RESUMO
Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.
Assuntos
Interações Hospedeiro-Patógeno , Humanos , Animais , Doença de Lyme/microbiologia , Doenças Transmitidas por Vetores , Interações entre Hospedeiro e Microrganismos , Borrelia burgdorferi/patogenicidade , Borrelia burgdorferi/metabolismoRESUMO
Grafting is possible in both animals and plants. Although in animals the process requires surgery and is often associated with rejection of non-self, in plants grafting is widespread, and has been used since antiquity for crop improvement1. However, in the monocotyledons, which represent the second largest group of terrestrial plants and include many staple crops, the absence of vascular cambium is thought to preclude grafting2. Here we show that the embryonic hypocotyl allows intra- and inter-specific grafting in all three monocotyledon groups: the commelinids, lilioids and alismatids. We show functional graft unions through histology, application of exogenous fluorescent dyes, complementation assays for movement of endogenous hormones, and growth of plants to maturity. Expression profiling identifies genes that unify the molecular response associated with grafting in monocotyledons and dicotyledons, but also gene families that have not previously been associated with tissue union. Fusion of susceptible wheat scions to oat rootstocks confers resistance to the soil-borne pathogen Gaeumannomyces graminis. Collectively, these data overturn the consensus that monocotyledons cannot form graft unions, and identify the hypocotyl (mesocotyl in grasses) as a meristematic tissue that allows this process. We conclude that graft compatibility is a shared ability among seed-bearing plants.
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Avena , Raízes de Plantas , Brotos de Planta , Transplantes , Triticum , Ascomicetos/patogenicidade , Avena/embriologia , Avena/microbiologia , Hipocótilo , Meristema , Raízes de Plantas/embriologia , Raízes de Plantas/microbiologia , Brotos de Planta/embriologia , Brotos de Planta/microbiologia , Triticum/embriologia , Triticum/microbiologiaRESUMO
Gynandropsis gynandra (Cleomaceae) is a cosmopolitan leafy vegetable and medicinal plant, which has also been used as a model to study C4 photosynthesis due to its evolutionary proximity to C3 Arabidopsis (Arabidopsis thaliana). Here, we present the genome sequence of G. gynandra, anchored onto 17 main pseudomolecules with a total length of 740 Mb, an N50 of 42 Mb and 30,933 well-supported gene models. The G. gynandra genome and previously released genomes of C3 relatives in the Cleomaceae and Brassicaceae make an excellent model for studying the role of genome evolution in the transition from C3 to C4 photosynthesis. Our analyses revealed that G. gynandra and its C3 relative Tarenaya hassleriana shared a whole-genome duplication event (Gg-α), then an addition of a third genome (Th-α, +1×) took place in T. hassleriana but not in G. gynandra. Analysis of syntenic copy number of C4 photosynthesis-related gene families indicates that G. gynandra generally retained more duplicated copies of these genes than C3T. hassleriana, and also that the G. gynandra C4 genes might have been under positive selection pressure. Both whole-genome and single-gene duplication were found to contribute to the expansion of the aforementioned gene families in G. gynandra. Collectively, this study enhances our understanding of the polyploidy history, gene duplication and retention, as well as their impact on the evolution of C4 photosynthesis in Cleomaceae.
Assuntos
Arabidopsis , Brassicaceae , Magnoliopsida , Duplicação Gênica , Magnoliopsida/genética , Brassicaceae/genética , Arabidopsis/genética , Fotossíntese/genética , Evolução MolecularRESUMO
Neurons are vulnerable to physical insults, which compromise the integrity of both dendrites and axons. Although several molecular pathways of axon regeneration are identified, our knowledge of dendrite regeneration is limited. To understand the mechanisms of dendrite regeneration, we used the PVD neurons in C. elegans with stereotyped branched dendrites. Using femtosecond laser, we severed the primary dendrites and axon of this neuron. After severing the primary dendrites near the cell body, we observed sprouting of new branches from the proximal site within 6 hours, which regrew further with time in an unstereotyped manner. This was accompanied by reconnection between the proximal and distal dendrites, and fusion among the higher-order branches as reported before. We quantified the regeneration pattern into three aspects-territory length, number of branches, and fusion phenomena. Axonal injury causes a retraction of the severed end followed by a Dual leucine zipper kinase-1 (DLK-1) dependent regrowth from the severed end. We tested the roles of the major axon regeneration signalling hubs such as DLK-1-RPM-1, cAMP elevation, let-7 miRNA, AKT-1, Phosphatidylserine (PS) exposure/PS in dendrite regeneration. We found that neither dendrite regrowth nor fusion was affected by the axon injury pathway molecules. Surprisingly, we found that the RAC GTPase, CED-10 and its upstream GEF, TIAM-1 play a cell-autonomous role in dendrite regeneration. Additionally, the function of CED-10 in epidermal cell is critical for post-dendrotomy fusion phenomena. This work describes a novel regulatory mechanism of dendrite regeneration and provides a framework for understanding the cellular mechanism of dendrite regeneration using PVD neuron as a model system.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , Proteínas rac de Ligação ao GTP , Animais , Axônios/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Dendritos/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , MAP Quinase Quinase Quinases/genética , Regeneração Nervosa/genética , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T/metabolismo , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Subcutaneous emphysema is a condition where air becomes trapped under the skin, typically resulting from surgery or skin trauma. It is mostly localized and its occurrence in blood donors is exceedingly rare. Phlebotomy poses minimal risk of subcutaneous emphysema, but procedural errors may lead to such complications. STUDY DESIGN AND METHOD: This is a case report of 29-year-old repeat blood donor who experienced subcutaneous emphysema following blood donation. The donor was vigorously squeezing sponge ball during donation resulting in displacement of the needle which required readjustment. Post-donation, the donor reported a crackling sensation and mild swelling near phlebotomy site. Non-contrast computed tomography (NCCT) scans confirmed subcutaneous emphysema, attributing its development to air trapping in subcutaneous plane due to ball valve mechanism. RESULTS: Computed tomography (CT) imaging revealed subcutaneous emphysematous changes in the right cubital region and no evidence of hematoma. The swelling spontaneously subsided in 10-12 days without any intervention. The case underscores the importance of differentiating subcutaneous emphysema from common complications like hematoma. DISCUSSION: Subcutaneous emphysema in blood donors is exceptionally rare but should be managed with clear communication. Donors should be reassured that the condition, although rare, is benign and self-resolving. Healthcare providers should be equipped to handle such rare complications, offering appropriate care and documenting incidents for future prevention.
Assuntos
Doação de Sangue , Enfisema Subcutâneo , Humanos , Adulto , Enfisema Subcutâneo/diagnóstico por imagem , Enfisema Subcutâneo/etiologia , Tomografia Computadorizada por Raios X/efeitos adversos , Doadores de Sangue , Hematoma/complicaçõesRESUMO
To better understand the structure and evolution of the genomes of four plant pathogenic species of Zymoseptoria, we analyzed the occurrence, relative abundance (RA), and density (RD) of simple sequence repeats (SSRs) in their whole genome and transcriptome sequences. In this study, SSRs are defined as repeats of more than 12 bases in length. The genome and transcriptome sequences of Zymoseptoria ardabiliae show the highest RA (201.1 and 129.9) and RD (3229.4 and 1928.2) of SSRs, while those of Zymoseptoria pseudotritici show the lowest RA (167.2 and 118.5) and RD (2482.2 and 1687.0). The majority of SSRs in the genomic and transcriptome sequences of species were trinucleotide SSRs, while dinucleotide SSRs were the least common. The most common trinucleotide motifs in the transcriptomic sequences across all species were those that encoded the amino acid arginine. As per our motif conservation study, Zymoseptoria tritici (12.4%) possessed the most unique motifs, while Z. pseudotritici (3.9%) had the fewest. Overall, only 38.1% of the motifs were found to be conserved among the species. Gene enrichment studies reveal that three of the species, Z. ardabiliae, Zymoseptoria brevis, and Z. pseudotritici, have SSRs in their genes related to cellular metabolism, while the remaining Z. tritici harbors SSRs in genes related to DNA synthesis and gene expression. In an effort to improve the genetic resources for the orphan species of pathogenic Zymoseptoria, a total of 73,134 primers were created. The genomic resources developed in this study could help with analyses of genetic relatedness within the population and the development of species-specific markers.
Assuntos
Genoma de Planta , Genômica , Plantas , Transcriptoma , Repetições de MicrossatélitesRESUMO
PURPOSE: To determine the prevalence, clinical features, and radiographic findings of superior ophthalmic vein periphlebitis (SOVP) in thyroid eye disease (TED). METHODS: Patients with a clinical diagnosis of thyroid eye disease and contrast-enhanced imaging were included. Imaging was reviewed for the presence of SOVP, and patients with SOVP were compared to those without. A random eye was determined to be the affected eye in patients without SOVP. RESULTS: A total of 212 patients met the inclusion criteria. Unilateral SOVP was identified in 4.7% of cases. There was no significant difference in age ( p = 0.22), gender ( p = 0.09), or disease duration ( p = 0.14) between patients with and without SOVP. There was a significant ( p < 0.05) difference in stage classification and clinical activity core between the groups. The affected eye in patients with SOVP had significantly ( p < 0.05) greater margin reflex distance 1, degree of relative proptosis, horizontal motility restriction, and vertical motility restriction than in patients without SOVP. There was no significant difference in horizontal strabismus ( p = 1.0), vertical strabismus ( p = 0.87), or relative intraocular pressure ( p = 0.77). On imaging, the maximal diameter of the SR and IR were found to be significantly ( p < 0.05) larger in the affected eye of patients with periphlebitis; however, there was no difference in measured diameter of the medial rectus and ( p = 0.30) or lateral rectus ( p = 0.78). CONCLUSIONS: SOVP is an under-reported imaging finding of thyroid eye disease. It is associated with significantly greater margin reflex distance 1, relative proptosis, and motility restriction on exam as well as larger superior rectus and inferior rectus diameter on imaging. These patients tend to present in the active stage of disease with greater clinical activity score.
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Oftalmopatia de Graves , Flebite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/epidemiologia , Oftalmopatia de Graves/complicações , Prevalência , Adulto , Idoso , Flebite/diagnóstico , Flebite/epidemiologia , Flebite/etiologia , Estudos Retrospectivos , Veias/diagnóstico por imagem , Idoso de 80 Anos ou mais , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To understand how thyroid eye disease (TED) impacts buccal fat pad (BFP) volume. METHODS: In this cohort study, computed tomography (CT) scans and charts of adult patients with and without TED were obtained from an institutional database. The primary outcome was BFP volume in cubic centimeters. Three independent, blinded observers analyzed scans using Horos, a free, open-source medical image viewing software. Bivariate and multivariable analyses were performed. We determined sample size using an effect size based on published reports of the minimum amount of fat excision needed to notice a clinical difference. Equivalence testing against upper and lower bounds set by the same effect size was conducted to assess practical significance of the results. RESULTS: Our sample was sufficient to detect a difference as large as 1.5cc with 95% power. 72 scans were included in our study, 24 TED patients and 48 controls. Mean BFP volume was not statistically different between TED patients and controls (3.96 cc vs 4.06 cc, p = .778). Analysis of covariance adjusting for relevant patient factors (age, sex, and BMI) also failed to find a significant difference between groups. Equivalence testing was significant (p < .001) and revealed the observed difference between groups was less than any clinically meaningful difference. For an effect size of 1.5cc, the data suggests there is a 5% risk of a false negative. CONCLUSIONS: TED was not associated with a significant difference in BFP volume, suggesting that the BFP is spared from TED-related soft-tissue expansion.
Assuntos
Oftalmopatia de Graves , Adulto , Humanos , Oftalmopatia de Graves/diagnóstico por imagem , Estudos de Coortes , Tomografia Computadorizada por Raios X , Tecido Adiposo/diagnóstico por imagem , DemografiaRESUMO
BACKGROUND: Globally, diabetes mellitus is the most common cause of premature mortality after cardiovascular diseases and tobacco chewing. It is a heterogeneous metabolic disorder characterised by the faulty metabolism of carbohydrates, fats and proteins as a result of defects in insulin secretion or resistance. It was estimated that approximately 463 million of the adult population are suffering from diabetes mellitus, which may grow up to 700 million by 2045. Solanum indicum is distributed all over India and all of the tropical and subtropical regions of the world. The different parts of the plant such as the roots, leaves and fruits were used traditionally in the treatment of cough, asthma and rhinitis. However, the hypoglycaemic activity of the plant is not scientifically validated. PURPOSE: The present study aimed to evaluate the antioxidant, antidiabetic and anti-hyperlipidaemic activity of methanolic fruit extract of Solanum indicum (SIE) in streptozotocin (STZ) induced diabetic rats. METHOD: Experimentally, type II diabetes was induced in rats by an i.p. injection of STZ at a dose of 60 mg/kg. The effect of the fruit extract was evaluated at doses of 100 and 200 mg/kg body weight in STZ-induced diabetic rats for 30 days. RESULT: The oral administration of fruit extract caused a significant (p < 0.05) reduction in the blood glucose level with a more prominent effect at 200 mg/kg. The fruit extract showed dose-dependent α-amylase and α-glycosidase inhibitory activity. It reduced the serum cholesterol and triglyceride levels remarkably in diabetic rats compared to normal. The extract showed the reduced activity of endogenous antioxidants, superoxide dismutase, glutathione peroxidase and catalase in the liver of STZ diabetic rats. CONCLUSION: The result confirmed that the fruit extract of Solanum indicum showed a dose-dependent blood glucose lowering effect and significantly reduced elevated blood cholesterol and triglycerides. It prevented oxidative stress associated with type II diabetes in STZ rats.
RESUMO
C4 photosynthesis has evolved multiple times in the angiosperms and typically involves alterations to the biochemistry, cell biology and development of leaves. One common modification found in C4 plants compared with the ancestral C3 state is an increase in vein density such that the leaf contains a larger proportion of bundle sheath cells. Recent findings indicate that there may be significant intraspecific variation in traits such as vein density in C4 plants but to use such natural variation for trait-mapping, rapid phenotyping would be required. Here we report a high-throughput method to quantify vein density that leverages the bundle sheath-specific accumulation of starch found in C4 species. Starch staining allowed high-contrast images to be acquired permitting image analysis with MATLAB- and Python-based programmes. The method works for dicotyledons and monocotolydons. We applied this method to Gynandropsis gynandra where significant variation in vein density was detected between natural accessions, and Zea mays where no variation was apparent in the genotypically diverse lines assessed. We anticipate this approach will be useful to map genes controlling vein density in C4 species demonstrating natural variation for this trait.
Assuntos
Magnoliopsida , Amido , Amido/metabolismo , Plantas/metabolismo , Folhas de Planta/metabolismo , Zea mays/metabolismo , Fotossíntese/genética , Magnoliopsida/metabolismoRESUMO
Social isolation is detrimental to the health of social mammals inducing neurochemical and hormonal changes related to depression and anxiety, as well as impairments of cardiovascular and immune functioning. Likewise, perceptions of loneliness are increasingly recognized as detrimental to human psychological well-being, cognitive functioning, and physical health. Few studies, however, have examined the impact of social isolation on the intestinal microbiome and metabolome. To better understand the impact of social isolation on these systems, intestinal microbiota, and the systemic impact via the gut-brain axis, we employed prairie voles. Physiological stress on female prairie voles (n = 22) either with a same-sex sibling (n = 11) or in isolation (n = 11) for four weeks demonstrated behavioral indicators of increased anxiety and depression in isolated voles (p ≤ 0.01). Bacterial DNA from fecal and colon samples, collected at five time points (T0-4), were sequenced for all nine hypervariable regions of the 16S rRNA gene. Microbiome analyses revealed several differences in gut communities of paired and isolated voles with greater differences at T4. Notably, several taxa associated with host health including Anaerostipes and Lactobacillaceae were more prevalent in paired voles, whereas several taxa associated with known pathogens (e.g., Staphylococcaceae and Enterococcus) or disease were elevated in isolated animals. Similarly, metabolome analyses suggested isolated voles, when compared to paired animals, exhibited differences in metabolites associated with diabetes and colitis. These findings further contribute to our understanding of the harmful effects of social isolation, which cause perturbations in the gut microbiome and serum metabolites.
Assuntos
Microbioma Gastrointestinal , Pradaria , Animais , Humanos , Feminino , RNA Ribossômico 16S/genética , Isolamento Social/psicologia , Arvicolinae , MetabolomaRESUMO
Human babesiosis is a malaria-like illness caused by tick-borne intraerythrocytic Babesia parasites of the Apicomplexa phylum. Whereas several species of Babesia can cause severe disease in humans, the ability to propagate Babesia duncani both in vitro in human erythrocytes and in mice makes it a unique pathogen to study Babesia biology and pathogenesis. Here we report an optimized B. duncani in culture-in mouse (ICIM) model that combines continuous in vitro culture of the parasite with a precise model of lethal infection in mice. We demonstrate that B. duncani-infected erythrocytes as well as free merozoites can cause lethal infection in C3H/HeJ mice. Highly reproducible parasitemia and survival outcomes could be established using specific parasite loads in different mouse genetic backgrounds. Using the ICIM model, we discovered 2 new endochin-like quinolone prodrugs (ELQ-331 and ELQ-468) that alone or in combination with atovaquone are highly efficacious against B. duncani and Babesia microti.
Assuntos
Babesia , Parasitos , Pró-Fármacos , Quinolonas , Carrapatos , Animais , Atovaquona/farmacologia , Babesia/genética , Humanos , Camundongos , Camundongos Endogâmicos C3H , VirulênciaRESUMO
The apicomplexan pathogen Babesia microti is responsible for most cases of human babesiosis worldwide. The disease, which presents as a malaria-like illness, is potentially fatal in immunocompromised or elderly patients, making the need for its accurate and early diagnosis an urgent public health concern. B. microti is transmitted primarily by Ixodes ticks but can also be transmitted via blood transfusion. The parasite completes its asexual reproduction in the host red blood cell, where each invading merozoite develops and multiplies to produce four daughter parasites. While various techniques, such as microscopy, PCR, and indirect fluorescence, have been used over the years for babesiosis diagnosis, detection of the secreted B. microti immunodominant antigen BmGPI12 using specific polyclonal antibodies was found to be the most effective method for the diagnosis of active infection and for evaluation of clearance following drug treatment. Here, we report the development of a panel of 16 monoclonal antibodies against BmGPI12. These antibodies detected secreted BmGPI12 in the plasma of infected humans. Antigen capture assays identified a combination of two monoclonal antibodies, 4C8 and 1E11, as a basis for a monoclonal antibody-based BmGPI12 capture assay (mGPAC) to detect active B. microti infection. Using a collection of 105 previously characterized human plasma samples, the mGPAC assay showed 97.1% correlation with RNA-based PCR (transcription-mediated amplification [TMA]) for positive and negative samples. The mGPAC assay also detected BmGPI12 in the plasma of six babesiosis patients at the time of diagnosis but not in three matched posttreatment samples. The mGPAC assay could thus be used alone or in combination with other assays for accurate detection of active B. microti infection.
Assuntos
Babesia microti , Babesiose , Idoso , Anticorpos Monoclonais , Antígenos de Protozoários , Babesia microti/genética , Babesiose/diagnóstico , Humanos , RNARESUMO
Reducing photorespiration in C3 crops could significantly increase rates of photosynthesis and yield. One method to achieve this would be to integrate C4 photosynthesis into C3 species. This objective is challenging as it involves engineering incompletely understood traits into C3 leaves, including complex changes to their biochemistry, cell biology, and anatomy. Quantitative genetics and selective breeding offer underexplored routes to identify regulators of these processes. We first review examples of natural intraspecific variation in C4 photosynthesis as well as the potential for hybridization between C3 and C4 species. We then discuss how quantitative genetic approaches including artificial selection and genome-wide association could be used to better understand the C4 syndrome and in so doing guide the engineering of the C4 pathway into C3 crops.
Assuntos
Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Produtos Agrícolas/genética , Fotossíntese/genética , Folhas de Planta/metabolismoRESUMO
The majority of plants use C3 photosynthesis, but over 60 independent lineages of angiosperms have evolved the C4 pathway. In most C4 species, photosynthesis gene expression is compartmented between mesophyll and bundle-sheath cells. We performed DNaseI sequencing to identify genome-wide profiles of transcription factor binding in leaves of the C4 grasses Zea mays, Sorghum bicolor, and Setaria italica as well as C3 Brachypodium distachyon In C4 species, while bundle-sheath strands and whole leaves shared similarity in the broad regions of DNA accessible to transcription factors, the short sequences bound varied. Transcription factor binding was prevalent in gene bodies as well as promoters, and many of these sites could represent duons that influence gene regulation in addition to amino acid sequence. Although globally there was little correlation between any individual DNaseI footprint and cell-specific gene expression, within individual species transcription factor binding to the same motifs in multiple genes provided evidence for shared mechanisms governing C4 photosynthesis gene expression. Furthermore, interspecific comparisons identified a small number of highly conserved transcription factor binding sites associated with leaves from species that diverged around 60 million years ago. These data therefore provide insight into the architecture associated with C4 photosynthesis gene expression in particular and characteristics of transcription factor binding in cereal crops in general.
Assuntos
Fotossíntese/genética , Proteínas de Plantas/metabolismo , Poaceae/genética , Fatores de Transcrição/metabolismo , Brachypodium/genética , Desoxirribonuclease I , Eucromatina/genética , Eucromatina/metabolismo , Evolução Molecular , Regulação da Expressão Gênica de Plantas/genética , Genoma de Planta , Motivos de Nucleotídeos , Fotossíntese/fisiologia , Complexo de Proteínas do Centro de Reação Fotossintética/genética , Filogenia , Folhas de Planta/enzimologia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Setaria (Planta)/genética , Setaria (Planta)/metabolismo , Sorghum/genética , Sorghum/metabolismo , Zea mays/genética , Zea mays/metabolismoRESUMO
Next-generation sequencing has allowed us to explore new methods, where comparative and population genomics can be used simultaneously. Keeping this in mind, we surveyed and analyzed the frequency and distribution of microsatellites in the Indian gharial (Gavialis gangeticus) and compared it with American alligator (Alligator mississippiensis) and saltwater crocodile (Crocodylus porosus) to enrich them with genomic resources. The Indian gharial has a low frequency, relative abundance (RA), and relative density (RD) of microsatellites as compared to other crocodilians. RA and RD were positively correlated with the GC content of genomic and transcriptomic sequences. The genomic sequences were dominated by dinucleotide repeats, whereas the transcriptomic sequences had an excess of trinucleotide repeats. Motif conservation studies among the three crocodilians revealed conservation of 69.2% of motifs. Species-specific unique motifs identified in this study could be used as molecular probes for species identification. A total of 67,311 primers were designed in all three species to enrich the crocodilians with genomic resources. The genomic resources developed in this study could accelerate diversity analysis within its individuals to design a proper mating plan to reduce inbreeding stress and further improve the species.
Assuntos
Jacarés e Crocodilos , Jacarés e Crocodilos/genética , Animais , Genoma , Genômica , Humanos , Repetições de Microssatélites , Especificidade da EspécieRESUMO
Here, we analysed the genomic evolution in extremophilic bacteria using long simple sequence repeats (SSRs). Frequencies of occurrence, relative abundance (RA) and relative density (RD) of long SSRs were analysed in the genomes of extremophilic bacteria. Thermus aquaticus had the most RA and RD of long SSRs in its coding sequences (110.6 and 1408.3), followed by Rhodoferax antarcticus (77.0 and 1187.4). A positive correlation was observed between G + C content and the RA-RD of long SSRs. Geobacillus kaustophilus, Geobacillus thermoleovorans, Halothermothrix orenii, R. antarcticus, and T. aquaticus preferred trinucleotide repeats within their genomes, whereas others preferred a higher number of tetranucleotide repeats. Gene enrichment showed the presence of these long SSRs in metabolic enzyme encoding genes related to stress tolerance. To analyse the functional implications of SSR insertions, three-dimensional protein structure modelling of SSR containing diguanylate cyclase (DGC) gene encoding protein was carried out. Removal of SSR sequence led to an inappropriate folding and instability of the modelled protein structure.
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Extremófilos , Bactérias/genética , Composição de Bases , Extremófilos/genética , Mutação com Ganho de Função , Repetições de MicrossatélitesRESUMO
Transmission of Plasmodium falciparum involves a complex process that starts with the ingestion of gametocytes by female Anopheles mosquitoes during a blood meal. Activation of gametocytes in the mosquito midgut triggers "rounding up" followed by egress of both male and female gametes. Egress requires secretion of a perforin-like protein, PfPLP2, from intracellular vesicles to the periphery, which leads to destabilization of peripheral membranes. Male gametes also develop flagella, which assist in binding female gametes for fertilization. This process of gametogenesis, which is key to malaria transmission, involves extensive membrane remodeling as well as vesicular discharge. Phospholipase A2 enzymes (PLA2) are known to mediate membrane remodeling and vesicle secretion in diverse organisms. Here, we show that a P. falciparum patatin-like phospholipase (PfPATPL1) with PLA2 activity plays a key role in gametogenesis. Conditional deletion of the gene encoding PfPATPL1 does not affect P. falciparum blood stage growth or gametocyte development but reduces efficiency of rounding up, egress, and exflagellation of gametocytes following activation. Interestingly, deletion of the PfPATPL1 gene inhibits secretion of PfPLP2, reducing the efficiency of gamete egress. Deletion of PfPATPL1 also reduces the efficiency of oocyst formation in mosquitoes. These studies demonstrate that PfPATPL1 plays a role in gametogenesis, thereby identifying PLA2 phospholipases such as PfPATPL1 as potential targets for the development of drugs to block malaria transmission.
Assuntos
Gametogênese , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Fosfolipases/metabolismo , Plasmodium falciparum/fisiologia , Proteínas de Protozoários/metabolismo , Biologia Computacional/métodos , Humanos , Estágios do Ciclo de Vida , Fosfolipases/genética , Plasmodium falciparum/ultraestrutura , Proteínas de Protozoários/genética , Deleção de SequênciaRESUMO
A 70-year-old male presented with diplopia and painless proptosis of the left eye for 5 months. Examination showed 6 mm of axial proptosis and restriction of supraduction, abduction and adduction, and mild limitation of infraduction of the left eye. Magnetic resonance imaging demonstrated a large, moderately well-circumscribed intraconal mass in the left lateral orbit, and excisional biopsy was performed. Histopathologic features of mixed fibrous and myxoid areas in a whorl-like pattern and immunohistochemical staining for MUC4 confirmed the diagnosis of low-grade fibromyxoid sarcoma (LGFMS). Next-generation sequencing revealed genetic fusion of EWSR1-CREB3L1. LGFMS is an extremely rare neoplasm with only two prior documented cases of orbital involvement. Here, we report the third case of orbital LGFMS.
RESUMO
The COVID-19 pandemic created significant challenges for the British pub industry, due to the uncertain conditions caused by the virus, changes in consumption patterns and government measures. Studies recommend that organisations adopt innovative and flexible business models to generate added value for customers and other stakeholders as a survival and growth strategy. However, such measures require business ecosystems which encourage co-creative engagement. This qualitative study extends the concept of value co-creation beyond its current boundary as a customer-driven experiential paradigm, reconceptualising it as a driver for societal benefits. Over the period March - December 2020, we carried out in-depth interviews with pub and brewery owners, managers, and customers, combined with netnographic and offline observations of pubs' engagement with customers. We uncovered three stages of strategies and innovation during this period, which we term 'survive', 'secure', and 'sustain'. We demonstrate how multiple stakeholders benefit from the innovations of pubs and breweries negotiating each stage, advancing current scholarship on sustainable value co-creation.