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Nanoscale Grain Boundary-Weakened Ce–O Covalency and Surface Confinement Intrinsically Boosting Ceria Surface Oxygen Reactivity

Optochemical control over mRNA translation by photocaged phosphorodiamidate morpholino oligonucleotides in vivo

Abstract We developed an efficient, robust, and broadly applicable system for light-induced protein translation to control the production of proteins of interest and study their function. The method is based on the displacement of a single type of antisense morpholino from RNA by the uncaged guanidinium-linked morpholino (GMO)-phosphorodiamidate morpholino oligonucleotide (PMO) chimera upon UV irradiation. The GMO-PMO chimera designed here is cell-permeable and the GMO part can be produced employing a mercury-free approach compatible with the synthesis on solid support. We demonstrate the function of this optochemical approach in live embryos by inducing, at desired times and locations, the expression of proteins that label specific cells, ablate tissue regions, and affect embryonic development. Together, our results demonstrate that the cell-permeable GMO-PMO chimera offers a strategy for controlling the function of mRNAs of interest. This method allows for the production of proteins at specific times and positions within live organisms, facilitating numerous applications in biomedical research and therapy.

The Association between PTPN22 SNPs and susceptibility to type 1 diabetes: An updated meta-analysis

Type 1 diabetes (T1D) is a significant global health concern, characterized by the autoimmune destruction of insulin-producing pancreatic β-cells, resulting in lifelong dependence on insulin therapy. Although genetic predisposition plays a crucial role in the pathogenesis of T1D, environmental factors also contribute to its onset and progression. Recent research has identified a number of genetic polymorphisms, particularly in the protein tyrosine phosphatase non-receptor 22 gene (PTPN22), that are strongly associated with an increased risk of T1D and may serve as potential biomarkers for early diagnosis and prevention. Despite this, studies investigating the relationship between PTPN22 rs2476601 and T1D risk have consistently demonstrated an association in certain populations, whereas research on rs1310182 has yielded conflicting and less conclusive results. This study presents an updated meta-analysis of two key PTPN22 polymorphic loci — rs2476601 (C1858T) and rs1310182 (A852G) — with the aim of clarifying their associations with T1D. The analysis revealed a significant association between PTPN22 rs2476601 and an increased risk of T1D. In contrast, no significant correlation was found for rs1310182. These findings suggest that PTPN22 rs2476601 as a marker for T1D susceptibility, offering insights into the development of early intervention strategies. However, further research is required to validate these associations and deepen our understanding of the genetic factors involved in T1D pathogenesis.

A SMOTE PCA HDBSCAN approach for enhancing water quality classification in imbalanced datasets

Structure of human MUTYH and functional profiling of cancer-associated variants reveal an allosteric network between its [4Fe-4S] cluster cofactor and active site required for DNA repair

Abstract MUTYH is a clinically important DNA glycosylase that thwarts mutations by initiating base-excision repair at 8-oxoguanine (OG):A lesions. The roles for its [4Fe-4S] cofactor in DNA repair remain enigmatic. Functional profiling of cancer-associated variants near the [4Fe-4S] cofactor reveals that most variations abrogate both retention of the cofactor and enzyme activity. Surprisingly, R241Q and N238S retained the metal cluster and bound substrate DNA tightly, but were completely inactive. We determine the crystal structure of human MUTYH bound to a transition state mimic and this shows that Arg241 and Asn238 build an H-bond network connecting the [4Fe-4S] cluster to the catalytic Asp236 that mediates base excision. The structure of the bacterial MutY variant R149Q, along with molecular dynamics simulations of the human enzyme, support a model in which the cofactor functions to position and activate the catalytic Asp. These results suggest that allosteric cross-talk between the DNA binding [4Fe-4S] cofactor and the base excision site of MUTYH regulate its DNA repair function.

Population structure of yellowtail snapper using age-based life history and otolith shape in southern Gulf of México

Yellowtail snapper Ocyurus chrysurus is commercially important throughout its distribution range. In southern Gulf of México, it is caught as part of a largely undocumented multispecific snapper fishery. Samplings were done at three fishing sites with the highest landings volume of Yucatán, México: Celestún, Dzilam de Bravo, and Río Lagartos. Age and growth parameters were generated with the von Bertalanffy growth model via annuli counts in otolith thin sections of 1,124 individuals. Marginal increment analysis confirmed that opaque zone formation is annual and occurs from July to September. Overall age range was 0 + to 12 years (17.7 to 38.9 cm fork length) but differed between Celestún (0 + to 9 years), Dzilam de Bravo (1 to 12 years), and Río Lagartos (2 to 12 years). Growth parameters and lifespan for combined sexes also varied between sites: Celestún (L ∞ =  41.59 cm, K =  0.11 year-1, tmax =  22.41 years); Dzilam de Bravo (L ∞ =  38.36 cm, K =  0.16 year-1, tmax = 15.5 years); and Río Lagartos (L ∞ =  40.28 cm, K =  0.12 year-1, tmax =  20.01 years). Age at maturity was 1.3 years for females and < 1 year for males. Natural mortality based on tmax was 0.28 year-1 overall. A principal coordinates analysis identified morphometric variables as explaining 92.2% of otolith differentiation by fishing site, with average centroid distances: Celestún, 1.98; Dzilam de Bravo, 2.22; and Río Lagartos, 2.75. Differences in growth rate, lifespan, natural mortality and otolith shape indicate that O. chrysurus in southern GoM exhibits structural complexities that suggest the occurrence of repercussions from fishing-induced demographic changes.

Molecular epidemiological surveillance of respiratory syncytial virus infection in Myanmar from 2019 to 2023

Enhanced Pyridine-Oxazoline Ligand-Enabled Pd(II)-Catalyzed Aminoacetoxylation of Alkenes for the Asymmetric Synthesis of Biaryl-Bridged 7-Membered <i>N</i>-Heterocycles and Atropisomers

An automated framework for assessing how well LLMs cite relevant medical references

Evaluation of Onco E6 point of care rapid diagnostic test for human papilloma virus in Bahir Dar, Amhara Regional State, Ethiopia

Introduction Cervical cancer is a malignant tumor arising from the cells of the uterine cervix. The oncogenic human papillomavirus (HPV) infection is the main causative agent of cervical cancer. Effective HPV screening program can lead to a significant reduction in the morbidity and mortality associated with this cancer. Objective The aim of the study was to evaluate the diagnostic performance of OncoE6™ cervical test kit for cervical precancer and cancer in Amhara Regional State, northwest Ethiopia. Methods An institute-based cross-sectional study was conducted at Felege Hiwot Compressive Specialized Hospital which is found in Bahir Dar, Amhara Regional state. A total of 297 samples were collected. A sterile, disposable speculum was inserted, without lubricant, and two swabs were taken using the “Tipped Polyester” (Dacron) swab provided with the Onco E6™ kit. Swabs taken were tested for onco E6 proteins testing as per the manufacturer’s protocol and pap smear for cytology test. A punch of biopsy was also taken for histopathological diagnosis. Data for all samples were collected using pre-prepared excel database for onco E6 test, pap cytology and punch histopathology. All the data were coded and entered into Epi-info and transported to SPSS version 26.0 software package for analysis. Results Out of 56 (18.86%) participants who tested positive on the histo-pathological diagnosis, Onco E6 was positive in 32 (57.14%), negative in 24 (42.85%). Of 241 participants who tested negative on the histo-pathological diagnosis, Onco E6 was positive in 5 (2.07%) and negative in 236 (97.9%). OncoE6™ cervical test kit had a sensitivity of 57.14% (95% CI: 43.22%–70.29%) and specificity of 98% (95% CI: 95.23%–99.32%) with positive predictive value of 86.6% (95% CI: 71.36%–95.53%), negative predictive value of 90.76% (95% CI: 86.49%–93.93%), and accuracy of 90.18% (95% CI: 86.21%–93.31%). Conclusion The HPV 16/18 OncoE6™ Cervical test kit test had sub-optimum sensitivity and high specificity for detection of cervical precancer and cancer cases. The sensitivity of the kit could be increased by incorporating other more prevalent genotypes like genotype 52, 58, 31 and 35. The HPV16/18-E6 test could be used either as primary screening tool or in conjunction with other diagnostic methods.

Celastrol loaded nanocomplex for painless tumor therapy via YAP inhibition

Divergent evolution of slip banding in CrCoNi alloys

Abstract Metallic materials under high stress often exhibit deformation localization, manifesting as slip banding. Over seven decades ago, Frank and Read introduced the well-known model of dislocation multiplication at a source, explaining slip band formation. Here, we reveal two distinct types of slip bands (confined and extended) in compressed CrCoNi alloys through multi-scale testing and modeling from microscopic to atomic scales. The confined slip band, characterized by a thin glide zone, arises from the conventional process of repetitive full dislocation emissions at Frank–Read source. Contrary to the classical model, the extended band stems from slip-induced deactivation of dislocation sources, followed by consequent generation of new sources on adjacent planes, leading to rapid band thickening. Our findings provide insights into atomic-scale collective dislocation motion and microscopic deformation instability in advanced structural materials.

A phylogenomic perspective reveals mitochondrial-nuclear discordance and previously undescribed species nested within a widespread East African Reed frog species (Hyperolius substriatus Ahl, 1931)

The sub-montane East African Reed Frog, Hyperolius substriatus Ahl, 1931 (Spotted Reed Frog) has a fragmented highland distribution throughout East Africa. Previous studies show extensive mitochondrial divergence between four lineages of African Spotted Reed Frogs that roughly correspond to previously-recognized subspecies. These may have conservation implications if formally described. However, as mitochondrial-based population models only track maternal patterns, further genomic datasets are necessary to assess the distinctness of these lineages in relation to historically recognized morphological subspecies. In this study, we expanded sampling to newly discovered localities and assessed mitochondrial and genomic data to better understand phylogeography and landscape genomics of this species. We found that genomic clades (biparentally inherited) confirm some of the mitochondrial structure (female inherited), but also revealed multiple cases of mitonuclear discordance particularly within the Udzungwa Mountain block, which may have two separate founding events based on peripatric mitochondrial lineages and panmictic genomic signals. Taken together, the three clades within the geographical range of H. substriatus through Tanzania, Malawi, and Mozambique correspond to three previously-identified subspecies and lineages, and have both spatially cohesive and population-specific patterns of geneflow and isolation with neighboring highland locations.

Artificial intelligence based automatic classification, annotation, and measurement of the fetal heart using HeartAssist

Cryo-EM of human P-glycoprotein reveals an intermediate occluded conformation during active drug transport

New U-Pb constraints and geochemistry of the East Kirkton Quarry, Scotland: Implications for early tetrapod evolution in the Carboniferous

The transition of vertebrates from aquatic to terrestrial environments during the late Devonian to early Carboniferous marks a crucial evolutionary milestone. However, this transition remains poorly understood due to a scarcity of early tetrapod fossils during the late Devonian to early Mississippian, creating a gap in the fossil record known as Romer’s Gap (~360–345 Ma). Recent discoveries have narrowed this gap, providing critical insights into early tetrapod evolution. The East Kirkton Quarry in Scotland’s Midland Valley, has yielded tetrapod fossils considered early stem amphibians and amniotes. They have been proposed to be Mississippian (early Carboniferous) in age, yet data to inform their precise ages remain limited. Here, zircon grains from two tuffaceous clastic limestones and shales were dated using Laser Ablation-Inductively Couple Plasma-Mass Spectrometry (LA-ICP-MS). The study presents detrital zircon U-Pb dates, which refine the current biostratigraphy ages assigned to Westlothiana lizziae, Silvanerpeton miripedes, Balanerpeton woodi, Ophiderpeton kirktonense, Eucritta melanolimnetes, and Kirktonecta milnerae to a maximum depositional age (MDA) of 341 ± 3 Ma (±2σ, n= 7 dates), placing them in the middle-lower Visean (Holkerian-Arundian) rather than the previous assigned upper Visean (Brigantian). This revised maximum depositional age places the East Kirkton Quarry fossils within the older, critical interval of Romer’s Gap, bridging a significant evolutionary time interval in the Mississippian fossil record, and allows for refining future tetrapod time trees. X-ray Fluorescence and X-ray Diffraction analyses reveal heterogeneity in the lower East Kirkton Limestone of the East Kirkton Quarry, with variations in elemental and mineralogical compositions, reflecting episodic volcanic and detrital inputs and hydrothermal activity.

Developing a decision support system for sustainable urban planning using machine learning-based scenario modeling

Hippocampal Neural Stem Cell Exosomes Promote Brain Resilience against the Impact of Tau Oligomers

A promising therapeutic intervention for preventing the onset and progression of Alzheimer's disease is to protect and improve synaptic resilience, a well-established early vulnerability associated with the toxic effects of oligomers of amyloid β (AβO) and Tau (TauO). We have previously reported that exosomes from hippocampal neural stem cells (NSCs) protect synapses against AβO. Here, we demonstrate how exosomes can also shield against TauO toxicity in adult mice synapses, potentially benefiting primary and secondary tauopathies. Exosomes from hippocampal NSCs (NSCexo) or mature neurons (MNexo) were delivered intracerebroventricularly to adult wild-type male mice (C57Bl6/J). After 24 h, TauO were administered to suppress long-term potentiation (LTP) and memory, measured by electrophysiology and contextual memory deficits measured using novel object recognition test. We also assessed TauO binding to synapses using isolated synaptosomes and cultured hippocampal neurons. Furthermore, mimics of select miRNAs present in NSCexo were delivered intracerebroventricularly to mice prior to assessment of TauO-induced suppression of hippocampal LTP. Our results showed that NSC-, not MN-, derived exosomes, prevented TauO-induced memory impairment, LTP suppression, and reduced Tau accumulation and TauO internalization in synaptosomes. These findings suggest that NSC-derived exosomes can protect against synaptic dysfunction and memory deficits induced by both AβO and TauO, offering a novel therapeutic strategy for multiple neurodegenerative states.

A modular artificial intelligence framework to facilitate fluorophore design

A comparison of fit, heat stress, oxygen saturation and comfort between a novel reusable mask and disposable N95 respirator

The effectiveness of face masks in infection prevention depends not only on filtration technology but also on user compliance. However, existing masks suffer from limitations impacting comfort, ease of use, and communication, leading to reduced compliance, especially during prolonged use in healthcare settings. Innovations in mask design are needed to address these issues to ensure effective protection. To provide insights into novel face mask design aimed at enhancing infection prevention in healthcare settings and to introduce new evaluation methods for novel face masks, a fit and usability study was conducted with 22 volunteers, comparing a novel reusable mask, Altus Hero 1 (Hero), to N95 respirators. Subjects performed Occupational Safety and Health Administration (OSHA)-accepted quantitative fit test and usability test, and completed a post-test survey. The survey assessed communication, breathability, humidity retention, eyeglasses fitting, and long-term wear preference. Face temperature and blood oxygen levels were recorded during testing. Hero showed significantly reduced heat retention (p&lt;0.05) compared to N95, aligning with survey responses indicating Hero felt cooler. No significant differences were found in blood oxygen levels between masks. Despite needing design refinements, most subjects preferred Hero for comfort and usability. This study discusses enhancements in design, fit, comfort, and materials to better meet users’ needs and ensure compliance. It highlights critical and universal design considerations for future face masks and introduces methodological innovations for evaluating mask fit and usability. The findings offer valuable insights for advancing personal protective equipment for preventing infections and future pandemics.