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1. Population structure of bla KPC-harbouring IncN plasmids at a New York City medical centre and evidence for multi-species horizontal transmission

   https://doi.org/10.1093/jac/dkac114  

   Gomez-Simmonds, Angela ; Annavajhala, Medini K. ; Tang, Nina ; Rozenberg, Felix D. ; Ahmad, Mehrose ; Park, Heekuk ; Lopatkin, Allison J. ; Uhlemann, Anne Catrin ( April 2022 , Journal of Antimicrobial Chemotherapy)

   Carbapenem-resistant Enterobacterales (CRE) are highly concerning MDR pathogens. Horizontal transfer of broad-host-range IncN plasmids may contribute to the dissemination of the Klebsiella pneumoniae carbapenemase (KPC), spreading carbapenem resistance among unrelated bacteria. However, the population structure and genetic diversity of IncN plasmids has not been fully elucidated.

   We reconstructed blaKPC-harbouring IncN plasmid genomes to characterize shared gene content, structural variability, and putative horizontal transfer within and across patients and diverse bacterial clones.

   We performed short- and long-read sequencing and hybrid assembly on 45 CRE isolates with blaKPC-harbouring IncN plasmids. Eight serial isolates from two patients were included to assess intra-patient plasmid dynamics. Comparative genomic analysis was performed to assess structural and sequence similarity across plasmids. Within IncN sublineages defined by plasmid MLST and kmer-based clustering, phylogenetic analysis was used to identify closely related plasmids.

   Comparative analysis of IncN plasmid genomes revealed substantial heterogeneity including large rearrangements in serial patient plasmids and differences in structure and content across plasmid clusters. Within plasmid sublineages, core genome content and resistance gene regions were largely conserved. Closely related plasmids (≤1 SNP) were found in highly diverse isolates, including ten pST6 plasmids found in eight bacterial clones from three different species.

   Genomic analysis of blaKPC-harbouringmore »IncN plasmids revealed the presence of several distinct sublineages as well as substantial host diversity within plasmid clusters suggestive of frequent mobilization. This study reveals complex plasmid dynamics within a single plasmid family, highlighting the challenge of tracking plasmid-mediated transmission of blaKPC in clinical settings.

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2. Analysis of blood-induced Anopheles gambiae midgut proteins and sexual stage Plasmodium falciparum interaction reveals mosquito genes important for malaria transmission

   https://doi.org/10.1038/s41598-020-71186-5  

   Cui, Yingjun ; Niu, Guodong ; Li, Vincent L. ; Wang, Xiaohong ; Li, Jun ( August 2020 , Scientific Reports)

   Plasmodiuminvasion of mosquito midguts is a mandatory step for malaria transmission. The roles of mosquito midgut proteins and parasite interaction during malaria transmission are not clear. This study aims to identify mosquito midgut proteins that interact with and affectP. falciparuminvasion. Based on gene expression profiles and protein sequences, 76 mosquito secretory proteins that are highly expressed in midguts and up-regulated by blood meals were chosen for analysis. About 61 candidate genes were successfully cloned fromAnopheles gambiaeand expressed in insect cells. ELISA analysis showed that 25 of the insect cell-expressed recombinant mosquito proteins interacted with theP. falciparum-infected cell lysates. Indirect immunofluorescence assays confirmed 17 of them interacted with sexual stage parasites significantly stronger than asexual stage parasites. Knockdown assays found that seven candidate genes significantly changed mosquitoes' susceptibility toP. falciparum. Four of them (AGAP006268, AGAP002848, AGAP006972, and AGAP002851) played a protective function against parasite invasion, and the other three (AGAP008138, FREP1, and HPX15) facilitatedP. falciparumtransmission to mosquitoes. Notably, AGAP008138 is a unique gene that only exists inAnophelinemosquitoes. These gene products are ideal targets to block malaria transmission.
3. Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals

   https://doi.org/10.1186/s13293-023-00520-z  

   Richardson, Victorya ; Engel, Nora ; Kulathinal, Rob J. ( May 2023 , Biology of Sex Differences)

   Mammalian gonadal sex is determined by the presence or absence of a Y chromosome and the subsequent production of sex hormones contributes to secondary sexual differentiation. However, sex chromosome-linked genes encoding dosage-sensitive transcription and epigenetic factors are expressed well before gonad formation and have the potential to establish sex-biased expression that persists beyond the appearance of gonadal hormones. Here, we apply a comparative bioinformatics analysis on a pair of published single-cell datasets from mouse and human during very early embryogenesis—from two-cell to pre-implantation stages—to characterize sex-specific signals and to assess the degree of conservation among early acting sex-specific genes and pathways.

   Clustering and regression analyses of gene expression across samples reveal that sex initially plays a significant role in overall gene expression patterns at the earliest stages of embryogenesis which potentially may be the byproduct of signals from male and female gametes during fertilization. Although these transcriptional sex effects rapidly diminish, sex-biased genes appear to form sex-specific protein–protein interaction networks across pre-implantation stages in both mammals providing evidence that sex-biased expression of epigenetic enzymes may establish sex-specific patterns that persist beyond pre-implantation. Non-negative matrix factorization (NMF) on male and female transcriptomes generated clusters of genes with similar expression patternsmore »across sex and developmental stages, including post-fertilization, epigenetic, and pre-implantation ontologies conserved between mouse and human. While the fraction of sex-differentially expressed genes (sexDEGs) in early embryonic stages is similar and functional ontologies are conserved, the genes involved are generally different in mouse and human.

   This comparative study uncovers much earlier than expected sex-specific signals in mouse and human embryos that pre-date hormonal signaling from the gonads. These early signals are diverged with respect to orthologs yet conserved in terms of function with important implications in the use of genetic models for sex-specific disease.

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4. Genetic diversity and population structure of Leishmania (Viannia) braziliensis in the Peruvian jungle

   https://doi.org/10.1371/journal.pntd.0010374  

   De los Santos, Maxy B. ; Ramírez, Ivonne Melissa ; Rodríguez, Jorge E. ; Beerli, Peter ; Valdivia, Hugo O. ( May 2022 , PLOS Neglected Tropical Diseases)

   Schönian, Gabriele (Ed.)

   Background Human cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis is highly prevalent in the Peruvian jungle, where it affects military forces deployed to fight against drug trafficking and civilian people that migrate from the highland to the lowland jungle for economic activities such as mining, agriculture, construction, and chestnut harvest. We explored the genetic diversity and population structure of 124 L . (V . ) braziliensis isolates collected from the highland (Junín, Cusco, and Ayacucho) and lowland Peruvian jungle (Loreto, Ucayali, and Madre de Dios). All samples were genotyped using Multilocus Microsatellite Typing (MLMT) of ten highly polymorphic markers. Principal findings High polymorphism and genetic diversity were found in Peruvian isolates of L . (V . ) braziliensis . Most markers are not in Hardy-Weinberg equilibrium; this deviation is most likely caused by local inbreeding, as shown by the positive F IS values. Linkage Disequilibrium in subpopulations was not strong, suggesting the reproduction was not strictly clonal. Likewise, for the first time, two genetic clusters of this parasite were determined, distributed in both areas of the Peruvian jungle, which suggested a possible recent colonization event of the highland jungle from the lowland jungle. Conclusions L . (V . ) braziliensismore »exhibits considerable genetic diversity with two different clusters in the Peruvian jungle. Migration analysis suggested a colonization event between geographical areas of distribution. Although no human migration was observed at the time of sampling, earlier displacement of humans, reservoirs, or vectors could have been responsible for the parasite spread in both regions.« less
5. Evolutionary analysis of the LORELEI gene family in plants reveals regulatory subfunctionalization

   https://doi.org/10.1093/plphys/kiac444  

   Noble, Jennifer A ; Bielski, Nicholas V ; Liu, Ming-Che James ; DeFalco, Thomas A ; Stegmann, Martin ; Nelson, Andrew D ; McNamara, Kara ; Sullivan, Brooke ; Dinh, Khanhlinh K ; Khuu, Nicholas ; et al ( September 2022 , Plant Physiology)

   Abstract A signaling complex comprising members of the LORELEI (LRE)-LIKE GPI-anchored protein (LLG) and Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE (CrRLK1L) families perceive RAPID ALKALINIZATION FACTOR (RALF) peptides and regulate growth, reproduction, immunity, and stress responses in Arabidopsis (Arabidopsis thaliana). Genes encoding these proteins are members of multigene families in most angiosperms and could generate thousands of signaling complex variants. However, the links between expansion of these gene families and the functional diversification of this critical signaling complex as well as the evolutionary factors underlying the maintenance of gene duplicates remain unknown. Here, we investigated LLG gene family evolution by sampling land plant genomes and explored the function and expression of angiosperm LLGs. We found that LLG diversity within major land plant lineages is primarily due to lineage-specific duplication events, and that these duplications occurred both early in the history of these lineages and more recently. Our complementation and expression analyses showed that expression divergence (i.e. regulatory subfunctionalization), rather than functional divergence, explains the retention of LLG paralogs. Interestingly, all but one monocot and all eudicot species examined had an LLG copy with preferential expression in male reproductive tissues, while the other duplicate copies showed highest levels of expression in femalemore »or vegetative tissues. The single LLG copy in Amborella trichopoda is expressed vastly higher in male compared to in female reproductive or vegetative tissues. We propose that expression divergence plays an important role in retention of LLG duplicates in angiosperms.« less