bluuebunny/crossref_metadata_2025 huggingface dataset:
Lead exposure from battery recycling in Indonesia
Authors: Haryanto Budi
Published: January 2016

In Indonesia, more than 200 illegal used lead acid battery (ULAB) smelters are currently operating. Only a few health studies support the finding of lead-related symptoms and diseases among populations living near the smelters. To assess the blood lead levels (BLLs) and potential health impacts among the population surrounding ULAB recycling smelters, we evaluated health effects reported from 2003 to 2013, conducted focus group discussions with lead smelter owner/workers and a group of 35 female partners of smelter owners or workers not actively engaged in smelter work, and retook and measured BLLs. It was found that many children in the areas were having difficulty achieving high grades at school and having stunting or other problems with physical development. The average mean of BLLs increased by almost double in 2015, compared with in 2011. The risk of having hypertension, interference in the ability to make red blood cells in females occurred among 24% of respondents; Elevated blood pressure, hearing loss, and interference in the ability to make red bloods cell occurred in 20% of males; Kidney damage, infertility in male, nerve problems, including decreased sensation and decreased ability to move quickly occurred in 13%; Decreased ability to make red blood cells (20%), and; Frank anemia, decreased life-span, coma/seizures were experienced by 22%. The populations living in areas surrounding ULAB smelters are experiencing severe chronic health problems. It is recommended that the smelters must be moved and placed far away from the municipality.
Health co-benefits in mortality avoidance from implementation of the mass rapid transit (MRT) system in Kuala Lumpur, Malaysia
Authors: Kwan Soo Chen , Tainio Marko , Woodcock James , Hashim Jamal Hisham
Published: January 2016

Introduction: The mass rapid transit (MRT) is the largest transport infrastructure project under the national key economic area (NKEA) in Malaysia. As urban rail is anticipated to be the future spine of public transport network in the Greater Kuala Lumpur city, it is important to mainstream climate change mitigation and public health benefits in the local transport development. This study quantifies the health co-benefits in terms of mortality among the urbanites when the first line of the 150 km MRT system in Kuala Lumpur commences by 2017.

Method: Using comparative health risk assessment, we estimated the potential health co-benefits from the establishment of the MRT system. We estimated the reduced CO2 emissions and air pollution (PM2.5) exposure reduction among the general population from the reduced use of motorized vehicles. Mortality avoided from traffic incidents involving motorcycles and passenger cars, and from increased physical activity from walking while using the MRT system was also estimated.

Results: A total of 363,130 tonnes of CO2 emissions could be reduced annually from the modal shift from cars and motorcycles to the MRT system. Atmospheric PM2.5 concentration could be reduced 0.61 μg/m3 annually (2%). This could avoid a total of 12 deaths, mostly from cardio-respiratory diseases among the city residents. For traffic injuries, 37 deaths could be avoided annually from motorcycle and passenger cars accidents especially among the younger age categories (aged 15–30). One additional death was attributed to pedestrian walking. The additional daily physical activity to access the MRT system could avoid 21 deaths among its riders. Most of the mortality avoided comes from cardiovascular diseases. Overall, a total of 70 deaths could be avoided annually among both the general population and the MRT users in the city.

Conclusion: The implementation of the MRT system in Greater Kuala Lumpur could bring substantial health co-benefits to both the general population and the MRT users mainly from the avoidance of mortality from traffic injuries.
Mercury exposure in the work place and human health: dental amalgam use in dentistry at dental teaching institutions and private dental clinics in selected cities of Pakistan
Authors: Khwaja Mahmood A. , Nawaz Sadaf , Ali Saeed Waqar
Published: January 2016

During the past two decades, mercury has come under increasing scrutiny with regard to its safety both in the general population and in occupationally exposed groups. It’s a growing issue of global concern because of its adverse environmental and health impacts. Very few investigations on mercury amalgam use in the dentistry sector have been carried out in South Asia and there is little data reported on mercury contamination of indoor/outdoor air at dental sites. According to an earlier SDPI study, reported in 2013, alarmingly high mercury levels were observed in air (indoor as well as outdoor) at 11 of the 34 visited dental sites (17 dental teaching institutions, 7 general hospitals & 10 dental clinics) in five main cities of Pakistan. 88% of the sites indicated indoor mercury levels in air above the USA EPA reference level of 300 ng/m3. According to our study, carried out at 38 dental teaching institutions in 12 main cities (in Khyber Pakhtunkhwa, Punjab and Sindh provinces) of Pakistan, respondents were of the opinion that the currently offered BDS curriculum does not effectively guide outgoing dental professionals and does not provide them adequate knowledge and training about mercury/mercury amalgam and other mercury related human health and mercury waste issues. 90% of respondents supported the review and revision of the present dental curriculum offered at dental teaching institutions in the country, at the earliest. A study has also been conducted to assess the status of mercury amalgam use in private dental clinics in Gilgit, Hunza, Peshawar, Rawalpindi and Islamabad. More than 90 private dental clinics were visited and dental professionals/private clinics in-charge were interviewed during June–July, 2015. The focus areas of the study were Hg amalgam toxicity, its waste management practices and safety measures practiced among the dental practitioners. In the light of the findings described and discussed in this brief report, to safeguard public health and for the protection of environment, it is strongly recommended that since mercury amalgam use cannot be banned immediately in the country, its use may be regularized and allowed subject to use of “Amalgam Separators,” “Capsulated Mercury” and “Mechanized Mixing,” use of mercury amalgam be banned for children (below 12 years age) and pregnant women. The curriculum currently being taught at medical and dental colleges in the country be reviewed and revised, to ensure adequate training towards minimizing mercury exposure.
Investigation Of Spontaneous Combustion Tendency Of Vegetable Oils By The Means Of Differential Thermal Analysis
Authors: Hrušovský Ivan , Martinka Jozef , Rantuch Peter , Balog Karol
Published: January 2016

The potential of vegetable oils to undergo violent thermal oxidation is long-known problem. The process of this oxidation is investigated by the means of differential thermal analysis. Polyurethane foam was saturated with Tung oil rich in unsaturated fatty acids at three different mass rations, and airflow at three different rates is introduces to the sample to ensure sufficient volume of air for oxidation. The samples were thermally stressed both dynamically and isothermally. The results were compared to results of standard differential Mackey test.
Analysis Of The Normative Requirements For Ensuring The Safety Of Powder Coating Booths In Terms Of The Risk Of Explosion
Authors: Veličková Eva , Štroch Petr , Velička Richard
Published: January 2016

During the process of electrostatic powder coating in coating booths, there is a probability of the risk of explosion. Compliance with the normative requirements referred to in the legislation in force minimize the hazards associated with the risk of explosion. This article focuses on the analysis of the current security level of coating booths in terms of the risk of explosion in relation to the lower explosive limit of the selected powder paints.
The Need Of Special Technique In Crisis Management
Authors: Lipták Peter , Kopecký Ivan , Štrba Ján , Dlugoš Ivan
Published: January 2016

Operation of special equipment is possible in crisis situations. It is because special equipment is designed for operation in non-standard often extreme conditions and situation, it is available, it has a high degree of crossing capability and it is able to provide basic living conditions even in field, e.g. provision of power for hospital, transportation of wounded and injured persons, supplies, medical care in field conditions, delivery of potable and utility water etc. The authors in the paper deal with a possibility to provide electric energy through advanced renewable sources, especially in meeting tasks in areas with no public mains, possible supplies of potable and non-potable water, embedding such assets into mobile systems. The authors in publication summarize results of research within the „Use of renewable sources of energy in practice project“. System of modeling and computer-aided simulation of renewable sources of energy has been proposed within this project. Application of a system for designing of power systems in logistic containers is expected. The knowledge on power balance of logistic containers operated by the SR Armed Forces in missions abroad is summarized in the last chapter of the paper. Experiences with operating the equipment in crisis and extreme conditions have proved a possibility to export and deploy machines and weaponry equipment of the SR Armed Forces into extreme climatic conditions, e.g. out of European conditions etc.
A tetranuclear ruthenium complex with bridging pyridine-2,4-dicarboxylato ligands forming a square metallamacrocycle
Authors: Xie Yu-Feng , Jia Ai-Quan , Zhu Hang , Shi Hua-Tian , Zhang Qian-Feng
Published: January 2016

Treatment of [RuCl2(PPh3)3] with equimolar amounts of 2,4-pyridinedicarboxylic acid (2,4-dipicH2) in the presence of Et3N afforded a tetranuclear complex [Ru(μ-2,4-dipic)(PPh3)2]4 (1) as red crystals. The crystal and molecular structure of [Ru(μ-2,4-dipic)(PPh3)2]4·CHCl3·8H2O (1·CHCl3·8H2O) was determined by single-crystal X-ray diffraction. Each ruthenium center in 1 is six-coordinated with two phosphorus atoms from triphenylphosphine ligands, one nitrogen atom from a pyridyl moiety and three oxygen atoms from two 2,4-dipic2– ligands. 2,4-Pyridinedicarboxylate dianions (2,4-dipic2–) act as bridging ligands to form the stable tetranuclear metallamacrocyclic compound. The electrochemical properties of 1 were also investigated.
Unguisin F, a new cyclic peptide from the endophytic fungus Mucor irregularis
Authors: Akone Sergi H. , Daletos Georgios , Lin Wenhan , Proksch Peter
Published: January 2016

The new cyclic heptapeptide unguisin F (1) and the known congener unguisin E (2), were obtained from the endophytic fungus Mucor irregularis, isolated from the medicinal plant Moringa stenopetala, collected in Cameroon. The structure of the new compound was unambiguously determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configuration of the amino acid residues of 1 and 2 was determined using Marfey’s analysis. Compounds 1 and 2 were evaluated for their antibacterial and antifungal potential, but failed to display significant activities.
IL-10 Controls Early Microglial Phenotypes and Disease Onset in ALS Caused by Misfolded Superoxide Dismutase 1
Authors: Gravel Mathieu , Béland Louis-Charles , Soucy Geneviève , Abdelhamid Essam , Rahimian Reza , Gravel Claude , Kriz Jasna
Published: January 2016

While reactive microgliosis is a hallmark of advanced stages of amyotrophic lateral sclerosis (ALS), the role of microglial cells in events initiating and/or precipitating disease onset is largely unknown. Here we provide novelin vivoevidence of a distinct adaptive shift in functional microglial phenotypes in preclinical stages of superoxide dismutase 1 (SOD1)-mutant-mediated disease. Using a mouse model for live imaging of microglial activation crossed withSOD1G93AandSOD1G37Rmouse models, we discovered that the preonset phase of SOD1-mediated disease is characterized by development of distinct anti-inflammatory profile and attenuated innate immune/TLR2 responses to lipopolysaccharide (LPS) challenge. This microglial phenotype was associated with a 16-fold overexpression of anti-inflammatory cytokine IL-10 in baseline conditions followed by a 4.5-fold increase following LPS challenge. While infusion of IL-10R blocking antibody, initiated at day 60, caused a significant increase in markers of microglial activation and precipitated clinical onset of disease, a targeted overexpression of IL-10 in microglial cells, delivered via viral vectors expressed under CD11b promoter, significantly delayed disease onset and increased survival ofSOD1G93Amice. We propose that the high IL-10 levels in resident microglia in early ALS represent a homeostatic and compensatory “adaptive immune escape” mechanism acting as a nonneuronal determinant of clinical onset of disease.

SIGNIFICANCE STATEMENTWe report here for the first time that changing the immune profile of brain microglia may significantly affect clinical onset and duration of disease in ALS models. We discovered that in presymptomatic disease microglial cells overexpress anti-inflammatory cytokine IL-10. Given that IL-10 is major homeostatic cytokine and its production becomes deregulated with aging, this may suggest that the capacity of microglia to adequately produce IL-10 may be compromised in ALS. We show that blocking IL-10 increased inflammation and precipitated clinical disease onset, whereas overexpression of IL-10 in microglia using a gene therapy approach significantly delayed disease onset and increased survival of ALS mice. Based on our results, we propose that targeted overexpression of IL-10 in microglia may have therapeutic potential in ALS.
Rapid Mechanically Controlled Rewiring of Neuronal Circuits
Authors: Magdesian Margaret H. , Lopez-Ayon G. Monserratt , Mori Megumi , Boudreau Dominic , Goulet-Hanssens Alexis , Sanz Ricardo , Miyahara Yoichi , Barrett Christopher J. , Fournier Alyson E. , De Koninck Yves , Grütter Peter
Published: January 2016

CNS injury may lead to permanent functional deficits because it is still not possible to regenerate axons over long distances and accurately reconnect them with an appropriate target. Using rat neurons, microtools, and nanotools, we show that new, functional neurites can be created and precisely positioned to directly (re)wire neuronal networks. We show that an adhesive contact made onto an axon or dendrite can be pulled to initiate a new neurite that can be mechanically guided to form new synapses at up to 0.8 mm distance in <1 h. Our findings challenge current understanding of the limits of neuronal growth and have direct implications for the development of new therapies and surgical techniques to achieve functional regeneration.

SIGNIFICANCE STATEMENTBrain and spinal cord injury may lead to permanent disability and death because it is still not possible to regenerate neurons over long distances and accurately reconnect them with an appropriate target. Using microtools and nanotools we have developed a new method to rapidly initiate, elongate, and precisely connect new functional neuronal circuits over long distances. The extension rates achieved are ≥60 times faster than previously reported. Our findings have direct implications for the development of new therapies and surgical techniques to achieve functional regeneration after trauma and in neurodegenerative diseases. It also opens the door for the direct wiring of robust brain–machine interfaces as well as for investigations of fundamental aspects of neuronal signal processing and neuronal function.
Rich-Club Organization in Effective Connectivity among Cortical Neurons
Authors: Nigam Sunny , Shimono Masanori , Ito Shinya , Yeh Fang-Chin , Timme Nicholas , Myroshnychenko Maxym , Lapish Christopher C. , Tosi Zachary , Hottowy Pawel , Smith Wesley C. , Masmanidis Sotiris C. , Litke Alan M. , Sporns Olaf , Beggs John M.
Published: January 2016

The performance of complex networks, like the brain, depends on how effectively their elements communicate. Despite the importance of communication, it is virtually unknown how information is transferred in local cortical networks, consisting of hundreds of closely spaced neurons. To address this, it is important to record simultaneously from hundreds of neurons at a spacing that matches typical axonal connection distances, and at a temporal resolution that matches synaptic delays. We used a 512-electrode array (60 μm spacing) to record spontaneous activity at 20 kHz from up to 500 neurons simultaneously in slice cultures of mouse somatosensory cortex for 1 h at a time. We applied a previously validated version of transfer entropy to quantify information transfer. Similar toin vivoreports, we found an approximately lognormal distribution of firing rates. Pairwise information transfer strengths also were nearly lognormally distributed, similar to reports of synaptic strengths. Some neurons transferred and received much more information than others, which is consistent with previous predictions. Neurons with the highest outgoing and incoming information transfer were more strongly connected to each other than chance, thus forming a “rich club.” We found similar results in networks recordedin vivofrom rodent cortex, suggesting the generality of these findings. A rich-club structure has been found previously in large-scale human brain networks and is thought to facilitate communication between cortical regions. The discovery of a small, but information-rich, subset of neurons within cortical regions suggests that this population will play a vital role in communication, learning, and memory.

SIGNIFICANCE STATEMENTMany studies have focused on communication networks between cortical brain regions. In contrast, very few studies have examined communication networks within a cortical region. This is the first study to combine such a large number of neurons (several hundred at a time) with such high temporal resolution (so we can know the direction of communication between neurons) for mapping networks within cortex. We found that information was not transferred equally through all neurons. Instead, ∼70% of the information passed through only 20% of the neurons. Network models suggest that this highly concentrated pattern of information transfer would be both efficient and robust to damage. Therefore, this work may help in understanding how the cortex processes information and responds to neurodegenerative diseases.
Neural Microstates Govern Perception of Auditory Input without Rhythmic Structure
Authors: Henry Molly J. , Herrmann Björn , Obleser Jonas
Published: January 2016

Human perception fluctuates with the phase of neural oscillations in the presence of environmental rhythmic structure by which neural oscillations become entrained. However, in the absence of predictability afforded by rhythmic structure, we hypothesize that the neural dynamical states associated with optimal psychophysical performance are more complex than what has been described previously for rhythmic stimuli. The current electroencephalography study characterized the brain dynamics associated with optimal detection of gaps embedded in narrow-band acoustic noise stimuli lacking low-frequency rhythmic structure. Optimal gap detection was associated with three spectrotemporally distinct delta-governed neural microstates. Individual microstates were characterized by unique instantaneous combinations of neural phase in the delta, theta, and alpha frequency bands. Critically, gap detection was not predictable from local fluctuations in stimulus acoustics. The current results suggest that, in the absence of rhythmic structure to entrain neural oscillations, good performance hinges on complex neural states that vary from moment to moment.

SIGNIFICANCE STATEMENTOur ability to hear faint sounds fluctuates together with slow brain activity that synchronizes with environmental rhythms. However, it is so far not known how brain activity at different time scales might interact to influence perception when there is no rhythm with which brain activity can synchronize. Here, we used electroencephalography to measure brain activity while participants listened for short silences that interrupted ongoing noise. We examined brain activity in three different frequency bands: delta, theta, and alpha. Participants' ability to detect gaps depended on different numbers of frequency bands—sometimes one, sometimes two, and sometimes three—at different times. Changes in the number of frequency bands that predict perception are a hallmark of a complex neural system.
The Behavioral Relevance of Cortical Neural Ensemble Responses Emerges Suddenly
Authors: Sadacca Brian F. , Mukherjee Narendra , Vladusich Tony , Li Jennifer X. , Katz Donald B. , Miller Paul
Published: January 2016

Whereas many laboratory-studied decisions involve a highly trained animal identifying an ambiguous stimulus, many naturalistic decisions do not. Consumption decisions, for instance, involve determining whether to eject or consume an already identified stimulus in the mouth and are decisions that can be made without training. By standard analyses, rodent cortical single-neuron taste responses come to predict such consumption decisions across the 500 ms preceding the consumption or rejection itself; decision-related firing emerges well after stimulus identification. Analyzing single-trial ensemble activity using hidden Markov models, we show these decision-related cortical responses to be part of a reliable sequence of states (each defined by the firing rates within the ensemble) separated by brief state-to-state transitions, the latencies of which vary widely between trials. When we aligned data to the onset of the (late-appearing) state that dominates during the time period in which single-neuron firing is correlated to taste palatability, the apparent ramp in stimulus-aligned choice-related firing was shown to be a much more precipitous coherent jump. This jump in choice-related firing resembled a step function more than it did the output of a standard (ramping) decision-making model, and provided a robust prediction of decision latency in single trials. Together, these results demonstrate that activity related to naturalistic consumption decisions emerges nearly instantaneously in cortical ensembles.

SIGNIFICANCE STATEMENTThis paper provides a description of how the brain makes evaluative decisions. The majority of work on the neurobiology of decision making deals with “what is it?” decisions; out of this work has emerged a model whereby neurons accumulate information about the stimulus in the form of slowly increasing firing rates and reach a decision when those firing rates reach a threshold. Here, we study a different kind of more naturalistic decision—a decision to evaluate “what shall I do with it?” after the identity of a taste in the mouth has been identified—and show that this decision is not made through the gradual increasing of stimulus-related firing, but rather that this decision appears to be made in a sudden moment of “insight.”
Chronic Neuropathic Pain: It's about the Rhythm
Authors: Alshelh Zeynab , Di Pietro Flavia , Youssef Andrew M. , Reeves Jenna M. , Macey Paul M. , Vickers E. Russell , Peck Christopher C. , Murray Greg M. , Henderson Luke A.
Published: January 2016

The neural mechanisms underlying the development and maintenance of chronic neuropathic pain remain unclear. Evidence from human investigations suggests that neuropathic pain is associated with altered thalamic burst firing and thalamocortical dysrhythmia. Additionally, experimental animal investigations show that neuropathic pain is associated with altered infra-slow (<0.1 Hz) frequency oscillations within the dorsal horn and somatosensory thalamus. The aim of this investigation was to determine whether, in humans, neuropathic pain was also associated with altered infra-slow oscillations within the ascending “pain” pathway. Using resting-state functional magnetic resonance imaging, we found that individuals with orofacial neuropathic pain have increased infra-slow oscillatory activity throughout the ascending pain pathway, including within the spinal trigeminal nucleus, somatosensory thalamus, thalamic reticular nucleus, and primary somatosensory cortex. Furthermore, these infra-slow oscillations were temporally coupled across these multiple sites and occurred at frequencies similar to calcium waves in activated astrocytes. The region encompassing the spinal trigeminal nucleus also displayed increased regional homogeneity, consistent with a local spread of neural activity by astrocyte activation. In contrast, no increase in oscillatory behavior within the ascending pain pathway occurred during acute noxious stimuli in healthy individuals. These data reveal increased oscillatory activity within the ascending pain pathway that likely underpins increased thalamocortical oscillatory activity, a self-sustaining thalamocortical dysrhythmia, and the constant perception of pain.

SIGNIFICANCE STATEMENTChronic neuropathic pain is associated with altered thalamic firing and thalamocortical dysrhythmia. The mechanisms responsible for these changes remain unknown. In this study, we report in individuals with neuropathic pain increased oscillatory neural activity within the ascending pain pathway with evidence that these changes result from altered neural–astrocyte coupling. We propose a series of neural and glial events after nerve injury that result in the generation of altered thalamocortical activity and a persistent neuropathic pain state. Defining the underlying mechanisms responsible for neuropathic pain is critical if we are to develop more effective treatment regimens.
Representation of Maximally Regular Textures in Human Visual Cortex
Authors: Kohler Peter J. , Clarke Alasdair , Yakovleva Alexandra , Liu Yanxi , Norcia Anthony M.
Published: January 2016

Naturalistic textures with an intermediate degree of statistical regularity can capture key structural features of natural images (Freeman and Simoncelli, 2011). V2 and later visual areas are sensitive to these features, while primary visual cortex is not (Freeman et al., 2013). Here we expand on this work by investigating a class of textures that have maximal formal regularity, the 17 crystallographic wallpaper groups (Fedorov, 1891). We used texture stimuli from four of the groups that differ in the maximum order of rotation symmetry they contain, and measured neural responses in human participants using functional MRI and high-density EEG. We found that cortical area V3 has a parametric representation of the rotation symmetries in the textures that is not present in either V1 or V2, the first discovery of a stimulus property that differentiates processing in V3 from that of lower-level areas. Parametric responses were also seen in higher-order ventral stream areas V4, VO1, and lateral occipital complex (LOC), but not in dorsal stream areas. The parametric response pattern was replicated in the EEG data, and source localization indicated that responses in V3 and V4 lead responses in LOC, which is consistent with a feedforward mechanism. Finally, we presented our stimuli to four well developed feedforward models and found that none of them were able to account for our results. Our results highlight structural regularity as an important stimulus dimension for distinguishing the early stages of visual processing, and suggest a previously unrecognized role for V3 in the visual form-processing hierarchy.

SIGNIFICANCE STATEMENTHierarchical processing is a fundamental organizing principle in visual neuroscience, with each successive processing stage being sensitive to increasingly complex stimulus properties. Here, we probe the encoding hierarchy in human visual cortex using a class of visual textures—wallpaper patterns—that are maximally regular. Through a combination of fMRI and EEG source imaging, we find specific responses to texture regularity that depend parametrically on the maximum order of rotation symmetry in the textures. These parametric responses are seen in several areas of the ventral visual processing stream, as well as in area V3, but not in V1 or V2. This is the first demonstration of a stimulus property that differentiates processing in V3 from that of lower-level visual areas.
Hyaluronidase and Hyaluronan Oligosaccharides Promote Neurological Recovery after Intraventricular Hemorrhage
Authors: Vinukonda Govindaiah , Dohare Preeti , Arshad Arslan , Zia Muhammad T. , Panda Sanjeet , Korumilli Ritesh , Kayton Robert , Hascall Vincent C. , Lauer Mark E. , Ballabh Praveen
Published: January 2016

Intraventricular hemorrhage (IVH) in premature infants results in inflammation, arrested oligodendrocyte progenitor cell (OPC) maturation, and reduced myelination of the white matter. Hyaluronan (HA) inhibits OPC maturation and complexes with the heavy chain (HC) of glycoprotein inter-α-inhibitor to form pathological HA (HC–HA complex), which exacerbates inflammation. Therefore, we hypothesized that IVH would result in accumulation of HA, and that either degradation of HA by hyaluronidase treatment or elimination of HCs from pathological HA by HA oligosaccharide administration would restore OPC maturation, myelination, and neurological function in survivors with IVH. To test these hypotheses, we used the preterm rabbit model of glycerol-induced IVH and analyzed autopsy samples from premature infants. We found that total HA levels were comparable in both preterm rabbit pups and human infants with and without IVH, but HA receptors—CD44, TLR2, TLR4—were elevated in the forebrain of both humans and rabbits with IVH. Hyaluronidase treatment of rabbits with IVH reduced CD44 and TLR4 expression, proinflammatory cytokine levels, and microglia infiltration. It also promoted OPC maturation, myelination, and neurological recovery. HC–HA and tumor necrosis factor-stimulated gene-6 were elevated in newborns with IVH; and depletion of HC–HA levels by HA oligosaccharide treatment reduced inflammation and enhanced myelination and neurological recovery in rabbits with IVH. Hence, hyaluronidase or HA oligosaccharide treatment represses inflammation, promotes OPC maturation, and restores myelination and neurological function in rabbits with IVH. These therapeutic strategies might improve the neurological outcome of premature infants with IVH.

SIGNIFICANCE STATEMENTApproximately 12,000 premature infants develop IVH every year in the United States, and a large number of survivors with IVH develop cerebral palsy and cognitive deficits. The onset of IVH induces inflammation of the periventricular white matter, which results in arrested maturation of OPCs and myelination failure. HA is a major component of the extracellular matrix of the brain, which regulates inflammation through CD44 and TLR2/4 receptors. Here, we show two mechanism-based strategies that effectively enhanced myelination and neurological recovery in preterm rabbit model of IVH. First, degrading HA by hyaluronidase treatment reduced CD44 and TLR4 expression, proinflammatory cytokines, and microglial infiltration, as well as promoted oligodendrocyte maturation and myelination. Second, intraventricular injection of HA oligosaccharide reduced inflammation and enhanced myelination, conceivably by depleting HC–HA levels.
Actin Filaments Regulate Exocytosis at the Hair Cell Ribbon Synapse
Authors: Guillet Marie , Sendin Gaston , Bourien Jérôme , Puel Jean-Luc , Nouvian Régis
Published: January 2016

Exocytosis at the inner hair cell ribbon synapse is achieved through the functional coupling between calcium channels and glutamate-filled synaptic vesicles. Using membrane capacitance measurements, we investigated whether the actin network regulates the exocytosis of synaptic vesicles at the mouse auditory hair cell. Our results suggest that actin network disruption increases exocytosis and that actin filaments may spatially organize a subfraction of synaptic vesicles with respect to the calcium channels.

SIGNIFICANCE STATEMENTInner hair cells (IHCs), the auditory sensory cells of the cochlea, release glutamate onto the afferent auditory nerve fibers to encode sound stimulation. To achieve this task, the IHC relies on the recruitment of glutamate-filled vesicles that can be located in close vicinity to the calcium channels or more remotely from them. The molecular determinants responsible for organizing these vesicle pools are not fully identified. Using pharmacological tools in combination with membrane capacitance measurements, we show that actin filament disruption increases exocytosis in IHCs and that actin filaments most likely position a fraction of vesicles away from the calcium channels.
Evidence for the Integration of Stress-Related Signals by the Rostral Posterior Hypothalamic Nucleus in the Regulation of Acute and Repeated Stress-Evoked Hypothalamo-Pituitary-Adrenal Response in Rat
Authors: Nyhuis Tara J. , Masini Cher V. , Day Heidi E.W. , Campeau Serge
Published: January 2016

A likely adaptive process mitigating the effects of chronic stress is the phenomenon of stress habituation, which frequently reduces multiple stress-evoked responses to the same (homotypic) stressor experienced repeatedly. The current studies investigated putative brain circuits that may coordinate the reduction of stress-related responses associated with stress habituation, a process that is inadequately understood. Initially, two rat premotor regions that respectively regulate neuroendocrine (medial parvicellular region of the paraventricular hypothalamic nucleus [PaMP]) and autonomic (rostral medullary raphe pallidus [RPa]) responses were targeted with distinguishable retrograde tracers. Two to 3 weeks later, injected animals underwent loud noise stress, and their brains were processed for fluorescent immunohistochemical detection of the tracers and the immediate early gene Fos. A rostral region of the posterior hypothalamic nucleus (rPH), and to a lesser extent, the median preoptic nucleus, exhibited the highest numbers of retrogradely labeled cells from both the RPa and PaMP that were colocalized with loud noise-induced Fos expression. Injections of an anterograde tracer in the rPH confirmed these connections and suggested that this region may contribute to the coordination of multiple stress-related responses. This hypothesis was partially tested by posterior hypothalamic injections of small volumes of muscimol, which disrupts normal synaptic functions, before acute and repeated loud noise or restraint exposures. In addition to significantly reduced corticosterone release in response to these two distinct stressors, rPH muscimol disrupted habituation to each stressor modality, suggesting a novel and important contribution of the rostral posterior hypothalamic nucleus in this category of adaptive processes.

SIGNIFICANCE STATEMENTHabituation to stress is a process that possibly diminishes the detrimental health consequences of chronic stress by reducing the amplitude of many responses when the same challenging conditions are experienced repeatedly. Stress elicits a highly coordinated set of neuroendocrine, autonomic, and behavioral responses that are independently and relatively well defined; however, how the brain achieves coordination of these responses and their habituation-related declines is not well understood. The current studies provide some of the first anatomical and functional results suggesting that a specific region of the hypothalamus, the rostral posterior hypothalamic nucleus, targets multiple premotor regions and contributes to the regulation of acute neuroendocrine responses and their habituation to repeated stress.
Clemastine Enhances Myelination in the Prefrontal Cortex and Rescues Behavioral Changes in Socially Isolated Mice
Authors: Liu Jia , Dupree Jeffrey L. , Gacias Mar , Frawley Rebecca , Sikder Tamjeed , Naik Payal , Casaccia Patrizia
Published: January 2016

Altered myelin structure and oligodendrocyte function have been shown to correlate with cognitive and motor dysfunction and deficits in social behavior. We and others have previously demonstrated that social isolation in mice induced behavioral, transcriptional, and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC). However, whether enhancing myelination and oligodendrocyte differentiation could be beneficial in reversing such changes remains unexplored. To test this hypothesis, we orally administered clemastine, an antimuscarinic compound that has been shown to enhance oligodendrocyte differentiation and myelinationin vitro, for 2 weeks in adult mice following social isolation. Clemastine successfully reversed social avoidance behavior in mice undergoing prolonged social isolation. Impaired myelination was rescued by oral clemastine treatment, and was associated with enhanced oligodendrocyte progenitor differentiation and epigenetic changes. Clemastine induced higher levels of repressive histone methylation (H3K9me3), a marker for heterochromatin, in oligodendrocytes, but not neurons, of the PFC. This was consistent with the capability of clemastine in elevating H3K9 histone methyltransferases activity in cultured primary mouse oligodendrocytes, an effect that could be antagonized by cotreatment with muscarine. Our data suggest that promoting adult myelination is a potential strategy for reversing depressive-like social behavior.

SIGNIFICANCE STATEMENTOligodendrocyte development and myelination are highly dynamic processes influenced by experience and neuronal activity. However, whether enhancing myelination and oligodendrocyte differentiation is beneficial to treat depressive-like behavior has been unexplored. Mice undergoing prolonged social isolation display impaired myelination in the prefrontal cortex. Clemastine, a Food and Drug Administration-approved antimuscarinic compound that has been shown to enhance myelination under demyelinating conditions, successfully reversed social avoidance behavior in adult socially isolated mice. This was associated with enhanced myelination and oligodendrocyte differentiation in the prefrontal cortex through epigenetic regulation. Thus, enhancing myelination may be a potential means of reversing depressive-like social behavior.
Synaptic Organization of the Neuronal Circuits of the Claustrum
Authors: Kim Juhyun , Matney Chanel J. , Roth Richard H. , Brown Solange P.
Published: January 2016

The claustrum, a poorly understood subcortical structure located between the cortex and the striatum, forms widespread connections with almost all cortical areas, but the cellular organization of claustral circuits remains largely unknown. Based primarily on anatomical data, it has been proposed that the claustrum integrates activity across sensory modalities. However, the extent to which the synaptic organization of claustral circuits supports this integration is unclear. Here, we used paired whole-cell recordings and optogenetic approaches in mouse brain slices to determine the cellular organization of the claustrum. We found that unitary synaptic connections among claustrocortical (ClaC) neurons were rare. In contrast, parvalbumin-positive (PV) inhibitory interneurons were highly interconnected with both chemical and electrical synapses. In addition, ClaC neurons and PV interneurons formed frequent synaptic connections. As suggested by anatomical data, we found that corticoclaustral afferents formed monosynaptic connections onto both ClaC neurons and PV interneurons. However, the responses to cortical input were comparatively stronger in PV interneurons. Consistent with this overall circuit organization, activation of corticoclaustral afferents generated monosynaptic excitatory responses as well as disynaptic inhibitory responses in ClaC neurons. These data indicate that recurrent excitatory circuits within the claustrum alone are unlikely to integrate across multiple sensory modalities. Rather, this cellular organization is typical of circuits sensitive to correlated inputs. Although single ClaC neurons may integrate corticoclaustral input from different cortical regions, these results are consistent with more recent proposals implicating the claustrum in detecting sensory novelty or in amplifying correlated cortical inputs to coordinate the activity of functionally related cortical regions.

SIGNIFICANCE STATEMENTThe function of the claustrum, a brain nucleus found in mammals, remains poorly understood. It has been proposed, based primarily on anatomical data, that claustral circuits play an integrative role and contribute to multimodal sensory integration. Here we show that the principal neurons of the claustrum, claustrocortical (ClaC) projection neurons, rarely form synaptic connections with one another and are unlikely to contribute to broad integration within the claustrum. We show that, although single ClaC neurons may integrate corticoclaustral inputs carrying information for different sensory modalities, the synaptic organization of ClaC neurons, local parvalbumin-positive interneurons within the claustrum, and cortical afferents is also consistent with recent proposals that the claustrum plays a role in detecting salient stimuli or amplifying correlated cortical inputs.
Reversible Recruitment of a Homeostatic Reserve Pool of Synaptic Vesicles Underlies Rapid Homeostatic Plasticity of Quantal Content
Authors: Wang Xueyong , Pinter Martin J. , Rich Mark M.
Published: January 2016

Homeostatic regulation is essential for the maintenance of synaptic strength within the physiological range. The current study is the first to demonstrate that both induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds of blocking or unblocking acetylcholine receptors at the mouse neuromuscular junction. Our data suggest that the homeostatic upregulation of release is due to Ca2+-dependent increase in the size of the readily releasable pool (RRP). Blocking vesicle refilling prevented upregulation of quantal content (QC), while leaving baseline release relatively unaffected. This suggested that the upregulation of QC was due to mobilization of a distinct pool of vesicles that were rapidly recycled and thus were dependent on continued vesicle refilling. We term this pool the “homeostatic reserve pool.” A detailed analysis of the time course of vesicle release triggered by a presynaptic action potential suggests that the homeostatic reserve pool of vesicles is normally released more slowly than other vesicles, but the rate of their release becomes similar to that of the major pool during homeostatic upregulation of QC. Remarkably, instead of finding a generalized increase in the recruitment of vesicles into RRP, we identified a distinct homeostatic reserve pool of vesicles that appear to only participate in synchronized release following homeostatic upregulation of QC. Once this small pool of vesicles is depleted by the block of vesicle refilling, homeostatic upregulation of QC is no longer observed. This is the first identification of the population of vesicles responsible for the blockade-induced upregulation of release previously described.

SIGNIFICANCE STATEMENTThe current study is the first to demonstrate that both the induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds. Our data suggest that homeostatic upregulation of release is due to Ca2+-dependent priming/docking of a small homeostatic reserve pool of vesicles that normally have slow-release kinetics. Following priming, the reserve pool of vesicles is released synchronously with the normal readily releasable pool of synaptic vesicles. This is the first description of this unique pool of synaptic vesicles.
The awesome lysosome
Authors: Ballabio Andrea
Published: January 2016

In the early 50s, Christian De Duve identified a new cellular structure, the lysosome, defined as the cell's “suicide bag” (de Duve, ). Sixty years later, it is clear that the lysosome greatly exceeded the expectations of its discoverer. Over 50 different types of lysosomal storage diseases have been identified, each due to the deficiency or malfunction of a specific lysosomal protein. In addition, an important role of the lysosome has been unveiled in several common human diseases, such as cancer, obesity, neurodegenerative diseases, and infection. Recent studies have led to the identification of a lysosome‐to‐nucleus signaling pathway and a lysosomal gene network that regulate cellular clearance and energy metabolism. These observations have opened a completely new field of research and changed our traditional view of the lysosome from a dead‐end organelle to a control center of cell metabolism. An important challenge for the future will be to exploit these discoveries to identify modulators of lysosomal function that may be used to treat human diseases.
HAK DAN KEWAJIBAN ASASI MANUSIA DALAM PERSPEKTIF ISLAM
Authors: Aji Ahmad Mukri
Published: January 2016

Islam lebih awal jika dibandingkan dengan konsep atau ajaran lainnya. Dengan kata lain, Islam datang secara inheren membawa ajaran tentang HAM. Ajaran Islam tentang HAM dapat dijumpai dalam sumber utama ajaran Islam yaitu al-Qur`an dan Hadis yang merupakan sumber ajaran normatif, juga terdapat dalam praktik kehidupan umat Islam. Selain Hak Asasi Manusia (HAM) ada Kewajiban Asasi Manusia (KAM) yang menjadi penyeimbang dan penyelaras guna mencapai kemaslahatan umat. Kata kunci: Hukum Islam, HAM, KAM.  DOI: 10.15408/sjsbs.v2i2.2386
Penerapan Wajib Militer di Indonesia
Authors: Marsella Ria , Badaria Putri Hilaliatu
Published: January 2016

Bangsa Yang Kuat Adalah Bangsa Yang Mampu Menjaga Dan Memperjuangkan Segenap Tumpah Darahnya Dari Segala Bentuk Intervensi Demi Mempertahankan Keutuhan Negara Kesatuan Republik Indonesia “ Jenderal Sudirman” Maka perlu adanya upaya negara untuk benar-benar dapat mempertahankan dan memperjuangkan kadualatannya dalam menciptakan Negara Kesatuan Republik Indonesia yang kuat dan berdaulat sehingga mampu memperjuangkan segala bentuk tumpah darahnya  di tengah-tengah kehidupan berbangsa dan bernegara. Wajib militer adalah kewajiban bagi seorang warga negara berusia muda terutama pria, biasanya antara 18 - 27 tahun untuk menyandang senjata dan menjadi anggota tentara dan mengikuti pendidikan militer guna meningkatkan ketangguhan dan kedisiplinan seorang itu sendiri. Wamil biasanya diadakan guna untuk meningkatkan kedisiplinan, ketangguhan, keberanian dan kemandirian seorang itu. Dasar hukum pelaksanaan wajib militer ini tertera dalam Rancangan Undang-undang Komponen Cadangan (Komcad), yang mana Komcad adalah pasukan cadangan militer, terdiri dari warga sipil yang mendapat pendidikan militer dasar, dipersiapkan untuk mendukung militer sebagai komponen utama pada masa darurat perang. Di masa damai, setelah mendapat pelatihan militer dasar atau selesai masa perang, Komcad kembali menjadi warga sipil biasa. Dengan adanya RUU Komcad yang mewajibkan warga negara untuk ikut wajib militer dalam hal implementasian bela negara dalam konstitusi Indonesia menimbulkan polemik di masyarakat. Sisi pro terhadap RUU Komcad mengatakan bahwa dengan adanya wajib militer ini maka akan, pertama, membantu kekuatan pertahanan Negara dengan melibatkan warga negara sebagai komponen cadangan dikarenakan posisi geografis Indonesia yang strategis, kedua menimbulkan rasa patriotism, nasionalisme, serta kedisiplinan di masyarakat, ketiga, penerapan wamil sebagai bentuk bela negara yang diwajibkan oleh UUD RI 1945. Di sisi lainnya pelaksanaan wajib militer dalam RUU Komcad menimbulkan kritik dan permasalahan, pertama, adanya pelanggaran hak asasi manusia khususnya hak sipil yang mana setiap orang mempunyai hak untuk menolak untuk ikut wajib militer, sedangkan dalam RUU Komcad apabila seseorang menolak wajib militer akan dikenakan sanksi pidana. Kedua, pelaksanaan wajib militer akan memerlukan dana yang besar. Kebutuhan anggaran TNI saat ini minimal Rp 100 triliun, padahal yang bisa dipenuhi pemerintah hanya Rp 33 triliun. Tentunya dengan adanya wajib militer akan menambah jumlah biaya yang besar untuk penyediaan sarana dan prasarananya.  DOI: 10.15408/sjsbs.v2i2.2390