bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allosteric Modulation of Sigma‐1 Receptors Elicits Rapid Antidepressant Activity
Authors: Wang Yun , Guo Lin , Jiang Hua‐Feng , Zheng Long‐Tai , Zhang Ao , Zhen Xue‐Chu 
Published: February 2016

SummaryAimsSigma‐1 receptors are involved in the pathophysiological process of several neuropsychiatric diseases such as epilepsy, depression. Allosteric modulation represents an important mechanism for receptor functional regulation. In this study, we examined antidepressant activity of the latest identified novel and selective allosteric modulator of sigma‐1 receptor 3‐methyl‐phenyl‐2, 3, 4, 5‐tetrahydro‐1H‐benzo[d]azepin‐7‐ol (SOMCL‐668).Methods and ResultsA single administration of SOMCL‐668 decreased the immobility time in the forced swimming test (FST) and tailing suspended test in mice, which were abolished by pretreatment of sigma‐1 receptor antagonist BD1047. In the chronic unpredicted mild stress (CUMS) model, chronic application of SOMCL‐668 rapidly ameliorated anhedonia‐like behavior (within a week), accompanying with the enhanced expression of brain‐derived neurotrophic factor (BDNF) and phosphorylation of glycogen synthase kinase 3β (GSK3β) (Ser‐9) in the hippocampus. SOMCL‐668 also rapidly promoted the phosphorylation of GSK3β (Ser‐9) in an allosteric manner in vitro. In the cultured primary neurons, SOMCL‐668 enhanced the sigma‐1 receptor agonist‐induced neurite outgrowth and the secretion of BDNF.ConclusionSOMCL‐668, a novel allosteric modulator of sigma‐1 receptors, elicits a potent and rapid acting antidepressant effect. The present data provide the first evidence that allosteric modulation of sigma‐1 receptors may represent a new approach for antidepressant drug discovery.
Rabbit biocontrol and landscape‐scale recovery of threatened desert mammals
Authors: Pedler Reece D. , Brandle Robert , Read John L. , Southgate Richard , Bird Peter , Moseby Katherine E. 
Published: February 2016

AbstractFunding for species conservation is insufficient to meet the current challenges facing global biodiversity, yet many programs use expensive single‐species recovery actions and neglect broader management that addresses threatening processes. Arid Australia has the world's worst modern mammalian extinction record, largely attributable to competition from introduced herbivores, particularly European rabbits (Oryctolagus cuniculus) and predation by feral cats (Felis catus) and foxes (Vulpes vulpes). The biological control agent rabbit hemorrhagic disease virus (RHDV) was introduced to Australia in 1995 and resulted in dramatic, widespread rabbit suppression. We compared the area of occupancy and extent of occurrence of 4 extant species of small mammals before and after RHDV outbreak, relative to rainfall, sampling effort, and rabbit and predator populations. Despite low rainfall during the first 14 years after RHDV, 2 native rodents listed by the International Union for Conservation of Nature (IUCN), the dusky hopping‐mouse (Notomys fuscus) and plains mouse (Pseudomys australis), increased their extent of occurrence by 241–365%. A threatened marsupial micropredator, the crest‐tailed mulgara (Dasycercus cristicauda), underwent a 70‐fold increase in extent of occurrence and a 20‐fold increase in area of occupancy. Both bottom‐up and top‐down trophic effects were attributed to RHDV, namely decreased competition for food resources and declines in rabbit‐dependent predators. Based on these sustained increases, these 3 previously threatened species now qualify for threat‐category downgrading on the IUCN Red List. These recoveries are on a scale rarely documented in mammals and give impetus to programs aimed at targeted use of RHDV in Australia, rather than simply employing top‐down threat‐based management of arid ecosystems. Conservation programs that take big‐picture approaches to addressing threatening processes over large spatial scales should be prioritized to maximize return from scarce conservation funding. Further, these should be coupled with long‐term ecological monitoring, a critical tool in detecting and understanding complex ecosystem change.
Probing the Link between Biodiversity‐Related Knowledge and Self‐Reported Proconservation Behavior in a Global Survey of Zoo Visitors
Authors: Moss Andrew , Jensen Eric , Gusset Markus 
Published: February 2016

AbstractMany environmental communication interventions are built on the assumption that increased knowledge will lead to changes in proenvironment behaviors. Our study probes the link between biodiversity‐related knowledge and self‐reported proconservation behavior, based on the largest and most international study of zoo visitors ever conducted. In total, 6,357 visitors to 30 zoos from 19 countries around the globe participated in the study. Biodiversity understanding and knowledge of actions to help protect biodiversity were significantly related, but only 0.6% of the variation in knowledge of actions to help protect biodiversity could be explained by those same respondents’ biodiversity understanding. Biodiversity understanding was only the sixth most important variable in significantly predicting knowledge of actions to help protect biodiversity. Moreover, biodiversity understanding was the least important variable of those that were significantly related to self‐reported proconservation behavior. Our study indicates that knowledge is a real, but relatively minor, factor in predicting whether members of the public – zoo visitors in this case – will know about specific proenvironment behaviors they can take, let alone whether they will actually undertake such behaviors.
Cryoballoon ablation for atrial fibrillation – is cryoenergy applied only to the pulmonary vein ostium?
Authors: Baran Jakub , Lewandowski Paweł , Piotrowski Roman , Kulakowski Piotr 
Published: February 2016

AbstractThis case report shows that cryoablation of pulmonary veins (PV) may occasionally result in deeper lesions than expected and collateral damage in spite of proper ostial positioning of cryoballoon. The use of intracardiac vascular ultrasound and repeated computed tomography enabled detailed examination of these findings.
Selection and use of immunosuppressive therapies after liver transplantation: current German practice
Authors: Herzer Kerstin , Strassburg Christian P. , Braun Felix , Engelmann Cornelius , Guba Markus , Lehner Frank , Nadalin Silvio , Pascher Andreas , Scherer Marcus N. , Schnitzbauer Andreas A. , Zimmermann Tim , Nashan Björn , Sterneck Martina 
Published: February 2016

AbstractIn recent years, immunosuppression (IS) after liver transplantation (LT) has become increasingly diversified as the choice of agents has expanded and clinicians seek to optimize the balance of immunosuppressive potency with the risk of adverse events in individual patients. Calcineurin inhibitors (CNIs) are the primary agents used for patients undergoing liver transplantation. Other therapeutic agents like interleukin‐2 receptor antagonists are not universally administered, but can be considered for the delay or reduction in CNI exposure. An early addition of mycophenolate mofetil (MMF) or the mTOR inhibitor everolimus also allows for the reduction in the CNI dose. To reduce the risk of malignancy, in particular of skin tumors, as well as to prevent the deterioration of renal function, everolimus‐based therapy may be advantageous. Apart from patients with autoimmune hepatitis, steroids are withdrawn within 3–6 months after transplantation. Overall, immunosuppression can only be standardized in a limited proportion of patients due to specific clinical requirements and risk factors. Future studies should attempt to refine accurate individualization of the immunosuppressive regimen in specific difficult‐to‐treat patient subpopulations.
Utility of mammography for chronic kidney disease patients undergoing kidney transplant evaluation
Authors: Stoecker Jordan B. , Cote Devan R. , Augustine Joshua J. , Sarabu Nagaraju , Schulak James A. , Sanchez Edmund Q. , Humphreville Vanessa R. , Ammori John B. , Woodside Kenneth J. 
Published: February 2016

AbstractTransplant centers typically require screening mammography (MMG) for women ≥40 during evaluation. American Cancer Society recommends starting annual MMG at 40, while USPSTF recommends biennial MMG at 50. We sought to determine the effect of age and other breast malignancy risk factors on screening MMG in the pre‐transplant renal failure population undergoing transplant evaluation.MethodsWe retrospectively examined women ≥40 undergoing kidney transplant evaluation from 2006 to 2012 (n = 541).ResultsPatients aged 40.0–49.9 and ≥50 had similar rates of breast biopsy and breast malignancy. African Americans underwent a higher rate of biopsies (OR 2.391, 95%CI 1.111–5.019, p = 0.026), with a lower rate of biopsy in those already on dialysis at presentation (OR 0.434, 95%CI 0.212–0.888, p = 0.022). Higher breast density (>50% fibroglandular tissue) increased both rate of biopsy (OR 2.876, 95%CI 1.377–6.010, p = 0.005) and malignancy (OR 5.061, 95%CI 1.012–25.315, p = 0.048).ConclusionsAs we found no independent differences in biopsy or malignancy between age groups, it is reasonable for transplant centers to use the same evaluation MMG screening policy for all women ≥40. However, as malignancy risk increased with higher breast density, a lower threshold for additional workup may be warranted in patients with dense breasts or an indeterminate lesion on MMG.
Spontaneous bacterial peritonitis is a risk factor for renal failure requiring dialysis in waitlisted liver transplant candidates
Authors: Karagozian Raffi , Rutherford Anna E. , Christopher Kenneth B. , Brown Robert S. 
Published: February 2016

AbstractAimsTo examine the relationship between and impact of spontaneous bacteria peritonitis (SBP) and renal failure requiring dialysis in waitlisted liver transplant (LT) candidates.BackgroundRenal failure is a common and severe complication in cirrhotic patients with SBP. Approximately one‐third of patients with SBP develop renal failure despite treatment of infection. However, the incidence of renal failure requiring dialysis in LT waitlisted patients who have developed SBP is unknown. The high mortality observed in this group has also raised debate about resource utilization in the care of these patients.MethodsData from the United Network for Organ Sharing Standard Transplant and Research files were collected retrospectively between 1994 and 2012. The primary endpoint measured was first time initiation of dialysis while on the LT wait list. Secondary endpoints included waitlist time and mortality on wait list.ResultsA total of 42,085 patients were included. SBP at time of listing was diagnosed in 2,352 patients (5.6%) and first time initiation of dialysis while on the wait list occurred in 2,367 patients (6.2%). Unadjusted OR for requiring dialysis for patients listed with SBP was 1.66 (p < 0.001). When controlled for age, gender, BMI, diabetes mellitus, baseline creatinine, MELD score, serum albumin at listing, the adjusted OR for dialysis was 1.24 (p = 0.007) in waitlisted patients with SBP. Patients with SBP at time of listing had a mean waitlist time 142.1 d vs. 198.7 d in non‐SBP patients (p < 0.001).ConclusionsSpontaneous bacteria peritonitis patients have a significantly increased likelihood to require dialysis and mean shorter waitlist time. Furthermore, the combined occurrence of SBP and dialysis is a strong risk factor for all‐cause mortality while on the LT wait list.
Locating host plants via orientation to standing visual targets has dispersal benefits for the monophagous leaf beetle Ambrostoma quadriimpressum
Authors: Sun Fan , Bao Chao , Jing Tian‐Zhong 
Published: February 2016

AbstractThe highly specialized chrysomelid Ambrostoma quadriimpressum Motschulsky (Coleoptera: Chrysomelidae) is strictly monophagous on elm trees, Ulmus pumila L. (Ulmaceae) and a few of its close relatives. In order to elucidate how the adult beetles find their host plants, we performed both choice and no‐choice arena field experiments to examine their spatial maneuvering under seminatural conditions. In the no‐choice experiments, three treatments were tested in which individual beetles in thanatosis were released in the vicinity of a host plant, in which they were released facing (1) toward the host, (2) away from the host but toward a black paper column, or (3) away from the host with no standing target in view. Videorecordings of the beetles’ walking tracks showed that a standing visual target in field of vision strongly influenced their behavior. The host plant and black paper column equally attracted beetles released facing toward them. In choice experiments, the beetles randomly moved to both host and non‐host plants, as well as to the host plant and the black paper column, indicating that they do not discriminate host plants from a distance. The results suggest that this monophagous beetle locates host plants via orientation to standing visual targets. The results also indicate that the beetle encounters hosts by chance. The benefit of such a host‐finding mechanism in light of dispersion and emigration of the beetle is discussed.
The effects of temperature, relative humidity, light, and resource quality on flight initiation in the red flour beetle, Tribolium castaneum
Authors: Drury Douglas W. , Whitesell Matthew E. , Wade Michael J. 
Published: February 2016

AbstractWe investigated the environmental conditions that induce a flight response in the red flour beetle, Tribolium castaneumHerbst (Coleoptera: Tenebrionidae), including resource quality, temperature, relative humidity, and light. Over 72‐h trial periods, we observed the proportion of individuals emigrating by flight to range from 0.0 in extreme heat or cold to 0.82 with starvation. Resource quality, presence of a light source, and temperature all directly influenced the initiation of the flight response. We did not detect any effect of relative humidity or sudden change in temperature on the incidence of flight. We discuss our findings in the context of Tribolium ecology and evolution.
Synergism of perampanel and zonisamide in the rat amygdala kindling model of temporal lobe epilepsy
Authors: Russmann Vera , Salvamoser Josephine D. , Rettenbeck Maruja L. , Komori Takafumi , Potschka Heidrun 
Published: February 2016

SummaryObjectiveAnticonvulsive monotherapy fails to be effective in one third of patients with epilepsy resulting in the need for polytherapy regimens. However, with the still limited knowledge, drug choices for polytherapy remain empirical. Here we report experimental data from a chronic epilepsy model for the combination of perampanel and zonisamide, which can render guidance for clinical studies and individual drug choices.MethodsThe anticonvulsant effects of the combination of perampanel and zonisamide were evaluated in a rat amygdala kindling model. Furthermore, the potential for motor impairment was evaluated. The type of interaction was quantitatively assessed based on isobolographic analysis.ResultsWhen administered alone, zonisamide dose‐dependently increased the afterdischarge threshold in fully kindled rats. Moreover, data confirmed efficacy of perampanel to inhibit seizure initiation and progression with an impact on propagation of activity from the focus. Pronounced threshold increases were observed following administration of a constant zonisamide dosage combined with different doses of perampanel. Isobolographic analysis of drug responses, which is based on individual drug dose–effect data, revealed a synergistic interaction substantiating the high efficacy of the combination. Furthermore, rotarod data indicated that the combination has a favorable tolerability profile when zonisamide is coadministered with low doses of perampanel. Plasma concentration analysis argued against a pharmacokinetic interaction as a basis for the synergism.SignificanceThe findings clearly indicate a pronounced synergistic anticonvulsant effect for the combination of the noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist perampanel with zonisamide, which modulates voltage‐sensitive sodium channels and T‐type calcium currents. Consequently, polytherapy using these two antiepileptic drugs might be efficacious for clinical management of partial‐onset seizures. The findings indicate that the impact of dose ratios on tolerability needs be taken into account. With regard to conclusions about the extent of the synergism and its implications further antiepileptic drug combinations need to be evaluated allowing direct comparison.
Transgenerational effects persist down the maternal line in marine sticklebacks: gene expression matches physiology in a warming ocean
Authors: Shama Lisa N.S. , Mark Felix C. , Strobel Anneli , Lokmer Ana , John Uwe , Mathias Wegner K. 
Published: February 2016

AbstractTransgenerational effects can buffer populations against environmental change, yet little is known about underlying mechanisms, their persistence or the influence of environmental cue timing. We investigated mitochondrial respiratory capacity (MRC) and gene expression of marine sticklebacks that experienced acute or developmental acclimation to simulated ocean warming (21°C) across three generations. Previous work showed that acute acclimation of grandmothers to 21°C led to lower (optimized) offspringMRCs. Here, developmental acclimation of mothers to 21°C led to higher, but more efficient offspringMRCs. Offspring with a 21°C × 17°C grandmother‐mother environment mismatch showed metabolic compensation: theirMRCs were as low as offspring with a 17°C thermal history across generations. Transcriptional analyses showed primarily maternal but also grandmaternal environment effects: genes involved in metabolism and mitochondrial protein biosynthesis were differentially expressed when mothers developed at 21°C, whereas 21°C grandmothers influenced genes involved in hemostasis and apoptosis. Genes involved in mitochondrial respiration all showed higher expression when mothers developed at 21° and lower expression in the 21°C × 17°C group, matching the phenotypic pattern forMRCs. Our study links transcriptomics to physiology under climate change, and demonstrates that mechanisms underlying transgenerational effects persist across multiple generations with specific outcomes depending on acclimation type and environmental mismatch between generations.
Crossing regimes of temperature dependence in animal movement
Authors: Gibert Jean P. , Chelini Marie‐Claire , Rosenthal Malcolm F. , DeLong John P. 
Published: February 2016

AbstractA pressing challenge in ecology is to understand the effects of changing global temperatures on food web structure and dynamics. The stability of these complex ecological networks largely depends on how predator–prey interactions may respond to temperature changes. Because predators and prey rely on their velocities to catch food or avoid being eaten, understanding how temperatures may affect animal movement is central to this quest. Despite our efforts, we still lack a mechanistic understanding of how the effect of temperature on metabolic processes scales up to animal movement and beyond. Here, we merge a biomechanical approach, the Metabolic Theory of Ecology and empirical data to show that animal movement displays multiple regimes of temperature dependence. We also show that crossing these regimes has important consequences for population dynamics and stability, which depend on the parameters controlling predator–prey interactions. We argue that this dependence upon interaction parameters may help explain why experimental work on the temperature dependence of interaction strengths has so far yielded conflicting results. More importantly, these changes in the temperature dependence of animal movement can have consequences that go well beyond ecological interactions and affect, for example, animal communication, mating, sensory detection, and any behavioral modality dependent on the movement of limbs. Finally, by not taking into account the changes in temperature dependence reported here we might not be able to properly forecast the impact of global warming on ecological processes and propose appropriate mitigation action when needed.
Chaperone complex BAG2–HSC70 regulates localization of Caenorhabditis elegans leucine‐rich repeat kinase LRK‐1 to the Golgi
Authors: Fukuzono Takashi , Pastuhov Strahil Iv. , Fukushima Okinobu , Li Chun , Hattori Ayuna , Iemura Shun‐ichiro , Natsume Tohru , Shibuya Hiroshi , Hanafusa Hiroshi , Matsumoto Kunihiro , Hisamoto Naoki 
Published: February 2016

Mutations in LRRK2 are linked to autosomal dominant forms of Parkinson's disease. We identified two human proteins that bind to LRRK2: BAG2 and HSC70, which are known to form a chaperone complex. We characterized the role of their Caenorhabditis elegans homologues, UNC‐23 and HSP‐1, in the regulation of LRK‐1, the sole homologue of human LRRK2. In C. elegans, LRK‐1 determines the polarized sorting of synaptic vesicle (SV) proteins to the axons by excluding SV proteins from the dendrite‐specific transport machinery in the Golgi. In unc‐23 mutants, SV proteins are localized to both presynaptic and dendritic endings in neurons, a phenotype also observed in lrk‐1 deletion mutants. Furthermore, we isolated mutations in the hsp‐1 gene that can suppress the unc‐23, but not the lrk‐1 defect. We show that UNC‐23 determines LRK‐1 localization to the Golgi apparatus in cooperation with HSP‐1. These results describe a chaperone‐dependent mechanism through which LRK‐1 localization is regulated.
Simeprevir/pegylated interferon/ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation
Authors: Shinoda Masahiro , Ebinuma Hirotoshi , Itano Osamu , Yamagishi Yoshiyuki , Obara Hideaki , Kitago Minoru , Nakamoto Nobuhiro , Hibi Taizo , Yagi Hiroshi , Abe Yuta , Matsubara Kentaro , Chu Po‐sung , Wakayama Yuko , Taniki Nobuhito , Yamaguchi Akihiro , Amemiya Ryusuke , Miyake Rei , Mizota Takamasa , Kanai Takanori , Kitagawa Yuko 
Published: February 2016

AimSimeprevir (SMV) is a protease inhibitor which demonstrates good tolerability and high antiviral response in patients with hepatitis C. The clinical outcomes of triple therapy using simeprevir, pegylated interferon and ribavirin (SMV/PEG IFN/RBV) for recurrent hepatitis C after living donor liver transplantation (LDLT) have not been well reported. In this study, we assessed the outcomes of patients with recurrent hepatitis C (genotype 1) after LDLT who received triple therapy at our hospital.MethodsSMV/PEG IFN/RBV was administrated for 12 weeks (triple therapy), followed by another 12 weeks or extended period of PEG IFN/RBV (dual therapy). Virological response, interaction with calcineurin inhibitors and adverse events were retrospectively analyzed.ResultsTen patients with recurrent hepatitis C after LDLT completed 12 weeks of triple therapy. Nine patients achieved rapid or early virological response, and one patient was a non‐responder. The nine responders received subsequent dual therapy, and the duration of dual therapy was extended (24 to 36 weeks) in five cases. Although one patient was in relapse 8 weeks after completing the standard duration (12 weeks) of dual therapy, eight patients achieved sustained virological response for 12 weeks (SVR12). The SVR12 rate was 80%. Trough levels of calcineurin inhibitor did not show marked changes after introduction of SMV in all cases. There were no major adverse events associated with SMV.ConclusionSMV treatment may be a safe and effective option for recurrent hepatitis C after LDLT.