P38α MAPK Coordinates Mitochondrial Adaptation to Caloric Surplus in Skeletal Muscle.

Excessive calorie intake leads to mitochondrial overload and triggers metabolic inflexibility and insulin resistance. In this study, we examined how attenuated p38α activity affects glucose and fat metabolism in the skeletal muscles of mice on a high-fat diet (HFD). Mice exhibiting diminished p38α activity (referred to as p38α) gained more weight and displayed elevated serum insulin levels, as well as a compromised response in the insulin tolerance test, compared to the control mice.

Heart Failure Promotes Cancer Progression in an Integrin β1-Dependent Manner.

Heart failure and cancer are currently the deadliest diseases in the Western world, posing the most pressing clinical challenges that remain unmet today. Both conditions share similar risk factors, including age, genetics, lifestyle, chronic inflammation, stress, and more. Furthermore, medications that are being used to counteract cancer frequently result in cardiotoxicity and the spontaneous emergence of heart failure.

Induction of heparanase 2 (Hpa2) expression by stress is mediated by ATF3.

Activity of heparanase, endoglycosidase that cleaves heparan sulfate side chains in heparan sulfate proteoglycans, is highly implicated in tumor progression and metastasis. Heparanase inhibitors are therefore being evaluated clinically as anti-cancer therapeutics. Heparanase 2 (Hpa2) is a close homolog of heparanase that lacks HS-degrading activity and functions as an endogenous inhibitor of heparanase.

p38 MAPK in Glucose Metabolism of Skeletal Muscle: Beneficial or Harmful?

Skeletal muscles respond to environmental and physiological changes by varying their size, fiber type, and metabolic properties. P38 mitogen-activated protein kinase (MAPK) is one of several signaling pathways that drive the metabolic adaptation of skeletal muscle to exercise. p38 MAPK also participates in the development of pathological traits resulting from excessive caloric intake and obesity that cause metabolic syndrome and type 2 diabetes (T2D).

ATF3 and JDP2 deficiency in cancer associated fibroblasts promotes tumor growth via SDF-1 transcription.

The activating transcription factor 3 (ATF3) and the c-Jun dimerization protein 2 (JDP2) are members of the basic leucine zipper (bZIP) family of transcription factors. These proteins share a high degree of homology and both can activate or repress transcription. Deficiency of either one of them in the non-cancer host cells was shown to reduce metastases.

WDR62 mediates TNFα-dependent JNK activation via TRAF2-MLK3 axis.

The mitogen-activated protein kinases (MAPKs) regulate a variety of cellular processes. The three main MAPK cascades are the extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 kinases. A typical MAPK cascade is composed of MAP3K-MAP2K-MAPK kinases that are held by scaffold proteins.

ATF3 expression in cardiomyocytes preserves homeostasis in the heart and controls peripheral glucose tolerance.

Aims: Obesity and type 2 diabetes (T2D) trigger a harmful stress-induced cardiac remodeling process known as cardiomyopathy. These diseases represent a serious and widespread health problem in the Western world; however the underlying molecular basis is not clear. ATF3 is an 'immediate early' gene whose expression is highly and transiently induced in response to multiple stressors such as metabolic, oxidative, endoplasmic reticulum and inflammation, stressors that are involved in T2D cardiomyopathy.

Investigation of the mechanisms of neuroprotection mediated by Ro5-4864 in brain injury.

Increasing evidence has established the involvement of the 18-kDa translocator protein (TSPO) in the process of mitochondrial membrane permeabilization and subsequent apoptosis through modulation of the mitochondrial permeability transition pore. Recent studies have shown that treatment with Ro5-4864, a TSPO ligand, resulted in a neuroprotective effect in traumatic brain injury. Yet, the nature of this effect remained uncertain as mature neurons are considered to be lacking the TSPO protein.

Syria civil war: Outcomes of humanitarian neurosurgical care provided to Syrian wounded refugees in Israel.

Background: As an expected consequence of the civil war in Syria, emergent neurosurgical care for battlefield trauma has been provided for severely head-injured Syrians transferred to Northern Israel.

Methods: Sixty-six patients suffering from brain injury were brought to the border and then referred to the institution after initial resuscitation. Both the time and type of injury were recorded based on paramedic testimony, forensic material or on details provided by patients.

APOL1 nephropathy: from gene to mechanisms of kidney injury.

The contribution of African ancestry to the risk of focal segmental glomerulosclerosis and chronic kidney disease has been partially explained by the recently described chromosome 22q variants in the gene apolipoprotein L1 (APOL1). The APOL1 variants appear at a high allele frequency in populations of West African ancestry as a result of apparent adaptive selection of the heterozygous state. Heterozygosity protects from infection with Trypanosoma brucei rhodesiense.

APOL1 risk variants enhance podocyte necrosis through compromising lysosomal membrane permeability.

Development of higher rates of nondiabetic glomerulosclerosis (GS) in African Americans has been attributed to two coding sequence variants (G1 and G2) in the APOL1 gene. To date, the cellular function and the role of APOL1 variants (Vs) in GS are still unknown. In this study, we examined the effects of overexpressing wild-type (G0) and kidney disease risk variants (G1 and G2) of APOL1 in human podocytes using a lentivirus expression system.

The ubiquitin ligase Hul5 promotes proteasomal processivity.

The 26S proteasome is a large cytoplasmic protease that degrades polyubiquitinated proteins to short peptides in a processive manner. The proteasome 19S regulatory subcomplex tethers the target protein via its polyubiquitin adduct and unfolds the target polypeptide, which is then threaded into the proteolytic site-containing 20S subcomplex. Hul5 is a 19S subcomplex-associated ubiquitin ligase that elongates ubiquitin chains on proteasome-bound substrates.

Autophosphorylation-induced degradation of the Pho85 cyclin Pcl5 is essential for response to amino acid limitation.

Pho85 cyclins (Pcls), activators of the yeast cyclin-dependent kinase (CDK) Pho85, belong together with the p35 activator of mammalian CDK5 to a distinct structural cyclin class. Different Pcls target Pho85 to distinct substrates. Pcl5 targets Pho85 specifically to Gcn4, a yeast transcription factor involved in the response to amino acid starvation, eventually causing the degradation of Gcn4.

Phylogenetic studies of Terfezia pfeilii and Choiromyces echinulatus (Pezizales) support new genera for southern African truffles: Kalaharituber and Eremiomyces.

The ITS region including the 5.8S rRNA gene as well as the 5' end of the 28S rRNA gene of hypogeous Pezizaceae and Tuberaceae were studied to clarify the generic placement of two southern African desert truffles, Terfezia pfeilii and Choiromyces echinulatus. The results show that neither species belongs in the genus to which it has been assigned on the basis of morphological characters.

Two ITS forms co-inhabiting a single genet of an isolate of Terfezia boudieri (Ascomycotina), a desert truffle.

Two fruit-bodies of Terfezia boudieri Chatin, each exhibiting a mixture of two ITS -RFLP profiles, were found in the Negev desert of Israel. A mycelial culture obtained from glebal out-growth maintained the double profile, as did proliferating cultures established using single hyphae isolated from the original cultures. The main difference between the two ITS variants lies in a 21 bp deletion in the smaller variant.