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Transceptors, solute transporters that facilitate intracellular entry of molecules and also initiate intracellular signaling events, have been primarily studied in lower-order species. Ammonia, a cytotoxic endogenous metabolite, is converted to urea in hepatocytes for urinary excretion in mammals. During hyperammonemia, when hepatic metabolism is impaired, nonureagenic ammonia disposal occurs primarily in skeletal muscle. Increased ammonia uptake in skeletal muscle is mediated by a membrane-bound, 12 transmembrane domain solute transporter, Rhesus blood group-associated B glycoprotein (RhBG). We show that in addition to its transport function, RhBG interacts with myeloid differentiation primary response-88 (MyD88) to initiate an intracellular signaling cascade that culminates in activation of NFκB. We also show that ammonia-induced MyD88 signaling is independent of the canonical toll-like receptor-initiated mechanism of MyD88-dependent NFκB activation. In silico, in vitro, and in situ experiments show that the conserved cytosolic J-domain of the RhBG protein interacts with the Toll-interleukin-1 receptor (TIR) domain of MyD88. In skeletal muscle from human patients, human-induced pluripotent stem cell-derived myotubes, and myobundles show an interaction of RhBG-MyD88 during hyperammonemia. Using complementary experimental and multiomics analyses in murine myotubes and mice with muscle-specific RhBG or MyD88 deletion, we show that the RhBG-MyD88 interaction is essential for the activation of NFkB but not ammonia transport. Our studies show a paradigm of substrate-dependent regulation of transceptor function with the potential for modulation of cellular responses in mammalian systems by decoupling transport and signaling functions of transceptors. [ABSTRACT FROM AUTHOR]

Aim In this study, we investigated culturable yeast community, present in grape must sampled from vineyards with apiaries on the borders, and in honey bees collected in these apiaries. Methods and results To this aim, yeasts isolated from spontaneously fermented grapes randomly collected in two vineyards (P1 and P2) with apiaries on the borders (A1 and A2) were compared to those isolated from spontaneously fermented grapes collected from a vineyard without apiary (P4). At the same time, yeast community was analyzed on bees collected in each apiary placed in the vineyards, in comparison to yeasts isolated from an apiary (A3) located far from the vineyards. The analysis was performed for two consecutive years (2021 and 2022). The isolated yeasts were identified by restriction analysis of amplified ITS region, followed by sequencing of ITS fragment. Our research showed that the presence of apiaries seems to increase yeast counts of grape must, in particular of Saccharomyces cerevisiae ; furthermore, the permanence of apiaries in the vineyards allowed the recovering of these yeasts also from bees. Conclusions Our findings seem to corroborate the role of bees as vectors and reservoirs of oenologically relevant yeasts, such as a source of non-conventional yeasts with potential biotechnological applications. [ABSTRACT FROM AUTHOR]

Background: The Hugo™ Robot-Assisted Surgery (RAS) system is a new cutting-edge robotic platform designed for clinical applications. Nevertheless, its application for cystic renal tumors has not yet been thoroughly investigated. In this context, we present an initial series of Robot-Assisted Partial Nephrectomy (RAPN) procedures carried out using the Hugo™ RAS system for cystic renal masses. Methods: Between October 2022 and January 2024, twenty-seven RAPN procedures for renal tumors were performed at Fondazione Policlinico Universitario Campus Bio-Medico. Our prospective board-approved dataset was queried for "cystic features" (n = 12). Perioperative data were collected. The eGFR was calculated according to the CKD-EPI formula. Post-operative complications were reported according to the Clavien–Dindo classification. Computed tomography (CT) scans for follow-up were performed according to the EAU guidelines. Trifecta was defined as the coexistence of negative surgical margin status, no Clavien–Dindo grade ≥ 3 complications, and eGFR decline ≤ 30%. Results: All the patients successfully underwent RAPN without the need for conversion or additional port placement. The median docking and console time were 5.5 (IQR, 4–6) and 79.5 min (IQR, 58–91 min), respectively. No intraoperative complications occurred, as well as clashes between instruments or with the bedside assistant. Two minor postoperative complications were recorded (Clavien–Dindo II). At discharge, serum creatinine and eGFR were comparable to preoperative values. Only one patient (8.4%) displayed positive surgical margins. The rate of trifecta achievement was 91.7%. Conclusions: RAPN for cystic renal masses using the novel Hugo™ RAS system can be safely and effectively performed. This robotic system provided satisfactory peri-operative outcomes, preserving renal function and displaying low postoperative complications and a high trifecta rate achievement. [ABSTRACT FROM AUTHOR]

Originally discovered as part of C1, the initiation component of the classical complement pathway, it is now appreciated that C1q regulates a variety of cellular processes independent of complement activation. C1q is a complex glycoprotein assembled from 18 polypeptide chains, with a C-terminal globular head region that mediates recognition of diverse molecular structures, and an N-terminal collagen-like tail that mediates immune effector mechanisms. C1q mediates a variety of immunoregulatory functions considered important in the prevention of autoimmunity such as the enhancement of phagocytosis, regulation of cytokine production by antigen presenting cells, and subsequent alteration in T-lymphocyte maturation. Furthermore, recent advances indicate additional roles for C1q in diverse physiologic and pathologic processes including pregnancy, tissue repair, and cancer. Finally, C1q is emerging as a critical component of neuronal network refinement and homeostatic regulation within the central nervous system. This review summarizes the classical functions of C1q and reviews novel discoveries within the field.

Facioscapulohumeral muscular dystrophy (FSHD) involves sporadic expression of DUX4, which inhibits myogenesis and is pro-apoptotic. To identify target genes, we over-expressed DUX4 in myoblasts and found that the receptor tyrosine kinase Ret was significantly up-regulated, suggesting a role in FSHD. RET is dynamically expressed during myogenic progression in mouse and human myoblasts. Constitutive expression of either RET9 or RET51 increased myoblast proliferation, whereas siRNA-mediated knockdown of Ret induced myogenic differentiation. Suppressing RET activity using Sunitinib, a clinically-approved tyrosine kinase inhibitor, rescued differentiation in both DUX4-expressing murine myoblasts and in FSHD patient-derived myoblasts. Importantly, Sunitinib also increased engraftment and differentiation of FSHD myoblasts in regenerating mouse muscle. Thus, DUX4-mediated activation of Ret prevents myogenic differentiation and could contribute to FSHD pathology by preventing satellite cell-mediated repair. Rescue of DUX4-induced pathology by Sunitinib highlights the therapeutic potential of tyrosine kinase inhibitors for treatment of FSHD.

(1) Background: Laparoscopic partial nephrectomy (LPN) is still performed in many referred urological institutions, representing a valid alternative to robot-assisted partial nephrectomy (RAPN). We aimed to compare trifecta outcomes of LPN and RAPN with the Hugo™ RAS System. (2) Methods: Between October 2022 and September 2023, eighty-nine patients underwent minimally invasive partial nephrectomy (group A, RAPN = 27; group B, Laparoscopic PN = 62) for localized renal tumors at our Institution. Continuous variables were presented as median and IQR and compared by means of the Mann–Whitney U test, while categorical variables were presented as frequencies (%) and compared by means of the χ2 test. (3) Results: Group A showed a higher rate of male patients (81.5% vs. 59.7%, p = 0.04) and a higher trend towards larger clinical tumor size (34 vs. 29 mm, p = 0.14). All the other baseline variables were comparable between the two groups (all p > 0.05). Regarding post-operative data, group A displayed a lower operative time (92 vs. 149.5 min, p = 0.005) and a shorter hospital stay (3 vs. 5, p = 0.002). A higher rate of malignant pathology was evidenced in group A (77.8% vs. 58.1%, p = 0.07) as well as a lower trend towards positive surgical margins (3.7% vs. 4.8%, p = 0.82), even if not statistically significant. (4) Conclusions: The rate of trifecta achievement was 92.6% and 82.3% for group A and B (p = 0.10), respectively. In terms of trifecta outcomes, RAPN using the Hugo™ RAS System showed comparable results to LPN performed by the same experienced surgeon. [ABSTRACT FROM AUTHOR]

The article discusses the use of the Hugo robot-assisted surgery system for off-clamp robot-assisted partial nephrectomy (RAPN). The Hugo system is a modular robotic platform with four independent arm-carts that allows for highly customized procedures. The study describes the first experience and surgical setting for off-clamp RAPN using the Hugo system, and reports successful outcomes without major complications or the need for conversion. The authors suggest that the Hugo system shows promise for use in complex renal masses, but further studies are needed to confirm its feasibility and safety. [Extracted from the article]