Showing papers by "Tel Aviv University published in 2015"

A global reference for human genetic variation.

Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

Global effects of land use on local terrestrial biodiversity

Abstract: Human activities, especially conversion and degradation of habitats, are causing global biodiversity declines. How local ecological assemblages are responding is less clear--a concern given their importance for many ecosystem functions and services. We analysed a terrestrial assemblage database of unprecedented geographic and taxonomic coverage to quantify local biodiversity responses to land use and related changes. Here we show that in the worst-affected habitats, these pressures reduce within-sample species richness by an average of 76.5%, total abundance by 39.5% and rarefaction-based richness by 40.3%. We estimate that, globally, these pressures have already slightly reduced average within-sample richness (by 13.6%), total abundance (10.7%) and rarefaction-based richness (8.1%), with changes showing marked spatial variation. Rapid further losses are predicted under a business-as-usual land-use scenario; within-sample richness is projected to fall by a further 3.4% globally by 2100, with losses concentrated in biodiverse but economically poor countries. Strong mitigation can deliver much more positive biodiversity changes (up to a 1.9% average increase) that are less strongly related to countries' socioeconomic status.

Clumpak: a program for identifying clustering modes and packaging population structure inferences across K

Abstract: The identification of the genetic structure of populations from multilocus genotype data has become a central component of modern population-genetic data analysis. Application of model-based clustering programs often entails a number of steps, in which the user considers different modelling assumptions, compares results across different predetermined values of the number of assumed clusters (a parameter typically denoted K), examines multiple independent runs for each fixed value of K, and distinguishes among runs belonging to substantially distinct clustering solutions. Here, we present CLUMPAK (Cluster Markov Packager Across K), a method that automates the postprocessing of results of model-based population structure analyses. For analysing multiple independent runs at a single K value, CLUMPAK identifies sets of highly similar runs, separating distinct groups of runs that represent distinct modes in the space of possible solutions. This procedure, which generates a consensus solution for each distinct mode, is performed by the use of a Markov clustering algorithm that relies on a similarity matrix between replicate runs, as computed by the software CLUMPP. Next, CLUMPAK identifies an optimal alignment of inferred clusters across different values of K, extending a similar approach implemented for a fixed K in CLUMPP and simplifying the comparison of clustering results across different K values. CLUMPAK incorporates additional features, such as implementations of methods for choosing K and comparing solutions obtained by different programs, models, or data subsets. CLUMPAK, available at http://clumpak.tau.ac.il, simplifies the use of model-based analyses of population structure in population genetics and molecular ecology.

Decentralizing Privacy: Using Blockchain to Protect Personal Data

Abstract: The recent increase in reported incidents of surveillance and security breaches compromising users' privacy call into question the current model, in which third-parties collect and control massive amounts of personal data. Bit coin has demonstrated in the financial space that trusted, auditable computing is possible using a decentralized network of peers accompanied by a public ledger. In this paper, we describe a decentralized personal data management system that ensures users own and control their data. We implement a protocol that turns a block chain into an automated access-control manager that does not require trust in a third party. Unlike Bit coin, transactions in our system are not strictly financial -- they are used to carry instructions, such as storing, querying and sharing data. Finally, we discuss possible future extensions to block chains that could harness them into a well-rounded solution for trusted computing problems in society.

Combined Measurement of the Higgs Boson Mass in pp Collisions at √s=7 and 8 TeV with the ATLAS and CMS Experiments

Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.

Optical communications using orbital angular momentum beams

Abstract: Orbital angular momentum (OAM), which describes the “phase twist” (helical phase pattern) of light beams, has recently gained interest due to its potential applications in many diverse areas. Particularly promising is the use of OAM for optical communications since: (i) coaxially propagating OAM beams with different azimuthal OAM states are mutually orthogonal, (ii) inter-beam crosstalk can be minimized, and (iii) the beams can be efficiently multiplexed and demultiplexed. As a result, multiple OAM states could be used as different carriers for multiplexing and transmitting multiple data streams, thereby potentially increasing the system capacity. In this paper, we review recent progress in OAM beam generation/detection, multiplexing/demultiplexing, and its potential applications in different scenarios including free-space optical communications, fiber-optic communications, and RF communications. Technical challenges and perspectives of OAM beams are also discussed.

Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Abstract: BACKGROUND Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. METHODS We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. RESULTS The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P = 0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. CONCLUSIONS Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

dendextend: an R package for visualizing, adjusting and comparing trees of hierarchical clustering

Abstract: Summary: dendextend is an R package for creating and comparing visually appealing tree diagrams. dendextend provides utility functions for manipulating dendrogram objects (their color, shape and content) as well as several advanced methods for comparing trees to one another (both statistically and visually). As such, dendextend offers a flexible framework for enhancing R's rich ecosystem of packages for performing hierarchical clustering of items. Availability and implementation: The dendextend R package (including detailed introductory vignettes) is available under the GPL-2 Open Source license and is freely available to download from CRAN at: (http://cran.r-project.org/package=dendextend) Contact: li.ca.uat.htam@ililaG.laT

Maintenance therapy with tumor-Treating fields plus temozolomide vs temozolomide alone for glioblastoma a randomized clinical trial

Abstract: Importance Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. Objective To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. Design, Setting, and Participants After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. Interventions Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m 2 /d) was given for 5 days of each 28-day cycle. Main Outcomes and Measures The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. Results The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). Conclusions and Relevance In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. Trial Registration clinicaltrials.gov Identifier:NCT00916409

The extended evolutionary synthesis: its structure, assumptions and predictions.

Abstract: Scientific activities take place within the structured sets of ideas and assumptions that define a field and its practices. The conceptual framework of evolutionary biology emerged with the Modern Synthesis in the early twentieth century and has since expanded into a highly successful research program to explore the processes of diversification and adaptation. Nonetheless, the ability of that framework satisfactorily to accommodate the rapid advances in developmental biology, genomics and ecology has been questioned. We review some of these arguments, focusing on literatures (evo-devo, developmental plasticity, inclusive inheritance and niche construction) whose implications for evolution can be interpreted in two ways—one that preserves the internal structure of contemporary evolutionary theory and one that points towards an alternative conceptual framework. The latter, which we label the 'extended evolutionary synthesis' (EES), retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution, and reciprocal portrayals of causation. In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism-environment complementarity. We spell out the structure, core assumptions and novel predictions of the EES, and show how it can be deployed to stimulate and advance research in those fields that study or use evolutionary biology.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

Abstract: Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population ex...

Emotion regulation and psychopathology.

Abstract: Emotional problems figure prominently in many clinical conditions. Recent efforts to explain and treat these conditions have emphasized the role of emotion dysregulation. However, emotional problems are not always the result of emotion dysregulation, and even when emotional problems do arise from emotion dysregulation, it is necessary to specify precisely what type of emotion dysregulation might be operative. In this review, we present an extended process model of emotion regulation, and we use this model to describe key points at which emotion-regulation difficulties can lead to various forms of psychopathology. These difficulties are associated with (a) identification of the need to regulate emotions, (b) selection among available regulatory options, (c) implementation of a selected regulatory tactic, and (d) monitoring of implemented emotion regulation across time. Implications and future directions for basic research, assessment, and intervention are discussed.

Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease

Abstract: Aβ(1–42) is the most pathogenic amyloid-β species in Alzheimer's disease (AD). The solid-state NMR–based atomic model of an Aβ(1–42) fibril elucidates the mechanism of fibril formation and propagation in AD and other amyloid diseases.

GUIDANCE2: accurate detection of unreliable alignment regions accounting for the uncertainty of multiple parameters

Abstract: Inference of multiple sequence alignments (MSAs) is a critical part of phylogenetic and comparative genomics studies. However, from the same set of sequences different MSAs are often inferred, depending on the methodologies used and the assumed parameters. Much effort has recently been devoted to improving the ability to identify unreliable alignment regions. Detecting such unreliable regions was previously shown to be important for downstream analyses relying on MSAs, such as the detection of positive selection. Here we developed GUIDANCE2, a new integrative methodology that accounts for: (i) uncertainty in the process of indel formation, (ii) uncertainty in the assumed guide tree and (iii) co-optimal solutions in the pairwise alignments, used as building blocks in progressive alignment algorithms. We compared GUIDANCE2 with seven methodologies to detect unreliable MSA regions using extensive simulations and empirical benchmarks. We show that GUIDANCE2 outperforms all previously developed methodologies. Furthermore, GUIDANCE2 also provides a set of alternative MSAs which can be useful for downstream analyses. The novel algorithm is implemented as a web-server, available at: http: //guidance.tau.ac.il.

Combined co and dust scaling relations of depletion time and molecular gas fractions with cosmic time, specific star-formation rate, and stellar mass

Abstract: We combine molecular gas masses inferred from CO emission in 500 star-forming galaxies (SFGs) between z = 0 and 3, from the IRAM-COLDGASS, PHIBSS1/2, and other surveys, with gas masses derived from Herschel far-IR dust measurements in 512 galaxy stacks over the same stellar mass/redshift range. We constrain the scaling relations of molecular gas depletion timescale (t depl) and gas to stellar mass ratio (M mol gas/M* ) of SFGs near the star formation "main-sequence" with redshift, specific star-formation rate (sSFR), and stellar mass (M* ). The CO- and dust-based scaling relations agree remarkably well. This suggests that the CO → H2 mass conversion factor varies little within ±0.6 dex of the main sequence (sSFR(ms, z, M *)), and less than 0.3 dex throughout this redshift range. This study builds on and strengthens the results of earlier work. We find that t depl scales as (1 + z)–0.3 × (sSFR/sSFR(ms, z, M *))–0.5, with little dependence on M *. The resulting steep redshift dependence of M mol gas/M * ≈ (1 + z)3 mirrors that of the sSFR and probably reflects the gas supply rate. The decreasing gas fractions at high M* are driven by the flattening of the SFR-M * relation. Throughout the probed redshift range a combination of an increasing gas fraction and a decreasing depletion timescale causes a larger sSFR at constant M *. As a result, galaxy integrated samples of the M mol gas-SFR rate relation exhibit a super-linear slope, which increases with the range of sSFR. With these new relations it is now possible to determine M mol gas with an accuracy of ±0.1 dex in relative terms, and ±0.2 dex including systematic uncertainties.

Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis

Abstract: Understanding cell-fate decisions during tumorigenesis and metastasis is a major challenge in modern cancer biology. One canonical cell-fate decision that cancer cells undergo is Epithelial-to-Mesenchymal Transition (EMT) and its reverse Mesenchymal-to-Epithelial Transition (MET). While transitioning between these two phenotypes – epithelial and mesenchymal, cells can also attain a hybrid epithelial/ mesenchymal (i.e. partial or intermediate EMT) phenotype. Cells in this phenotype have mixed epithelial (eg. adhesion) and mesenchymal (eg. migration) properties, thereby allowing them to move collectively as clusters of Circulating Tumor Cells (CTCs). If these clusters enter the circulation, they can be more apoptosis-resistant and more capable of initiating metastatic lesions than cancer cells moving individually with wholly mesenchymal phenotypes, having undergone a complete EMT. Here, we review the operating principles of the core regulatory network for EMT/MET that acts as a ‘three-way’ switch giving rise to three distinct phenotypes – epithelial, mesenchymal and hybrid epithelial/mesenchymal. We further characterize this hybrid E/M phenotype in terms of its capabilities in terms of collective cell migration, tumor-initiation, cell-cell communication, and drug resistance. We elucidate how the highly interconnected coupling between these modules coordinates cell-fate decisions among a population of cancer cells in the dynamic tumor, hence facilitating tumor-stroma interactions, formation of CTC clusters, and consequently cancer metastasis. Finally, we discuss the multiple advantages that the hybrid epithelial/mesenchymal phenotype have as compared to a complete EMT phenotype and argue that these collectively migrating cells are the primary ‘bad actors’ of metastasis.

Combination of Measurements of Inclusive Deep Inelastic $e^{\pm}p$ Scattering Cross Sections and QCD Analysis of HERA Data

Abstract: A combination is presented of all inclusive deep inelastic cross sections previously published by the H1 and ZEUS collaborations at HERA for neutral and charged current $e^{\pm}p$ scattering for zero beam polarisation. The data were taken at proton beam energies of 920, 820, 575 and 460 GeV and an electron beam energy of 27.5 GeV. The data correspond to an integrated luminosity of about 1 fb$^{-1}$ and span six orders of magnitude in negative four-momentum-transfer squared, $Q^2$, and Bjorken $x$. The correlations of the systematic uncertainties were evaluated and taken into account for the combination. The combined cross sections were input to QCD analyses at leading order, next-to-leading order and at next-to-next-to-leading order, providing a new set of parton distribution functions, called HERAPDF2.0. In addition to the experimental uncertainties, model and parameterisation uncertainties were assessed for these parton distribution functions. Variants of HERAPDF2.0 with an alternative gluon parameterisation, HERAPDF2.0AG, and using fixed-flavour-number schemes, HERAPDF2.0FF, are presented. The analysis was extended by including HERA data on charm and jet production, resulting in the variant HERAPDF2.0Jets. The inclusion of jet-production cross sections made a simultaneous determination of these parton distributions and the strong coupling constant possible, resulting in $\alpha_s(M_Z)=0.1183 \pm 0.0009 {\rm(exp)} \pm 0.0005{\rm (model/parameterisation)} \pm 0.0012{\rm (hadronisation)} ^{+0.0037}_{-0.0030}{\rm (scale)}$. An extraction of $xF_3^{\gamma Z}$ and results on electroweak unification and scaling violations are also presented.

Emotion Regulation Flexibility

Abstract: How do people flexibly regulate their emotions in order to manage the diverse demands of varying situations? This question assumes particular importance given the central role that emotion regulation (ER) deficits play in many forms of psychopathology. In this review, we propose a translational framework for the study of ER flexibility that is relevant to normative and clinical populations. We also offer a set of computational tools that are useful for work on ER flexibility. We specify how such tools can be used in a variety of settings, such as basic research, experimental psychopathology, and clinical practice. Our goal is to encourage the theoretical and methodological precision that is needed in order to facilitate progress in this important area.

RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL

Abstract: RIPK3 and its substrate MLKL are essential for necroptosis, a lytic cell death proposed to cause inflammation via the release of intracellular molecules. Whether and how RIPK3 might drive inflammation in a manner independent of MLKL and cell lysis remains unclear. Here we show that following LPS treatment, or LPS-induced necroptosis, the TLR adaptor protein TRIF and inhibitor of apoptosis proteins (IAPs: X-linked IAP, cellular IAP1 and IAP2) regulate RIPK3 and MLKL ubiquitylation. Hence, when IAPs are absent, LPS triggers RIPK3 to activate caspase-8, promoting apoptosis and NLRP3-caspase-1 activation, independent of RIPK3 kinase activity and MLKL. In contrast, in the absence of both IAPs and caspase-8, RIPK3 kinase activity and MLKL are essential for TLR-induced NLRP3 activation. Consistent with in vitro experiments, interleukin-1 (IL-1)-dependent autoantibody-mediated arthritis is exacerbated in mice lacking IAPs, and is reduced by deletion of RIPK3, but not MLKL. Therefore RIPK3 can promote NLRP3 inflammasome and IL-1β inflammatory responses independent of MLKL and necroptotic cell death.

The Chromosome Counts Database (CCDB) – a community resource of plant chromosome numbers

Abstract: For nearly a century, biologists, and botanists in particular, have been interested in the determination and documentation of chromosome numbers for extant taxa (reviewed in Goldblatt & Lowry, 2011) as well as extinct ones (Laane & Hoiland, 1986; Masterson, 1994). These data have beenwidely used to evaluate the evolutionary pattern of chromosome number change and to estimate the base chromosome number of clades of interest. Chromosome numbers have also been extensively utilized as an important phylogenetic character in the context of cytotaxonomy (Chatterjee & Kumar Sharma, 1969; Schlarbaum & Tsuchiya, 1984; Guerra, 2012). Perhaps the most influential use of chromosome number data has been in the inference of major genomic events such aswhole genomeduplications (polyploidy), as well as changes in single chromosome numbers (e.g. dysploidy). Early researchers analyzed the distribution of chromosome numbers within a group of interest and employed various threshold techniques to estimate ploidy levels for the analyzed taxa (Stebbins, 1938; Grant, 1963; Goldblatt, 1980).More recently, phylogenetic information was incorporated into the analyses, allowing researchers to infer transitions in chromosome numbers along branches of the tree using either the maximum parsimony principle (Schultheis, 2001; Hansen et al., 2006; Ohi-Toma et al., 2006; Wood et al., 2009) or by using a probabilistic evolutionary model within the likelihood paradigm (Mayrose et al., 2010; Cusimano et al., 2012; Glick & Mayrose, 2014). Due to their significance and the relative ease by which chromosome numbers can be obtained, it is not surprising that chromosome number is the most extensively and consistently recorded cytological property in most plant families and genera (Guerra, 2008). These data have been documented along the years in an array of journal manuscripts, printed books (L€ove & L€ove, 1948; Darlington & Wylie, 1955; Fedorov, 1969) and, more recently, in the form of online databases (Goldblatt & Johnson, 1979; Watanabe, 2002; Bennett & Leitch, 2011). To date, the most comprehensive data source is the Index to PlantChromosome Numbers (IPCN; Goldblatt & Johnson, 1979), which provides reference point to original chromosome counts reported in the literature. IPCN was initially established at the University of California Berkeley in the 1950s and was later maintained by Canada Department of Agriculture, Missouri Botanical Garden, and currently by the International Association for Plant Taxonomy (IAPT). A large portion of the counts referenced during 1979– 2006, the years that IPCN has been housed in the Missouri Botanical Garden, can be accessed and searched online. Counts reported in more recent years are currently published under IAPT/ IOPBChromosomeData series (Marhold, 2006) but are not stored within a central, easily searched, database. In addition to IPCN, several other online data sources are available, most of which are dedicated to either a specific geographical region (Slovakia – Marhold et al., 2007; Poland –G oralski et al., 2009 onwards) or to a certain taxonomic group (e.g. Hieracium – Schuhwerk, 1996; Asteraceae –Watanabe, 2002). The amount of chromosome counts that exist to date is extensive, and searching the large number of resources that contain such information is a daunting task, particularly when a large number of taxa is examined. Consequently, many researchers search for chromosome number information only through the largest online database(s), while smaller but nonetheless valuable sources are ignored.This usually results inmissing data for someof the species in question, which may lead to erroneous conclusions drawn from the analysis. Obviously, a large accessible database that unifies all currently known databases, including both printed and online sources, would be of great value to the botanical community and wouldmake the task of data collectionmuch easier. In addition, such a central resource would enable researchers to add new counts as soon as they are being reported, facilitating the task of data sharing. Here, we present the Chromosome Counts Database (CCDB), as a community resource of plant chromosome numbers. The database incorporates data from dozens of sources, more than doubling the amount of data available within any single resource. The online database additionally enables researchers to add new counts or to comment on existing data entries, thereby facilitating data sharing. The extensive amount of data currently available in CCDB further allowed us to analyze the patterns of chromosome number distribution among major plant groups. We estimate the percentage of plant species exhibiting intraspecific variation in chromosome numbers as well as in their ploidy levels.

Sex beyond the genitalia: The human brain mosaic

Abstract: Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only “male” or only “female” features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the “maleness-femaleness” continuum are rare. Rather, most brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain.

67P/Churyumov-Gerasimenko, a Jupiter family comet with a high D/H ratio

Abstract: The provenance of water and organic compounds on Earth and other terrestrial planets has been discussed for a long time without reaching a consensus. One of the best means to distinguish between different scenarios is by determining the deuterium-to-hydrogen (D/H) ratios in the reservoirs for comets and Earth’s oceans. Here, we report the direct in situ measurement of the D/H ratio in the Jupiter family comet 67P/Churyumov-Gerasimenko by the ROSINA mass spectrometer aboard the European Space Agency’s Rosetta spacecraft, which is found to be (5.3 ± 0.7) × 10−4—that is, approximately three times the terrestrial value. Previous cometary measurements and our new finding suggest a wide range of D/H ratios in the water within Jupiter family objects and preclude the idea that this reservoir is solely composed of Earth ocean–like water.

The Forced Swim Test as a Model of Depressive-like Behavior

Abstract: The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

Abstract: Aicardi-Goutieres syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutieres syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.