julilili42/papers huggingface dataset:
Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence
2021-06-05

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI.
The Global Convergence of the Nonlinear Power Method for Mixed-Subordinate Matrix Norms
2021-06-05

Abstract We analyze the global convergence of the power iterates for the computation of a general mixed-subordinate matrix norm. We prove a new global convergence theorem for a class of entrywise nonnegative matrices that generalizes and improves a well-known results for mixed-subordinate <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mi>l</mml:mi> <mml:mi>p</mml:mi> </mml:msup> </mml:math> matrix norms. In particular, exploiting the Birkoff–Hopf contraction ratio of nonnegative matrices, we obtain novel and explicit global convergence guarantees for a range of matrix norms whose computation has been recently proven to be NP-hard in the general case, including the case of mixed-subordinate norms induced by the vector norms made by the sum of different <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mi>l</mml:mi> <mml:mi>p</mml:mi> </mml:msup> </mml:math> -norms of subsets of entries.
CBM Performance for Λ Hyperon Directed Flow Measurements in Au + Au Collisions at 12A GeV/c
2021-06-05

We present the current status of the performance studies of Λ hyperon directed flow measurement with the CBM experiment at the future FAIR facility in Darmstadt. Kalman Filter mathematics is used to reconstruct Λ→pπ− weak decay kinematics, while the Particle Finder Simple package is used to optimize criteria for Λ hyperon candidate selection. Directed flow of Λ hyperons is studied as a function of rapidity, transverse momentum and collision centrality. The effects on flow measurement due to non-uniformity of the CBM detector response in the azimuthal angle, transverse momentum and rapidity are corrected using the QnTools analysis framework.
Zonisamide‐responsive myoclonus in SEMA6B‐associated progressive myoclonic epilepsy
2021-06-06

Abstract We present a female patient in her early twenties with global development delay, progressive ataxia, epilepsy, and myoclonus caused by a stop mutation in the SEMA6B gene. Truncating DNA variants located in the last exon of SEMA6B have recently been identified as a cause of autosomal dominant progressive myoclonus epilepsy. In many cases, myoclonus in the context of progressive myoclonic epilepsy is refractory to medical treatment. In the present case, treatment with zonisamide caused clinical improvement, particularly of positive and negative truncal myoclonus, considerably improving patient’s gait and thus mobility.
Multi-omics profiling of Earth’s biomes reveals patterns of diversity and co-occurrence in microbial and metabolite composition across environments
2021-06-06

ABSTRACT As our understanding of the structure and diversity of the microbial world grows, interpreting its function is of critical interest for understanding and managing the many systems microbes influence. Despite advances in sequencing, lack of standardization challenges comparisons among studies that could provide insight into the structure and function of microbial communities across multiple habitats on a planetary scale. Technical variation among distinct studies without proper standardization of approaches prevents robust meta-analysis. Here, we present a multi-omics, meta-analysis of a novel, diverse set of microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry), centering our description on relationships and co-occurrences of microbially-related metabolites and microbial taxa across environments. Standardized protocols and analytical methods for characterizing microbial communities, including assessment of molecular diversity using untargeted metabolomics, facilitate identification of shared microbial and metabolite features, permitting us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of a community resource that will become more valuable with time. To provide examples of applying this database, we outline important ecological questions that can be addressed, and test the hypotheses that every microbe and metabolite is everywhere, but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment. The relative abundances of microbially-related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner, and highlight the power of certain chemistry – in particular terpenoids – in distinguishing Earth’s environments.
Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel–Lindau disease‐related tumours
2021-06-06

Abstract Aims Although inactivation of the von Hippel–Lindau gene ( VHL ) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL‐disease‐related tumours. Methods Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL‐disease‐related ELSTs by targeted sequencing and DNA methylation analysis. Results VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer‐related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL‐disease‐related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL‐disease‐related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL‐disease‐related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p &lt; 0.0001, Fisher's exact test). VHL‐disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression‐free survival ( p = 0.0002, log‐rank test). Conclusion Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs.
Bone-related behaviours of captive chimpanzees (Pan troglodytes) during an excavating experiment
2021-06-06

After stone tools, bone tools are the most abundant artefact type in the Early Pleistocene archaeological record. That said, they are still relatively scarce, limiting our understanding of the behaviors that led to their production and use. Observations of extant primates constitute a unique source of behavioural data with which to construct hypotheses about the potential uses of bone tools by our ancient hominin ancestors. In this study, we investigated the behavioural responses of two groups of captive chimpanzees (Pan troglodytes) (Ntotal=42) to the availability of isolated, disarticulated, defleshed, ungulate bones while participating in a foraging task aimed at eliciting excavating behavior involving those same bone specimens. Each chimpanzee group was provided with bone specimens of different characteristics and the two groups differed in their respective levels of experience with using tools to excavate (one group was mostly inexperienced while the other had ample experience utilizing sticks as excavating tools). We found that several individuals from the inexperienced group used the provided bone specimens as tools during the task. In contrast, none of the individuals from the experienced group used bones as excavating tools. Instead, these experienced chimpanzees performed other bone-related behaviours (not observed in the inexperienced group), such as hammering and extracting marrow with wooden tools. Given that previous experience in tool excavation did not predict the use of bones as tools in the excavating task, we hypothesize that the differences in behavior observed between the two chimpanzee groups were the result of the varying characteristics of the bones provided to each. Furthermore, our results suggest that it is the intrinsic characteristics of raw materials rather than the material itself that determines whether chimpanzees perceive an object as a suitable excavating tool.
The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets
2021-06-07

Abstract Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1 −/− mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo. In conclusion, we identified a mechanism for the control of tissue neovascularization through C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic factor CXCL4.
Novel soluble guanylyl cyclase activators increase glomerular cGMP, induce vasodilation and improve blood flow in the murine kidney
2021-06-07

Background and Purpose Generation of cGMP via NO‐sensitive soluble guanylyl cyclase (sGC) has been implicated in the regulation of renal functions. Chronic kidney disease (CKD) is associated with decreased NO bioavailability, increased oxidative stress and oxidation of sGC to its haem‐free form, apo‐sGC. Apo‐sGC cannot be activated by NO, resulting in impaired cGMP signalling that is associated with chronic kidney disease progression. We hypothesised that sGC activators, which activate apo‐sGC independently of NO, increase renal cGMP production under conditions of oxidative stress, thereby improving renal blood flow (RBF) and kidney function. Experimental Approach Two novel sGC activators, runcaciguat and BAY‐543, were tested on murine kidney. We measured cGMP levels in real time in kidney slices of cGMP sensor mice, vasodilation of pre‐constricted glomerular arterioles and RBF in isolated perfused kidneys. Experiments were performed at baseline conditions, under L‐NAME‐induced NO deficiency, and in the presence of oxidative stress induced by ODQ. Key Results Mouse glomeruli showed NO‐induced cGMP increases. Under baseline conditions, sGC activator did not alter glomerular cGMP concentration or NO‐induced cGMP generation. In the presence of ODQ, NO‐induced glomerular cGMP signals were markedly reduced, whereas sGC activator induced strong cGMP increases. L‐NAME and ODQ pretreated isolated glomerular arterioles were strongly dilated by sGC activator. sGC activator also increased cGMP and RBF in ODQ‐perfused kidneys. Conclusion and Implication sGC activators increase glomerular cGMP, dilate glomerular arterioles and improve RBF under disease‐relevant oxidative stress conditions. Therefore, sGC activators represent a promising class of drugs for chronic kidney disease treatment. LINKED ARTICLES This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
Contesting large-scale land acquisitions in the Global South
2021-06-07

As agricultural investors have acquired large tracts of land in the Global South recently, many affected communities and civil society groups have contested what they perceive as land grabbing. These communities have struggled to retain their land, protect their livelihoods, or benefit from the investment. There has been much academic interest in these conflicts. Studying the emerging literature, this review identifies the main theoretical perspectives and synthesizes the case study evidence. The goal is to better understand how communities contest large-scale land acquisitions (LSLAs) and to explain their tactics. For this purpose, a sample was collected that consists of 46 studies and 28 LSLA cases from the Global South. Since most of these studies adopt single theoretical perspectives from resistance research, the present study links multiple theoretical strands, most importantly everyday resistance, contentious politics, and legal mobilization. Based on the cases reviewed, the analysis shows that the tactics of contention are diverse but can also be grouped into three repertoires. It is found that affected communities use everyday resistance mostly when they face particularly unfavorable circumstances. In contrast, certain political opportunities and involvement of local leaders enable organized protests through either collective action or rights-based contention. Overall, this study contributes to the literature not only by bringing together case observations to see the big picture, but also by identifying the main repertoires, tentative frequencies of tactics, and less relevant circumstances and mechanisms. In practical terms, the findings suggest that development and civil society actors can play important roles for assisting rural populations and local leaders in fending off land grabs.
Learning divisive normalization in primary visual cortex
2021-06-07

Divisive normalization (DN) is a prominent computational building block in the brain that has been proposed as a canonical cortical operation. Numerous experimental studies have verified its importance for capturing nonlinear neural response properties to simple, artificial stimuli, and computational studies suggest that DN is also an important component for processing natural stimuli. However, we lack quantitative models of DN that are directly informed by measurements of spiking responses in the brain and applicable to arbitrary stimuli. Here, we propose a DN model that is applicable to arbitrary input images. We test its ability to predict how neurons in macaque primary visual cortex (V1) respond to natural images, with a focus on nonlinear response properties within the classical receptive field. Our model consists of one layer of subunits followed by learned orientation-specific DN. It outperforms linear-nonlinear and wavelet-based feature representations and makes a significant step towards the performance of state-of-the-art convolutional neural network (CNN) models. Unlike deep CNNs, our compact DN model offers a direct interpretation of the nature of normalization. By inspecting the learned normalization pool of our model, we gained insights into a long-standing question about the tuning properties of DN that update the current textbook description: we found that within the receptive field oriented features were normalized preferentially by features with similar orientation rather than non-specifically as currently assumed.
BIOINSECTICIDES AS FUTURE MAINSTREAM PEST CONTROL AGENTS: OPPORTUNITIES AND CHALLENGES
2021-06-07

&lt;List&gt; &lt;ListItem&gt;&lt;ItemContent&gt;&lt;p&gt;&#8226;Wide use of botanical insecticides is limited by the availability of certain plants.&lt;/p&gt;&lt;/ItemContent&gt;&lt;/ListItem&gt; &lt;ListItem&gt;&lt;ItemContent&gt;&lt;p&gt;&#8226;Studies are needed to improve RNAi efficiency and to assess their safety risk.&lt;/p&gt;&lt;/ItemContent&gt;&lt;/ListItem&gt; &lt;ListItem&gt;&lt;ItemContent&gt;&lt;p&gt;&#8226;Microbial insecticides are promising, but they only control a narrow range of pests.&lt;/p&gt;&lt;/ItemContent&gt;&lt;/ListItem&gt; &lt;ListItem&gt;&lt;ItemContent&gt;&lt;p&gt;&#8226;Multitarget approach should be a promising strategy in future pest control.&lt;/p&gt;&lt;/ItemContent&gt;&lt;/ListItem&gt; &lt;ListItem&gt;&lt;ItemContent&gt;&lt;p&gt;&#8226;Nanoformulation could enhance stability and control the release of bioinsecticides.&lt;/p&gt;&lt;/ItemContent&gt;&lt;/ListItem&gt;&lt;/List&gt;&lt;/p&gt; &lt;p&gt;Bioinsecticides are naturally-occurring substances from different sources that control insect pests. Ideal bioinsecticides should have low toxicity to non-target organisms. They should also be easily degraded in sewage treatment works and natural environments, highly effective in small quantities and affect target pests only. Public concerns about possible side-effects of synthetic pesticides have accelerated bioinsecticide research and development. However, to develop bioinsecticides into mainstream products, their high production costs, short shelf-life and often uncertain modes of action need to be considered. This review summarizes current progress on bioinsecticides which are categorized as biochemical insecticides and their derivatives, plant-incorporated protectants, and microbial bioinsecticides. The current constraints that prevent bioinsecticides from being widely used are discussed and future research directions are proposed.
Absence of Non-Canonical, Inhibitory MYD88 Splice Variants in B Cell Lymphomas Correlates With Sustained NF-κB Signaling
2021-06-07

Gain-of-function mutations of the TLR adaptor and oncoprotein MyD88 drive B cell lymphomagenesis via sustained NF-κB activation. In myeloid cells, both short and sustained TLR activation and NF-κB activation lead to the induction of inhibitory MYD88 splice variants that restrain prolonged NF-κB activation. We therefore sought to investigate whether such a negative feedback loop exists in B cells. Analyzing MYD88 splice variants in normal B cells and different primary B cell malignancies, we observed that MYD88 splice variants in transformed B cells are dominated by the canonical, strongly NF-κB-activating isoform of MYD88 and contain at least three novel, so far uncharacterized signaling-competent splice isoforms. Sustained TLR stimulation in B cells unexpectedly reinforces splicing of NF-κB-promoting, canonical isoforms rather than the ‘MyD88s’, a negative regulatory isoform reported to be typically induced by TLRs in myeloid cells. This suggests that an essential negative feedback loop restricting TLR signaling in myeloid cells at the level of alternative splicing, is missing in B cells when they undergo proliferation, rendering B cells vulnerable to sustained NF-κB activation and eventual lymphomagenesis. Our results uncover MYD88 alternative splicing as an unappreciated promoter of B cell lymphomagenesis and provide a rationale why oncogenic MYD88 mutations are exclusively found in B cells.
Attentional Processing of Disgust and Fear and Its Relationship With Contamination-Based Obsessive–Compulsive Symptoms: Stronger Response Urgency to Disgusting Stimuli in Disgust-Prone Individuals
2021-06-07

Disgust has recently been characterized as a low-urgency emotion, particularly compared to fear. The aim of the present study is to clarify whether behavioral inhibition during disgust engagement is characteristic of a low-urgency emotion and thus indicates self-imposed attentional avoidance in comparison to fear. Therefore, 54 healthy participants performed an emotional go/no-go task with disgust- and fear-relevant as well as neutral pictures. Furthermore, heart rate activity and facial muscle activity on the fear-specific m. corrugator supercilli and the disgust-specific m. levator labii were assessed. The results partially support the temporal urgency hypothesis of disgust. The emotion conditions significantly differed in emotional engagement and in the facial muscle activity of the m. levator labii as expected. However, contrary to our expectations, no differences between the emotion conditions regarding behavioral inhibition as well as heart rate change could be found. Furthermore, individuals with a higher-trait disgust proneness showed faster reactions and higher activity of the m. levator labii in response to disgust stimuli. The results show that different trait levels influence attentional engagement and physiological parameters but have only a small effect on behavioral inhibition.
Impaired Executive Function and Depression as Independent Risk Factors for Reported Delirium Symptoms: An Observational Cohort Study Over 8 Years
2021-06-07

Background Acute medical illnesses, surgical interventions, or admissions to hospital in older individuals are frequently associated with a delirium. In this cohort study, we investigated the impact of specific cognitive domains and depression before the occurrence of delirium symptoms in an 8-year observation of older non-hospitalized individuals. Methods In total, we included 807 participants (48–83 years). Deficits in specific cognitive domains were measured using the CERAD test battery, and depressive symptoms were measured using Beck Depression Inventory and the Geriatric Depression Scale (GDS) before the onset of a delirium. Delirium symptoms were retrospectively assessed by a questionnaire based on the established Nursing Delirium Screening Scale. Results Fifty-eight of eight hundred seven participants (7.2%) reported delirium symptoms over the 8-year course of the study. Sixty-nine percent ( n = 40) of reported delirium symptoms were related to surgeries. In multivariate regression analysis, impaired executive function was an independent risk factor ( p = 0.034) for the occurrence of delirium symptoms. Furthermore, age ( p = 0.014), comorbidities [captured by the Charlson Comorbidity Index (CCI)] ( p &amp;lt; 0.001), and depression ( p = 0.012) were significantly associated with reported delirium symptoms. Conclusion Especially prior to elective surgery or medical interventions, screening for impaired executive function and depression could be helpful to identify patients who are at risk to develop delirium symptoms.