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Background Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model. Methods Three hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers. Results Six novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis. Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood. Conclusion We expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Context During pregnancy, the immune system is altered, putting women at increased risk of complications from respiratory viruses. There is limited information about the effects of COVID-19 on pregnant women and obstetrics programs, particularly in rural regions. Aims Most published reports have been from large urban hospitals. This study sought to gain insight into how the COVID-19 pandemic is impacting rural obstetrics programs. Materials and methods This qualitative study surveyed participants who worked in rural obstetrics programs in New Mexico using a free response questionnaire. Results The pandemic has changed the obstetrics experience in rural New Mexico by impacting the relationship between patients and providers and altering the family-centered model of birth. Difficulties unique to rural obstetrics included lack of transportation, limited hospital rooms and limited staff, including OB providers, nurses and housekeeping. Wellness has been impacted for providers, manifested in increased anxiety, stress and burnout. Patients reported increased anxiety, decreased family support, and potential disruptions in maternal-infant bonding. Conclusions Rural hospitals and clinics in New Mexico and across the United States operate with challenges at baseline, with many clinics across the nation closing, leading to increasing shortages of healthcare services in rural areas. This study showed that COVID-19 has increased the challenges that rural obstetrics providers face, altering the way they practice and creating uncertainty for the future due to potentially permanent changes to their practice. Future research will explore the lasting effects of the pandemic on rural obstetrics providers specifically, and rural hospitals generally.

Introduction Frailty is an increasingly recognised concept, with 25–50% of over 85’s estimated to be frail1,. Previous research considered medical students’ attitudes towards older people2, yet despite the correlation between frailty and increased age3, little is known about attitudes of healthcare professionals towards frailty. We researched attitudes towards, and understanding of, frailty in undergraduate and postgraduate trainees, with a view to guiding future educational interventions. Method Approval was granted by Northumbria Healthcare NHS Foundation Trust (NHCT) Research and Development department, Newcastle University’s Research Management Group and the HRA. 3 cohorts were recruited; 3rd year Newcastle University MBBS Students, 5th year Newcastle University MBBS Students and Foundation Year 2 and Core Medical Trainees working for NHCT (junior doctors). Data was collected during scheduled teaching at NHCT and individuals were invited to participate via email prior to this. Those not participating were still required to attend the teaching. Participants provided written consent. Within each cohort, small group discussions around frailty and Comprehensive Geriatric Assessment (CGA) were prompted using open questions (e.g. “what does frailty mean to you?”), during which participants anonymously submitted phrases to an online word-cloud generator. Discussions were audio recorded and transcribed. Transcriptions and word-clouds were analysed using Simple Content Analysis. The over-arching themes within each cohort were identified and compared with other cohorts. Interpretations were reviewed by an independent researcher to enhance rigour. Results Each cohort associated frailty with older age and weakness, and often used it as a byword for complexity. Frailty was described as an abstract construct composed of personal experiences rather than an objectively defined descriptor. All associated it with negative emotions. Cohorts differed in their approach, with 3rd year students primarily focussed on defining frailty, whereas junior doctors prioritised the clinical challenges it presented. Junior doctors demonstrated limited understanding of CGA whilst undergraduate students were almost universally ignorant of it. Conclusions The lack of understanding around frailty and CGA is concerning given its high prevalence. The identification of negative emotions increases this concern. To challenge this, focussed educational interventions addressing understanding and attitudes ought to be developed for tomorrow’s doctors. References 1. Clegg et al. Lancet 2013; 381: 752–62. 2. Samra et al. Age Ageing 2017; 46: 911–9. 3. Romero-Ortuno et al. Age Ageing 2012; 41: 684–9.

Insect nephrocytes are ultrafiltration cells that remove circulating proteins and exogenous toxins from the haemolymph. Experimental disruption of nephrocyte development or function leads to systemic impairment of insect physiology as evidenced by cardiomyopathy, chronic activation of immune signalling and shortening of lifespan. The genetic and structural basis of the nephrocyte's ultrafiltration mechanism is conserved between arthropods and mammals, making them an attractive model for studying human renal function and systemic clearance mechanisms in general. Although dynamic changes to intracellular calcium are fundamental to the function of many cell types, there are currently no studies of intracellular calcium signalling in nephrocytes. In this work we aimed to characterise calcium signalling in the pericardial nephrocytes of Drosophila melanogaster. To achieve this, a genetically encoded calcium reporter (GCaMP6) was expressed in nephrocytes to monitor intracellular calcium both in vivo within larvae and in vitro within dissected adults. Larval nephrocytes exhibited stochastically timed calcium waves. A calcium signal could be initiated in preparations of adult nephrocytes and abolished by EGTA, or the store operated calcium entry (SOCE) blocker 2-APB, as well as RNAi mediated knockdown of the SOCE genes Stim and Orai. Neither the presence of calcium-free buffer nor EGTA affected the binding of the endocytic cargo albumin to nephrocytes but they did impair the subsequent accumulation of albumin within nephrocytes. Pre-treatment with EGTA, calcium-free buffer or 2-APB led to significantly reduced albumin binding. Knock-down of Stim and Orai was non-lethal, caused an increase to nephrocyte size and reduced albumin binding, reduced the abundance of the endocytic cargo receptor Amnionless and disrupted the localisation of Dumbfounded at the filtration slit diaphragm. These data indicate that pericardial nephrocytes exhibit stochastically timed calcium waves in vivo and that SOCE mediates the localisation of the endocytic co-receptor Amnionless. Identifying the signals both up and downstream of SOCE may highlight mechanisms relevant to the renal and excretory functions of a broad range of species, including humans.

ObjectiveThe pharmacokinetic/pharmacodynamic (PK/PD) relationship between blood tétrahydrocannabinol (THC) concentrations after smoking and the ability to drive is poorly documented.MethodsTHC and its metabolites were measured in the blood of chronic users (CC, 1–2 joints/day) and 15 occasional users (CO, 1–2 joints/week) 12 times over 24 h after randomized placebo-controlled smoking containing 10 mg or 30 mg of THC. The effects were evaluated 7 times by a vigilance test (reaction time) and a driving simulator during the same period.ResultsThere is no PK/PD relationship. The blood concentration for THC and 11-OH-THC is maximal at the end of the consumption whereas the effects are strongest about 5 h later. After the same dose consumed, the blood concentration of THC is almost twice as high in CC than in CO. CC always have THC in the blood (>1 ng/mL) after 24 h whereas it is < 0.5 ng/mL in CO after approximately 6 h. The effects on reaction time are greater for CO (+19% at 10 mg and +27% at 30 mg) than for CC (+11% at 10 mg and +19% at 30 mg). This is also the case for the ability to drive where there is no dose effect (+25% driving error for CC vs. +34% in CO). The total effect on driving lasts about 8 h in CC and up to 13 h in CO.ConclusionCannabis has a deleterious effect on the ability to drive, delayed in time compared to the blood kinetics of THC., ObjectifLa relation pharmacocinétique/pharmacodynamique (PK/PD) après une prise fumée de cannabis et l’aptitude à conduire est peu documentée.MéthodesLe tétrahydrocannabinol (THC) et ses deux principaux métabolites ont été mesurés dans le sang de 15 consommateurs chroniques (CC, 1–2 joints/j) et de 15 consommateurs occasionnels (CO, 1–2 joints/semaine) 12 fois pendant 24 h après consommation d’une cigarette contenant de manière randomisée du placebo, 10 mg ou 30 mg de THC. Les effets ont été évalués 7 fois par un test de vigilance (temps de réaction) et un simulateur de conduite durant la même période.RésultatsIl n’existe pas de relation PK/PD. La concentration sanguine en THC et 11-OH-THC est maximale dès la fin de la consommation alors que les effets sont maximums 5 à 6 h après. Après une même dose consommée, la concentration sanguine de THC est pratiquement deux fois plus élevée chez les CC que chez les CO. Les CC ont toujours du THC dans le sang (>1 ng/mL) après 24 h alors qu’il est < 0,5 ng/mL chez les CO après 6 h environ. Les effets sur l’allongement du temps de réaction sont plus importants pour les CO (+19 % à 10 mg et +27 % à 30 mg) que pour les CC (+11 % à 10 mg et +19 % à 30 mg), de même sur l’aptitude à conduire où on ne retrouve pas d’effet dose (+25 % d’erreur pour les CC vs +34 % chez les CO). L’effet total sur la conduite dure environ 8 h chez les CC et jusqu’à 13 h chez les CO.ConclusionLe cannabis a un effet délétère sur la conduite, décalé dans le temps par rapport à la cinétique sanguine du THC.

Aging is associated with a decline in heart function across the tissue, cellular, and molecular levels. The risk of cardiovascular disease grows significantly over time, and as developed countries continue to see an increase in lifespan, the cost of cardiovascular healthcare for the elderly will undoubtedly rise. The molecular basis for cardiac function deterioration with age is multifaceted and not entirely clear, and there is a limit to what investigations can be performed on human subjects or mammalian models. Drosophila melanogaster has emerged as a useful model organism for studying aging in a short timeframe, benefitting from a suite of molecular and genetic tools and displaying highly conserved traits of cardiac senescence. Here, we discuss recent advances in our understanding of cardiac aging and how the fruit fly has aided in these developments.

Many medical schools have transitioned to teaching anatomy with prosections and models1. The efficacy of these curricular approaches as they compare to the gold standard of dissection anatomy has been evaluated2. In addition to helping students acquire professional competencies3, students who participate in dissection achieve higher scores on written examinations than students who participate in prosection1,4. Dissection helps students develop integrated three‐dimensional models of the human body, which is fundamental to clinical practice2. In a typical year, medical students at our university take Clinical Morphology which includes histology, embryology, imaging, and dissection anatomy. In 2020, due to the global COVID‐19 pandemic, laboratory access was significantly restricted, requiring a shift to a prosection and virtual learning hybrid model. All other components of the course were retained. This necessary change in curriculum provided a natural experiment to investigate the impact of eliminating dissection anatomy on students’ academic performance. We hypothesized a negative impact. Students in the 2020 cohort worked in small groups to complete a weekly two‐hour online simulated dissection, and attended an optional weekly in‐person prosection lab. Faculty‐produced prosection videos were available to view asynchronously. Virtual office hours were held in the laboratory. In contrast, the 2019 cohort participated in a traditional dissection anatomy lab that included six hours of instructor‐supported dissection each week and 24‐hour lab access. All other course components were comparable. Respectively, for the 2020 and 2019 cohorts, mean quiz scores were 86.2 and 85.6; lab practical averages were 92.5 and 86.3; mean NBME scores were 80.9 and 82.2; and course numeric score means were 84.7 and 84.8 (no significant differences, t‐test). The frequency of passing and failing scores followed a similar pattern with no differences identified between the two cohorts (Chi Square). All 2020 students had a passing average for lab practicals; significantly better than the 2019 cohort (p < 0.05, Chi Square). Pairwise Pearson r correlation coefficients showed a strong relationship (r > 0.75) for quiz, NBME, and lab practical scores in the 2019 cohort. For the 2020 cohort, there was a strong relationship (r = 0.72) only for quiz and NBME scores. Dissection anatomy correlates strongly with quizzes and the NBME exam performance, while virtual‐prosection anatomy does not. The lack of strong pairwise correlations between virtual anatomy with either NBME or quiz performance suggest that the virtual‐prosection model did not align well with academic objectives. These data support the continued inclusion of dissection in medical school anatomy. 1. Eppler E, Serowy S, Link K, Filgueira L. Anat Sci Educ. 2018;11:32‐43. doi:10.1002/ase.1707 2. Keerti Singh, Uma Gaur, Kiana Hall, Keisha Mascoll, Damian Cohall, Md Anwarul Azim Majumder. Advances in human biology. 2020;10(3):90‐94. doi:10.4103/AIHB.AIHB_87_20 3. McDaniel KG, Brown T, Radford CC, et al. Anat Sci Educ. 2020;10.1002/ase.2000. doi:10.1002/ase.2000 4. Thompson AR, Marshall AM. Anat Sci Educ. 2020;13(1):30‐36. doi:10.1002/ase.1859

Résumé Objectif Déterminer l’évolution du sommeil chez les Français pendant le confinement motivé par la pandémie du SARS-CoV-2 et définir les facteurs comportementaux associés à un sommeil détérioré. Méthodologie Une enquête en ligne via les réseaux sociaux pendant la période de confinement. Les questions ont ciblé les conditions de confinement, les comportements relatifs au sommeil et les éléments de l’environnement potentiellement perturbateurs du sommeil (exposition à la lumière et activités sportives). Résultats Au total, 1777 participants ont été inclus dont 77 % femmes, 72 % âgés de 25–54 ans. Les conditions de confinement les plus fréquentes étaient en couple avec enfants (36 %) et en maison avec jardin (51 %). Quarante-sept pour cent rapportent une diminution de la qualité du sommeil en confinement. Les facteurs associés à une détérioration du sommeil retenus par l’analyse multivariée sont une diminution de la durée du sommeil (OR 15,52 — p

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Tissue fibrosis, an accumulation of extracellular matrix proteins such as collagen, accompanies cardiac ageing in humans and this is linked to an increased risk of cardiac failure. The mechanisms driving age-related tissue fibrosis and cardiac dysfunction are unclear, yet clinically important. Drosophila is amenable to the study of cardiac ageing as well as collagen deposition; however it is unclear whether collagen accumulates in the ageing Drosophila heart. This work examined collagen deposition and cardiac function in ageing Drosophila, in the context of reduced expression of collagen-interacting protein SPARC (Secreted Protein Acidic and Rich in Cysteine) an evolutionarily conserved protein linked with fibrosis. Heart function was measured using high frame rate videomicroscopy. Collagen deposition was monitored using a fluorescently-tagged collagen IV reporter (encoded by the Viking gene) and staining of the cardiac collagen, Pericardin. The Drosophila heart accumulated collagen IV and Pericardin as flies aged. Associated with this was a decline in cardiac function. SPARC heterozygous flies lived longer than controls and showed little to no age-related cardiac dysfunction. As flies of both genotypes aged, cardiac levels of collagen IV (Viking) and Pericardin increased similarly. Over-expression of SPARC caused cardiomyopathy and increased Pericardin deposition. The findings demonstrate that, like humans, the Drosophila heart develops a fibrosis-like phenotype as it ages. Although having no gross impact on collagen accumulation, reduced SPARC expression extended Drosophila lifespan and cardiac health span. It is proposed that cardiac fibrosis in humans may develop due to the activation of conserved mechanisms and that SPARC may mediate cardiac ageing by mechanisms more subtle than gross accumulation of collagen., Highlights • The ageing Drosophila heart accumulates collagens (Viking and Pericardin). • This fibrosis-like phenotype accompanied age-dependent cardiac dysfunction. • Reduced expression of the collagen-interacting protein SPARC prevented the age-related cardiac dysfunction. • SPARC overexpression in nephrocytes drives cardiomyopathy and Pericardin deposition. • Reduced SPARC did not prevent collagen accumulation in the ageing heart.

Here we show that a labyrinth channel compartment and slit diaphragms, which are the histological structures\ud enabling insect nephrocytes ultrafiltration, are established during embryogenesis first by the garland nephrocytes (GCNs). The later pericardial nephrocytes, which represent the majority of functional nephrocytes in larvae and adults, lack these characteristic features at the embryonic stage. During larval development, a subpopulation of the pericardial cells survives and matures into functional nephrocytes (PCNs) displaying a fully differentiated slit diaphragm and a labyrinth channel compartment. Likely the embryonic pericardial cells have primary functions other than ultrafiltration (e.g. in production and secretion of ECM constituents). We also show, for the first time, that PCNs in the adult fly undergo dramatic histological degeneration upon ageing. The slit diaphragms disappear, the labyrinth channel system degenerates and the lysosomal compartment becomes highly enriched with electron-dense material. When using nephrocytes as a model for genetic screening purposes or to investigate the specific role of genes involved in endocytosis, histological changes occurring upon ageing need to be taken into account when interpreting structural data.

Vertebrate podocytes are kidney glomerular cells critically required for normal renal filtration. To fulfill their role, podocytes form molecular sieves known as slit diaphragms that contribute to the glomerular filtration barrier. The disruption of podocyte biology or slit diaphragm formation in humans is a precursor to albuminuria, renal failure, and cardiovascular morbidity. Due to genetic and functional similarities, the nephrocytes of Drosophila are increasingly used to model the genetic and metabolic basis of human podocyte biology. They have the advantage that they are a much quicker system to study compared to other murine transgenic models. In this chapter we present methods to modulate and study Drosophila nephrocyte function and diaphragm formation.

BACKGROUND The pharmacokinetic–pharmacodynamic relationship between whole blood δ-9-tetrahydrocannabinol (THC) and driving risk is poorly understood. METHODS Fifteen chronic cannabis consumers (1–2 joints/day; CC) and 15 occasional cannabis consumers (1–2 joints/week; OC) of 18 to 34 years of age were included. A pharmacokinetic study was conducted with 12 blood samplings over a 24-h period before and after controlled random inhalation of placebo or 10 mg or 30 mg of THC. THC and metabolites were quantified using LC-MS/MS. Effects on reaction time by psychomotor vigilance tests and driving performance through a York driving simulator were evaluated 7 times. A pharmacokinetic–pharmacodynamic analysis was performed using R software. RESULTS Whole blood peak THC was 2 times higher in CC than in OC for a same dose and occurred 5 min after the end of consumption. THC remained detectable only in CC after 24 h. Despite standardized consumption, CC consumed more available THC from each cigarette regardless of dose. Maximal effect for reaction time was dose- and group-dependent and only group-dependent for driving performance, both being decreased and more marked in OC than in CC. These effects were maximal around 5 h after administration, and the duration was longer in OC than in CC. A significant pharmacokinetic–pharmacodynamic relationship was observed only between Tmax for blood THC and the duration effect on mean reciprocal reaction time. CONCLUSIONS Inhalation from cannabis joints leads to a rapid increase in blood THC with a delayed decrease in vigilance and driving performance, more pronounced and lasting longer in OC than in CC. ClinicalTrials.gov Identifier: NCT02061020

Supplemental Digital Content is available in the text., Background— The Drosophila heart is an important model for studying the genetics underpinning mammalian cardiac function. The system comprises contractile cardiomyocytes, adjacent to which are pairs of highly endocytic pericardial nephrocytes that modulate cardiac function by uncharacterized mechanisms. Identifying these mechanisms and the molecules involved is important because they may be relevant to human cardiac physiology. Methods and Results— This work aimed to identify circulating cardiomodulatory factors of potential relevance to humans using the Drosophila nephrocyte–cardiomyocyte system. A Kruppel-like factor 15 (dKlf15) loss-of-function strategy was used to ablate nephrocytes and then heart function and the hemolymph proteome were analyzed. Ablation of nephrocytes led to a severe cardiomyopathy characterized by a lengthening of diastolic interval. Rendering adult nephrocytes dysfunctional by disrupting their endocytic function or temporally conditional knockdown of dKlf15 led to a similar cardiomyopathy. Proteomics revealed that nephrocytes regulate the circulating levels of many secreted proteins, the most notable of which was the evolutionarily conserved matricellular protein Secreted Protein Acidic and Rich in Cysteine (SPARC), a protein involved in mammalian cardiac function. Finally, reducing SPARC gene dosage ameliorated the cardiomyopathy that developed in the absence of nephrocytes. Conclusions— The data implicate SPARC in the noncell autonomous control of cardiac function in Drosophila and suggest that modulation of SPARC gene expression may ameliorate cardiac dysfunction in humans.

Deformation studies of a metal or alloy single crystal under plane strain boundary conditions have proved valuable for providing information on the deformation behavior of such materials under multiaxial states of stress and strain. Examples include the initiation and propagation of cracks during brittle fracture and the development of deformation textures in metal forming operations. Restrictions imposed by plane strain boundary conditions on the values of global strain components and on active slip systems by the principle of maximum plastic work confine slip to subsets of physically possible crystallographic slip system (CSS). Such ensembles produce components of global strain that independently satisfy plane strain constraints. This leads to the definition of Pseudo Slip Systems (PSS) having basis vectors formed from the resultants of corresponding basis vectors in participating CSS. Nye’s State of Dislocation tensor applied at both macro- and micro-structural scales describes global and local lattice rotations resulting from the geometrically necessary dislocation (GND) content. Local Nye Tensors (LNT) for each active CSS are dyadic products of their Burgers vector and a Dislocation Density Vector (DDV) describing the GND population. This vector, lying in the slip plane, has a magnitude equal to that of the local GND, and a direction given by the character of the resultant population. The Global Nye Tensor (GNT), A, is the sum of LNTs for each active CSS and expresses in global specimen coordinates the resultant Burgers vector flux from all active CSS. We demonstrate these relationships by analyzing plane strain deformation in a Ni single crystal caused by wedge indentation along a 〈 110 〉 direction.

Despite significant interest in developing extracellular matrix (ECM)-inspired biomaterials to recreate native cell-instructive microenvironments, the major challenge in the biomaterial field is to recapitulate the complex structural and biophysical features of native ECM. These biophysical features include multiscale hierarchy, electrical conductivity, optimum wettability, and mechanical properties. These features are critical to the design of cell-instructive biomaterials for bioengineering applications such as skeletal muscle tissue engineering. In this study, we used a custom-designed film fabrication assembly, which consists of a microfluidic chamber to allow electrostatic charge-based self-assembly of oppositely charged polymer solutions forming a hydrogel fiber and eventually, a nanocomposite fibrous hydrogel film. The film recapitulates unidirectional hierarchical fibrous structure along with the conductive properties to guide initial alignment and myotube formation from cultured myoblasts. We combined high conductivity, and charge carrier mobility of graphene with biocompatibility of polysaccharides to develop graphene-polysaccharide nanocomposite fibrous hydrogel films. The incorporation of graphene in fibrous hydrogel films enhanced their wettability, electrical conductivity, tensile strength, and toughness without significantly altering their elastic properties (Young's modulus). In a proof-of-concept study, the mouse myoblast cells (C2C12) seeded on these nanocomposite fibrous hydrogel films showed improved spreading and enhanced myogenesis as evident by the formation of multinucleated myotubes, an early indicator of myogenesis. Overall, graphene-polysaccharide nanocomposite fibrous hydrogel films provide a potential biomaterial to promote skeletal muscle tissue regeneration.

The change in reflectivity of black-Si (b-Si) upon optical excitation was measured by the pump-probe technique using picosecond laser pulses at 532 (pump) and 1064 nm (probe) wavelengths. The specular reflection from the random pattern of plasma-etched b-Si nano-needles was dominated by the photo-excited free-carrier contribution to the reflectivity. The kinetics of the reflectivity were found to be consistent with surface structural and chemical analysis, performed by scanning and transmission electron microscopy, and spectroscopic ellipsometry. The surface recombination velocity on the b-Si needles was estimated to be ~ 10 2 cm / s . Metalization of b-Si led to much faster recombination and alteration of reflectivity. The reflectivity spectra of random b-Si surfaces with different needle lengths was modeled by a multi-step refractive index profile in the Drude formalism. The dip in the reflectivity spectra and the sign reversal in the differential reflectivity signal at certain b-Si needle sizes is explained by the model.

RNA binding protein (RBPs) and microRNAs (miRNAs or miRs) are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR) containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC). Despite this, miR-16 and HuR do not affect the other’s expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.

RNA binding proteins (RBPs) play key roles in RNA dynamics, including subcellular localization, translational efficiency and metabolism. Cold-inducible RNA binding protein (CIRP) is a stress-induced protein that was initially described as a DNA damage-induced transcript (A18 hnRNP), as well as a cold-shock domain containing cold-stress response protein (CIRBP) that alters the translational efficiency of its target messenger RNAs (mRNAs). This review summarizes recent work on the roles of CIRP in the context of inflammation and cancer. The function of CIRP in cancer appeared to be solely driven though its functions as an RBP that targeted cancer-associated mRNAs, but it is increasingly clear that CIRP also modulates inflammation. Several recent studies highlight roles for CIRP in immune responses, ranging from sepsis to wound healing and tumor-promoting inflammation. While modulating inflammation is an established role for RBPs that target cytokine mRNAs, CIRP appears to modulate inflammation by several different mechanisms. CIRP has been found in serum, where it binds the TLR4-MD2 complex, acting as a Damage-associated molecular pattern (DAMP). CIRP activates the NF-κB pathway, increasing phosphorylation of Iκκ and IκBα, and stabilizes mRNAs encoding pro-inflammatory cytokines. While CIRP promotes higher levels of pro-inflammatory cytokines in certain cancers, it also decreases inflammation to accelerate wound healing. This dichotomy suggests that the influence of CIRP on inflammation is context dependent and highlights the importance of detailing the mechanisms by which CIRP modulates inflammation. WIREs RNA 2018, 9:e1462. doi: 10.1002/wrna.1462 This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.