Whole-Genome Omics Elucidates the Role of CCM1 and Progesterone in Cerebral Cavernous Malformations within CmPn Networks.

Cerebral cavernous malformations (CCMs) are abnormal expansions of brain capillaries that increase the risk of hemorrhagic strokes, with CCM1 mutations responsible for about 50% of familial cases. The disorder can cause irreversible brain damage by compromising the blood-brain barrier (BBB), leading to fatal brain hemorrhages. Studies show that progesterone and its derivatives significantly impact BBB integrity.

Plasma water T detects age-stratified differences in cardiometabolic health among familial CCM patients with Hispanic CCM1 mutation.

Cerebral cavernous malformations (CCMs) are abnormal clusters of capillaries in the nervous system. This pilot study analyzed the cardiometabolic health status of individuals with familial CCMs caused by a rare mutation in the CCM1 gene (fCCM1). The aim was to compare plasma water T values from individuals with fCCM1 with values from metabolically unhealthy and healthy individuals with no known CCM mutations.

Biomarkers derived from CmP signal network in triple negative breast cancers.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in women, accounting for approximately 30% of all new cancer cases. The prognosis of breast cancer heavily depends on the stage of diagnosis, with early detection resulting in higher survival rates. Various risk factors, including family history, alcohol consumption and hormone exposure, contribute to breast cancer development.

Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs).

Cerebral cavernous malformations (CCMs) are a neurological disorder characterized by enlarged intracranial capillaries in the brain, increasing the susceptibility to hemorrhagic strokes, a major cause of death and disability worldwide. The limited treatment options for CCMs underscore the importance of prognostic biomarkers to predict the likelihood of hemorrhagic events, aiding in treatment decisions and identifying potential pharmacological targets. This study aimed to identify blood biomarkers capable of diagnosing and predicting the risk of hemorrhage in CCM1 patients, establishing an initial set of circulating biomarker signatures.

Deep-Learning Uncovers certain CCM Isoforms as Transcription Factors.

Background: Cerebral Cavernous Malformations (CCMs) are brain vascular abnormalities associated with an increased risk of hemorrhagic strokes. Familial CCMs result from autosomal dominant inheritance involving three genes: (), (), and (). CCM1 and CCM3 form the CCM Signal Complex (CSC) by binding to CCM2.

Plasma water T2 detects age-stratified differences in cardiometabolic health among familial CCM patients with Hispanic CCM1 mutation.

Introduction: Cerebral cavernous malformations (CCMs) are abnormal clusters of capillaries in the nervous system. This pilot study analyzed the cardiometabolic health status of individuals with familial CCMs caused by a rare mutation in the gene (fCCM1). The aim was to compare plasma water T values from individuals with fCCM1 with values from metabolically unhealthy and healthy individuals with no known CCM mutations.

Plasma water T detects age-stratified differences in cardiometabolic health among familial CCM patients with Hispanic CCM1 mutation.

Introduction: Cerebral cavernous malformations (CCMs) are abnormal clusters of capillaries in the nervous system. This pilot study analyzed the cardiometabolic health status of individuals with familial CCMs caused by a rare mutation in the gene (fCCM1). The aim was to compare plasma water T values from individuals with fCCM1 with values from metabolically unhealthy and healthy individuals with no known CCM mutations.

De novo design of monomeric helical bundles for pH-controlled membrane lysis.

Targeted intracellular delivery via receptor-mediated endocytosis requires the delivered cargo to escape the endosome to prevent lysosomal degradation. This can in principle be achieved by membrane lysis tightly restricted to endosomal membranes upon internalization to avoid general membrane insertion and lysis. Here, we describe the design of small monomeric proteins with buried histidine containing pH-responsive hydrogen bond networks and membrane permeating amphipathic helices.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection.

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines.

CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier.

Cerebral cavernous malformations (CCMs) arise when capillaries within the brain enlarge abnormally, causing the blood-brain barrier (BBB) to break down. The BBB serves as a sophisticated interface that controls molecular interactions between the bloodstream and the central nervous system. The neurovascular unit (NVU) is a complex structure made up of neurons, astrocytes, endothelial cells (ECs), pericytes, microglia, and basement membranes, which work together to maintain blood-brain barrier (BBB) permeability.

Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations.

Cerebral cavernous malformations (CCMs) are abnormally dilated intracranial capillaries that form cerebrovascular lesions with a high risk of hemorrhagic stroke. Recently, several somatic "activating" gain-of-function (GOF) point mutations in PIK3CA (phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit p110α) were discovered as a dominant mutation in the lesions of sporadic forms of cerebral cavernous malformation (sCCM), raising the possibility that CCMs, like other types of vascular malformations, fall in the PIK3CA-related overgrowth spectrum (PROS). However, this possibility has been challenged with different interpretations.

Key Members of the CmPn as Biomarkers Distinguish Histological and Immune Subtypes of Hepatic Cancers.

Liver cancer, comprising hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a leading cause of cancer-related deaths worldwide. The liver is a primary metabolic organ for progesterone (PRG) and PRG exerts its effects through classic nuclear PRG receptors (nPRs) and non-classic membrane PRG receptors (mPRs) or a combination of both. Previous studies have shown that the CCM signaling complex (CSC) couples both nPRs and mPRs to form the CmPn (CSC-mPR-PRG-nPR) signaling network, which is involved in multiple cellular signaling pathways, including tumorigenesis of various cancers.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection.

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines.

SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules.

The cilium-centrosome complex contains triplet, doublet, and singlet microtubules. The lumenal surfaces of each microtubule within this diverse array are decorated by microtubule inner proteins (MIPs). Here, we used single-particle cryo-electron microscopy methods to build atomic models of two types of human ciliary microtubule: the doublet microtubules of multiciliated respiratory cells and the distal singlet microtubules of monoflagellated human spermatozoa.

Cryo-ET of Env on intact HIV virions reveals structural variation and positioning on the Gag lattice.

HIV-1 Env mediates viral entry into host cells and is the sole target for neutralizing antibodies. However, Env structure and organization in its native virion context has eluded detailed characterization. Here, we used cryo-electron tomography to analyze Env in mature and immature HIV-1 particles.

Nuclear envelope budding is a response to cellular stress.

Nuclear envelope budding (NEB) is a recently discovered alternative pathway for nucleocytoplasmic communication distinct from the movement of material through the nuclear pore complex. Through quantitative electron microscopy and tomography, we demonstrate how NEB is evolutionarily conserved from early protists to human cells. In the yeast , NEB events occur with higher frequency during heat shock, upon exposure to arsenite or hydrogen peroxide, and when the proteasome is inhibited.

Instability in a coiled-coil signaling helix is conserved for signal transduction in soluble guanylyl cyclase.

How nitric oxide (NO) activates its primary receptor, α1/β1 soluble guanylyl cyclase (sGC or GC-1), remains unknown. Likewise, how stimulatory compounds enhance sGC activity is poorly understood, hampering development of new treatments for cardiovascular disease. NO binding to ferrous heme near the N-terminus in sGC activates cyclase activity near the C-terminus, yielding cGMP production and physiological response.

Axonemal doublet microtubules can split into two complete singlets in human sperm flagellum tips.

Motile flagella are crucial for human fertility and embryonic development. The distal tip of the flagellum is where growth and intra-flagellar transport are coordinated. In most model organisms, but not all, the distal tip includes a 'singlet region', where axonemal doublet microtubules (dMT) terminate and only complete A-tubules extend as singlet microtubules (sMT) to the tip.

Composition, structure and function of the eukaryotic flagellum distal tip.

Cilia and flagella are long extensions commonly found on the surface of eukaryotic cells. In fact, most human cells have a flagellum, and failure to correctly form cilia leads to a spectrum of diseases gathered under the name 'ciliopathies'. The cilium distal tip is where it grows and signals.