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A bstract We propose worldsheet formulae for wavefunction coefficients of the massive non-linear sigma model (NLSM), scalar Dirac-Born-Infeld (DBI), and special Galileon (sGal) theories in de Sitter momentum space in terms of the recently proposed cosmological scattering equations constructed from conformal generators in the future boundary. The four-point integrands are assembled from simple building blocks and we identify a double copy prescription mapping the NLSM wavefunction coefficient to the DBI and sGal wavefunction coefficients, including mass deformations and curvature corrections. Finally, we compute the soft limits of these wavefunction coefficients and find that they can be written in terms of boundary conformal generators acting on contact diagrams.

Noble gas molecules have not hitherto been detected in space. From spectra obtained with the Herschel Space Observatory, we report the detection of emission in the 617.5- and 1234.6-gigahertz J = 1-0 and 2-1 rotational lines of ³⁶ArH⁺ at several positions in the Crab Nebula, a supernova remnant known to contain both molecular hydrogen and regions of enhanced ionized argon emission. Argon-36 is believed to have originated from explosive nucleosynthesis in massive stars during core-collapse supernova events. Its detection in the Crab Nebula, the product of such a supernova event, confirms this expectation. The likely excitation mechanism for the observed ³⁶ArH⁺ emission lines is electron collisions in partially ionized regions with electron densities of a few hundred per centimeter cubed.

The American grape berry moth (GBM), Paralobesia viteana (Clemens) (Lepidoptera: Tortricidae) is an economically important pest of grapes. The larvae of this insect burrow inside the fruit upon hatching, consuming, and contaminating grapes and clusters. Current GBM management relies on pesticide applications, which do not offer complete protection due to the cryptic behavior of the larvae and asynchrony in egg-laying, highlighting the need to develop new management strategies. In this study, we identified GBM larval parasitoids in commercial vineyards and quantified their parasitism rates. Parasitoid samplings were conducted biweekly in six conventionally managed ‘Concord’ vineyards in Erie County, Pennsylvania, during the 2023 and 2024 growing seasons. GBM-infested samples were monitored daily to track the emergence of both parasitoids and GBM, enabling the calculation of parasitism rates. We identified eight parasitoid species: Enytus obliteratus (Cresson) (Hymenoptera: Ichneumonidae), Campoplex tortricidis (Cushman) (Hymenoptera: Ichneumonidae), Scambus spp. Hartig (Hymenoptera: Ichneumonidae), Glypta cf . depressa Dasch, Glypta cf. ohioensis Dasch, and Glypta cf. ignota Dasch (Hymenoptera: Ichneumonidae); Bracon variabilis (Provancher) (Hymenoptera: Braconidae), and Goniozus fratellus Evans (Hymenoptera: Bethylidae) preying on GBM larvae. From these, B. variabilis , E. obliteratus , and G. fratellus were the most abundant. We also designed a graphic taxonomic key to facilitate the identification of these species. The parasitoid abundance differed over the growing season but was greatest in early August, reaching parasitism rates of up to 39% and 52.1% in 2023 and 2024, respectively. Our results demonstrate that GBM has several larval parasitoids that help reduce its populations in commercial vineyards. This research represents a first step toward our understanding of the GBM native natural enemies present in the Lake Erie Region and their potential use in pest management programs.

Separation of eukaryotic sister chromatids during the cell cycle is timed by the spindle assembly checkpoint (SAC) and ultimately triggered when separase cleaves cohesion-mediating cohesin 1 – 3 . Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin 1 . In the absence of securin, mammalian chromosomes still segregate on schedule, but it is unclear how separase is regulated under these conditions 4 , 5 . Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma 6 , 7 , is turned into a separase inhibitor upon association with SAC-activated MAD2. SGO2–MAD2 can functionally replace securin and sequesters most separase in securin-knockout cells. Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. Similar to securin 8 , 9 , SGO2 is a competitive inhibitor that uses a pseudo-substrate sequence to block the active site of separase. APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 in conjunction with the MAD2-specific adaptor p31 comet liberate separase from SGO2–MAD2 in vitro. The latter mechanism facilitates a considerable degree of sister chromatid separation in securin-knockout cells that lack APC/C activity. Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC. Shugoshin and MAD2 regulate separase-mediated chromosome separation during mitosis, in parallel to a previously identified mechanism involving the anaphase inhibitor securin.

Genetic progress for yield has been assessed globally in the semi-arid wheat yield trials (SAWYTs) of the International Maize and Wheat Improvement Center (CIMMYT) over a 17-yr period. Grain yield expressed as a percentage of the long-term check cultivar Dharwar Dry has increased at approximately 1% yr(−1) between 1994 and 2010. In real terms, yield has been increased at a rate of 31 kg ha(−1) yr(−1). The rate of yield increase in high-yielding environments was twice that of low-yielding environments. The average yield of low-yielding sites are significantly correlated with the average yield of high-yielding sites (p < 0.001), and many of the highest-yielding lines of the various SAWYT performed well at both low- and high-yielding sites. The key parents Attila and Pastor were consistently high yielding in several of the early SAWYT. In later trials their derivatives were also high yielding. The line Vorobey, developed by crossing Pastor with a synthetic derivative, showed outstanding yield in SAWYT 11 and 12. The performance of CIMMYT lines compared to local check cultivars was relatively stable over time. A success rate was calculated as the ratio of the number of sites where a given line is superior to the local check divided by the total number of sites. On average, the success rate of the 10% best lines was 61% in low-yielding sites and 62% in high-yielding sites.

Background:Neurosarcoidosis is a rare and severe manifestation, affecting between 3% and 15% of patients with sarcoidosis. The cornerstone of treatment is corticosteroid therapy. Several drug are available in the therapeutic arsenal: Cyclophosphamide (CYC), anti-TNFα biotherapy, conventional immunosuppressants, in particular Methotrexate (MTX). However, the current therapeutic strategy is not clearly defined.Objectives:The primary endpoint was relapse, defined as an increase of at least 1 point of the Extrapulmonary Organ Severity Tool (ePOST) score after initial improvement. Secondary endpoints included therapeutic response, cortisone sparing and adverse events.Methods:We conducted a French multicenter retrospective study. Patients with definite or probable neurosarcoidosis (histologically proven sarcoidosis and presence of a neurological localization) were divided into 3 groups according to the treatment received: CYC group, infliximab (IFX) group and MTX group.Results:403 cases were screened, 40 patients (11 treated with CYC, 8 treated with IFX and 21 treated with MTX) were included, predominantly male (53%) with a median age of 43 years. Preferred neurological locations were the meninges (50%), cranial nerves (52%) and encephalon (55%). Twelve patients suffered a relapse: 7 (58%) on CYC, 1 (8%) on IFX and 4 (33%) on MTX. The overall relapse-free survival rate was 97.5% at 6 months, 85% at 1 year and 76% at 2 years. Relapse-free survival medians differed statistically between the 3 groups (p = 0.02), with a median survival for the CYC group of 36 months, while median survival for the IFX and MTX groups could not be calculated due to lack of occurrence of the relapse event. Relapse was more frequent in the CYC subgroup (Odds ratio = 7.8, CI95 [1.4-53], p = 0.007). Relapse was associated with cerebral location (p = 0.03), multi-system involvement of sarcoidosis (p = 0.03) and young age (p = 0.02). Thirty-six patients (90%) were classified as responders at 12 months of treatment, reflected by a decrease in the initial ePOST score from 3 [3-4] to 1 [0-2]. There was no statistical difference in therapeutic response between the 3 groups. A significant decrease in corticosteroid therapy was observed in all 3 treatment groups, with no statistical difference between them. Infections were more frequent with CYC (p = 0.03) and rash were associated with IFX (p=0.02).Conclusion:Our study shows that Infliximab and Methotrexate are two effective therapeutic options for relapse prevention in neurosarcoidosis. Today, Cyclophosphamide, the historic treatment for severe sarcoidosis, appears to be a third-line choice, given the risk of relapse and its tolerability profileREFERENCES:[1] Sève P, Pacheco Y, Durupt F, Jamilloux Y, Gerfaud-Valentin M, Isaac S, et al. Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis. Cells. 31 mars 2021;10(4):766.[2] Kidd DP. Neurosarcoidosis: clinical manifestations, investigation and treatment. Practical Neurology. 1 mai 2020;20(3):199-212.[3] Stern BJ, Royal W III, Gelfand JM, Clifford DB, Tavee J, Pawate S, et al. Definition and Consensus Diagnostic Criteria for Neurosarcoidosis: From the Neurosarcoidosis Consortium Consensus Group. JAMA Neurology. 1 déc 2018;75(12):1546-53.[4] Joubert B, Chapelon-Abric C, Biard L, Saadoun D, Demeret S, Dormont D, et al. Association of Prognostic Factors and Immunosuppressive Treatment With Long-term Outcomes in Neurosarcoidosis. JAMA Neurol. nov 2017;74(11):1336-44.[5] Bitoun S, Bouvry D, Borie R, Mahevas M, Sacre K, Haroche J, et al. Treatment of neurosarcoidosis: A comparative study of methotrexate and mycophenolate mofetil. Neurology. 13 déc 2016;87(24):2517-21.[6] Fritz D, Timmermans WMC, van Laar JAM, van Hagen PM, Siepman TAM, van de Beek D, et al. Infliximab treatment in pathology-confirmed neurosarcoidosis. Neurol Neuroimmunol Neuroinflamm. sept 2020;7(5):e847.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background: Solar water disinfection (SODIS) is an appropriate technology for household treatment of drinking water in low-to-middle-income communities, as it is effective, low cost and easy to use. Nevertheless, uptake is low due partially to the burden of using small volume polyethylene terephthalate bottles (1.5–2 L). A major challenge is to develop a low-cost transparent container for disinfecting larger volumes of water. (2) Methods: This study examines the capability of transparent polypropylene (PP) buckets of 5 L- and 20 L- volume as SODIS containers using three waterborne pathogen indicators: Escherichia coli, MS2-phage and Cryptosporidium parvum. (3) Results: Similar inactivation kinetics were observed under natural sunlight for the inactivation of all three organisms in well water using 5 L- and 20 L-buckets compared to 1.5 L-polyethylene-terephthalate (PET) bottles. The PP materials were exposed to natural and accelerated solar ageing (ISO-16474). UV transmission of the 20 L-buckets remained stable and with physical integrity even after the longest ageing periods (9 months or 900 h of natural or artificial solar UV exposure, respectively). The 5 L-buckets were physically degraded and lost significant UV-transmission, due to the thinner wall compared to the 20 L-bucket. (4) Conclusion: This work demonstrates that the 20 L SODIS bucket technology produces excellent bacterial, viral and protozoan inactivation and is obtained using a simple transparent polypropylene bucket fabricated locally at very low cost ($2.90 USD per unit). The increased bucket volume of 20 L allows for a ten-fold increase in treatment batch volume and can thus more easily provide for the drinking water requirements of most households. The use of buckets in households across low to middle income countries is an already accepted practice.

Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365), 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014) and indoleamine 2,3-dioxygenase (p = 0.012), and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs) between baseline and 3 weeks after start of treatment (p = 0.005). Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with ipilimumab clinical activity. The observed pharmacodynamic changes in gene expression warrant further analysis to determine whether treatment-emergent changes in gene expression may be associated with clinical efficacy. Further studies are required to determine the predictive value of these and other potential biomarkers associated with clinical response to ipilimumab.

Faithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners, allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects the centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover.

Meiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a ‘zipper’-like protein assembly that synapses homologue pairs together and provides the structural framework for processing recombination sites into crossovers. Humans show individual differences in the number of crossovers generated across the genome. Recently, an anonymous gene variant in C14ORF39/SIX6OS1 was identified that influences the recombination rate in humans. Here we show that C14ORF39/SIX6OS1 encodes a component of the central element of the synaptonemal complex. Yeast two-hybrid analysis reveals that SIX6OS1 interacts with the well-established protein synaptonemal complex central element 1 (SYCE1). Mice lacking SIX6OS1 are defective in chromosome synapsis at meiotic prophase I, which provokes an arrest at the pachytene-like stage and results in infertility. In accordance with its role as a modifier of the human recombination rate, SIX6OS1 is essential for the appropriate processing of intermediate recombination nodules before crossover formation. The synaptonemal complex is a meiosis-specific proteinaceous structure that supports homologous chromosome pairs during meiosis. Here, the authors show that SIX6OS1 (of previously unknown function) is part of the synaptonemal complex central element and upon deletion in mice, causes defective chromosome synapsis and infertility.