bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Neuronal Oxygen Responses inC. elegansIs Mediated through Interactions between Globin 5 and the H-NOX Domains of Soluble Guanylate Cyclases
Authors: Abergel Zohar , Chatterjee Arijit Kumar , Zuckerman Binyamin , Gross Einav 
Published: January 2016

Soluble guanylate cyclases (sGCs) are gas-binding proteins that control diverse physiological processes such as vasodilation, platelet aggregation, and synaptic plasticity. In the nematodeCaenorhabditis elegans, a complex of sGCs, GCY-35 and GCY-36, functions in oxygen (O2) sensing. Previous studies suggested that the neuroglobin GLB-5 genetically interacts with GCY-35, and that the inhibitory effect of GLB-5 on GCY-35 function is necessary for fast recovery from prolonged hypoxia. In this study, we identified mutations ingcy-35andgcy-36that impact fast recovery and other phenotypes associated with GLB-5, without undermining sGC activity. These mutations,heb1andheb3, change conserved amino acid residues in the regulatory H-NOX domains of GCY-35 and GCY-36, respectively, and appear to suppress GLB-5 activity by different mechanisms. Moreover, we observed that short exposure to 35% O2desensitized the neurons responsible for ambient O2sensing and that this phenomenon does not occur inheb1animals. These observations may implicate sGCs in neuronal desensitization mechanisms far beyond the specific case of O2sensing in nematodes. The conservation of functionally important regions of sGCs is supported by examining site-directed mutants of GCY-35, which suggested that similar regions in the H-NOX domains of O2and NO-sensing sGCs are important for heme/gas interactions. Overall, our studies provide novel insights into sGC activity and regulation, and implicate similar structural determinants in the control of both O2and NO sensors.SIGNIFICANCE STATEMENTSoluble guanylate cyclases (sGCs) control essential and diverse physiological processes, including memory processing. We usedCaenorhabditis elegansto explore how a neuroglobin inhibits a complex of oxygen-sensing sGCs, identifying sGC mutants that resist inhibition. Resistance appears to arise by two different mechanisms: increased basal sGC activity or disruption of an interaction with neuroglobin. Our findings demonstrate that the inhibition of sGCs by neuroglobin is essential for rapid adaptation to either low or high oxygen levels, and that similar structural regions are key for regulating both oxygen and nitric oxide sensors. Based on our structural and functional analyses, we present the hypothesis that neuroglobin-sGC interactions may be generally important for adaptation processes, including those in organisms with more complex neurological functions.
Short Fibrils Constitute the Major Species of Seed-Competent Tau in the Brains of Mice Transgenic for Human P301S Tau
Authors: Jackson Samuel J. , Kerridge Caroline , Cooper Jane , Cavallini Annalisa , Falcon Benjamin , Cella Claire V. , Landi Alessia , Szekeres Philip G. , Murray Tracey K. , Ahmed Zeshan , Goedert Michel , Hutton Michael , O'Neill Michael J. , Bose Suchira 
Published: January 2016

The interneuronal propagation of aggregated tau is believed to play an important role in the pathogenesis of human tauopathies. It requires the uptake of seed-competent tau into cells, seeding of soluble tau in recipient neurons and release of seeded tau into the extracellular space to complete the cycle. At present, it is not known which tau species are seed-competent. Here, we have dissected the molecular characteristics of seed-competent tau species from the TgP301S tau mouse model using various biochemical techniques and assessed their seeding ability in cell and animal models. We found that sucrose gradient fractions from brain lysates seeded cellular tau aggregation only when large (>10 mer) aggregated, hyperphosphorylated (AT8- and AT100-positive) and nitrated tau was present. In contrast, there was no detectable seeding by fractions containing small, oligomeric (<6 mer) tau. Immunodepletion of the large aggregated AT8-positive tau strongly reduced seeding; moreover, fractions containing these species initiated the formation and spreading of filamentous tau pathologyin vivo, whereas fractions containing tau monomers and small oligomeric assemblies did not. By electron microscopy, seed-competent sucrose gradient fractions contained aggregated tau species ranging from ring-like structures to small filaments. Together, these findings indicate that a range of filamentous tau aggregates are the major species that underlie the spreading of tau pathology in the P301S transgenic model.SIGNIFICANCE STATEMENTThe spread of tau pathology from neuron to neuron is postulated to account for, or at least to contribute to, the overall propagation of tau pathology during the development of human tauopathies including Alzheimer's disease. It is therefore important to characterize the native tau species responsible for this process of seeding and pathology spreading. Here, we use several biochemical techniques to dissect the molecular characteristics of native tau protein conformers from TgP301S tau mice and show that seed-competent tau species comprise small fibrils capable of seeding tau pathology in cell and animal models. Characterization of seed-competent tau gives insight into disease mechanisms and therapeutic interventions.
Direct Transcriptional Effects of Apolipoprotein E
Authors: Theendakara Veena , Peters-Libeu Clare A. , Spilman Patricia , Poksay Karen S. , Bredesen Dale E. , Rao Rammohan V. 
Published: January 2016

A major unanswered question in biology and medicine is the mechanism by which the product of the apolipoprotein E ε4 allele, the lipid-binding protein apolipoprotein E4 (ApoE4), plays a pivotal role in processes as disparate as Alzheimer's disease (AD; in which it is the single most important genetic risk factor), atherosclerotic cardiovascular disease, Lewy body dementia, hominid evolution, and inflammation. Using a combination of neural cell lines, skin fibroblasts from AD patients, and ApoE targeted replacement mouse brains, we show in the present report that ApoE4 undergoes nuclear translocation, binds double-stranded DNA with high affinity (low nanomolar), and functions as a transcription factor. Using chromatin immunoprecipitation and high-throughput DNA sequencing, our results indicate that the ApoE4 DNA binding sites include ∼1700 gene promoter regions. The genes associated with these promoters provide new insight into the mechanism by which AD risk is conferred by ApoE4, because they include genes associated with trophic support, programmed cell death, microtubule disassembly, synaptic function, aging, and insulin resistance, all processes that have been implicated in AD pathogenesis.SIGNIFICANCE STATEMENTThis study shows for the first time that apolipoprotein E4 binds DNA with high affinity and that its binding sites include 1700 promoter regions that include genes associated with neurotrophins, programmed cell death, synaptic function, sirtuins and aging, and insulin resistance, all processes that have been implicated in Alzheimer's disease pathogenesis.
PENEGAKAN HUKUM PIDANA TERHADAP KORBAN PECANDU NARKOBA DI INDONESIA
Authors: Siagian Amrizal 
Published: January 2016

Kebijakan kriminal pemerintah atas terbitnya undang-undang terkait narkoba no 35 tahun 2009 khususnya bagi pecandu narkoba perlu diimplementasikan sesuai amanat konstitusi. Bahwa pemerintah memiliki kewajiban untuk menjaga tanah tumpah darah dan warganya dari bentuk ancaman apapun. Termasuk ancaman bahaya narkoba, yang secara sadar dan sengaja disebarkan kekalangan masyarakat, utamanya generasi muda sebagai penerus bangsa. Saat ini, pemakai narkoba diduga mencapai 5,1 juta, bahkan lebih. Karena jumlah pemakai narkoba itu ibarat gunung es (ice berg) dan mengalami angka gelap (dark number). Sangat diharapkan dari kebijakan kriminal atas terbitnya undang-udang tadi mampu mengatasi atau setidaknya mengurangi jumlah pemakai narkoba, yang salah satunya menciptakan terobosan baru dengan men-dekriminalisasi pemakai narkoba tanpa harus mendapatkan sanksi pinjara. Sebagaimana disebutkan bahwa jaminan perlindungan hukum yang diberikan bagi pecandu narkotika diatur melalui UU No 35 Tahun 2009 Tentang Narkotika dengan memberikan rehabilitasi baik medis maupun rehabilitasi sosial sebagaimana tercantum pada Pasal 54 pada undang-undang narkotika itu. Yaitu bahwa ”pecandu narkotika dan pecandu penyalahguna narkotika wajib menjalani rehabilitasi medis dan rehabilitasi sosial”. Kata kunci: kebijakan krimanal, narkoba, korban, dekriminalisasiDOI: 10.15408/sjsbs.v2i2.2380
PENGARUH ANGGARAN BELANJA DAERAH DAN SENJANGAN ANGGARAN TERHADAP TINGKAT KORUPSI DI INDONESIA
Authors: Windarti Anissa 
Published: January 2016

Penelitian ini mengkaji tentang pengaruh Anggaran Belanja Daerah dan Senjangan Anggaran terhadap Tingkat Korupsi di Indonesia dengan menggunakan variabel senjangan anggaran sebagai intervening variable.Korupsi di tingkat Pemerintah daerah Kabupaten/Kota masih sangat tinggi. Salah satu sumber dana yang menjadi sasaran korupsi adalah anggaran belanja daerah yang didorong oleh perilaku oportunistik pihak eksekutif berupa tindakan membuat senjangan anggaran. Hal ini sesuai dengan apa yang disebutkan dalam Agency Theory. Terdapat tujuh hipotesis dalam penelitian ini yangakan diuji menggunakan metode analisis jalur (Path Analysis). Hasil penelitian menunjukkan bahwa hanya besarnya anggaran Bantuan Sosial dan Belanja Pegawai yang berpengaruh terhadap Senjangan Anggaran. Pengaruh Senjangan Anggaran terhadap semakin tinggi Tingkat Korupsi di Indonesia juga terbukti secara empirik. Selain itu, terdapat pengaruh Belanja Hibah, Bantuan Sosial, Belanja Pegawai, Belanja Barang dan Jasa, Belanja Modal terhadap Tingkat Korupsi di Indonesia dengan Senjangan Anggaran sebagai pemoderasi. Sehingga, Senjangan Anggaran dapat menciptakan terjadinya Korupsi pada Anggaran Belanja Daerah. Kata kunci : belanja daerah, senjangan anggaran, korupsi, integritas DOI: 10.15408/sjsbs.v2i2.2384
Intra-Articular Osteotomy for Genu Valgum in the Knee with a Lateral Compartment Deficiency
Authors: Feldman David S. , Goldstein Rachel Y. , Kurland Adam M. , Sheikh Taha Abdel Majid 
Published: January 2016

Background:
A deficiency of the lateral compartment of the knee, often in the setting of skeletal dysplasia, is an intra-articular deformity resulting in genu valgum. Historically, this abnormality has been treated using an extra-articular approach. Lateral hypoplasia of the femoral condyle can be treated with advancement of the lateral femoral condyle without creating a secondary deformity. The purpose of this study was to present the technique and results of lateral condylar advancement, with or without tibial hemiplateau elevation, in patients with intra-articular valgus deformity secondary to skeletal dysplasia.

Methods:
A retrospective review of the cases of five patients, from seven to twenty-one years old, with skeletal dysplasia and unilateral or bilateral severe genu valgum deformity was performed. For all patients, the etiology of the deformity was a deficient lateral compartment of the knee—that is, lateral femoral condylar hypoplasia with or without concomitant lateral hemiplateau depression. Lateral femoral condylar advancement with or without lateral tibial hemiplateau elevation was performed in eight knees.

Results:
The average tibiofemoral angle was 34.7° of valgus preoperatively and improved to 9.4° of valgus at the most recent follow-up. The average length of follow-up was 2.9 years (range, 1.0 to 5.2 years). The average range of motion at the time of final follow-up was an arc of 108° starting from full extension. All osteotomies healed uneventfully. All five patients were satisfied with both the cosmetic appearance and the function of the involved limb and were able to walk without assistive devices.

Conclusions:
In patients with a deficient lateral compartment of the knee, lateral femoral condylar advancement with or without hemiplateau elevation allowed correction of severe genu valgum without the creation of an oblique joint line. This technique allows correction of the overall mechanical axis, restoring both function and the cosmetic appearance of the limb.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Three-Dimensional Magnetic Resonance Imaging of Glenohumeral Dysplasia in Neonatal Brachial Plexus Palsy
Authors: Eismann Emily A. , Laor Tal , Cornwall Roger 
Published: January 2016

Background:
Existing quantitative measurements of glenohumeral dysplasia in children with unresolved neonatal brachial plexus palsy (NBPP) have been mostly limited to the axial plane. The purpose of this study was to describe the three-dimensional (3D) pathoanatomy of glenohumeral dysplasia using 3D magnetic resonance imaging (MRI) reformations.

Methods:
3D MRI reformations of the scapula, glenoid labrum, and proximal part of the humerus were created from a volume-acquisition proton-density-weighted MRI sequence of both the affected and the unaffected shoulder of seventeen children less than six years of age with unresolved NBPP who had not undergone shoulder surgery. Glenoid retroversion and posterior humeral head displacement were measured on axial 2D images. Humeral head displacement in all planes, labral circumference, glenoid retroversion, glenoid declination, and scapular morphometric values were measured on 3D reformations. Contiguity of the humeral head with the labrum and the shape of the glenoid were classified. Measurements were compared between the affected and unaffected sides.

Results:
On 3D evaluation, the humeral head was completely posteriorly translated in ten patients but was never outside the glenoid labrum. Instead, in these patients, the humeral head was eccentrically articulating with the dysplastic glenoid and was contained by a posteriorly elongated labrum. Glenoid dysplasia was not limited to the axial plane. Less declination of the glenoid in the coronal plane correlated with greater 3D glenoid retroversion. Glenoid retroversion resulted from underdevelopment of the posterior aspect of the glenoid rather than overdevelopment of the anterior aspect of the glenoid. 3D measurements of greater glenoid retroversion and less declination correlated with 2D measurements of glenoid retroversion and posterior humeral head displacement.

Conclusions:
Posterior humeral head displacement in NBPP should not be considered a simple “dislocation.” Glenohumeral dysplasia is not limited to the axial plane. Abnormal glenoid declination may have potential implications for the evaluation and treatment of shoulder weakness and contractures.
No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial
Authors: Wagner Henrik , Alvarsson Michael , Mannheimer Buster , Degerblad Marie , Östenson Claes-Göran 
Published: January 2016

OBJECTIVEThere has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This study was designed to investigate the effect of high-dose vitamin D3 treatment on β-cell function, insulin sensitivity, and glucose tolerance in subjects with prediabetes or diet-treated type 2 diabetes.RESEARCH DESIGN AND METHODSSubjects (n = 44) were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks. Hyperglycemic clamp assessed first-phase (0–12 min) and second-phase (12–120 min) insulin response, insulin sensitivity, and disposition index (DI). An oral glucose tolerance test assessed glucose tolerance and glycosylated hemoglobin assessed glycemic control.RESULTSA total of 21 (vitamin D) and 22 (placebo) subjects completed the study, respectively. Season-adjusted 25-OH-vitamin D [25(OH)D] levels were doubled in the active treated group (43–82 nmol/L). No effect of vitamin D treatment, compared with placebo, was seen on first-phase or second-phase insulin secretion. There were no group differences in insulin sensitivity, DI, or any measures of glycemic control. No hypercalcemia or other adverse effects of vitamin D treatment were seen compared with placebo. Subgroup analyses of those with the lowest basal and greatest increase in 25(OH)D levels did not change these results.CONCLUSIONSThis study gives no support for any substantial effect of high-dose vitamin D treatment for 8 weeks in prediabetes or diet-treated type 2 diabetes on β-cell function, insulin sensitivity, or glycemic control.
Findings of Paediatric Upper Gastrointestinal Endoscopy at a Tertiary Care Centre
Authors: Thapa Surya Bahadur , Sharma Arun Kumar 
Published: January 2016

Introduction: Endoscopy is an important diagnostic tool for gastrointestinal disorders in children. Practitioners still debate the need and utility of endoscopy in children and this important evaluation is potentially underutilized. There is a paucity of paediatric endoscopy data in Nepal. This report describes an initial three-year experience on profile of upper gastrointestinal endoscopy at Tribhuvan University Teaching Hospital (TUTH).Material and Methods: This retrospective study was conducted by reviewing hospital records for children undergoing endoscopy for various indications at TUTH during November 2011 to October 2014 (3 years).Results: We performed 362 endoscopies during this period. Mean age of patients was 9.49 years (range 2 months to 18 years) and 199 (54.9%) patients were under 10 years of age. Common indications were upper gastrointestinal bleeding (27.6%), recurrent abdominal pain (26.2%), acute abdominal pain (24.6%), recurrent vomiting (5.2%), and caustic ingestion (3.6%). An abnormality was detected in 159 (42.2%) patients. Varices (16.6%), gastritis/duodenitis (14.9%), ulcer (3.3%), oesophagitis (1.9%) were common diagnoses. Etiology of upper gastrointestinal bleed was identified in 65% of patients. Majority of patients with recurrent abdominal pain had negative results (80%). Failure to thrive constituted a very small proportion of children (0.2%) evaluated. All children received sedation/ analgesia and tolerated the procedure well.Conclusion: Paediatric upper gastrointestinal endoscopy can be safely performed across wide age range with proper sedation/ analgesia. Endoscopic diagnosis may improve management and children requiring such evaluation should be timely referred. Paediatricians should be encouraged to refer patients with growth failure early to ensure proper management. J Nepal Paediatr Soc 2015;35(2):123-128
Diuretic activity of the bark of <i>Eysenhardtia polystachya</i>
Authors: Pablo-Pérez Saudy Saret , Estévez-Carmona María Mirian , Meléndez-Camargo María Estela 
Published: January 2016

<p class="Abstract">The aim of this study was to evaluate the diuretic activity of <em>Eysenhardtia polystachya</em> bark aqueous extract at different doses in a rat model. Different doses of <em>E. polystachya</em> (125, 250, 500 and 750 mg/kg body weight), furosemide (4 mg/kg) and vehicle were administered per os to female rats (n=6 animals per group). After 6 hours in metabolic cages, the effect on urinary flow, glomerular ﬁltration rate and electrolyte balance of sodium and potassium were assessed in all animals. <em>E. polystachya</em> at the doses of 500 and 750 mg/kg induced diuretic activity, since markedly increased (p&lt;0.05) the urinary flow rate, similar to that of furosemide treated group. Only the dose of 750 mg/kg produced an increment in urinary excretion of sodium but not of potassium compared with control group. These findings indicate that<em> E. polystachya</em> bark-induced diuretic activity, providing evidence for its folkloric use.</p><p> </p>
Fécondité et ambiguïté de la notion de séduction en psychanalyse
Authors: Périer Antoine 
Published: January 2016

Cet article développe, dans une perspective historique et théorique, l’évolution de la théorie de la séduction chez Freud, de ses « neurotica » postulant l’effet traumatique de la séduction réelle précoce, à la place centrale du fantasme et de la réalité psychique. Ces deux modélisations apparaissent plus comme une évolution vers une forme d’intégration des facteurs externes et internes plutôt qu’une rupture théorique radicale. La théorie de la séduction généralisée de Jean Laplanche est également abordée, dans son lien aux modèles freudiens, comme une prise de distance vis-à-vis de la question de l’étiologie des névroses, et une inscription de la séduction précoce mère-bébé comme moteur général du développement de la vie psychique et de la sexualité infantile.
Les balbutiements de la séduction
Authors: Durieux Marie-José 
Published: January 2016

L’ infans , l’enfant qui ne parle pas encore, ne pourra accéder à une pensée complexe et symbolisée qu’en faisant un long détour par l’appareil psychique de sa mère, si elle veut bien toutefois se prêter à ce jeu. Car l’enjeu est d’importance. Ce n’est pas moins que d’entrer dans le monde du langage et des échanges. Il faut d’abord réussir à séduire sa mère, ou le substitut maternel, pour avoir une chance de faire quelque chose de sa vie. Toutes les grandes théories qui tentent de modéliser l’origine de la pensée s’efforcent de décrire et de nommer cela. Et il est remarquable de noter que pour entrer dans ce langage qui le fera humain, le bébé devra prendre la voie de ce que la rhétorique la plus classique définit comme une figure de style majeure du procès linguistique : la métonymie, figure du manque et du désir.
L’adolescent séduisant son corps : une émersion sensorielle
Authors: Andrieu Bernard 
Published: January 2016

En se filmant, l’adolescent se montre séduisant dans cet usage du corps à la fois physique et narcissique : il rend son corps séduisant dans le vif de l’expérience. Ce n’est pas tant une disparition de soi qu’un désir de ressentir une sensation anesthésiée par l’habitude corporelle. Cette re-narcissisation de soi s’effectue par une prise de risque inédite et sur un sport inédit ; mais le dispositif de mise en scène de soi est ici dans un point de vue en 1 re personne afin de montrer le degré et le niveau de son engagement corporel. La motricité inédite donne le point de vue vécu par le sujet qui voudrait, par le film en 1 re personne, saisir sa propre pulsion scopique dans un espace vertigineux en 3D. Cette écologisation du corps vivant place le moi suspendu en l’air au centre de la présentation de soi. C’est moins le corps qui est mouvant que le soi qui voudrait se maintenir en l’air en voulant séduire par le spectacle de son plaisir sensoriel.
La psychomotricité au risque de la séduction
Authors: Potel Baranes Catherine 
Published: January 2016

Le travail psychocorporel, et en particulier la psychomotricité, peut effrayer par sa facilité à entrer en relation « de corps et de sensorialité » avec les patients. Ceci est encore plus vrai quand on s’adresse à des adolescents, pour qui, pendant longtemps, on a pensé que les thérapies corporelles étaient à proscrire. Même si on n’en est plus là, penser à une thérapie de relaxation ou de conscience corporelle n’est pas encore rentré dans les préconisations thérapeutiques habituelles, par crainte d’un trop de séduction activant les flambées pubertaires. À partir de deux histoires cliniques, Hugues et Nina, l’auteur défend l’idée d’une séduction tempérée, qui retravaille la matière même du processus de subjectivation primaire, au cœur de la construction identitaire.