Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis.

Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples.

Use of the D4H Probe to Track Sterols in Yeast.

Cholesterol is a fundamental component of cellular membranes, and its organization, distribution, and recycling are tightly regulated. Cholesterol can form, together with other lipids and proteins, membrane nanodomains, which play important roles in membrane trafficking, the spatiotemporal organization of signal transduction, or the modulation of plasma membrane transporters, among others. Not surprisingly then, the misregulation of cholesterol biosynthetic and transport pathways has been related to numerous diseases, including neurodegenerative and metabolic disorders.

Diverse phage communities are maintained stably on a clonal bacterial host.

Bacteriophages are the most abundant and phylogenetically diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. In this study, we discovered that phage diversity consistently outstripped the diversity of their bacterial hosts under simple experimental conditions. We assembled and passaged dozens of diverse phage communities on a single, nonevolving strain of until the phage communities reached equilibrium.

TET3 regulates terminal cell differentiation at the metabolic level.

TET-family members play a critical role in cell fate commitment. Indeed, TET3 is essential to postnatal development due to yet unknown reasons. To define TET3 function in cell differentiation, we have profiled the intestinal epithelium at single-cell level from wild-type and Tet3 knockout mice.

Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke.

The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions.

Transcriptomic and metabolic signatures of neural cells cultured under a physiologic-like environment.

Cultured brain cells are used conventionally to investigate fundamental neurobiology and identify therapeutic targets against neural diseases. However, standard culture conditions do not simulate the natural cell microenvironment, thus hampering in vivo translational insight. Major weaknesses include atmospheric (21%) O tension and lack of intercellular communication, the two factors likely impacting metabolism and signaling.

Suppression of hepatic steatosis in non-alcoholic steatohepatitis model by modified Xiaoyao San formula: Evidence, mechanisms and perspective.

In this letter, we comment on a recent publication by Mei , in the , investigating the hepatoprotective effects of the modified Xiaoyao San (MXS) formula in a male rat model of non-alcoholic steatohepatitis (NASH). The authors found that MXS treatment mitigated hepatic steatosis and inflammation in the NASH model, as evidenced by the reduction in lipid droplets (LDs), fibrosis markers and lipogenic factors. Interestingly, these hepatoprotective effects were associated with androgen upregulation (based on metabolomics analysis of male steroid hormone metabolites), adenosine 5'-monophosphate-activated protein kinase (AMPK) activation, and restoration of phosphatase and tensin homolog (PTEN) expression.

Analysis of Meiotic Progression by Ex Vivo Culture of Mouse Embryonic Ovaries.

Oogenesis is the central process required to produce viable oocytes in female mammals. It is initiated during embryonic development, and it involves the specification of primordial germ cells (PGCs) and progresses through the activation of the meiotic program, reaching a crucial phase in prophase I before pausing at diplotene around the time of birth. The significance of meiosis, particularly the prophase I stage, cannot be overstated, as it plays a pivotal role in ensuring the formation of healthy gametes, a prerequisite for successful reproduction.

SPO-Seq: An Accessible Method for Efficient Evaluation of Spo11 Catalytic Activity and Profiling Meiotic DSB Hotspots in Saccharomyces cerevisiae.

Meiotic recombination is a key process facilitating the formation of crossovers and the exchange of genetic material between homologous chromosomes in early meiosis. This involves controlled double-strand breaks (DSBs) formation catalyzed by Spo11. DSBs exhibit a preferential location in specific genomic regions referred to as hotspots, and their variability is tied to varying Spo11 activity levels.

A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice.

Astrocytes control brain activity via both metabolic processes and gliotransmission, but the physiological links between these functions are scantly known. Here we show that endogenous activation of astrocyte type-1 cannabinoid (CB1) receptors determines a shift of glycolysis towards the lactate-dependent production of D-serine, thereby gating synaptic and cognitive functions in male mice. Mutant mice lacking the CB1 receptor gene in astrocytes (GFAP-CB1-KO) are impaired in novel object recognition (NOR) memory.

Weak neuronal glycolysis sustains cognition and organismal fitness.

The energy cost of neuronal activity is mainly sustained by glucose. However, in an apparent paradox, neurons modestly metabolize glucose through glycolysis, a circumstance that can be accounted for by the constant degradation of 6-phosphofructo-2-kinase-fructose-2,6-bisphosphatase-3 (PFKFB3), a key glycolysis-promoting enzyme. To evaluate the in vivo physiological importance of this hypoglycolytic metabolism, here we genetically engineered mice with their neurons transformed into active glycolytic cells through Pfkfb3 expression.

Global epistasis and the emergence of function in microbial consortia.

The many functions of microbial communities emerge from a complex web of interactions between organisms and their environment. This poses a significant obstacle to engineering microbial consortia, hindering our ability to harness the potential of microorganisms for biotechnological applications. In this study, we demonstrate that the collective effect of ecological interactions between microbes in a community can be captured by simple statistical models that predict how adding a new species to a community will affect its function.

Melatonin: A Myriad of Functions to Discover.

Melatonin is an indoleamine that has captured our attention since 1958 [...

Potent, selective and reversible hMAO-B inhibition by benzalphthalides: Synthesis, enzymatic and cellular evaluations and virtual docking and predictive studies.

Monoaminooxidases (MAOs) are important targets for drugs used in the treatment of neurological and psychiatric disorders and particularly on Parkinson's Disease (PD). Compounds containing a trans-stilbenoid skeleton have demonstrated good selective and reversible MAO-B inhibition. Here, twenty-two (Z)-3-benzylidenephthalides (benzalphthalides, BPHs) displaying a trans-stilbenoid skeleton have been synthesised and evaluated as inhibitors of the MAO-A and MAO-B isoforms.

A Missense Variant in Could Be a Genetic Biomarker Associated with Bone Tissue Alterations.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations in bone metabolism that lead to a defective skeleton, which is associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, with being one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of is a genetic factor associated with several pathologies, including cancer, stroke, and osteoporosis.

Muscle Hypertrophy Is Linked to Changes in the Oxidative and Proteolytic Systems during Early Tenderization of the Spanish Breed "Asturiana de los Valles".

For fresh meat consumers, eating satisfaction is of utmost importance and tenderness is one of the most important characteristics in this regard. Our study examined beef of different animal biotypes of the autochthonous breed "Asturiana de los Valles" (AV) to determine if early postmortem oxidative and proteolytic processes may influence the final tenderness of the product. This meat-specialized breed shows different biotypes depending on the frequency of a myostatin mutation "" that induces double-muscling or muscular hypertrophy (/, /+, +/+).

Diversity of Microorganisms and Their Metabolites in Food.

Throughout history as well as the present, food microorganisms have been proven to play a significant role in human life [...

REDOX Balance in Oligodendrocytes Is Important for Zebrafish Visual System Regeneration.

Zebrafish () present continuous growth and regenerate many parts of their body after an injury. Fish oligodendrocytes, microglia and astrocytes support the formation of new connections producing effective regeneration of the central nervous system after a lesion. To understand the role of oligodendrocytes and the signals that mediate regeneration, we use the well-established optic nerve (ON) crush model.

Environmental modulation of global epistasis in a drug resistance fitness landscape.

Interactions between mutations (epistasis) can add substantial complexity to genotype-phenotype maps, hampering our ability to predict evolution. Yet, recent studies have shown that the fitness effect of a mutation can often be predicted from the fitness of its genetic background using simple, linear relationships. This phenomenon, termed global epistasis, has been leveraged to reconstruct fitness landscapes and infer adaptive trajectories in a wide variety of contexts.

Beyond tradition: exploring the non-canonical functions of telomeres in meiosis.

The telomere bouquet is a specific chromosomal configuration that forms during meiosis at the zygotene stage, when telomeres cluster together at the nuclear envelope. This clustering allows cytoskeleton-induced movements to be transmitted to the chromosomes, thereby facilitating homologous chromosome search and pairing. However, loss of the bouquet results in more severe meiotic defects than can be attributed solely to recombination problems, suggesting that the bouquet's full function remains elusive.

Rapid, efficient auxin-inducible protein degradation in pathogens.

A variety of inducible protein degradation (IPD) systems have been developed as powerful tools for protein functional characterization. IPD systems provide a convenient mechanism for rapid inactivation of almost any target protein of interest. Auxin-inducible degradation (AID) is one of the most common IPD systems and has been established in diverse eukaryotic research model organisms.

Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition.

Having direct access to brain vasculature, astrocytes can take up available blood nutrients and metabolize them to fulfil their own energy needs and deliver metabolic intermediates to local synapses. These glial cells should be, therefore, metabolically adaptable to swap different substrates. However, in vitro and in vivo studies consistently show that astrocytes are primarily glycolytic, suggesting glucose is their main metabolic precursor.