Miracle-dz/UniFAR-FTUs huggingface dataset:
Glutaredoxin Exerts an Antiapoptotic Effect by Regulating the Redox State of Akt*

Glutaredoxin (GRX) is a small dithiol protein involved in various cellular functions, including the redox regulation of certain enzyme activities. GRX functions via a disulfide exchange reaction by utilizing the active site Cys-Pro-Tyr-Cys. Here we demonstrated that overexpression of GRX protected cells from hydrogen peroxide (H2O2)-induced apoptosis by regulating the redox state of Akt. Akt was transiently phosphorylated, dephosphorylated, and then degraded in cardiac H9c2 cells undergoing H2O2-induced apoptosis. Under stress, Akt underwent disulfide bond formation between Cys-297 and Cys-311 and dephosphorylation in accordance with an increased association with protein phosphatase 2A. Overexpression of GRX protected Akt from H2O2-induced oxidation and suppressed recruitment of protein phosphatase 2A to Akt, resulting in a sustained phosphorylation of Akt and inhibition of apoptosis. This effect was reversed by cadmium, an inhibitor of GRX. Furthermore an in vitro assay revealed that GRX reduced oxidized Akt in concert with glutathione, NADPH, and glutathione-disulfide reductase. Thus, GRX plays an important role in protecting cells from apoptosis by regulating the redox state of Akt.
Prospects and application of nanobiotechnology in food preservation: molecular perspectives

Abstract Applications of biotechnological tools in food preservation have shown promising results in minimizing food spoilage. Design and development of highly efficient food preservatives are one of the key success factors in this application field. However, due to the inherent shortcomings of the bulk forms of such preservatives, research was in progress to find suitable alternatives to replace conventional modalities. The intervention of nanotechnology has made this approach feasible in almost every aspect of food preservation. This interface domain of nanobiotechnology has been very well explored in the last few decades and vast literature has been reported. Researchers have developed efficient nanopreservatives (NPRs) for diverse applications. However, the literature available on nano-based food preservation is not inclusive of molecular perspectives involved in food preservation. There is a large knowledge gap in the interface domain concerning the physics of intermolecular and interfacial forces and nanotechnology which play decisive roles in designing edible coatings (ECs). There is an urgent need for identifying the nano and molecular level contributing factors for developing efficient NPRs. Moreover, it is imperative to understand the possible health impact of NPRs in public interest and concern. This review revisits the fundamental aspects of food preservation and navigates through the applicability, safety, molecular aspects and future direction of NPRs.
Influence of Cognition on Length of Stay and Rehospitalization in Older Veterans Admitted for Post-Acute Care

Objectives: Evaluate the relative contribution of cognitive test performance to post-acute care (PAC) length of stay (LOS) and rehospitalization while controlling for key demographic, medical, and functional outcomes. Methods: Retrospective medical record review of 160 older Veterans, including cognitive test performance (Addenbrooke’s Cognitive Examination–Revised [ACE-R]), on admission to a Veterans Administration Hospital Community Living Center (CLC) PAC. Results: Individuals with impaired scores on the ACE-R had a longer LOS (10 median days longer; U = 2,547.00, p = .028). Of those rehospitalized, 71.4% (n = 20) screened positive for cognitive impairment. Key medical factors explained the largest amount of variance in CLC-PAC LOS (29.8%), followed by admission ADL (activities of daily living) dependency (4.6%) and ACE-R total score (3.30%). Discussion: Cognitive screening should be considered on PAC admission, with impairment on ACE-R predicting geriatric rehabilitation outcomes such as risk of increased LOS and rehospitalization.
Sleep Duration as an Indirect Link Between Sleep Timing and Weight in Midlife Women.

Objective: Midlife women are at risk of obesity. Poor sleep outcomes including inadequate sleep duration and variable sleep timing are risk factors for obesity, but there is a lack of understanding on how specific sleep constructs uniquely or concurrently are associated with weight outcomes in this population. This study examined the unique association of sleep timing with weight outcomes and how sleep timing works in conjunction with sleep duration to influence weight in midlife women. Materials and Methods: An archival analysis was performed using the Midlife in the United States-II study (MIDUS-II). The sample consisted of 132 midlife women (40-64; M = 52.9, standard deviation = 6.94). Sleep timing (mean sleep time, variability) and duration were measured through actigraphy and daily sleep diaries. Weight was assessed using body mass index (BMI) and waist circumference measures. Results: PROCESS mediation and moderation analyses assessed direct, indirect, and moderating pathways. Sleep duration emerged as an indirect link between sleep timing (mean and variability) and weight outcomes (95% CI = 0.0001-0.0123; 95% CI = 0.0007-0.0378; 95% CI = 0.0079-0.1006). Sleep timing (95% CI = -0.0144 to 0.0076; 95% CI = -0.0358 to 0.0219) and sleep time variability (95% CI = -0.0124 to 0.0438; 95% CI = -0.0533 to 0.0939) were not directly associated with BMI or waist circumference. Also, sleep timing and duration did not interact to influence weight outcomes. Conclusions: Sleep duration, rather than sleep timing, is associated with weight outcomes, and is an indirect link in the sleep timing and weight outcomes association. Future work is needed to further disentangle the impact of sleep on weight in midlife women using prospective studies, implementing daily assessments of sleep behavior.
Sensory Axon Response to Substrate-Bound Slit2 Is Modulated by Laminin and Cyclic GMP

In vertebrates, Slit2 is a chemorepellent for some developing axons but stimulates axonal elongation and branching of sensory axons. In vivo, Slit2 is cleaved into 140-kDa N-terminal (Slit2-N) and 55- to 60-kDa C-terminal fragments, but the uncleaved/full-length form can also be isolated from brain extracts. As Slit2-N and full-length Slit2 bind tightly to cell membranes, we decided to explore the response of rat dorsal root ganglia (DRG) axons to substrate-bound Slit2 fragments in the stripe assay. Slit2 fragments were avoided by DRG axons when expressed on membranes or coated as stripes on laminin. However, when the Slit2 stripes were coated on fibronectin, DRG axons still avoided full-length Slit2 but grew preferentially on Slit2-N. DRG axon response to Slit2 fragments could be modulated by cGMP and by a laminin-1 peptide. These results strongly support the idea that extracellular matrix proteins modulate the response of growth cones to chemotropic molecules by modulating cyclic nucleotide levels.
Paleoproteomics of Mesozoic Dinosaurs and Other Mesozoic Fossils

Molecular studies have contributed greatly to our understanding of evolutionary processes that act upon virtually every aspect of living organisms. However, these studies are limited with regard to extinct organisms, particularly those from the Mesozoic because fossils pose unique challenges to molecular workflows, and because prevailing wisdom suggests no endogenous molecular components can persist into deep time. Here, the power and potential of a molecular approach to Mesozoic fossils is discussed. Molecular methods that have been applied to Mesozoic fossils—including iconic, non‐avian dinosaurs— and the challenges inherent in such analyses, are compared and evaluated. Taphonomic processes resulting in the transition of living organisms from the biosphere into the fossil record are reviewed, and the possible effects of taphonomic alteration on downstream analyses that can be problematic for very old material (e.g., molecular modifications, limitations of on comparative databases) are addressed. Molecular studies applied to ancient remains are placed in historical context, and past and current studies are evaluated with respect to producing phylogenetically and/or evolutionarily significant data. Finally, some criteria for assessing the presence of endogenous biomolecules in very ancient fossil remains are suggested as a starting framework for such studies.
Population-level diagnosis and care cascade for chlamydia in Australia

Objectives Key strategies to control chlamydia include testing, treatment, partner management and re-testing. We developed a diagnosis and care cascade for chlamydia to highlight gaps in control strategies nationally and to inform efforts to optimise control programmes. Methods The Australian Chlamydia Cascade was organised into four steps: (1) annual number of new chlamydia infections (including re-infections); (2) annual number of chlamydia diagnoses; (3) annual number of diagnoses treated; (4) annual number of diagnoses followed by a re-test for chlamydia within 42–180 days of diagnosis. For 2016, we estimated the number of infections among young men and women aged 15–29 years in each of these steps using a combination of mathematical modelling, national notification data, sentinel surveillance data and previous research studies. Results Among young people in Australia, there were an estimated 248 580 (range, 240 690–256 470) new chlamydia infections in 2016 (96 470 in women; 152 100 in men) of which 70 164 were diagnosed (28.2% overall: women 43.4%, men 18.6%). Of the chlamydia infections diagnosed, 65 490 (range, 59 640–70 160) were treated (93.3% across all populations), but only 11 330 (range, 7660–16 285) diagnoses were followed by a re-test within 42–180 days (17.3% overall: women 20.6%, men 12.5%) of diagnosis. Conclusions The greatest gaps in the Australian Chlamydia Cascade for young people were in the diagnosis and re-testing steps, with 72% of infections undiagnosed and 83% of those diagnosed not re-tested: both were especially low among men. Treatment rates were also lower than recommended by guidelines. Our cascade highlights the need for enhanced strategies to improve treatment and re-testing coverage such as short message service reminders, point-of-care and postal test kits.
Complement in Renal Transplantation

Previous research and therapy in renal transplantation largely focused on the cellular arm of the adaptive immune response. Evidence is emerging that innate immune mechanisms, particularly complement, play a greater role in inflammatory and immune responses against the graft than has been previously recognized. Alternative complement pathway activation appears to mediate renal ischaemia/reperfusion injury, and proximal tubular cells may be both the source and the site of attack of complement components in this setting. Locally produced complement also plays a role in the development of both cellular and antibody-mediated immune responses against the graft. C4d staining has emerged as a useful marker of humoral rejection both in the acute and in the chronic setting and led to renewed interest in the significance of anti-donor antibody formation. A number of therapies are in development which inhibit complement or reduce local synthesis, and may lead to an improved clinical outcome following renal transplantation.
Acute Yellow Phosphorus Poisoning Causing Fulminant Hepatic Failure with Parenchymal Hemorrhages and Contained Duodenal Perforation

White phosphorus is well known as a potent hepatotoxin and a severe local and systemic toxin causing damage to gastrointestinal, hepatic, cardiovascular, and renal systems. It is used in the manufacture of matches, fireworks, rodenticide, and fertilizers. Death results due to acute liver failure. Management of yellow phosphorus (YP) poisoning is supportive with no antidote available. Here, we present a case of acute YP poisoning in a 25-year-old female presenting with fulminant hepatic failure and duodenal perforation.
CDK4, CDK6, Cyclin D1 and Notch1 immunocytochemical expression of oral brush liquid-based cytology for the diagnosis of oral leukoplakia and oral cancer.

OBJECTIVES This study aimed to investigate the feasibility of using oral liquid-based brush cytology (OLBC) coupled with immunocytochemistry as a minimally-invasive approach to stratify the cancer risk in patients with oral leukoplakia. METHODS 55 patients diagnosed with either oral leukoplakia (OLK) or oral squamous cell carcinoma (OSCC) were recruited. All patients underwent oral brush biopsy followed by surgical biopsy. 275 liquid-based cytology preparations were made. Pap stained OLBC slides were assessed using the modified 2014 Bethesda Cytology system. The expression of CDK4, CDK6, Cyclin D1, and Notch 1 was immunocytochemically analysed and compared against the histopathological diagnosis. A combined index score of OLBC grading and protein expression was calculated. RESULTS A significant association was found between the definitive histopathological diagnosis and the cytological interpretation (p = 0.0005). The index scores of CDK4, CDK6, and Cyclin D1 were significantly associated with the development of disease from non-dysplastic epithelium to OSCC. No significant association was observed between the Notch 1 index score and disease stage. The diagnostic accuracy of OLBC showed the highest values of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy; 84.6%, 70.4%, 73.3%, 82.6%, and 78.8%, respectively, compared to the cumulative protein index, CDK4/6 index, and the combined OLBC grading and CDK4/6 index. CONCLUSION This study has also demonstrated the efficacy of the use of OLBC in the detection of OED and OSCC, and showed that the use of CDK4, CDK6, Cyclin D1 and Notch 1 immunocytochemistry failed to improve the diagnostic accuracy of OLBC suggesting they are not useful in the early detection of OSCC. This article is protected by copyright. All rights reserved.
Effects of ribosomal proteins S1, S2 and the DeaD/CsdA DEAD‐box helicase on translation of leaderless and canonical mRNAs in Escherichia coli

Leaderless mRNAs beginning with the AUG initiating codon occur in all kingdoms of life. It has been previously reported that translation of the leaderless λcI mRNA is stimulated in an Escherichia coli rpsB mutant deficient in ribosomal protein S2. Here, we have studied this phenomenon at the molecular level by making use of an E. coli rpsBts mutant. The analysis of the ribosomes isolated under the non‐permissive conditions revealed that in addition to ribosomal protein S2, ribosomal protein S1 was absent, demonstrating that S2 is essential for binding of S1 to the 30S ribosomal subunit. In vitro translation assays and the selective translation of a leaderless mRNA in vivo at the non‐permissive temperature corroborate and extend previous in vitro ribosome binding studies in that S1 is indeed dispensable for translation of leaderless mRNAs. The deaD/csdA gene, encoding the ‘DeaD/CsdA’ DEAD‐box helicase, has been isolated as a multicopy suppressor of rpsBts mutations. Here, we show that expression of a plasmid borne deaD/csdA gene restores both S1 and S2 on the ribosome at the non‐permissive temperature in the rpsBts strain, which in turn leads to suppression of the translational defect affecting canonical mRNAs. These data are discussed in terms of a model, wherein DeaD/CsdA is involved in ribosome biogenesis rather than acting directly on mRNA.
The effects of sleep extension on cardiometabolic risk factors: A systematic review

Studies have shown bidirectional relationships between short‐ or long‐sleep duration and risk for obesity, non‐communicable diseases, all‐cause mortality and cardiovascular disease mortality. Increasing sleep duration may be an appropriate strategy to reduce cardiometabolic risk in short‐sleeping individuals. The aim is to review the effects of sleep extension interventions on cardiometabolic risk in adults. The PubMed and Scopus databases were searched for relevant, English, peer‐reviewed scientific publications (until August 2018). Seven studies that aimed to increase sleep duration in adults by any sleep extension intervention and described at least one cardiometabolic risk factor were included. These studies had a combined sample size of 138 participants who were either healthy (n = 14), healthy short‐sleeping (n = 92), overweight short‐sleeping (n = 10), or pre‐ or hypertensive short‐sleeping (n = 22) individuals. The durations of the sleep extension interventions ranged from 3 days to 6 weeks, and all successfully increased total sleep time by between 21 and 177 min. Sleep extension was associated with improved direct and indirect measures of insulin sensitivity, decreased leptin and peptide tyrosine‐tyrosine, and reductions in overall appetite, desire for sweet and salty foods, intake of daily free sugar, and percentage of daily caloric intake from protein. This review provides preliminary evidence for a role for sleep extension to improve cardiometabolic outcomes and directive towards future studies in the field of cardiometabolic health and sleep.
An architectural understanding of natural sway frequencies in trees

The relationship between form and function in trees is the subject of a longstanding debate in forest ecology and provides the basis for theories concerning forest ecosystem structure and metabolism. Trees interact with the wind in a dynamic manner and exhibit natural sway frequencies and damping processes that are important in understanding wind damage. Tree-wind dynamics are related to tree architecture, but this relationship is not well understood. We present a comprehensive view of natural sway frequencies in trees by compiling a dataset of field measurement spanning conifers and broadleaves, tropical and temperate forests. The field data show that a cantilever beam approximation adequately predicts the fundamental frequency of conifers, but not that of broadleaf trees. We also use structurally detailed tree dynamics simulations to test fundamental assumptions underpinning models of natural frequencies in trees. We model the dynamic properties of greater than 1000 trees using a finite-element approach based on accurate three-dimensional model trees derived from terrestrial laser scanning data. We show that (1) residual variation, the variation not explained by the cantilever beam approximation, in fundamental frequencies of broadleaf trees is driven by their architecture; (2) slender trees behave like a simple pendulum, with a single natural frequency dominating their motion, which makes them vulnerable to wind damage and (3) the presence of leaves decreases both the fundamental frequency and the damping ratio. These findings demonstrate the value of new three-dimensional measurements for understanding wind impacts on trees and suggest new directions for improving our understanding of tree dynamics from conifer plantations to natural forests.
RNA interference of STAT6 rapidly attenuates ongoing interleukin‐13‐mediated events in lung epithelial cells

Signal transducer and activator of transcription 6 (STAT6) expression in lung epithelial cells plays a central role in asthma pathogenesis, with its activation driving the development of airway hyper‐reactivity and local inflammation. Therefore, inhibition of local STAT6 expression provides a rationale for therapeutic intervention in bronchial asthma. Given the absence of specific inhibitory drugs, we tested the ability of small interfering RNAs (siRNAs) to target STAT6 gene expression through the molecular process of RNA interference (RNAi). At pico‐molar concentrations, STAT6‐specific siRNAs potently inhibited STAT6 mRNA expression in lung epithelial cells (50% inhibitory concentration range = 134–861 pm) without inducing cellular interferon responses. Detectable STAT6 protein expression was rapidly abolished within 48 hr of treatment (t1/2 range = < 12–37 hr) and this was unaffected by pretreatment with STAT6‐activating cytokines. Furthermore, STAT6 suppression by RNAi produced downstream functional inhibitory effects in that interleukin (IL)‐13‐ or IL‐4‐driven eotaxin chemokine family [chemokine (C‐C motif) ligand 11 (CCL11), CCL24 and CCL26] mRNA expression was markedly inhibited. Induction of detectable CCL26 protein synthesis was completely ablated by pretreating cells with STAT6‐specific siRNA. The therapeutic potential of this approach is further demonstrated by novel findings that cells pre‐exposed to IL‐13 or IL‐4 and subsequently treated with STAT6‐targeting siRNA exhibited a rapid and significant attenuation of ongoing CCL26 protein expression, suggesting that chronic asthma‐associated lung inflammation will be responsive to this approach.
Effects of chronic ramipril treatment in streptozotocin-induced diabetic rats.

The present investigation was undertaken to study the effects of chronic oral ramipril (1 mg/kg) treatment in streptozotocin (STZ) induced diabetic rats. Single tail vein injection of STZ (45 mg/kg, i.v.) produced a diabetic state exhibiting all the cardinal symptoms such as loss of body weight, polydipsia, polyuria, glucosuria, polyphagia, hypoinsulinaemia and hyperglycaemia. The diabetic state was also found to be associated with bradycardia, hypothyroidism, cardiac depression and cardiomyopathy. Ramipril treatment prevented STZ-induced hypertension, bradycardia, hypothyroidism, hyperchosesterolaemia and partially the cardiomayopathy. Ramipril treatment could not, however prevent STZ-induced loss of body weight, polyuria, polydipsia, polyphagia, hyperglycaemia, hypoinsulinaemia, hypertriglyceridaemia and cardiac depression. Our data suggests that ramipril has a few beneficial effects in the STZ-treated diabetic rats.
Influence of Yoga on Cancer-Related Fatigue and on Mediational Relationships Between Changes in Sleep and Cancer-Related Fatigue: A Nationwide, Multicenter Randomized Controlled Trial of Yoga in Cancer Survivors

Background: Cancer-related fatigue (CRF) often co-occurs with sleep disturbance and is one of the most pervasive toxicities resulting from cancer and its treatment. We and other investigators have previously reported that yoga therapy can improve sleep quality in cancer patients and survivors. No nationwide multicenter phase III randomized controlled trial (RCT) has investigated whether yoga therapy improves CRF or whether improvements in sleep mediate the effect of yoga on CRF. We examined the effect of a standardized, 4-week, yoga therapy program (Yoga for Cancer Survivors [YOCAS©®]) on CRF and whether YOCAS©®-induced changes in sleep mediated changes in CRF among survivors. Study Design and Methods: Four hundred and ten cancer survivors were recruited to a nationwide multicenter phase III RCT comparing the effect of YOCAS©® to standard survivorship care on CRF and examining the mediating effects of changes in sleep, stemming from yoga, on changes in CRF. CRF was assessed by the Multidimensional Fatigue Symptom Inventory. Sleep was assessed via the Pittsburgh Sleep Quality Index. Between- and within-group intervention effects on CRF were assessed by analysis of covariance and 2-tailed t test, respectively. Path analysis was used to evaluate mediation. Results: YOCAS©® participants demonstrated significantly greater improvements in CRF compared with participants in standard survivorship care at post-intervention (P < .01). Improvements in overall sleep quality and reductions in daytime dysfunction (eg, excessive napping) resulting from yoga significantly mediated the effect of yoga on CRF (22% and 37%, respectively, both P < .01). Conclusions: YOCAS©® is effective for treating CRF among cancer survivors; 22% to 37% of the improvements in CRF from yoga therapy result from improvements in sleep quality and daytime dysfunction. Oncologists should consider prescribing yoga to cancer survivors for treating CRF and sleep disturbance.