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1.
Mol Biol Evol ; 39(3)2022 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-35106603

RESUMEN

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.


Asunto(s)
COVID-19 , SARS-CoV-2 , Hospitales , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2/genética
2.
Rapid Commun Mass Spectrom ; 35(18): e9159, 2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34224610

RESUMEN

RATIONALE: The diet of wild Nile crocodiles (Crocodylus niloticus) is difficult to assess because they are cryptic and nocturnal predators that are extremely sensitive to disturbance by observers, and stomach content analysis is challenging, especially in large specimens. Stable light isotope analysis provides a means of assessing their diet, but diet-to-tissue discrimination factors have yet to be established for the species. METHODS: Isotope ratio (15 N/14 N and 13 C/12 C expressed as δ15 N and δ13 C) analyses of scutes, claws, and blood of farmed crocodiles of different sizes were compared with the isotope values of their lifelong diet, which comprises chickens from a single supplier. RESULTS: Systematic size dependence in the diet-to-tissue discrimination factors for scute collagen, scute keratin, and claw keratin is described in regression relationships against the snout to vent length. Fixed values are presented for erythrocytes and blood plasma because blood was not sampled from juveniles. CONCLUSIONS: The diet-to-tissue discrimination factors help assess the diet of wild crocodiles. The diet of crocodiles from Lake Flag Boshielo shows a clear ontogenic shift, as has been seen in other studies, and the results strongly indicate a dependence on the terrestrial food web rather than a fish diet. That this population may exploit a terrestrial diet highlights potential conflicts for conserving Nile crocodiles outside protected areas.


Asunto(s)
Caimanes y Cocodrilos/metabolismo , Alimentación Animal/análisis , Isótopos de Carbono/análisis , Isótopos de Nitrógeno/análisis , Animales , Pollos , Dieta/veterinaria , Cadena Alimentaria , Espectrometría de Masas
3.
Glob Chang Biol ; 2020 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-33319502

RESUMEN

Rapid anthropogenic environmental change is expected to impact a host of ecological parameters in Southern Ocean ecosystems. Of critical concern are the consequences of these changes on the range of species that show fidelity to migratory destinations, as philopatry is hypothesized to help or hinder adaptation to climate change depending on the circumstances. Many baleen whales show philopatry to feeding grounds and are also capital breeders that meet migratory and reproductive costs through seasonal energy intake. Southern right whales (Eubalaena australis, SRWs) are capital breeders that have a strong relationship between reproductive output and foraging success. The population dynamics of South Africa's population of SRWs are characterized by two distinct periods: the 1990s, a period of high calving rates; and the late 2010s, a period associated with lowered calving rates. Here we use analyses of stable carbon (δ13 C) and nitrogen (δ15 N) isotope values from SRW biopsy samples (n = 122) collected during these two distinct periods to investigate foraging ecology of the South African population of SRWs over a time period coincident with the demographic shift. We show that South African SRWs underwent a dramatic northward shift, and diversification, in foraging strategy from 1990s to 2010s. Bayesian mixing model results suggest that during the 1990s, South African SRWs foraged on prey isotopically similar to South Georgia/Islas Georgias del Sur krill. In contrast, in the 2010s, South African SRWs foraged on prey isotopically consistent with the waters of the Subtropical Convergence, Polar Front and Marion Island. We hypothesize that this shift represents a response to changes in preferred habitat or prey, for example, the decrease in abundance and southward range contraction of Antarctic krill. By linking reproductive decline to changing foraging strategies for the first time in SRWs, we show that altering foraging strategies may not be sufficient to adapt to a changing ocean.

4.
Rapid Commun Mass Spectrom ; 33(3): 291-302, 2019 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-30414205

RESUMEN

RATIONALE: Stable isotope analysis (SIA) has revolutionised ecological studies over the past thirty years. One of the major fields where SIA is applied in the marine environment is related to the definition of ecosystem structure and function. With marine top predators such as sharks, SIA is a method of choice because tissue samples can be collected without the sacrifice of the animal. In elasmobranch research, the influence of compounds such as urea, trimethylamine oxide and lipids must be considered when using stable isotopes as ecological markers. Currently, a range of pre-treatments are used to chemically remove these molecules prior to SIA. METHODS: This study investigated the impact of eleven commonly used pre-treatments on carbon and nitrogen contents and C:N atomic ratio, as well as carbon and nitrogen SI ratios in elasmobranch tissues and its prey, measured by isotope ratio mass spectrometry. Three tissues were tested: blood and muscle of the ragged-tooth shark Carcharias taurus, and muscle of one teleost species, the Cape knifejaw Oplegnathus conwayi. RESULTS: Compared with untreated samples, no trend or generalisation could be highlighted with the influence of pre-treatments being species-, tissue- and chemical-element-dependent. For the δ13 C and δ15 N values, differences among pre-treatments were as high as 3‰, therefore potentially leading to erroneous ecological interpretation. CONCLUSIONS: The chemical properties of compounds (e.g. urea, lipids) combined with the polarity of solutions (e.g. water, solvents) explained a large part of these observations. This study highlights that pre-treatments need to be considered especially when comparing carbon and nitrogen stable isotope ratios between studies. The results of this study provide a call to all stable isotope researchers to make a concerted effort to standardise pre-treatment methods. This is crucial as global reviews are becoming increasingly more informative.


Asunto(s)
Bioquímica/métodos , Isótopos de Carbono/análisis , Peces/fisiología , Isótopos de Nitrógeno/análisis , Animales , Espectrometría de Masas/métodos , Músculos/química , Tiburones
5.
Front Cell Infect Microbiol ; 13: 1236814, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37600947

RESUMEN

Introduction: Cryptosporidiosis is a leading cause of diarrheal-associated morbidity and mortality, predominantly affecting children under 5 years old in low-and-middle-income countries. There is no effective treatment and no vaccine. New therapeutics are emerging from drug discovery efforts. It is critical that mode of action studies are performed alongside drug discovery to ensure the best clinical outcomes. Unfortunately, technology to identify and validate drug targets for Cryptosporidium is severely lacking. Methods: We used C. parvum lysyl-tRNA synthetase (CpKRS) and DDD01510706 as a target-compound pair to develop both chemical and genetic tools for mode of action studies for Cryptosporidium. We adapted thermal proteome profiling (TPP) for Cryptosporidium, an unbiased approach for target identification. Results: Using TPP we identified the molecular target of DDD01510706 and confirm that it is CpKRS. Genetic tools confirm that CpKRS is expressed throughout the life cycle and that this target is essential for parasite survival. Parasites genetically modified to over-express CpKRS or parasites with a mutation at the compound-binding site are resistant to treatment with DDD01510706. We leveraged these mutations to generate a second drug selection marker for genetic modification of Cryptosporidium, KRSR. This second selection marker is interchangeable with the original selection marker, NeoR, and expands the range of reverse genetic approaches available to study parasite biology. Due to the sexual nature of the Cryptosporidium life cycle, parental strains containing different drug selection markers can be crossed in vivo. Discussion: Selection with both drug markers produces highly efficient genetic crosses (>99% hybrid progeny), paving the way for forward genetics approaches in Cryptosporidium.


Asunto(s)
Criptosporidiosis , Cryptosporidium , Lisina-ARNt Ligasa , Niño , Humanos , Preescolar , Cryptosporidium/genética , Criptosporidiosis/tratamiento farmacológico , Lisina-ARNt Ligasa/genética , Sitios de Unión , Diarrea , Propionibacterium acnes
6.
Open Res Eur ; 2: 134, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37645274

RESUMEN

G-protein coupled receptors (GPCRs) are seven-transmembrane proteins and constitute the largest group of receptors within eukaryotes. The presence of a large set of GPCRs in the unicellular Amoebozoa was surprising and is indicative of the largely undiscovered environmental sensing capabilities in this group. Evolutionary transitions from unicellular to multicellular lifestyles, like we see in social amoebas, have occurred several times independently in the Amoebozoa, and GPCRs may have been co-opted for new functions in cell-cell communication. Methods We have analysed a set of GPCRs from fully sequenced Amoebozoan genomes by Bayesian inference, compared their phylogenetic distribution and domain composition, and analysed their temporal and spatial expression patterns in five species of dictyostelids. Results We found evidence that most GPCRs are conserved deeply in the Amoebozoa and are probably performing roles in general cell functions and complex environmental sensing. All families of GPCRs (apart from the family 4 fungal pheromone receptors) are present in dictyostelids with family 5 being the largest and family 2 the one with the fewest members. For the first time, we identify the presence of family 1 rhodopsin-like GPCRs in dictyostelids. Some GPCRs have been amplified in the dictyostelids and in specific lineages thereof and through changes in expression patterns may have been repurposed for signalling in multicellular development. Discussion Our phylogenetic analysis suggests that GPCR families 1, 2 and 6 already diverged early in the Amoebozoa, whereas families 3 and 5 expanded later within the dictyostelids. The family 6 cAMP receptors that have experimentally supported roles in multicellular development in dictyostelids ( carA-carD; tasA/B) originated at the root of all dictyostelids and only have weakly associated homologs in Physarum polycephalum. Our analysis identified candidate GPCRs which have evolved in the dictyostelids and could have been co-opted for multicellular development.

7.
Nat Commun ; 13(1): 751, 2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35136068

RESUMEN

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.


Asunto(s)
COVID-19/epidemiología , COVID-19/transmisión , SARS-CoV-2/genética , Universidades , COVID-19/prevención & control , COVID-19/virología , Trazado de Contacto , Genoma Viral/genética , Genómica , Humanos , Filogenia , ARN Viral/genética , Factores de Riesgo , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , Estudiantes , Reino Unido/epidemiología , Universidades/estadística & datos numéricos
8.
Elife ; 102021 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-34387545

RESUMEN

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95.1% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within- and between-host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.


The COVID-19 pandemic has had major health impacts across the globe. The scientific community has focused much attention on finding ways to monitor how the virus responsible for the pandemic, SARS-CoV-2, spreads. One option is to perform genetic tests, known as sequencing, on SARS-CoV-2 samples to determine the genetic code of the virus and to find any differences or mutations in the genes between the viral samples. Viruses mutate within their hosts and can develop into variants that are able to more easily transmit between hosts. Genetic sequencing can reveal how genetically similar two SARS-CoV-2 samples are. But tracking how SARS-CoV-2 moves from one person to the next through sequencing can be tricky. Even a sample of SARS-CoV-2 viruses from the same individual can display differences in their genetic material or within-host variants. Could genetic testing of within-host variants shed light on factors driving SARS-CoV-2 to evolve in humans? To get to the bottom of this, Tonkin-Hill, Martincorena et al. probed the genetics of SARS-CoV-2 within-host variants using 1,181 samples. The analyses revealed that 95.1% of samples contained within-host variants. A number of variants occurred frequently in many samples, which were consistent with mutational hotspots in the SARS-CoV-2 genome. In addition, within-host variants displayed mutation patterns that were similar to patterns found between infected individuals. The shared within-host variants between samples can help to reconstruct transmission chains. However, the observed mutational hotspots and the detection of multiple strains within an individual can make this challenging. These findings could be used to help predict how SARS-CoV-2 evolves in response to interventions such as vaccines. They also suggest that caution is needed when using information on within-host variants to determine transmission between individuals.


Asunto(s)
COVID-19/genética , COVID-19/fisiopatología , Variación Genética , Genoma Viral , Interacciones Huésped-Patógeno/genética , Mutación , SARS-CoV-2/genética , Secuencia de Bases , Humanos , Pandemias , Filogenia
9.
Elife ; 102021 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-34425938

RESUMEN

SARS-CoV-2 is notable both for its rapid spread, and for the heterogeneity of its patterns of transmission, with multiple published incidences of superspreading behaviour. Here, we applied a novel network reconstruction algorithm to infer patterns of viral transmission occurring between patients and health care workers (HCWs) in the largest clusters of COVID-19 infection identified during the first wave of the epidemic at Cambridge University Hospitals NHS Foundation Trust, UK. Based upon dates of individuals reporting symptoms, recorded individual locations, and viral genome sequence data, we show an uneven pattern of transmission between individuals, with patients being much more likely to be infected by other patients than by HCWs. Further, the data were consistent with a pattern of superspreading, whereby 21% of individuals caused 80% of transmission events. Our study provides a detailed retrospective analysis of nosocomial SARS-CoV-2 transmission, and sheds light on the need for intensive and pervasive infection control procedures.


The COVID-19 pandemic, caused by the SARS-CoV-2 virus, presents a global public health challenge. Hospitals have been at the forefront of this battle, treating large numbers of sick patients over several waves of infection. Finding ways to manage the spread of the virus in hospitals is key to protecting vulnerable patients and workers, while keeping hospitals running, but to generate effective infection control, researchers must understand how SARS-CoV-2 spreads. A range of factors make studying the transmission of SARS-CoV-2 in hospitals tricky. For instance, some people do not present any symptoms, and, amongst those who do, it can be difficult to determine whether they caught the virus in the hospital or somewhere else. However, comparing the genetic information of the SARS-CoV-2 virus from different people in a hospital could allow scientists to understand how it spreads. Samples of the genetic material of SARS-CoV-2 can be obtained by swabbing infected individuals. If the genetic sequences of two samples are very different, it is unlikely that the individuals who provided the samples transmitted the virus to one another. Illingworth, Hamilton et al. used this information, along with other data about how SARS-CoV-2 is transmitted, to develop an algorithm that can determine how the virus spreads from person to person in different hospital wards. To build their algorithm, Illingworth, Hamilton et al. collected SARS-CoV-2 genetic data from patients and staff in a hospital, and combined it with information about how SARS-CoV-2 spreads and how these people moved in the hospital . The algorithm showed that, for the most part, patients were infected by other patients (20 out of 22 cases), while staff were infected equally by patients and staff. By further probing these data, Illingworth, Hamilton et al. revealed that 80% of hospital-acquired infections were caused by a group of just 21% of individuals in the study, identifying a 'superspreader' pattern. These findings may help to inform SARS-CoV-2 infection control measures to reduce spread within hospitals, and could potentially be used to improve infection control in other contexts.


Asunto(s)
COVID-19/epidemiología , COVID-19/transmisión , Brotes de Enfermedades/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
10.
Elife ; 102021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33650490

RESUMEN

COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.


Asunto(s)
COVID-19/epidemiología , COVID-19/transmisión , Casas de Salud , SARS-CoV-2/genética , Anciano de 80 o más Años , COVID-19/virología , Brotes de Enfermedades , Inglaterra/epidemiología , Femenino , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Transmisión de Enfermedad Infecciosa de Profesional a Paciente , Masculino , Polimorfismo de Nucleótido Simple , Análisis de Secuencia , Factores de Tiempo
11.
bioRxiv ; 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32908977

RESUMEN

Genome sequencing has been widely deployed to study the evolution of SARS-CoV-2 with more than 90,000 genome sequences uploaded to the GISAID database. We published a method for SARS-CoV-2 genome sequencing (https://www.protocols.io/view/ncov-2019-sequencing-protocol-bbmuik6w) online on January 22, 2020. This approach has rapidly become the most popular method for sequencing SARS-CoV-2 due to its simplicity and cost-effectiveness. Here we present improvements to the original protocol: i) an updated primer scheme with 22 additional primers to improve genome coverage, ii) a streamlined library preparation workflow which improves demultiplexing rate for up to 96 samples and reduces hands-on time by several hours and iii) cost savings which bring the reagent cost down to £10 per sample making it practical for individual labs to sequence thousands of SARS-CoV-2 genomes to support national and international genomic epidemiology efforts.

12.
Microbiome ; 8(1): 62, 2020 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-32375874

RESUMEN

BACKGROUND: The archaeological incidence of ancient human faecal material provides a rare opportunity to explore the taxonomic composition and metabolic capacity of the ancestral human intestinal microbiome (IM). Here, we report the results of the shotgun metagenomic analyses of an ancient South African palaeo-faecal specimen. METHODS: Following the recovery of a single desiccated palaeo-faecal specimen from Bushman Rock Shelter in Limpopo Province, South Africa, we applied a multi-proxy analytical protocol to the sample. The extraction of ancient DNA from the specimen and its subsequent shotgun metagenomic sequencing facilitated the taxonomic and metabolic characterisation of this ancient human IM. RESULTS: Our results indicate that the distal IM of the Neolithic 'Middle Iron Age' (c. AD 1460) Bantu-speaking individual exhibits features indicative of a largely mixed forager-agro-pastoralist diet. Subsequent comparison with the IMs of the Tyrolean Iceman (Ötzi) and contemporary Hadza hunter-gatherers, Malawian agro-pastoralists and Italians reveals that this IM precedes recent adaptation to 'Western' diets, including the consumption of coffee, tea, chocolate, citrus and soy, and the use of antibiotics, analgesics and also exposure to various toxic environmental pollutants. CONCLUSIONS: Our analyses reveal some of the causes and means by which current human IMs are likely to have responded to recent dietary changes, prescription medications and environmental pollutants, providing rare insight into human IM evolution following the advent of the Neolithic c. 12,000 years ago. Video Abtract.


Asunto(s)
Arqueología , Heces/microbiología , Microbioma Gastrointestinal , África del Sur del Sahara , Historia del Siglo XV , Humanos , Metagenómica
13.
Lancet Infect Dis ; 20(11): 1263-1272, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32679081

RESUMEN

BACKGROUND: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures. METHODS: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. FINDINGS: Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting. INTERPRETATION: We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings. FUNDING: COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Control de Infecciones/métodos , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Niño , Preescolar , Infecciones por Coronavirus/virología , Infección Hospitalaria/virología , Inglaterra/epidemiología , Femenino , Genoma Viral/genética , Hospitales Universitarios , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Filogenia , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , SARS-CoV-2 , Secuenciación Completa del Genoma/métodos , Adulto Joven
14.
Viruses ; 11(8)2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31374901

RESUMEN

Successful in vivo infection following pathogen entry requires the evasion and subversion of multiple immunological barriers. Antimicrobial peptides (AMPs) are one of the first immune pathways upregulated during infection by multiple pathogens, in multiple organs in vivo. In humans, there are many classes of AMPs exhibiting broad antimicrobial activities, with defensins and the human cathelicidin LL-37 being the best studied examples. Whereas historically the efficacy and therapeutic potential of AMPs against bacterial infection has been the primary focus of research, recent studies have begun to elucidate the antiviral properties of AMPs as well as their role in regulation of inflammation and chemoattraction. AMPs as therapeutic tools seem especially promising against emerging infectious viral pathogens for which no approved vaccines or treatments are currently available, such as dengue virus (DENV) and Zika virus (ZIKV). In this review, we summarize recent studies elucidating the efficacy and diverse mechanisms of action of various classes of AMPs against multiple viral pathogens, as well as the potential use of human AMPs in novel antiviral therapeutic strategies.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/uso terapéutico , Antivirales/uso terapéutico , Virosis/tratamiento farmacológico , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/farmacología , Antivirales/farmacología , Humanos , Inmunomodulación , Virosis/prevención & control , Replicación Viral/efectos de los fármacos , Virus/efectos de los fármacos
15.
R Soc Open Sci ; 5(12): 180849, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30662720

RESUMEN

Bats play important ecological roles in tropical systems, yet how these communities are structured is still poorly understood. Our study explores the structure of African bat communities using morphological characters to define the morphospace occupied by these bats and stable isotope analysis to define their dietary niche breadth. We compared two communities, one in rainforest (Liberia) and one in savannah (South Africa), and asked whether the greater richness in the rainforest was due to more species 'packing' into the same morphospace and trophic space than bats from the savannah, or some other arrangement. In the rainforest, bats occupied a larger area in morphospace and species packing was higher than in the savannah; although this difference disappeared when comparing insectivorous bats only. There were also differences in morphospace occupied by different foraging groups (aerial, edge, clutter and fruitbat). Stable isotope analysis revealed that the range of δ 13C values was almost double in rainforest than in savannah indicating a greater range of utilization of basal C3 and C4 resources in the former site, covering primary productivity from both these sources. The ranges in δ 15N, however, were similar between the two habitats suggesting a similar number of trophic levels. Niche breadth, as defined by either standard ellipse area or convex hull, was greater for the bat community in rainforest than in savannah, with all four foraging groups having larger niche breadths in the former than the latter. The higher inter-species morphospace and niche breadth in forest bats suggest that species packing is not necessarily competitive. By employing morphometrics and stable isotope analysis, we have shown that the rainforest bat community packs more species in morphospace and uses a larger niche breadth than the one in savannah.

16.
Sci Rep ; 8(1): 6921, 2018 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-29720684

RESUMEN

Carbon exchange in drylands is typically low, but during significant rainfall events (wet anomalies) drylands act as a C sink. During these anomalies the limitation on C uptake switches from water to nitrogen. In the Namib Desert of southern Africa, the N inventory in soil organic matter available for mineralisation is insufficient to support the observed increase in primary productivity. The C4 grasses that flourish after rainfall events are not capable of N fixation, and so there is no clear mechanism for adequate N fixation in dryland ecosystems to support rapid C uptake. Here we demonstrate that N fixation by photoautotrophic hypolithic communities forms the basis for the N budget for plant productivity events in the Namib Desert. Stable N isotope (δ15N) values of Namib Desert hypolithic biomass, and surface and subsurface soils were measured over 3 years across dune and gravel plain biotopes. Hypoliths showed significantly higher biomass and lower δ15N values than soil organic matter. The δ15N values of hypoliths approach the theoretical values for nitrogen fixation. Our results are strongly indicative that hypolithic communities are the foundation of productivity after rain events in the Namib Desert and are likely to play similar roles in other arid environments.


Asunto(s)
Clima Desértico , Microbiota , Fijación del Nitrógeno , África Austral , Biodiversidad , Carbono , Ecosistema , Plantas , Microbiología del Suelo
17.
Nat Plants ; 4(7): 505, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29967518

RESUMEN

In Supplementary Table 1 originally published with this Brief Communication, the authors gave an incorrect GPS easterly coordinate for tree number 12 (Makulu Makete Big baobab); the coordinate '2° 34.584' S, 25° 52.261' E' should have read '22° 34.584' S, 28° 52.261' E'. This has now been amended in the online Supplementary Information file for this Brief Communication.

18.
Nat Plants ; 4(7): 423-426, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29892092

RESUMEN

The African baobab is the biggest and longest-living angiosperm tree. By using radiocarbon dating we identified the stable architectures that enable baobabs to reach large sizes and great ages. We report that 9 of the 13 oldest and 5 of the 6 largest individuals have died, or at least their oldest parts/stems have collapsed and died, over the past 12 years; the cause of the mortalities is still unclear.


Asunto(s)
Adansonia , Adansonia/crecimiento & desarrollo , África del Sur del Sahara , Tallos de la Planta/crecimiento & desarrollo , Datación Radiométrica , Árboles/crecimiento & desarrollo , Madera/crecimiento & desarrollo
19.
PLoS One ; 11(7): e0159361, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27427912

RESUMEN

Carbon isotope analysis of four baobab (Adansonia digitata L.) trees from the Pafuri region of South Africa yielded a 1000-year proxy rainfall record. The Pafuri record age model was based on 17 radiocarbon dates, cross correlation of the climate record, and ring structures that were presumed to be annual for two of the trees. Here we present the analysis of five additional baobabs from the Mapungubwe region, approximately 200km west of Pafuri. The Mapungubwe chronology demonstrates that ring structures are not necessarily annually formed, and accordingly the Pafuri chronology is revised. Changes in intrinsic water-use efficiency indicate an active response by the trees to elevated atmospheric CO2, but this has little effect on the environmental signal. The revised Pafuri record, and the new Mapungubwe record correlate significantly with local rainfall. Both records confirm that the Medieval Warm Period was substantially wetter than present, and the Little Ice Age was the driest period in the last 1000 years. Although Mapungubwe is generally drier than Pafuri, both regions experience elevated rainfall peaking between AD 1570 and AD 1620 after which dry conditions persist in the Mapungubwe area until about AD 1840. Differences between the two records correlate with Agulhas Current sea-surface temperature variations suggesting east/west displacement of the temperate tropical trough system as an underlying mechanism. The Pafuri and Mapungubwe records are combined to provide a regional climate proxy record for the northern summer rainfall area of southern Africa.


Asunto(s)
Adansonia/fisiología , Dióxido de Carbono/historia , Meteorología/métodos , Modelos Estadísticos , Árboles/fisiología , África Austral , Dióxido de Carbono/metabolismo , Isótopos de Carbono , Historia Antigua , Lluvia , Estaciones del Año , Temperatura , Clima Tropical
20.
PLoS One ; 10(5): e0124202, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25970402

RESUMEN

A proxy rainfall record for northeastern South Africa based on carbon isotope analysis of four baobab (Adansonia digitata L.) trees shows centennial and decadal scale variability over the last 1,000 years. The record is in good agreement with a 200-year tree ring record from Zimbabwe, and it indicates the existence of a rainfall dipole between the summer and winter rainfall areas of South Africa. The wettest period was c. AD 1075 in the Medieval Warm Period, and the driest periods were c. AD 1635, c. AD 1695 and c. AD1805 during the Little Ice Age. Decadal-scale variability suggests that the rainfall forcing mechanisms are a complex interaction between proximal and distal factors. Periods of higher rainfall are significantly associated with lower sea-surface temperatures in the Agulhas Current core region and a negative Dipole Moment Index in the Indian Ocean. The correlation between rainfall and the El Niño/Southern Oscillation Index is non-static. Wetter conditions are associated with predominantly El Niño conditions over most of the record, but since about AD 1970 this relationship inverted and wet conditions are currently associated with la Nina conditions. The effect of both proximal and distal oceanic influences are insufficient to explain the rainfall regime shift between the Medieval Warm Period and the Little Ice Age, and the evidence suggests that this was the result of a northward shift of the subtropical westerlies rather than a southward shift of the Intertropical Convergence Zone.


Asunto(s)
Adansonia/fisiología , Isótopos de Carbono/química , El Niño Oscilación del Sur/historia , Lluvia/química , Árboles/fisiología , Adansonia/química , Sedimentos Geológicos/química , Historia Medieval , Océano Índico , Estaciones del Año , Sudáfrica , Temperatura , Árboles/química
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