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Infections by endemic viruses, and the vaccines used to control them, often provide cross-protection against related viruses, potentially altering the transmission dynamics and likelihood of emergence of new zoonotic viruses with pandemic potential. Here, we investigate how population immunity after the COVID-19 pandemic has impacted the likelihood of emergence of a novel sarbecovirus, termed SARS-CoV-X. To this end, we combined empirical cross-neutralisation data with mathematical modelling to identify key immunological and epidemiological factors shaping sarbecovirus emergence. We show that sera from individuals with different COVID-19 immunological histories contained cross-neutralising antibodies against the spike (S) protein of multiple zoonotic sarbecoviruses. Simulations parameterised by these data predict that the likelihood of emergence of a novel sarbecovirus has been reduced significantly by population cross-immunity, with outcomes determined by the extent of cross-protection and R0 of the novel virus. Preventative vaccination against SARS-CoV-X using available COVID-19 vaccines can help resist emergence even in the presence of co-circulating SARS-CoV-2. However, a theoretical vaccine with high specificity to SARS-CoV-2 can increase emergence probability by suppressing SARS-CoV-2 prevalence and, by extension, levels of natural cross-protection. Overall, SARS-CoV-2 circulation and vaccination have generated widespread immunity against related sarbecoviruses, creating an immunological barrier to novel sarbecovirus emergence in humans. Population immunity to SARS-CoV-2 may alter the epidemic potential of a novel coronavirus through cross-protection. Here, the authors investigate the extent of cross-protection against existing coronaviruses and estimate the extent to which this would influence transmission dynamics of a novel virus.

Noncoding DNA is central to our understanding of human gene regulation and complex diseases 1 , 2 , and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome 3 – 9 . Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA 10 , the relatively short timescales separating primate species 11 , and the previously limited availability of whole-genome sequences 12 . Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis -regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals. Whole-genome alignment of 239 primate species reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals, that are enriched for variants that affect human gene expression and complex traits in diseases.

Accurate investigations of neural circuitry require specific genetic access to individual circuit elements, i.e., the myriad neuronal cell-types in the brain. However, native promoters cannot achieve this because while most genes are expressed in the brain, few are expressed in a single neuronal cell-type. We recently used enhancers, the subcomponents of the transcriptional apparatus which tell promoters when and where to express, combined with heterologous minimal promoters to increase specificity of transgene expression, an approach we call Enhancer-Driven Gene Expression (EDGE). As we discuss, EDGE is a marked improvement in specificity over native promoters, but still requires careful anatomical analysis to avoid off-target effects. In this study we present a more complete set of genomic markers from the mouse brain and characterize a novel EDGE viral vector capable of specifically driving expression in distinct subtypes of hippocampal neurons, even though it can express in other cell-types elsewhere. The advent of cell-type specific viral tools in wild-type animals provides a powerful strategy for neural circuit investigation and holds promise for studies using animal models for which transgenic tools are not available.

Engineered nanomaterials can alter the structure and/or function of biological membranes and membrane proteins but the underlying mechanisms remain unclear. We addressed this using a Langmuir phospholipid monolayer containing an active transmembrane protein, glucose-6-phosphatase (G6Pase). Gold nanoparticles (nAu) with varying ligand shell composition and hydrophobicity were synthesized, and their partitioning in the membrane and effects on protein activity characterized. nAu incorporation did not alter the macroscopic properties of the membrane. Atomic force microscopy showed that when co-spread with other components prior to membrane compression, nAu preferentially interacted with G6Pase and each other in a functional group-dependent manner. Under these conditions, all nAu formulations reduced G6Pase aggregation in the membrane, enhancing catalytic activity 5-6 fold. When injected into the subphase beneath pre-compressed monolayers, nAu did not affect G6Pase activity over 60 minutes, implying they were unable to interact with the protein under these conditions. A small but significant quenching of tryptophan fluorescence showed that nAu interacted with G6Pase in aqueous suspension. nAu also significantly reduced the hydrodynamic diameter of G6Pase in aqueous suspension and promoted catalytic activity, likely via a similar mechanism to that observed in co-spread monolayers. Overall, our results show that nAu can incorporate into membranes and associate preferentially with membrane proteins under certain conditions and that partitioning is dependent upon ligand shell chemistry and composition. Once incorporated, nAu can alter the distribution of membrane proteins and indirectly affect their function by improving active site accessibility, or potentially by changing their native structure and distribution in the membrane.

Live microorganisms in the fermented foods termed probiotics and their secondary metabolites with bioactive potential were considered as potential anti-viral capabilities through various mechanisms. Given the importance of functional and fermented foods in disease prevention, there is a need to discuss the contextualization and deep understanding of the mechanism of action of these foods, particularly considering the appearance of coronavirus (COVID-19) pandemic, which is causing health concerns and increased social services globally. The mechanism of probiotic strains or their bioactive metabolites is due to stimulation of immune response through boosting T-lymphocytes, cytokines, and cell toxicity of natural killer cells. Proper consumption of these functional and fermented foods may provide additional antiviral approaches for public benefit by modulating the immune functions in the hosts.

Bio-based fuels and chemicals through the biorefinery approach has gained significant interest as an alternative platform for the petroleum-derived processes as these biobased processes are noticed to have positive environmental and societal impacts. Decades of research was involved in understanding the diversity of microorganisms in different habitats that could synthesize various secondary metabolites that have functional potential as fuels, chemicals, nutraceuticals, food ingredients, and many more. Later, due to the substrate-related process economics, the diverse low-value, high-carbon feedstocks like lignocellulosic biomass, industrial byproducts, and waste streams were investigated to have greater potential. Among them, municipal solid wastes can be used as the source of substrates for the production of commercially viable gaseous and liquid fuels, as well as short-chain fattyacids and carboxylic acids. In this work, technologies and processes demanding the production of value-added products were explained in detail to understand and inculcate the value of municipal solid wastes and the economy, and it can provide to the biorefinery aspect.

Genome editing for the treatment of human disease (GenE-HumDi) is an EU-funded COST Action for the development and consolidation of academic, industrial and healthcare feedback networks aiming to accelerate, foster and harmonize the approval of genome-editing (GE) therapies. GenE-HumDi offers mobility grants, supports educational courses, and hosts conferences and meetings to promote synergistic interactions among and across partners active in the discovery, validation, optimization, manufacturing and clinical application of genomic medicines. Furthermore, it provides young and early career scientists with a supportive and world-class environment to foster networking and international collaborations within the GE field. We compiled the proceedings of the second Annual GenE-HumDi Meeting held in Limassol, Cyprus, in 2024. Over three days, renowned experts from the field updated an audience of over 70 GenE-HumDi members and non-member scientists on the latest discoveries and ongoing projects, discussed the status of the field, and identified GenE-HumDi action priorities to advance research and development for GE medicines. Seven focused discussion groups identified gaps in knowledge, standardization and dissemination for new GE tools, delivery methods, safety monitoring, validation for clinical use, and progress in industrial manufacturing and regulatory issues. Simultaneously, publicity about the event itself contributed to outreach and dissemination of GE for human diseases. Therefore, the conclusions of that meeting, summarized here, serve as a compass toward GE application in Europe through coordination, enhanced collaboration and focus on critical developments.

Background This study identified the risk factors for severe acute respiratory syndrome coronavirus 2 infection among household contacts of index patients and determined the incubation period (IP), serial interval, and estimates of secondary infection rate in Kerala, India. Methods We conducted a cohort study in three districts of Kerala among the inhabitants of households of reverse transcriptase polymerase chain reaction‐positive coronavirus disease 2019 patients between January and July 2021. About 147 index patients and 362 household contacts were followed up for 28 days to determine reverse transcriptase polymerase chain reaction positivity and the presence of total antibodies against SARS‐CoV‐2 on days 1, 7, 14, and 28. Results The mean IP, serial interval, and generation time were 1.6, 3, and 3.9 days, respectively. The secondary infection rate at 14 days was 43.0%. According to multivariable regression analysis persons who worked outside the home were protected (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.24–0.85), whereas those who had kissed the coronavirus disease 2019‐positive patients during illness were more than twice at risk of infection (aOR, 2.23; 95% CI, 1.01–5.2) than those who had not kissed the patients. Sharing a toilet with the index patient increased the risk by more than twice (aOR, 2.5; 95% CI, 1.42–4.64) than not sharing a toilet. However, the contacts who reported using masks (aOR, 2.5; 95% CI, 1.4–4.4) were at a higher risk of infection in household settings. Conclusions Household settings have a high secondary infection rate and the changing transmissibility dynamics such as IP, serial interval should be considered in the prevention and control of SARS‐CoV‐2.

Long-acting growth hormone (LAGH) has the potential to improve adherence and outcomes over daily somatropin in growth hormone deficiency (GHD). Whereas daily somatropin products are molecularly identical, LAGHs are molecularly distinct; additional moieties or mechanisms that prolong LAGH action confer unique pharmacodynamic/pharmacokinetic properties that could affect efficacy and safety. Only one LAGH available in the United States and Europe (lonapegsomatropin) delivers unmodified somatropin. With no head-to-head clinical trials of LAGHs available, this systematic literature review and network meta-analysis were conducted to compare the relative efficacy and safety of LAGHs in pediatric GHD. Five trials were eligible for inclusion in a Bayesian network meta-analysis; 3 contributed to the base case network, including 3 LAGHs (lonapegsomatropin, somapacitan, and somatrogon) and daily somatropin. Treatment with lonapegsomatropin was associated with statistically significantly higher annualized height velocity and change from baseline in height SD score (SDS) at week 52 compared to daily somatropin and somapacitan; no other significant differences in these outcomes were found. The change from baseline in average insulin-like growth factor-1 (IGF-1) SDS at week 52 was significantly higher for somatrogon vs all comparators and for lonapegsomatropin vs daily somatropin and somapacitan; average IGF-1 SDS was within normal range in all trials. No significant differences were seen in progression in bone age-to-chronological age ratio or serious adverse events (SAEs). Sensitivity analyses were consistent with the base case. In this network meta-analysis, lonapegsomatropin was the only LAGH associated with better growth outcomes. No significant differences were detected regarding SAEs; other safety outcomes could not be analyzed.