The role of ER exit sites in maintaining P-body organization and integrity during Drosophila melanogaster oogenesis.

Processing bodies (P-bodies) are cytoplasmic membrane-less organelles which host multiple mRNA processing events. While the fundamental principles of P-body organization are beginning to be elucidated in vitro, a nuanced understanding of how their assembly is regulated in vivo remains elusive. Here, we investigate the potential link between ER exit sites and P-bodies in Drosophila melanogaster egg chambers.

Post-transcriptional regulation of and mRNAs is mediated by Bruno 1 and Cup, and further fine-tuned within P-bodies.

Cell cycle progression is tightly controlled by the regulated synthesis and degradation of Cyclins, such as Cyclin A and Cyclin B, which activate CDK1 to trigger mitosis. Mutations affecting Cyclin regulation are often linked to tumorigenesis, making the study of cyclin mRNA regulation critical for identifying new cancer therapies. In this study, we demonstrate via super-resolution microscopy that and mRNAs associate with Bruno 1 and Cup in nurse cells.

The mRNA dynamics underpinning translational control mechanisms of Drosophila melanogaster oogenesis.

Advances in the study of mRNAs have yielded major new insights into post-transcriptional control of gene expression. Focus on the spatial regulation of mRNAs in highly polarized cells has demonstrated that mRNAs translocate through cells as mRNA:protein granules (mRNPs). These complex self-assemblies containing nuclear and cytoplasmic proteins are fundamental to the coordinated translation throughout cellular development.

Distinct conformational states enable transglutaminase 2 to promote cancer cell survival versus cell death.

Transglutaminase 2 (TG2) is a GTP-binding, protein-crosslinking enzyme that has been investigated as a therapeutic target for Celiac disease, neurological disorders, and aggressive cancers. TG2 has been suggested to adopt two conformational states that regulate its functions: a GTP-bound, closed conformation, and a calcium-bound, crosslinking-active open conformation. TG2 mutants that constitutively adopt an open conformation are cytotoxic to cancer cells.

The role of ER exit sites in maintaining P-body organization and transmitting ER stress response during oogenesis.

Processing bodies (P-bodies) are cytoplasmic membrane-less organelles which host multiple mRNA processing events. While the fundamental principles of P-body organization are beginning to be elucidated , a nuanced understanding of how their assembly is regulated remains elusive. Here, we investigate the potential link between ER exit sites and P-bodies in egg chambers.

Is There a Relationship between Psychotic Disorders and the Radicalization Process? A Systematic Review.

: Radicalization, a complex and multifaceted phenomenon, has been a subject of increasing concern in recent years, particularly due to its potential connection to acts of mass violence and terrorism. This systematic review examines the intricate link between radicalization and psychotic disorders, utilizing various sources such as observational studies, case reports, and series. It aims to highlight the prevalence of schizophrenia spectrum and other psychotic disorders among radicalized individuals and to define the role of mental health professionals in dealing with this issue, contributing to the development of prevention and treatment strategies.

Influence of the dietary contribution of terrestrial insects to the condition factor of bleak Alburnus alburnus in a highly polluted lowland river.

Bleak Alburnus alburnus is a highly abundant but understudied fish species, and we know little about the trophic ecology of populations inhabiting rivers in central Europe. From an ecosystem perspective, this fish species is interesting as it is known to feed on surface insects, thereby linking the terrestrial with the aquatic habitat. In a previous study, we demonstrated that this flux is intensified, and dietary contribution of terrestrial insects is higher in fish inhabiting sections of the Spree River, Germany, that are polluted from iron oxides occurring from former lignite mining activities, and thus are characterized by lower abundances of aquatic insects.

The β3-AR agonist BRL37344 ameliorates the main symptoms of X-linked nephrogenic diabetes insipidus in the mouse model of the disease.

X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3-adrenergic receptor could be such an ideal candidate.

Effects of mining activities on fish communities and food web dynamics in a lowland river.

Fish communities of streams and rivers might be substantially subsidized by terrestrial insects that fall into the water. Although such animal-mediated fluxes are increasingly recognized, little is known about how anthropogenic perturbations may influence the strength of such exchanges. Intense land use, such as lignite mining, may impact a river ecosystem due to the flocculation of iron (III) oxides, thus altering food web dynamics.

β3-Adrenoceptor as a new player in the sympathetic regulation of the renal acid-base homeostasis.

Efferent sympathetic nerve fibers regulate several renal functions activating norepinephrine receptors on tubular epithelial cells. Of the beta-adrenoceptors (β-ARs), we previously demonstrated the renal expression of β3-AR in the thick ascending limb (TAL), the distal convoluted tubule (DCT), and the collecting duct (CD), where it participates in salt and water reabsorption. Here, for the first time, we reported β3-AR expression in the CD intercalated cells (ICCs), where it regulates acid-base homeostasis.

Filament formation drives catalysis by glutaminase enzymes important in cancer progression.

The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the 'glutamine addiction' of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide a view of the conformational states essential for catalysis.

Defining the conformational states that enable transglutaminase 2 to promote cancer cell survival versus cell death.

Transglutaminase 2 (TG2) is a GTP-binding/protein-crosslinking enzyme that has been investigated as a therapeutic target for Celiac disease, neurological disorders, and aggressive cancers. TG2 has been suggested to adopt two conformational states that regulate its functions: a GTP-bound, closed conformation, and a calcium-bound, crosslinking-active open conformation. TG2 mutants that constitutively adopt an open conformation are cytotoxic to cancer cells.

Stable isotopes in the shell organic matrix for (paleo)environmental reconstructions.

Stable isotope ratios of mollusc shell carbonates have long been used to reconstruct past environmental conditions. Although shells also contain organics, they are seldom used in (paleo)climatic studies. Here, we extract the acid-soluble and insoluble fractions of the organic matrix of modern Mytilus galloprovincialis shells from three sites along a coast-to-upper-estuary environmental gradient to measure their hydrogen (δH) and oxygen (δO) isotope compositions.

Cup is essential for mRNA translational repression during early oogenesis.

Study of the timing and location for mRNA translation across model systems has begun to shed light on molecular events fundamental to such processes as intercellular communication, morphogenesis, and body pattern formation. In , the posterior mRNA determinant, , is transcribed maternally but translated only when properly localized at the oocyte's posterior cortex. Two effector proteins, Bruno1 and Cup, mediate steps of mRNA regulation.

Detection of Antibodies against the Acetylcholine Receptor in Patients with Myasthenia Gravis: A Comparison of Two Enzyme Immunoassays and a Fixed Cell-Based Assay.

The detection of serum anti-acetylcholine receptor (AChR) antibodies is currently an important tool for diagnosing myasthenia gravis (MG) since they are present in about 85% of MG patients. Many serological tests are now available. Nevertheless, results from these tests can be different in some patients.

Chaotic advection mixer for capturing transient states of diverse biological macromolecular systems with time-resolved small-angle X-ray scattering.

Advances in time-resolved structural techniques, mainly in macromolecular crystallography and small-angle X-ray scattering (SAXS), allow for a detailed view of the dynamics of biological macromolecules and reactions between binding partners. Of particular promise, are mix-and-inject techniques, which offer a wide range of experimental possibility as microfluidic mixers are used to rapidly combine two species just prior to data collection. Most mix-and-inject approaches rely on diffusive mixers, which have been effectively used within crystallography and SAXS for a variety of systems, but their success is dependent on a specific set of conditions to facilitate fast diffusion for mixing.

Filament formation drives catalysis by glutaminase enzymes important in cancer progression.

The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the 'glutamine addiction' of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide an unprecedented view of the conformational states essential for catalysis.

TRPML1-Induced Lysosomal Ca Signals Activate AQP2 Translocation and Water Flux in Renal Collecting Duct Cells.

Lysosomes are acidic Ca storage organelles that actively generate local Ca signaling events to regulate a plethora of cell functions. Here, we characterized lysosomal Ca signals in mouse renal collecting duct (CD) cells and we assessed their putative role in aquaporin 2 (AQP2)-dependent water reabsorption. Bafilomycin A1 and ML-SA1 triggered similar Ca oscillations, in the absence of extracellular Ca, by alkalizing the acidic lysosomal pH or activating the lysosomal cation channel mucolipin 1 (TRPML1), respectively.

β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus.

We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved.

Serial Room Temperature Crystal Loading, Data Collection, and Data Processing of Human Glutaminase C in Complex with Allosteric Inhibitors.

Cancer cells often overexpress glutaminase enzymes, in particular glutaminase C (GAC). GAC resides in the mitochondria and catalyzes the hydrolysis of glutamine to glutamate. High levels of GAC have been observed in aggressive cancers and the inhibition of its enzymatic activity has been shown to reduce their growth and survival.

Evolving Experimental Techniques for Structure-Based Drug Design.

Structure-based drug design (SBDD) is a prominent method in rational drug development and has traditionally benefitted from the atomic models of protein targets obtained using X-ray crystallography at cryogenic temperatures. In this perspective, we highlight recent advances in the development of structural techniques that are capable of probing dynamic information about protein targets. First, we discuss advances in the field of X-ray crystallography including serial room-temperature crystallography as a method for obtaining high-resolution conformational dynamics of protein-inhibitor complexes.

Role of Nuclear Lamin A/C in the Regulation of Nav1.5 Channel and Microtubules: Lesson From the Pathogenic Lamin A/C Variant Q517X.

In this work, we studied an nonsense mutation encoding for the C-terminally truncated Lamin A/C (LMNA) variant Q517X, which was described in patients affected by a severe arrhythmogenic cardiomyopathy with history of sudden death. We found that LMNA Q517X stably expressed in HL-1 cardiomyocytes abnormally aggregates at the nuclear envelope and within the nucleoplasm. Whole-cell patch clamp experiments showed that LMNA Q517X-expressing cardiomyocytes generated action potentials with reduced amplitude, overshoot, upstroke velocity and diastolic potential compared with LMNA WT-expressing cardiomyocytes.

Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry.

Background: Findings from the T.O.S.

Thirty-day readmission rates in a cohort of people living with HIV in southern Brazil, 2015 to 2017.

Background: The intense use of antiretroviral therapy (ART) has reduced morbidity and mortality of HIV infection. In Brazil, the specific contribution of diseases related to HIV infection leading to hospital admission and readmission is not well known.

Aims: The study aimed to determine the clinico-epidemiological profile, 30-day readmission rate, and factors associated with this outcome in a cohort of adults with HIV infection in southern Brazil.

Temporal and spatial variability of prehistoric aquatic resource procurement: a case study from Mesolithic Northern Iberia.

Prehistoric shell middens hold valuable evidence of past human-environment interactions. In this study, we used carbon (δC) and oxygen (δO) stable isotopes of Mytilus galloprovincialis shells excavated from El Perro, La Fragua and La Chora, three Mesolithic middens in Cantabria, Northern Spain, to examine hunter-gatherer subsistence strategies in terms of seasonality and collection areas. Furthermore, we used shell δO to reconstruct water temperature during the early Holocene.