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      A male steroid controls female sexual behaviour in the malaria mosquito

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          Abstract

          Insects, unlike vertebrates, are widely believed to lack male-biased sex steroid hormones 1 . In the malaria mosquito Anopheles gambiae, the ecdysteroid 20-hydroxyecdysone (20E) appears to have evolved to both control egg development when synthesized by females 2 and to induce mating refractoriness when sexually transferred by males 3 . Because egg development and mating are essential reproductive traits, understanding how Anopheles females integrate these hormonal signals can spur the design of new malaria control programs. Here we reveal that these reproductive functions are regulated by distinct sex steroids through a sophisticated network of ecdysteroid-activating/inactivating enzymes. We identify a male-specific oxidized ecdysteroid, 3-dehydro-20E (3D20E), which safeguards paternity by turning off female sexual receptivity following its sexual transfer and activation by dephosphorylation. Notably, 3D20E transfer also induces expression of a reproductive gene that preserves egg development during Plasmodium infection, ensuring fitness of infected females. Female-derived 20E does not trigger sexual refractoriness but instead licenses oviposition in mated individuals once a 20E-inhibiting kinase is repressed. Identifying this male-specific insect steroid hormone and its roles in regulating female sexual receptivity, fertility and interactions with Plasmodium parasites suggests the possibility for reducing the reproductive success of malaria-transmitting mosquitoes.

          Abstract

          The discovery of a male-specific sex hormone in the mosquito <em>Anopheles gambiae</em> may allow new strategies for the control of this notorious disease vector.

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          Most cited references36

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          Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction

          Background Choosing appropriate primers is probably the single most important factor affecting the polymerase chain reaction (PCR). Specific amplification of the intended target requires that primers do not have matches to other targets in certain orientations and within certain distances that allow undesired amplification. The process of designing specific primers typically involves two stages. First, the primers flanking regions of interest are generated either manually or using software tools; then they are searched against an appropriate nucleotide sequence database using tools such as BLAST to examine the potential targets. However, the latter is not an easy process as one needs to examine many details between primers and targets, such as the number and the positions of matched bases, the primer orientations and distance between forward and reverse primers. The complexity of such analysis usually makes this a time-consuming and very difficult task for users, especially when the primers have a large number of hits. Furthermore, although the BLAST program has been widely used for primer target detection, it is in fact not an ideal tool for this purpose as BLAST is a local alignment algorithm and does not necessarily return complete match information over the entire primer range. Results We present a new software tool called Primer-BLAST to alleviate the difficulty in designing target-specific primers. This tool combines BLAST with a global alignment algorithm to ensure a full primer-target alignment and is sensitive enough to detect targets that have a significant number of mismatches to primers. Primer-BLAST allows users to design new target-specific primers in one step as well as to check the specificity of pre-existing primers. Primer-BLAST also supports placing primers based on exon/intron locations and excluding single nucleotide polymorphism (SNP) sites in primers. Conclusions We describe a robust and fully implemented general purpose primer design tool that designs target-specific PCR primers. Primer-BLAST offers flexible options to adjust the specificity threshold and other primer properties. This tool is publicly available at http://www.ncbi.nlm.nih.gov/tools/primer-blast.
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            CDD: NCBI's conserved domain database

            NCBI's CDD, the Conserved Domain Database, enters its 15th year as a public resource for the annotation of proteins with the location of conserved domain footprints. Going forward, we strive to improve the coverage and consistency of domain annotation provided by CDD. We maintain a live search system as well as an archive of pre-computed domain annotation for sequences tracked in NCBI's Entrez protein database, which can be retrieved for single sequences or in bulk. We also maintain import procedures so that CDD contains domain models and domain definitions provided by several collections available in the public domain, as well as those produced by an in-house curation effort. The curation effort aims at increasing coverage and providing finer-grained classifications of common protein domains, for which a wealth of functional and structural data has become available. CDD curation generates alignment models of representative sequence fragments, which are in agreement with domain boundaries as observed in protein 3D structure, and which model the structurally conserved cores of domain families as well as annotate conserved features. CDD can be accessed at http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.
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              Semi-supervised learning for peptide identification from shotgun proteomics datasets.

              Shotgun proteomics uses liquid chromatography-tandem mass spectrometry to identify proteins in complex biological samples. We describe an algorithm, called Percolator, for improving the rate of confident peptide identifications from a collection of tandem mass spectra. Percolator uses semi-supervised machine learning to discriminate between correct and decoy spectrum identifications, correctly assigning peptides to 17% more spectra from a tryptic Saccharomyces cerevisiae dataset, and up to 77% more spectra from non-tryptic digests, relative to a fully supervised approach.
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                Author and article information

                Contributors
                fcatter@hsph.harvard.edu
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                6 July 2022
                6 July 2022
                2022
                : 608
                : 7921
                : 93-97
                Affiliations
                [1 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Immunology and Infectious Diseases, , Harvard T.H. Chan School of Public Health, ; Boston, MA USA
                [2 ]Harvard Center for Mass Spectrometry, Cambridge, MA USA
                [3 ]GRID grid.34477.33, ISNI 0000000122986657, Department of Genome Sciences, , University of Washington, ; Seattle, WA USA
                [4 ]GRID grid.413575.1, ISNI 0000 0001 2167 1581, Howard Hughes Medical Institute, ; Chevy Chase, MD USA
                [5 ]GRID grid.497059.6, Present Address: Verily Life Sciences, ; South San Francisco, CA USA
                [6 ]GRID grid.38142.3c, ISNI 000000041936754X, Present Address: Department of Genetics, Blavatnik Institute, , Harvard Medical School, ; Boston, MA USA
                Author information
                http://orcid.org/0000-0001-7540-8623
                http://orcid.org/0000-0002-0172-8090
                http://orcid.org/0000-0003-0953-7800
                http://orcid.org/0000-0003-4903-0318
                http://orcid.org/0000-0003-1853-0256
                http://orcid.org/0000-0002-1184-8360
                http://orcid.org/0000-0002-2806-9718
                http://orcid.org/0000-0003-3295-6683
                Article
                4908
                10.1038/s41586-022-04908-6
                9352575
                35794471
                6cb105d6-472f-416f-8101-1d281e73aa43
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 January 2022
                : 25 May 2022
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                © The Author(s), under exclusive licence to Springer Nature Limited 2022

                Uncategorized
                entomology,reproductive biology,insect hormones
                Uncategorized
                entomology, reproductive biology, insect hormones

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