Prevention of dsRNA-induced interferon signaling by AGO1x is linked to breast cancer cell proliferation.

Translational readthrough, i.e., elongation of polypeptide chains beyond the stop codon, was initially reported for viral RNA, but later found also on eukaryotic transcripts, resulting in proteome diversification and protein-level modulation. Here, we report that AGO1x, an evolutionarily conserved translational readthrough isoform of Argonaute 1, is generated in highly proliferative breast cancer cells, where it curbs accumulation of double-stranded RNAs (dsRNAs) and consequent induction of interferon responses and apoptosis. In contrast to other mammalian Argonaute protein family members with primarily cytoplasmic functions, AGO1x exhibits nuclear localization in the vicinity of nucleoli. We identify AGO1x interaction with the polyribonucleotide nucleotidyltransferase 1 (PNPT1) and show that the depletion of this protein further augments dsRNA accumulation. Our study thus uncovers a novel function of an Argonaute protein in buffering the endogenous dsRNA-induced interferon responses, different than the canonical function of AGO proteins in the miRNA effector pathway. As AGO1x expression is tightly linked to breast cancer cell proliferation, our study thus suggests a new direction for limiting tumor growth.

Asymmetric distribution of glucose transporter mRNA provides a growth advantage in yeast.

Asymmetric localization of mRNA is important for cell fate decisions in eukaryotes and provides the means for localized protein synthesis in a variety of cell types. Here, we show that hexose transporter mRNAs are retained in the mother cell of S. cerevisiae until metaphase-anaphase transition (MAT) and then are released into the bud. The retained mRNA was translationally less active but bound to ribosomes before MAT Importantly, when cells were shifted from starvation to glucose-rich conditions, HXT2 mRNA, but none of the other HXT mRNAs, was enriched in the bud after MAT This enrichment was dependent on the Ras/cAMP/PKA pathway, the APC ortholog Kar9, and nuclear segregation into the bud. Competition experiments between strains that only expressed one hexose transporter at a time revealed that HXT2 only cells grow faster than their counterparts when released from starvation. Therefore, asymmetric distribution of HXT2 mRNA provides a growth advantage for daughters, who are better prepared for nutritional changes in the environment. Our data provide evidence that asymmetric mRNA localization is an important factor in determining cellular fitness.

Protein synthesis rates and ribosome occupancies reveal determinants of translation elongation rates.

Although protein synthesis dynamics has been studied both with theoretical models and by profiling ribosome footprints, the determinants of ribosome flux along open reading frames (ORFs) are not fully understood. Combining measurements of protein synthesis rate with ribosome footprinting data, we here inferred translation initiation and elongation rates for over a 1,000 ORFs in exponentially growing wild-type yeast cells. We found that the amino acid composition of synthesized proteins is as important a determinant of translation elongation rate as parameters related to codon and transfer RNA (tRNA) adaptation. We did not find evidence of ribosome collisions curbing the protein output of yeast transcripts, either in high translation conditions associated with exponential growth, or in strains in which deletion of individual ribosomal protein (RP) genes leads to globally increased or decreased translation. Slow translation elongation is characteristic of RP-encoding transcripts, which have markedly lower protein output compared with other transcripts with equally high ribosome densities.

Local translation of yeast ERG4 mRNA at the endoplasmic reticulum requires the brefeldin A resistance protein Bfr1.

Brefeldin A resistance factor 1 (Bfr1p) is a nonessential RNA-binding protein and multicopy suppressor of brefeldin A sensitivity in Saccharomyces cerevisiae Deletion of BFR1 leads to multiple defects, including altered cell shape and size, change in ploidy, induction of P-bodies and chromosomal missegregation. Bfr1p has been shown to associate with polysomes, binds to several hundred mRNAs, and can target some of them to P-bodies. Although this implies a role of Bfr1p in translational control of mRNAs, its molecular function remains elusive. In the present study, we show that mutations in RNA-binding residues of Bfr1p impede its RNA-dependent colocalization with ER, yet do not mimic the known cellular defects seen upon BFR1 deletion. However, a Bfr1 RNA-binding mutant is impaired in binding to ERG4 mRNA, which encodes an enzyme required for the final step of ergosterol biosynthesis. Consistently, bfr1Δ strains show a strong reduction in Erg4p protein levels, most likely because of degradation of misfolded Erg4p. Polysome profiling of bfr1Δ or bfr1 mutant strains reveals a strong shift of ERG4 mRNA to polysomes, consistent with a function of Bfr1p in elongation or increased ribosome loading. Collectively, our data reveal that Bfr1 has at least two separable functions: one in RNA binding and cotranslational protein translocation into the ER and one in ploidy control or chromosome segregation.

Rodent ultrasonic vocalizations as biomarkers of future alcohol use: A predictive analytic approach.

Excessive alcohol consumption has a vast, negative impact on society. Rodent models have been successful in furthering our understanding of the biological underpinnings that drive alcohol consumption. Rodents emit ultrasonic vocalizations (USVs) that are each composed of several acoustic characteristics (e.g., frequency, duration, bandwidth, power). USVs reflect neurotransmitter activity in the ascending limb of the mesolimbic dopaminergic and cholinergic neurotransmitter systems and serve as noninvasive, real-time biomarkers of dopaminergic and cholinergic neurotransmission in the limbic system. In the present study, we recorded spontaneously emitted USVs from alcohol-naïve Long-Evans (LE) rats and then measured their alcohol intake. We compared the USV acoustic characteristics and alcohol consumption data from these LE rats with previously published data from selectively bred high-alcohol (P and HAD-1) and low-alcohol (NP and LAD-1) drinking lines from studies with the same experimental method. Predictive analytic techniques were applied simultaneously to this combined data set and revealed that (a) USVs emitted by alcohol-naïve rats accurately discriminated among high-alcohol consuming, LE, and low-alcohol consuming rat lines, and (b) future alcohol consumption in these same rat lines was reliably predicted from the USV data collected in an alcohol-naïve state. To our knowledge, this is the first study to show that alcohol consumption is predicted directly from USV profiles of alcohol-naïve rats. Because USV acoustic characteristics are sensitive to underlying neural activity, these findings suggest that baseline differences in mesolimbic cholinergic and dopaminergic tone could determine the propensity for future alcohol consumption in rodents.

Understanding the unique sorption of alkane-α, ω-diols in silicalite-1.

Adsorption equilibria of alkane-α, ω-diols (propane-1,3-diol, butane-1,4-diol, pentane-1,5-diol, and hexane-1,6-diol) from aqueous solution onto an all-silica zeolite of the type mordenite framework inverted (MFI, also known as silicalite-1) are obtained by simulations and experiments at T = 323 K and also for pentane-1,5-diol (C5) at 348 and 383 K. After an initial slow rise, isotherms at T = 323 K exhibit steep changes in loading, reaching saturation at 10, 9, 8, and 7 molec/uc as the number of carbon atoms of the diols increases from 3 to 6. The abrupt change in loading corresponds to a minimum in the free energy of adsorption (from vapor to zeolite) that is associated with a rapid rise in the number of hydrogen bonds per sorbate molecule due to the formation of large clusters. For C5 at low loading, the centers-of-mass primarily occupy the channel intersections with oxygens oriented along the straight channels where intermolecular hydrogen bonds are formed. At saturation loading, the C5 centers-of-mass instead occupy the straight and zig-zag channels, and nearly all C5 molecules are involved in a percolating hydrogen-bonding network (this also occurs for C6). With increasing temperature, the C5 isotherm decreases in steepness as the minimum in free energy of adsorption decreases in depth and a less-ordered structure of the adsorbed molecules results in a lower number of diol-diol hydrogen bonds. However, the C5 isotherm does not shift significantly in concentration of the adsorption onset, as the free energies of solvation and adsorption increase by similar and compensating amounts. At T = 323 and 348 K, the steep change for the C5 adsorption isotherm is found to be a phase transition (as indicated by a bimodal distribution of unit cell occupancies at intermediate loading) from a less-dense phase with only small hydrogen-bonded clusters to an ordered solid phase with loadings of 8 molec/uc. At T = 383 K, the sorbates are less ordered, the distribution of occupancies becomes unimodal at intermediate loading, and the loading rises more gradually with concentration. Several different enhanced sampling methods are utilized for these simulations.

miR-CLIP capture of a miRNA targetome uncovers a lincRNA H19-miR-106a interaction.

Identifying the interaction partners of noncoding RNAs is essential for elucidating their functions. We have developed an approach, termed microRNA crosslinking and immunoprecipitation (miR-CLIP), using pre-miRNAs modified with psoralen and biotin to capture their targets in cells. Photo-crosslinking and Argonaute 2 immunopurification followed by streptavidin affinity purification of probe-linked RNAs provided selectivity in the capture of targets, which were identified by deep sequencing. miR-CLIP with pre-miR-106a, a miR-17-5p family member, identified hundreds of putative targets in HeLa cells, many carrying conserved sequences complementary to the miRNA seed but also many that were not predicted computationally. miR-106a overexpression experiments confirmed that miR-CLIP captured functional targets, including H19, a long noncoding RNA that is expressed during skeletal muscle cell differentiation. We showed that miR-17-5p family members bind H19 in HeLa cells and myoblasts. During myoblast differentiation, levels of H19, miR-17-5p family members and mRNA targets changed in a manner suggesting that H19 acts as a 'sponge' for these miRNAs.

Safety and Efficacy of Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy of Littoral Cell Angioma.

Littoral cell angioma (LCA) is a rare vascular tumor of the spleen that often requires histopathological analysis for diagnosis due to non-specific imaging features. The current approach is either splenectomy or image-guided percutaneous biopsy which carries notable procedure-associated morbidity and limited accuracy. We present a novel case of LCA successfully diagnosed with endoscopic ultrasound fine-needle aspiration biopsy (EUS-FNAB), demonstrating its potential to reduce the morbidity associated with traditional percutaneous biopsy methods. This case highlights EUS-FNAB's advantage in minimizing complications and its effectiveness in diagnosing vascular tumors of the spleen, supporting its inclusion in the diagnostic algorithm for splenic lesions. Further cases are encouraged to explore EUS-FNAB's role in diagnosing rare vascular tumors such as LCA to establish its efficacy and safety profile.

Deciphering the Association of Epstein-Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice.

The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146-157 (gM146-157) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM146-157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM146-157 peptide to the neuropathologies.

The Impact of Intraoperative Glucagon on the Diagnostic Accuracy of Intraoperative Cholangiogram for the Diagnosis of Choledocholithiasis: Experience from a Large Tertiary Care Center.

A proportion of patients who undergo intraoperative cholangiogram (IOC) do not have bile duct stones at the time of endoscopic retrograde cholangiopancreatography (ERCP), either due to the spontaneous passage of stones or a false-positive IOC. Glucagon has been utilized as an inexpensive tool to allow the passage of micro-choledocholithiasis to the duodenum and resolve filling defects caused by stones or air bubbles. The purpose of our study is to understand the change in diagnostic accuracy of IOC to detect choledocholithiasis with intraoperative glucagon. We conducted a retrospective study at a tertiary care center on adult patients who underwent laparoscopic cholecystectomy with IOC. The diagnostic accuracy of IOC was assessed before and after the administration of intravenous glucagon. Of 1455 patients, 374 (25.7%) received intraoperative glucagon, and 103 of these 374 patients (27.5%) showed resolution of the filling defect with the passage of contrast to the duodenum. Pre- and post-glucagon administration comparison showed enhancement in specificity from 78% to 83%, an increase in positive predictive value from 67.3% to 72.4%, and an improvement in the diagnostic accuracy of IOC from 81.5% to 84.3%. Our findings suggest that intraoperative glucagon administration carries the potential to reduce the rate of false-positive IOCs, thereby reducing the performance of unnecessary ERCPs.

Cardiac Muscle Injury and Echocardiographic Plus Electrocardiographic Findings in Patients With 2019 Novel Coronavirus (COVID-19): A Retrospective Cohort Study.

Background: Myocardial injury has been described in coronavirus-2019 (COVID-19). Few studies have reported cardiovascular imaging data with transthoracic echocardiography (TTE) and electrocardiography (ECG) findings in COVID-19 patients, and their correlation with mortality. Methods: We conducted a retrospective cohort study that included COVID-19 patients from March 2020 through February 2021 who had TTE and ECG during hospital admission. Myocardial injury was defined by an elevated high-sensitivity troponin T level > 20 ng/L. Bivariate analysis was used to compare patients with myocardial injury and those without. Multivariate logistic regression analysis was performed to identify the variables associated with mortality. Results: A total of 438 patients were included. The mean age was 62.1 ± 14.9 years, and 58.9% were male. A total of 149 patients died, with a mortality rate of 34%. A total of 260 patients (59.4%) had myocardial injury. The average left ventricular ejection fraction was 59.8% ± 11.2%, with 30 patients (6.8%) having an ejection fraction of < 40%. Patients with myocardial injury had higher mortality than those without (P < 0.05, χ2 test). A multiple regression analysis model indicated that age, race and/or ethnicity, the development of acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the variables significantly associated with mortality. Conclusion: COVID-19 patients with myocardial injury had higher mortality than those without. Age, race and/or ethnicity, acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the clinical variables associated with mortality. The TEE and ECG variables studied were not significantly associated with mortality.

Contexte: Des atteintes myocardiques ont été décrites en présence d'une infection par le coronavirus 2019 (COVID-19). Quelques études ont rapporté des données d'imagerie cardiovasculaire obtenues par échocardiographie transthoracique (ETT) et électrocardiographie (ECG) chez des patients atteints de la COVID-19, et leur corrélation avec la mortalité. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant des patients atteints de la COVID-19 entre mars 2020 et février 2021 qui ont été soumis à une ETT ou à une ECG pendant leur hospitalisation. L'atteinte myocardique était définie comme un taux élevé de troponine T de haute sensibilité > 20 ng/L. Une analyse à deux variables a été utilisée pour comparer les patients présentant une atteinte myocardique et ceux qui n'en présentaient pas. Une analyse de régression logistique à multiples variables a été menée pour définir les variables qui étaient associées à la mortalité. Résultats: L'étude comptait un total de 438 patients. L'âge moyen était de 62,1 ± 14,9 ans; 58,9 % étaient des hommes. Un total de 149 patients sont décédés, soit un taux de mortalité de 34 %. Un total de 260 patients (59,4 %) présentaient une atteinte myocardique. La fraction d'éjection ventriculaire gauche moyenne était de 59,8 % ± 11,2 %, alors que 30 patients (6,8 %) affichaient une fraction d'éjection inférieure à 40 %. Le taux de mortalité était plus élevé chez les patients qui présentaient une atteinte myocardique que chez ceux qui n'en présentaient pas (p < 0,05, test χ2). Selon un modèle d'analyse de régression multiple, l'âge, la race et/ou l'ethnicité, l'apparition du syndrome de détresse respiratoire aiguë, l'état de choc, le besoin de vasopresseurs, la ventilation artificielle et l'hémodialyse étaient les variables fortement liées à la mortalité. Conclusion: Parmi les patients atteints de la COVID-19, la mortalité était plus élevée chez ceux qui présentaient une atteinte myocardique que chez ceux qui n'en présentaient pas. L'âge, la race et/ou l'ethnicité, le syndrome de détresse respiratoire aiguë, l'état de choc, le besoin de vasopresseurs, la ventilation artificielle et l'hémodialyse étaient les variables cliniques liées à la mortalité. Les variables d'ETT et d'ECG étudiées n'avaient pas de lien important avec la mortalité.

Refractory cardiogenic shock caused by zinc phosphide toxicity.

Zinc phosphide toxicity is a rare entity that presents most frequently among farmers in developing countries who use it as a rodenticide. The phosphine gas released after the ingestion inhibits cytochrome c oxidase, disrupting the mitochondrial physiology and oxidative phosphorylation and causing myocardial stunning. Here we present a case of a 20-year-old man who attempted suicide with zinc phosphide toxicity. Initially, he was hemodynamically stable with a normal ejection fraction; however, in a few hours, he deteriorated quickly and became hemodynamically unstable, with rapid deterioration of his ejection fraction to 20%. He was started on norepinephrine and then dobutamine; however, he had cardiac arrest from refractory cardiogenic shock despite resuscitative measures.

Dissecting the expression dynamics of RNA-binding proteins in posttranscriptional regulatory networks.

In eukaryotic organisms, gene expression requires an additional level of coordination that links transcriptional and posttranslational processes. Messenger RNAs have traditionally been viewed as passive molecules in the pathway from transcription to translation. However, it is now clear that RNA-binding proteins (RBPs) play an important role in cellular homeostasis by controlling gene expression at the posttranscriptional level. Here, we show that RBPs, as a class of proteins, show distinct gene expression dynamics compared to other protein coding genes in the eukaryote Sacchoromyces cerevisiae. We find that RBPs generally exhibit high protein stability, translational efficiency, and protein abundance but their encoding transcripts tend to have a low half-life. We show that RBPs are also most often posttranslationally modified, indicating their potential for regulation at the protein level to control diverse cellular processes. Further analysis of the RBP-RNA interaction network showed that the number of distinct targets bound by an RBP (connectivity) is strongly correlated with its protein stability, translational efficiency, and abundance. We also note that RBPs show less noise in their expression in a population of cells, with highly connected RBPs showing significantly lower noise. Our results indicate that highly connected RBPs are likely to be tightly regulated at the protein level as significant changes in their expression may bring about large-scale changes in global expression levels by affecting their targets. These observations might explain the molecular basis behind the cause of a number of disorders associated with misexpression or mutation in RBPs. Future studies uncovering the posttranscriptional networks in higher eukaryotes can help our understanding of the link between different levels of regulation and their role in pathological conditions.

Cardiovascular complications of catastrophic antiphospholipid syndrome: a case report and review of literature.

Background: Antiphospholipid syndrome (APS) is an autoimmune response characterized clinically by arterial or venous thrombosis. One of the rare and series forms of APS is the catastrophic APS (CAPS). The incidence of CAPS has been reported in 0.8% of patients with APS. There have been very few case reports with cardiac involvement in CAPS. Common cardiac manifestations include valvular thickening and lesions, coronary artery disease, and myocardial infarction due to microvascular thrombosis. Here, we are reporting a case of CAPS associated with heart failure and a literature review of similar cases. Case summary: A 24-year-old woman with a history of APS presented with shortness of breath and right-sided pleuritic chest pain. Computed tomography pulmonary angiogram revealed new pulmonary emboli in the right lung. After 5 days, she developed high-grade fever with negative infectious workup, acute hypoxic respiratory failure with pulmonary oedema, shock, acute kidney injury, and transthoracic echocardiography showed reduced ejection fraction and global hypokinesia. The constellation of multi-organ failure, symptoms within a week, the presence of antiphospholipid antibodies, and exclusion of other causes, CAPS was diagnosed. The patient showed significant improvement with pulse steroids, IV plasmapheresis and got discharged on oral prednisone taper and anticoagulation with home health. Conclusion: There are different cardiac complications associated with CAPS, including congestive heart failure, acute coronary syndrome, valvular lesions, and thrombus. Heart failure management in CAPS includes triple therapy of intravenous immune globulin, IV plasmapheresis, and corticosteroids rather than conventional treatment.

COVID-19 causing rhabdomyolysis requiring hemodialysis in a young adult.

Cases of rhabdomyolysis causing myoglobinuria in post-COVID-19 patients have been seen, and exact mechanisms behind it seem multifactorial. Some patients have severe myoglobinuria with highly elevated creatinine phosphokinase levels requiring urgent hemodialysis to keep creatinine and blood urea nitrogen levels under control and protect the kidneys from long-term damage. Here, we present a case of a 34-year-old man with a history notable for autism and hypertension who was admitted to the hospital for COVID-19 viral pneumonia and discharged without major complications. After 3 weeks, he came to the emergency room with decreased mental status and asterixis. He had red-colored urine and acute kidney injury secondary to rhabdomyolysis. His creatinine phosphokinase was 289,500 mcg/L-a level never reported before. The patient did not respond to aggressive intravenous fluids, so he was started on hemodialysis. After 1 week, he showed clinical improvement, and he was taken off dialysis in 2 weeks.

Dermatomal rash after Shingrix vaccination: cause or coincidence?

Dermatological reactions have been reported following Shingrix vaccine administration in previous published cases, but dermatomal rash after Shingrix vaccination has not been reported in the United States. This case describes a 73-year-old immunocompetent woman with a dermatomal rash after Shingrix recombinant vaccine administration. This case highlights the rare possibility of an acute reaction after Shingrix vaccine administration, which should be recognized. Nonetheless, the vaccine has been shown to be very effective at preventing varicella zoster virus reactivation and postherpetic neuralgia, so the benefit of receiving the vaccination significantly outweighs the risk.

Unraveling the links between neurodegeneration and Epstein-Barr virus-mediated cell cycle dysregulation.

The Epstein-Barr virus is a well-known cell cycle modulator. To establish successful infection in the host, EBV alters the cell cycle at multiple steps via antigens such as EBNAs, LMPs, and certain other EBV-encoded transcripts. Interestingly, several recent studies have indicated the possibility of EBV's neurotrophic potential. However, the effects and outcomes of EBV infection in the CNS are under-explored. Additionally, more and more epidemiological evidence implicates the cell-cycle dysregulation in neurodegeneration. Numerous hypotheses which describe the triggers that force post-mitotic neurons to re-enter the cell cycle are prevalent. Apart from the known genetic and epigenetic factors responsible, several reports have shown the association of microbial infections with neurodegenerative pathology. Although, studies implicating the herpesvirus family members in neurodegeneration exist, the involvement of Epstein-Barr virus (EBV), in particular, is under-evaluated. Interestingly, a few clinical studies have reported patients of AD or PD to be seropositive for EBV. Based on the findings mentioned above, in this review, we propose that EBV infection in neurons could drive it towards neurodegeneration through dysregulation of cell-cycle events and induction of apoptosis.

A Novel Technique Debulking Vegetations in Tricuspid Endocarditis and Venacava Utilizing AngioVac Aspiration System.

The AngioVac system (AngioDynamics Inc., Latham, NY) is used for the removal of commonly encountered intravascular material, such as thrombus or vegetations in the right atrium, right ventricle, superior vena cava, and inferior vena cava. Patients with high surgical risk having tricuspid endocarditis and superior vena cava thrombus can be treated with the AngioVac system, hence mitigating the risks for this patient population. We present a case series with the utilization of the AngioVac device to reduce the vegetation size and decrease the risk of emboli with effective antibiotic penetration. Transesophageal echocardiography shows a reduction in the size of the vegetations in all three cases with no postoperative complications. This case series demonstrates a novel technique debulking vegetations in tricuspid endocarditis and vena cava.

PGC-1ß modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds.

OBJECTIVE: Skeletal muscle is a pivotal organ for the coordination of systemic metabolism, constituting one of the largest storage site for glucose, lipids and amino acids. Tight temporal orchestration of protein breakdown in times of fasting has to be balanced with preservation of muscle mass and function. However, the molecular mechanisms that control the fasting response in muscle are poorly understood. METHODS: We now have identified a role for the peroxisome proliferator-activated receptor γ coactivator 1ß (PGC-1ß) in the regulation of catabolic pathways in this context in muscle-specific loss-of-function mouse models. RESULTS: Muscle-specific knockouts for PGC-1ß experience mitigated muscle atrophy in fasting, linked to reduced expression of myostatin, atrogenes, activation of AMP-dependent protein kinase (AMPK) and other energy deprivation signaling pathways. At least in part, the muscle fasting response is modulated by a negative effect of PGC-1ß on the nuclear factor of activated T-cells 1 (NFATC1). CONCLUSIONS: Collectively, these data highlight the complex regulation of muscle metabolism and reveal a new role for muscle PGC-1ß in the control of proteostasis in fasting.

Covaxin-Induced Lymphocytic Myocarditis.

We report the case of a young adult male with endomyocardial biopsy-proven lymphocytic myocarditis following Covaxin administration. Covaxin differs from the mRNA vaccines in that it is an inactivated virus developed using the whole virion inactivated using the Vero cell platform. We successfully managed the patient with complete resolution of symptoms.