bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Men's Body Attitudes and Motivation for Gym Attendance
Authors: Caudwell Kim M. , Keatley David A.
Published: January 2016

Caudwell, KM and Keatley, DA. The effect of men's body attitudes and motivation for gym attendance. J Strength Cond Res 30(9): 2550–2556, 2016—The current study integrates men's body attitudes with implicitly and explicitly measured motivation to investigate the role of these factors in predicting gym attendance. Male participants (N = 99) who regularly attended a gym were recruited to participate in an online questionnaire. Participants completed implicit and explicit measures of motivation, explicitly measured men's body attitudes, and reported the average number of gym visits per week. Attitudes related to body fat and explicitly measured autonomous motivation significantly predicted typical gym attendance. Implicitly measured motivation significantly and negatively predicted gym attendance. Results indicate some support for a dual-systems account of gym attendance. Men's body attitudes and autonomous motivation influences gym attendance; however, implicitly measured motivation showed antagonistic effects. Although individuals may explicitly state their autonomous motivation for gym attendance, attendance may also be influenced at the explicit level. Health and fitness professionals may improve gym attendance by focusing on people's reasons for attending a gym, facilitating autonomous motivation in clients, and minimizing the influence of controlled reasons for exercise.
Exercise Type Affects Cardiac Vagal Autonomic Recovery After a Resistance Training Session
Authors: Mayo Xián , Iglesias-Soler Eliseo , Fariñas-Rodríguez Juán , Fernández-del-Olmo Miguel , Kingsley J. Derek
Published: January 2016

Mayo, X, Iglesias-Soler, E, Fariñas-Rodríguez, J, Fernández-del-Olmo, M, and Kingsley, JD. Exercise type affects cardiac vagal autonomic recovery after a resistance training session. J Strength Cond Res 30(9): 2565–2573, 2016—Resistance training sessions involving different exercises and set configurations may affect the acute cardiovascular recovery pattern. We explored the interaction between exercise type and set configuration on the postexercise cardiovagal withdrawal measured by heart rate variability and their hypotensive effect. Thirteen healthy participants (10 repetitions maximum [RM] bench press: 56 ± 10 kg; parallel squat: 91 ± 13 kg) performed 6 sessions corresponding to 2 exercises (Bench press vs. Parallel squat), 2 set configurations (Failure session vs. Interrepetition rest session), and a Control session of each exercise. Load (10RM), volume (5 sets), and rest (720 seconds) were equated between exercises and set configurations. Parallel squat produced higher reductions in cardiovagal recovery vs. Bench press (p = 0.001). These differences were dependent on the set configuration, with lower values in Parallel squat vs. Bench press for Interrepetition rest session (1.816 ± 0.711 vs. 2.399 ± 0.739 Ln HF/IRR2 × 104, p = 0.002), but not for Failure session (1.647 ± 0.904 vs. 1.808 ± 0.703 Ln HF/IRR2 × 104, p > 0.05). Set configuration affected the cardiovagal recovery, with lower values in Failure session in comparison with Interrepetition rest (p = 0.027) and Control session (p = 0.022). Postexercise hypotension was not dependent on the exercise type (p > 0.05) but was dependent on the set configuration, with lower values of systolic (p = 0.004) and diastolic (p = 0.011) blood pressure after the Failure session but not after an Interrepetition rest session in comparison with the Control session (p > 0.05). These results suggest that the exercise type and an Interrepetition rest design could blunt the decrease of cardiac vagal activity after exercise while exercising to muscular failure may contribute to the onset of postexercise hypotension.
Functional Topography of Human Auditory Cortex
Authors: Leaver Amber M. , Rauschecker Josef P.
Published: January 2016

Functional and anatomical studies have clearly demonstrated that auditory cortex is populated by multiple subfields. However, functional characterization of those fields has been largely the domain of animal electrophysiology, limiting the extent to which human and animal research can inform each other. In this study, we used high-resolution functional magnetic resonance imaging to characterize human auditory cortical subfields using a variety of low-level acoustic features in the spectral and temporal domains. Specifically, we show that topographic gradients of frequency preference, or tonotopy, extend along two axes in human auditory cortex, thus reconciling historical accounts of a tonotopic axis oriented medial to lateral along Heschl's gyrus and more recent findings emphasizing tonotopic organization along the anterior–posterior axis. Contradictory findings regarding topographic organization according to temporal modulation rate in acoustic stimuli, or “periodotopy,” are also addressed. Although isolated subregions show a preference for high rates of amplitude-modulated white noise (AMWN) in our data, large-scale “periodotopic” organization was not found. Organization by AM rate was correlated with dominant pitch percepts in AMWN in many regions. In short, our data expose early auditory cortex chiefly as a frequency analyzer, and spectral frequency, as imposed by the sensory receptor surface in the cochlea, seems to be the dominant feature governing large-scale topographic organization across human auditory cortex.

SIGNIFICANCE STATEMENTIn this study, we examine the nature of topographic organization in human auditory cortex with fMRI. Topographic organization by spectral frequency (tonotopy) extended in two directions: medial to lateral, consistent with early neuroimaging studies, and anterior to posterior, consistent with more recent reports. Large-scale organization by rates of temporal modulation (periodotopy) was correlated with confounding spectral content of amplitude-modulated white-noise stimuli. Together, our results suggest that the organization of human auditory cortex is driven primarily by its response to spectral acoustic features, and large-scale periodotopy spanning across multiple regions is not supported. This fundamental information regarding the functional organization of early auditory cortex will inform our growing understanding of speech perception and the processing of other complex sounds.
Pannexin 1 Differentially Affects Neural Precursor Cell Maintenance in the Ventricular Zone and Peri-Infarct Cortex
Authors: Wicki-Stordeur Leigh E. , Sanchez-Arias Juan C. , Dhaliwal Jagroop , Carmona-Wagner Esther O. , Shestopalov Valery I. , Lagace Diane C. , Swayne Leigh Anne
Published: January 2016

We demonstrated previously that Pannexin 1 (Panx1), an ion and metabolite channel, promotes the growth and proliferation of ventricular zone (VZ) neural precursor cells (NPCs)in vitro. To investigate its rolein vivo, we used floxed Panx1 mice in combination with viruses to delete Panx1 in VZ NPCs and to track numbers of Panx1-null and Panx1-expressing VZ NPCs over time. Two days after virus injection, Panx1-null cells were less abundant than Panx1-expressing cells, suggesting that Panx1 is required for the maintenance of VZ NPCs. We also investigated the effect of Panx1 deletion in VZ NPCs after focal cortical stroke via photothrombosis. Panx1 is essential for maintaining elevated VZ NPC numbers after stroke. In contrast, Panx1-null NPCs were more abundant than Panx1-expressing NPCs in the peri-infarct cortex. Together, these findings suggest that Panx1 plays an important role in NPC maintenance in the VZ niche in the naive and stroke brain and could be a key target for improving NPC survival in the peri-infarct cortex.

SIGNIFICANCE STATEMENTHere, we demonstrate that Pannexin 1 (Panx1) maintains a consistent population size of neural precursor cells in the ventricular zone, both in the healthy brain and in the context of stroke. In contrast, Panx1 appears to be detrimental to the survival of neural precursor cells that surround damaged cortical tissue in the stroke brain. This suggests that targeting Panx1 in the peri-infarct cortex, in combination with other therapies, could improve cell survival around the injury site.
Investigating the Stability of Fine-Grain Digit Somatotopy in Individual Human Participants
Authors: Kolasinski James , Makin Tamar R. , Jbabdi Saad , Clare Stuart , Stagg Charlotte J. , Johansen-Berg Heidi
Published: January 2016

Studies of human primary somatosensory cortex (S1) have placed a strong emphasis on the cortical representation of the hand and the propensity for plasticity therein. Despite many reports of group differences and experience-dependent changes in cortical digit somatotopy, relatively little work has considered the variability of these maps across individuals and to what extent this detailed functional architecture is dynamic over time. With the advent of 7 T fMRI, it is increasingly feasible to map such detailed organization noninvasively in individual human participants. Here, we extend the ability of ultra-high-field imaging beyond a technological proof of principle to investigate the intersubject variability of digit somatotopy across participants and the stability of this organization across a range of intervals. Using a well validated phase-encoding paradigm and an active task, we demonstrate the presence of highly reproducible maps of individual digits in S1, sharply contrasted by a striking degree of intersubject variability in the shape, extent, and relative position of individual digit representations. Our results demonstrate the presence of very stable fine-grain somatotopy of the digits in human S1 and raise the issue of population variability in such detailed functional architecture of the human brain. These findings have implications for the study of detailed sensorimotor plasticity in the context of both learning and pathological dysfunction. The simple task and 10 min scan required to derive these maps also raises the potential for this paradigm as a tool in the clinical setting.

SIGNIFICANCE STATEMENTWe applied ultra-high-resolution fMRI at 7 T to map sensory digit representations in the human primary somatosensory cortex (S1) at the level of individual participants across multiple time points. The resulting fine-grain maps of individual digits in S1 reveal the stability in this fine-grain functional organization over time, contrasted with the variability in these maps across individuals.
MEKK4 Signaling Regulates Sensory Cell Development and Function in the Mouse Inner Ear
Authors: Haque Khujista , Pandey Atul K. , Zheng Hong-Wei , Riazuddin Saima , Sha Su-Hua , Puligilla Chandrakala
Published: January 2016

Mechanosensory hair cells (HCs) residing in the inner ear are critical for hearing and balance. Precise coordination of proliferation, sensory specification, and differentiation during development is essential to ensure the correct patterning of HCs in the cochlear and vestibular epithelium. Recent studies have revealed that FGF20 signaling is vital for proper HC differentiation. However, the mechanisms by which FGF20 signaling promotes HC differentiation remain unknown. Here, we show that mitogen-activated protein 3 kinase 4 (MEKK4) expression is highly regulated during inner ear development and is critical to normal cytoarchitecture and function. Mice homozygous for a kinase-inactive MEKK4 mutation exhibit significant hearing loss. Lack of MEKK4 activityin vivoalso leads to a significant reduction in the number of cochlear and vestibular HCs, suggesting that MEKK4 activity is essential for overall development of HCs within the inner ear. Furthermore, we show that loss of FGF20 signalingin vivoinhibits MEKK4 activity, whereas gain of Fgf20 function stimulates MEKK4 expression, suggesting that Fgf20 modulates MEKK4 activity to regulate cellular differentiation. Finally, we demonstrate, for the first time, that MEKK4 acts as a critical node to integrate FGF20-FGFR1 signaling responses to specifically influence HC development and that FGFR1 signaling through activation of MEKK4 is necessary for outer hair cell differentiation. Collectively, this study provides compelling evidence of an essential role for MEKK4 in inner ear morphogenesis and identifies the requirement of MEKK4 expression in regulating the specific response of FGFR1 during HC development and FGF20/FGFR1 signaling activated MEKK4 for normal sensory cell differentiation.

SIGNIFICANCE STATEMENTSensory hair cells (HCs) are the mechanoreceptors within the inner ear responsible for our sense of hearing. HCs are formed before birth, and mammals lack the ability to restore the sensory deficits associated with their loss. In this study, we show, for the first time, that MEKK4 signaling is essential for the development of normal cytoarchitecture and hearing function as MEKK4 signaling-deficient mice exhibit a significant reduction of HCs and a hearing loss. We also identify MEKK4 as a critical hub kinase for FGF20-FGFR1 signaling to induce HC differentiation in the mammalian cochlea. These results reveal a new paradigm in the regulation of HC differentiation and provide significant new insights into the mechanism of Fgf signaling governing HC formation.
Rho Kinase Inhibition as a Therapeutic for Progressive Supranuclear Palsy and Corticobasal Degeneration
Authors: Gentry Erik G. , Henderson Benjamin W. , Arrant Andrew E. , Gearing Marla , Feng Yangbo , Riddle Nicole C. , Herskowitz Jeremy H.
Published: January 2016

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative four-repeat tauopathies with no cure. Mitigating pathogenic tau levels is a rational strategy for tauopathy treatment, but therapeutic targets with clinically available drugs are lacking. Here, we report that protein levels of the Rho-associated protein kinases (ROCK1 and ROCK2), p70 S6 kinase (S6K), and mammalian target of rapamycin (mTOR) were increased in PSP and CBD brains. RNAi depletion of ROCK1 or ROCK2 reduced tau mRNA and protein level in human neuroblastoma cells. However, additional phenotypes were observed under ROCK2 knockdown, including decreased S6K and phosphorylated mTOR levels. Pharmacologic inhibition of Rho kinases in neurons diminished detergent-soluble and -insoluble tau through a combination of autophagy enhancement and tau mRNA reduction. Fasudil, a clinically approved ROCK inhibitor, suppressed rough eye phenotype and mitigated pathogenic tau levels by inducing autophagic pathways in aDrosophilamodel of tauopathy. Collectively, these findings highlight the Rho kinases as rational therapeutic targets to combat tau accumulation in PSP and CBD.

SIGNIFICANCE STATEMENTStudies of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) suggest that mitigating pathogenic tau levels is a rational strategy for tauopathy treatment. In this report, the Rho-associated protein kinases (ROCK1 and ROCK2) are identified as novel drug targets for PSP and CBD. We show that elevated insoluble tau levels are associated with increased ROCK1 and ROCK2 in PSP and CBD brains, whereas experiments in cellular and animal models identify pharmacologic inhibition of ROCKs as a mechanism-based approach to reduce tau levels. Our study correlates bona fide changes in PSP and CBD brains with cellular models, identifies drug targets, and tests the therapeuticin vivo.
Neurodegeneration Triggers Peripheral Immune Cell Recruitment into the Forebrain
Authors: Scheld Miriam , Rüther Bernhard Josef , Große-Veldmann René , Ohl Kim , Tenbrock Klaus , Dreymüller Daniela , Fallier-Becker Petra , Zendedel Adib , Beyer Cordian , Clarner Tim , Kipp Markus
Published: January 2016

Brain-intrinsic degenerative cascades have been proposed to be an initial factor driving lesion formation in multiple sclerosis (MS). Here, we identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the mouse forebrain. Female C57BL/6 mice were fed cuprizone for 3 weeks, followed by a period of 2 weeks on normal chow to induce the formation of lesion foci in the forebrain. Subsequent immunization with myelin oligodendrocyte glycoprotein 35–55 peptide, which induces myelin autoreactive T cells in the periphery, resulted in massive immune cell recruitment into the affected forebrain. Additional adoptive transfer experiments together with flow cytometry analysis underline the importance of brain-derived signals for immune cell recruitment. This study clearly illustrates the significance of brain-intrinsic degenerative cascades for immune cell recruitment and MS lesion formation. Additional studies have to address the signaling cascades and mechanistic processes that form the top-down communication between the affected brain area, neurovascular unit, and peripheral immune cells.

SIGNIFICANCE STATEMENTWe identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the forebrain. Thus, immune cell recruitment might be a second step during the formation of new inflammatory lesions in multiple sclerosis. A better understanding of factors regulating neurodegeneration-induced immune cell recruitment will pave the way for the development of novel therapeutic treatment strategies.
Nucleus Accumbens Core and Shell Differentially Encode Reward-Associated Cues after Reinforcer Devaluation
Authors: West Elizabeth A. , Carelli Regina M.
Published: January 2016

Nucleus accumbens (NAc) neurons encode features of stimulus learning and action selection associated with rewards. The NAc is necessary for using information about expected outcome values to guide behavior after reinforcer devaluation. Evidence suggests that core and shell subregions may play dissociable roles in guiding motivated behavior. Here, we recorded neural activity in the NAc core and shell during training and performance of a reinforcer devaluation task. Long–Evans male rats were trained that presses on a lever under an illuminated cue light delivered a flavored sucrose reward. On subsequent test days, each rat was given free access to one of two distinctly flavored foods to consume to satiation and were then immediately tested on the lever pressing task under extinction conditions. Rats decreased pressing on the test day when the reinforcer earned during training was the sated flavor (devalued) compared with the test day when the reinforcer was not the sated flavor (nondevalued), demonstrating evidence of outcome-selective devaluation. Cue-selective encoding during training by NAc core (but not shell) neurons reliably predicted subsequent behavioral performance; that is, the greater the percentage of neurons that responded to the cue, the better the rats suppressed responding after devaluation. In contrast, NAc shell (but not core) neurons significantly decreased cue-selective encoding in the devalued condition compared with the nondevalued condition. These data reveal that NAc core and shell neurons encode information differentially about outcome-specific cues after reinforcer devaluation that are related to behavioral performance and outcome value, respectively.

SIGNIFICANCE STATEMENTMany neuropsychiatric disorders are marked by impairments in behavioral flexibility. Although the nucleus accumbens (NAc) is required for behavioral flexibility, it is not known how NAc neurons encode this information. Here, we recorded NAc neurons during a training session in which rats learned that a cue predicted a specific reward and during a test session when that reward value was changed. Although encoding in the core during training predicted the ability of rats to change behavior after the reward value was altered, the NAc shell encoded information about the change in reward value during the test session. These findings suggest differential roles of the core and shell in behavioral flexibility.
Modulation of Orthographic Decoding by Frontal Cortex
Authors: Whaley Meagan Lee , Kadipasaoglu Cihan Mehmet , Cox Steven James , Tandon Nitin
Published: January 2016

Opinions are divided on whether word reading processes occur in a hierarchical, feedforward fashion or within an interactive framework. To critically evaluate these competing theories, we recorded electrocorticographic (ECoG) data from 15 human patients with intractable epilepsy during a word completion task and evaluated brain network dynamics across individuals. We used a novel technique of analyzing multihuman ECoG recordings to identify cortical regions most relevant to processing lexical information. The mid fusiform gyrus showed the strongest, earliest response after stimulus onset, whereas activity was maximal in frontal, dorsal lateral prefrontal, and sensorimotor regions toward articulation onset. To evaluate interregional functional connectivity, ECoG data from electrodes situated over specific cortical regions of interest were fit into linear multivariate autoregressive (MVAR) models. Spectral characteristics of the MVAR models were used to precisely reveal the timing and the magnitude of information flow between localized brain regions. This is the first application of MVAR for developing a comprehensive account of interregional interactions from a word reading ECoG dataset. Our comprehensive findings revealed both top-down and bottom-up influences between higher-level language areas and the mid fusiform gyrus. Our findings thus challenge strictly hierarchical, feedforward views of word reading and suggest that orthographic processes are modulated by prefrontal and sensorimotor regions via an interactive framework.

SIGNIFICANCE STATEMENTWord reading is a critical part of everyday life. When the ability to read is disrupted, it can lead to learning disorders, as well as emotional and academic difficulties. The neural mechanisms underlying word reading are not well understood due to limitations in the spatial and temporal specificity of prior word reading studies. Our research analyzed data recorded from sensors implanted directly from surface of human brains while these individuals performed a word reading task. Our research analyzed these recordings to infer how brain regions communicate during word reading. Our original results improve upon current models of word reading and can be used to develop treatment plans for individuals with reading disabilities.
Phase of Spontaneous Slow Oscillations during Sleep Influences Memory-Related Processing of Auditory Cues
Authors: Batterink Laura J. , Creery Jessica D. , Paller Ken A.
Published: January 2016

Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned arbitrary spatial locations for objects that were each paired with a characteristic sound (eg, cat–meow). Then, during SWS periods of an afternoon nap, one-half of the sounds were presented at low intensity. When object location memory was subsequently tested, recall accuracy was significantly better for those objects cued during sleep. We report here for the first time that this memory benefit was predicted by slow-wave phase at the time of stimulation. For cued objects, location memories were categorized according to amount of forgetting from pre- to post-nap. Conditions of high versus low forgetting corresponded to stimulation timing at different slow-oscillation phases, suggesting that learning-related stimuli were more likely to be processed and trigger memory reactivation when they occurred at the optimal phase of a slow oscillation. These findings provide insight into mechanisms of memory reactivation during sleep, supporting the idea that reactivation is most likely during cortical upstates.

SIGNIFICANCE STATEMENTSlow-wave sleep (SWS) is characterized by synchronized neural activity alternating between active upstates and quiet downstates. The slow-oscillation upstates are thought to provide a window of opportunity for memory consolidation, particularly conducive to cortical plasticity. Recent evidence shows that sensory cues associated with previous learning can be delivered subtly during SWS to selectively enhance memory consolidation. Our results demonstrate that this behavioral benefit is predicted by slow-oscillation phase at stimulus presentation time. Cues associated with high versus low forgetting based on analysis of subsequent recall performance were delivered at opposite slow-oscillation phases. These results provide evidence of an optimal slow-oscillation phase for memory consolidation during sleep, supporting the idea that memory processing occurs preferentially during cortical upstates.
Dynamics of Phosphoinositide-Dependent Signaling in Sympathetic Neurons
Authors: Kruse Martin , Vivas Oscar , Traynor-Kaplan Alexis , Hille Bertil
Published: January 2016

In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] leads to a decrease in exocytosis and changes in electrical excitability. Restoration of PI(4,5)P2levels after phospholipase C activation is therefore essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We measured dynamic changes of PI(4,5)P2, phosphatidylinositol 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, and Ca2+upon muscarinic stimulation in sympathetic neurons from adult male Sprague-Dawley rats with electrophysiological and optical approaches. We used this kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show and explain faster synthesis of PI(4,5)P2in sympathetic neurons than in electrically nonexcitable tsA201 cells. They can be used to understand dynamic effects of receptor-mediated phospholipase C activation on excitability and other PI(4,5)P2-dependent processes in neurons.

SIGNIFICANCE STATEMENTPhosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2is essential for a return to basal neuronal activity. However, the dynamics of phosphoinositide metabolism have not been analyzed in neurons. We studied the dynamics of phosphoinositide metabolism in sympathetic neurons upon muscarinic stimulation and used the kinetic information to develop a quantitative description of neuronal phosphoinositide metabolism. The measurements and analysis show a several-fold faster synthesis of PI(4,5)P2in sympathetic neurons than in an electrically nonexcitable cell line, and provide a framework for future studies of PI(4,5)P2-dependent processes in neurons.
Genetic Demonstration of a Role for Stathmin in Adult Hippocampal Neurogenesis, Spinogenesis, and NMDA Receptor-Dependent Memory
Authors: Martel Guillaume , Uchida Shusaku , Hevi Charles , Chévere-Torres Itzamarie , Fuentes Ileana , Park Young Jin , Hafeez Hannah , Yamagata Hirotaka , Watanabe Yoshifumi , Shumyatsky Gleb P.
Published: January 2016

Neurogenesis and memory formation are essential features of the dentate gyrus (DG) area of the hippocampus, but to what extent the mechanisms responsible for both processes overlap remains poorly understood. Stathmin protein, whose tubulin-binding and microtubule-destabilizing activity is negatively regulated by its phosphorylation, is prominently expressed in the DG. We show here that stathmin is involved in neurogenesis, spinogenesis, and memory formation in the DG.tTA/tetO-regulated bitransgenic mice, expressing the unphosphorylatable constitutively activeStathmin4Amutant (Stat4A), exhibit impaired adult hippocampal neurogenesis and reduced spine density in the DG granule neurons. AlthoughStat4Amice display deficient NMDA receptor-dependent memory in contextual discrimination learning, which is dependent on hippocampal neurogenesis, their NMDA receptor-independent memory is normal. Confirming NMDA receptor involvement in the memory deficits,Stat4Amutant mice have a decrease in the level of synaptic NMDA receptors and a reduction in learning-dependent CREB-mediated gene transcription. The deficits in neurogenesis, spinogenesis, and memory inStat4Amice are not present in mice in whichtTA/tetO-dependent transgene transcription is blocked by doxycycline through their life. The memory deficits are also rescued within 3 d by intrahippocampal infusion of doxycycline, further indicating a role for stathmin expressed in the DG in contextual memory. Our findings therefore point to stathmin and microtubules as a mechanistic link between neurogenesis, spinogenesis, and NMDA receptor-dependent memory formation in the DG.

SIGNIFICANCE STATEMENTIn the present study, we aimed to clarify the role of stathmin in neuronal and behavioral functions. We characterized the neurogenic, behavioral, and molecular consequences of the gain-of-function stathmin mutation using a bitransgenic mouse expressing a constitutively active form of stathmin. We found that stathmin plays an important role in adult hippocampal neurogenesis and spinogenesis. In addition, stathmin mutation led to impaired NMDA receptor-dependent and neurogenesis-associated memory and did not affect NMDA receptor-independent memory. Moreover, biochemical analysis suggested that stathmin regulates the synaptic transport of NMDA receptors, which in turn influence CREB-mediated gene transcription machinery. Overall, these data suggest that stathmin is an important molecule for neurogenesis, spinogenesis, and NMDA receptor-dependent learning and memory.
Conformational Changes in Transmembrane Domain 4 of Presenilin 1 Are Associated with Altered Amyloid-β 42 Production
Authors: Tominaga Aya , Cai Tetsuo , Takagi-Niidome Shizuka , Iwatsubo Takeshi , Tomita Taisuke
Published: January 2016

γ-Secretase is an intramembrane-cleaving protease that produces amyloid-β peptide 42 (Aβ42), which is the toxic and aggregation-prone species of Aβ that causes Alzheimer's disease. Here, we used the substituted cysteine accessibility method to analyze the structure of transmembrane domains (TMDs) 4 and 5 of human presenilin 1 (PS1), a catalytic subunit of γ-secretase. We revealed that TMD4 and TMD5 face the intramembranous hydrophilic milieu together with TMD1, TMD6, TMD7, and TMD9 of PS1 to form the catalytic pore structure. Notably, we found a correlation in the distance between the cytosolic sides of TMD4/TMD7 and Aβ42production levels, suggesting that allosteric conformational changes of the cytosolic side of TMD4 affect Aβ42-generating γ-secretase activity. Our results provide new insights into the relationship between the structure and activity of human PS1.

SIGNIFICANCE STATEMENTModulation of γ-secretase activity to reduce toxic amyloid-β peptide species is one plausible therapeutic approaches for Alzheimer's disease. However, precise mechanistic information of γ-secretase still remains unclear. Here we identified the conformational changes in transmembrane domains of presenilin 1 that affect the proteolytic activity of the γ-secretase. Our results highlight the importance of understanding the structural dynamics of presenilin 1 in drug development against Alzheimer's disease.
TFEB and TFE3 are novel components of the integrated stress response
Authors: Martina José A , Diab Heba I , Brady Owen A , Puertollano Rosa
Published: January 2016

To reestablish homeostasis and mitigate stress, cells must activate a series of adaptive intracellular signaling pathways. The participation of the transcription factors TFEB and TFE3 in cellular adaptation to starvation is well established. Here, we show that TFEB and TFE3 also play an important role in the cellular response to ER stress. Treatment with ER stressors causes translocation of TFEB and TFE3 to the nucleus in a process that is dependent on PERK and calcineurin but not on mTORC1. Activated TFEB and TFE3 enhance cellular response to stress by inducing direct transcriptional upregulation of ATF4 and other UPR genes. Under conditions of prolonged ER stress, TFEB and TFE3 contribute to cell death, thus revealing an unexpected role for these proteins in controlling cell fate. This work evidences a broader role of TFEB and TFE3 in the cellular response to stress than previously anticipated and reveals an integrated cooperation between different cellular stress pathways.
On Trade and Assimilation in European Agricultural Origins
Authors: Tangri Daniel
Published: January 2016

The article by Runnels and van Andel on 'Trade and the Origins of Agriculture' JMA 1.1 is significant because it represents the latest of many 'explanations' for the origins of agriculture. The authors follow those who have proposed that agriculture rose from the intensification of trade networks and of the social relations of production (e.g. Ames 1985; Bender 1978, 1981; Davidson 1986; Ingold 1980; Price and Brown 1985 - though the authors mistakenly argue that Bender assigns a 'causal role in the emergence of agricultural societies to demographic factors' - 1988;85). The aim of this comment is to examine the authors' hypothesis and their potential applicability to explanations of the emergence of agriculture in Europe.
Delay and queue lengths at stop/go control during half-width construction
Authors: Venter L , Bester C
Published: January 2016

It is common practice in South Africa that road reseal projects, road reconstruction projects or road upgrade projects on two-lane, two-way roads are constructed in half-widths, resulting in a situation where traffic on the remaining roadway is reduced to one-way operation. There is currently no method for determining a suitable length of work zone for half-width construction based on traffic volumes, and also no method for determining waiting time for the vehicle in the front of the stationary queue at the STOP/GO control, and of the back-of-queue position at such a work zone. An Excel-based calculation sheet for determining the back-of-queue position and the maximum waiting time, was developed. This was used to develop design tables, graphs and equations that can be used by designers and contractors to estimate the back-of-queue position and maximum waiting time. Based on the conclusions of this paper and the fact that this project was largely based on literature studies of traffic conditions not related to work zones for half-width construction, the main recommendation of the study is that all the input parameters which were investigated need to be verified and calibrated specifically for work zones for half-width construction.
Design aspects of concrete towers for wind turbines
Authors: von der Haar C , Marx S
Published: January 2016

All over the world an increase in the use of renewable energy sources is being sought, and here the utilisation of wind energy plays an important role. Germany currently represents one of the world's largest markets for wind energy. At the end of 2013, nearly 24 000 onshore wind turbines with a total output of approximately 34 000 MW had been installed in Germany. Hub heights of up to 140 m and outputs of 3 to 4 MW are now no longer unusual features of new onshore wind turbines. The focus of this paper is on concrete support structures for wind turbines. Different concrete tower concepts are presented, and the influence of the construction method on the design and verification processes is described. In particular, the text deals with the eigenfrequency analysis, as well as the bearing, shear and torsional resistances of concrete towers. The differences between cast-in-place and precast towers are listed.
Dynamic behaviour of normally reinforced concrete wind turbine support structures
Authors: van Zyl W , van Zijl G
Published: January 2016

Transportation logistics of large steel towers have led to concrete towers becoming a viable option. There are currently no design codes dealing exclusively with the design of concrete wind turbine towers. Wind turbine towers have strict constraints on the fundamental frequency of the tower to avoid resonance. This paper investigates the dynamic behaviour of wind turbine towers using nonlinear finite element modelling. Focus is placed on the effect of crack formation and soil stiffness on the fundamental frequency of the tower. An analytical model is then proposed that can be used in the primary design stage to determine the geometry of the tower that satisfies the fundamental frequency requirements.
Chloride conductivity testing of concrete - past and recent developments
Authors: Otieno M , Alexander M
Published: January 2016

The chloride conductivity index (CCI) is a quality control parameter used to assess the resistanc of concrete to chloride ingress. It is determined from the chloride conductivity (CC) test which has been in use in South Africa for close to two decades. During this time, it has undergone a number of changes to improve on its robustness, reproducibility, and repeatability. Plans are now under way to incorporate the test and other durability index tests (oxygen permeability and water sorptivity) into the SANS standards, and it is important that the end user is aware of the changes and why they were made. Specifically, aspects concerning a new design of the CC testing rig which is already in use, and a modified old design which is still being used in some laboratories, are highlighted, such as the significant but variable differences in CCI results that could occur between the old and new CC test rigs. Experimental investigations were carried out to establish the cause of these differences, which was identified as largely due to possible incomplete filling of the original device. Modifications were therefore made to the old CC test rig to ensure that both the new and the modified CC test rigs give similar results.
Parenting a child with haemophilia while living in a non-metropolitan area
Authors: Little Trudi , Strodl Esben , Brown Simon , Mooney Tara
Published: January 2016

The experience of living in a non-metropolitan area and parenting a child with haemophilia is relatively unknown. Using Interpretive Phenomenological Analysis (IPA), the following study explored the experiences of seven parents, from which four themes emerged: ‘bearing the brunt of diagnosis’ captures the impact of the diagnosis; ‘if you can’t help me, who can?’ reveals experiences with the health system; ‘tackling the challenge of treatment’ encompasses difficulties in adhering to the treatment regime; ‘I need you to understand’ reflects desires for others support and understanding. These themes should be considered when developing support systems and interventions for parents living in non-metropolitan areas.
How the classification of von Willebrand Disease can guide therapy
Authors: Laffan Michael A
Published: January 2016

In a recent editorial published in Haemophilia, Millar asks ‘Why and how do we classify von Willebrand disease?’ [1]. This may seem like a philosophical question, but two case reports in this edition of The Journal of Haemophilia Practice illustrate good practical answers to both parts of the question.
As línguas românicas do/no Magrebe: percurso histórico e presença contemporânea
Authors: Olmo Francisco Javier Calvo del
Published: January 2016

Este artigo propõe-se reunir e examinar elementos que permitam traçar o percurso histórico das línguas românicas no Magrebe. Desde uma abordagem interdisciplinar, apresentam-se as comunidades latinizadas durante a dominação romana, os contatos linguísticos que produziram a Língua Franca mediterrânea no período medieval, as minorias de mouriscos e sefardim procedentes da Península Ibérica estabelecidas no norte da África nos séculos XIV e XV, o processo da colonização francesa nos séc. XIX e XX e o mosaico linguístico das últimas décadas, após a independência. Dessa forma, identificam-se os componentes linguísticos latinos e românicos, cindidos e descontínuos, constitutivos do Magrebe enquanto espaço geográfico, cultural e humano.   This paper aims to gather and examine some elements to draw the historical course of the Romance languages in the Maghreb. It employs an interdisciplinary approach to present the Latinized communities during Roman domination, language contacts that produced the Mediterranean Lingua Franca during Middle Age, Moorish and Sephardic minorities settled in fifteenth and sixteenth centuries, the process of French colonization in nineteenth and twentieth centuries and the linguistic mosaic of last decades, after national independences. This itinerary permits to pinpoint a linguistic Latin-Romance component, fragmented and discontinuous, constitutive of the Maghreb as a geographic, cultural and human space.
Uma análise de relativas livres em posição de sujeito e efeitos de compatibilidade no português brasileiro
Authors: Medeiros Júnior Paulo
Published: January 2016

Entende-se que relativas livres sejam sujeitas ao que se chama efeito de compatibilidade, que prevê que a categoria/Caso do sintagma-wh integrando essa sentença precisa ser compatível com os requerimentos do predicador da matriz. Alguns estudos como os de Suñer (1983, 1984) e Harbert (1983) propõem que relativas livres em posição de sujeito estão livres dos efeitos de compatibilidade em línguas pro-Drop. Os dados do PB parecem contradizer essa ideia; mesmo em posição de sujeito, relativas livres precisam “combinar”. Os dados avaliados neste paper, por seu comportamento sintático e semântico, são interpretados não como relativas livres em posição de sujeito, e sim como perguntas indiretas em posição de tópico. A proposta final é a de que o PB é uma língua de 100% de matching.   Free relatives are supposed to be affected by the so-called matching effects, according to which the category/Case of the Wh-element integrating this sentence must match the requirements of the matrix predicate. Some works, as the ones by Suñer (1983, 1984) and Harbert (1983), have proposed that subject free relatives are free from matching effects in pro-Drop languages. Brazilian Portuguese data seem though to contradict this idea; even in subject position, free relatives must match. Focused data are interpreted in this paper (considering their syntactic and semantic behavior) not as subject free relatives, but as topicalized indirect questions. The conclusion is: Brazilian Portuguese is a 100% matching language.
As construções resultativas nas línguas românicas: um estudo com base na Gramática Cognitiva das Construções
Authors: Ribeiro Roza Maria Palomanes
Published: January 2016

Com base na Gramática Cognitiva das Construções, tal como vem sendo desenvolvida por Adele Goldberg (1995, 2006), esta pesquisa objetiva descrever construções que sinalizam resultatividade do português, uma vez que, através de estudos translinguísticos, tem-se defendido que as línguas românicas não apresentam tal construção, não havendo estudo significativo em língua portuguesa, por conseguinte. Para tanto, utilizaram-se as entrevistas do corpus Discurso & Gramática (1995) para seleção de dados com o padrão construcional SN ficar SADJ. Promoveu-se uma extensa revisão bibliográfica de autores que estudaram, ainda que seguindo outras linhas de análise, o fenômeno das construções resultativas. Após seleção e análise dos dados, constatou-se que, corroborando a hipótese inicial, o português criou mecanismos para expressar a resultatividade – não pode haver construção causativa, sem que haja uma resultativa que expresse o evento final – e que este mecanismo utiliza, preferencialmente, a forma sintática intransitiva [SN ficar SR], cuja semântica é [X torna-se Y].Based on Cognitive Construction Grammar, such as it has been developed by Adele Goldberg (1995, 2006), this research aims to describe portuguese constructions that express resultativity, since throughout crosslinguistics studies, it has been defended that it is an impossible phenomenon in romance languages and there is not a significative study in Portuguese, thus. Therefore, we used interviews from Discurso & Gramática corpus (1995) for selecting data with the constructional pattern NP ficar AP. It was made an extensive bibliographic revision of authors who study the resultative constructions phenomenon, even following other analytical lines. After data selection and analysis, it was noticed that Portuguese has created mechanisms to express resultativity – It cannot have a causative construction without a resultative to express the final event – and that this mechanism preferably uses the intransitive syntactic form [SN ficar SR], which semantics is [X torna-se Y].
Tribunais de contas e accountability por resultados: um estudo de caso das auditorias operacionais realizadas pelo Tribunal de Contas do Estado de Minas Gerais
Authors: Uchôa Daniel
Published: January 2016

A competência para realização de auditorias operacionais (AOPs), importante instrumento de fiscalização do desempenho de órgãos e entidades governamentais e de políticas e programas públicos, fortaleceu o papel dos tribunais de contas (TCs) para a accountability, notadamente para a accountability por resultados. Porém, a realização de AOPs impõe desafios aos TCs, uma vez que, historicamente, exerciam prioritariamente a accountability de regularidade, ou seja, no exame do cumprimento de normas e de procedimentos, com a eventual responsabilização dos gestores em caso de irregularidade, em detrimento das AOPs, muito mais eficazes para a responsabilização no caso de irregularidades. A partir do estudo de caso de AOPs no âmbito do Tribunal de Contas do Estado de Minas Gerais (TCEMG), este artigo busca examinar as dificuldades para o desempenho de tais auditorias bem como os benefícios advindos de sua realização, de acordo com a percepção de atores do TCEMG e de representantes de órgãos ou entidades governamentais. Foram oito as auditorias selecionadas, do período de 2007 a 2012, abrangendo o exame do desempenho de determinada Secretaria de Estado quanto aos procedimentos de celebração de convênios com municípios mineiros; ao exame dos resultados de um programa de assistência jurídica da Defensoria Pública do Estado de Minas Gerais e aos programas relacionados a distintas áreas de atuação do governo estadual. O estudo coletou dados mediante aplicação de questionários, no período de outubro de 2013 a janeiro de 2014 — no âmbito interno do TCEMG — aos conselheiros, aos conselheiros substitutos e aos analistas da Coordenadoria de Auditoria Operacional, atores considerados estratégicos para a adoção e o aprimoramento das AOPs. E, no âmbito externo, a interlocutores dos órgãos ou entidades envolvidos nos programas auditados. Os resultados revelaram a necessidade de investimentos e de aprimoramentos para a execução das AOPs, tanto no que se refere aos auditores do TCEMG quanto aos órgãos e entidades submetidas a tais auditorias. Quanto aos auditados, o grande desafio, na realização das AOPs, é vencer a resistência e o receio quanto à possível repercussão política negativa das constatações das referidas auditorias. O desafio, em suma, consiste em considerar as AOPs ferramenta imprescindível de contribuição para a melhoria dos programas públicos e para a efetivação da accountability, tendo em vista a maior transparência da gestão pública e o fomento do controle social.