hnRNP Q and PTB modulate the circadian oscillation of mouse Rev-erb α via IRES-mediated translation

The physiological and behavioral circadian rhythms of most creatures are controlled by a harmony of functional relationships between clock genes. In mammals, several core clock genes show rhythmic profiles of their mRNA and protein expression. Among them, Rev-erb α functions as a transcriptional repressor, affecting expression patterns of other clock genes. For the continuous and robust oscillation of the molecular clock system, the levels of Rev-erb α protein are expected to be tightly regulated with the correct timing. Here, we demonstrate that Rev-erb α has an internal ribosomal entry site (IRES) in its 5′ untranslated region. Furthermore, we demonstrate that heterogeneous nuclear ribonucleoprotein Q and polypyrimidine tract-binding protein (PTB) modulate the IRES-mediated translation of Rev-erb α. We suggest that the rhythmic binding affinity of hnRNP Q to the Rev-erb α IRES and the change in PTB cytosolic levels lead to maintenance of the oscillation profile of the Rev-erb α protein

Cross-talk between circadian clocks, sleep-wake cycles, and metabolic networks: Dispelling the darkness.

Integration of knowledge concerning circadian rhythms, metabolic networks, and sleep-wake cycles is imperative for unraveling the mysteries of biological cycles and their underlying mechanisms. During the last decade, enormous progress in circadian biology research has provided a plethora of new insights into the molecular architecture of circadian clocks. However, the recent identification of autonomous redox oscillations in cells has expanded our view of the clockwork beyond conventional transcription/translation feedback loop models, which have been dominant since the first circadian period mutants were identified in fruit fly. Consequently, non-transcriptional timekeeping mechanisms have been proposed, and the antioxidant peroxiredoxin proteins have been identified as conserved markers for 24-hour rhythms. Here, we review recent advances in our understanding of interdependencies amongst circadian rhythms, sleep homeostasis, redox cycles, and other cellular metabolic networks. We speculate that systems-level investigations implementing integrated multi-omics approaches could provide novel mechanistic insights into the connectivity between daily cycles and metabolic systems.ABR is a Wellcome Trust Senior Clinical Fellow and receives funding from the Wellcome Trust (Grant No. 100333/Z/12/Z), the European Research Council (ERC Starting Grant No. 281348, MetaCLOCK), the European Molecular Biology Organization (EMBO) Young Investigators Programme, and the Lister Institute of Preventative Medicine. SR is supported by the Wellcome Trust.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/bies.20150005

Circadian influences on myocardial infarction

Components of circadian rhythm maintenance, or “clock genes,� are endogenous entrainable oscillations of about 24 h that regulate biological processes and are found in the suprachaismatic nucleus (SCN) and many peripheral tissues, including the heart. They are influenced by external cues, or Zeitgebers, such as light and heat, and can influence such diverse phenomena as cytokine expression immune cells, metabolic activity of cardiac myocytes, and vasodilator regulation by vascular endothelial cells. While it is known that the central master clock in the SCN synchronizes peripheral physiologic rhythms, the mechanisms by which the information is transmitted are complex and may include hormonal, metabolic, and neuronal inputs. Whether circadian patterns are causally related to the observed periodicity of events, or whether they are simply epi-phenomena is not well established, but a few studies suggest that the circadian effects likely are real in their impact on myocardial infarct incidence. Cycle disturbances may be harbingers of predisposition and subsequent response to acute and chronic cardiac injury, and identifying the complex interactions of circadian rhythms and myocardial infarction may provide insights into possible preventative and therapeutic strategies for susceptible populations.ECU Open Access Publishing Support Fun

Diurnal rhythmic expression of the rhythm-related genes, rPeriod1, rPeriod2, and rClock , in the rat brain

High densities of the mRNA of three rhythm-related genes, rPeriod1 (rPer1), rPer2 , and rClock , which share high homology in Drosophila and mammals, are found in the rat hypothalamic suprachiasmatic nucleus (SCN). The SCN, however, is not the only brain region that expresses these genes. To understand the possible physiological roles of these rhythm-related genes, we examined expression of these genes in different brain regions at various time points in male Sprague--Dawley rats. Using semi quantitative in situ hybridization with 35 S-riboprobes to evaluate mRNA levels, the diurnal rhythmicity of rPer1, and rPer2 mRNA levels was found in the SCN, arcuate nucleus, and median eminence/pars tuberalis. Expression patterns of mRNA for rPer1 and rPer2 , however, were not similar in these brain regions. The rhythmicity in these brain regions was specific, because it was not observed in the cerebellum or hippocampus. Moreover, diurnal changes in rClock mRNA expression were not detected in any of the brain regions examined. These findings suggest that the different expression patterns observed for rPer1, rPer2 , and rClock mRNAs may be attributed to their different physiological roles in these brain regions, and support previous work indicating that circadian rhythms in the brain are widespread.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43939/1/11373_2004_Article_8176.pd

REal-world treatment outcomes after delayed intRavitreal therapy in center-involving diabetic macular edema – RETORT study

Abstract Purpose To compare real-life data on delayed intravitreal treatment of diabetic macular edema (DME) patients to early treatment. Methods In this single-centre, retrospective, interventional, comparative study, DME patients were divided into two groups based on when they received treatment: Group 1 - received treatment within 24 weeks and Group 2 - at or after 24 weeks from the time of treatment advice. Visual acuity and central subfield thickness (CSFT) changes were compared at various time points. Reasons for delaying treatment were noted. Results The study included 109 (Group 1–94; Group 2–15) eyes. When treatment was advised, demographic profile, diabetes duration, glucose control and VA between two groups were comparable. At this point, CSFT was higher in Group 1 than in Group 2 (p = 0.036). At injection time, Group 2 had better VA and lower CSFT than Group 1 (p < 0.05). Group 2’s VA (53.4 ± 12.67) was significantly lower than Group 1’s (57.38 ± 20.01) after 1-year treatment. At 1-year, CSFT decreased in Group 1 and increased in Group 2. Group 1 had mean improvement of + 7.6 letters and Group 2 had a decline of -6.9 letters. Group 2 required more intravitreal anti-VEGF (median – 3; IQR: 2–4), steroid injections (median – 4; IQR: 2–4) and focal laser sessions (median – 4; IQR: 2–4). Conclusion Late-treated DME eyes needed more injections and focal laser sessions than early treated eyes. Adherence to early treatment of DME in real-life will help prevent long-term vision loss

Ocular manifestations following COVID-19 vaccination

Abstract Background Immunologic and inflammatory adverse effects following vaccination against COVID-19 are being reported. While some reactions may develop denovo others concern its immunogenic effect in patients with pre-existing inflammatory conditions. Methods Retrospective consecutive patients diagnosed with ocular inflammatory manifestations within 8 weeks of receiving COVID-19 vaccination who presented to a tertiary eye care centre in South India. Results Ninety-eight eyes of 67 patients presenting with ocular inflammatory manifestations within 8 weeks following COVID-19 vaccination were studied. The mean age was 43 years (+/- 14.82; range 19–80 years). The most common presentations were anterior uveitis (n = 31, 31.7%), followed by panuveitis (n = 24, 24.5%). The mean time to onset of symptoms was 25 days (+/- 15.48; range 2–55 days) following a dose of vaccine. Among all patients, 39 (58.2%) had a previous history of ocular inflammation. Mean presenting visual acuity was 0.4 (0-4) logMAR units and mean final visual acuity was 0.2 (0-4) logMAR units. The causes for reduced vision included of cystoid macular edema (n=2, 2%), chorioretinal atrophy (n=2.2%), optic atrophy (n=1.1%), retinal vascular occlusion (n=1.1%) and acute retinal necrosis (n=1.1%). Conclusion Infective and immunogenic adverse events should be watched out for after COVID-19 vaccination. It is difficult to establish causality for such manifestations, nevertheless, most of them were mild and had good final visual outcomes

Comparative Study of Aragvadha Phalamajja (Cassia fistula Linn.) w.s.r. to its Sangrahana Vidhi

Ayurved advocates that drug should be collected with proper classical methods. In Ayurvedic texts, specific time, season and procedures or methods have been highlighted for getting better potency, efficacy and therapeutic properties of drug by describing the standard methods of drug collection and preservation in details. Now a day, due to lack of proper traditional knowledge and time very few people bother to follow all these methods of collection given by Acharya. Hence, the potency of medicines is of question. Aragvadha (Cassia fistula Linn.) has been popular as a common drug of choice treatment since ancient time. Classic text like Charaka Samhita has quoted the classical and particular method for the collection and preservation of Aragvadha Phalamajja (Cassia fistula Linn.). Acharya Charaka has quoted this collection method of Aragvadha Phalamajja(Cassia fistula Linn.)as follows- The good qualities of collected pods should be kept covered in river bed sand for seven days. After seven days these pods should be removed and kept in sunlight for some time. And thereafter, fruit pulp (phalamajja) should be extracted and stored in a clean vessel. Therefore, study of classically collected Aragvadha Phalamajja (Cassia fistula Linn.) and Market sample of Aragvadha Phalamajja (Cassia fistula Linn.) was carried out

Retinal OCT findings in acute central retinal artery occlusion of varying severity at different disease stages – a retrospective, observational study

Abstract Purpose To study the optical coherence tomography (OCT) changes in eyes with acute central retinal artery occlusion (CRAO) of different severity and at different disease stages. Methods The study included acute CRAO cases of < 7 days duration, imaged on OCT at various time points. Based on the OCT findings at presentation, cases were classified into three severity groups: mild, moderate, and severe. OCT scans were evaluated and classified into four-time intervals based on symptom duration. Results There were 39 eyes from 38 patients with acute CRAO who underwent 96 OCT scans. At presentation, the study had 11, 16, and 12 cases of mild, moderate, and severe CRAO, respectively. Middle retinal layer opacification was more common in mild CRAO cases, which caused inner retinal layer thinning over time. Moderate CRAO cases had total inner retinal layer opacification, which resulted in retinal thinning over time. Prominent middle limiting membrane (p-MLM) sign was seen in mild and moderate CRAO eyes while were not visualised in severe CRAO. This sign gradually faded out over time. Other OCT findings in higher grades of CRAO included inner retinal fluid, neurosensory detachment, internal limiting membrane detachment, hyperreflective foci, and posterior vitreous opacities. Regardless of the CRAO grade, the final end-point seen was inner retinal layer thinning over time. Conclusion OCT in CRAO is a useful for determining the severity of retinal ischemia, disease stage, tissue damage mechanism, and final visual outcome. More prospective studies analysing a larger number of cases at fixed time points will be required in the future. Trial Registration Trial Registration Number: Not applicable