Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact. This notion, ...however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.
Engagement of cytokine receptors by specific ligands activate Janus kinase-signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte ...behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21-induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients.
•Adults with serious mental illness have an elevated rate of 30-day readmissions after medical hospitalizations, but little is known about the differential experiences of people with schizophrenia, ...bipolar disorder, and major depression.•In a multivariable analysis, compared to those with no SMI, people with schizophrenia had the highest odds of 30-day readmission, followed by those with bipolar disorder, and those with major depressive disorder.•Readmissions also were more likely among those with substance use disorders, males, those with Medicaid eligibility due to disability, patients with longer index hospitalizations, and those with 2 or more medical co-morbidities.•The study's findings can be used to design transition interventions and service delivery systems that address the complex needs of people with schizophrenia and co-occurring medical conditions.
While evidence suggests that adults with serious mental illness have an elevated rate of 30-day readmissions after medical hospitalizations, most studies are of patients who are privately insured or Medicare beneficiaries, and little is known about the differential experiences of people with schizophrenia, bipolar disorder, and major depression. We used the Truven Health Analytics MarketScan® Medicaid Multi-State Database to study 43,817 Medicaid enrollees from 11 states, age 18-64, who were discharged from medical hospitalizations in 2011. Our outcome was unplanned all-cause readmissions within 30 days of discharge. In a multivariable analysis, compared to those with no SMI, people with schizophrenia had the highest odds of 30-day readmission (aOR: 1.46, 95% CI: 1.33-1.59), followed by those with bipolar disorder (aOR: 1.25, 95% CI: 1.14-1.38), and those with major depressive disorder (aOR: 1.18, 95% CI: 1.06-1.30). Readmissions also were more likely among those with substance use disorders, males, those with Medicaid eligibility due to disability, patients with longer index hospitalizations, and those with 2 or more medical co-morbidities. This is the first large-scale study to demonstrate the elevated risk of hospital readmission among low-income, working-age adults with schizophrenia. Given their greater psychological, social, and economic vulnerability, our findings can be used to design transition interventions and service delivery systems that address their complex needs.
Vitrinite reflectance generally is considered the most robust thermal maturity parameter available for application to hydrocarbon exploration and petroleum system evaluation. However, until 2011 ...there was no standardized methodology available to provide guidelines for vitrinite reflectance measurements in shale. Efforts to correct this deficiency resulted in publication of ASTM D7708: Standard test method for microscopical determination of the reflectance of vitrinite dispersed in sedimentary rocks. In 2012–2013, an interlaboratory exercise was conducted to establish precision limits for the D7708 measurement technique. Six samples, representing a wide variety of shale, were tested in duplicate by 28 analysts in 22 laboratories from 14 countries. Samples ranged from immature to overmature (0.31–1.53% Ro), from organic-lean to organic-rich (1–22 wt.% total organic carbon), and contained Type I (lacustrine), Type II (marine), and Type III (terrestrial) kerogens. Repeatability limits (maximum difference between valid repetitive results from same operator, same conditions) ranged from 0.03 to 0.11% absolute reflectance, whereas reproducibility limits (maximum difference between valid results obtained on same test material by different operators, different laboratories) ranged from 0.12 to 0.54% absolute reflectance. Repeatability and reproducibility limits degraded consistently with increasing maturity and decreasing organic content. However, samples with terrestrial kerogens (Type III) fell off this trend, showing improved levels of reproducibility due to higher vitrinite content and improved ease of identification. Operators did not consistently meet the reporting requirements of the test method, indicating that a common reporting template is required to improve data quality. The most difficult problem encountered was the petrographic distinction of solid bitumens and low-reflecting inert macerals from vitrinite when vitrinite occurred with reflectance ranges overlapping the other components. Discussion among participants suggested this problem could not be easily corrected via kerogen concentration or solvent extraction and is related to operator training and background. No statistical difference in mean reflectance was identified between participants reporting bitumen reflectance vs. vitrinite reflectance vs. a mixture of bitumen and vitrinite reflectance values, suggesting empirical conversion schemes should be treated with caution. Analysis of reproducibility limits obtained during this exercise in comparison to reproducibility limits from historical interlaboratory exercises suggests use of a common methodology (D7708) improves interlaboratory precision. Future work will investigate opportunities to improve reproducibility in high maturity, organic-lean shale varieties.
•ASTM method D7708 was tested by an interlaboratory study.•Six shale samples were tested by 28 analysts in 22 laboratories from 14 countries.•Repeatability limits (intralaboratory) ranged from 0.03 to 0.11% absolute reflectance.•Reproducibility limits (interlaboratory) ranged from 0.12 to 0.54% absolute reflectance.•Using D7708 improved reproducibility compared to historical interlaboratory studies.
We herein report the synthesis and biological and computational evaluation of 12 linear analogues of the cyclic lipopeptide battacin, enabled by Cysteine Lipidation on a Peptide or Amino Acid ...(CLipPA) technology. Several of the novel "CLipP"ed lipopeptides exhibited low micromolar MICs and MBCs against both Gram-negative and Gram-positive bacteria. The mechanism of action was then simulated with the MIC data using computational methods.
We herein report the synthesis and biological and computational evaluation of 12 linear analogues of the cyclic lipopeptide battacin, enabled by Cysteine Lipidation on a Peptide or Amino Acid (CLipPA) technology.
Two-week-old chicks of a line highly resistant (line C) or highly susceptible (line 151) to infectious bronchitis virus (IBV) were inoculated with the Massachusetts-41 strain of IBV. Trachéal ...washings, saliva, lachrymal fluid and serum were collected at intervals after inoculation and titrated for their antibody content using neutralization tests and ELISAs. There was no marked difference in antibody concentrations in trachéal washings of the two lines, nor in neutralizing antibody or IBV-specific IgG titres in serum or respiratory tract secretions. However, more IBV-specific IgA was detected in both saliva and lachrymal fluid of the line C chicks following either intranasal or eyedrop inoculation. The different IgA response in lachrymal fluid, but not saliva, was also observed in another pair of inbred chicken lines of different susceptibility to IBV infection, namely lines 6, and 7
2
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The authors sought to determine whether staff at a peer-run agency could deliver supported employment services with high fidelity to the individual placement and support (IPS) model and whether ...employment outcomes of peer-delivered IPS plus work-specific health promotion were superior to usual supported employment services.
Two teams from a vocational program of a large peer-run agency were studied from July 2015 to July 2017. One team received training and supervision in delivering IPS plus employment-focused physical wellness support and mentoring. The other team continued providing usual supported employment services. Study data included vocational outcomes from 348 clients served by the two teams (IPS, N=184; comparison condition, N=164) and the results of IPS fidelity reviews of the IPS team at study baseline, midpoint, and end. The authors modeled the primary outcome of competitive employment with random-effects logistic regression and adjusted propensity scores for age, gender, race, ethnicity, education, and months of service receipt.
Following training, the IPS team demonstrated acceptable and increasing fidelity to the IPS model, achieving "good fidelity" by the end of the 25-month observation period. Among IPS recipients, 43% achieved competitive employment versus 21% of comparison recipients (p<0.001). Multivariable analysis indicated that IPS recipients were significantly more likely to achieve competitive employment than individuals in the comparison group (OR=4.06, p<0.001).
Providing training in IPS along with health promotion to the behavioral health peer workforce may help address the severe shortage of IPS services and enhance the competitive employment outcomes of people served by peer-run programs.
Viruses and bacteria colonize hosts by invading epithelial barriers. Recent studies have shown that interactions between the microbiota, pathogens and the host can potentiate infection through poorly ...understood mechanisms. Here, we investigated whether diverse bacterial species could modulate virus internalization into host cells, often a rate-limiting step in establishing infections. Lentiviral pseudoviruses expressing influenza, measles, Ebola, Lassa or vesicular stomatitis virus envelope glycoproteins enabled us to study entry of viruses that exploit diverse internalization pathways. Salmonella Typhimurium, Escherichia coli and Pseudomonas aeruginosa significantly increased viral uptake, even at low bacterial frequencies. This did not require bacterial contact with or invasion of host cells. Studies determined that the bacterial antigen responsible for this pro-viral activity was the Toll-Like Receptor 5 (TLR5) agonist flagellin. Exposure to flagellin increased virus attachment to epithelial cells in a temperature-dependent manner via TLR5-dependent activation of NF-ΚB. Importantly, this phenotype was both long lasting and detectable at low multiplicities of infection. Flagellin is shed from bacteria and our studies uncover a new bystander role for this protein in regulating virus entry. This highlights a new aspect of viral-bacterial interplay with significant implications for our understanding of polymicrobial-associated pathogenesis.
The genome of the fire ant Solenopsis invicta Wurm, Yannick; Wang, John; Riba-Grognuz, Oksana ...
Proceedings of the National Academy of Sciences - PNAS,
04/2011, Letnik:
108, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Ants have evolved very complex societies and are key ecosystem members. Some ants, such as the fire ant Solenopsis invicta, are also major pests. Here, we present a draft genome of S. invicta, ...assembled from Roche 454 and Illumina sequencing reads obtained from a focal haploid male and his brothers. We used comparative genomic methods to obtain insight into the unique features of the 5. invicta genome. For example, we found that this genome harbors four adjacent copies of vitellogenin. A phylogenetic analysis revealed that an ancestral vitellogenin gene first underwent a duplication that was followed by possibly independent duplications of each of the daughter vitellogenins. The vitellogenin genes have undergone subfunctionalization with queen-and worker-specific expression, possibly reflecting differential selection acting on the queen and worker castes. Additionally, we identified more than 400 putative olfactory receptors of which at least 297 are intact. This represents the largest repertoire reported so far in insects. S. invicta also harbors an expansion of a specific family of lipid-processing genes, two putative orthologs to the transformer/feminizer sex differentiation gene, a functional DNA methylation system, and a single putative telomerase ortholog. EST data indicate that this 5. invicta telomerase ortholog has at least four spliceforms that differ in their use of two sets of mutually exclusive exons. Some of these and other unique aspects of the fire ant genome are likely linked to the complex social behavior of this species.
By inoculating chickens intranasally with a collection of strains of infectious bronchitis virus (IBV) of the Massachusetts serotype and of Escherichia coli of different serotypes, a pool of viral ...and bacterial strains was selected which, on inoculation, consistently produced a highly lethal disease closely resembling the natural disease produced by these two organisms. The conditions for reproducing the experimental disease were not rigorous in that, within broad limits, the size of the viral and bacterial inocula were not important; neither were the times at which both organisms were administered in relation to each other. The breed or strain of chicken used was important and the resistance of chickens to fatal infection increased with age. When the E. coli strains of the pool were inoculated intranasally without the IBV component, the chickens remained well; bacteriological examination of chickens inoculated with one of the E. coli strains, O18, revealed little evidence of invasion of the tissues or even of persistence of the inoculated E. coli strain in the upper respiratory tract. A minority of the IBV strains examined were lethal for chickens when inoculated without E. coli but many of them only produced a substantial mortality when the E. coli were included in the inoculum; IBV strains in this latter category included the vaccine strains H52 and H120. High concentrations of IBV strain M41 and E. coli O18 persisted in the upper respiratory tract for a number of days after they had been inoculated together. Much lower concentrations of IBV M41 were found in the internal organs, such as the spleen; E. coli O18 was only found in these sites in some of the inoculated chickens. Coliform organisms proliferated in the upper respiratory tract of chickens inoculated with IBV alone; they were rarely found in their internal organs.
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