Extremal structure in ultrapowers of Banach spaces

Given a bounded convex subset C of a Banach space X and a free ultrafilter U, we study which points (xi)U are extreme points of the ultrapower CU in XU. In general, we obtain that when { xi} is made of extreme points (respectively denting points, strongly exposed points) and they satisfy some kind of uniformity, then (xi)U is an extreme point (respectively denting point, strongly exposed point) of CU. We also show that every extreme point of CU is strongly extreme, and that every point exposed by a functional in (X*)U is strongly exposed, provided that U is a countably incomplete ultrafilter. Finally, we analyse the extremal structure of CU in the case that C is a super weakly compact or uniformly convex set. © 2022, The Author(s)

Presbyvestibulopathy, Comorbidities, and Perception of Disability: A Cross-Sectional Study

Objective: To assess the perception of disability in patients with presbyvestibulopathy and to determine the factors (demographic, balance test scores, and comorbidities) that determine higher levels of disability. Material and Methods: This was a cross-sectional study conducted in a tertiary university hospital. There were 103 patients who fulfilled the diagnostic criteria for presbyvestibulopathy and were included. Dizziness Handicap Inventory (DHI) score was the main variable used to quantify disability. Influence on DHI score, sex, age, time of evolution, equilibriometric parameters (posturographic scores and timed up and go test), history of falls, comorbidities (high blood pressure, diabetes, and dyslipidemia), psychotropic drug use, tobacco or alcohol use, living environment (urban or rural), and active lifestyle were analyzed. Results: Most of the DHI scores showed a moderate (46 patients, 44.7%) or severe (39 participants, 37.9%) handicap. DHI scores were higher in women (59.8 vs. 36.1, p < 0.001), patients with obesity (58.92 vs. 48.68; p = 0.019), benzodiazepine (59.9 vs. 49.1, p = 0.008) or other psychotropic drug (60.7 vs. 49.2, p = 0.017) users, and fallers (57.1 vs. 47.3, p = 0.048). There was also a significant positive correlation between DHI score, time (Rho coefficient: 0.371, p < 0.001), and steps (Rho coefficient: 0.284, p = 0.004) used in the TUG and with the short FES-I questionnaire (a shortened version of the Falls Efficacy Scale-International) score (Rho coefficient: 0.695, p < 0.001). DHI scores were lower in alcohol consumers than in non-drinkers (46.6 vs. 56, p = 0.048). No significant correlation was found between DHI scores and age, time of evolution, posturographic scores, comorbidities, environment (rural or urban), or active lifestyle. Conclusion: Most patients with presbyvestibulopathy show an important subjective perception of disability in relation to their symptoms. This perception is substantially higher in women than in men. The most influential factors are difficulties in walking, fear of falling, and obesity. Unique Identifier: NCT03034655, www.clinicaltrials.gov

Modified Timed Up and Go Test for Tendency to Fall and Balance Assessment in Elderly Patients With Gait Instability

Objective: To compare the results from the modified Timed Up and Go Test (TUG) with posturographic variables, the subjective perception of disability due to gait instability, and the number of falls in a sample of the elderly population with imbalance, to confirm that the TUG Test is a useful clinical instrument to assess the tendency to fall in individuals of this age group. Materials and Methods: Cross-sectional study conducted in a tertiary university hospital, in 174 people aged 65 years or older with gait instability. Modified TUG Test was performed; time, step count and the need for support during the test were the analyzed variables. They were compared with the number of falls, Computerized Dynamic Posturography scores, and questionnaires scores (Dizziness Handicap Inventory and a shortened version of the Falls Efficacy Scale-International). Results: The average time to complete the TUG Test was 21.24 +/- 8.18 s, and the average step count was 27.36 +/- 7.93. One hundred two patients (58.6%) required no support to complete the test, whereas the other 72 (41.4%) used supports. The time taken to complete the Test was significantly related with having or not having fallen in the previous year, with the scores of the questionnaires, and with various parameters of dynamic posturography. A higher percentage of patients who took more than 15 s had fallen in the previous year than those who took up to 15 s to complete the test [P = 0.012; OR = 2.378; 95% CI (1.183, 4.780)]. No significant correlation was found between the step count and the number of falls in the previous year, with falling during the test or not, or with being a single or a frequent faller. No relation was found between the need for supports and the number of falls, with having or not having fallen in the previous year, or with being a single or frequent faller. Conclusion: The modified TUG Test is in relation with the presence or absence of falls. Time is the essential parameter for analyzing the risk of falling and the 15-s threshold is a good value to differentiate elderly patients at high risk of falling. Unique Identifier: NCT03034655, www.clinicaltrials.gov

Detection of porcine reproductive and respiratory syndrome virus (PRRSV)-specific IgM-IgA in oral fluid samples reveals PRRSV infection in the presence of maternal antibody

The ontogeny of PRRSV antibody in oral fluids has been described using isotype-specific ELISAs. Mirroring the serum response, IgM appears in oral fluid by 7 days post inoculation (DPI), IgA after 7 DPI, and IgG by 9 to 10 DPI. Commercial PRRSV ELISAs target the detection of IgG because the higher concentration of IgG relative to other isotypes provides the best diagnostic discrimination. Oral fluids are increasingly used for PRRSV surveillance in commercial herds, but in younger pigs, a positive ELISA result may be due either to maternal antibody or to antibody produced by the pigs in response to infection. To address this issue, a combined IgM-IgA PRRSV oral fluid ELISA was developed and evaluated for its capacity to detect pig-derived PRRSV antibody in the presence of maternal antibody. Two longitudinal studies were conducted. In Study 1 (modified-live PRRS vaccinated pigs), testing of individual pig oral fluid samples by isotype-specific ELISAs demonstrated that the combined IgM-IgA PRRSV ELISA provided better discrimination than individual IgM or IgA ELISAs. In Study 2 (field data), testing of pen-based oral fluid samples confirmed the findings in Study 1 and established that the IgM-IgA ELISA was able to detect antibody produced by pigs in response to wild-type PRRSV infection, despite the presence of maternal IgG. Overall, the combined PRRSV IgM-IgA oral fluid ELISA described in this study is a potential tool for PRRSV surveillance, particularly in populations of growing pigs originating from PRRSV-positive or vaccinated breeding herds

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery

An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks

Pch2 Acts through Xrs2 and Tel1/ATM to Modulate Interhomolog Bias and Checkpoint Function during Meiosis

Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks (DSBs) to form crossovers. Repair is biased toward using the homolog as a substrate rather than the sister chromatid. Pch2 is a conserved member of the AAA+-ATPase family of proteins and is implicated in a wide range of meiosis-specific processes including the recombination checkpoint, maturation of the chromosome axis, crossover control, and synapsis. We demonstrate a role for Pch2 in promoting and regulating interhomolog bias and the meiotic recombination checkpoint in response to unprocessed DSBs through the activation of axial proteins Hop1 and Mek1 in budding yeast. We show that Pch2 physically interacts with the putative BRCT repeats in the N-terminal region of Xrs2, a member of the MRX complex that acts at sites of unprocessed DSBs. Pch2, Xrs2, and the ATM ortholog Tel1 function in the same pathway leading to the phosphorylation of Hop1, independent of Rad17 and the ATR ortholog Mec1, which respond to the presence of single-stranded DNA. An N-terminal deletion of Xrs2 recapitulates the pch2Δ phenotypes for signaling unresected breaks. We propose that interaction with Xrs2 may enable Pch2 to remodel chromosome structure adjacent to the site of a DSB and thereby promote accessibility of Hop1 to the Tel1 kinase. In addition, Xrs2, like Pch2, is required for checkpoint-mediated delay conferred by the failure to synapse chromosomes