bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Expression of a Specific Hyperpolarization-Activated Cyclic Nucleotide-Gated Cation Channel (HCN) in Surviving Dentate Gyrus Granule Cells of Human and Experimental Epileptic Hippocampus
Authors: Bender Roland A. , Soleymani Sheila V. , Brewster Amy L. , Nguyen Snow T. , Beck Heinz , Mathern Gary W. , Baram Tallie Z. 
Published: April 2018

Changes in the expression of ion channels, contributing to altered neuronal excitability, are emerging as possible mechanisms in the development of certain human epilepsies. In previous immature rodent studies of experimental prolonged febrile seizures, isoform-specific changes in the expression of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCNs) correlated with long-lasting hippocampal hyperexcitability and enhanced seizure susceptibility. Prolonged early-life seizures commonly precede human temporal lobe epilepsy (TLE), suggesting that transcriptional dysregulation of HCNs might contribute to the epileptogenic process. Therefore, we determined whether HCN isoform expression was modified in hippocampi of individuals with TLE. HCN1 and HCN2 expression were measured usingin situhybridization and immunocytochemistry in hippocampi from three groups: TLE with hippocampal sclerosis (HS;n= 17), epileptic hippocampi without HS, or non-HS (NHS;n= 10), and autopsy material (n= 10). The results obtained in chronic human epilepsy were validated by examining hippocampi from the pilocarpine model of chronic TLE.In autopsy and most NHS hippocampi, HCN1 mRNA expression was substantial in pyramidal cell layers and lower in dentate gyrus granule cells (GCs). In contrast, HCN1 mRNA expression over the GC layer and in individual GCs from epileptic hippocampus was markedly increased once GC neuronal density was reduced by >50%. HCN1 mRNA changes were accompanied by enhanced immunoreactivity in the GC dendritic fields and more modest changes in HCN2 mRNA expression. Furthermore, similar robust and isoform-selective augmentation of HCN1 mRNA expression was evident also in the pilocarpine animal model of TLE. These findings indicate that the expression of HCN isoforms is dynamically regulated in human as well as in experimental hippocampal epilepsy. After experimental febrile seizures (i.e., early in the epileptogenic process), the preserved and augmented inhibition onto principal cells may lead to reduced HCN1 expression. In contrast, in chronic epileptic HS hippocampus studied here, the profound loss of interneuronal and principal cell populations and consequent reduced inhibition, coupled with increased dendritic excitation of surviving GCs, might provoke a “compensatory” enhancement of HCN1 mRNA and protein expression.
Apamin-Sensitive Small Conductance Calcium-Activated Potassium Channels, through their Selective Coupling to Voltage-Gated Calcium Channels, Are Critical Determinants of the Precision, Pace, and Pattern of Action Potential Generation in Rat Subthalamic Nucleus NeuronsIn Vitro
Authors: Hallworth Nicholas E. , Wilson Charles J. , Bevan Mark D. 
Published: April 2018

Distinct activity patterns in subthalamic nucleus (STN) neurons are observed during normal voluntary movement and abnormal movement in Parkinson's disease (PD). To determine how such patterns of activity are regulated by small conductance (SK) calcium-activated potassium channels (KCa) and voltage-gated calcium (Cav) channels, STN neurons were recorded in the perforated patch configuration in slices, [which were prepared from postnatal day 16 (P16)-P30 rats and held at 37°C] and then treated with the SK KCachannel antagonist apamin or the SK KCaagonist 1-ethyl-2-benzimidazolinone or the Cavchannel antagonists ω-conotoxin GVIA (Cav2.2-selective) or nifedipine (Cav1.2-1.3-selective). In other experiments, fura-2 was introduced as an indicator of intracellular calcium dynamics.A component of the current underlying single-spike afterhyperpolarization was sensitive to apamin, phase-locked to calcium entry via Cav2.2 channels, and necessary for precise, autonomous, single-spike oscillation. SK KCa/Cav2.2 channel coupling did not underlie spike-frequency adaptation but limited activity in response to current injection by encoding the accumulation of intracellular calcium, maintained the characteristic sigmoidal frequency-intensity relationship and generated a post-train afterhyperpolarization. In addition, SK KCachannels terminated rebound burst activity more effectively in neurons with short-duration bursts (<100 msec) than neurons with long-duration bursts (>100 msec), presumably through their activation by Cav3 channels. Cav1.2-1.3 channels were not strongly coupled to SK KCachannels and therefore supported secondary range and long-duration rebound burst firing. In summary, SK KCachannels play a fundamental role in autonomous, driven, and rebound activity and oppose the transition from autonomous, rhythmic, single-spike activity to burst firing in STN neurons.
Diadenosine Tetraphosphate Protects against Injuries Induced by Ischemia and 6-Hydroxydopamine in Rat Brain
Authors: Wang Yun , Chang Chen-Fu , Morales Marisela , Chiang Yung-Hsiao , Harvey Brandon K. , Su Tsung-Ping , Tsao Li-I , Chen Suyu , Thiemermann Christoph 
Published: April 2018

Diadenosine tetraphosphate (AP4A), an endogenous diadenosine polyphosphate, reduces ischemic injury in the heart. In this study, we report the potent and protective effects of AP4A in rodent models of stroke and Parkinson's disease. AP4A, given intracerebroventricularly before middle cerebral artery (MCA) ligation, reduced cerebral infarction size and enhanced locomotor activity in adult rats. The intravenous administration of AP4A also induced protection when given early after MCA ligation. AP4A suppressed terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) induced by hypoxia/reperfusion in primary cortical cultures, and reduced both ischemia-induced translocation of mitochondrial cytochromecand the increase in cytoplasmic caspase-3 activityin vivo. The purinergic P2/P4antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2-receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an anti-apoptotic mechanism and the activation of P1- and P4-purinergic receptors.AP4A also afforded protection from toxicity induced by unilateral medial forebrain bundle injection of 6-hydroxydopamine (6-OHDA). One month after lesioning, vehicle-treated rats exhibited amphetamine-induced rotation. Minimal tyrosine hydroxylase immunoreactivity was detected in the lesioned nigra or striatum. No KCl-induced dopamine release was found in the lesioned striatum. All of these indices of dopaminergic degeneration were attenuated by pretreatment with AP4A. In addition, AP4A reduced TUNEL in the lesioned nigra 2 d after 6-OHDA administration. Collectively, our data suggest that AP4A is protective against neuronal injuries induced by ischemia or 6-OHDA through the inhibition of apoptosis. We propose that AP4A may be a potentially useful target molecule in the therapy of stroke and Parkinson's disease.
Cell-Type-Specific Contributions of Medial Prefrontal Neurons to Flexible Behaviors
Authors: Nakayama Hirofumi , Ibañez-Tallon Ines , Heintz Nathaniel 
Published: April 2018

Behavioral flexibility and impulse control are necessary for successful execution of adaptive behavior. They are impaired in patients with damage to the prefrontal cortex (PFC) and in some clinically important conditions, such as obsessive-compulsive disorder. Although the medial prefrontal cortex (mPFC) has been investigated as a critical structure for behavioral flexibility and impulse control, the contribution of the underlying pyramidal neuron cell types in the mPFC remained to be understood. Here we show that interneuron-mediated local inactivation of pyramidal neurons in the mPFC of male and female mice induces both premature responses and choice bias, and establish that these impulsive and compulsive responses are modulated independently. Cell-type-specific photoinhibition of pyramidal deep layer corticostriatal or corticothalamic neurons reduces behavioral flexibility without inducing premature responses. Together, our data confirm the role of corticostriatal neurons in behavioral flexibility and demonstrate that flexible behaviors are also modulated by direct projections from deep layer corticothalamic neurons in the mPFC to midline thalamic nuclei.SIGNIFICANCE STATEMENTBehavioral flexibility and impulse control are indispensable for animals to adapt to changes in the environment and often affected in patients with PFC damage and obsessive-compulsive disorder. We used a probabilistic reversal task to dissect the underlying neural circuitry in the mPFC. Through characterization of the three major pyramidal cell types in the mPFC with optogenetic silencing, we demonstrated that corticostriatal and corticothalamic but not corticocortical pyramidal neurons are temporally recruited for behavioral flexibility. Together, our findings confirm the role of corticostriatal projections in cognitive flexibility and identify corticothalamic neurons as equally important for behavioral flexibility.
Growth trajectory and pubertal tempo from birth till final height in a girl with Wolf-Hirschhorn syndrome
Authors: Siew Jia Xuan , Yap Fabian 
Published: April 2018

SummaryGrowth anomaly is a prominent feature in Wolf-Hirschhorn syndrome (WHS), a rare congenital disorder caused by variable deletion of chromosome 4p. While growth charts have been developed for WHS patients 0–4 years of age and growth data available for Japanese WHS patients 0–17 years, information on pubertal growth and final height among WHS children remain lacking. Growth hormone (GH) therapy has been reported in two GH-sufficient children with WHS, allowing for pre-puberty catch up growth; however, pubertal growth and final height information was also unavailable. We describe the complete growth journey of a GH-sufficient girl with WHS from birth until final height (FH), in relation to her mid parental height (MPH) and target range (TR). Her growth trajectory and pubertal changes during childhood, when she was treated with growth hormone (GH) from 3 years 8 months old till 6 months post-menarche at age 11 years was fully detailed.Learning points:Pubertal growth characteristics and FH information in WHS is lacking.While pre-pubertal growth may be improved by GH, GH therapy may not translate to improvement in FH in WHS patients.Longitudinal growth, puberty and FH data of more WHS patients may improve the understanding of growth in its various phases (infancy/childhood/puberty).
AŞAMALI ÇÜRÜK TEDAVİSİ
Authors: OZ Fatma Dilsad , GÖKALP Saadet 
Published: April 2018

Günümüzde diş dokusunun
sağlıklı olarak kalmasında pulpanın önemi daha iyi anlaşıldıkça, diş hekimleri
çürük temizlenmesi sırasında pulpa ekspoz olsa bile pulpanın canlılığının
korunması için daha çok çaba sarf etmeye başlamışlardır. Çünkü pulpasız dişlerde
dişin kırılması gibi kritik komplikasyonlar ortaya çıkabilmektedir. Diş
hekimliği uygulamalarında diş hekimleri, eğer çürük tamamen uzaklaştırılacaksa
pulpa ekspozu ile sonuçlanabilecek derin çürüklerle çok sık karşılaşırlar.
Pulpanın doğal rejenerasyon yeteneğinin çok yüksek olduğu araştırmacılar
tarafından gözlenmektedir. Direk pulpa kaplaması tipik olarak pulpanın
korunması için uygulanır. Bununla birlikte çürük kaldırılmasına bağlı olarak
ekspoz olan pulpaya direk pulpa kaplaması uygulamasına alternatif olarak çürük
dokunun tamamı kaldırılmadan ilk randevude yumuşak dentinin sadece bir kısmı
kaldırılarak kavite geçici restore
edilir ve bir süre sonra tekrar açılır. İleri ekskavasyon bu randevuda yapılır
ve kavite kalıcı olarak restore edilir. Bu uygulamanın amacı lezyonun
ilerlemesini durdurmaktır ve pulpal ekspoz olmadan tersiyer dentin oluşumuna
izin vermektir. Bu tedavi yöntemi ile ilgili literatürde bulunan pek çok
çalışma incelenerek tedavinin prognozu hakkında bilgi edinilmiştir.
Das grundlegend reformierte Wertpapierhandelsgesetz – Umsetzung von MiFID II (Conduct of Business im Kundenverhältnis)
Authors: Grundmann Stefan 
Published: April 2018

Zusammenfassung
Das Wertpapierhandelsgesetz (WpHG) erlebt mit dem 2. Finanzmarktnovellierungsgesetz zum Jahresbeginn 2018 die wohl grundlegendste Reform seiner gut zwanzigjährigen Geschichte – insbesondere, wenn man die noch während des Umsetzungszeitraums stattgefundene Auslagerung des gesamten Rechts der Marktintegrität und Ad-hoc-Publizität hinzudenkt. Deutlicher Ausdruck von alldem ist die umfassende neue Nummerierung des Gesetzes, von der auch im Folgenden ausgegangen wird. Inhaltlich zielt die Novelle vor allem auf ein noch tieferes Eingehen auf die individuellen Verhältnisse des jeweiligen Anlegers (mit dem sog. Zielmarktkonzept) und auf eine noch intensivere Ausräumung von bzw. Warnung vor Interessenkonflikten (im Vergütungsregime, in Alternativmodellen der Beratung, in Warnung durch Aufklärung). Das prägende Umfeld bleibt europäisch, mit MiFID II und MiFIR als den Rechtsakten nochmals vertieft und noch stärker primäre Richtschnur bei der Anwendung.
Kartellrechtlicher Schutz von Lieferanten vor Nachfragemacht
Authors: Latzel Clemens 
Published: April 2018

Zusammenfassung
Nicht nur Anbieter, sondern auch Nachfrager von Waren oder Dienstleistungen können sehr marktmächtig werden. Sie können dann von ihren Lieferanten niedrigere Preise, unentgeltliche Zusatzleistungen oder gar eine bestimmte Unternehmenspolitik verlangen. Wann überschreiten „harte Verhandlungen“ und „wohlwollende Einflussnahmen“ die Grenzen der unternehmerischen Freiheit, wie sie Art. 102 AEUV und §§ 18 ff. GWB (i. d. F. der am 9. 6. 2017 in Kraft getretenen 9. GWB-Novelle) nachfragemächtigen Unternehmen ziehen?
Occurrence of the non-indigenous brittle star Ophiothela cf. mirabilis Verrill, 1867 (Echinodermata, Ophiuroidea) in natural and anthropogenic habitats off Santa Catarina, Brazil
Authors: Lawley Jonathan W. , Fonseca Adriana Carvalhal , Júnior Edson Faria , Lindner Alberto 
Published: April 2018

The brittle star Ophiothela mirabilis, thought to be confined to Pacific waters, was first observed in the Atlantic in 2000. Since then, it has expanded its range north to Trinidad and Tobago and south to Paraná, Brazil. By monitoring the coast of Santa Catarina, Brazil, with both recruitment plates in harbors and SCUBA diving, we were able to observe specimens of Ophiothela mirabilis in both natural and anthropogenic habitats. This presents a range extension of ~80 km south and emphasizes the importance of anthropogenic means for their spread and establishment.
STRATEGI PENGEMBANGAN PARIWISATA BERBASIS SUMBER DAYA ALAM PESISIR DAN LAUT DI PANTAI DEPOK DAERAH ISTIMEWA YOGYAKARTA
Authors: Setyaningrum Agustina , Setyorini Heny Budi , Masduqi Edy 
Published: April 2018

Kawasan pariwisata Pantai Depok dewasa ini mulai dikenal luas oleh masyarakat. Selama ini tempat wisata ini dikenal dengan wisata kulinernya. Sumber daya alam pesisir dan laut yang ada di Pantai Depok beragam baik itu sumber daya hayati maupun sumber daya non hayati. Tujuan dari penelitian ini adalah untuk merumuskan strategi pengembangan pariwisata berbasis sumber daya alam pesisir dan laut di Pantai Depok. Data yang digunakan dalam penelitian ini meliputi data primer dan data sekunder. Teknik Rapid Rural Apraisal digunakan dalam penelitian ini. Keberagaman sumber daya alam pesisir dan laut dapat menjadi salah satu daya tarik wisata baru di Pantai Depok. Salah satunya adalah dengan pengolahan produk hasil kelautan. Produk tersebut perlu dimaksimalkan agar produk tersebut memiliki nilai tambah dan nilai jual yang tinggi. Pengolahan produk hasil kelautan ini dapat dijadikan sebagai produk unggulan baru yang mendukung kegiatan pariwisata di Pantai Depok.Title: Develompment Strategy of Tourism Activity Base on Coastal and Marine Resources in Depok Beach, Daerah Istimewa YogyakartaDepok Beach tourism area today is becoming widely known by the public. This tourist spot known as culinary tour. The coastal and marine natural resources in Depok Beach are both biological and nonbiological resources. The purpose of this research is to formulate coastal and marine natural resourcebased tourism development strategy in Depok Beach. Data used in this research include primary data and secondary data. Rapid Rural Apraisal techniques were used in this study. The diversity of coastal and marine natural resources can be one of the new tourist attraction in Depok Beach. One of them is the processing of marine products. The product needs to be maximized so that the product has added value and high selling value. Processing of marine products can be used as a new flagship product that supports tourism activities in Depok Beach..
İkinci El Otomobil Talep Fiyatının Regresyon Analizi: TR83 Bölgesi Örneği
Authors: YAYAR Rüştü , YILMAZ Erkan 
Published: April 2018

Yeni ve ikinci el araçlardan oluşan otomotiv piyasası
ekonomide önemli bir yere sahiptir. İkinci el otomobil piyasasında fiyatı
etkileyen birçok etken vardır. Bu çalışmada otomobil talep fiyatını etkileyen
unsurlar ortaya konmuştur. Çalışma TR83 Bölgesi’nde yer alan kent merkezlerini
kapsamaktadır. Veriler Şubat-Nisan 2015 döneminde ikinci el araç satışı yapan
firmalardan elde edilmiştir. Çalışmada yarı logaritmik regresyon modeli
kullanılmıştır. Otomobil markasının
Mercedes olması fiyatı artıran en önemli unsur iken, markanın Hyundai olması
fiyatı azaltan en önemli unsur olarak bulunmuştur.
A RESPONSABILIDADE CIVIL E CRIMINAL NOS CRIMES VIRTUAIS
Authors: Martins Jilia Diane , Rech Francieli 
Published: April 2018

Esta pesquisa visa analisar a forma de responsabilização cível e criminal dos atos atentatórios à honra ocorridos na internet, sob o enfoque da eficácia da tutela de direitos e garantias fundamentais. Observa-se que, dentre os diversos direitos e garantias assegurados
aos cidadãos, estão a inviolabilidade da honra e a liberdade de expressão, de forma que a primeira é limitadora da segunda. O ordenamento jurídico brasileiro, em virtude de tal limitação, prescreve condutas criminais que violam a honra, objetiva e subjetiva, ainda que estas tenham sido cometidas na internet. A responsabilidade, conforme a lei penal, recai sobre quem pratica a conduta, podendo o provedor ser responsabilizado se recusar ceder informações. Na esfera cível, a responsabilidade do provedor é objetiva, em razão do risco da atividade, conforme o código do consumidor.
GOVERNANÇA DE TI: ANÁLISE DAS CONTRIBUIÇÕES DE MECANISMOS PRIVADOS NO GERENCIAMENTO PÚBLICO DE TI
Authors: Filho José Walter Santos 
Published: April 2018

O presente estudo, de natureza teórica, tem como objetivo analisar as contribuições dos mecanismos privados de governança de TI no gerenciamento público de TI, diante do contexto atual que demanda
por eficiência, transparência, ética, prestação de contas e responsabilidade. Dentro deste propósito, construiu-se uma revisão teórica sustentada nos pilares e princípios das boas práticas de governança de corporativa e governança pública identificados na literatura nacional e internacional sobre Governança de TI. Os resultados mostram que mecanismos como os aplicados no Código de Governança KING III, parâmetros administrativos baseados na Teoria da Agência, nos mecanismos da norma ISO 38500/2015 e frameworks para Governança de TI têm sido aplicados com sucesso e obtenção de bons, mas o Brasil ainda necessita avançar bastante na utilização dos mecanismos privados.
Children with Standard Risk Acute Lymphoblastic Leukemia in Induction And Consolidation Phase
Authors: Amarullah Adinugraha , Hasmono Didik , Ugrasena IGD , Yulistiani Yulistiani 
Published: April 2018

Prednisone has an important role in the therapy of patient with standard risk ALL. Patients with standard risk ALL receiving high dose prednisone as therapy and supraphysiology dose of prednisone are expected to cause suppression in HPA-axis (Hypothalamic Pituitary Adrenal axis). This suppression could reduce immune system in children with ALL and increase infection risk because reduction of cortisol level. In Indonesia, we did not find study about the incident of adrenal suppression after high dose prednisone therapy, especially in induction to consolidation phase ALL patient. The aim of this study was to analyze adrenal suppression after high dose prednisone therapy on children with standard risk acute lymphoblastic leukemia in induction and consolidation phase. This study has received a certificate of Ethical Clearance No. 588/Panke.KKE/X/2016, a longitudinal observational, prospective, non-randomized trial involving children with ALL who received prednisone for 49 days during the induction phase. We collected and compared laboratory result of cortisol level in children with ALL and received prednisone therapy during induction to consolidation phase. Sample was taken at week 0,4,5,6,7,8,10,12 in the course of ALL chemotheraphy Indonesian protocol year 2013. Serum was examined using methods CLIA ADVIA Centaur® XP. Between June 2016 – January 2017, 13 patients (8 males, 5 females) were included in this study. Decrease of cortisol level after prednisone therapy occured in week-10 as much as 53% compared with week-0 (p=0.027). Cortisol level increased 64% of week-12 compared with week-10 (p=0.003). In conclusion, high dose prednisone is not significant to causing adrenal suppression in induction phase of ALL patients, and the reducing cortisol level is reversible.
Diagnosis and management of vaginal dryness in menopause
Authors: Baziad Ali 
Published: April 2018

Objective: To review the diagnosis and management of vaginal dryness in menopausal womenMethods: Literature reviewResults: Lack of estrogen negatively impacts the vagina and the urinary tract. The vagina becomes dry (atrophic) and then causing pain during sexual intercourse. Vaginal atrophy can be diagnosed in the form of vaginal dryness (75%), painful sexual intercourse (38%), itching and discharge complaints. Sometimes the patient complained pain in urinating, frequent night urination, in-continence and recurrent urinary tract infections. Mucose of the cervix, vagina and vulva are thin. Vagina can bleed easi-ly. Diagnosis can also be made by measuring the pH of the vagina by using litmus paper and vaginal cytology. The management involves administration of local estrogen treatment using weak estrogen (E3) in the form of a cream. E3 cream does not need to be combined with progestogen. Other type of local hormonal therapy (TH) is DHEA cream. Giving a strong estrogen (E2) or equin estrogen should always be combined with progestogen to prevent endometrium hyperplasia, either administered locally or systemically. E3 cream is also safe in women with breast cancer who experienced vaginal atrophy.Conclusion: Lack of estrogen causes vaginal atrophy with symptoms of vaginal dryness. Vaginal atrophy also causes urinary problems. Diagnosis is based on symptoms, examination of vaginal pH and vaginal cytology. The management is by adminis-tering HT with estrogen. E3 creams is the most effective in relieving complaints caused by vaginal dryness and complaints caused by the bladder.