- HSF4 transcriptional regulates HMOX-1 expression in HLECs. [Journal Article]
- GENEGene 2018 Feb 14
- The major causes for cataract formation are free radicals, which are neutralized by the endogenous antioxidants. However, how the human lens clean these harmful free radicals is still unclear. Transc...
The major causes for cataract formation are free radicals, which are neutralized by the endogenous antioxidants. However, how the human lens clean these harmful free radicals is still unclear. Transcriptional factor heat shock factor 4 (HSF4) is a cataract-causing gene and plays important roles during lens development. Here we show that HMOX-1, an anti-oxidase, is a bona fide transcriptional target gene of HSF4 in HLECs (human lens epithelial cells). HSF4 directly binds to the HSE element in HMOX-1 promoter to mediate its mRNA transcription and protein accumulation. The HSE element located at the region of -389 bp to -362 bp upstream from the TSS (transcription start site), which is critical for HMOX-1 transcriptional activation. Furthermore, knockdown of HSF4 by siRNA inhibited HMOX-1 expression. Thus, these data revealed a novel transcription target of HSF4 and provided new insights into anti-oxidation regulation in lens and age-related cataract.
- Analysis of transactivation potential of rice (Oryza sativa L.) heat shock factors. [Journal Article]
- PPlanta 2018 Feb 16
- CONCLUSIONS: Based on yeast one-hybrid assays, we show that the presence of C-terminal AHA motifs is not a prerequisite for transactivation potential in rice heat shock factors. Transcriptional activation or transactivation (TA) of heat stress responsive genes takes place by binding of heat shock factors (Hsfs) to heat shock elements. Analysis of TA potential of thirteen rice (Oryza sativa L.) Hsfs (OsHsfs) carried out in this study by yeast one-hybrid assay showed that OsHsfsA3 possesses strong TA potential while OsHsfs A1a, A2a, A2b, A4a, A4d, A5, A7b, B1, B2a, B2b, B2c and B4d lack TA potential. From a near complete picture of TA potential of the OsHsf family (comprising of 25 members) emerging from this study and an earlier report from our group (Mittal et al. in FEBS J 278(17):3076-3085, 2011), it is concluded that (1) overall, six OsHsfs, namely A3, A6a, A6b, A8, C1a and C1b possess TA potential; (2) four class A OsHsfs, namely A3, A6a, A6b and A8 have TA potential out of which A6a and A6b contain AHA motifs while A3 and A8 lack AHA motifs; (3) nine class A OsHsfs, namely A1a, A2a, A2b, A2e, A4a, A4d, A5, A7a and A7b containing AHA motif(s) lack TA function in the yeast assay system; (4) all class B OsHsfs lack AHA motifs and TA potential (B4a not analyzed) and (5) though all class C OsHsf members lack AHA motifs, two members C1a and C1b possess TA function, while one member C2a lacks TA potential (C2b not analyzed). Thus, the presence or absence of AHA motif is possibly not the only factor determining TA potential of OsHsfs. Our findings will help to identify the transcriptional activators of rice heat shock response.
- Late Presentation of Post Diphtheritic Myocarditis in a 15-year Male. [Journal Article]
- JJJNMA J Nepal Med Assoc 2017 Oct-Dec; 56(208):475-477
- A 15-year old male patient presented to us with dyspnoea for four days. He had a history of fever, pseudo-membranous tonsillitis and cervical adenopathy twenty-five days prior to the presentation. On...
A 15-year old male patient presented to us with dyspnoea for four days. He had a history of fever, pseudo-membranous tonsillitis and cervical adenopathy twenty-five days prior to the presentation. On examination and laboratory investigations, he had features suggestive of myocarditis with biventricular failure. There was no reliable history of immunisation and he had a positive history of contact. He was planned for anti-diphtheria toxin but before the anti-toxin could be initiated, the patient succumbed to refractory cardiogenic shock. This was a rare case of late onset diphtheritic myocarditis in an unimmunised adult. With the advent of universal immunisation, there has been a significant decline in the incidence but there is still some road to cover.
- Effects of Bilateral Nasal Packing on Oxygen Saturation and Blood Pressure. [Journal Article]
- JJJNMA J Nepal Med Assoc 2017 Oct-Dec; 56(208):442-446
- CONCLUSIONS: Bilateral nasal packing can lead to significant rise in systolic and diastolic blood pressure and a dip in blood oxygen saturation. Thus care has to be taken while performing bilateral nasal packing in normal patients but much more in high risk patients.
- Ultrasound and shock-wave stimulation to promote axonal regeneration following nerve surgery: a systematic review and meta-analysis of preclinical studies. [Journal Article]
- SRSci Rep 2018 Feb 16; 8(1):3168
- Limited regeneration after nerve injury often leads to delayed or incomplete reinnervation and consequently insufficient muscle function. Following nerve surgery, application of low-intensity ultraso...
Limited regeneration after nerve injury often leads to delayed or incomplete reinnervation and consequently insufficient muscle function. Following nerve surgery, application of low-intensity ultrasound or extracorporeal shock waves may promote nerve regeneration and improve functional outcomes. Because currently clinical data is unavailable, we performed a meta-analysis following the PRISMA-guidelines to investigate the therapeutic effect of ultrasound and shock wave therapies on motor nerve regeneration. Ten ultrasound-studies (N = 445 rats) and three shock-wave studies (N = 110 rats) were identified from multiple databases. We calculated the difference in means or standardized mean difference with 95% confidence intervals for motor function, nerve conduction velocity and histomorphological parameters of treated versus sham or non-treated animals. Ultrasound treatment showed significantly faster nerve conduction, increased axonal regeneration with thicker myelin and improved motor function on sciatic functional index scale (week two: DM[95%CI]: 19,03[13,2 to 25,6], 71 animals; week four: 7,4[5,4 to 9,5], 47 animals). Shock wave induced recovery improvements were temporarily significant. In conclusion, there is significant evidence for low-intensity ultrasound but not for extracorporeal shock wave treatment to improve nerve regeneration. Prospective clinical trials should therefore investigate available FDA-approved ultrasound devices as adjunct postoperative treatment following nerve surgery.
- Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. [Journal Article]
- JBJ Biol Chem 2018 Feb 16
- The stress sensors ATF6, IRE1 and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits...
The stress sensors ATF6, IRE1 and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to re-establish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans or redox homeostasis. Cell responses to variations in luminal load with unfolded proteins are, in contrast, poorly characterized. Here, we compared gene and protein expression profiles in HEK 293 cells challenged with ER stress-inducing drugs or expressing model polypeptides. Drug titration to limit up-regulation of the endogenous ER stress reporters heat shock protein family A (Hsp70) member 5 (BiP/HSPA5) and homocysteine-inducible ER protein with ubiquitin-like domain 1 (HERP/HERPUD1) to levels comparable to luminal accumulation of unfolded proteins substantially reduced the amplitude of both transcriptional and translational responses. However, these drug-induced changes remained pleiotropic and failed to recapitulate responses to ER load with unfolded proteins. These required unfolded protein association with BiP and induced a much smaller subset of genes participating in a chaperone complex that binds unfolded peptide chains. In conclusion, UPR resulting from ER load with unfolded proteins proceed via a well-defined and fine-tuned pathway, whereas even mild chemical stresses caused by compounds often used to stimulate UPR induce cellular responses largely unrelated to the UPR or ER-mediated protein secretion.
- Syncope and cardiogenic shock in an 80-year-old woman. [Journal Article]
- BCBMJ Case Rep 2018 Feb 16; 2018
- Immune barriers of Ebola virus infection. [Review]
- COCurr Opin Virol 2018 Feb 13; 28:152-160
- Since its initial emergence in 1976 in northern Democratic Republic of Congo (DRC), Ebola virus (EBOV) has been a global health concern due to its virulence in humans, the mystery surrounding the ide...
Since its initial emergence in 1976 in northern Democratic Republic of Congo (DRC), Ebola virus (EBOV) has been a global health concern due to its virulence in humans, the mystery surrounding the identity of its host reservoir and the unpredictable nature of Ebola virus disease (EVD) outbreaks. Early after the first clinical descriptions of a disease resembling a 'septic-shock-like syndrome', with coagulation abnormalities and multi-system organ failure, researchers began to evaluate the role of the host immune response in EVD pathophysiology. In this review, we summarize how data gathered during the last 40 years in the laboratory as well as in the field have provided insight into EBOV immunity. From molecular mechanisms involved in EBOV recognition in infected cells, to antigen processing and adaptive immune responses, we discuss current knowledge on the main immune barriers of infection as well as outstanding research questions.
- Clinical correlates of cerebral white matter abnormalities in patients with Parkinson's disease: Methodological issues. [Letter]
- PRParkinsonism Relat Disord 2018 Feb 09
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- High dose insulin for beta-blocker and calcium channel-blocker poisoning: 17years of experience from a single poison center. [Journal Article]
- AJAm J Emerg Med 2018 Feb 06
- CONCLUSIONS: HDI, initiated by emergency physicians in consultation with a poison center, was feasible and safe in this large series. Metabolic abnormalities were common, highlighting the need for close monitoring. Hypoglycemia was more common when less concentrated dextrose maintenance infusions were utilized.