Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and represses c-myc transcription

Transcriptional control plays a key role in regulating epidermal proliferation and differentiation. Although ample information has been obtained on how epidermal homeostasis is controlled in adult skin, less is known about the control of proliferation/differentiation of epidermal stem/progenitor cells in the developing embryo. Ovol1, encoding a zinc finger protein homologous to Drosophila melanogaster Ovo, is expressed in embryonic epidermal progenitor cells that are transiting from proliferation to terminal differentiation. In this study, we demonstrate a function for Ovol1 in interfollicular epidermal development. In its absence, developing epidermis fails to properly restrict the proliferative potential of progenitor cells, and cultured keratinocytes fail to efficiently undergo growth arrest in response to extrinsic growth-inhibitory signals. We present molecular evidence that c-myc expression is up-regulated in Ovol1-deficient suprabasal cells and that Ovol1 represses c-myc transcription by directly binding to its promoter. Collectively, our findings indicate that Ovol1 is required for proliferation exit of committed epidermal progenitor cells and identify c-myc as an Ovol1 target

A novel method for the genome-wide high resolution analysis of DNA damage

DNA damage occurs via endogenous and exogenous genotoxic agents and compromises a genome’s integrity. Knowing where damage occurs within a genome is crucial to understanding the repair mechanisms which protect this integrity. This paper describes a new development based on microarray technology which uses ultraviolet light induced DNA damage as a paradigm to determine the position and frequency of DNA damage and its subsequent repair throughout the entire yeast genome

Screening Spin Lattice Interaction Using Deep Learning Approach

Atomic simulations hold significant value in clarifying crucial matters such as phase transitions and energy transport in materials science. Their success stems from the presence of potential energy functions capable of accurately depicting the relationship between system energy and lattice changes. In magnetic materials, two atomic scale degrees of freedom come into play: the lattice and the magnetic moment. Nonetheless, precisely portraying the interaction energy and its impact on lattice and spin-driving forces, such as atomic force and magnetic torque, remains a formidable task in the computational domain. Consequently, there is no atomic-scale approach capable of elucidating the evolution of lattice and spin at the same time in magnetic materials. Addressing this knowledge deficit, we present DeepSPIN, a versatile approach that generates high-precision predictive models of energy, atomic forces, and magnetic torque in magnetic systems. This is achieved by integrating first-principles calculations of magnetic excited states with advanced deep learning techniques via active learning. We thoroughly explore the methodology, accuracy, and scalability of our proposed model in this paper. Our technique adeptly connects first-principles computations and atomic-scale simulations of magnetic materials. This synergy presents opportunities to utilize these calculations in devising and tackling theoretical and practical obstacles concerning magnetic materials.Comment: 8 pages, 4 figure

Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci

Streptococcus pneumoniae (pneumococcus) is a nasopharyngeal commensal and respiratory pathogen. This study characterises the immunoglobulin G (IgG) repertoire recognising pneumococci from birth to 24 months old (mo) in a prospectively-sampled cohort of 63 children using a panproteome array. IgG levels are highest at birth, due to transplacental transmission of maternal antibodies. The subsequent emergence of responses to individual antigens exhibit distinct kinetics across the cohort. Stable differences in the strength of individuals’ responses, correlating with maternal IgG concentrations, are established by 6 mo. By 12 mo, children develop unique antibody profiles that are boosted by re-exposure. However, some proteins only stimulate substantial responses in adults. Integrating genomic data on nasopharyngeal colonisation demonstrates rare pneumococcal antigens can elicit strong IgG levels post-exposure. Quantifying such responses to the diverse core loci (DCL) proteins is complicated by cross-immunity between variants. In particular, the conserved N terminus of DCL protein zinc metalloprotease B provokes the strongest early IgG responses. DCL proteins’ ability to inhibit mucosal immunity likely explains continued pneumococcal carriage despite hosts’ polyvalent antibody repertoire. Yet higher IgG levels are associated with reduced incidence, and severity, of pneumonia, demonstrating the importance of the heterogeneity in response strength and kinetics across antigens and individuals

Differences in Hemoglobin A 1c Between Hispanics/Latinos and Non-Hispanic Whites: An Analysis of the Hispanic Community Health Study/Study of Latinos and the 2007–2012 National Health and Nutrition Examination Survey

To determine whether, after adjustment for glycemia and other selected covariates, hemoglobin A1c (HbA1c) differed among adults from six Hispanic/Latino heritage groups (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) and between Hispanic/Latino and non-Hispanic white adults without self-reported diabetes

Removal of phosphate from River water using a new baffle plates electrochemical reactor

During the last 50 years, the human activities have significantly altered the natural cycle of phosphate in this planet, causing phosphate to accumulate in the freshwater ecosystems of some countries to at least 75% greater than preindustrial levels, which indicates an urgent need to develop efficient phosphate treatment methods. Therefore, the current study investigates the removal of phosphate from river water using a new electrochemical cell (PBPR). This new cell utilises perforated baffle plates as a water mixer rather than magnetic stirrers that require power to work. This study investigates the influence of key operational parameters such as initial pH (ipH), current density (Ј), inter-electrode distance (ID), detention time (t) and initial phosphate concentration (IC) on the removal efficiency, and influence of the electrocoagulation process on the morphology of the surface of electrodes. Overall, the results showed that the new reactor was efficient enough to reduce the concentration of phosphate to the permissible limits. Additionally, SEM images showed that the Al anode became rough and nonuniform due to the production of aluminium hydroxides. The main advantages of the electrocoagulation technique are: 1- The EC method does not produce secondary pollutants as it does not required chemical additives, while other traditional treatment methods required either chemical or biological additives [[1], [2], [3], [4]]. 2- It has a large treatment capacity and a relatively short treatment time in comparison with other treatment methods, such as the biological methods [1,[5], [6], [7]]. 3- The EC method produces less sludge than traditional treatment traditional chemical and biological treatment methods [8,9]. EC technology, like any other treatment method, has some drawbacks that could limit its performance. For instance, it still has a clear deficiency in the variety of reactor design, and the electrodes should be periodically replaced as they dissolve into the solution due to the oxidation process [2,10]

Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes

Proteome-wide analysis of a malaria vaccine study reveals personalized humoral immune profiles in Tanzanian adults

Tanzanian adult male volunteers were immunized by direct venous inoculation with radiation-attenuated, aseptic, purified, cryopreserved; Plasmodium falciparum; (Pf) sporozoites (PfSPZ Vaccine) and protective efficacy assessed by homologous controlled human malaria infection (CHMI). Serum immunoglobulin G (IgG) responses were analyzed longitudinally using a Pf protein microarray covering 91% of the proteome, providing first insights into naturally acquired and PfSPZ Vaccine-induced whole parasite antibody profiles in malaria pre-exposed Africans. Immunoreactivity was identified against 2239 functionally diverse Pf proteins, showing a wide breadth of humoral response. Antibody-based immune 'fingerprints' in these individuals indicated a strong person-specific immune response at baseline, with little changes in the overall humoral immunoreactivity pattern measured after immunization. The moderate increase in immunogenicity following immunization and the extensive and variable breadth of humoral immune response observed in the volunteers at baseline suggest that pre-exposure reduces vaccine-induced antigen reactivity in unanticipated ways

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting