bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABAergic inhibition through synergistic astrocytic neuronal interaction transiently decreases vasopressin neuronal activity during hypoosmotic challenge
Authors: Wang Yu‐Feng , Sun Min‐Yu , Hou Qiuling , Hamilton Kathryn A. 
Published: February 2013

AbstractThe neuropeptide vasopressin is crucial to mammalian osmotic regulation. Local hypoosmotic challenge transiently decreases and then increases vasopressin secretion. To investigate mechanisms underlying this transient response, we examined the effects of hypoosmotic challenge on the electrical activity of rat hypothalamic supraoptic nucleus (SON) vasopressin neurons using patch‐clamp recordings. We found that 5 min exposure of hypothalamic slices to hypoosmotic solution transiently increased inhibitory postsynaptic current (IPSC) frequency and reduced the firing rate of vasopressin neurons. Recovery occurred by 10 min of exposure, even though the osmolality remained low. The γ‐aminobutyric acid (GABA)A receptor blocker, gabazine, blocked the IPSCs and the hypoosmotic suppression of firing. The gliotoxin l‐aminoadipic acid blocked the increase in IPSC frequency at 5 min and the recovery of firing at 10 min, indicating astrocytic involvement in hypoosmotic modulation of vasopressin neuronal activity. Moreover, β‐alanine, an osmolyte of astrocytes and GABA transporter (GAT) inhibitor, blocked the increase in IPSC frequency at 5 min of hypoosmotic challenge. Confocal microscopy of immunostained SON sections revealed that astrocytes and magnocellular neurons both showed positive staining of vesicular GATs (VGAT). Hypoosmotic stimulation in vivo reduced the number of VGAT‐expressing neurons, and increased co‐localisation and molecular association of VGAT with glial fibrillary acidic protein that increased significantly by 10 min. By 30 min, neuronal VGAT labelling was partially restored, and astrocytic VGAT was relocated to the ventral portion while it decreased in the somatic zone of the SON. Thus, synergistic astrocytic and neuronal GABAergic inhibition could ensure that vasopressin neuron firing is only transiently suppressed under hypoosmotic conditions.
Effects of antidepressant treatment on mice lacking brain‐derived neurotrophic factor expression through promoter IV
Authors: Sakata Kazuko , Mastin Joshua R. , Duke Sean M. , Vail Meghan G. , Overacre Abigail E. , Dong Brittany E. , Jha Shanker 
Published: February 2013

AbstractBrain‐derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depression; mice lacking BDNF expression through promoter IV (BDNF‐KIV) exhibit a depression‐like phenotype. We tested our hypothesis that deficits caused by promoter IV deficiency (depression‐like behavior, decreased levels of BDNF, and neurogenesis in the hippocampus) could be rescued by a 3‐week treatment with different types of antidepressants: fluoxetine, phenelzine, duloxetine, or imipramine. Each antidepressant reduced immobility time in the tail suspension test without affecting locomotor activity in the open field test in both BDNF‐KIV and control wild type mice, except that phenelzine increased locomotor activity in wild type mice and anxiety‐like behavior in BDNF‐KIV mice. The antidepressant treatments were insufficient to reverse decreased BDNF levels caused by promoter IV deficiency. No antidepressant treatment increased the hippocampal progenitors of either genotype, whereas phenelzine decreased the surviving progenitors in both genotypes. The antidepressant treatments differently affected the dendritic extension of hippocampal immature neurons: fluoxetine and imipramine increased extension in both genotypes, duloxetine increased it only in BDNF‐KIV mice, and phenelzine decreased it only in wild type mice. Interestingly, a saline‐only injection increased neurogenesis and dendrite extensions in both genotypes. Our results indicate that the behavioral effects in the tail suspension test by antidepressants do not require promoter IV‐driven BDNF expression and occur without a detectable increase in hippocampal BDNF levels and neurogenesis but may involve increased dendritic reorganisation of immature neurons. In conclusion, the antidepressant treatment demonstrated limited efficacy; it partially reversed the defective phenotypes caused by promoter IV deficiency but not hippocampal BDNF levels.
Glyoxalase 1 and its substrate methylglyoxal are novel regulators of seizure susceptibility
Authors: Distler Margaret G. , Gorfinkle Naomi , Papale Ligia A. , Wuenschell Gerald E. , Termini John , Escayg Andrew , Winawer Melodie R. , Palmer Abraham A. 
Published: February 2013

SummaryPurposeEpilepsy is a complex disease characterized by a predisposition toward seizures. There are numerous barriers to the successful treatment of epilepsy. For instance, current antiepileptic drugs have adverse side effects and variable efficacies. Furthermore, the pathophysiologic basis of epilepsy remains largely elusive. Therefore, investigating novel genes and biologic processes underlying epilepsy may provide valuable insight and enable the development of new therapeutic agents. We previously identified methylglyoxal (MG) as an endogenous γ‐aminobutyric acid (GABAA) receptor agonist. Here, we investigated the role of MG and its catabolic enzyme, glyoxalase 1 (GLO1), in seizures.MethodsWe pretreated mice with MG before seizure induction with picrotoxin or pilocarpine and then assessed seizures behaviorally or by electroencephalography (EEG). We then investigated the role of GLO1 in seizures by treating mice with a pharmacologic inhibitor of GLO1 before seizure induction with pilocarpine and measured subsequent seizure phenotypes. Next, we explored the genetic relationship between Glo1 expression and seizures. We analyzed seizure phenotypes among C57BL/6J × DBA/2J (BXD) recombinant inbred (RI) mice with differential Glo1 expression. Lastly, we investigated a causal role for Glo1 in seizures by administering pilocarpine to transgenic (Tg) mice that overexpress Glo1.Key FindingsPretreatment with MG attenuated pharmacologically‐induced seizures at both the behavioral and EEG levels. GLO1 inhibition, which increases MG concentration in vivo, also attenuated seizures. Among BXD RI mice, high Glo1 expression was correlated with increased seizure susceptibility. Tg mice overexpressing Glo1 displayed reduced MG concentration in the brain and increased seizure severity.SignificanceThese data identify MG as an endogenous regulator of seizures. Similarly, inhibition of GLO1 attenuates seizures, suggesting that this may be a novel therapeutic approach for epilepsy. Furthermore, this system may represent an endogenous negative feedback loop whereby high metabolic activity increases inhibitory tone via local accumulation of MG. Finally, Glo1 may contribute to the genetic architecture of epilepsy, as Glo1 expression regulates both MG concentration and seizure severity.
Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers
Authors: Weckhuysen Sarah , Holmgren Philip , Hendrickx Rik , Jansen Anna C. , Hasaerts Daniele , Dielman Charlotte , de Bellescize Julitta , Boutry‐Kryza Nadia , Lesca Gaetan , Spiczak Sarah Von , Helbig Ingo , Gill Deepak , Yendle Simone , Møller Rikke S. , Klitten Laura , Korff Christian , Godfraind Catherine , Van Rijckevorsel Kenou , De Jonghe Peter , Hjalgrim Helle , Scheffer Ingrid E. , Suls Arvid 
Published: February 2013

SummaryMutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated. Therefore, we screened a cohort of 160 patients with an unexplained EE, including patients with early myoclonic encephalopathy (EME), Ohtahara syndrome, West syndrome, nonsyndromic EE with onset in the first year, and Lennox‐Gastaut syndrome (LGS). We found six de novo mutations in six patients presenting as Ohtahara syndrome (2/6, 33%), West syndrome (1/65, 2%), and nonsyndromic early onset EE (3/64, 5%). No mutations were found in LGS or EME. Only two of four mutation carriers with neonatal seizures had Ohtahara syndrome. Epileptic spasms were present in five of six patients. One patient with normal magnetic resonance imaging (MRI) but focal seizures underwent epilepsy surgery and seizure frequency dropped drastically. Neuropathology showed a focal cortical dysplasia type 1a. There is a need for additional neuropathologic studies to explore whether STXBP1 mutations can lead to structural brain abnormalities.
Risk factors for hyperammonemia in pediatric patients with epilepsy
Authors: Yamamoto Yoshiaki , Takahashi Yukitoshi , Imai Katsumi , Mishima Nobuyuki , Yazawa Rei , Inoue Kazuyuki , Itoh Kunihiko , Kagawa Yoshiyuki , Inoue Yushi 
Published: February 2013

SummaryPurposeTo identify risk factors for hyperammonemia in pediatric patients with epilepsy.MethodsA total of 2,944 pediatric patients (ages 0–15 years) were classified into the following three groups: a group without drug treatment (n = 445, group I), a group receiving antiepileptic drugs other than valproic acid (VPA) (n = 673, group II), and a VPA‐treated group (n = 1,826, group III). Hyperammonemia was defined as a plasma ammonia level exceeding 100 μg/dl with reference to the standard range and previous reports.Key FindingsThe mean ammonia level of groups I, II, and III was 36.0, 56.0, and 86.8 μg/dl, respectively, and the incidence of hyperammonemia was 1.6%, 7.7%, and 31.7%, respectively. In each group, the mean ammonia level of patients aged 3 years or younger was significantly higher than that of patients aged 4–15 years. In group II, concomitant use of topiramate and zonisamide were risk factors for hyperammonemia (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI] 1.7–9.2, and OR 3.5, 95% CI 1.9–6.5, respectively). In group III, the ammonia level increased in a VPA dose–dependent manner. At a VPA dose of 30 mg/kg, there was 4.3‐fold increase in the incidence of hyperammonemia. The other significant risk factors identified were female gender (OR 1.3, 95% CI 1.0–1.6), symptomatic generalized epilepsy (OR 1.4, 95% CI 1.1–1.8), and the concomitant use of phenytoin (OR 4.7, 95% CI 3.3–6.9), phenobarbital (OR 2.2. 95% CI 1.6–3.2), acetazolamide (OR 6.6, 95% CI 2.5–17.2), topiramate, or zonisamide.SignificanceA young age and concomitant use of carbonic anhydrase inhibitors are associated with an increased risk of hyperammonemia regardless of whether the patient is taking VPA. In patients receiving VPA, concomitant use of phenytoin and/or phenobarbital enhances the risk of hyperammonemia. An increase in ammonia can be caused by multiple factors. Our results may help clinicians to avoid problems of hyperammonemia.
Non‐invasive diffuse reflectance measurements of cutaneous melanin content can predict human sensitivity to ultraviolet radiation
Authors: Coelho Sergio G. , Zmudzka Barbara Z. , Yin Lanlan , Miller Sharon A. , Yamaguchi Yuji , Tadokoro Taketsugu , Hearing Vincent J. , Beer Janusz Z. 
Published: February 2013

AbstractThe diversity of human skin phenotypes and the ubiquitous exposure to ultraviolet radiation (UVR) underscore the need for a non‐invasive tool to predict an individual's UVR sensitivity. We analysed correlations between UVR sensitivity, melanin content, diffuse reflectance spectroscopy (DR) and UVR‐induced DNA damage in the skin of subjects from three racial/ethnic groups: Asian, Black or African American and White. UVR sensitivity was determined by evaluating each subject's response to one minimal erythemal dose (MED) of UVR one day after the exposure. Melanin content was measured using DR and by densitometric analysis of Fontana‐Masson staining (FM) in skin biopsies taken from unexposed areas. An individual's UVR sensitivity based on MED was highly correlated with melanin content measured by DR and by FM. Therefore, a predictive model for the non‐invasive determination of UVR sensitivity using DR was developed. The MED precision was further improved when we took race/ethnicity into consideration. The use of DR serves as a tool for predicting UVR sensitivity in humans that should be invaluable for determining appropriate UVR doses for therapeutic, diagnostic and/or cosmetic devices.
Assessing the food web impacts of an anadromousArctic charr introduction to a sub‐Arctic watershed using stable isotopes
Authors: Murdoch A. , Klein G. , Doidge D. W. , Power M. 
Published: February 2013

AbstractAnadromousArctic charr,Salvelinus alpinus(L.), was introduced to a sub‐Arctic river–lake system near the village ofKujjuuaq,Nunavik, and the stable isotope values and diets of key resident fish species were used to assess changes in feeding patterns. Stable isotope values for most species did not differ significantly between the pre‐ and post‐introduction periods, with observed shifts being within the bounds of expected natural variation. Lake chub,Couesius plumbeus(Agassiz), were the single species to show a difference between study periods, with a small but significant increase in δ15N. No significant post‐introduction changes were seen in lake trout,Salvelinus namaycush(Walbaum), omnivory or in any of the assessed quantitative food web metrics. Gut contents of major fish species similarly showed significant temporal overlap between the pre‐ and post‐introduction periods, and there was no significant change in species' weight–length relationships. The minor ecological impact was interpreted in relation to the availability of open niches exploitable by ecological generalists such asArctic charr. The explanation accords with the known habitat and feeding flexibility ofArctic charr and the ecological immaturity of sub‐Arctic lakes known to have driven adaptive variation amongArctic charr. Findings suggest that anadromousArctic charr may be introduced at moderate densities to other sub‐Arctic watersheds without major negative food web consequences for other resident fish species.
Transgenerational marking of brown trout Salmo trutta f.f., using an 84Sr spike
Authors: Zitek A. , Irrgeher J. , Kletzl M. , Weismann T. , Prohaska T. 
Published: February 2013

AbstractThe maternal transmission of a naturally occurring and non‐toxic minor isotope of strontium (84Sr) to the central otolith region of the progeny of a typical European freshwater fish species, brown trout, Salmo trutta f.f. L. was accomplished. The focus was to apply minimum doses of a non‐toxic solution at physiological salt concentration to minimise potential adverse effects on the fish. Female spawners were intraperitoneally injected with doses of 12.5 and 30.2 μg 84Sr kg−1 fish. Eggs were stripped and the resulting progeny were reared in a hatchery for about 1 year before sampling the otoliths. Strontium isotope ratios in the otoliths of the offspring were measured by cross‐sectional line scans using laser ablation‐multiple collector‐inductively coupled plasma mass spectrometry (LA‐MC‐ICPMS). Otolith cores of marked juveniles showed a significantly elevated 84Sr/86Sr ratio compared with control fish and to otolith regions created after hatching. Mass marking of cohorts of progeny from individually spiked brown trout with Sr isotopes is therefore possible for dispersal and migration studies without the necessity of handling eggs and applying other larval marking methods like immersion.
Association Between Helicobacter pylori Infection Detected by the 13C‐Urea Breath Test and Low Serum Ferritin Levels among Japanese Adults
Authors: Nakagawa Hiroko , Tamura Takashi , Mitsuda Yoko , Kurata Mio , Goto Yasuyuki , Kamiya Yoshikazu , Kondo Takaaki , Hamajima Nobuyuki 
Published: February 2013

AbstractBackgroundHelicobacter pylori infection is a major risk factor for chronic gastritis, digestive ulcers, and gastric cancer. Previous studies have shown associations between H. pylori infection and decreased iron storage. Therefore, this study aimed to examine the associations between H. pylori infection and serum iron and ferritin levels in Japan.Materials and MethodsOverall, 268 Japanese individuals who visited a clinic located in an urban area for H. pylori infection tests and subsequent eradication were enrolled. H. pylori infection was diagnosed by a 13C‐urea breath test, with positive results defined as values ≥2.5‰.ResultsThe overall infection rate was 65.3% (175/268). The geometric mean serum iron levels in uninfected and infected subjects were 115.7 μg/dL and 108.9 μg/dL, respectively, in men, and 83.9 and 91.8 μg/dL, respectively, in women. The geometric mean serum ferritin levels were 128.9 and 81.0 ng/mL, respectively, in men, and 25.5 and 27.0 ng/mL, respectively, in women. Regression analysis adjusted for age showed that lower geometric mean serum ferritin levels were significantly associated with H. pylori infection in men (131.8 vs 79.4 ng/mL p = .009) and in women (33.9 vs 23.4 ng/mL p = .041). The difference was greater in subjects ≥50 years old, although the interaction was not statistically significant. Helicobacter pylori infection was not significantly associated with serum iron levels.ConclusionThis study showed that H. pylori infection was significantly associated with altered serum ferritin levels in Japanese individuals, particularly in those aged ≥50 years.
Adolescent Resilience in Northern Uganda: The Role of Social Support and Prosocial Behavior in Reducing Mental Health Problems
Authors: Haroz Emily E. , Murray Laura K. , Bolton Paul , Betancourt Theresa , Bass Judith K. 
Published: February 2013

We investigated relations between prosocial behavior, perceived social support, and improvement in depression and anxiety symptoms over 6 months among 102 Acholi adolescent (14–17 years, 58% female adolescents) survivors of war and displacement in Northern Uganda. Adolescents were assessed using a locally developed screener. Regression analyses measured the association between resilience factors and mental health outcomes. Findings indicated that high levels of baseline prosocial behaviors were associated with improvement in anxiety symptoms among adolescents with high symptom improvement. This same trend was seen for depression symptoms (p = .06). Experiencing caregiver loss modified this association for depression symptoms. Baseline social support was not associated with improvement in depression or anxiety. Results suggest that prosocial behavior is associated with increased resilience.
Gender‐Typed Behaviors in Friendships and Well‐Being: A Cross‐Cultural Study of Chinese and American Boys
Authors: Gupta Taveeshi , Way Niobe , McGill Rebecca K. , Hughes Diane , Santos Carlos , Jia Yueming , Yoshikawa Hirokazu , Chen Xinyin , Deng Huihua 
Published: February 2013

This 3‐year, longitudinal analysis examined the psychological and social correlates of adhering to gender‐typed behaviors in friendships among boys during middle school in United States (N = 446, Mage = 11.37 years) and in China (N = 368, Mage = 12.20 years). Results indicated that boys did not differ by nationality in the mean levels or in the increase over time in adherence to gender‐typed behaviors. Furthermore, adherence over time was associated with higher depressive symptoms, lower self‐esteem, and lower friendship quality for boys in both countries. However, the associations between gender‐typed behaviors and friendship quality and depressive symptoms were stronger for boys in the United States. Our study suggests that gender‐typed behaviors play an important role in the well‐being of youth in different parts of the world.
Depressive Symptoms and Somatic Complaints Among Zambian Adolescents: Associations With Stress and Coping
Authors: Neese Angela L. , Pittman Laura D. , Hunemorder Rebecca 
Published: February 2013

This study explored the possible links between perceived stress, coping strategies, depression, and somatic complaints, which have often been supported in other populations, in a school‐based sample of Zambian adolescents ages 11–19 years (N = 230; 60% males). Zambian adolescents reported elevated levels of depressive symptoms and somatic complaints, suggesting a need to study this population further. Like previous studies, perceived stress was found to be positively associated with both depressive symptoms and somatic complaints. Unexpectedly, coping was found to be positively associated with depressive symptoms, perhaps because of the cross‐sectional nature of the design. The possible influence of culture on the findings (e.g., construct validity, difference in how coping functions adaptively) is discussed.
Does the Threat of Insurer Liability for “Bad Faith” Affect Insurance Settlements?
Authors: Asmat Danial P. , Tennyson Sharon 
Published: February 2013

AbstractEconomic reasoning predicts that policyholders in states that treat for insurer bad faith in settling claims as a tort should receive higher payments from insurers because of the greater potential damages insurers face in claims disputed in court. We test this hypothesis using data on automobile insurance claims for accidents occurring during 1972–1997, exploiting differences in states “laws and variation in timing of states” adoption of bad faith rules to identify the effects of tort liability. We find that the presence of tort liability for insurer bad faith increases settlement amounts and reduces the likelihood that a claim is underpaid.
The Impact of Private Equity on a Life Insurer's Capital Charges Under Solvency II and the Swiss Solvency Test
Authors: Braun Alexander , Schmeiser Hato , Siegel Caroline 
Published: February 2013

AbstractIn this article, we conduct an in‐depth analysis of the impact of private equity investments on the capital requirements faced by a representative life insurance company under Solvency II as well as the Swiss Solvency Test. Our discussion begins with an empirical performance measurement of the asset class over the period from 2001 to 2010, suggesting that limited partnership private equity funds may be suited for the purpose of portfolio enhancement. Subsequently, we review the market risk standard approaches set out by both regulatory regimes and outline a potential framework for an internal model. Based on an implementation of these solvency models, it is possible to demonstrate that private equity is overly penalized by the standard approaches. Hence, life insurers aiming to exploit the asset class's return potential may expect significantly lower capital charges when applying an economically sound internal model. Finally, we show that, from a regulatory capital perspective, it can even be less costly to increase the exposure to private rather than public equity.