bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐specific ablation in the testis: what have we learned?
Authors: Smith L. B. , O'Shaughnessy P. J. , Rebourcet D. 
Published: October 2015

SummaryTesticular development and function is the culmination of a complex process of autocrine, paracrine and endocrine interactions between multiple cell types. Dissecting this has classically involved the use of systemic treatments to perturb endocrine function, or more recently, transgenic models to knockout individual genes. However, targeting genes one at a time does not capture the more wide‐ranging role of each cell type in its entirety. An often overlooked, but extremely powerful approach to elucidate cellular function is the use of cell ablation strategies, specifically removing one cellular population and examining the resultant impacts on development and function. Cell ablation studies reveal a more holistic overview of cell–cell interactions. This not only identifies important roles for the ablated cell type, which warrant further downstream study, but also, and importantly, reveals functions within the tissue that occur completely independently of the ablated cell type. To date, cell ablation studies in the testis have specifically removed germ cells, Leydig cells, macrophages and recently Sertoli cells. These studies have provided great leaps in understanding not possible via other approaches; as such, cell ablation represents an essential component in the researchers’ tool‐kit, and should be viewed as a complement to the more mainstream approaches to advancing our understanding of testis biology. In this review, we summarise the cell ablation models used in the testis, and discuss what each of these have taught us about testis development and function.
Genetic aetiology of ophthalmological manifestations in children – a focus on mitochondrial disease‐related symptoms
Authors: Widgren Paula , Hurme Anri , Falck Aura , Keski‐Filppula Riikka , Remes Anne M , Moilanen Jukka , Majamaa Kari , Kervinen Marko , Uusimaa Johanna 
Published: October 2015

AbstractPurposeTo investigate the association of mutations in the mitochondrial DNA (mtDNA) or nuclear candidate genes with mitochondrial disease‐related ophthalmic manifestations (nystagmus, ptosis, ophthalmoplegia, optic neuropathy and retinopathy) in children.MethodsA retrospective cohort of children (n = 98) was identified from the medical record files of a tertiary care hospital. The entire mtDNA and nuclear genes POLG1, OPA1 and PEO1 were analysed from the available DNA samples (n = 38). Furthermore, some nuclear candidate genes were investigated based on family history and phenotype. Rare mtDNA mutations were evaluated using in silico predictors and sequence alignment.ResultsThree patients had previously identified mutations in mtDNA that are associated with optic neuropathy (in MT‐ND6 and MT‐ND1) and nystagmus (in tRNA Arg). Nine rare mutations in MT‐ATP6 were identified in seven patients, of whom four manifested with retinopathy and three had clusters of MT‐ATP6 mutations. Nuclear PEO1 and OPA1 were unchanged in all samples, but a patient with nystagmus had a heterozygous POLG1 mutation. The analysis of nuclear candidate genes revealed mutations in NDUF8 (patient with nystagmus), TULP1 (patient with optic neuropathy, nystagmus and retinopathy) and RP2 (patient with retinopathy) genes.ConclusionsChildren with retinopathy, nystagmus or optic neuropathy, especially together with developmental delay or positive family history, should be considered for mitochondrial disease. MT‐ATP6 should be taken into account for children with retinopathy of unknown aetiology.
Altered Loyalties of Neuronal Markers in Cultured Slices of Resected Human Brain Tissue
Authors: Verwer Ronald W. H. , Sluiter Arja A. , Balesar Rawien A. , Baayen Johannes C. , Speijer Dave , Idema Sander , Swaab Dick F. 
Published: October 2015

AbstractOrganotypic cultures from normal neocortical tissue obtained at epilepsy surgery show a severe injury response. This response involves both neuronal degeneration and the proliferation of reactive cells. A salient feature of the reactive cells is the co‐expression of microglial and astrocytic markers. Surprisingly, the reactive cells also began to express neuronal markers Tubulin βIII and MAP2 adding to the confusion about their origin. Concomitant with their appearance in reactive cells MAP2 and Tubulin βIII expression disappeared from neurons. While NeuN expression decreased significantly, it did not entirely disappear from many neurons. Moreover, it was not observed in reactive cells, showing that NeuN is a reliable marker of neurons.
Identification of a resveratrol tetramer as a potent inhibitor of hepatitis C virus helicase
Authors: Lee Sungjin , Yoon Kee Dong , Lee Myungeun , Cho Yoojin , Choi Gahee , Jang Hongje , Kim BeomSeok , Jung Da‐Hee , Oh Jin‐Gyo , Kim Geon‐Woo , Oh Jong‐Won , Jeong Yong‐Joo , Kwon Ho Jeong , Bae Soo Kyung , Min Dal‐Hee , Windisch Marc P , Heo Tae‐Hwe , Lee Choongho 
Published: October 2015

Background and PurposeHepatitis C virus (HCV) infection is responsible for various chronic inflammatory liver diseases. Here, we have identified a naturally occurring compound with anti‐HCV activity and have elucidated its mode of antiviral action.Experimental ApproachLuciferase reporter and real‐time RT‐PCR assays were used to measure HCV replication. Western blot, fluorescence‐labelled HCV replicons and infectious clones were employed to quantitate expression levels of viral proteins. Resistant HCV mutant mapping, in vitro NS3 protease, helicase, NS5B polymerase and drug affinity responsive target stability assays were also used to study the antiviral mechanism.Key ResultsA resveratrol tetramer, vitisin B from grapevine root extract showed high potency against HCV replication (EC50 = 6 nM) with relatively low cytotoxicity (EC50 >10 μM). Combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B‐resistant HCV variants suggested an NS3 helicase as its potential target. We confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. Vitisin B was a potent inhibitor of a HCV NS3 helicase (IC50 = 3 nM). In vivo, Finally, we observed a preferred tissue distribution of vitisin B in the liver after i.p. injection in rats, at clinically attainable concentrations.Conclusion and ImplicationsVitisin B is one of the most potent HCV helicase inhibitors identified so far. Vitisin B is thus a prime candidate to be developed as the first HCV drug derived from natural products.
Mechanisms by which the thiazolidinedione troglitazone protects against sucrose‐induced hepatic fat accumulation and hyperinsulinaemia
Authors: Martins Fátima O , Delgado Teresa C , Viegas Joana , Gaspar Joana M , Scott Donald K , O'Doherty Robert M , Paula Macedo M , Jones John G 
Published: October 2015

Background and PurposeThiazolidinediones (TZD) are known to ameliorate fatty liver in type 2 diabetes. To date, the underlying mechanisms of their hepatic actions remain unclear.Experimental ApproachHepatic triglyceride content and export rates were assessed in 2 week high‐sucrose‐fed Wistar rats treated with troglitazone and compared with untreated high‐sucrose rodent controls. Fractional de novo lipogenesis (DNL) contributions to hepatic triglyceride were quantified by analysis of triglyceride enrichment from deuterated water. Hepatic insulin clearance and NO status during a meal tolerance test were also evaluated.Key ResultsTZD significantly reduced hepatic triglyceride (P < 0.01) by 48%, decreased DNL contribution to hepatic triglyceride (P < 0.01) and increased postprandial non‐esterified fatty acids clearance rates (P < 0.01) in comparison with the high‐sucrose rodent control group. During a meal tolerance test, plasma insulin AUC was significantly lower (P < 0.01), while blood glucose and plasma C‐peptide levels were not different. Insulin clearance was increased (P < 0.001) by 24% and was associated with a 22% augmentation of hepatic insulin‐degrading enzyme activity (P < 0.05). Finally, hepatic NO was decreased by 24% (P < 0.05).ConclusionsOverall, TZD show direct actions on liver by reducing hepatic DNL and increasing hepatic insulin clearance. The alterations in hepatic insulin clearance were associated with changes in insulin‐degrading enzyme activity, with possible modulation of NO levels.
Long‐term Spatial Changes in the Distribution of the Brazilian Atlantic Forest
Authors: Ledru Marie‐Pierre , Montade Vincent , Blanchard Grégoire , Hély Christelle 
Published: October 2015

AbstractThe aim of this study is to represent simultaneously changes in the spatial distribution of the Atlantic forest during the last 17,000 years. To characterize such changes, here we focused on three different forest physiognomies, evergreen, semi‐deciduous, and Araucaria, and we provide a list of indicator taxa for each class retrieved from the original published datasets. A review of the published fossil pollen records allowed us to classify regional behaviors in three main areas of distribution, north of 15°S, between 15° and 23°S and south of 23°S latitude that correspond to three climatic geographical barriers. Statistical probability density function method was used to illustrate changes in forest physiognomies throughout the three distribution areas. We show that the three modern barriers also functioned through the past. Asynchronous patterns of forest physiognomies are linked to an antiphasing pattern of monsoon precipitation between the northern and central area, whereas in the southern area, it is linked to the frequency and intensity of the polar advection in the subtropics. Our results attest to strong climate forcing on forest distribution between the late glacial and the interglacial period. They call into question the common reference to the last glacial maximum as a major (and sometimes as the only) driver of forest‐related vicariance and genetic diversity patterns, but suggest that instead, orbital cycles were the main drivers of the successive expansion/contraction of the Atlantic forest throughout the Quaternary.
The inferior impact of antibody‐mediated rejection on the clinical outcome of kidney allografts that develop de novo thrombotic microangiopathy
Authors: Wu Kaiyin , Budde Klemens , Schmidt Danilo , Neumayer Hans‐Hellmut , Lehner Lukas , Bamoulid Jamal , Rudolph Birgit 
Published: October 2015

AbstractBackgroundAntibody‐mediated rejection (AMR) can induce and develop thrombotic microangiopathy (TMA) in renal allografts. A definitive AMR (dAMR) co‐presents three diagnostic features. A suspicious AMR (sAMR) is designated when one of the three features is missing.MethodsThirty‐two TMA cases overlapping with AMR (AMR+ TMA) were studied, which involved 14 cases of sAMR+ TMA and 18 cases of dAMR+ TMA. Thirty TMA cases free of AMR features (AMR− TMA) were enrolled as control group.ResultsThe ratio of complete response to treatment was similar between AMR− TMA and AMR+ TMA group (23.3% vs. 12.5%, p = 0.33), or between sAMR+ TMA and dAMR+ TMA group (14.3% vs. 11.1%, p = 0.79). At eight yr post‐transplantation, the death‐censored graft survival (DCGS) rate of AMR− TMA group was 62.8%, which was significantly higher than 28.0% of AMR+ TMA group (p = 0.01), but similar between sAMR+ TMA and dAMR+ TMA group (30.0% vs. 26.7%, p = 0.92). Overall, the intimal arteritis and the broad HLA (Human leukocyte antigens) mismatches were closely associated with over time renal allograft failure.ConclusionThe AMR+ TMA has inferior long‐term graft survival, but grafts with sAMR+ TMA or dAMR+ TMA have similar characteristics and clinical courses.
The incidence and risk factors for deep vein thrombosis after kidney transplantation in Korea: single‐center experience
Authors: Ahn Sanghyun , Kim Mi‐Hyeong , Jun Kang‐Woong , Hwang Jeong‐Kye , Park Soon‐Chul , Moon In‐Sung , Kim Ji‐Iil 
Published: October 2015

AbstractBackgroundThe incidence of deep vein thrombosis (DVT) after kidney transplantation (KT) and the risk factors are still unknown in Korean patients. Determining the need for appropriate DVT prophylaxis is difficult when considering the low incidence of DVT in the Asian population. The aim of this study was to investigate the incidence of DVT occurring 3 months after KT, the DVT occurrence pattern, and risk factors in Korean patients.MethodsData from a total of 393 patients who underwent KT from November 2009 to December 2012 were analyzed. Color duplex ultrasonography was used for the diagnosis or screening of DVT in all patients pre‐operatively and on post‐operative days 7, 14, 28, and 90.ResultsThe cumulative 3‐month incidence of DVT after KT was 4.6%, and there was one symptomatic DVT. Patients with DVT were older than those without DVT at the time of transplantation (52.8 vs. 44.6, p < 0.001). According to univariate and multivariate analysis, older age was identified as a risk factor for DVT at the time of transplantation, whereas history of DVT did not reach statistical significance. There were no deaths related to DVT or pulmonary embolism.ConclusionsPharmacological prophylaxis after KT is not necessary because of the low incidence of DVT in Korean patients, and instead, we suggest that long‐term mechanical prophylaxis of at least 3 months can be a suitable option. Patients older than 50 years of age have a higher risk of developing DVT, and careful observation is needed in these patients.
Electric crows: powerlines, climate change and the emergence of a native invader
Authors: Cunningham S. J. , Madden C. F. , Barnard P. , Amar A. 
Published: October 2015

AbstractAimClimate change and other anthropogenic global change drivers act in complex, mutually exacerbating ways to alter the abundance and distribution of species. In South Africa, pied crows Corvus albus have increased in numbers and range in recent decades. Popular opinion links these changes to urbanisation and infrastructure development, but there has been no empirical test of this idea. We aimed to clarify the drivers of pied crow population changes in South Africa.LocationSouth Africa.MethodsWe used publicly available long‐term datasets, the Southern African Bird Atlas Project and University of Delaware Gridded Climate Database, and spatial data from government bodies, to assess relationships between pied crow population and range changes, land use, infrastructure, urbanisation and climate change.ResultsPied crow numbers have increased significantly in the past three decades, but rate of increase varied geographically, with crows declining in the northeast and increasing in the south‐west of South Africa. Pied crow population changes were strongly correlated with climate change. Crows have benefited most from climate warming in the shrubland biomes of south‐western South Africa. Pied crows are tree nesters, and within these shrublands, there is a strong positive relationship between the rate of population increase and the density of powerline infrastructure, which may facilitate pied crows’ increase by providing nesting sites.Main conclusionsPied crow numbers have increased in response to climate warming, with their spread facilitated by electrical infrastructure in south‐western South Africa, providing a clear example of compound influence of multiple global change drivers promoting a significant change in species range and reporting rate. Pied crows are generalist predators and there is popular concern about their ecological impact in areas where increases have occurred. We highlight the importance of understanding the ecosystem‐level implications of increased numbers of pied crows in South Africa's shrubland biomes.
Phylogenetic analysis of niche divergence reveals distinct evolutionary histories and climate change implications for tropical carnivorous pitcher plants
Authors: Schwallier Rachel , Raes Niels , de Boer Hugo J. , Vos Rutger A. , van Vugt Rogier R. , Gravendeel Barbara 
Published: October 2015

AbstractAimTo analyse the underpinnings of historical drivers of diversity and their contributions to current distributions and future roles in a changing climate, we studied the relationship between ecological niche divergence and phylogenetic signal in tropical carnivorous pitcher plants.LocationSoutheast Asia.MethodsEstimates of realized ecological niches were reconstructed and plotted along a newly created multilocus molecular phylogeny. Phylogenetic signal was analysed by comparisons of calculated phylogenetic relatedness with ecological niche divergence. Current and projected future potentially suitable habitats were mapped for several species of plants with variable evolutionary histories and distributions.ResultsHighland and lowland species had distinct phylogenetic signals. Higher altitude species had significantly lower molecular divergence as compared with the lowland species, yet ecological niches with less overlap. When projected onto a future climate scenario, highland species lose a greater amount of potentially suitable habitat compared to lower altitude species, and the majority of studied higher altitude species will face an overall loss of future suitable habitat.Main conclusionWe conclude that distinct phylogenetic signals not only unravel differing evolutionary histories but also show that the implications of species' tolerances to future changing climate vary. Over the past million years, historical climate change shaped the differing evolution and ecological niches of highland and lowland tropical pitcher plant species. Rapid, recent radiations of the higher altitude species are reflected in limited molecular divergence, which is in sharp contrast with the more gradually evolved and genetically distinct lower altitude species in our study. Our projections for future potentially suitable habitats show that on‐going climate shifts will have detrimental effects on especially the higher altitude species due to a narrower niche tolerance and dramatic loss of potentially suitable habitat.
Left ventricular outflow tract gradient is associated with reduced capillary density in hypertrophic cardiomyopathy irrespective of genotype
Authors: Güçlü Ahmet , Happé Chris , Eren Seyma , Korkmaz Ibrahim H. , Niessen Hans W. M. , Klein Patrick , van Slegtenhorst Marjon , Schinkel Arend F. , Michels Michelle , van Rossum Albert C. , Germans Tjeerd , van der Velden Jolanda 
Published: October 2015

AbstractBackgroundCoronary microvascular dysfunction (CMD) is an important feature of hypertrophic cardiomyopathy (HCM), which contributes negatively to symptoms and long‐term outcome. Previous in vivo imaging studies in HCM suggest that left ventricular outflow tract (LVOT) gradient and genetic status are important contributors to CMD. CMD may be caused by reduced capillary density. Here, we investigated whether a reduction in capillary density is related to genetic status or LVOT gradient severity in an in vitro study of HCM cardiac samples.MethodsUsing immunofluorescence microscopy, we analysed capillaries (Cap) and cardiomyocytes (CM) in myectomy specimens from 18 HCM patients with maximum left ventricular (LV) wall thickness ≥15 mm. All subjects exhibited significant LVOT obstruction, necessitating septal myectomy. In addition, control myocardium from the LV septal wall was collected at autopsy of 6 individuals that suffered a noncardiac death.ResultsCM area was higher in patients with HCM compared to controls. Capillary density was significantly lower in patients with HCM compared with controls (1425 ± 262 vs. 2543 ± 509 Cap/mm2, P < 0·001), as was the number of Cap per CM corrected for CM area (2·2 ± 0·5 vs. 4·2 ± 0·9 Cap/CM area, P < 0·001). Capillary density did not differ between genotype‐negative and genotype‐positive HCM patients at similar resting LVOT gradients. A significant correlation was present between resting LVOT gradient and CM area (r = 0·73, P < 0·001), capillary density (r = −0·74, P < 0·001) and the number of Cap per CM corrected for CM area (r = −0·82, P < 0·001).ConclusionsOur data indicate that LVOT gradient, rather than genetic status, is associated with reduced capillary density in HCM.
A new rescue regimen with plasma exchange and rituximab in high‐risk membranous glomerulonephritis
Authors: Müller‐Deile Janina , Schiffer Lena , Hiss Marcus , Haller Hermann , Schiffer Mario 
Published: October 2015

AbstractBackgroundEven though current treatment guidelines for idiopathic membranous glomerulonephritis (iMGN) exist, many questions regarding an optimal therapy remain unanswered. Complete remission cannot be achieved in all patients; relapses occur, in some cases frequently, and side effects from the immunosuppressive therapy are common. Therapeutic options in high‐risk patients not responding to standard immunosuppressive therapies are limited. Recent research reveals that the human M‐type phospholipase A2 receptor (PLA2R) is a causative factor in iMGN that parallels clinical disease activity. However, in some patients, this correlation is not evident and additional undetermined factors seem to play a role.DesignWe evaluated a new rescue protocol including plasma exchanges (PE) against albumin, intravenous immunoglobulins (IVIGs) and rituximab for 10 patients with a biopsy‐proven diagnosis of iMGN who were therapy‐resistant to all conventional regimens and had a urinary protein to creatinine ratio of more than 10 000 mg/g Crea. We compared this protocol with standard immunosuppressive protocols including monthly alternating prednisolone plus cyclophosphamide (18 patients), cyclosporine plus prednisolone (23 patients) and rituximab alone (eight patients) in a retrospective design.ResultsOur rescue regimen with PE, IVIGs and rituximab achieved partial remission in 90% of patients who had been otherwise refractory to therapy. The mean time to partial remission was 2·1 months. Furthermore, two anti‐PLA2R‐antibody negative patients were also treated with this rescue regimen, achieving partial remission after 1 and 4 months.ConclusionA combination of PE, IVIGs and rituximab is a treatment option to consider for high‐risk patients with iMGN who are refractory to conventional therapy.
Spatial transformations between superior colliculus visual and motor response fields during head‐unrestrained gaze shifts
Authors: Sadeh Morteza , Sajad Amirsaman , Wang Hongying , Yan Xiaogang , Crawford John Douglas 
Published: October 2015

AbstractWe previously reported that visuomotor activity in the superior colliculus (SC) – a key midbrain structure for the generation of rapid eye movements – preferentially encodes target position relative to the eye (Te) during low‐latency head‐unrestrained gaze shifts (DeSouza et al., 2011). Here, we trained two monkeys to perform head‐unrestrained gaze shifts after a variable post‐stimulus delay (400–700 ms), to test whether temporally separated SC visual and motor responses show different spatial codes. Target positions, final gaze positions and various frames of reference (eye, head, and space) were dissociated through natural (untrained) trial‐to‐trial variations in behaviour. 3D eye and head orientations were recorded, and 2D response field data were fitted against multiple models by use of a statistical method reported previously (Keith et al., 2009). Of 60 neurons, 17 showed a visual response, 12 showed a motor response, and 31 showed both visual and motor responses. The combined visual response field population (n = 48) showed a significant preference for Te, which was also preferred in each visual subpopulation. In contrast, the motor response field population (n = 43) showed a preference for final (relative to initial) gaze position models, and the Te model was statistically eliminated in the motor‐only population. There was also a significant shift of coding from the visual to motor response within visuomotor neurons. These data confirm that SC response fields are gaze‐centred, and show a target‐to‐gaze transformation between visual and motor responses. Thus, visuomotor transformations can occur between, and even within, neurons within a single frame of reference and brain structure.