An Addendum to the Chemiosmotic Theory of Mitochondrial Activity: The Role of RNA as a Proton Sink.

Mitochondrial ATP synthesis is driven by harnessing the electrochemical gradient of protons (proton motive force) across the mitochondrial inner membrane via the process of chemiosmosis. While there is consensus that the proton gradient is generated by components of the electron transport chain, the mechanism by which protons are supplied to ATP synthase remains controversial. As opposed to a global coupling model whereby protons diffuse into the intermembrane space, a localised coupling model predicts that protons remain closely associated with the lipid membrane prior to interaction with ATP synthase.

Neural differentiation in perspective: mitochondria as early programmers.

Neural differentiation during development of the nervous system has been extensively studied for decades. These efforts have culminated in the generation of a detailed map of developmental events that appear to be associated with emergence of committed cells in the nervous system. In this review the landscape of neural differentiation is revisited by focusing on abiotic signals that play a role in induction of neural differentiation.

Mitochondria facilitate neuronal differentiation by metabolising nuclear-encoded RNA.

Mitochondrial activity directs neuronal differentiation dynamics during brain development. In this context, the long-established metabolic coupling of mitochondria and the eukaryotic host falls short of a satisfactory mechanistic explanation, hinting at an undisclosed facet of mitochondrial function. Here, we reveal an RNA-based inter-organellar communication mode that complements metabolic coupling of host-mitochondria and underpins neuronal differentiation.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine (FAKHRAVAC®) in healthy adults aged 18-55 years: Randomized, double-blind, placebo-controlled, phase I clinical trial.

Background: The FAKHRAVAC®, an inactivated SARS-CoV-2 vaccine, was assessed for safety and immunogenicity.

Methods And Findings: In this double-blind, placebo-controlled, phase I trial, we randomly assigned 135 healthy adults between 18 and 55 to receive vaccine strengths of 5 or 10 μg/dose or placebo (adjuvant only) in 0-14 or 0-21 schedules. This trial was conducted in a single center in a community setting.

Redox-Mediated Rewiring of Signalling Pathways: The Role of a Cellular Clock in Brain Health and Disease.

Metazoan signalling pathways can be rewired to dampen or amplify the rate of events, such as those that occur in development and aging. Given that a linear network topology restricts the capacity to rewire signalling pathways, such scalability of the pace of biological events suggests the existence of programmable non-linear elements in the underlying signalling pathways. Here, we review the network topology of key signalling pathways with a focus on redox-sensitive proteins, including PTEN and Ras GTPase, that reshape the connectivity profile of signalling pathways in response to an altered redox state.

Effect of fluvoxamine on preventing neuropsychiatric symptoms of post COVID syndrome in mild to moderate patients, a randomized placebo-controlled double-blind clinical trial.

Background: Shortly after the Coronavirus disease 2019 (COVID-19) pandemic, a considerable number of recovered patients reported persisting symptoms, especially neuropsychological manifestations, which were later named post-COVID syndrome (PCS). Immune dysregulation was suggested as one of the main mechanisms for PCS. Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) that is mostly used to treat depression, anxiety disorders, and obsessive-compulsive disorder, has been suggested as an anti-COVID drug due to its anti-inflammatory effects, mainly through the sigma-1 receptor.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study.

Background: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity.

Methods: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS).

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study.

Background: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity.

Methods: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS).

Cellular self-organization: An overdrive in Cambrian diversity?

During the early Cambrian period metazoan life forms diverged at an accelerated rate to occupy multiple ecological niches on earth. A variety of explanations have been proposed to address this major evolutionary phenomenon termed the "Cambrian explosion." While most hypotheses address environmental, developmental, and ecological factors that facilitated evolutionary innovations, the biological basis for accelerated emergence of species diversity in the Cambrian period remains largely conjectural.

Evaluation of the efficacy of oral nano-silymarin formulation in hospitalized patients with COVID-19: A double-blind placebo-controlled clinical trial.

Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID-19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID-19. The participants were assigned to the nano-silymarin (n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups (n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow-up period (one week and one month after the beginning of the treatment).

Thalamic hemi-chorea: a rare complication after receiving the adenoviral vector-based COVID-19 vaccine: a case report.

Lacunar strokes occur when a branch of a large cerebral artery is blocked. The thalamus is often affected, causing uncontrollable motions. A 72-year-old previously healthy man presented with involuntary motions in the right limbs, which were present at rest, and exacerbated during voluntary actions.

Notch ankyrin domain: evolutionary rise of a thermodynamic sensor.

Notch signalling pathway plays a key role in metazoan biology by contributing to resolution of binary decisions in the life cycle of cells during development. Outcomes such as proliferation/differentiation dichotomy are resolved by transcriptional remodelling that follows a switch from Notch to Notch state, characterised by dissociation of Notch intracellular domain (NICD) from DNA-bound RBPJ. Here we provide evidence that transitioning to the Notch state is regulated by heat flux, a phenomenon that aligns resolution of fate dichotomies to mitochondrial activity.

Neural pericytes: A genomic archival state programmed by CHromatin topology.

Accumulating evidence suggests that mural pericytes, apart from stabilizing the associated microvessels, play additional roles in regeneration of local cellular elements. Herein, the mechanistic basis for such diverse and at times contradictory roles adopted by pericytes in the brain is reviewed. Core concepts of an emerging model are discussed wherein mural pericytes reside in a metastable "archival state" that conceals a neural progenitor identity.

The effect of IGF-1 plasma concentration on COVID-19 severity.

Background: The severity and fatality of Coronavirus disease 2019 (COVID-19) infection are not the same in the infected population. The host immune response and Immune-stimulating factors appear to play a role in COVID-19 infection outcome. insulin-like growth factor-1 (IGF-1) affects the immune system by controlling the endocrine system.

Programmed genomic instability regulates neural transdifferentiation of human brain microvascular pericytes.

Background: Transdifferentiation describes transformation in vivo of specialized cells from one lineage into another. While there is extensive literature on forced induction of lineage reprogramming in vitro, endogenous mechanisms that govern transdifferentiation remain largely unknown. The observation that human microvascular pericytes transdifferentiate into neurons provided an opportunity to explore the endogenous molecular basis for lineage reprogramming.

Frequency of HLA Alleles in a Group of Severe COVID-19 Iranian Patients.

Background: Human Leukocyte Antigen (HLA) system composed of a group of related proteins with important functions in the immune system. Several studies have reported that there is a significant association between specific HLA alleles and the susceptibility to different infectious diseases. This study aimed to detect the specific HLA alleles that cause higher susceptibility to COVID-19, we analyzed the HLA allele frequency distribution in Iranian patients with a severe form of COVID-19.

Use of Azelastine and Sodium Chloride Spray for Prevention of Sinusitis in ICU Admitted Patients: A Randomized Clinical Trial.

Background: Nosocomial sinusitis is a common and less attended complication in patients admitted to intensive care units (ICU). It can cause several problems, such as prolongation of hospitalization, comorbidity, and mortality in patients. The present study aimed to evaluate the effect of azelastine (second-generation antihistamine) and sodium chloride spray on sinusitis prevention in ICU admitted patients.

The fate of notch-1 transcript is linked to cell cycle dynamics by activity of a natural antisense transcript.

A core imprint of metazoan life is that perturbations of cell cycle are offset by compensatory changes in successive cellular generations. This trait enhances robustness of multicellular growth and requires transmission of signaling cues within a cell lineage. Notably, the identity and mode of activity of transgenerational signals remain largely unknown.

Cannibalized erythroblasts accelerate developmental neurogenesis by regulating mitochondrial dynamics.

Metabolic support was long considered to be the only developmental function of hematopoiesis, a view that is gradually changing. Here, we disclose a mechanism triggered during neurulation that programs brain development by donation of sacrificial yolk sac erythroblasts to neuroepithelial cells. At embryonic day (E) 8.

Acute transverse myelitis after SARS-CoV-2 infection: a rare complicated case of rapid onset paraplegia.

A 63-year-old Caucasian male, known case of controlled type 2 diabetes, chronic renal failure, and ischemic heart disease, was presented with weakness and loss of movement in lower limbs, an absent sensation from the chest below, constipation, and urinary retention. About 4 days before these symptoms, he experienced a flu-like syndrome. Suspicious for COVID-19, his nasopharyngeal specimen's reverse transcription-polymerase chain reaction (RT-PCR) resulted positive.

Evaluating the Prevalence of PTSD among Children and Adolescents after Earthquakes and Floods: a Systematic Review and Meta-Analysis.

Our study systematically reviews articles about the prevalence of Post-traumatic Stress Disorder (PTSD) among children and adolescents, aiming to evaluate its prevalence after earthquakes and floods.Three databases (PubMed, Scopus, and Web of Science) were searched for articles published from 1981 to 2019 containing information on PTSD prevalence among survivors of earthquakes and floods. Articles with insufficient data on the prevalence of PTSD or without any available full-text were excluded.

Genomic competition for noise reduction shaped evolutionary landscape of mir-4673.

The genomic platform that informs evolution of microRNA cascades remains unknown. Here we capitalised on the recent evolutionary trajectory of hominin-specific miRNA-4673, encoded in intron 4 of notch-1, to uncover the identity of one such precursor genomic element and the selective forces acting upon it. The miRNA targets genes that regulate Wnt/β-catenin signalling cascade.

Coupled cycling and regulation of metazoan morphogenesis.

Metazoan animals are characterized by restricted phenotypic heterogeneity (i.e. morphological disparity) of organisms within various species, a feature that contrasts sharply with intra-species morphological diversity observed in the plant kingdom.

β-Catenin: A Metazoan Filter for Biological Noise?

Molecular noise refers to fluctuations of biological signals that facilitate phenotypic heterogeneity in a population. While endogenous mechanisms exist to limit genetic noise in biological systems, such restrictions are sometimes removed to propel phenotypic variability as an adaptive strategy. Herein, we review evidence for the potential role of β-catenin in restricting gene expression noise by transcriptional and post-transcriptional mechanisms.