213476 research outputs found
Sort by
Novel VARS1 variants define new clinical and molecular subtypes of a rare neurodevelopmental syndrome
No full textPURPOSE: We aimed to broaden the understanding of autosomal recessive neurodevelopmental disorders caused by VARS1 by describing new clinical and molecular findings and assessing the predicted structural impact of identified variants. METHODS: We clinically evaluated 13 affected individuals from 10 unrelated families presenting with a neurodevelopmental disorder. We used exome sequencing and cosegregation analyses to identify disease-causing variants, followed by three-dimensional in silico analyses and molecular dynamics simulations to assess the likely functional consequences of both previously reported and novel variants. RESULTS: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability, we identified biallelic disease-causing variants in VARS1. Two variants were predicted to induce premature protein truncation leading to loss of VARS1 function. The remaining 13 detected missense variants were located in the catalytic and aminoacylation domains, and in silico analysis of the affected residues showed that such substitutions can disrupt local protein dynamics, RNA-interaction surfaces, or catalytic geometry, thereby affecting ligand recognition, substrate specificity, and tRNA interaction. CONCLUSION: Together with prior reports, our results provide strong additional evidence supporting VARS1 as a recurrent cause of autosomal recessive neurodevelopmental disorders and expand the known clinical and allelic spectrum. While in silico analyses provide mechanistic plausibility for novel variants, functional studies will be important to confirm variant-specific effects and disease mechanisms
Gender differences in social networks under subsistence changes
No full textSexual selection theory suggests that gendered social strategies are universal outcomes of reproductive competition, yet recent cross-cultural studies show that these strategies are shaped by socio-ecological factors although they remain insufficiently examined. In particular, little is known about how gendered strategies adapt during periods of rapid social and economic changes. To this end, we examine gender differences in scale and composition of ego-networks, guided by two main hypotheses: that gender roles are shaped by (i) market participation, and (ii) post-marital residence pattern. Using data from 1169 married women and men across 14 Tibetan villages undergoing economic and kinship-system transitions, we applied Bayesian multilevel models to analyse core social relationships. Our findings show that, as men increase their participation in market economies, their networks become more kin-centred – strengthening biological kin ties while loosening friend ties – reflecting an instrumental restructuring of social relationships in response to changing economic roles. In contrast, women's networks remain largely unaffected, likely reflecting the persistence of caregiving responsibilities and strong local embeddedness. Post-marital residence patterns impose comparable trade-offs for both sexes: philopatric individuals prioritise biological kin, while affinal kin can effectively substitute for natal relatives when biological kin become less accessible, forming a balanced, bilateral cooperative network that integrates both kin types. This study underscores that women sustain stable and cohesive social ties across socio-economic transitions, while men adapt their networks more flexibly in response to shifting economic roles
Exome-wide association study of suicidal ideation and behaviour has unclear implications
No full textEvaluation of histopathologic changes associated with placentation in a cesarean delivery scar
No full textBACKGROUND: Most cesarean scar ectopic pregnancies fail during the first 2 months of pregnancy, but ongoing cesarean scar ectopic pregnancies are the precursors of placenta accreta spectrum. OBJECTIVE: The aim of this study was to evaluate placentation inside a cesarean scar defect of the lower uterine segment and its relation to development of placenta accreta spectrum. STUDY DESIGN: We reviewed the ultrasound and histopathologic findings of 94 patients diagnosed with a first-trimester cesarean scar ectopic pregnancy including 92 managed by transcervical suction curettage and 2 managed by hysterectomy after failed conservative surgery and of 10 patients with ultrasound signs suggestive of accreta placentation during the second (n=2) and third trimester of pregnancy (n=8), managed by cesarean hysterectomy. The ultrasound features of both groups were compared with general histopathological examination. Cytokeratin 7 immunostaining was used to evaluate the migration pattern of extravillous trophoblast in 13 cases of live cesarean scar ectopic pregnancies after surgical evacuation and samples from 9 hysterectomy specimens with placental tissue in situ. RESULTS: In the cesarean scar ectopic pregnancy group there were 61/92 (65%) with a live pregnancy and 33 (35%) with a failed pregnancy and 2 with prolonged retention of placental tissue that required an emergency secondary hysterectomy due to uncontrollable hemorrhage after transcervical suction curettage. All cesarean scar ectopic pregnancies presented with marked dilatation of the vascular network around the gestational sac and 32 (34%) cases were reported as presenting with abnormally increased vascularity. Anchoring villi directly attached to the decidua were found in only 7 (11.5%) live pregnancies and not in failed pregnancy. Histopathological examination in failed cesarean scar ectopic pregnancies showed signs of villous retention and degeneration including fibrotic and edematous villi and diffuse perivillous fibrin deposition following embryonic demise but no signs of aneuploidy or trophoblastic hyperplasia. Extravillous trophoblast cells arranged in deep confluent sheets or scattered deep inside the decidua below the anchoring villi were observed in 4 cases of live cesarean scar ectopic pregnancies and deep inside the scar area in 2 samples from the hysterectomy specimens. In second trimester placenta accreta spectrum, there was increased subplacental vascularity and intraplacental lacunae in both cases. Extended remodeling of the lower uterine segment and anomalies of the utero- and intraplacental circulation were found on preoperative ultrasound examination in all third-trimester placenta accreta spectrum cases. All samples (n=35) from the accreta area in cesarean hysterectomy specimens showed histological evidence of myometrial thinning, disarray of myofibers and tissue edema. In 28 of these samples, thick fibrinoid depositions between the scar and the villous tissue were found. Immunostaining of accreta areas showed extravillous trophoblast cells deep below the placental basal plate. They reached but did not breach the uterine serosa in any case. CONCLUSION: Accreta placentation is a progressive phenomenon where villi become abnormally attached inside the myometrial scar, requiring surgical removal. While the adherent villi give rise to large numbers of migratory extravillous trophoblast, the placenta does not spontaneously breach the outer layer of the scar even when it bulges outside the normal uterine boundary
Persistent oxygenation of the Mesoproterozoic shallow ocean: evidence from the c. 1.44-billion-year-old Tieling Formation, North China Craton
No full textThe Mesoproterozoic era experienced dynamic variability in atmosphere–ocean oxygen levels. Recent studies suggest that a pulse of oxygenation is recorded in the c. 1.44 Ga Tieling Formation but the duration of this event remains unclear. Here, we report relatively high-resolution carbonate carbon isotope ((Formula presented.) 13C), rare earth element (REE) and I/(Ca + Mg) data from the Tieling Formation at Jixian, North China. The (Formula presented.) 13C values reveal a limited range, mainly between −2 and +1‰, and systematic stratigraphic trends. The lower member of the formation is characterized by manganiferous carbonates with light and middle REE-enriched patterns and relatively high but scattered I/(Ca + Mg) values. We interpret these geochemical signals in terms of the early diagenetic reduction of primary Mn oxides. The upper member, by contrast, exhibits stratigraphic covariation between negative Ce anomalies and I/(Ca + Mg) ratios that we attribute to sea-level change rather than oxygenation. The geochemical data from both lower and upper members support vigorous oxidative Mn cycling, thus suggesting that an oxygenated shallow ocean probably persisted for millions of years in the Mesoproterozoic
Embedding Student Voices in a Mentoring Programme for Underrepresented Student Groups: A Staff-Student Partnership
No full textThe Engineering Coalition Mentoring Programme is an integrated peer and industrial
mentoring scheme, designed for undergraduate engineering students from
underrepresented student groups and disadvantaged socio-economic backgrounds.
The programme was initiated in the academic year 2022-2023 and can support up to
60 students each year. It is a staff-student partnership with students and staff
engaged in equal capacity during the programme design, delivery and leadership,
ensuring that student voice is embedded all though the programme. The peer
mentoring sessions are structured based on student inputs, with focus on wellbeing,
inclusivity and networking, as well as more practical issues related to regular
academic activities such as effectively using assessment feedback and handling
conflicts within the team during group activities. The industrial mentoring sessions
focus on career advancement and securing internships and jobs in a competitive
market. All sessions are mostly held online, with only a few face-to-face events.
Based on students’ feedback, both the peer and industrial mentoring have been
effective for the mentees, enabling them to enhance their professional network and
gain insights from the peer mentors about navigating any barrier faced during their
academic journey. There has been emphasis on appropriate conduct for both
mentors and mentees, for creating a safe space for conversation
Thomas Cranmer's Register: A record of archiepiscopal administration in diocese and province
No full textThomas Cranmer’s Register records turbulent change in England and Wales between 1533 and 1553. The crown abolished Roman jurisdiction, and the first steps towards the creation of a Protestant state were made. As archbishop of Canterbury, Thomas Cranmer was a seminal figure in these developments, and his register is a key Reformation document.
The physical register at Lambeth Palace has been out of reach for many scholars. Paul Ayris’s extraordinary edition makes more of the text available to readers than ever before, with transcriptions and editorial introductions that illuminate the sometimes cryptic sixteeenth-century text. Here, the appointment of Cranmer to Canterbury (at the hands of the papacy) in 1533 is recorded. Commissions and letters reveal how the crown assumed authority over the church and, through Thomas Cromwell as vicegerent in spirituals, supplanted the role of the archbishop as the principal minister of the king’s spiritual jurisdiction. The work suggests a new explanation for the inclusion/exclusion of the stipulation in the 1536 royal Injunctions concerning the Bible in English. Moreover, unpublished records for the diocese of Norwich in 1550 reveal that the order for removing altars in English churches emanated from Thomas Cranmer not, as is usually thought, from the bishop of London, Nicholas Ridley. This edition will be a touchstone reference for global scholars of the Tudor period.
Published in association with the Canterbury and York Societ
Uniform spectral asymptotics for high-contrast periodic media
No full textFor an elliptic operator with high-contrast periodic matrix-inclusion coefficients in Rn, n ≥ 2, we obtain improved results on uniform approximations of
typical Floquet-Bloch eigenvalues in terms of those of an explicit two-scale limit operator. As a result, we obtain not only improved rates for convergence of the spectra
to the limit spectrum displaying band gaps, but also improved uniform estimates for
an explicit asymptotics for the integrated density of states
FEMINISTS VERSUS MONUMENTS? From Protests to Anti-monuments in Mexico City
No full textThis article examines the role of heritage spaces and monuments in the Historic Centre of Mexico City during ongoing feminist mobilizations. Feminists have claimed that the Mexican government is more concerned about protecting monuments and urban heritage than acting to prevent gender‐based violence and femicide. While feminists have demanded actions and solutions from the authorities, some have also sought to distance themselves from the state, utilizing counter‐hegemonic tactics. The research shows how feminist activists have used cultural demonstrations and established alternative memorials to commemorate women who have suffered from violence and crime. These approaches differ from those of other social movements in Mexico. By occupying symbolic historic spaces and, in some cases, damaging monuments, feminists have also established what they call anti‐monumentas. Such tactics reflect how politics, memory and public space continuously intertwine during demonstrations
Hydration State Measurement in Polymer Electrolyte Fuel Cells from Correlated Neutron Imaging and Single-Point Impedance
No full textEffective water management remains a critical challenge for polymer electrolyte fuel cell (PEFC) durability and reliability, necessitating accurate real-time hydration state monitoring. Full-spectrum electrochemical impedance spectroscopy (EIS) struggles to balance diagnostic speed with accuracy, and the linkage between microscopic liquid water distribution and macroscopic EIS parameters remains inadequately resolved. This study introduces a novel method using the 40 Hz single-frequency impedance phase angle, integrated with operando neutron imaging, for non-invasive, rapid hydration state assessment in operating PEFCs. The methodology was validated across three operational modes (Drying, Normal, Flooding). While conventional parameters like high-frequency resistance (HFR) effectively identified membrane dehydration and low-frequency resistance (LFR) detected cathodic flooding, neutron imaging revealed that neither HFR nor LFR consistently correlated with total liquid water mass across all states. Specifically, LFR showed strong water mass correlation in Drying mode (r = 0.98) but declined significantly in Normal (r = 0.76) and Flooding (r = 0.39) modes. In contrast, the 40 Hz phase angle maintained strong positive correlations (r ≥ 0.89) universally across all hydration states and operational regimes. Crucially, terminal voltage remained stable despite substantial hydration fluctuations during Normal mode operation (e.g., water mass: 98–111 mg; phase angle: 25.1°–27.5°), underscoring its inadequacy for hydration detection. The phase angle also dynamically captured pore-blocking and channel-clearing events during Flooding mode, while voltage responses lagged behind mass transport limitations. These findings establish the 40 Hz impedance phase angle as a rapid, accurate, and robust indicator for real-time PEFC hydration assessment, enabling future advanced water management strategies