1,308 research outputs found

    The Evolution of the Thermal Niche Across Locally Adapted Populations of the Copepod Tigriopus californicus

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    Local adaptation to different thermal environments is often expected to result in trade-offs in other measures of performance, thermal or otherwise. Populations of the copepod Tigriopus californicus found along the Pacific coast of North America have previously been shown to display patterns consistent with local adaptation and thermal trade-offs. Much of the work on this species has focused on performance at high and moderate temperatures with the lower thermal performance explored to a lesser degree. In this study, measures of both high and low thermal performance are examined for a set of eight T. californicus populations spanning a range from Central Baja California, Mexico to the State of Washington, USA. High temperature survival decreases with increasing latitude while chill coma recovery improves with increasing latitude. Comparisons of these measures among populations along with previous results suggest that there is a shift in the thermal niche in this species rather than other forms of trade-offs such as specialist/generalist trade-offs

    Vietnam's responses to provincial economic disparities through central-provincial government financial relations

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    The paper examines key changes in central-provincial government financial arrangements and their effects on provincial economic disparities in Vietnam over the period 2000-2008. We find that after 2004, transfers from the central to provincial governments conformed much more closely to objective and pre-determined criteria than before. Econometric estimations indicate that in the post-2004 sub-period, poorer provinces obtained more-than-proportionate assistance from the central government, and the favourable treatment was statistically significant. Responses from interviews and statistical data suggest that transfers from the central government played an important role in reducing poverty and provincial output disparities after 2004. The difficulties experienced by the central government in securing adequate resources to finance such transfers, the over-reliance of some provinces on the transfers, and related policy implications are also discussed in the paper

    High resolution clustering of Salmonella enterica serovar Montevideo strains using a next-generation sequencing approach

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    <p>Abstract</p> <p>Background</p> <p>Next-Generation Sequencing (NGS) is increasingly being used as a molecular epidemiologic tool for discerning ancestry and traceback of the most complicated, difficult to resolve bacterial pathogens. Making a linkage between possible food sources and clinical isolates requires distinguishing the suspected pathogen from an environmental background and placing the variation observed into the wider context of variation occurring within a serovar and among other closely related foodborne pathogens. Equally important is the need to validate these high resolution molecular tools for use in molecular epidemiologic traceback. Such efforts include the examination of strain cluster stability as well as the cumulative genetic effects of sub-culturing on these clusters. Numerous isolates of <it>S</it>. Montevideo were shot-gun sequenced including diverse lineage representatives as well as numerous replicate clones to determine how much variability is due to bias, sequencing error, and or the culturing of isolates. All new draft genomes were compared to 34 <it>S</it>. Montevideo isolates previously published during an NGS-based molecular epidemiological case study.</p> <p>Results</p> <p>Intraserovar lineages of <it>S</it>. Montevideo differ by thousands of SNPs, that are only slightly less than the number of SNPs observed between <it>S</it>. Montevideo and other distinct serovars. Much less variability was discovered within an individual <it>S</it>. Montevideo clade implicated in a recent foodborne outbreak as well as among individual NGS replicates. These findings were similar to previous reports documenting homopolymeric and deletion error rates with the Roche 454 GS Titanium technology. In no case, however, did variability associated with sequencing methods or sample preparations create inconsistencies with our current phylogenetic results or the subsequent molecular epidemiological evidence gleaned from these data.</p> <p>Conclusions</p> <p>Implementation of a validated pipeline for NGS data acquisition and analysis provides highly reproducible results that are stable and predictable for molecular epidemiological applications. When draft genomes are collected at 15×-20× coverage and passed through a quality filter as part of a data analysis pipeline, including sub-passaged replicates defined by a few SNPs, they can be accurately placed in a phylogenetic context. This reproducibility applies to all levels within and between serovars of <it>Salmonella </it>suggesting that investigators using these methods can have confidence in their conclusions.</p

    Formation and fate of low metallicity stars in IllustrisTNG50

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    Low metallicity stars give rise to unique spectacular transients and are of immense interest for understanding stellar evolution. Their importance has only grown further with the recent detections of mergers of stellar mass black holes that likely originate mainly from low metallicity progenitor systems. Moreover, the formation of low metallicity stars is intricately linked to galaxy evolution, in particular to early enrichment and to later accretion and mixing of lower metallicity gas. Because low metallicity stars are difficult to observe directly, cosmological simulations are crucial for understanding their formation. Here we quantify the rates and locations of low metallicity star formation using the high-resolution TNG50 magnetohydrodynamical cosmological simulation, and we examine where low metallicity stars end up at z=0z=0. We find that 20%20\% of stars with Z<0.1ZZ_*<0.1\,\mathrm{Z_\odot} form after z=2z=2, and that such stars are still forming in galaxies of all masses at z=0z=0 today. Moreover, most low-metallicity stars at z=0z=0 reside in massive galaxies. We analyse the radial distribution of low metallicity star formation, and discuss the curious case of seven galaxies in TNG50 that form stars from primordial gas even at z=0z=0.Comment: 15 pages, 11 figures, accepted by MNRAS, comments welcom

    A systematic review of primary large cell neuroendocrine carcinoma of the prostate

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    BackgroundLarge cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported.Materials and methodsA systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from de novo or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes.ResultsA total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with de novo LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with de novo prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies.ConclusionLCNEC of the prostate is a rare disease that can occur de novo or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy

    Iron Overload during Follow-up after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma

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    Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects

    Use Of Touch Screen Tablets to Support Social Connections and Reduce Responsive Behaviours among People with Dementia in Care Settings: A Scoping Review Protocol

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    Introduction The disabilities associated with dementia make the adjustment to staying in a care setting stressful. Separation from family can exacerbate the effects of stress. The use of touch screen tablets such as an iPad may offer potential to support the person with dementia staying in a care setting. Although electronic devices are used among people with dementia for a variety of purposes, a comprehensive review of studies focusing on their impact in care settings for social connection and patient/resident behaviour is lacking. This scoping review will focus on the use of touch screen tablets to support social connections and reducing responsive behaviours of people with dementia while in a care setting, such as a hospital ward. Methods and analysis This scoping review will follow Joanna Briggs Institute scoping review methodology. The review team consists of two patient partners and three family partners, a nurse researcher, a research assistant and an academic professor. All authors including patient and family partners were involved in preparing this scoping review protocol. In the scoping review, we will search the following databases: MEDLINE, AgeLine, Cochrane, CINAHL, PsycINFO and IEEE. Google and Google Scholar will be used to search for additional literature. A hand search will be conducted using the reference lists of included studies to identify additional relevant articles. Included studies must report on the impact of using a touch screen technology intervention that involves older adults with dementia in care settings, published in English since 2009. Ethics and dissemination This review study does not require ethics approval. By examining the current state of using touch screen tablets to support older people with dementia in care settings, this scoping review can offer useful insight into users’ needs (eg, patients’ and care providers’ needs) and inform future research and practice. We will share the scoping review results through conference presentations and an open access publication in a peer-reviewed journal

    Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes

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    Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli, which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology

    Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes.

    Get PDF
    Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli, which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology

    Conditional Immortalization of Human B Cells by CD40 Ligation

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    It is generally assumed that human differentiated cells have a limited life-span and proliferation capacity in vivo, and that genetic modifications are a prerequisite for their immortalization in vitro. Here we readdress this issue, studying the long-term proliferation potential of human B cells. It was shown earlier that human B cells from peripheral blood of healthy donors can be efficiently induced to proliferate for up to ten weeks in vitro by stimulating their receptor CD40 in the presence of interleukin-4. When we applied the same stimuli under conditions of modified cell number and culture size, we were surprised to find that our treatment induced B cells to proliferate throughout an observation period of presently up to 1650 days, representing more than 370 population doublings, which suggested that these B cells were immortalized in vitro. Long-term CD40-stimulated B cell cultures could be established from most healthy adult human donors. These B cells had a constant phenotype, were free from Epstein-Barr virus, and remained dependent on CD40 ligation. They had constitutive telomerase activity and stabilized telomere length. Moreover, they were susceptible to activation by Toll-like receptor 9 ligands, and could be used to expand antigen-specific cytotoxic T cells in vitro. Our results indicate that human somatic cells can evade senescence and be conditionally immortalized by external stimulation only, without a requirement for genetic manipulation or oncoviral infection. Conditionally immortalized human B cells are a new tool for immunotherapy and studies of B cell oncogenesis, activation, and function
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