Systemic inhibition of purine biosynthesis prevents weight gain and improves metabolic health by increasing thermogenesis and decreasing food intake.

Objective: Obesity is a major health concern, largely because it contributes to type 2 diabetes mellitus (T2DM), cardiovascular disease, and various malignancies. Increase in circulating amino acids and lipids, in part due to adipose dysfunction, have been shown to drive obesity-mediated diseases. Similarly, elevated purines and uric acid, a degradation product of purine metabolism, are found in the bloodstream and in adipose tissue.

Disruption of nucleotide biosynthesis reprograms mitochondrial metabolism to inhibit adipogenesis.

A key organismal response to overnutrition involves the development of new adipocytes through the process of adipogenesis. Preadipocytes sense changes in the systemic nutrient status and metabolites can directly modulate adipogenesis. We previously identified a role of de novo nucleotide biosynthesis in adipogenesis induction, whereby inhibition of nucleotide biosynthesis suppresses the expression of the transcriptional regulators PPARγ and C/EBPα.

Toward the Development of a Pan-Lyssavirus Vaccine.

In addition to the rabies virus (RABV), 16 more lyssavirus species have been identified worldwide, causing a disease similar to RABV. Non-rabies-related human deaths have been described, but the number of cases is unknown, and the potential of such lyssaviruses causing human disease is unpredictable. The current rabies vaccine does not protect against divergent lyssaviruses such as Mokola virus (MOKV) or Lagos bat virus (LBV).

Inhibition of nucleotide biosynthesis disrupts lipid accumulation and adipogenesis.

Energy balance and nutrient availability are key determinants of cellular decisions to remain quiescent, proliferate, or differentiate into a mature cell. After assessing its environmental state, the cell must rewire its metabolism to support distinct cellular outcomes. Mechanistically, how metabolites regulate cell fate decisions is poorly understood.

Hip Abductor Power and Velocity: Reliability and Association With Physical Function.

Lanza, MB, Jin, KH, Karl, H, Myers, J, Ryan, E, and Gray, VL. Hip abductor power and velocity: reliability and association with physical function. J Strength Cond Res 37(2): 284-290, 2023-Muscle power, defined as the ability of the muscle to produce torque quickly, has received little attention and may be critical for understanding physical function and performance.

Balanced engagement of activating and inhibitory receptors mitigates human NK cell exhaustion.

NK cell exhaustion is caused by chronic exposure to activating stimuli during viral infection, tumorigenesis, and prolonged cytokine treatment. Evidence suggests that exhaustion may play a role in disease progression. However, relative to T cell exhaustion, the mechanisms underlying NK cell exhaustion and methods of reversing it are poorly understood.

Current vaccine strategies against SARS-CoV-2: Promises and challenges.

In the years since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began and spread across the globe, lessons have been learned about the challenges and opportunities that a pandemic brings to humankind. Researchers have produced many vaccines at unprecedented speed to protect people, but they have also been cognizant of the challenges presented by a new and unexpected infectious disease. The scope of this review is to examine the path of vaccine discovery so far and identify potential targets.

Arsenic Toxicity on Metabolism and Autophagy in Adipose and Muscle Tissues.

Arsenic, a naturally occurring metalloid derived from the environment, has been studied worldwide for its causative effects in various cancers. However, the effects of arsenic toxicity on the development and progression of metabolic syndrome, including obesity and diabetes, has received less attention. Many studies suggest that metabolic dysfunction and autophagy dysregulation of adipose and muscle tissues are closely related to the development of metabolic disease.

Exploring the NK cell platform for cancer immunotherapy.

Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system that are capable of killing virally infected and/or cancerous cells. Nearly 20 years ago, NK cell-mediated immunotherapy emerged as a safe and effective treatment approach for patients with advanced-stage leukaemia. Subsequently, the field of NK cell-based cancer therapy has grown exponentially and currently constitutes a major area of immunotherapy innovation.

Sestrin2 Phosphorylation by ULK1 Induces Autophagic Degradation of Mitochondria Damaged by Copper-Induced Oxidative Stress.

Selective autolysosomal degradation of damaged mitochondria, also called mitophagy, is an indispensable process for maintaining integrity and homeostasis of mitochondria. One well-established mechanism mediating selective removal of mitochondria under relatively mild mitochondria-depolarizing stress is PINK1-Parkin-mediated or ubiquitin-dependent mitophagy. However, additional mechanisms such as LC3-mediated or ubiquitin-independent mitophagy induction by heavy environmental stress exist and remain poorly understood.

Limited-Montage EEG as a Tool for the Detection of Nonconvulsive Seizures.

Purpose: Prefabricated arrays with a limited number of electrodes offer an opportunity to hasten the diagnosis of seizures; however, their accuracy to detect seizures is unknown. We examined the utility of two limited-montage EEG setups for the detection of nonconvulsive seizures.

Methods: Thirty previously interpreted EEG segments with nonconvulsive seizures from 30 patients and 60 segments with background slowing or normal EEG from 60 patients were rendered in a bipolar "double banana" montage, a double distance "neonatal" montage, and a circumferential "hatband" montage.

Tetracyclines Modify Translation by Targeting Key Human rRNA Substructures.

Apart from their antimicrobial properties, tetracyclines demonstrate clinically validated effects in the amelioration of pathological inflammation and human cancer. Delineation of the target(s) and mechanism(s) responsible for these effects, however, has remained elusive. Here, employing quantitative mass spectrometry-based proteomics, we identified human 80S ribosomes as targets of the tetracyclines Col-3 and doxycycline.

(1E,2E)-1,2-Bis[(1-benzyloxymethyl-1H-indol-3-yl)methylidene]hydrazine.

The title compound, C(34)H(30)N(4)O(2), lies on an inversion center and consists of two 3-substituted-1H-indole units linked by a 1,2-dimethyl-enehydrazine bridge. It is one of numerous examples in which two aromatic ring systems are joined by this 4-atom bridge. The geometry of the centrosymmetric bridge is: C(arom)-C = 1.

Effect of inclining strain on the crystal lattice along an extended series of lanthanide hydroxysulfates Ln(OH)SO4 (Ln = Pr-Yb, except Pm).

A series of trivalent lanthanide hydroxysulfates, Ln(OH)SO(4), (Ln = Pr through Yb, except radioactive Pm) has been synthesized via hydrothermal methods from Ln(2)(SO(4))(3)·8H(2)O by reaction with aqueous NaOH at 170 °C in Teflon lined Parr steel autoclaves, and were characterized by single crystal X-ray diffraction and FT-IR spectroscopy. Two types of arrangements were found in the solid state. The lighter (Ln = Pr-Nd, Sm-Gd) and heavier lanthanide(III) hydroxysulfates (Tb-Yb) are each isostructural.