bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of relaxant mechanism of H2S in mouse corpus cavernosum
Authors: Aydinoglu Fatma , Ogulener Nuran 
Published: February 2016

SummaryThe aim of this study was to investigate the mechanism of H2S‐induced relaxation in mouse corpus cavernosal tissue. l‐cysteine (10−6 × 10−3 mol/L) and exogenous H2S (NaHS; 10−6 to 10−3 mol/L) induced concentration‐dependent relaxation. l‐cysteine‐induced relaxations was reduced by d,l‐propargylglycine, a cystathionine gamma lyase (CSE) inhibitor but not influenced by aminooxyacetic acid, a cystathionine beta synthase (CBS) inhibitor. l‐cysteine induced relaxations, but not of those of H2S diminished in endothelium‐denuded tissues. Nω‐nitro‐l‐arginine (l‐NA; 10−4 mol/L), a nitric oxide synthase inhibitor, and ODQ (10−4 mol/L), a guanylyl cyclase inhibitor, increased the H2S‐induced relaxation. Zaprinast (5 × 10−6 mol/L) and sildenafil (10−6 mol/L), phosphodiesterase inhibitors, inhibited H2S‐induced relaxation. Adenylyl cyclase inhibitors N‐ethylmaleimide (2.5 × 10−5 mol/L) and SQ22536 (10−4 mol/L) reduced relaxation to H2S. Also, H2S‐induced relaxation was reduced by KCl (50 mmol/L), 4‐aminopyridine (10−3 mol/L), a Kv inhibitor, glibenclamide (10−5 mol/L), a KATP inhibitor or barium chloride (10−5 mol/L), a KIR inhibitor. However, H2S‐induced relaxation was not influenced by apamin (10−6 mol/L), a SKCa2+ inhibitor, charybdotoxin (10−7 mol/L), an IKCa2+ and BKCa2+ inhibitor or combination of apamin and charybdotoxin. Nifedipine (10−6 mol/L), an L‐type calcium channel blocker and atropine (10−6 mol/L), a muscarinic receptor blocker, inhibited H2S‐induced relaxation. However, H2S‐induced relaxation was not influenced by ouabain (10−4 mol/L), a Na+/K+‐ATPase inhibitor. This study suggests that H2S endogenously synthesizes from l‐cysteine by CSE endothelium‐dependent in mouse corpus cavernosum tissue, and exogenous H2S may cause endothelium‐independent relaxations via activation of K channels (KATP channel, KV channels, KIR channels), L‐type voltage‐gated Ca2+ channels, adenylyl cyclase/cAMP pathway and muscarinic receptor, and there is the interaction between H2S and NO/cGMP.
Perforin expression in eyelid sebaceous carcinomas: a useful and specific immunomarker for the differential diagnosis of eyelid carcinomas
Authors: Mittal Ruchi , Araujo Iguaracyra , Czanner Gabriela , Coupland Sarah E. 
Published: February 2016

AbstractPurposeEyelid sebaceous carcinoma (SC) remains a common diagnostic pitfall for both the clinician and histopathologist. The aim of this study was to describe perforin as a new marker in the immunohistochemistry panel for SC.MethodsA total of 29 cases were retrieved from the Pathology archives, including 11 sebaceous neoplasms (nine SC; two sebaceomas), 10 squamous cell carcinomas (SCC) and eight basal cell carcinomas (BCC). These were stained using the monoclonal antibody for perforin, epithelial membrane antigen (EMA), Ber‐EP4 and adipophilin (ADP). Sensitivity and specificity of perforin as an immunohistologic marker for sebaceous tumours were compared to EMA, ADP and Ber‐EP4.ResultsPerforin stained strongly 9/11 (81%) of the sebaceous neoplasms (SN), 7/9 SC and 2/2 of sebaceomas (2/2), similar to ADP. Epithelial membrane antigen (EMA) stained 8/9 SC and was negative (1/2) or only very weakly expressed (1/2) in sebaceomas. The specificity of perforin in identifying SN versus SCC and BCC was 100% (95% CI 69–100), while EMA specificity in identifying SN varied according the comparison group (SCC: 50%, 95% CI 18–81, 100% (95% CI 63–100). Perforin better highlighted the intraepithelial spread of SC than EMA. Ber‐EP4 was strongly expressed in six of nine SC, but was consistently negative in sebaceomas.ConclusionsThe expression pattern of perforin in sebaceous neoplasms enables us to recommend the use of perforin as a new immunohistochemical marker for sebaceous neoplasms.
Unbiased Estimation of Biomarker Panel Performance When Combining Training and Testing Data in a Group Sequential Design
Authors: Tayob Nabihah , Do Kim-Anh , Feng Ziding 
Published: February 2016

Summary
Motivated by an ongoing study to develop a screening test able to identify patients with undiagnosed Sjögren's Syndrome in a symptomatic population, we propose methodology to combine multiple biomarkers and evaluate their performance in a two-stage group sequential design that proceeds as follows: biomarker data is collected from first stage samples; the biomarker panel is built and evaluated; if the panel meets pre-specified performance criteria the study continues to the second stage and the remaining samples are assayed. The design allows us to conserve valuable specimens in the case of inadequate biomarker panel performance. We propose a nonparametric conditional resampling algorithm that uses all the study data to provide unbiased estimates of the biomarker combination rule and the sensitivity of the panel corresponding to specificity of 1-t on the receiver operating characteristic curve (ROC). The Copas and Corbett (2002) correction, for bias resulting from using the same data to derive the combination rule and estimate the ROC, was also evaluated and an improved version was incorporated. An extensive simulation study was conducted to evaluate finite sample performance and propose guidelines for designing studies of this type. The methods were implemented in the National Cancer Institutes Early Detection Network Urinary PCA3 Evaluation Trial.
Pancreatic polypeptide and its central Y4 receptors are essential for cued fear extinction and permanent suppression of fear
Authors: Verma D , Hörmer B , Bellmann‐Sickert K , Thieme V , Beck‐Sickinger A G , Herzog H , Sperk G , Tasan R O 
Published: February 2016

Background and purposeAvoiding danger and finding food are closely related behaviours that are essential for surviving in a natural environment. Growing evidence supports an important role of gut‐brain peptides in modulating energy homeostasis and emotional‐affective behaviour. For instance, postprandial release of pancreatic polypeptide (PP) reduced food intake and altered stress‐induced motor activity and anxiety by activating central Y4 receptors.Experimental approachWe characterized [K30(PEG2)]hPP2‐36 as long‐acting Y4 receptor agonist and injected it peripherally into wildtype and Y4 receptor knockout (Y4KO) C57Bl/6NCrl mice to investigate the role of Y4 receptors in fear conditioning. Extinction and relapse after extinction was measured by spontaneous recovery and renewal.Key resultsThe Y4KO mice showed impaired cued and context fear extinction without affecting acquisition, consolidation or recall of fear. Correspondingly, peripheral injection of [K30(PEG2)]hPP2‐36 facilitated extinction learning upon fasting, an effect that was long‐lasting and generalized. Furthermore, peripherally applied [K30(PEG2)]hPP2‐36 before extinction inhibited the activation of orexin‐expressing neurons in the lateral hypothalamus in WT, but not in Y4KO mice.Conclusions and implicationsOur findings suggests suppression of excessive arousal as a possible mechanism for the extinction‐promoting effect of central Y4 receptors and provide strong evidence that fear extinction requires integration of vegetative stimuli with cortical and subcortical information, a process crucially depending on Y4 receptors. Importantly, in the lateral hypothalamus two peptide systems, PP and orexin, interact to generate an emotional response adapted to the current homeostatic state. Detailed investigations of feeding‐relevant genes may thus deliver multiple intervention points for treating anxiety‐related disorders.
‘I want to be better than you:’ lived experiences of intergenerational child maltreatment prevention among teenage mothers in and beyond foster care
Authors: Aparicio Elizabeth M. 
Published: February 2016

AbstractThe growing body of research on teenage motherhood in foster care has largely focused on the risks involved for both mother and child, yet these mothers depict a much more complex picture of their own experience of becoming and being mothers. The current study employed interpretative phenomenological analysis to explore 18 in‐depth, qualitative interviews from six participants on the meaning and experience of motherhood among teenage mothers in foster care and in the years immediately after ageing out. This study focused on a particular dimension of motherhood: participants' efforts to break the cycle of child abuse and neglect with their own children. Two themes emerged as characteristic of these experiences: (i) treating children well/parenting differently and avoiding the system; and (ii) reducing isolation and enhancing support. Given the increased likelihood of the children of teen mothers – particularly those who have been maltreated – becoming involved with the child welfare system, study findings suggest possible strategies for disrupting cycles of intergenerational child welfare involvement generated by young mothers themselves. Practice implications for addressing possible substance abuse, mental health and relational and parenting needs are discussed.
Increased Expression of Transient Receptor Potential Vanilloid 4 in Cortical Lesions of Patients with Focal Cortical Dysplasia
Authors: Chen Xin , Sun Fei‐Ji , Wei Yu‐Jia , Wang Lu‐Kang , Zang Zhen‐Le , Chen Bing , Li Song , Liu Shi‐Yong , Yang Hui 
Published: February 2016

SummaryAimFocal cortical dysplasia (FCD) represents a well‐known cause of medically intractable epilepsy. Studies found that transient receptor potential vanilloid receptor 4 (TRPV4) may participate in the occurrence of seizures. This study investigated the expression patterns of TRPV4 in FCD and the cascade that regulate functional state of TRPV4 in cortical neurons.MethodsThirty‐nine surgical specimens from FCD patients and 10 age‐matched control samples from autopsies were included in this study. Protein expression and distribution were detected by Western blot, immunohistochemistry, and immunofluorescence staining. Calcium imaging was used to detect the TRPV4‐mediated Ca2+ influx in cortical neurons.Results(1) The protein levels of TRPV4 and of an upstream factor, protein kinase C (PKC), were markedly elevated in FCD. (2) TRPV4 staining was stronger in the dysplastic cortices of FCD and mainly observed in neuronal microcolumns and malformed cells. (3) The activation of TRPV4 was central for [Ca2+]i elevation in cortical neurons, and this activity of TRPV4 in cortical neurons was regulated by the PKC, but not the PKA, pathway.ConclusionThe overexpression and altered cellular distribution of TRPV4 in FCD suggest that TRPV4 may potentially contribute to the epileptogenesis of FCD.
Is an Investing Institution One Shareholder or a Collection of Separate Funds?
Authors: Armitage Seth , Haig Alistair , Hodgkinson Lynn 
Published: February 2016

AbstractManuscript TypeEmpiricalResearch Question/IssueThe paper examines whether the fund managers in a given investing institution behave in a coordinated manner, in terms of their trading around the announcement of a major takeover by a company in which the institution has two or more separate holdings.Research Findings/InsightsOur data show that many institutional holdings consist of subholdings managed by separate fund managers. We find that trading around takeover announcements is coordinated in a majority of cases, but there is material disagreement within institutions in a substantial minority of cases, depending on how disagreement is measured. This suggests that blocks, at the level of the institution, do not always exist in the sense of being controlled by a single agent. Institutional ownership is less concentrated than it might appear to be from lists of shareholders in annual reports and databases.Theoretical/Academic ImplicationsResearch in corporate governance tends to assume implicitly that an institutional holding is a single block. Our findings indicate that it is not safe to make this assumption, especially in the case of larger blocks which are more likely to consist of several subholdings. Some types of research would benefit from using data at the level of the managed fund.Practitioner/Policy ImplicationsThere is much discussion about the merits of coordinated shareholder action between investing institutions, for example in the Kay Review. The findings imply that there is scope for greater coordination within institutions as well as across institutions.
β‐adrenergic receptor signalling and its functional consequences in the diseased heart
Authors: Najafi Aref , Sequeira Vasco , Kuster Diederik W.D. , van der Velden Jolanda 
Published: February 2016

AbstractBackgroundTo maintain the balance between the demand of the body and supply (cardiac output), cardiac performance is tightly regulated via the parasympathetic and sympathetic nervous systems. In heart failure, cardiac output (supply) is decreased due to pathologic remodelling of the heart. To meet the demands of the body, the sympathetic system is activated and catecholamines stimulate β‐adrenergic receptors (β‐ARs) to increase contractile performance and cardiac output. Although this is beneficial in the acute phase, chronic β‐ARs stimulation initiates a cascade of alterations at the cellular level, resulting in a diminished contractile performance of the heart.Materials and methodsThis narrative review includes results from previously published systematic reviews and clinical and basic research publications obtained via PubMed up to May 2015.ResultsWe discuss the alterations that occur during sustained β‐AR stimulation in diseased myocardium and emphasize the consequences of β‐AR overstimulation for cardiac function. In addition, current treatment options as well as future therapeutic strategies to treat patients with heart failure to normalize consequences of β‐AR overstimulation are discussed.ConclusionsThe heart is able to protect itself from chronic stimulation of the β‐ARs via desensitization and reduced membrane availability of the β‐ARs. However, ultimately this leads to an impaired downstream signalling and decreased protein kinase A (PKA)‐mediated protein phosphorylation. β‐blockers are widely used to prevent β‐AR overstimulation and restore β‐ARs in the failing hearts. However, novel and more specific therapeutic treatments are needed to improve treatment of HF in the future.
Inter‐hemispheric connectivity in the fusiform gyrus supports memory consolidation for faces
Authors: Geiger Maximilian J. , O'Gorman Tuura Ruth , Klaver Peter 
Published: February 2016

AbstractThis study investigated how changes of functional connectivity over time accompany consolidation of face memories. Based on previous research, it was hypothesized that connectivity changes in networks initially active during face perception and face encoding would be associated with individual recognition memory performance. Resting‐state functional connectivity was examined shortly before, shortly after and about 40 min after incidental learning of faces. Memory performance was assessed in a surprise recognition test shortly after the last resting‐state session. Results reveal that memory performance‐related connectivity between the left fusiform face area and other brain areas gradually changed over the course of the experiment. Specifically, the increase in connectivity with the contralateral fusiform gyrus, the hippocampus, the amygdala and the inferior frontal gyrus correlated with recognition memory performance. As the increase in connectivity in the two final resting‐state sessions was associated with memory performance, the present results demonstrate that memory formation is not restricted to the incidental learning phase but continues and increases in the following 40 min. It is discussed that the delayed increase in inter‐hemisphere connectivity between the left and right fusiform gyrus is an indicator for memory formation and consolidation processes.
Endovascular stroke therapy in Austria: a nationwide 1‐year experience
Authors: Serles W. , Gattringer T. , Mutzenbach S. , Seyfang L. , Trenkler J. , Killer‐Oberpfalzer M. , Deutschmann H. , Niederkorn K. , Wolf F. , Gruber A. , Hausegger K. , Weber J. , Thurnher S. , Gizewski E. , Willeit J. , Karaic R. , Fertl E. , Našel C. , Brainin M. , Erian J. , Oberndorfer S. , Karnel F. , Grisold W. , Auff E. , Fazekas F. , Haring H.‐P. , Lang W. ,   the Austrian Stroke Unit Registry Collaborators
Published: February 2016

Background and purposeBased on a tight network of stroke units (SUs) and interventional centres, endovascular treatment of acute major intracranial vessel occlusion has been widely implemented in Austria. Documentation of all patients in the nationwide SU registry has thereby become mandatory.MethodsDemographic, clinical and interventional characteristics of patients who underwent endovascular treatment for acute ischaemic stroke in 11 Austrian interventional centres between 1 October 2013 and 30 September 2014 were analysed.ResultsIn total, 301 patients (50.5% women; median age 70.5 years; median National Institutes of Health Stroke Scale score 17) were identified.193 patients (64.1%) additionally received intravenous thrombolysis. The most frequent vessel occlusion sites were the M1 segment of the middle cerebral artery (n = 161, 53.5%), the intracranial internal carotid artery (n = 60, 19.9%) and the basilar artery (n = 40, 13.3%). Stent retrievers were used in 235 patients (78.1%) and adequate reperfusion (modified Thrombolysis in Cerebral Infarction scores 2b and 3, median onset to reperfusion time 254 min) was achieved in 242 patients (81.4%). Symptomatic intracranial haemorrhage occurred in 7%. 43.8% of patients (n = 132) had good functional outcome (modified Rankin Scale score 0–2) and the mortality rate was 20.9% (n = 63) after 3 months. Compared to the anterior circulation, vertebrobasilar stroke patients had higher mortality. Patients with secondary hospital transportation had better outcomes after 3 months than in‐house treated patients.ConclusionOur results document nationwide favourable outcome and safety rates of endovascular stroke treatment comparable to recent randomized trials. The ability to provide such data and the need to further optimize such an approach also underscore the contribution of respective registries.
Ambient insect pressure and recipient genotypes determine fecundity of transgenic crop‐weed rice hybrid progeny: Implications for environmental biosafety assessment
Authors: Xia Hui , Zhang Hongbin , Wang Wei , Yang Xiao , Wang Feng , Su Jun , Xia Hanbing , Xu Kai , Cai Xingxing , Lu Bao‐Rong 
Published: February 2016

AbstractTransgene introgression into crop weedy/wild relatives can provide natural selective advantages, probably causing undesirable environmental impact. The advantages are likely associated with factors such as transgenes, selective pressure, and genetic background of transgene recipients. To explore the role of the environment and background of transgene recipients in affecting the advantages, we estimated the fitness of crop‐weed hybrid lineages derived from crosses between marker‐free insect‐resistant transgenic (Bt/CpTI) rice with five weedy rice populations under varied insect pressure. Multiway anova indicated the significant effect of both transgenes and weedy rice genotypes on the performance of crop‐weed hybrid lineages in the high‐insect environment. Increased fecundity was detected in most transgene‐present F1 and F2 hybrid lineages under high‐insect pressure, but varied among crop‐weed hybrid lineages with different weedy rice parents. Increased fecundity of transgenic crop‐weed hybrid lineages was associated with the environmental insect pressure and genotypes of their weedy rice parents. The findings suggest that the fitness effects of an insect‐resistant transgene introgressed into weedy populations are not uniform across different environments and genotypes of the recipient plants that have acquired the transgene. Therefore, these factors should be considered when assessing the environmental impact of transgene flow to weedy or wild rice relatives.
Infrared A radiation promotes survival of human melanocytes carrying ultraviolet radiation‐induced DNA damage
Authors: Kimeswenger Susanne , Schwarz Agatha , Födinger Dagmar , Müller Susanne , Pehamberger Hubert , Schwarz Thomas , Jantschitsch Christian 
Published: February 2016

AbstractThe link between solar radiation and melanoma is still elusive. Although infrared radiation (IR) accounts for over 50% of terrestrial solar energy, its influence on human skin is not well explored. There is increasing evidence that IR influences the expression patterns of several molecules independently of heat. A previous in vivo study revealed that pretreatment with IR might promote the development of UVR‐induced non‐epithelial skin cancer and possibly of melanoma in mice. To expand on this, the aim of the present study was to evaluate the impact of IR on UVR‐induced apoptosis and DNA repair in normal human epidermal melanocytes. The balance between these two effects is a key factor of malignant transformation. Human melanocytes were exposed to physiologic doses of IR and UVR. Compared to cells irradiated with UVR only, simultaneous exposure to IR significantly reduced the apoptotic rate. However, IR did not influence the repair of UVR‐induced DNA damage. IR partly reversed the pro‐apoptotic effects of UVR via modification of the expression and activity of proteins mainly of the extrinsic apoptotic pathway. In conclusion, IR enhances the survival of melanocytes carrying UVR‐induced DNA damage and thereby might contribute to melanomagenesis.
Low‐cycle fatigue of 316L stainless steel under proportional and nonproportional loadings
Authors: Jin D. , Tian D.J. , Li J.H. , Sakane M. 
Published: February 2016

AbstractThis paper discusses low‐cycle fatigue characteristics of 316L stainless steel under proportional and nonproportional loadings. Tension–torsion multiaxial low‐cycle fatigue tests were performed using five strain paths. Additional hardening was observed under nonproportional loadings and was more significant in tests with larger nonproportionality. Mises equivalent strain, Smith–Watson–Topper, Fatemi–Socie, Kandil–Brown–Miller and nonproportional strain parameters were applied to the experimental data to evaluate the multiaxial low‐cycle fatigue damage. The applicability of the damage laws to practical design was discussed.
Early signs of range disjunction of submountainous plant species: an unexplored consequence of future and contemporary climate changes
Authors: Kuhn Emilien , Lenoir Jonathan , Piedallu Christian , Gégout Jean‐Claude 
Published: February 2016

AbstractPoleward and upward species range shifts are the most commonly anticipated and studied consequences of climate warming. However, these global responses to climate change obscure more complex distribution change patterns. We hypothesize that the spatial arrangement of mountain ranges and, consequently, climatic gradients in Europe, will result in range disjunctions. This hypothesis was investigated for submountainous forest plant species at two temporal and spatial scales: (i) under future climate change (between 1950–2000 and 2061–2080 periods) at the European scale and (ii) under contemporary climate change (between 1914–1987 and 1997–2013 periods) at the French scale. We selected 97 submountainous forest plant species occurring in France, among which distribution data across Europe are available for 25 species. By projecting future distribution changes for the 25 submountainous plant species across Europe, we demonstrated that range disjunction is a likely consequence of future climate change. To assess whether it is already taking place, we used a large forest vegetation‐plot database covering the entire French territory over 100 years (1914–2013) and found an average decrease in frequency (−0.01 ± 0.004) in lowland areas for the 97 submountainous species – corresponding to a loss of 6% of their historical frequency – along with southward and upward range shifts, suggesting early signs of range disjunctions. Climate‐induced range disjunctions should be considered more carefully since they could have dramatic consequences on population genetics and the ability of species to face future climate changes.