A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia.

Objective: Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species.

Deciphering maternal-fetal cross-talk in the human placenta during parturition using single-cell RNA sequencing.

Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal cross-talk in labor have not been fully elucidated. Here, single-cell RNA sequencing (scRNA-seq) was applied to decipher maternal-fetal signaling in the human placenta during term labor.

Direct effects of adipocyte lipolysis on AMPK through intracellular long-chain acyl-CoA signaling.

Long-chain acyl-CoAs (LC-acyl-CoAs) are important intermediary metabolites and are also thought to function as intracellular signaling molecules; however, the direct effects of LC-acyl-CoAs have been difficult to determine in real-time and dissociate from Protein Kinase A (PKA) signaling. Here, we examined the direct role of lipolysis in generating intracellular LC-acyl-CoAs and activating AMPK in white adipocytes by pharmacological activation of ABHD5 (also known as CGI-58), a lipase co-activator. Activation of lipolysis in 3T3-L1 adipocytes independent of PKA with synthetic ABHD5 ligands, resulted in greater activation of AMPK compared to receptor-mediated activation with isoproterenol, a β-adrenergic receptor agonist.

Classification of preeclampsia according to molecular clusters with the goal of achieving personalized prevention.

The prevention of pre-eclampsia is difficult due to the syndromic nature and multiple underlying mechanisms of this severe complication of pregnancy. The current clinical distinction between early- and late-onset disease, although clinically useful, does not reflect the true nature and complexity of the pathologic processes leading to pre-eclampsia. The current gaps in knowledge on the heterogeneous molecular pathways of this syndrome and the lack of adequate, specific diagnostic methods are major obstacles to early screening and tailored preventive strategies.

Mitochondrial Oxidative Phosphorylation in Viral Infections.

Mitochondria have been identified as the "powerhouse" of the cell, generating the cellular energy, ATP, for almost seven decades. Research over time has uncovered a multifaceted role of the mitochondrion in processes such as cellular stress signaling, generating precursor molecules, immune response, and apoptosis to name a few. Dysfunctional mitochondria resulting from a departure in homeostasis results in cellular degeneration.

Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research.

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; <37 weeks) or (2) early preterm birth (ePTB; <32 weeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from public raw data via phylogenetic harmonization. The predictive models are validated on two independent unpublished datasets representing 331 samples from 148 pregnant individuals.

Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest.

Background: Brain injury is a leading cause of morbidity and mortality in patients resuscitated from cardiac arrest. Mitochondrial dysfunction contributes to brain injury following cardiac arrest; therefore, therapies that limit mitochondrial dysfunction have the potential to improve neurological outcomes. Generation of reactive oxygen species (ROS) during ischemia-reperfusion injury in the brain is a critical component of mitochondrial injury and is dependent on hyperactivation of mitochondria following resuscitation.

Enhancing anti-AML activity of venetoclax by isoflavone ME-344 through suppression of OXPHOS and/or purine biosynthesis in vitro.

Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy. Despite high response rates to these therapies, most patients succumb to the disease due to relapse and/or drug resistance, providing an unmet clinical need for novel therapies to improve AML patient survival. ME-344 is a potent isoflavone with demonstrated inhibitory activity toward oxidative phosphorylation (OXPHOS) and clinical activity in solid tumors.

Host-microbiome interactions in distinct subsets of preterm labor and birth.

Preterm birth, the leading cause of perinatal morbidity, often follows premature labor, a syndrome whose prevention remains a challenge. To better understand the relationship between premature labor and host-microbiome interactions, we conducted a mechanistic investigation using three preterm birth models. We report that intra-amniotic delivery of LPS triggers inflammatory responses in the amniotic cavity and cervico-vaginal microenvironment, causing vaginal microbiome changes and signs of active labor.

Transcriptome-wide association analyses reveal the impact of regulatory variants on rice panicle architecture and causal gene regulatory networks.

Panicle architecture is a key determinant of rice grain yield and is mainly determined at the 1-2 mm young panicle stage. Here, we investigated the transcriptome of the 1-2 mm young panicles from 275 rice varieties and identified thousands of genes whose expression levels were associated with panicle traits. Multimodel association studies suggested that many small-effect genetic loci determine spikelet per panicle (SPP) by regulating the expression of genes associated with panicle traits.

Multifunctional Nanocarriers for Alzheimer's Disease: Befriending the Barriers.

Neurodegenerative diseases (NDDs) have been increasing in incidence in recent years and are now widespread worldwide. Neuronal death is defined as the progressive loss of neuronal structure or function which is closely associated with NDDs and represents the intrinsic features of such disorders. Amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's, Parkinson's, and Huntington's diseases (AD, PD, and HD, respectively) are considered neurodegenerative diseases that affect a large number of people worldwide.

Medical students' self-perceived knowledge and clinical comfort with genetics in Pakistan.

Pakistan has a high rate of genetic disorders and neonatal mortality concurrent with noted lack of genetic counselors and geneticists. To meet the needs of the patient population, the responsibility of providing clinical genetic services falls on general and specialty physicians. However, their education regarding these essential services is not standardized in medical school curricula nor has it ever been evaluated.

Blockade of IL-6R prevents preterm birth and adverse neonatal outcomes.

Background: Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment.

Methods: Proteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1α in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth was developed by the ultrasound-guided intra-amniotic injection of IL-1α.

Hyperphosphorylated Tau Inflicts Intracellular Stress Responses that Are Mitigated by Apomorphine.

Abnormal phosphorylation of the microtubule-binding protein tau in the brain is a key pathological marker for Alzheimer's disease and additional neurodegenerative tauopathies. However, how hyperphosphorylated tau causes cellular dysfunction or death that underlies neurodegeneration remains an unsolved question critical for the understanding of disease mechanism and the design of efficacious drugs. Using a recombinant hyperphosphorylated tau protein (p-tau) synthesized by the PIMAX approach, we examined how cells responded to the cytotoxic tau and explored means to enhance cellular resistance to tau attack.

Identifying Human miRNA Target Sites via Learning the Interaction Patterns between miRNA and mRNA Segments.

miRNAs (microRNAs) target specific mRNA (messenger RNA) sites to regulate their translation expression. Although miRNA targeting can rely on seed region base pairing, animal miRNAs, including human miRNAs, typically cooperate with several cofactors, leading to various noncanonical pairing rules. Therefore, identifying the binding sites of animal miRNAs remains challenging.

Racial disparities in cancer genetic counseling encounters: study protocol for investigating patient-genetic counselor communication in the naturalistic clinical setting using a convergent mixed methods design.

Background: Despite decades of effort to reduce racial cancer disparities, Black people continue to die at higher rates from cancer than any other U.S. racial group.

Preeclampsia at term: evidence of disease heterogeneity based on the profile of circulating cytokines and angiogenic factors.

Background: Intravascular inflammation and an antiangiogenic state have been implicated in the pathophysiology of preeclampsia. On the basis of the profiles of their angiogenic/antiangiogenic factors, women with preeclampsia at term may be classified into 2 subgroups with different characteristics and prevalence of adverse outcomes. This study was undertaken to examine whether these 2 subgroups of preeclampsia at term also show differences in their profiles of intravascular inflammation.

A comparative analysis of gene and protein expression in chronic and acute models of photoreceptor degeneration in adult zebrafish.

Adult zebrafish are capable of photoreceptor (PR) regeneration following acute phototoxic lesion (AL). We developed a chronic low light (CLL) exposure model that more accurately reflects chronic PR degeneration observed in many human retinal diseases. Here, we characterize the morphological and transcriptomic changes associated with acute and chronic models of PR degeneration at 8 time-points over a 28-day window using immunohistochemistry and 3'mRNA-seq.

Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder.

Dynamic interactions of neurons and glia in the ventral midbrain mediate reward and addiction behavior. We studied gene expression in 212,713 ventral midbrain single nuclei from 95 individuals with history of opioid misuse, and individuals without drug exposure. Chronic exposure to opioids was not associated with change in proportions of glial and neuronal subtypes, however glial transcriptomes were broadly altered, involving 9.

Integrated of multi-omics and molecular docking reveal PHGDH, PSAT1 and PSPH in the serine synthetic pathway as potential targets of T-2 toxin exposure in pig intestinal tract.

T-2 toxin (T-2) with a molecular weight of 466.52 g/mol is an inevitable mycotoxin in food products and feeds, posing a significant threat to human and animal health. However, the underlying molecular mechanisms of the cytotoxic effects of T-2 exposure on porcine intestinal epithelial cells (IPEC-J2) remain unclear.