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Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency (\"dual haplotypes\") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.

BackgroundONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes.MethodsIn this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×1011 virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed.ResultsIn total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort.ConclusionsONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18.

Ethylene is a gaseous plant hormone that controls a wide array of physiologically relevant processes, including plant responses to biotic and abiotic stress, and induces ripening in climacteric fruits. To monitor ethylene in plants, analytical methods, phenotypic assays, gene expression analysis and transcriptional or translational reporters are typically employed. In the model plant Arabidopsis, two ethylene‐sensitive synthetic transcriptional reporters have been described, 5xEBS:GUS and 10x2EBS‐S10:GUS. These reporters harbour a different type, arrangement and number of homotypic cis‐elements in their promoters and thus may recruit the ethylene master regulator EIN3 in the context of alternative transcriptional complexes. Accordingly, the patterns of GUS activity in these transgenic lines differ and neither of them encompasses all plant tissues even in the presence of saturating levels of exogenous ethylene. Herein, we set out to develop and test a more sensitive version of the ethylene‐inducible promoter that we refer to as EBSnew (abbreviated as EBSn). EBSn leverages a tandem of 10 non‐identical, natural copies of a novel, dual, everted, 11 bp‐long EIN3‐binding site, 2EBS(−1). We show that in Arabidopsis, EBSn outperforms its predecessors in terms of its ethylene sensitivity, having the capacity to monitor endogenous levels of ethylene and displaying more ubiquitous expression in response to the exogenous hormone. We demonstrate that the EBSn promoter is also functional in tomato, opening new avenues to manipulating ethylene‐regulated processes, such as ripening and senescence, in crops.

Many tumors express tumor-specific antigens capable of being presented to CD8$^+$ T cells by major histocompatibility complex (MHC) class I molecules. Antigen presentation models predict that the tumor cell itself should present these antigens to T cells. However, when conditions for the priming of tumor-specific responses were examined in mice, no detectable presentation of MHC class I-restricted tumor antigens by the tumor itself was found. Rather, tumor antigens were exclusively presented by host bone marrow-derived cells. Thus, MHC class I-restricted antigens are efficiently transferred in vivo to bone marrow-derived antigen-presenting cells, which suggests that human leukocyte antigen matching may be less critical in the application of tumor vaccines than previously thought.

Ethylene is a gaseous plant hormone that controls a wide array of physiologically relevant processes, including plant responses to biotic and abiotic stress, and induces ripening in climacteric fruits. To monitor ethylene in plants, analytical methods, phenotypic assays, gene expression analysis, and transcriptional or translational reporters are typically employed. In the model plant Arabidopsis, two ethylene-sensitive synthetic transcriptional reporters have been described, and . These reporters harbor a different type, arrangement, and number of homotypic -elements in their promoters and thus may recruit the ethylene master regulator EIN3 in the context of alternative transcriptional complexes. Accordingly, the patterns of GUS activity in these transgenic lines differ and neither of them encompasses all plant tissues even in the presence of saturating levels of exogenous ethylene. Herein, we set out to develop and test a more sensitive version of the ethylene-inducible promoter that we refer to as (abbreviated as ). leverages a tandem of ten non-identical, natural copies of a novel, dual, everted, 11bp-long EIN3-binding site, . We show that in Arabidopsis, outperforms its predecessors in terms of its ethylene sensitivity, having the capacity to monitor endogenous levels of ethylene and displaying more ubiquitous expression in response to the exogenous hormone. We demonstrate that the promoter is also functional in tomato, opening new avenues to manipulating ethylene-regulated processes, such as ripening and senescence, in crops.

Generative AI (GenAI) browser assistants integrate powerful capabilities of GenAI in web browsers to provide rich experiences such as question answering, content summarization, and agentic navigation. These assistants, available today as browser extensions, can not only track detailed browsing activity such as search and click data, but can also autonomously perform tasks such as filling forms, raising significant privacy concerns. It is crucial to understand the design and operation of GenAI browser extensions, including how they collect, store, process, and share user data. To this end, we study their ability to profile users and personalize their responses based on explicit or inferred demographic attributes and interests of users. We perform network traffic analysis and use a novel prompting framework to audit tracking, profiling, and personalization by the ten most popular GenAI browser assistant extensions. We find that instead of relying on local in-browser models, these assistants largely depend on server-side APIs, which can be auto-invoked without explicit user interaction. When invoked, they collect and share webpage content, often the full HTML DOM and sometimes even the user's form inputs, with their first-party servers. Some assistants also share identifiers and user prompts with third-party trackers such as Google Analytics. The collection and sharing continues even if a webpage contains sensitive information such as health or personal information such as name or SSN entered in a web form. We find that several GenAI browser assistants infer demographic attributes such as age, gender, income, and interests and use this profile--which carries across browsing contexts--to personalize responses. In summary, our work shows that GenAI browser assistants can and do collect personal and sensitive information for profiling and personalization with little to no safeguards.