto2) is also expressed in DRG. We show here that it is a developmentally downregulated but dynamic component of KARs in these neurons, that it contributes to regulated neurite regrowth in adult neurons, and that it is increased in adult mice after nerve injury. Our data confirm Neto2 as a KAR auxiliary subunit and expand our knowledge of the molecular composition of KARs in nociceptive neurons, a key piece in understanding the mechanistic contribution of KAR signaling to pain-processing circuits.
GABAergic Neurons of the Central Amygdala Promote Cataplexy
Authors: Mahoney Carrie E. , Agostinelli Lindsay J. , Brooks Jessica N.K. , Lowell Bradford B. , Scammell Thomas E. 
Published: February 2017

Narcolepsy is characterized by chronic sleepiness and cataplexy—sudden muscle paralysis triggered by strong, positive emotions. This condition is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. Because GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy. We injected adeno-associated viral vectors coding for Cre-dependent DREADDs or a control vector into the CeA of orexin knock-out mice crossed with vGAT-Cre mice, resulting in selective expression of the excitatory hM3 receptor or the inhibitory hM4 receptor in GABAergic neurons of the CeA. We measured sleep/wake behavior and cataplexy after injection of saline or the hM3/hM4 ligand clozapine-N-oxide (CNO) under baseline conditions and under conditions that should elicit positive emotions. In mice expressing hM3, CNO approximately doubled the amount of cataplexy in the first 3 h after dosing under baseline conditions. Rewarding stimuli (chocolate or running wheels) also increased cataplexy, but CNO produced no further increase. In mice expressing hM4, CNO reduced cataplexy in the presence of chocolate or running wheels. These results demonstrate that GABAergic neurons of the CeA are sufficient and necessary for the production of cataplexy in mice, and they likely are a key part of the mechanism through which positive emotions trigger cataplexy.SIGNIFICANCE STATEMENTCataplexy is one of the major symptoms of narcolepsy, but little is known about how strong, positive emotions trigger these episodes of muscle paralysis. Prior research shows that amygdala neurons are active during cataplexy and cataplexy is reduced by lesions of the amygdala. We found that cataplexy is substantially increased by selective activation of GABAergic neurons in the central nucleus of the amygdala (CeA). We also demonstrate that inhibition of these neurons reduces reward-promoted cataplexy. These results build upon prior work to establish the CeA as a crucial element in the neural mechanisms of cataplexy. These results demonstrate the importance of the CeA in regulating responses to rewarding stimuli, shedding light on the broader neurobiology of emotions and motor control.
Genome-Wide Screen Reveals sec21 Mutants of Saccharomyces cerevisiae Are Methotrexate-Resistant
Authors: Wong Lai H , Flibotte Stephane , Sinha Sunita , Chiang Jennifer , Giaever Guri , Nislow Corey 
Published: February 2017

Abstract
Drug resistance is a consequence of how most modern medicines work. Drugs exert pressure on cells that causes death or the evolution of resistance. Indeed, highly specific drugs are rendered ineffective by a single DNA mutation. In this study, we apply the drug methotrexate, which is widely used in cancer and rheumatoid arthritis, and perform evolution experiments on Baker’s yeast to ask the different ways in which cells become drug resistant. Because of the conserved nature of biological pathways between yeast and man, our results can inform how the same mechanism may operate to render human cells resistant to treatment. Exposure of cells to small molecules and drug therapies imposes a strong selective pressure. As a result, cells rapidly acquire mutations in order to survive. These include resistant variants of the drug target as well as those that modulate drug transport and detoxification. To systematically explore how cells acquire drug resistance in an unbiased manner, rapid cost-effective approaches are required. Methotrexate, as one of the first rationally designed anticancer drugs, has served as a prototypic example of such acquired resistance. Known methotrexate resistance mechanisms include mutations that increase expression of the dihydrofolate reductase (DHFR) target as well as those that maintain function yet reduce the drug’s binding affinity. Recent evidence suggests that target-independent, epistatic mutations can also result in resistance to methotrexate. Currently, however, the relative contribution of such unlinked resistance mutations is not well understood. To address this issue, we took advantage of Saccharomyces cerevisiae as a model eukaryotic system that combined with whole-genome sequencing and a rapid screening methodology, allowed the identification of causative mutations that modulate resistance to methotrexate. We found a recurrent missense mutation in SEC21 (orthologous to human COPG1), which we confirmed in 10 de novo methotrexate-resistant strains. This sec21 allele (S96L) behaves as a recessive, gain-of-function allele, conferring methotrexate resistance that is abrogated by the presence of a wild-type copy of SEC21. These observations indicate that the Sec21p/COPI transport complex has previously uncharacterized roles in modulating methotrexate stress.