julilili42/papers huggingface dataset:
Protein phase separation and determinants of in cell crystallization
2019-10-30

Abstract Liquid‐liquid phase separation (LLPS) in cells is known as a complex physicochemical process causing the formation of membrane‐less organelles (MLOs). Cells have well‐defined different membrane‐surrounded organelles like mitochondria, endoplasmic reticulum, lysosomes, peroxisomes, etc., however, on demand they can create MLOs as stress granules, nucleoli and P bodies to cover vital functions and regulatory activities. However, the mechanism of intracellular molecule assembly into functional compartments within a living cell remains till now not fully understood. in vitro and in vivo investigations unveiled that MLOs emerge after preceding liquid‐liquid, liquid‐gel, liquid‐semi‐crystalline, or liquid‐crystalline phase separations. Liquid‐liquid and liquid‐gel MLOs form the majority of cellular phase separation events, while the occurrence of micro‐sized crystals in cells was only rarely observed, however can be considered as a result of a preceding protein phase separation event. In vivo, also known and termed as in cellulo crystals, are reported since 1853. In some cases, they have been linked to vital cellular functions, such as storage and detoxification. However, the occurrence of in cellulo crystals is also associated to diseases like cataract, hemoglobin C diseases, etc. Therefore, better knowledge about the involved molecular processes will support drug discovery investigations to cure diseases related to in cellulo crystallization. We summarize physical and chemical determinants known today required for phase separation initiation and formation and in cellulo crystal growth. In recent years it has been demonstrated that LLPS plays a crucial role in cell compartmentalization and formation of MLOs. Here we discuss potential mechanisms and potential crowding agents involved in protein phase separation and in cellulo crystallization.
Selective Removal of Water Generated during Hydrogenotrophic Methanation from Culture Medium Using Membrane Distillation
2019-10-30

Methane production was carried out in two different types of reactors using a thermophilic and hydrogenotrophic methanogen, Methanothermobacter sp. KEPCO-1, which converts hydrogen and carbon dioxide into methane at 60 °C. The two reactors used for methane production were stirred-tank reactor (ST) and a bubble column reactor (BC), which were selected because they can provide a good comparison between the medium agitation type and gas–liquid mass transfer. The specific growth rate of KEPCO-1 in the ST and BC was 0.03 h−1 and 0.07 h−1, respectively. The methane conversion rate increased to 77.8 L/L/d in the ST and 19.8 L/L/d in the BC. To prevent the dilution of nutrients in the medium by the water generated during the hydrogenotrophic methanation reaction, a membrane distillation (MD) process was applied to selectively remove water from the culture medium. The MD process selectively removed only water from the medium. Fouling by KEPCO-1 had a negligible effect on flux and showed a high removal performance flux of 16.3 ± 3.1 L/m2/h. By operating the MD process in conjunction with the hydrogenotrophic methanation process, it is possible to prevent the dilution of the nutrients in the medium by the water generated during the methanation process, thereby maintaining stable microbial growth and methanation activity.
Differential deletion of GDNF in the auditory system leads to altered sound responsiveness
2019-10-30

Abstract Glial‐derived neurotrophic factor (GDNF) has been proposed as a potent neurotrophic factor with the potential to cure neurodegenerative diseases. In the cochlea, GDNF has been detected in auditory neurons and sensory receptor cells and its expression is upregulated upon trauma. Moreover, the application of GDNF in different animal models of deafness has shown its capacity to prevent hearing loss and promoted its future use in therapeutic trials in humans. In the present study we have examined the endogenous requirement of GDNF during auditory development in mice. Using a lacZ knockin allele we have confirmed the expression of GDNF in the cochlea including its sensory regions during development. Global inactivation of GDNF throughout the hearing system using a Foxg1‐ Cre line causes perinatal lethality but reveals no apparent defects during formation of the cochlea. Using TrkC‐ Cre and Atoh1‐ Cre lines, we were able to generate viable mutants lacking GDNF in auditory neurons or both auditory neurons and sensory hair cells. These mutants show normal frequency‐dependent auditory thresholds. However, mechanoelectrical response properties of outer hair cells (OHCs) in TrkC‐ Cre GDNF mutants are altered at low thresholds. Furthermore, auditory brainstem wave analysis shows an abnormal increase of wave I. On the other hand, Atoh1‐ Cre GDNF mutants show normal OHC function but their auditory brainstem wave pattern is reduced at the levels of wave I, III and IV. These results show that GDNF expression during the development is required to maintain functional hearing at different levels of the auditory system.
Collaborative open science as a way to reproducibility and new insights in primate cognition research
2019-10-31

The field of primate cognition studies how primates, including humans, perceive, process, store, retrieve, and use information to guide decision making and other behavior. Much of this research is motivated by a desire to understand how these abilities evolved. Large and diverse samples from a wide range of species are vital to achieving this goal. In reality, however, primate cognition research suffers from small sample sizes and is often limited to a handful of species, which constrains the evolutionary inferences we can draw. We conducted a systematic review of primate cognition research published between 2014 and 2019 to quantify the extent of this problem. Across 574 studies, the median sample size was 7 individuals. Less than 15% of primate species were studied at all, and only 19% of studies included more than one species. Further, the species that were studied varied widely in how much research attention they received, partly because a small number of test sites contributed most of the studies. These results suggest that the generalizability of primate cognition studies may be severely limited. Publication bias, questionable research practices, and a lack of replication attempts may exacerbate these problems. We describe the ManyPrimates project as one approach to overcoming some of these issues by establishing an infrastructure for large-scale collaboration in primate cognition research. Building on similar initiatives in other areas of psychology, this approach has already yielded one of the largest and most diverse primate samples to date and enables us to ask many research questions that can only be addressed through collaboration.
Placental gene expression and antibody levels of mother-neonate pairs reveal an enhanced risk for inflammation in a helminth endemic country
2019-10-31

Abstract In utero exposure to environmental factors can modify the development of allergies later in life whereby the mechanisms of the feto-maternal crosstalk still remain largely unknown. Murine studies revealed that inflammatory maternal signals elicited by chronic helminth infection within the placenta imprint a distinct gene expression profile related to the Vitamin-D-receptor (VDR)-inflammation-axis. We thus investigated whether pro- or anti- inflammatory immune responses as well as VDR and related gene expression within the placenta differ between women from helminth-endemic and non-endemic areas. A prospective pilot study was conducted in Munich, Germany (helminth non-endemic) and Lambaréné, Gabon (helminth-endemic). At delivery, clinical information alongside placenta tissue samples and maternal and cord blood were obtained for further laboratory analysis. Schistosoma haematobium infection was detected in 13/54 (23%) Gabonese women. RT PCR revealed significantly lower gene expression of VDR, Cyp27b1, Foxp3 and IL10 in Gabonese compared to German placentae as well as significantly lower levels of plasma IgG4 in newborns resulting in a significantly higher IgE/IgG4 ratio. These findings demonstrate that exposure in utero to different environments alters placental gene expression and thus possibly plays a role in the development and modulation of the immune system of the offspring.
Ligand‐ and Structure‐Based Approaches of Escherichia coli FabI Inhibition by Triclosan Derivatives: From Chemical Similarity to Protein Dynamics Influence
2019-10-31

Abstract Enoyl‐acyl carrier protein reductase (FabI) is the limiting step to complete the elongation cycle in type II fatty acid synthase (FAS) systems and is a relevant target for antibacterial drugs. E. coli FabI has been employed as a model to develop new inhibitors against FAS, especially triclosan and diphenyl ether derivatives. Chemical similarity models (CSM) were used to understand which features were relevant for FabI inhibition. Exhaustive screening of different CSM parameter combinations featured chemical groups, such as the hydroxy group, as relevant to distinguish between active/decoy compounds. Those chemical features can interact with the catalytic Tyr156. Further molecular dynamics simulation of FabI revealed the ionization state as a relevant for ligand stability. Also, our models point the balance between potency and the occupancy of the hydrophobic pocket. This work discusses the strengths and weak points of each technique, highlighting the importance of complementarity among approaches to elucidate Ec FabI inhibitor's binding mode and offers insights for future drug discovery.
Site formation processes and urban transformations during Late Antiquity from a high‐resolution geoarchaeological perspective:Baelo Claudia, Spain
2019-10-31

Abstract To understand abandonment processes and secondary uses of public buildings is a key‐challenge to recognize the scope of the urban transformations in Roman cities during Late Antiquity. In this sense, administrative and religious public spaces such as the fora underwent a great variety of transformations resulting in the genesis of a complex stratigraphy of anthropogenic and natural deposits. Baelo Claudia is a well‐known Roman city located in the Atlantic coast of southern Spain. Recent excavations in the forum have provided new data that elucidate Late Roman urban transformations. In this study, we use archaeological soil micromorphology, physico‐chemical analyses and geochemistry to investigate site formation processes and to document nontraditional forms of occupation not visible in the macroscopic archaeological record. This methodology allowed for the distinction of several anthropogenic activities such as glass recycling, reflooring practices, plundering of ornamental marbles, middening of organic and penning residues, together with the progressive decay of earth‐based constructions. The complex superposition of site formation processes seen at Baelo Claudia underlines the role of micromorphology in the identification of behavioral signatures and its relevance in deciphering urban transformation in Late Antiquity.
Mitigating climate change: using the physician’s tool of the trade
2019-10-31

Climate change is happening now and is an omnipresent topic in the media. The debate is dominated by discussion about climate objectives and deep emission cuts on an international level. But what about individual steps and personal actions to mitigate climate change? What tools of the trade do physicians possess? Wynes and Nicholas identified four key actions that most substantially decrease an individual’s carbon footprint1 including eating a plant-based diet, avoiding air travel, living car-free, and having one fewer child. How expedient are these actions in daily care and what potential barriers exist? A physician without a car is hard to imagine when it comes to home visits in remote and rural areas. Older people are often immobile and dependent upon the doctor visiting them at home. In many countries home visits are an integral aspect of primary care.2 Imagine the 84-year-old woman living several miles down the road and phoning ...
Distributed Analytics on Sensitive Medical Data: The Personal Health Train
2019-11-01

In recent years, as newer technologies have evolved around the healthcare ecosystem, more and more data have been generated. Advanced analytics could power the data collected from numerous sources, both from healthcare institutions, or generated by individuals themselves via apps and devices, and lead to innovations in treatment and diagnosis of diseases; improve the care given to the patient; and empower citizens to participate in the decision-making process regarding their own health and well-being. However, the sensitive nature of the health data prohibits healthcare organizations from sharing the data. The Personal Health Train (PHT) is a novel approach, aiming to establish a distributed data analytics infrastructure enabling the (re)use of distributed healthcare data, while data owners stay in control of their own data. The main principle of the PHT is that data remain in their original location, and analytical tasks visit data sources and execute the tasks. The PHT provides a distributed, flexible approach to use data in a network of participants, incorporating the FAIR principles. It facilitates the responsible use of sensitive and/or personal data by adopting international principles and regulations. This paper presents the concepts and main components of the PHT and demonstrates how it complies with FAIR principles.
Effects of Hormonal Contraceptives on Mood: A Focus on Emotion Recognition and Reactivity, Reward Processing, and Stress Response
2019-11-01

Abstract Purpose of Review We review recent research investigating the relationship of hormonal contraceptives and mood with a focus on relevant underlying mechanisms, such as emotion recognition and reactivity, reward processing, and stress response. Recent Findings Adverse effects of hormonal contraceptives (HCs) on mood seem most consistent in women with a history of depressive symptoms and/or previous negative experience with HC-intake. Current evidence supports a negativity bias in emotion recognition and reactivity in HC-users, although inconsistent to some extent. Some data, however, do indicate a trend towards a blunted reward response and a potential dysregulation of the stress response in some HC-users. Summary HC-effects on psychological and neurophysiological mechanisms underlying mood are likely context-dependent. We provide suggestions on how to address some of the contributing factors to this variability in future studies, such as HC-dose, timing, administration-mode, and individual risk. A better understanding of how and when HCs affect mood is critical to provide adequate contraceptive choices to women worldwide.
The areal typology of western Middle and South America: Towards a comprehensive view
2019-11-01

Abstract Against a multidisciplinary background this contribution explores the areal typology of western Middle and South America. Based on a new language sample and a typological questionnaire that is specifically designed to bring some of the poorly documented and extinct languages into the debate, we explore the areal distribution of 77 linguistic traits in 44 languages. While one of the goals of the present article is to provide a general up-to-date view of the areal patterning of these traits on a large scale, we also explore a number of specific questions in more detail. In particular, we address the relationship between known language areas like Mesoamerica and the Central Andes with their respective peripheries, the possibility of detecting an areal-typological signal that predates the rise of these linguistic areas, and, finally, the question of linguistic convergence along the Pacific coast. We find that, while the languages of the Mesoamerican periphery are rather diffuse typologically, the structural profiles of the Central Andean languages are embedded organically into a more general cluster of Andean typological affinities that alters continuously as one moves through geographical space. In different ways, the typological properties of the peripheral languages may reflect a situation that goes back to time depths which are greater than that of the emergence of the Mesoamerican and Central Andean linguistic areas. Finally, while we can confirm typological affinities with Mesoamerica for some languages of coastal South America, we do not find support for large-scale linguistic convergence on the Pacific coast.
Terahertz emission from Bi2Sr2CaCu2O8+x intrinsic Josephson junction stacks
2019-11-01

Electromagnetic radiation at frequencies in the terahertz (THz) range is highly interesting for potential applications in biology or medical diagnostics, high-bandwidth communication, security and defence, nondestructive evaluation, and other fields. However, particularly, the frequency range between 0.5 and 1.5 THz has turned out to be difficult to fill with powerful coherent solid-state sources. Suitably patterned structures made of the high critical temperature superconductor Bi2Sr2CaCu2O8+δ can operate in this frequency range, and the best devices presently reach an output power around 100μW. In this tutorial, we will give an introduction into the basic physics of this type of oscillator and into the challenges that appear. We will explain how the generators are fabricated, which measurement techniques are used for characterization, and which models are used to describe their dynamics. We will also give some examples demonstrating potential applications in the fields of THz imaging and THz spectroscopy.
Pathogenicity of Clinical OXA-48 Isolates and Impact of the OXA-48 IncL Plasmid on Virulence and Bacterial Fitness
2019-11-01

OXA-48 is the most common carbapenemase in Enterobacterales in Germany and one of the most frequent carbapenemases worldwide. Several reports have associated <i>bla</i> <sub>OXA</sub> <sub>-</sub> <sub>48</sub> with a virulent host phenotype. To challenge this hypothesis, 35 OXA-48-producing clinical isolates of <i>Escherichia coli</i> (<i>n</i> = 15) and <i>Klebsiella pneumoniae</i> (<i>n</i> = 20) were studied <i>in vitro</i>, <i>in vivo</i> employing the <i>Galleria mellonella</i> infection model and by whole-genome sequencing. Clinical isolates belonged to 7 different sequence types (STs) in <i>E. coli</i> and 12 different STs in <i>K. pneumoniae</i>. In 26/35 isolates <i>bla</i> <sub>OXA-</sub> <sub>48</sub> was located on a 63 kb IncL plasmid. Horizontal gene transfer (HGT) to <i>E. coli</i> J53 was high in isolates with the 63 kb IncL plasmid (transconjugation frequency: ∼10<sup>3</sup>/donor) but low in isolates with non-IncL plasmids (<10<sup>-6</sup>/donor). Several clinical isolates were both highly cytotoxic against human cells and virulent <i>in vivo</i>. However, 63 kb IncL transconjugants generated from these highly virulent isolates were not more cytotoxic or virulent when compared to the recipient strain. Additionally, no genes associated with virulence were detected by <i>in silico</i> analysis of OXA-48 plasmids. The 63 kb plasmid was highly stable and did not impair growth or fitness in <i>E. coli</i> J53. In conclusion, OXA-48 clinical isolates in Germany are diverse but typically harbor the same 63 kb IncL plasmid which has been reported worldwide. We demonstrate that this 63 kb IncL plasmid has a low fitness burden, high plasmid stability and can be transferred by highly efficient HGT which is likely the cause of the rapid dissemination of OXA-48 rather than the expansion of a single clone or gain of virulence.
<p>Real-World Data: Ranibizumab Treatment For Retinal Vein Occlusion In The OCEAN Study</p>
2019-11-01

Patients with RVO in routine practice in Germany received fewer injections and fewer OCT examinations than in clinical trials. CRVO patients showed less and later improvement compared to BRVO patients.
Efficacy of Bifidobacterium longum, B. infantis and Lactobacillus acidophilus probiotics to prevent gut dysbiosis in preterm infants of 28+0–32+6 weeks of gestation: a randomised, placebo-controlled, double-blind, multicentre trial: the PRIMAL Clinical Study protocol
2019-11-01

Introduction The healthy ‘eubiosis’ microbiome in infancy is regarded as the microbiome derived from term, vaginally delivered, antibiotic free, breastfed infants at 4–6 months. Dysbiosis is regarded as a deviation from a healthy state with reduced microbial diversity and deficient capacity to control drug-resistant organisms. Preterm infants are highly sensitive to early gut dysbiosis. Latter has been associated with sepsis and necrotising enterocolitis, but may also contribute to long-term health problems. Probiotics hold promise to reduce the risk for adverse short-term outcomes but the evidence from clinical trials remains inconclusive and none has directly assessed the effects of probiotics on the microbiome at high resolution. Methods and analysis A randomised, double blind, placebo-controlled study has been designed to assess the safety and efficacy of the probiotic mix of Bifidobacterium longum and infantis and Lactobacillus acidophilus in the prevention of gut dysbiosis in preterm infants between 28+0 and 32+6 weeks of gestation. The study is conducted in 18 German neonatal intensive care units. Between April 2018 and March 2020, 654 preterm infants of 28+0–32+6 weeks of gestation will be randomised in the first 48 hours of life to 28 days of once daily treatment with either probiotics or placebo. The efficacy endpoint is the prevention of gut dysbiosis at day 30 of life. A compound definition of gut dysbosis is used: (1) colonisation with multidrug-resistant organisms or gram-negative bacteria with high epidemic potential or (2) a significant deviation of the gut microbiota composition as compared with healthy term infants. Dysbiosis is determined by (1) conventional microbiological culture and (2) phylogenetic microbiome analysis by high-throughput 16S rRNA and metagenome sequencing. Persistence of dysbiosis will be assessed at 12-month follow-up visits. Side effects and adverse events related to the intervention will be recorded. Key secondary endpoint(s) are putative consequences of dysbiosis. A subgroup of infants will be thoroughly phenotyped for immune parameters using chipcytometry. Ethics and dissemination Ethics approval was obtained in all participating sites. Results of the trial will be published in peer-review journals, at scientific meetings, on the website ( www.primal-study.de ) and via social media of parent organisations. Trial registration number DRKS00013197; Pre-results.