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Introduction Thanks to next-generation sequencing (NGS) approaches, the list of genetic syndromes that cause thrombocytopenia has grown in recent years and now includes over 40 genes (1). However, there are [...], The ubiquitously expressed small GTPase Ras-related protein 1B (RAP1B) acts as a molecular switch that regulates cell signaling, cytoskeletal remodeling, and cell trafficking and activates integrins in platelets and lymphocytes. The residue G12 in the P-loop is required for the RAP1B-GTPase conformational switch. Heterozygous germline RAP1B variants have been described in patients with syndromic thrombocytopenia. However, the causality and pathophysiological impact remained unexplored. We report a boy with neonatal thrombocytopenia, combined immunodeficiency, neutropenia, and monocytopenia caused by a heterozygous de novo single nucleotide substitution, c.35G>A (p.G12E) in RAP1B. We demonstrate that G12E and the previously described G12V and G60R were gain-of-function variants that increased RAP1B activation, talin recruitment, and integrin activation, thereby modifying late responses such as platelet activation, T cell proliferation, and migration. We show that in our patient, G12E was a somatic variant whose allele frequency decreased over time in the peripheral immune compartment, but remained stable in bone marrow cells, suggesting a differential effect in distinct cell populations. Allogeneic hematopoietic stem cell transplantation fully restored the patient's hemato-immunological phenotype. Our findings define monoallelic RAP1B gain-of-function variants as a cause for constitutive immunodeficiency and thrombocytopenia. The phenotypic spectrum ranged from isolated hematological manifestations in our patient with somatic mosaicism to complex syndromic features in patients with reported germline RAP1B variants.

The present study analyzes the microstrip antenna design for wireless power transfer in smart buildings, harnessing the ambient electromagnetic radiation due to common electronic gadgets that energize wireless sensor networks, computing devices, and connected appliances. With the increased number of these devices, so does the potential for health problems caused by electromagnetic radiation. However, these devices also provide a renewable energy source through their emissions. This study suggests the creation of a 5G Microstrip antenna that enhances the absorption of this radiation for the purpose of recharging batteries in smart buildings. The design capitalizes on the inherent low-profile and cost-effective features of microstrip antennas, making them well-suited for incorporation into building infrastructure and 5G wireless technologies. Although each individual device emits a little amount of energy, the combined effect achieved by advanced antenna design and power converters is anticipated to result in a substantial energy production. The antenna designer tool from MATLAB was used to carry out a conceptual simulation of the microstrip antenna. This has set up the framework of a feasible way of predicting the performance with high efficiency and sustainability for a wireless power transfer (WPT) system. [ABSTRACT FROM AUTHOR]

Summary MYSM1 deficiency causes inherited bone marrow failure syndrome (IBMFS). We have previously identified an IBMFS patient with a homozygous pathogenic variant in MYSM1 who recovered from cytopenia due to spontaneous correction of one MYSM1 variant in the haematopoietic compartment, an event called somatic genetic rescue (SGR). The study of the genetic and biological aspects of the patient's haematopoietic/lymphopoietic system over a decade after SGR shows that one genetically corrected haematopoietic stem cell (HSC) can restore a healthy and stable haematopoietic system. This supports in vivo gene correction of HSCs as a promising treatment for IBMFS, including MYSM1 deficiency. [ABSTRACT FROM AUTHOR]

Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≅ 0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a [MAIT.sup.hi] congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory ([CD44.sup.+]) [CD4.sup.-][CD8.sup.lo/neg] T cells with tissue-homing properties ([CCR6.sup.+][CCR7.sup.-]). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the [MAIT.sup.hi] congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease., Introduction Mucosal-associated invariant T cells (MAITs) express an invariant TCR-α (iTCR-α) chain (iVα7.2-Jα33 in human and iVα19-Jα33 in mouse) restricted by the major histocompatibility complex (MHC) class I-related protein 1 [...]

Lymphocyte functions triggered by antigen recognition and costimulation signals are associated with a rapid and intense cell division, and hence with metabolism adaptation (1). The nucleotide cytidine 5' triphosphate (CTP) is a precursor required for the metabolism of DNA, RNA and phospholipids (2-4). CTP originates from two sources: a salvage pathway and a denovosynthesis pathway that depends on two enzymes, the CTP synthases (or synthetases) 1 and 2 (CTPS1 with CTPS2); the respective roles of these two enzymes are not known (5-7). CTP synthase activity is a potentially important step for DNA synthesis in lymphocytes (8,9). Here we report the identification of a loss-of-functionhomozygous mutation (rs145092287) in CTPS1 inhumans that causes a novel and life-threatening immunodeficiency, characterized by an impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. In contrast, proximal and distal T-cell receptor (TCR) signalling events and responses were only weakly affected by the absence of CTPS1. Activated CTPS1-deficient cells had decreased levels of CTP. Normal T-cell proliferation was restored in CTPS1 -deficient cells by expressing wild-type CTPS1 or by addition of exogenous CTP or its nucleoside precursor, cytidine. CTPS1 expression was found to be low in resting T cells, but rapidly upregulated following TCR activation. These results highlight a key and specific role of CTPS1 in the immune system by its capacity to sustain the proliferation of activated lymphocytes during the immune response. CTPS1 may therefore represent a therapeutic target of immunosuppressive drugs that could specifically dampen lymphocyte activation., We initially studied two unrelated families (family 1 and 2) originating from the northwest region of England, whose four children suffered from severe and recurrent Epstein-Barr virus (EBV) infection, in [...]

Background: Scalp conditions such as flaky or oily scalp affect people across ethnicities and age groups. In addition to flaking, increased sebum secretion, itching, and compromised scalp barrier function were described. Scalp conditions are aesthetically disturbing and may cause psychological distress in affected individuals who are looking for mild and effective treatment at the same time. Saccharide isomerate has a long history as a skin moisturizer, and it was found to improve skin barrier function, also suggesting possible beneficial effects on scalp. Aims: To provide relevant claim substantiation to introduce saccharide isomerate as a new scalp care active against scalp flaking condition. Material and Methods: We conducted a placebo‐controlled clinical study in an adult Chinese population affected by dandruff scalp as assessed by an adherent scalp flaking score. We monitored transepidermal water loss (TEWL), sebum secretion, and scalp flaking during 28 days. Results: Formulations containing Saccharide isomerate significantly improved all parameters both over time as well as compared to the placebo formulation. Conclusion: We propose Saccharide isomerate for cosmetic formulations directed toward improving scalp conditions such as dandruff or oily scalp. [ABSTRACT FROM AUTHOR]

Cell and developmental biology increasingly require live imaging of protein dynamics in cells, tissues or living organisms. Thanks to the discovery and development of a panel of fluorescent proteins over the last decades, live imaging has become a powerful and commonly used approach. However, multicolor live imaging remains challenging. The generation of long Stokes shift red fluorescent proteins offers interesting new perspectives to bypass this limitation. Here, we provide a detailed characterization of mBeRFP for in vivo live imaging and its applications in Drosophila. Briefly, we show that a single illumination source is sufficient to stimulate mBeRFP and GFP simultaneously. We demonstrate that mBeRFP can be easily combined with classical green and red fluorescent proteins without any crosstalk. We also show that the low photobleaching of mBeRFP is suitable for live imaging, and that this protein can be used for quantitative applications, such as FRAP or laser ablation. Finally, we believe that this fluorescent protein, with the set of new possibilities it offers, constitutes an important tool for cell, developmental and mechano-biologists in their current research. [ABSTRACT FROM AUTHOR]

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These stakeholders are (a) the Ngorongoro Pastoral Council, representing NCA residents; (b) tourism industry workers from outside the NCA; (c) NCA Authority and government managers, who have direct fiscal and operational responsibility; and (d) natural scientists, social scientists and conservation organisations, both local and global, concerned with conservation of the natural resources of the NCA and human welfare. The NCA has international conservation prominence due to its populations of black rhinoceros ( I Diceros bicornis michaeli i ), African elephant ( I Loxodonta africana i ), and a wide range of herbivore and large predator species (Homewood et al., 2004). The Ngorongoro Conservation Area (NCA) is a protected area and UNESCO World Heritage Site and part of the Serengeti-Ngorongoro Biosphere reserve in northern Tanzania. [Extracted from the article]

Autophagy is the process where cytosolic components are digested by the cell. This process is required for cell survival in stressful conditions. It was also shown to control cell division and more recently, cell morphology and migration. We characterized signalling pathways enabling embryonic epidermal cells of the nematode Caenorhabditis elegans to elongate along their antero-posterior axis. Previous studies revealed that epidermal cells can adopt either a RhoA-like or a Rac1-like morphogenic program. We show here that the AMP-activated protein kinase (AMPK) and genes controlling autophagy are required for proper elongation of epidermal cells following the RhoA-like program and are dispensable for other cells. This suggests that AMPK-autophagy is used by the embryo to fuel the most energy-demanding morphogenic processes promoting early elongation. [ABSTRACT FROM AUTHOR]