Miracle-dz/UniFAR-FTUs huggingface dataset:
Independent initiation of primary electron transfer in the two branches of the photosystem I reaction center

Photosystem I (PSI) is a large pigment-protein complex that unites a reaction center (RC) at the core with ∼100 core antenna chlorophylls surrounding it. The RC is composed of two cofactor branches related by a pseudo-C2 symmetry axis. The ultimate electron donor, P700 (a pair of chlorophylls), and the tertiary acceptor, FX (a Fe4S4 cluster), are both located on this axis, while each of the two branches is made up of a pair of chlorophylls (ec2 and ec3) and a phylloquinone (PhQ). Based on the observed biphasic reduction of FX, it has been suggested that both branches in PSI are competent for electron transfer (ET), but the nature and rate of the initial electron transfer steps have not been established. We report an ultrafast transient absorption study of Chlamydomonas reinhardtii mutants in which specific amino acids donating H-bonds to the 131-keto oxygen of either ec3A (PsaA-Tyr696) or ec3B (PsaB-Tyr676) are converted to Phe, thus breaking the H-bond to a specific ec3 cofactor. We find that the rate of primary charge separation (CS) is lowered in both mutants, providing direct evidence that the primary ET event can be initiated independently in each branch. Furthermore, the data provide further support for the previously published model in which the initial CS event occurs within an ec2/ec3 pair, generating a primary ec2+ec3- radical pair, followed by rapid reduction by P700 in the second ET step. A unique kinetic modeling approach allows estimation of the individual ET rates within the two cofactor branches.
SH3TC2/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system

Charcot–Marie–Tooth disease type 4C (CMT4C) is an early-onset, autosomal recessive form of demyelinating neuropathy. The clinical manifestations include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. The gene mutated in CMT4C disease, SH3TC2/KIAA1985, was recently identified; however, the function of the protein it encodes remains unknown. We have generated knockout mice where the first exon of the Sh3tc2 gene is replaced with an enhanced GFP cassette. The Sh3tc2ΔEx1/ΔEx1 knockout animals develop progressive peripheral neuropathy manifested by decreased motor and sensory nerve conduction velocity and hypomyelination. We show that Sh3tc2 is specifically expressed in Schwann cells and localizes to the plasma membrane and to the perinuclear endocytic recycling compartment, concordant with its possible function in myelination and/or in regions of axoglial interactions. Concomitantly, transcriptional profiling performed on the endoneurial compartment of peripheral nerves isolated from control and Sh3tc2ΔEx1/ΔEx1 animals uncovered changes in transcripts encoding genes involved in myelination and cell adhesion. Finally, detailed analyses of the structures composed of compact and noncompact myelin in the peripheral nerve of Sh3tc2ΔEx1/ΔEx1 animals revealed abnormal organization of the node of Ranvier, a phenotype that we confirmed in CMT4C patient nerve biopsies. The generated Sh3tc2 knockout mice thus present a reliable model of CMT4C neuropathy that was instrumental in establishing a role for Sh3tc2 in myelination and in the integrity of the node of Ranvier, a morphological phenotype that can be used as an additional CMT4C diagnostic marker.
MiSTIC, an integrated platform for the analysis of heterogeneity in large tumour transcriptome datasets

Abstract Genome-wide transcriptome profiling has enabled non-supervised classification of tumours, revealing different sub-groups characterized by specific gene expression features. However, the biological significance of these subtypes remains for the most part unclear. We describe herein an interactive platform, Minimum Spanning Trees Inferred Clustering (MiSTIC), that integrates the direct visualization and comparison of the gene correlation structure between datasets, the analysis of the molecular causes underlying co-variations in gene expression in cancer samples, and the clinical annotation of tumour sets defined by the combined expression of selected biomarkers. We have used MiSTIC to highlight the roles of specific transcription factors in breast cancer subtype specification, to compare the aspects of tumour heterogeneity targeted by different prognostic signatures, and to highlight biomarker interactions in AML. A version of MiSTIC preloaded with datasets described herein can be accessed through a public web server (http://mistic.iric.ca); in addition, the MiSTIC software package can be obtained (github.com/iric-soft/MiSTIC) for local use with personalized datasets.
Efficient Polymer Solar Cells Based on a Low Bandgap Semi‐crystalline DPP Polymer‐PCBM Blends

Solar cell performance and morphology characterization of a diketopyrrolopyrrole-based low bandgap polymer is reported. The polymer adopts an H-type aggregation and solvent mixture processing gives a better morphology. The morphology evolution is characterized by combined GIXD and GISAXS experiments and a four step morphology development mechanism is proposed.
The Antibiotic Resistant Target Seeker (ARTS), an exploration engine for antibiotic cluster prioritization and novel drug target discovery

Abstract With the rise of multi-drug resistant pathogens and the decline in number of potential new antibiotics in development there is a fervent need to reinvigorate the natural products discovery pipeline. Most antibiotics are derived from secondary metabolites produced by microorganisms and plants. To avoid suicide, an antibiotic producer harbors resistance genes often found within the same biosynthetic gene cluster (BGC) responsible for manufacturing the antibiotic. Existing mining tools are excellent at detecting BGCs or resistant genes in general, but provide little help in prioritizing and identifying gene clusters for compounds active against specific and novel targets. Here we introduce the ‘Antibiotic Resistant Target Seeker’ (ARTS) available at https://arts.ziemertlab. com. ARTS allows for specific and efficient genome mining for antibiotics with interesting and novel targets. The aim of this web server is to automate the screening of large amounts of sequence data and to focus on the most promising strains that produce antibiotics with new modes of action. ARTS integrates target directed genome mining methods, antibiotic gene cluster predictions and ‘essential gene screening’ to provide an interactive page for rapid identification of known and putative targets in BGCs.
MiR-221/222 Promote the Growth of Malignant Glioma Cells by Regulating Its Target Genes

Zhang Chunzhi1,2, Jiang Tao3, Wang Jinhuan4, Cheng Jinquan5, Pu Peiyu2 and Kang Chunsheng2 1Department of Radiation Oncology, Tianjin Huanhu hospital, Tianjin, 2Department of Neurosurgery, Laboratory of Neuro-Oncology, Tianjin Medical University General Hospital, Tianjin Key Laboratory of Nerve Injury, Variation and Regeneration, Tianjin, 3Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, 4Department of Neurosurgery, Tianjin Huanhu hospital, Tianjin 5Department of Molecular Oncology, H.Lee Moffitt Cancer and Research Institute, Tampa, 1,2,3,4China 5USA
PhD-SNPg: a webserver and lightweight tool for scoring single nucleotide variants

Abstract One of the major challenges in human genetics is to identify functional effects of coding and non-coding single nucleotide variants (SNVs). In the past, several methods have been developed to identify disease-related single amino acid changes but only few tools are able to score the impact of non-coding variants. Among the most popular algorithms, CADD and FATHMM predict the effect of SNVs in non-coding regions combining sequence conservation with several functional features derived from the ENCODE project data. Thus, to run CADD or FATHMM locally, the installation process requires to download a large set of pre-calculated information. To facilitate the process of variant annotation we develop PhD-SNPg, a new easy-to-install and lightweight machine learning method that depends only on sequence-based features. Despite this, PhD-SNPg performs similarly or better than more complex methods. This makes PhD-SNPg ideal for quick SNV interpretation, and as benchmark for tool development. Availability: PhD-SNPg is accessible at http://snps.biofold. org/phd-snpg.
Carboxylated molecules regulate magnesium content of amorphous calcium carbonates during calcification

With the realization that many calcified skeletons form by processes involving a precursor phase of amorphous calcium carbonate (ACC), a new paradigm for mineralization is emerging. There is evidence the Mg content in biogenic ACC is regulated by carboxylated (acidic) proteins and other macromolecules, but the physical basis for such a process is unknown. We test the hypothesis that ACC compositions express a systematic relationship to the chemistry of carboxyl-rich biomolecules. A series of inorganic control experiments were conducted to establish the dependence of Mg/Ca ratios in ACC on solution composition. We then determined the influence of a suite of simple carboxylated organic acids on Mg content. Molecules with a strong affinity for binding Ca compared with Mg promote the formation of Mg-enriched ACC that is compositionally equivalent to high-magnesium calcites and dolomite. Measurements show Mg/Ca ratios are controlled by a predictable dependence upon the binding properties of the organic molecules. The trend appears rooted in the conformation and electrostatic potential topology of each molecule, but dynamic factors also may be involved. The dependence suggests a physical basis for reports that specific sequences of calcifying proteins are critical to modulating mineralization. Insights from this study may provide a plausible explanation for why some biogenic carbonates and carbonaceous cements often contain higher Mg signatures than those that are possible by classical crystal growth processes. The findings reiterate the controls of microenvironment on mineralization and suggest an origin of compositional offsets, or vital effects, long recognized by the paleoclimate community.
Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice

Epsins are endocytic adaptors with putative functions in general aspects of clathrin-mediated endocytosis as well as in the internalization of specific membrane proteins. We have now tested the role of the ubiquitously expressed epsin genes, Epn1 and Epn2, by a genetic approach in mice. While either gene is dispensable for life, their combined inactivation results in embryonic lethality at E9.5–E10, i.e., at the beginning of organogenesis. Consistent with studies in Drosophila, where epsin endocytic function was linked to Notch activation, developmental defects observed in epsin 1/2 double knockout (DKO) embryos recapitulated those produced by a global impairment of Notch signaling. Accordingly, expression of Notch primary target genes was severely reduced in DKO embryos. However, housekeeping forms of clathrin-mediated endocytosis were not impaired in cells derived from these embryos. These findings support a role of epsin as a specialized endocytic adaptor, with a critical role in the activation of Notch signaling in mammals.
Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain

The sodium-potassium pump (Na+,K+-ATPase) is responsible for establishing Na+ and K+ concentration gradients across the plasma membrane and therefore plays an essential role in, for instance, generating action potentials. Cardiac glycosides, prescribed for congestive heart failure for more than 2 centuries, are efficient inhibitors of this ATPase. Here we describe a crystal structure of Na+,K+-ATPase with bound ouabain, a representative cardiac glycoside, at 2.8 Å resolution in a state analogous to E2·2K+·Pi. Ouabain is deeply inserted into the transmembrane domain with the lactone ring very close to the bound K+, in marked contrast to previous models. Due to antagonism between ouabain and K+, the structure represents a low-affinity ouabain-bound state. Yet, most of the mutagenesis data obtained with the high-affinity state are readily explained by the present crystal structure, indicating that the binding site for ouabain is essentially the same. According to a homology model for the high affinity state, it is a closure of the binding cavity that confers a high affinity.
GaS and GaSe Ultrathin Layer Transistors

Room-temperature, bottom-gate, field-effect transistor characteristics of 2D ultrathin layer GaS and GaSe prepared from the bulk crystals using a micromechanical cleavage technique are reported. The transistors based on active GaS and GaSe ultrathin layers demonstrate typical n-and p-type conductance transistor operation along with a good ON/OFF ratio and electron differential mobility.
Priority setting of foodborne pathogens: disease burden and costs of selected enteric pathogens

Toxoplasmose veroorzaakt van zeven onderzochte voedseloverdraagbare micro-organismen de hoogste ziektelast. Dit is een voorlopige conclusie in een groot onderzoek naar ziektelast van door voedseloverdraagbare micro-organismen en de daaraan gerelateerde kosten. De andere onderzochte micro-organismen zijn Campylobacter spp. , Salmonella spp. , Listeria monocytogenes, Escherichia coli O157, norovirussen en rotavirussen. De virussen brachten de hoogste kosten met zich mee (vooral vanwege ziekteverzuim). Het onderzoek is bedoeld als basis voor het stellen van prioriteiten bij het voedselveiligheidsbeleid. Tot dusverre zijn alle overdrachtsroutes van de micro-organismen beschouwd, later zal de specifieke bijdrage van voedsel worden onderzocht. Er zal ook aandacht worden besteed aan trends, de effectiviteit van preventieve maatregelen en de perceptie van het risico door consumenten.
The Murray Springs Clovis site, Pleistocene extinction, and the question of extraterrestrial impact

Some of the evidence for the recent hypothesis of an extraterrestrial impact that caused late Pleistocene megafaunal extinctions [Firestone et al. (2007) Proc Natl Acad Sci USA 104:16016–16021] was based upon samples collected at Murray Springs, a Clovis archaeological site in southeastern Arizona. Here we describe sampling and analyses of magnetic separates from within, above, and below the lower Younger Dryas boundary (LYDB) black mat at Murray Springs, as well as radiation measurements from the LYDB at Murray Springs and two other well-stratified Clovis sites. The main magnetic fraction at Murray Springs is maghemite. Magnetic microspherules have terrestrial origins but also occur as cosmic dust particles. We failed to find iridium or radiation anomalies. The evidence for massive biomass burning at Murray Springs is addressed and found to be lacking. We could not substantiate some of the claims by Firestone and others, but our findings do not preclude a terminal Pleistocene cosmic event.
Modulation of neuronal responses during covert search for visual feature conjunctions

While searching for an object in a visual scene, an observer's attentional focus and eye movements are often guided by information about object features and spatial locations. Both spatial and feature-specific attention are known to modulate neuronal responses in visual cortex, but little is known of the dynamics and interplay of these mechanisms as visual search progresses. To address this issue, we recorded from directionally selective cells in visual area MT of monkeys trained to covertly search for targets defined by a unique conjunction of color and motion features and to signal target detection with an eye movement to the putative target. Two patterns of response modulation were observed. One pattern consisted of enhanced responses to targets presented in the receptive field (RF). These modulations occurred at the end-stage of search and were more potent during correct target identification than during erroneous saccades to a distractor in RF, thus suggesting that this modulation is not a mere presaccadic enhancement. A second pattern of modulation was observed when RF stimuli were nontargets that shared a feature with the target. The latter effect was observed during early stages of search and is consistent with a global feature-specific mechanism. This effect often terminated before target identification, thus suggesting that it interacts with spatial attention. This modulation was exhibited not only for motion but also for color cue, although MT neurons are known to be insensitive to color. Such cue-invariant attentional effects may contribute to a feature binding mechanism acting across visual dimensions.
The α2δ subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function

Voltage-gated calcium channels are thought to exist in the plasma membrane as heteromeric proteins, in which the α1 subunit is associated with two auxiliary subunits, the intracellular β subunit and the α2δ subunit; both of these subunits influence the trafficking and properties of CaV1 and CaV2 channels. The α2δ subunits have been described as type I transmembrane proteins, because they have an N-terminal signal peptide and a C-terminal hydrophobic and potentially transmembrane region. However, because they have very short C-terminal cytoplasmic domains, we hypothesized that the α2δ proteins might be associated with the plasma membrane through a glycosylphosphatidylinositol (GPI) anchor attached to δ rather than a transmembrane domain. Here, we provide biochemical, immunocytochemical, and mutational evidence to show that all of the α2δ subunits studied, α2δ-1, α2δ-2, and α2δ-3, show all of the properties expected of GPI-anchored proteins, both when heterologously expressed and in native tissues. They are substrates for prokaryotic phosphatidylinositol-phospholipase C (PI-PLC) and trypanosomal GPI-PLC, which release the α2δ proteins from membranes and intact cells and expose a cross-reacting determinant epitope. PI-PLC does not affect control transmembrane or membrane-associated proteins. Furthermore, mutation of the predicted GPI-anchor sites markedly reduced plasma membrane and detergent-resistant membrane localization of α2δ subunits. We also show that GPI anchoring of α2δ subunits is necessary for their function to enhance calcium currents, and PI-PLC treatment only reduces calcium current density when α2δ subunits are coexpressed. In conclusion, this study redefines our understanding of α2δ subunits, both in terms of their role in calcium-channel function and other roles in synaptogenesis.
Sintomatología depresiva en pacientes con fibromialgia

Introduccion: La fibromialgia es una entidad frecuente en la practica clinica y se ha considerado que esta asociada con desordenes psiquiatricos, en particular con depresion, lo cual podria tener un impacto en el tratamiento de esta entidad. Objetivo: Evaluar la prevalencia de sintomas depresivos en pacientes con fibromialgia. Diseno: Estudio observacional y de tipo transversal. Lugar: Servicio de Reumatologia, Hospital Departamental Maria Auxiliadora. Participantes: Pacientes de ambos sexos con diagnostico de fibromialgia. Intervenciones: Se utilizo la escala de Hamilton para la depresion (HDRS) y el recuento de puntos dolorosos para fibromialgia. Principales medidas de resultados: Porcentaje de pacientes con sintomas depresivos. Puntaje total de la HDRS en relacion al recuento de puntos dolorosos. Resultados: La edad promedio fue 54,9 ± 14 anos, 80% fue del sexo femenino y el numero promedio de puntos dolorosos, 14,4 ± 1,5. El 32,7% de pacientes no tenia sintomas de animo depresivo, en 27,7% los sintomas fueron leves, en 30,9% moderados y solo en 9% severos. Ningun paciente presento sintomas compatibles con animo depresivo muy severo. Encontramos una correlacion significativa entre el numero de puntos dolorosos y el puntaje de la escala HDRS (r= 0,740), p< 0,001. Conclusiones: Los sintomas depresivos severos se encuentran en una proporcion baja en pacientes con fibromialgia y parecen estar directamente asociados con el numero de puntos dolorosos.
High‐Detectivity Multilayer MoS2 Phototransistors with Spectral Response from Ultraviolet to Infrared

Phototransistors based on multilayer MoS(2) crystals are demonstrated with a wider spectral response and higher photoresponsivity than single-layer MoS(2) phototransistors. Multilayer MoS(2) phototransistors further exhibit high room temperature mobilities (>70 cm(2) V(-1) s(-1) ), near-ideal subthreshold swings (~70 mV decade(-1) ), low operating gate biases (<5 V), and negligible shifts in the threshold voltages during illumination.
Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy

Abstract While having multiple aminoacyl-tRNA synthetases implicated in Charcot-Marie-Tooth (CMT) disease suggests a common mechanism, a defect in enzymatic activity is not shared among the CMT-causing mutants. Protein misfolding is a common hypothesis underlying the development of many neurological diseases. Its process usually involves an initial reduction in protein stability and then the subsequent oligomerization and aggregation. Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS). Through various approaches, we found that the mutations do not induce changes in protein secondary structures, or shared effects on oligomerization state and stability. However, all mutations provide access to a surface masked in the wild-type enzyme, and that access correlates with protein misinteraction. With recent data on another CMT-linked tRNA synthetase, we suggest that an inherent plasticity, engendering the formation of alternative stable conformations capable of aberrant interactions, links the tRNA synthetase family to CMT.
Optically Tunable Amino‐Functionalized Graphene Quantum Dots

Amino-functionalized graphene quantum dots (af-GQDs) with discrete molecular weights and specific edges were self-limitedly extracted from oxidized graphene sheet. Their optical properties can be precisely controlled only by the selective and quantitative functionalization at the edge sites. The af-GQDS exhibit bright colorful fluorescence under a single-wavelength excitation.
A survey into the prevalence and incidence of school bullying in Wales: summary report

"The Welsh Assembly Government commissioned the People & Work Unit (PWU) to undertake a survey of school bullying in Wales. The survey focuses on pupils’ experiences of bullying by other pupils within their school life. The survey aimed to provide baseline evidence of the “incidence and prevalence of bullying” among compulsory school aged pupils in Wales and allow the Assembly Government to “measure future changes to the level of bullying in Wales”. " - background.