julilili42/papers huggingface dataset:
Neolithic genomes reveal a distinct ancient HLA allele pool and population transformation in Europe
2019-11-21

Abstract The Wartberg culture (WBC, 3,500-2,800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We perform a genome-wide analysis of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3,300-3,200 cal. BCE). Our results highlight that the Niedertiefenbach population indeed emerged at the beginning of the WBC. This farming community was genetically heterogeneous and carried a surprisingly large hunter-gatherer ancestry component (40%). We detect considerable differences in the human leukocyte antigen gene pool between contemporary Europeans and the Niedertiefenbach individuals whose immune response was primarily geared towards defending viral infections.
Neuro-Sweet syndrome - a rare differential diagnosis in aseptic meningoencephalitis
2019-11-21

Abstract Acute febrile neutrophilic dermatosis (Sweet‘s syndrome) is a dermatological entity, which may be associated with malignancies, drugs, and infections and which is characterized by high fever, elevated neutrophils, and tender erythematous skin lesions. Involvement of the nervous system – Neuro-Sweet syndrome (NSS) - is rare, manifesting most commonly with an encephalitic syndrome in addition to fever and dermal lesions. Here, we report an unusual case of NSS in a Caucasian male patient in the setting of B-cell-lymphocytosis, with encephalitis preceding dermal lesions. Symptoms resolved completely in response to corticoids. NSS is a rare, but important differential diagnosis in the work-up of febrile aseptic meningoencephalitis unresponsive to anti-infectious treatment. Due to its rarity and clinical variability, diagnosis of NSS might be challenging. Knowledge of this entity may facilitate proper diagnosis and differentiation from conditions with similar clinical presentation, especially Neuro-Behçet‘s disease. It may further lead to early detection of a potentially underlying malignancy and help in initiating adequate therapy.
Cyanobacterial Heterocysts
2019-11-21

Abstract Cyanobacteria are phototrophic bacteria carrying out oxygen‐producing photosynthesis. Besides showing the capability of building their cellular carbon from carbon dioxide (CO 2 ), available in the atmosphere, several strains of cyanobacteria have also acquired the ability to fix molecular dinitrogen (N 2 ), a ubiquitous source of nitrogen. As the enzyme responsible for nitrogen fixation (nitrogenase) is highly sensitive to oxygen, nitrogen fixation and oxygenic photosynthesis cannot take place simultaneously in cyanobacterial cells. To solve this problem, some filamentous strains are able to restrict N 2 fixation to a specialised cell type, the heterocyst. Heterocysts are morphologically distinct, terminally differentiated cells that develop, in the absence of alternative sources of combined nitrogen, mostly in a semiregular pattern along the filaments. Thus, a filament containing heterocysts provides division of labour between vegetative cells (photosynthetic CO 2 fixation) and heterocysts (anaerobic N 2 fixation). These cyanobacteria represent true multicellular organisms with profound morphological cell differentiation and sophisticated intercellular communication systems, ultimately orchestrated by complex gene expression patterns. Key Concepts Although bacteria, some filamentous cyanobacteria are true multicellular organisms, showing different cell types performing specialised tasks. When lacking a source of combined nitrogen, these cyanobacteria start a program of cell differentiation resulting in a pattern of semiregularly spaced heterocysts along the filament. Heterocysts differentiate from vegetative cells, which carry out oxygenic photosynthesis, and provide a microoxic environment for the activity of oxygen‐labile nitrogenase. Nitrogenase is the enzyme responsible for N 2 fixation and allows the organism to live from sunlight, air (CO 2 and N 2 ) and some minerals. The two cell types rely on each other and exchange metabolites and signalling molecules, via septal junctions mediating cell‐to‐cell contact. Two transcription factors, HetR and NtcA, regulate the changes in gene expression during heterocyst differentiation. The pattern of spaced heterocysts is regulated by inhibitor gradients that promote the decay of HetR, confirming mathematical models of two‐dimensional pattern formation in heterocystous cyanobacteria.
OMSI (Optically Masked Size Increase): Einstein’s Fourth 1907 Miracle, Exposed
2019-11-21

Rossler OE* and Kuske F Author Affiliations University of Tuebingen, Germany Received: November 15, 2019 | Published: November 21, 2019 Corresponding author: Rossler OE, Faculty of Science, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany DOI: 10.26717/BJSTR.2019.23.003855
ThermoRawFileParser: Modular, Scalable, and Cross-Platform RAW File Conversion
2019-11-22

The field of computational proteomics is approaching the big data age, driven both by a continuous growth in the number of samples analyzed per experiment as well as by the growing amount of data obtained in each analytical run. In order to process these large amounts of data, it is increasingly necessary to use elastic compute resources such as Linux-based cluster environments and cloud infrastructures. Unfortunately, the vast majority of cross-platform proteomics tools are not able to operate directly on the proprietary formats generated by the diverse mass spectrometers. Here, we present ThermoRawFileParser, an open-source, cross-platform tool that converts Thermo RAW files into open file formats such as MGF and the HUPO-PSI standard file format mzML. To ensure the broadest possible availability and to increase integration capabilities with popular workflow systems such as Galaxy or Nextflow, we have also built Conda package and BioContainers container around ThermoRawFileParser. In addition, we implemented a user-friendly interface (ThermoRawFileParserGUI) for those users not familiar with command-line tools. Finally, we performed a benchmark of ThermoRawFileParser and msconvert to verify that the converted mzML files contain reliable quantitative results.
Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice
2019-11-22

Mixed signals at tumor margins The Hippo signaling pathway has been implicated in tumor growth, sparking interest in the pathway as a potential therapeutic target. In a study of liver cancer in genetically manipulated mice, Moya et al. discovered that the role of this pathway in tumorigenesis is more complex than previously appreciated. They confirmed that activation of the Hippo pathway within tumor cells drives tumor growth; however, they also found that activation of the pathway in adjacent healthy cells has the opposite effect, suppressing tumor growth. Whether tumor cells survive or are eliminated thus appears to depend on competing signals produced by the tumor and surrounding tissue. Science , this issue p. 1029
Cross‐Domain Trajectories of Students’ Ability Self‐Concepts and Intrinsic Values in Math and Language Arts
2019-11-22

Different cross‐domain trajectories in the development of students’ ability self‐concepts (ASCs) and their intrinsic valuing of math and language arts were examined in a cross‐sequential study spanning Grades 1 through 12 ( n = 1,069). Growth mixture modeling analyses identified a Moderate Math Decline/Stable High Language Arts class and a Moderate Math Decline/Strong Language Arts Decline class for students’ ASC trajectories. Students’ intrinsic value trajectories included a Strong Math Decline/Language Arts Decline Leveling Off , a Moderate Math Decline/Strong Language Arts Decline , and a Stable Math and Language Arts Trajectories class. These classes differed with regard to student characteristics, including gender, family background, and math and reading aptitudes. They also resulted in different high school math course enrollments, career aspirations, and adult careers.
Deep Brain Stimulation for Freezing of Gait in Parkinson's Disease With Early Motor Complications
2019-11-22

Abstract Background Effects of DBS on freezing of gait and other axial signs in PD patients are unclear. Objective Secondary analysis to assess whether DBS affects these symptoms within a large randomized controlled trial comparing DBS of the STN combined with best medical treatment and best medical treatment alone in patients with early motor complications (EARLYSTIM‐trial). Methods One hundred twenty‐four patients were randomized in the stimulation group and 127 patients in the best medical treatment group. Presence of freezing of gait was assessed in the worst condition based on item‐14 of the UPDRS‐II at baseline and follow‐up. The posture, instability, and gait‐difficulty subscore of the UPDRS‐III, and a gait test including quantification of freezing of gait and number of steps, were performed in both medication‐ off and medication‐ on conditions. Results Fifty‐two percent in both groups had freezing of gait at baseline based on UPDRS‐II. This proportion decreased in the stimulation group to 34%, but did not change in the best medical treatment group at 24 months ( P = 0.018). The steps needed to complete the gait test decreased in the stimulation group and was superior to the best medical treatment group ( P = 0.016). The axial signs improved in the stimulation group compared to the best medical treatment group ( P &lt; 0.01) in both medication‐ off and medication‐ on conditions. Conclusions Within the first 2 years of DBS, freezing of gait and other axial signs improved in the medication‐ off condition compared to best medical treatment in these patients. © 2019 International Parkinson and Movement Disorder Society
Open-source QCD analysis of nuclear parton distribution functions at NLO and NNLO
2019-11-22

We present new sets of nuclear parton distribution functions (nPDFs) at\\nnext-to-leading order (NLO) and next-to-next-to-leading order (NNLO). Our\\nanalyses are based on deeply inelastic scattering data with charged-lepton and\\nneutrino beams on nuclear targets. In addition, a set of proton baseline PDFs\\nis fitted within the same framework with the same theoretical assumptions. The\\nresults of this global QCD analysis are compared to existing nPDF sets and to\\nthe fitted cross sections. Also, the uncertainties resulting from the limited\\nconstraining power of the included experimental data are presented. The\\npublished work is based on an open-source tool, xFitter, which has been\\nmodified to be applicable also for a nuclear PDF analysis. The required\\nextensions of the code are discussed as well.\\n
Coupled supercontinent–mantle plume events evidenced by oceanic plume record
2019-11-22

Abstract The most dominant features in the present-day lower mantle are the two antipodal African and Pacific large low-shear-velocity provinces (LLSVPs). How and when these two structures formed, and whether they are fixed and long lived through Earth history or dynamic and linked to the supercontinent cycles, remain first-order geodynamic questions. Hotspots and large igneous provinces (LIPs) are mostly generated above LLSVPs, and it is widely accepted that the African LLSVP existed by at least ca. 200 Ma beneath the supercontinent Pangea. Whereas the continental LIP record has been used to decipher the spatial and temporal variations of plume activity under the continents, plume records of the oceanic realm before ca. 170 Ma are mostly missing due to oceanic subduction. Here, we present the first compilation of an Oceanic Large Igneous Provinces database (O-LIPdb), which represents the preserved oceanic LIP and oceanic island basalt occurrences preserved in ophiolites. Using this database, we are able to reconstruct and compare the record of mantle plume activity in both the continental and oceanic realms for the past 2 b.y., spanning three supercontinent cycles. Time-series analysis reveals hints of similar cyclicity of the plume activity in the continent and oceanic realms, both exhibiting a periodicity of ∼500 m.y. that is comparable to the supercontinent cycle, albeit with a slight phase delay. Our results argue for dynamic LLSVPs where the supercontinent cycle and global subduction geometry control the formation and locations of the plumes.
1,25(OH)2D3 in Brain Function and Neuropsychiatric Disease
2019-11-22

1,25(OH)<sub>2</sub>D<sub>3</sub> (1,25-dihydroxy-vitamin D3 = calcitriol) is a powerful regulator of mineral metabolism. The hormone increases calcium and phosphate plasma concentrations in part by stimulation of intestinal absorption and renal reabsorption of calcium and phosphate. It is primarily, but not exclusively, produced in the kidney. Renal 1,25(OH)<sub>2</sub>D<sub>3</sub> formation is stimulated by calcium and phosphate deficiency and by parathyroid hormone which is up-regulated by hypocalcemia. 1,25(OH)<sub>2</sub>D<sub>3</sub> formation is inhibited by fibroblast growth factor FGF23, which is up-regulated by phosphate excess and requires Klotho to become effective. Klotho- or FGF23-deficiency leads to excessive plasma 1,25(OH)<sub>2</sub>D<sub>3</sub>-, Ca<sup>2+</sup>- and phosphate-concentrations with severe soft tissue calcification and accelerated aging. Tissue calcification and premature aging are prevented by NH<sub>4</sub>Cl without affecting 1,25(OH)<sub>2</sub>D<sub>3</sub>-formation. 1,25(OH)<sub>2</sub>D<sub>3</sub> has powerful effects apparently unrelated to mineral metabolism, including anti-inflammatory actions and modification of multiple brain functions. Excessive 1,25(OH)<sub>2</sub>D<sub>3</sub> formation in klotho-deficient NH<sub>4</sub>Cl-treated mice leads to an amazing surge of exploratory behavior, lack of anxiety and decreased depression, effects dissipated by low vitamin D diet. Conversely, vitamin D deficient mice display reduced explorative behavior, enhanced anxiety, aberrant grooming, submissive social behavior, social neglect and maternal cannibalism. 1,25(OH)<sub>2</sub>D<sub>3</sub> is generated in human brain, and acts on diverse structures including prefrontal cortex, hippocampus, cingulate gyrus, thalamus, hypothalamus, and substantia nigra. In neurons 1,25(OH)<sub>2</sub>D<sub>3</sub> suppresses oxidative stress, inhibits inflammation, provides neuroprotection, down-regulates a variety of inflammatory mediators and up-regulates a wide variety of neurotrophins. Diseases postulated to be favorably modified by 1,25(OH)<sub>2</sub>D<sub>3</sub> include multiple sclerosis, Parkinson ́s disease, Alzheimer ́s disease, depression, bipolar disorder and schizophrenia. Clearly, substantial additional experimentation is required to fully understand the neuro-psycho-pathophysiological role of 1,25(OH)<sub>2</sub>D<sub>3</sub> and to exploit 1,25(OH)<sub>2</sub>D<sub>3</sub> or related agonists in the treatment of neuro-psychiatric disorders.
Every-Other-Day Feeding Decreases Glycolytic and Mitochondrial Energy-Producing Potentials in the Brain and Liver of Young Mice
2019-11-22

Intermittent fasting is used to reduce body mass in obese adult humans and animals. However, information on the impact of one type of intermittent fasting (IF) called every-other-day feeding (EODF) on young animals is scarce. In this study, 1-month-old mice of both sexes were subjected to a 4-week regimen of EODF using age-matched counterparts fed <i>ad libitum</i> as controls. At the end of EODF exposure, experimental male and female mice weighed 14 and 13% less than the control counterparts. The EODF regimen resulted in lower liver levels of glycogen, glucose, and lactate, but did not affect lactate level in mouse cerebral cortex of both sexes. Activities of key glycolytic enzymes (hexokinase, phosphofructokinase, and pyruvate kinase) in liver of experimental mice were lower than those in controls. In the cerebral cortex, only hexokinase and pyruvate kinase activities were lower than in controls, but phosphofructokinase activity was not affected in IF females and was higher in IF males as compared with <i>ad libitum</i> fed males. Mitochondria isolated from liver of IF mice had lower respiratory control ratios, but those from the cortex had the same values as control animals. The concentration of β-hydroxybutyrate and the activity of β-hydroxybutyrate dehydrogenase were lower in the IF mouse liver, but not changed or enhanced in the IF cerebral cortex. Thus, animal responses to IF do not depend significantly on sex and are directed to decrease energy metabolism to save resources, and the effects are more pronounced in the liver than in the brain.
Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia
2019-11-22

Abstract INTRODUCTION The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial Frontotemporal dementia (FTD). METHODS We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. RESULTS There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviourally-relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. DISCUSSION Our findings suggest that maintenance of functional network connectivity enables carriers to maintain cognitive performance.
<strong></strong>The Striking Flower-in-Flower Phenotype of Arabidopsis Thaliana Nossen (No-0) is Caused by a Novel <em>LEAFY</em> Allele
2019-11-22

The transition to reproduction is a crucial step in the life cycle of any organism. In Arabidopsis thaliana the establishment of reproductive growth can be divided into two phases: Firstly, cauline leaves with axillary meristems are formed and internode elongation begins. Secondly, lateral meristems develop into flowers with defined organs. Floral shoots are usually determinate and suppress the development of lateral shoots. Here, we describe a transposon insertion mutant in the Nossen accession with defects in floral development and growth. Most strikingly is the outgrowth of stems from the axillary bracts of the primary flower carrying secondary flowers. Therefore, we named this mutant flower-in-flower (fif). However, the transposon insertion in the annotated gene is not the cause for the fif phenotype. By means of classical and genome sequencing-based mapping, the mutation responsible for the fif phenotype was found to be in the LEAFY gene. The mutation, a G-to-A exchange in the second exon of LEAFY, creates a novel lfy allele and results in a cysteine-to-tyrosine exchange in the &amp;alpha;1-helix of LEAFY&amp;acute;s DNA-binding domain. This exchange abolishes target DNA-binding, whereas subcellular localization and homomerization are not affected. To explain the strong fif phenotype against this molecular findings, several hypotheses are discussed.
Temperature-related disasters in Europe – a cross-sectional analysis of the emergency events database from a pediatric perspective
2019-11-22

Abstract This study investigates patterns of extreme temperature-related events in Europe and its significance for the public health, with a focus on the vulnerable pediatric population. A generalized additive model of average surface temperature development for the European countries is described and discussed with an in-depth analysis of the influence of temperature on evolutional and behavioral aspects. Methods Extreme temperature related events are recorded in the publicly available epidemiological database of Emergency Events (EM-DAT). A comparative and descriptive statistical analysis of this data was conducted with a focus on (prospective) records from 1988 onwards. Average surface temperature data was provided by the World Bank’s Climate Change Knowledge Portal. The criteria for strengthening the reporting of observational studies in epidemiology (STROBE) were respected. Results Within EM-DAT, extreme temperature-related disasters in Europe were categorized as either heat waves, drought, forest or land fires, or cold waves and severe winter conditions, accordingly. The most frequent type of event recorded were cold waves (36.2%). However, cold waves and severe winter conditions only accounted for about 6,460 casualties (4.4%), while heat waves were responsible for a total of 137,533 casualties (95.1%). During the prospective observational period of the EM-DAT database, heat waves in 2003, 2006, 2010, and 2015, claimed a total of 119,760 casualties. These most severe heatwaves were geographically distributed over Russia (2010), as well as France, Italy, Spain, and Germany, each in 2003. Accordingly, analysis of temperature data revealed an increasing average surface temperature for all assessed European countries, correlating with in an increasing frequency of extreme temperature-related events. Conclusion This study shows that according to EM-DAT data extreme temperatures are an increasingly important public health threat to the European population as the average European surface temperatures are rising. Although cold waves are more frequently reported in EM-DAT, heat waves are the major cause for temperature-related casualties. Therefore, we conclude that evolutional and cultural resilience against cold and drought is significantly higher than it is against heat. Our results project that the frequency, duration and intensity of heat waves will further increase due to current climatic changes and become a more prevalent problem for future generations. Hence, we propose an emergency plan to inform the public and authorities about measurements to be taken in such extreme heat conditions to overcome the prevailing lack of information available to the public.