julilili42/papers huggingface dataset:
Human Islets Exhibit Electrical Activity on Microelectrode Arrays (MEA)
2015-04-08

This study demonstrates for the first time that the microelectrode array (MEA) technique allows analysis of electrical activity of islets isolated from human biopsies. We have shown before that this method, i.e., measuring beta cell electrical activity with extracellular electrodes, is a powerful tool to assess glucose responsiveness of isolated murine islets. In the present study, human islets were shown to exhibit glucose-dependent oscillatory electrical activity. The glucose responsiveness could be furthermore demonstrated by an increase of insulin secretion in response to glucose. Electrical activity was increased by tolbutamide and inhibited by diazoxide. In human islets bursts of electrical activity were markedly blunted by the Na(+) channel inhibitor tetrodotoxin which does not affect electrical activity in mouse islets. Thus, the MEA technique emerges as a powerful tool to decipher online the unique features of human islets.Additionally, this technique will enable research with human islets even if only a few islets are available and it will allow a fast and easy test of metabolic integrity of islets destined for transplantation.
Adverbial Modifiers in Adjectival Passives
2015-04-08

The combination of adjectival passives with adverbial modifiers poses a problem for current adjectival conversion analyzes of the adjectival passive. An influential proposal by Kratzer (&lt;cross-ref type="bib" refid="ffv004-B40"&gt;1994&lt;/cross-ref&gt;, &lt;cross-ref type="bib" refid="ffv004-B42"&gt;2000&lt;/cross-ref&gt;) has been to explain the appearance of adverbial modifiers by assuming adjectival conversion not only at the lexical but also at the phrasal VP level. The present article develops an alternative account for the semantics of adjectival passives and their combination with adverbial modifiers and contrasts it with the verbal passive case. It takes adjectival passives in German to be a grammatical means for generating contextually shaped states of the subject referent that result from an (possibly complex) event type provided by the verb plus additional predicative material. The structural condition that allows adverbial modifiers to take part in the formation of the event type predicate is that they attach structurally low (V-adjuncts). The pragmatic condition is that they provide an informative restriction to the resulting state type. The article provides evidence from different domains of the grammar—prosody, syntax and semantics—that point to the particular structural status of adverbial modifiers in adjectival passives (V-adjuncts) as opposed to verbal passives (VP-adjuncts). These findings are corroborated by two psycholinguistic experiments that test the different syntactic and semantic status of adverbial modifiers in adjectival and verbal passives. On this basis, the article develops a compositional semantics for adjectival passives and their adverbial modifiers. In more general terms, the study provides an interesting test case for exploring the semantics of the verbal cluster in German.
The Greater Affinity of JC Polyomavirus Capsid for α2,6-Linked Lactoseries Tetrasaccharide c than for Other Sialylated Glycans Is a Major Determinant of Infectivity
2015-04-09

ABSTRACT The human JC polyomavirus (JCPyV) establishes an asymptomatic, persistent infection in the kidneys of the majority of the population and is the causative agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals. The Mad-1 strain of JCPyV, a brain isolate, was shown earlier to require α2,6-linked sialic acid on the lactoseries tetrasaccharide c (LSTc) glycan for attachment to host cells. In contrast, a JCPyV kidney isolate type 3 strain, WT3, has been reported to interact with sialic acid-containing gangliosides, but the role of these glycans in JCPyV infection has remained unclear. To help rationalize these findings and probe the effects of strain-specific differences on receptor binding, we performed a comprehensive analysis of the glycan receptor specificities of these two representative JCPyV strains using high-resolution X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, and correlated these data with the results of infectivity assays. We show here that capsid proteins of Mad-1 and WT3 JCPyV can both engage LSTc as well as multiple sialylated gangliosides. However, the binding affinities exhibit subtle differences, with the highest affinity observed for LSTc. Engagement of LSTc is a prerequisite for functional receptor engagement, while the more weakly binding gangliosides are not required for productive infection. Our findings highlight the complexity of virus-carbohydrate interactions and demonstrate that subtle differences in binding affinities, rather than the binding event alone, help determine tissue tropism and viral pathogenesis. IMPORTANCE Viral infection is initiated by attachment to receptors on host cells, and this event plays an important role in viral disease. We investigated the receptor-binding properties of human JC polyomavirus (JCPyV), a virus that resides in the kidneys of the majority of the population and can cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in the brains of immunosuppressed individuals. JCPyV has been reported to interact with multiple carbohydrate receptors, and we sought to clarify how the interactions between JCPyV and cellular carbohydrate receptors influenced infection. Here we demonstrate that JCPyV can engage numerous sialylated carbohydrate receptors. However, the virus displays preferential binding to LSTc, and only LSTc mediates a productive infection. Our findings demonstrate that subtle differences in binding affinity, rather than receptor engagement alone, are a key determinant of viral infection.
Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents
2015-04-09

Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson’s disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft–host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions.
Axions in gravity with torsion
2015-04-10

We study a scenario allowing a solution of the strong charge parity problem via the Peccei-Quinn mechanism, implemented in gravity with torsion. In this framework there appears a torsion-related pseudoscalar field known as Kalb-Ramond axion. We compare it with the so-called Barbero-Immirzi axion recently proposed in the literature also in the context of the gravity with torsion. We show that they are equivalent from the viewpoint of the effective theory. The phenomenology of these torsion-descended axions is completely determined by the Planck scale without any additional model parameters. These axions are very light and very weakly interacting with ordinary matter. We briefly comment on their astrophysical and cosmological implications in view of the recent BICEP2 and Planck data.
Management of Crohn's disease – are guidelines transferred to clinical practice?
2015-04-10

Background Management of Crohn's disease (CD) is a clinical challenge. In terms of an evidence‐based approach, clinical guidelines help to deal with this challenge. However, little is known about guideline adherence concerning the management of CD in Germany. Objective To survey German gastroenterologists with regards to their guideline adherence in daily clinical care. Method A web‐based national survey was conducted among German gastroenterologists. Results A total of 175 inflammatory bowel disease (IBD) practitioners responded to the survey. Overall, in the different clinical situations covered in the questionnaire guideline adherence is good. However, the 5‐aminosalicylic acid (5‐ASA) prescribing habits represent a striking exception. About 10–36% use 5‐ASA as mono‐therapy in CD, depending on the clinical scenario. Predominantly it is used in mild CD and in colonic involvement. To maintain a surgically achieved remission, therapeutic decisions broadly rely on individual approaches with azathioprine and 5‐ASA being used by about 30% of the respondents. Cessation of smoking as a “therapeutic” strategy of maintenance therapy is used by only half of the surveyed physicians. Conclusion Amongst German IBD practitioners, the guideline adherence is good overall. Reflecting ongoing uncertainty about the efficacy of mesalazine, its use in Crohn's disease is still heterogeneous.
Reprogramming of myeloid angiogenic cells byBartonella henselaeleads to microenvironmental regulation of pathological angiogenesis
2015-04-10

The contribution of myeloid cells to tumour microenvironments is a decisive factor in cancer progression. Tumour-associated macrophages (TAMs) mediate tumour invasion and angiogenesis through matrix remodelling, immune modulation and release of pro-angiogenic cytokines. Nothing is known about how pathogenic bacteria affect myeloid cells in these processes. Here we show that Bartonella henselae, a bacterial pathogen causing vasculoproliferative diseases (bacillary angiomatosis), reprogrammes human myeloid angiogenic cells (MACs), a pro-angiogenic subset of circulating progenitor cells, towards a TAM-like phenotype with increased pro-angiogenic capacity. B. henselae infection resulted in inhibition of cell death, activation of angiogenic cellular programmes and induction of M2 macrophage polarization. MACs infected with B. henselae incorporated into endothelial sprouts and increased angiogenic growth. Infected MACs developed a vascular mimicry phenotype in vitro, and expression of B. henselae adhesin A was essential in inducing these angiogenic effects. Secretome analysis revealed that increased pro-angiogenic activities were associated with the creation of a tumour-like microenvironment dominated by angiogenic inflammatory cytokines and matrix remodelling compounds. Our results demonstrate that manipulation of myeloid cells by pathogenic bacteria can contribute to microenvironmental regulation of pathological tissue growth and suggest parallels underlying both bacterial infections and cancer.
The Arab East and the Bedouin Component in Modern History: Emerging Perspectives on the Arid Lands as a Social Space
2015-04-10

In this paper we argue that historians of the eastern Arab lands (Ar. al-mashriq al-ʿarabī ) should turn their attention to the Bedouins for two main reasons. First, the societies in the Arab East cannot be adequately understood without a full evaluation of their Bedouin component, especially outside urban areas. Second, studying the Bedouins can open new perspectives on important debates in Middle Eastern historiography. The paper further contends that the arid lands of the Arab East still need to be explored as a historical region with its own distinct patterns of regional connectivity and political organisation. Finally, we highlight environmental history and the study of emic categories as promising avenues for future research on this region.
Simple multiplex PCR assays to detect common pathogens and associated genes encoding for acquired extended spectrum betalactamases (ESBL) or carbapenemases from surgical site specimens in Vietnam
2015-04-11

The novel in-house multiplex PCR assays are comparable to the bacterial culture approach in screening for common pathogens causing SSI and for relevant genotypes conferring betalactam/carbapenem resistance for bacteria. This is the first report of Turkey-specific ESBL gene (PER-1) and two Oxacilinase families (Oxa23 and Oxa 58) in Vietnam.
Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase
2015-04-13

Significance Ammonia metabolism in the liver is critical to prevent serious clinical conditions, such as hepatic encephalopathy. It was hypothesized that the Gln synthetase (GS) can metabolize ammonia with high affinity in the perivenous region of the liver. However, the in vivo relevance of this metabolic pathway remains unclear in view of other intra- and extrahepatic ammonia metabolizing pathways. Here, we show by creating a conditional GS KO mouse that specific deletion of the GS in the liver results in increased ammonia levels in the blood, induction of oxidative stress in brain tissue, and behavior abnormalities. In conclusion, GS in the liver is a key player in the maintenance of ammonia homeostasis.
Duration of Purkinje cell complex spikes increases with their firing frequency
2015-04-13

Climbing fiber (CF) triggered complex spikes (CS) are massive depolarization bursts in the cerebellar Purkinje cell (PC), showing several high frequency spikelet components (±600 Hz). Since its early observations, the CS is known to vary in shape. In this study we describe CS waveforms, extracellularly recorded in awake primates (Macaca mulatta) performing saccades. Every PC analyzed showed a range of CS shapes with profoundly different duration and number of spikelets. The initial part of the CS was rather constant but the later part differed greatly, with a pronounced jitter of the last spikelets causing a large variation in total CS duration. Waveforms did not effect the following pause duration in the simple spike (SS) train, nor were SS firing rates predictive of the waveform shapes or vice versa. The waveforms did not differ between experimental conditions nor was there a preferred sequential order of CS shapes throughout the recordings. Instead, part of their variability, the timing jitter of the CS's last spikelets, strongly correlated with interval length to the preceding CS: shorter CS intervals resulted in later appearance of the last spikelets in the CS burst, and vice versa. A similar phenomenon was observed in rat PCs recorded in vitro upon repeated extracellular stimulation of CFs at different frequencies in slice experiments. All together these results strongly suggest that the variability in the timing of the last spikelet is due to CS frequency dependent changes in PC excitability.
Subretinal Visual Implant Alpha IMS – Clinical trial interim report
2015-04-14

A subretinal visual implant (Alpha IMS, Retina Implant AG, Reutlingen, Germany) was implanted in 29 blind participants with outer retinal degeneration in an international multicenter clinical trial. Primary efficacy endpoints of the study protocol were a significant improvement of activities of daily living and mobility to be assessed by activities of daily living tasks, recognition tasks, mobility, or a combination thereof. Secondary efficacy endpoints were a significant improvement of visual acuity/light perception and/or object recognition (clinicaltrials.gov, NCT01024803). During up to 12 months observation time twenty-one participants (72%) reached the primary endpoints, of which thirteen participants (45%) reported restoration of visual function which they use in daily life. Additionally, detection, localization, and identification of objects were significantly better with the implant power switched on in the first 3 months. Twenty-five participants (86%) reached the secondary endpoints. Measurable grating acuity was up to 3.3 cycles per degree, visual acuities using standardized Landolt C-rings were 20/2000, 20/2000, 20/606 and 20/546. Maximal correct motion perception ranged from 3 to 35 degrees per second. These results show that subretinal implants can restore very-low-vision or low vision in blind (light perception or less) patients with end-stage hereditary retinal degenerations.
Thermal and exhumation history of the Eocene Chumstick Basin, Washington State, USA
2015-04-14

Abstract This study investigates the Cenozoic evolution of the Cascades Mountains, USA, by means of reconstructing the thermal history of the Chumstick Basin deposits that are located on the eastern flank of the orogen. We present new detrital apatite (U‐Th‐Sm)/He and detrital apatite fission‐track ages from the middle Eocene (~48–37 Ma) Chumstick Formation and modern river detritus. These data are integrated with the published thermochronometric ages of the adjoining Cascade Mountains basement. The new thermochronometer results are combined with existing vitrinite reflectance data for modeling of the basin's thermal history. Results suggest constant temperatures throughout the late Oligocene to early Miocene followed by rapid cooling since 17–10 Ma. Results indicate that the middle to late Miocene uplift of the Cascades resulted in reactivation of the fault zones bounding the Chumstick Basin. The structural reactivation and the weaker lithology of the basin strata in comparison to the harder and more resistant basement rocks of the Cascades resulted in significant basin exhumation. This interpretation is determined from younger apatite (U‐Th‐Sm)/He cooling ages observed in the reset detrital bedrock of the Chumstick Formation than in the adjoining basement rocks. These observations suggest a structural and lithological control on exhumation magnitudes in this region.
Copulatory Wounding and Traumatic Insemination
2015-04-15

Copulatory wounding (CW) is widespread in the animal kingdom, but likely underreported because of its cryptic nature. We use four case studies (Drosophila flies, Siphopteron slugs, Cimex bugs, and Callosobruchus beetles) to show that CW entails physiological and life-history costs, but can evolve into a routine mating strategy that, in some species, involves insemination through the wound. Although interspecific variation in CW is documented, few data exist on intraspecific and none on individual differences. Although defensive mechanisms evolve in the wound recipient, our review also indicates that mating costs in species with CW are slightly higher than in other species. Whether such costs are dose- or frequency-dependent, and whether defense occurs as resistance or tolerance, decisively affects the evolutionary outcome. In addition to sexual conflict, CW may also become a model system for reproductive isolation. In this context, we put forward a number of predictions, including (1) occasional CW is more costly than routine CW, (2) CW is more costly in between- than within-population matings, and (3) in the presence of CW, selection may favor the transmission of sexually transmitted diseases if they induce resource allocation. Finally, we outline, and briefly discuss, several medical implications of CW in humans.
Smooth Particle Hydrodynamics with nonlinear Moving-Least-Squares WENO reconstruction to model anisotropic dispersion in porous media
2015-04-15

Most numerical schemes applied to solve the advection–diffusion equation are affected by numerical diffusion. Moreover, unphysical results, such as oscillations and negative concentrations, may emerge when an anisotropic dispersion tensor is used, which induces even more severe errors in the solution of multispecies reactive transport. To cope with this long standing problem we propose a modified version of the standard Smoothed Particle Hydrodynamics (SPH) method based on a Moving-Least-Squares-Weighted-Essentially-Non-Oscillatory (MLS-WENO) reconstruction of concentrations. This scheme formulation (called MWSPH) approximates the diffusive fluxes with a Rusanov-type Riemann solver based on high order WENO scheme. We compare the standard SPH with the MWSPH for different a few test cases, considering both homogeneous and heterogeneous flow fields and different anisotropic ratios of the dispersion tensor. We show that, MWSPH is stable and accurate and that it reduces the occurrence of negative concentrations compared to standard SPH. When negative concentrations are observed, their absolute values are several orders of magnitude smaller compared to standard SPH. In addition, MWSPH limits spurious oscillations in the numerical solution more effectively than classical SPH. Convergence analysis shows that MWSPH is computationally more demanding than SPH, but with the payoff a more accurate solution, which in addition is less sensitive to particles position. The latter property simplifies the time consuming and often user dependent procedure to define the initial dislocation of the particles.
The Role of the Interstitium of the Renal Cortex in Renal Disease
2015-04-16

Morphometrical investigations (point-counting method) showed that in different inflammatory (endocapillary -- acute -- GN, mesangioproliferative GN, membranoproliferative GN) glomerulonephritides and in non-inflammatory glomerular diseases (perireticular amyloidosis), there are statistically significant correlation between serum creatine concentrations at the time of biopsy and the enlargement of the cortical interstitium by fibrosis. Similar results were obtained in investigating different grades of benign nephrosclerosis with transition into secondary malignant nephrosclerosis conditioned by hypertension and in chronic diffuse sclerosing interstitial nephritides of different etiologies. As hypothesis, we assume that a narrowing of the postglomerular vessel network by interstitial fibrosis take place. This could lead to an increase resistance of the renal cortical blood flow. In spite of an elevated effective filtration pressure, the slowing of the glomerular blood flow may lead to the reduction of GRF and to an increase of the serum creatinine concentration. Additionally, in the case of interstitial fibrosis the tubules look atrophied. This could be the consequence of the reduced GFR as a sign of inactivity. On the other hand, tubular atrophy could result from malnutrition in the case of interstitial fibrosis. The resorptive capacity of these atrophied-looking tubules could be lowered and the GFR could be diminished by the so-called Thurau mechanism.
Genome Mining of Streptomyces sp. Tü 6176: Characterization of the Nataxazole Biosynthesis Pathway
2015-04-16

Abstract Streptomyces sp. Tü 6176 produces the cytotoxic benzoxazole nataxazole. Bioinformatic analysis of the genome of this organism predicts the presence of 38 putative secondary‐metabolite biosynthesis gene clusters, including those involved in the biosynthesis of AJI9561 and its derivative nataxazole, the antibiotic hygromycin B, and ionophores enterobactin and coelibactin. The nataxazole biosynthesis gene cluster was identified and characterized: it lacks the O‐methyltransferase gene required to convert AJI9561 into nataxazole. This O‐methyltransferase activity might act as a resistance mechanism, as AJI9561 shows antibiotic activity whereas nataxazole is inactive. Moreover, heterologous expression of the nataxazole biosynthesis gene cluster in S. lividans JT46 resulted in the production of AJI9561. Nataxazole biosynthesis requires the shikimate pathway to generate 3‐hydroxyanthranilate and an iterative type I PKS to generate 6‐methylsalicylate. Production of nataxazole was improved up to fourfold by disrupting one regulatory gene in the cluster. An additional benzoxazole, 5‐hydroxynataxazole is produced by Streptomyces sp. Tü 6176. 5‐Hydroxynataxazole derives from nataxazole by the activity of an as yet unidentified oxygenase; this implies cross‐talk between the nataxazole biosynthesis pathway and an unknown pathway.