Miracle-dz/UniFAR-FTUs huggingface dataset:
Implications of present‐day abiogenic methane fluxes for the early Archean atmosphere

During Earth's early history, greenhouse warming by atmospheric methane helped to maintain elevated surface temperatures. Here, we estimate the present‐day abiogenic CH4 flux generated by mineral alteration (serpentinization) at mid‐ocean ridges, volcanic emissions, and geothermal sources; in addition, we assess the impact that abiogenic methane may have had on greenhouse warming during the early prebiotic Archean. Based on estimates of the rate of seafloor spreading and the degree of serpentinization within the oceanic crust, the flux of methane generated by serpentinized lithosphere is calculated to be ∼1.35 Mt CH4 y−1, while volcanic and geothermal sources are estimated to contribute ∼0.1 and ∼0.9 Mt CH4 y−1, respectively. Furthermore, it is shown that if atmospheric CO2 partial pressures were above 0.01 bar, the present‐day level of abiogenic methane production could have been sufficient to maintain above‐freezing surface temperatures during the Archean. The very high temperatures (∼70°C) that have been suggested for the early Archean, however, would have required extremely high methane fluxes or, more likely, greatly elevated atmospheric CO2 levels.
Sequencing

With the emergence of zebrafish as an important model organism, a concerted effort has been made to study its transcriptome. This effort is limited, however, by gaps in zebrafish annotation, which are especially pronounced concerning transcripts dynamically expressed during zygotic genome activation (ZGA). To date, short read sequencing has been the principal technology for zebrafish transcriptome annotation. In part because these sequence reads are too short for assembly methods to resolve the full complexity of the transcriptome, the current annotation is rudimentary. By providing direct observation of full-length transcripts, recently refined long-read sequencing platforms can dramatically improve annotation coverage and accuracy. Here, we leveraged the SMRT platform to study transcriptome of zebrafish embryos before and after ZGA. Our analysis revealed additional novelty and complexity in the zebrafish transcriptome, identifying 2748 high confidence novel transcripts that originated from previously unannotated loci and 1835 high confidence new isoforms in previously annotated genes. We validated these findings using a suite of computational approaches including structural prediction, sequence homology and functional conservation analyses, as well as by confirmatory transcript quantification with short-read sequencing data. Our analyses provided insight into new homologs and paralogs of functionally important proteins and non-coding RNAs, isoform switching occurrences and different classes of novel splicing events. Several novel isoforms representing distinct splicing events were validated through PCR experiments, including the discovery and validation of a novel 8 kb transcript spanning multiple miR-430 elements, an important driver of early development. Our study provides a significantly improved zebrafish transcriptome annotation resource.
Diffraction peak profiles of surface relaxed spherical nanocrystals

Abstract A model is proposed for surface relaxation of spherical nanocrystals. Besides reproducing the primary effect of changing the average unit cell parameter, the model accounts for the inhomogeneous atomic displacement caused by surface relaxation and its effect on the diffraction line profiles. Based on three parameters with clear physical meanings - extension of the sub-coordination effect, maximum radial displacement due to sub-coordination, and effective hydrostatic pressure - the model also considers elastic anisotropy and provides parametric expressions of the diffraction line profiles directly applicable in data analysis. The model was tested on spherical nanocrystals of several fcc metals, matching atomic positions with those provided by Molecular Dynamics (MD) simulations based on embedded atom potentials. Agreement was also verified between powder diffraction patterns generated by the Debye scattering equation, using atomic positions from MD and the proposed model.
Effect of Patterned Surfaces of Adhesive Islands on the Shape, Cytoskeleton, Adhesion and Behaviour of Swiss Mouse 3T3 Fibroblasts

SUMMARY A pattern of circular islands of adhesive substratum can be used to control cell shape and behaviour. We have shown previously that the proportion of Swiss 3T3 cells that synthesize DNA varies with the area of the island to which they are attached, within the range 500–5000 μm2. In this paper we investigate the cytoskeleton and adhesions of cells on islands using a variety of techniques including phalloidin staining and interference reflection microscopy. Islands of area 2000 μm2 or less constrain cell shape, and cause focal contacts and actin microfilament bundles to accumulate in a circle at the margin. These changes are most obvious in islands of about 1000 μm2, in which a complete ring of adhesion is sometimes formed in the periphery of the cell. This peripheral distribution is less common in cells on even smaller islands, and the focal contacts become smaller and less numerous. It is not yet clear whether any of these structural changes are associated directly with the proliferative stimulus due to contact with the substratum. However, we expect that the use of patterned substrata will contribute to the study of how cell shape and structure regulate many cell functions.
Prevention and Treatment of Respiratory Consequences Induced by Sulfur Mustard in Iranian Casualties

Background: About 100,000 Iranian have been exposed to chemical weapons during Iraq-Iran conflict (1980-88). After being spent of more than two decades, still about 30,000 of them are under follow-up treatment. The main aim of this study was to review various preventive and therapeutic methods for injured patients with sulfur mustard in different phases. Methods: For gathering information, we have used the electronic databases including Scopus, Medline, ISI, IranMedex, Irandoc sites. According to this search strategy, 104 published articles associated to respiratory problems and among them 50 articles related to prevention and treatment of respiratory problems were found and reviewed. Results: There is not any curative treatment for sulfur mustard induced lung injuries, but some valuable experienced measures for prevention and palliative treatments are available. Some useful measures in acute phase include: Symptomatic management, oxygen supplementation, tracheostomy in laryngospasm, use of moist air, respiratory physical therapy, mucolytic agents and bronchodilators. In the chronic phases, these measures include: Periodic clinical examinations, administration of inhaled corticosteroids alone or with long-acting beta 2 agonists, use of antioxidants, magnesium ions, long term oxygen supplement, therapeutic bronchoscopy, laser therapy, and use of respiratory tract stents. Conclusions: Most treatments are symptomatic but using preventive points immediately after exposure could improve following outcomes.
Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

Objective Limited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors. Methods Data from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis. Results The study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033). Conclusion Major protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.
Status of radiation protection in various interventional cardiology procedures in the Asia Pacific region

Objective Increasing use of interventional procedures in cardiology with unknown levels of radiation protection in many countries of Asia-Pacific region necessitates the need for status assessment. The study was part of an International Atomic Energy Agency (IAEA) project for achieving improved radiation protection in interventional cardiology (IC) in developing countries. Design The survey covers 18 cardiac catheterisation laboratories in seven countries (Bangladesh, India, Malaysia, Myanmar, Singapore, Thailand and Vietnam). An important step was the creation of the ‘Asian network of Cardiologists in Radiation Protection’ and a newsletter. Data were collected on: radiation protection tools, number of IC laboratories, and annual number of various IC paediatric and adult procedures in the hospital and in the country. Patient radiation dose data were collected in terms of Kerma Area Product (KAP) and cumulative dose (CD). Results It is encouraging that protection devices for staff are largely used in the routine practice. Only 39% of the angiographic machines were equipped with a KAP meter. Operators' initial lack of awareness on radiation-protection optimisation improved significantly after participation in IAEA radiation-protection training. Only two out of five countries reporting patient percutaneous coronary intervention radiation-dose data were fully within the international guidance levels. Data from 51 patients who underwent multiple therapeutic procedures (median 2–3) indicated a total KAP reaching 995 Gy.cm2 (range 10.1–995) and CD 15.1 Gy (range 0.4–15.1), stressing the importance of dose monitoring and optimisation. Conclusions There is a need for interventional cardiology societies to play an active role in training actions and implementation of radiation protection.
Probing confined fields with single molecules and vice versa

Single dye molecules are used as local probes to map the spatial distribution of the squared electric field components in the focus of a high numerical aperture lens. Simulated field distributions are quantitatively verified by experimentally obtained fluorescence excitation maps. We show that annular illumination can be used to engineer the field distribution in the focus at a dielectric/air interface such that electric field components in all directions acquire comparable magnitudes. The 3D orientation of molecular absorption dipoles can be determined by comparing measured to simulated image patterns. The presence of longitudinal electric field components in a focus is of particular interest in tip‐enhanced scanning near‐field optical microscopy.
Nonisothermal crystallization and microstructural behavior of poly(ε-caprolactone) and granular tapioca starch-based biocomposites

ABSTRACT The nonisothermal crystallization behavior of poly(ε-caprolactone) (PCL) in the presence of varying concentrations of granular tapioca starch (GTS) was studied. Various crystallization parameters were studied by differential scanning calorimeter at four different cooling rates and these parameters were analyzed using Jeziorny, Ozawa, and Liu models. Kissinger method was used to estimate the activation energy (ΔE) of the PCL/GTS composites. The ΔE results suggested that the speed of crystallization was inhibited by GTS particles. Polarized light optical microscopy suggests formation of spherulite structure in PCL and PCL/GTS composites while no evidence of nucleation by GTS particles was observed.
West Nile Virus Discriminates between DC-SIGN and DC-SIGNR for Cellular Attachment and Infection

ABSTRACT The C-type lectins DC-SIGN and DC-SIGNR bind mannose-rich glycans with high affinity. In vitro, cells expressing these attachment factors efficiently capture, and are infected by, a diverse array of appropriately glycosylated pathogens, including dengue virus. In this study, we investigated whether these lectins could enhance cellular infection by West Nile virus (WNV), a mosquito-borne flavivirus related to dengue virus. We discovered that DC-SIGNR promoted WNV infection much more efficiently than did DC-SIGN, particularly when the virus was grown in human cell types. The presence of a single N-linked glycosylation site on either the prM or E glycoprotein of WNV was sufficient to allow DC-SIGNR-mediated infection, demonstrating that uncleaved prM protein present on a flavivirus virion can influence viral tropism under certain circumstances. Preferential utilization of DC-SIGNR was a specific property conferred by the WNV envelope glycoproteins. Chimeras between DC-SIGN and DC-SIGNR demonstrated that the ability of DC-SIGNR to promote WNV infection maps to its carbohydrate recognition domain. WNV virions and subviral particles bound to DC-SIGNR with much greater affinity than DC-SIGN. We believe this is the first report of a pathogen interacting more efficiently with DC-SIGNR than with DC-SIGN. Our results should lead to the discovery of new mechanisms by which these well-studied lectins discriminate among ligands.
Isolation and Characterization of Proinsulin-Producing Medullary Thymic Epithelial Cell Clones

Proinsulin, like many tissue-specific antigens, is expressed by rare (1–3%) cells of the thymus medullary stroma, presumably for the purpose of self-tolerance. Levels of this expression are associated with type 1 diabetes susceptibility in humans and in the NOD mouse. To further understand the mechanism of central tolerance induction by these rare cells, we have isolated and cultured two proinsulin-producing epithelial cell clones from murine thymus. These cells have a typical epithelial morphology and, by flow cytometry, a surface phenotype representative of mature thymic medullary epithelial cells (G8.8+/UEA-1+/DEC205−/CD45−/MHC II+). By RT-PCR, they express predominantly Ins2 as opposed to Ins1, as does whole thymus. Expression of the transcription factor Aire, implicated in enhancing promiscuous thymic expression of tissue-specific antigens, fell to very low levels after a few passages but increased 20-fold upon exposure to an agonistic anti-lymphotoxin B antibody, concurrent with 2.5-fold enhanced insulin expression. RNA of Pdx-1, Glut-2, and Gck was detectable by RT-PCR in whole thymus but not in the clones, suggesting thymic proinsulin expression is Pdx-1 independent and that Pdx-1, Glut-2, and Gck are likely expressed in the thymus as antigens, not as regulatory molecules.
Human Neuroscience

How much of the " unconscious " is just pre – threshold? Visual awareness is a specific form of consciousness. Binocular rivalry, the alternation of visual consciousness resulting when the two eyes view differing stimuli, allows one to experimentally investigate visual awareness. Observers usually indicate the gradual changes of conscious perception in binocular rivalry by a binary measure: pressing a button. However, in our experiments we used gradual measures such as pupil and joystick movements and found reactions to start around 590 ms before observers press a button , apparently accessing even pre-conscious processes. Our gradual measures permit monitoring the somewhat gradual built-up of decision processes. Therefore these decision processes should not be considered as abrupt events. This is best illustrated by the fact that the process to take a decision may start but then stop before an action has been taken – which we will call an abandoned decision process here. Changes in analog measures occurring before button presses by which observers have to communicate that a decision process has taken place do not prove that these decisions are taken by a force other than the observer – hence eliminating " free will " – but just that they are prepared " pre-thresholdly, " before the observer considers the decision as taken.
Presence of a plant-like proton-translocating pyrophosphatase in a scuticociliate parasite and its role as a possible drug target

SUMMARY The proton-translocating inorganic pyrophosphatases (H+-PPases) are primary electrogenic H+ pumps that derive energy from the hydrolysis of inorganic pyrophosphate (PPi). They are widely distributed among most land plants and have also been found in several species of protozoan parasites. Here we describe, for the first time, the molecular cloning and functional characterization of a gene encoding an H+-pyrophosphatase in the protozoan scuticociliate parasite Philasterides dicentrarchi, which infects turbot. The predicted P. dicentrarchi PPase (PdPPase) consists of 587 amino acids of molecular mass 61·7 kDa and an isoelectric point of 5·0. Several motifs characteristic of plant vacuolar H+-PPases (V–H+-PPases) were also found in the PdPPase, which contains all the sequence motifs of the prototypical type I V–H+-PPase from Arabidopsis thaliana vacuolar pyrophosphatase type I (AVP1) plant. The PdPPase has a characteristic residue that determines strict K+-dependence, but unlike AVP1, PdPPase contains an N-terminal signal peptide (SP) sequence. Antibodies generated by vaccination of mice with a genetic or recombinant protein containing a partial sequence of the PdPPase and a common motif with the polyclonal antibody PABHK specific to AVP1 recognized a single band of about 62 kDa in western blots. These antibodies specifically stained both vacuole and the alveolar membranes of trophozoites of P. dicentrarchi. H+ transport was partially inhibited by the bisphosphonate pamidronate (PAM) and completely inhibited by NaF. The bisphosphonate PAM inhibited both H+-translocation and gene expression. PdPPase and PAM also inhibited in vitro growth of the ciliates. The apparent lack of V–H+-PPases in vertebrates and the parasite sensitivity to PPI analogues may provide a molecular target for developing new drugs to control scuticociliatosis.
Melanocytes don’t always take the high road

A central dogma of pigment cell development has been that the truncal neural crest (NC) cells that will ultimately give rise to skin melanocytes migrate under the epidermis along a dorsolateral route in developing embryos, while NC cells migrating along the ventral pathway between the neural tube and the dermamyotome contribute to the neurons and glia of the peripheral nervous system (Figure 1A) (Le Douarin and Kalcheim, 1999). The seminal work by Adameyko et al., recently published in Cell (Adameyko et al., 2009), challenges this simplistic dichotomy by providing strong evidence that NC derivatives in the ventral pathway are also an important origin of melanocytes in the skin.
Adoptive transfer of cross-protection among alphaviruses in mice requires allogeneic stimulation

Cell-mediated (T-effector cell) immunity is proposed as playing the major role in cross-protection between Sindbis and Semliki Forest viruses, which are alphaviruses that do not elicit cross-neutralizing antibodies. In adoptive transfer experiments, T-cells from spleens of Sindbis virus-immunized mice were found to confer specific cross-protection to Semliki Forest virus upon recipient mice. This cross-protection was observed in the outbred ICR strain of mice and when transfers were made between several combinations of inbred and hybrid strains. Cross-protection was substantially reduced if syngeneic rather than allogeneic cell transfers of one spleen equivalent per mouse were made. The results suggest that allogeneic stimulation (mixed lymphocyte reaction in vivo) is necessary to increase the number of effector cells (donor) in the recipient. This was supported by the observation that blastogenic stimulation of donor cells in vitro by concanavalin A induces cross-protection in syngeneic animals. Conversion of recipient cells to specific effector cells also appears to play a role in protecting mice against Semliki Forest virus. This was concluded from the experiments described above, a time course study, and the results of experiments that involved serial passages of transferred cells across histocompatibility barriers. Thus, we propose that both donor and recipient cells are active in protecting recipient mice against challenge with Semliki Forest virus after adoptive transfer.
Estimating cellular pathways from an ensemble of heterogeneous data sources

Building better models of cellular pathways is one of the major challenges of systems biology and functional genomics. There is a need for methods to build on established expert knowledge and reconcile it with results of high-throughput studies. Moreover, the available data sources are heterogeneous and need to be combined in a way specific for the part of the pathway in which they are most informative. Here, we present a compartment specific strategy to integrate edge, node and path data for the refinement of a network hypothesis. Specifically, we use a local-move Gibbs sampler for refining pathway hypotheses from a compendium of heterogeneous data sources, including novel methodology for integrating protein attributes. We demonstrate the utility of this approach in a case study of the pheromone response MAPK pathway in the yeast S. cerevisiae.
Mitochondrial DNA variability in the Titicaca basin: Matches and mismatches with linguistics and ethnohistory

The Titicaca basin was the cradle of some of the major complex societies of pre‐Columbian South America and is today home to three surviving native languages: Quechua, Aymara, and Uro. This study seeks to contribute to reconstructing the population prehistory of the region, by providing a first genetic profile of its inhabitants, set also into the wider context of South American genetic background.