bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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
Teacher-offered Forms of Support for Learners with Low Self-esteem and Suffering from Bullying
Authors: Meškauskienė Asta , Barkauskaitė Marijona 
Published: January 2016

Purpose. The problem of bullying remains one of the major social problems in Lithuanian schools. But the acquired experience of practices in fighting the negative phenomenon enables professionals to improve the measures already taken and to foresee new methods in overcoming the problem. The purpose of the present article is to explore the teacher-offered forms of support for teenagers with low self-esteem and suffering from bullying.
Methods and resources. The methods used in the study are research literature analysis and qualitative methods. The sample of the qualitative research comprises 86 teachers from schools of general secondary education, of different subjects, with different professional qualifications and experience, of different age groups. The teachers were asked to respond to half-structured questionnaires.
Results. On the basis of the obtained data, it has been established that the most efficient forms of support for teenagers with low self-esteem and suffering from bullying were the ones involving the development of the sense of learner responsibility within school and class community (including the encouragement of empathy and tolerance, raising the awareness of human rights, creating the atmosphere of intolerance towards bullying, and initiating peer-support groups) as well as the enhancement of personal responsibility on the part of every individual who comes into contact with teenagers suffering from bullying (namely, peers, form tutor, social pedagogue, school psychologist, parents and others).
The Literariness of Literature and the History of Emotion
Authors: McNamer Sarah 
Published: January 2016

The middle english pearl is one of the most moving and beautiful poems ever composed. occasioned, it seems, by the death of a two-year-old daughter, whose identity has never been determined, it casts the grieving narrator-father as one who has treasured the child as a jewel beyond compare. She was round and smooth, rare and radiant—a precious pearl fit for a prince. Yet this dear small thing just slipped away one day in the garden, tumbling down through the grass into the dark earth:Perle, plesaunte to prynces payeTo clanly clos in golde so clere,Oute of oryent, I hardyly saye,Ne proved I never her precious pere.So rounde, so reken in uche arayeSo smal, so smothe her sydes were,Quere-so-ever I jugged gemmes gaye,I sette hyr sengeley in synglere.Allas! I leste hyr in on erbere;Thurgh gresse to grounde hit fro me yot.I dewyne, fordolked of luf-daungereOf that pryvy perle wythouten spot. (lines 1-12)Pearl, pleasing and delightful for a prince to enclose in fine gold: of all those from the orient, I declare that I never knew one as precious. So round, so radiant in every setting; so small, so smooth her sides were; wherever I judged beautiful gems, I appraised her as singularly rare. Alas! I lost her in a garden; through grass to ground it sped from me. I mourn, overcome with love-longing for my own precious, spotless pearl.As this opening stanza reveals, Pearl relies on the polyvalence and sensuous power of poetic language for its affective effects, gathering associative resonance through shifting meanings, working through indirection and allusiveness, tapping into the sensory power of visual and tactile images and patterned sound, and leaving much unsaid, to be grasped and felt between the lines. But the poem's broad emotional arc is clear. It scripts a therapeutic narrative of affective experience, taking its reader, whom it enfolds within the textual “I” of the poem, from “woe” to “weal” (56, 1187).