Ultraviolet attenuates centromere-mediated meiotic genome stability and alters gametophytic ploidy consistency in flowering plants.

Ultraviolet (UV) radiation influences development and genome stability in organisms; however, its impact on meiosis, a special cell division essential for the delivery of genetic information across generations in eukaryotes, has not yet been elucidated. In this study, by performing cytogenetic studies, we reported that UV radiation does not damage meiotic chromosome integrity but attenuates centromere-mediated chromosome stability and induces unreduced gametes in Arabidopsis thaliana. We showed that functional centromere-specific histone 3 (CENH3) is required for obligate crossover formation and plays a role in the protection of sister chromatid cohesion under UV stress. Moreover, we found that UV specifically alters the orientation and organization of spindles and phragmoplasts at meiosis II, resulting in meiotic restitution and unreduced gametes. We determined that UV-induced meiotic restitution does not rely on the UV Resistance Locus8-mediated UV perception and the Tapetal Development and Function1- and Aborted Microspores-dependent tapetum development, but possibly occurs via altered JASON function and downregulated Parallel Spindle1. This study provides evidence that UV radiation influences meiotic genome stability and gametophytic ploidy consistency in flowering plants.

Submicrometer Particle Impact Dynamics and Chemistry.

Experimental studies of the collision phenomena of submicrometer particles is a developing field. This review examines the range of phenomena that can be observed with new experimental approaches. The primary focus is on single-particle impact studies enabled by charge detection mass spectrometry (CDMS) implemented using the Aerosol Impact Spectrometer (AIS) at the University of California, San Diego. The AIS combines electrospray ionization, aerodynamic lens techniques, CDMS, and an electrostatic linear accelerator to study the dynamics of particle impact over a wide range of incident velocities. The AIS has been used for single-particle impact experiments on positively charged particles of diverse composition, including polystyrene latex spheres, tin particles, and ice grains, over a wide range of impact velocities. Detection schemes based on induced charge measurements and time-of-flight mass spectrometry have enabled measurements of the impact inelasticity through the determination of the coefficient of restitution, measurements of the angular distributions of scattered submicrometer particles, and the chemical composition and dissociation of solute molecules in hypervelocity ice grain impacts.

Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L-type Ca+ current.

OBJECTIVE: To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs). METHODS AND RESULTS: Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli-extra-stimulus (S1-S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol-12-myristate-13-acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p < .01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (p < .05) and decreased the thresholds of the VA and APD alternans (p < .01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) (n = 10), reversibly flattened the APD restitution curves at each site (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch-clamp, peak amplitude of L-type Ca2+ current was significantly increased by addition of PMA compared with control (CTL) group (p < .05). Antagonize this current with verapamil (n = 10) can fully inhibited the PMA induced increasing of Smax and inducibility of VA and alternans. CONCLUSION: PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx.

Behavior and morphology combine to influence energy dissipation in mantis shrimp (Stomatopoda).

Animals deliver and withstand physical impacts in diverse behavioral contexts, from competing rams clashing their antlers together to archerfish impacting prey with jets of water. Though the ability of animals to withstand impact has generally been studied by focusing on morphology, behaviors may also influence impact resistance. Mantis shrimp exchange high-force strikes on each other's coiled, armored telsons (tailplates) during contests over territory. Prior work has shown that telson morphology has high impact resistance. I hypothesized that the behavior of coiling the telson also contributes to impact energy dissipation. By measuring impact dynamics from high-speed videos of strikes exchanged during contests between freely moving animals, I found that approximately 20% more impact energy was dissipated by the telson as compared with findings from a prior study that focused solely on morphology. This increase is likely due to behavior: because the telson is lifted off the substrate, the entire body flexes after contact, dissipating more energy than exoskeletal morphology does on its own. While variation in the degree of telson coil did not affect energy dissipation, proportionally more energy was dissipated from higher velocity strikes and from strikes from more massive appendages. Overall, these findings show that analysis of both behavior and morphology is crucial to understanding impact resistance, and suggest future research on the evolution of structure and function under the selective pressure of biological impacts.

Restitution versus repatriation: Terminology and concepts matter.

INTRODUCTION: Through museum collecting practice, the deceased, possessions, plants and animals were turned into objects, removed from their communities and places of origin, and were segregated and divided into museum classificatory systems. In the decolonial work of embarking upon purposeful and proactive acts of return, the terms "repatriation" and "restitution" have often been used interchangeably. OBJECTIVE: To assess the terminological differences between repatriation and restitution. METHODS: Here, we critically discuss the politics of these terms and present an argument for restitution as restitutionary work. RESULTS: Repatriation refers to the legal, administrative and logistical matters of returning across national borders. However, restitution is a preferred concept highlighting deeper meanings of return to the proper owner, with restitutionary work being time-consuming, emotional, often painful, enriching acts of restoration, and transitional justice. Restitution is about the embodiment and empowerment of choice over all aspects of the return. CONCLUSION: Here, we argue that terminology matters. While restitution may involve repatriation, repatriation is not a substitute for acts of restoration embodied in restitutionary work.

The electrical restitution of the non-propagated cardiac ventricular action potential.

Sudden changes in pacing cycle length are frequently associated with repolarization abnormalities initiating cardiac arrhythmias, and physiologists have long been interested in measuring the likelihood of these events before their manifestation. A marker of repolarization stability has been found in the electrical restitution (ER), the response of the ventricular action potential duration to a pre- or post-mature stimulation, graphically represented by the so-called ER curve. According to the restitution hypothesis (ERH), the slope of this curve provides a quantitative discrimination between stable repolarization and proneness to arrhythmias. ER has been studied at the body surface, whole organ, and tissue level, and ERH has soon become a key reference point in theoretical, clinical, and pharmacological studies concerning arrhythmia development, and, despite criticisms, it is still widely adopted. The ionic mechanism of ER and cellular applications of ERH are covered in the present review. The main criticism on ERH concerns its dependence from the way ER is measured. Over the years, in fact, several different experimental protocols have been established to measure ER, which are also described in this article. In reviewing the state-of-the art on cardiac cellular ER, I have introduced a notation specifying protocols and graphical representations, with the aim of unifying a sometime confusing nomenclature, and providing a physiological tool, better defined in its scope and limitations, to meet the growing expectations of clinical and pharmacological research.

Journey for a cure: Illness narratives of obstetric fistula survivors in North Central Nigeria.

Obstetric fistula is a life transforming event resulting in embodied biographical disruption. Survivors suffer myriad long-term physical and emotional consequences. This paper is an account of a narrative inquiry, conducted with 15 fistula survivors in North-central, Nigeria, who described how their identities had been transformed by their condition. A narrative therapeutic approach, using Frank's 'chaos, restitution and quest' typology, was used to map their recovery narratives. 'Chaos', described by Frank as the opposite of restitution, dominated, with women losing hope of recovery. Women's shift towards 'restitution' began with treatment, but inadequate health-care access often delayed this process. In their quest narratives, women's life and identify changes enabled them to derive meaning from their experience of obstetric fistula within the context of their own lives. The findings highlight socio-structural factors raising the risk of obstetric fistula, which in turn causes biographical disruption and hampers sufferers' treatment and recovery. Rehabilitation should include income-generating skills to bring succour to survivors, particularly those whose incontinence persists after repairs.

Enteric glial cell network function is required for epithelial barrier restitution following intestinal ischemic injury in the early postnatal period.

Ischemic damage to the intestinal epithelial barrier, such as in necrotizing enterocolitis or small intestinal volvulus, is associated with higher mortality rates in younger patients. We have recently reported a powerful pig model to investigate these age-dependent outcomes in which mucosal barrier restitution is strikingly absent in neonates but can be rescued by direct application of homogenized mucosa from older, juvenile pigs by a yet-undefined mechanism. Within the mucosa, a postnatally developing network of enteric glial cells (EGCs) is gaining recognition as a key regulator of the mucosal barrier. Therefore, we hypothesized that the developing EGC network may play an important role in coordinating intestinal barrier repair in neonates. Neonatal and juvenile jejunal mucosa recovering from surgically induced intestinal ischemia was visualized by scanning electron microscopy and the transcriptomic phenotypes were assessed by bulk RNA sequencing. EGC network density and glial activity were examined by Gene Set Enrichment Analysis, three-dimensional (3-D) volume imaging, and Western blot and its function in regulating epithelial restitution was assessed ex vivo in Ussing chamber using the glia-specific inhibitor fluoroacetate (FA), and in vitro by coculture assay. Here we refine and elaborate our translational model, confirming a neonatal phenotype characterized by a complete lack of coordinated reparative signaling in the mucosal microenvironment. Furthermore, we report important evidence that the subepithelial EGC network changes significantly over the early postnatal period and demonstrate that the proximity of a specific functional population of EGC to wounded intestinal epithelium contributes to intestinal barrier restitution following ischemic injury.NEW & NOTEWORTHY This study refines a powerful translational pig model, defining an age-dependent relationship between enteric glia and the intestinal epithelium during intestinal ischemic injury and confirming an important role for enteric glial cell (EGC) activity in driving mucosal barrier restitution. This study suggests that targeting the enteric glial network could lead to novel interventions to improve recovery from intestinal injury in neonatal patients.

Autonomic neuro-cardiac profile of electrical, structural and neuronal remodeling in myocardial infarction-induced heart failure.

Aims: Heart failure is a clinical syndrome typified by abnormal autonomic tone, impaired ventricular function, and increased arrhythmic vulnerability. This study aims to examine electrophysiological, structural and neuronal remodeling following myocardial infarction in a rabbit heart failure model to establish its neuro-cardiac profile. Methods and results: Weight-matched adult male New Zealand White rabbits (3.2 ± 0.1 kg, n = 25) were randomized to have coronary ligation surgeries (HF group, n = 13) or sham procedures (SHM group, n = 12). Transthoracic echocardiography was performed six weeks post-operatively. On week 8, dual-innervated Langendorff-perfused heart preparations were set up for terminal experiments. Seventeen hearts (HF group, n = 10) underwent ex-vivo cardiac MRI. Twenty-two hearts (HF group, n = 7) were examined histologically. Electrical remodeling and abnormal autonomic profile were evident in HF rabbits with exaggerated sympathetic and attenuated vagal effect on ventricular fibrillation threshold, ventricular refractoriness and restitution curves, in addition to increased spatial restitution dispersion. Histologically, there was significant neuronal enlargement at the heart hila and conus arteriosus in HF. Structural remodeling was characterized by quantifiable myocardial scarring, enlarged left ventricles, altered ventricular geometry and impaired contractility. Conclusion: In an infarct-induced rabbit heart failure model, extensive structural, neuronal and electrophysiological remodeling in conjunction with abnormal autonomic profile provide substrates for ventricular arrhythmias.

Placebo effect after visual restitution training: no eye-tracking controlled perimetric improvement after visual border stimulation in late subacute and chronic visual field defects after stroke.

Introduction: A significant number of Restitution Training (RT) paradigms claim to ameliorate visual field loss after stroke by re-activating neuronal connections in the residual visual cortex due to repeated bright light-stimulation at the border of the blind and intact fields. However, the effectiveness of RT has been considered controversial both in science and clinical practice for years. The main points of the controversy are (1) the reliability of perimetric results which may be affected by compensatory eye movements and (2) heterogeneous samples consisting of patients with visual field defects and/or visuospatial neglect. Methods: By means of our newly developed and validated Virtual Reality goggles Salzburg Visual Field Trainer (SVFT) 16 stroke patients performed RT on a regular basis for 5 months. By means of our newly developed and validated Eye Tracking Based Visual Field Analysis (EFA), we conducted a first-time full eye-movement-controlled perimetric pre-post intervention study. Additionally, patients subjectively rated the size of their intact visual field. Results: Analysis showed that patients' mean self-assessment of their subjective visual field size indicated statistically significant improvement while, in contrast, objective eye tracking controlled perimetric results revealed no statistically significant effect. Discussion: Bright-light detection RT at the blind-field border solely induced a placebo effect and did not lead to training-induced neuroplasticity in the visual cortex of the type needed to ameliorate the visual field size of stroke patients.

Asynapsis and meiotic restitution in tomato male meiosis induced by heat stress.

Susceptibility of the reproductive system to temperature fluctuations is a recurrent problem for crop production under a changing climate. The damage is complex as multiple processes in male and female gamete formation are affected, but in general, particularly pollen production is impaired. Here, the impact of short periods of elevated temperature on male meiosis of tomato (Solanum lycopersicon L.) is reported. Meiocytes in early stage flower buds exposed to heat stress (>35°C) exhibit impaired homolog synapsis resulting in partial to complete omission of chiasmata formation. In the absence of chiasmata, univalents segregate randomly developing unbalanced tetrads and polyads resulting in aneuploid spores. However, most heat-stressed meiotic buds primarily contain balanced dyads, indicating a propensity to execute meiotic restitution. With most meiocytes exhibiting a complete loss of chiasma formation and concomitantly showing a mitotic-like division, heat stress triggers first division restitution resulting in clonal spores. These findings corroborate with the plasticity of male meiosis under heat and establish a natural route for the induction of sexual polyploidization in plants and the engineering of clonal seed.

Divergent roles of estrogen receptor subtypes in regulating estrogen-modulated colonic ion transports and epithelial repair.

Although it was described previously for estrogen (E2) regulation of intestinal epithelial Cl- and HCO3- secretion in sex difference, almost nothing is known about the roles of estrogen receptor (ER) subtypes in regulating E2-modulated epithelial ion transports and epithelial restitution. Here, we aimed to investigate ERα and ERß subtypes in the regulation of E2-modulated colonic epithelial HCO3- and Cl- secretion and epithelial restitution. Through physiological and biochemical studies, in combination of genetic knockdown, we showed that ERα attenuated female colonic Cl- secretion but promoted Ca2+-dependent HCO3- secretion via store-operated calcium entry (SOCE) mechanism in mice. However, ERß attenuated HCO3- secretion by inhibiting Ca2+via the SOCE and inhibiting cAMP via protein kinases. Moreover, ERα but not ERß promoted epithelial cell restitution via SOCE/Ca2+ signaling. ERα also enhanced cyclin D1, proliferating cell nuclear antigen, and ß-catenin expression in normal human colonic epithelial cells. All ERα-mediated biological effects could be attenuated by its selective antagonist and genetic knockdown. Finally, both ERα and ERß were expressed in human colonic epithelial cells and mouse colonic tissues. We therefore conclude that E2 modulates complex colonic epithelial HCO3- and Cl- secretion via ER subtype-dependent mechanisms and that ERα is specifically responsible for colonic epithelial regeneration. This study provides novel insights into the molecular mechanisms of how ERα and ERß subtypes orchestrate functional homeostasis of normal colonic epithelial cells.

Responsiveness of the Reaching Performance Scale for Stroke.

OBJECTIVE: The objective of the study was to estimate the internal and external responsiveness of the Reaching Performance Scale for Stroke (RPSS) in individuals with stroke. DESIGN: Retrospective analysis of data from 4 randomized controlled trials. SETTING: Recruitment locations spanning rehabilitation centers and hospitals in Canada, Italy, Argentina, Peru, and Thailand. PARTICIPANTS: Data from 567 participants (acute to chronic stroke; N=567) were available. INTERVENTIONS: All 4 studies involved training using virtual reality for upper limb rehabilitation. MAIN OUTCOME MEASURES: RPSS and upper extremity Fugl-Meyer Assessment (FMA-UE) scores. Responsiveness was quantified for all data and across different stages of stroke. Internal responsiveness of the RPSS was quantified as effect-sizes calculated using post and preintervention change data. External responsiveness was quantified using orthogonal regressions between FMA-UE and RPSS scores. The area under the Receiver Operating Characteristic curve (AUC) was quantified based on the ability of RPSS scores to detect change above FMA-UE minimal clinically important different values across different stages of stroke. RESULTS: The RPSS had high internal responsiveness overall and across the acute or subacute and chronic stages of stroke. For external responsiveness, orthogonal regression analyses indicated that change in FMA-UE scores had positive moderate correlations with both RPSS Close and Far Target scores for all data and across the acute or subacute and chronic stages of stroke (0.6

Dynamics of differentiated-renal epithelial cell monolayer after calcium oxalate injury: The role of cyclooxygenase-2.

AIMS: Calcium oxalate (Oxa), constituent of most common kidney stones, damages renal tubular epithelial cells leading to kidney disease. Most in vitro studies designed to evaluate how Oxa exerts its harmful effects were performed in proliferative or confluent non-differentiated renal epithelial cultures; none of them considered physiological hyperosmolarity of renal medullary interstitium. Cyclooxygenase 2 (COX2) has been associated to Oxa deleterious actions; however, up to now, it is not clear how COX2 acts. In this work, we proposed an in vitro experimental system resembling renal differentiated-epithelial cells that compose medullary tubular structures which were grown and maintained in a physiological hyperosmolar environment and evaluated whether COX2 â†’ PGE2 axis (COX2 considered a cytoprotective protein for renal cells) induces Oxa damage or epithelial restitution. MAIN METHODS: MDCK cells were differentiated with NaCl hyperosmolar medium for 72 h where cells acquired the typical apical and basolateral membrane domains and a primary cilium. Then, cultures were treated with 1.5 mM Oxa for 24, 48, and 72 h to evaluate epithelial monolayer restitution dynamics and COX2-PGE2 effect. KEY FINDINGS: Oxa completely turned the differentiated phenotype into mesenchymal one (epithelial-mesenchymal transition). Such effect was partially and totally reverted after 48 and 72 h, respectively. Oxa damage was even deeper when COX2 was blocked by NS398. PGE2 addition restituted the differentiated-epithelial phenotype in a time and concentration dependence. SIGNIFICANCE: This work presents an experimental system that approaches in vitro to in vivo renal epithelial studies and, more important, warns about NSAIDS use in patients suffering from kidney stones.

MEDICAL CONTRACTS WITH CONDITIONS CONTRARY TO PUBLIC POLICY.

OBJECTIVE: The aim: To reveal some features of medical contracts with conditions contrary to public policy. PATIENTS AND METHODS: Materials and methods: The study is based on the statutory acts of countries of European Union. The author also uses acts of international law in the field of medical services, the law and cases court practice of EU. CONCLUSION: Conclusions: The sphere of medical services objectively requires increased control by the state. There are various legal mechanisms for ensuring the rights of the patient and the proper level of medicine. It is important to invalidate the unfair terms of medical contracts, compensation for losses and moral damage. These remedies are obtained through judicial protection and, in some cases, through other jurisdictional means. It is important to implement European standards in national legislation.

Climate Justice and the Duty of Restitution.

Much of the climate justice discussion revolves around how the remaining carbon budget should be globally allocated. Some authors defend the unjust enrichment interpretation of the beneficiary pays principle (BPP). According to this principle, those states unjustly enriched from historical emissions should pay. I argue that if the BPP is to be constructed along the lines of the unjust enrichment doctrine, countervailing reasons that might be able to block the existence of a duty of restitution should be assessed. One might think that the duty to provide restitution no longer has moral weight if many benefits were already consumed, if the particular benefits obtained from historical emissions cannot be transferred from one country to another, or if present members of developed countries framed their life plans based upon the expectation of continued possession of those benefits. I show that none of these reasons negate the duty to provide restitution.

Intra-Individual Comparison of Sinus and Ectopic Beats Probing the Ventricular Gradient's Activation Dependence.

Wilson assumed that the ventricular gradient (VG) is independent of the ventricular activation order. This paradigm has often been refuted and was never convincingly corroborated. We sought to validate Wilson's concept by intra-individual comparison of the VG of sinus beats and ectopic beats, thus assessing the effects of both altered ventricular conduction (caused by the ectopic focus) and restitution (caused by ectopic prematurity). We studied standard diagnostic ECGs of 118 patients with accidental extrasystoles: normally conducted supraventricular ectopic beats (SN, N = 6) and aberrantly conducted supraventricular ectopic beats (SA, N = 20) or ventricular ectopic beats (V, N = 92). In each patient, we computed the VG vectors of the predominant beat, VGp→, of the ectopic beat, VGe→, and of the VG difference vector, ΔVGep→, and compared their sizes. VGe→ of the SA and V ectopic beats were significantly larger than VGp→ (53.7 ± 25.0 vs. 47.8 ± 24.6 mV∙ms, respectively; p < 0.001). ΔVGep→ were three times larger than the difference of VGe→ and VGp→ (19.94 ± 9.76 vs. 5.94 mV∙ms, respectively), demonstrating differences in the VGp→ and VGe→ spatial directions. The amount of ectopic prematurity was not correlated with ΔVGep→, although the larger VG difference vectors were observed for the more premature (<80%) extrasystoles. Electrical restitution properties and electrotonic interactions likely explain our findings. We conclude that the concept of a conduction-independent VG should be tested at equal heart rates and without including premature extrasystoles.

Stories of restitution: Family experiences of diagnosis and help-seeking for a child with cerebral palsy.

BACKGROUND: The experience of living with children with CP is dominated by the voice of the mother while others are rarely reported. Incorporation of the voices of other family members is important for a holistic understanding. METHODS: Drawing on the philosophical perspectives of pragmatism, generic qualitative methodology, and Frank's narratives, this article highlights how restitution was constructed by 30 family members. FINDINGS: They constructed restitution by hoping for a cure through either biomedical and/or alternative models of treatment, followed by intransitive and transcendent restitution. DISCUSSION: This appears to be the first time that restitution has been extended to families living with children with chronic illnesses. APPLICATION TO PRACTICE: This would mean that paediatric nursing professionals and other health professionals dealing with family members living with children with CP could attend to their stories in an open and focused manner to honour and validate their stories as well as their experiences.

The enigmatic roles of epithelial gasdermin B: Recent discoveries and controversies.

Gasdermin B (GSDMB) belongs to a family of structurally related proteins [(i.e., gasdermins (GSDMs)]. It distinguishes itself from other members by the lack of autoinhibition but clear bioactivity of its full-length form, its preference to bind to phosphatidylinositol phosphates and sulfatides, and the ability to promote both lytic and nonlytic cellular functions. It is the only gasdermin that lacks a mouse ortholog, making in vivo mechanistic studies challenging to perform. GSDMB is abundantly expressed in epithelial cells lining organs that directly interface with the external environment, such as the gastrointestinal tract, with emerging evidence supporting its role in enteric infections, inflammatory bowel disease (IBD), and colorectal cancer. This review discusses the unique features of GSDMB among other gasdermin family members and controversies surrounding GSDMB-dependent mammalian inflammatory cell death (i.e., pyroptosis), including recent discoveries revealing both lytic and nonlytic functions of epithelial-derived GSDMB, particularly during gut health and disease.