Since Last Glacial Maximum (23–19 ka), Earth climate warming and deglaciation occurred in two major steps (Bølling‐Allerød and Preboreal), interrupted by a short cooling interval referred to as the ...Younger Dryas (12.5–11.5 ka B.P.). In this study, three cores (MV‐33, MV‐66, and MD‐40) collected in the central part of Pandora Trough (Gulf of Papua) have been analyzed, and they reveal a detailed sedimentary pattern at millennial timescale. Siliciclastic turbidites disappeared during the Bølling‐Allerød and Preboreal intervals to systematically reoccur during the Younger Dryas interval. Subsequent to the final disappearance of the siliciclastic turbidites a calciturbidite occurred during meltwater pulse 1B. The Holocene interval was characterized by a lack of siliciclastic turbidites, relatively high carbonate content, and fine bank‐derived aragonitic sediment. The observed millennial timescale sedimentary variability can be explained by sea level fluctuations. During the Last Glacial Maximum, siliciclastic turbidites were numerous when the lowstand coastal system was located along the modern shelf edge. Although they did not occur during the intervals of maximum flooding of the shelf (during meltwater pulses 1A and 1B), siliciclastic turbidites reappear briefly during the Younger Dryas, an interval when sea level rise slowed, stopped, or perhaps even fell. The timing of the calciturbidite coincides with the first reflooding of Eastern Fields Reef, an atoll that remained exposed for most of the glacial stages.
This paper outlines the evolution of the late Cenozoic mixed carbonate‐siliciclastic depositional system in the Gulf of Papua (GoP), using seismic, gravity, multibeam bathymetry, well data sets, and ...Landsat imagery. The deposition of the mixed sedimentary sequences was influenced by dynamic interplay of tectonics, eustasy, in situ carbonate production, and siliciclastic sediment supply. The roles of these major factors are estimated during different periods of the GoP margin evolution. The Cenozoic mixed system in the GoP formed in distinct phases. The first phase (Late Cretaceous–Paleocene) was mostly driven by tectonics. Rifting created grabens and uplifted structural blocks which served later as pedestals for carbonate edifices. Active neritic carbonate accumulation characterized the second phase (Eocene–middle Miocene). During this phase, mostly eustatic fluctuations controlled the large‐scale sedimentary geometries of the carbonate system. The third phase (late Miocene–early Pliocene) was characterized by extensive demise of the carbonate platforms in the central part of the study area, which can be triggered by one or combination of several factors, such as eustatic sea level fluctuations, increased tectonic subsidence, uplift, sudden influx of siliciclastics, or dramatic changes in environmental conditions and climate. The fourth phase (late Pliocene‐Holocene) was dominated by siliciclastics, which resulted in the burial of drowned and/or active carbonate platforms, although some platforms still remain alive until present‐day.
Ashmore Trough in the western Gulf of Papua (GoP) represents an outstanding modern example of a tropical mixed siliciclastic‐carbonate depositional system where significant masses of both river‐borne ...silicates and bank‐derived neritic carbonates accumulate. In this study, we examine how benthic foraminiferal populations within Ashmore Trough vary in response to sea level–driven paleoenvironmental changes, particularly organic matter and sediment supply. Two 11.3‐m‐long piston cores and a trigger core were collected from the slope of Ashmore Trough and dated using radiocarbon and oxygen isotope measurements of planktic foraminifera. Relative abundances, principal component analyses, and cluster analyses of benthic foraminiferal assemblages in sediment samples identify three distinct assemblages whose proportions changed over time. Assemblage 1, with high abundances of Uvigerina peregrina and Bolivina robusta, dominated between ∼83 and 70 ka (early regression); assemblage 2, with high abundances of Globocassidulina subglobosa, dominated between ∼70 and 11 ka (late regression through lowstand and early transgression); and assemblage 3, with high abundances of neritic benthic species such as Planorbulina mediterranensis, dominated from ∼11 ka to the present (late transgression through early highstand). Assemblage 1 represents heightened organic carbon flux or lowered bottom water oxygen concentration, and corresponds to a time of maximum siliciclastic fluxes to the slope with falling sea level. Assemblage 2 reflects lowered organic carbon flux or elevated bottom water oxygen concentration, and corresponds to an interval of lowered siliciclastic fluxes to the slope due to sediment bypass during sea level lowstand. Assemblage 3 signals increased off‐shelf delivery of neritic carbonates, likely when carbonate productivity on the outer shelf (Great Barrier Reef) increased significantly when it was reflooded. Benthic foraminiferal assemblages in the sediment sink (slopes of Ashmore Trough) likely respond to the amount and type of sediment supplied from the proximal source (outer GoP shelf).
SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase and a nuclease that restricts HIV-1 in noncycling cells. Germ-line mutations in SAMHD1 have been described in patients with ...Aicardi-Goutières syndrome (AGS), a congenital autoimmune disease. In a previous longitudinal whole genome sequencing study of chronic lymphocytic leukemia (CLL), we revealed a SAMHD1 mutation as a potential founding event. Here, we describe an AGS patient carrying a pathogenic germ-line SAMHD1 mutation who developed CLL at 24 years of age. Using clinical trial samples, we show that acquired SAMHD1 mutations are associated with high variant allele frequency and reduced SAMHD1 expression and occur in 11% of relapsed/refractory CLL patients. We provide evidence that SAMHD1 regulates cell proliferation and survival and engages in specific protein interactions in response to DNA damage. We propose that SAMHD1 may have a function in DNA repair and that the presence of SAMHD1 mutations in CLL promotes leukemia development.
•Acquired pathogenic mutations in SAMHD1 are found in up to 11% of relapsed/refractory patients with CLL.•SAMHD1 is mobilized to sites of DNA damage.
The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). ...Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180).
A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain's evolution.
GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage ϕOXC141. Prior to the introduction of PCV13, this clade's composition shifted towards a ϕOXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also ϕOXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the ~100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage ϕOXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in ~30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation.
This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics.
The lack of population health surveillance for companion animal populations leaves them vulnerable to the effects of novel diseases without means of early detection. We present evidence on the ...effectiveness of a system that enabled early detection and rapid response a canine gastroenteritis outbreak in the United Kingdom. In January 2020, prolific vomiting among dogs was sporadically reported in the United Kingdom. Electronic health records from a nationwide sentinel network of veterinary practices confirmed a significant increase in dogs with signs of gastroenteric disease. Male dogs and dogs living with other vomiting dogs were more likely to be affected. Diet and vaccination status were not associated with the disease; however, a canine enteric coronavirus was significantly associated with illness. The system we describe potentially fills a gap in surveillance in neglected populations and could provide a blueprint for other countries.
Understanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients is generally attributed to the selection of drug ...resistant mutants during inadequate therapy rather than transmission of a resistant strain. Traditional genotyping methods are not sufficient to distinguish strains in populations with a high burden of tuberculosis and it has previously been difficult to assess the degree of transmission in these settings. We have used whole genome analysis to investigate M. tuberculosis strains isolated from treatment experienced patients with MDR-TB in Uganda over a period of four years.
We used high throughput genome sequencing technology to investigate small polymorphisms and large deletions in 51 Mycobacterium tuberculosis samples from 41 treatment-experienced TB patients attending a TB referral and treatment clinic in Kampala. This was a convenience sample representing 69% of MDR-TB cases identified over the four year period. Low polymorphism was observed in longitudinal samples from individual patients (2-15 SNPs). Clusters of samples with less than 50 SNPs variation were examined. Three clusters comprising a total of 8 patients were found with almost identical genetic profiles, including mutations predictive for resistance to rifampicin and isoniazid, suggesting transmission of MDR-TB. Two patients with previous drug susceptible disease were found to have acquired MDR strains, one of which shared its genotype with an isolate from another patient in the cohort.
Whole genome sequence analysis identified MDR-TB strains that were shared by more than one patient. The transmission of multidrug-resistant disease in this cohort of retreatment patients emphasises the importance of early detection and need for infection control. Consideration should be given to rapid testing for drug resistance in patients undergoing treatment to monitor the emergence of resistance and permit early intervention to avoid onward transmission.
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