RNA-seq transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis

Bovine tuberculosis, caused by infection with Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including gene expression microarrays and RNA-sequencing (RNA-seq), has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analyzed the peripheral blood leukocyte (PBL) transcriptome of eight natural M. bovis-infected and eight age- and sex-matched non-infected control Holstein-Friesian animals using RNA-seq. In addition, we compared gene expression profiles generated using RNA-seq with those previously generated using the high-density Affymetrix(®) GeneChip(®) Bovine Genome Array platform from the same PBL-extracted RNA. A total of 3,250 differentially expressed (DE) annotated genes were detected in the M. bovis-infected samples relative to the controls (adjusted P-value ≤0.05), with the number of genes displaying decreased relative expression (1,671) exceeding those with increased relative expression (1,579). Ingenuity(®) Systems Pathway Analysis (IPA) of all DE genes revealed enrichment for genes with immune function. Notably, transcriptional suppression was observed among several of the top-ranking canonical pathways including Leukocyte Extravasation Signaling. Comparative platform analysis demonstrated that RNA-seq detected a larger number of annotated DE genes (3,250) relative to the microarray (1,398), of which 917 genes were common to both technologies and displayed the same direction of expression. Finally, we show that RNA-seq had an increased dynamic range compared to the microarray for estimating differential gene expression

Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro

BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular pathogen that can persist inside host macrophages during infection via a diverse range of mechanisms that subvert the host immune response. In the current study, we have analysed and compared the transcriptomes of M. bovis-infected monocyte-derived macrophages (MDM) purified from six Holstein-Friesian females with the transcriptomes of non-infected control MDM from the same animals over a 24 h period using strand-specific RNA sequencing (RNA-seq). In addition, we compare gene expression profiles generated using RNA-seq with those previously generated by us using the high-density Affymetrix® GeneChip® Bovine Genome Array platform from the same MDM-extracted RNA. RESULTS: A mean of 7.2 million reads from each MDM sample mapped uniquely and unambiguously to single Bos taurus reference genome locations. Analysis of these mapped reads showed 2,584 genes (1,392 upregulated; 1,192 downregulated) and 757 putative natural antisense transcripts (558 upregulated; 119 downregulated) that were differentially expressed based on sense and antisense strand data, respectively (adjusted P-value ≤ 0.05). Of the differentially expressed genes, 694 were common to both the sense and antisense data sets, with the direction of expression (i.e. up- or downregulation) positively correlated for 693 genes and negatively correlated for the remaining gene. Gene ontology analysis of the differentially expressed genes revealed an enrichment of immune, apoptotic and cell signalling genes. Notably, the number of differentially expressed genes identified from RNA-seq sense strand analysis was greater than the number of differentially expressed genes detected from microarray analysis (2,584 genes versus 2,015 genes). Furthermore, our data reveal a greater dynamic range in the detection and quantification of gene transcripts for RNA-seq compared to microarray technology. CONCLUSIONS: This study highlights the value of RNA-seq in identifying novel immunomodulatory mechanisms that underlie host-mycobacterial pathogen interactions during infection, including possible complex post-transcriptional regulation of host gene expression involving antisense RNA

Etiology of nocturia response in men with diminished bladder capacity

Aims: To test the hypothesis that patients with nocturia owing to diminished global or nocturnal bladder capacity improve via increased bladder capacity. Methods: This is a retrospective analysis of voiding diaries completed at a VA urology clinic between 2008-2017. Inclusion required patients aged at least 18 years, male, undergoing treatment for nocturia, and having completed at least two 24-hour voiding diaries >= 1 month apart. Patients were divided into two cohorts: responders (any decline in nocturia) and non-responders (no change or any increase in nocturia). Patients were further sub-stratified as having low global bladder capacity (maximum voided volume [MVV] = 200 mL). Wilcoxon rank-sum was applied with a Bonferroni correction to test significance. Results: Forty pre- and post-treatment diaries from 27 patients, and 19 pre- and post-treatment diaries from 17 patients were identified as having low global and low nocturnal bladder capacity, respectively. Nocturia responders with low global bladder capacity demonstrated significant decline compared to non-responders in nocturnal urine volume (NUV) (-140 vs +75, P < 0.01) and nocturnal bladder capacity index (NBCi) (-0.59 vs +0.23, P < 0.01). Patients with low nocturnal bladder capacity similarly demonstrated decreased NUV (-30 vs +160, P = 0.04) and NBCi (-1.4 vs +0.33, P < 0.01). There was no significant change in MVV or NMVV for either group. Conclusions: Treatment directed at lowering nocturnal urine production and enabling patients to consistently void at capacity is a rational strategy to treat nocturia in patients with low bladder capacity

Precision measurement of the η→π+π−π0\eta\to\pi^+\pi^-\pi^0 Dalitz plot distribution with the KLOE detector

Using $1.6$ fb$^{-1}$ of $e^+ e^-\to\phi\to\eta\gamma$ data collected with the KLOE detector at DA$\Phi$NE, the Dalitz plot distribution for the $\eta \to \pi^+ \pi^- \pi^0$ decay is studied with the world's largest sample of $\sim 4.7 \cdot 10^6$ events. The Dalitz plot density is parametrized as a polynomial expansion up to cubic terms in the normalized dimensionless variables $X$ and $Y$. The experiment is sensitive to all charge conjugation conserving terms of the expansion, including a $gX^2Y$ term. The statistical uncertainty of all parameters is improved by a factor two with respect to earlier measurements.Comment: 11 pages, 9 figures, supplement: an ascii tabl

Performance of foreign banks in developing countries: Evidence from sub-Saharan African banking markets

Do foreign banks perform better than domestic banks in host developing economies? Relying on financial statements and survey data I compare the performance of three different categories of foreign banks to the group of domestic banks in sub-Saharan Africa: global banks from developed countries, regional African banks and banks from non-African emerging economies. While emerging-market banks and global banks consistently outperform domestic banks, the difference is not significant for regional African banks. The higher performance of global banks and emerging-market banks is related to higher operational efficiency and lower cost of funding, while there is no strong evidence of segmentation by business segment in the loans market. Regional African banks, which started their foreign expansion more recently, are less able to generate interest income compared to domestic banks. These findings highlight the importance of taking into account foreign banks’ heterogeneity when assessing the impact of financial FDI on the host economy

A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773)

Background: Headache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort. Methods: We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls. Results: We identified 3343 SNPs which reached the genome-wide significance level of P < 5 × 10−8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92 × 10−47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87 × 10−15 in the LINC02210-CRHR1 gene was the top SNP. Significant relationships between multiple brain tissues and genetic associations were identified through tissue expression analysis. We also identified significant positive genetic correlations between headache and many psychological traits. Conclusions: Our results suggest that brain function is closely related to broadly-defined headache. In addition, we found that many psychological traits have genetic correlations with headache

On the formal foundations of cash management systems

[EN] Cash management aims to find a balance between what is held in cash and what is allocated in other investments in exchange for a given return. Dealing with cash management systems with multiple accounts and different links between them is a complex task. Current cash management models provide analytic solutions without exploring the underlying structure of accounts and its main properties. There is a need for a formal definition of cash management systems. In this work, we introduce a formal approach to manage cash with multiple accounts based on graph theory. Our approach allows a formal reasoning on the relation between accounts in cash management systems. A critical part of this formal reasoning is the characterization of desirable and non-desirable cash management policies. Novel theoretical results guide cash managers in the analysis of complex cash management systems.This work is partially funded by projects Logistar (H2020-769142), AI4EU (H2020-825619) and 2017 SGR 172.Salas-Molina, F.; Rodriguez-Aguilar, JA.; Pla Santamaría, D.; Garcia-Bernabeu, A. (2021). On the formal foundations of cash management systems. Operational Research. 21(2):1081-1095. https://doi.org/10.1007/s12351-019-00464-6S10811095212Baccarin S (2009) Optimal impulse control for a multidimensional cash management system with generalized cost functions. Eur J Oper Res 196(1):198–206Bollobás B (2013) Modern graph theory, vol 184. Springer, BerlinBondy JA, Murty USR (1976) Graph theory with applications, vol 290. Macmillan, LondonChartrand G, Oellermann OR (1993) Applied and algorithmic graph theory, vol 993. McGraw-Hill, New YorkConstantinides GM, Richard SF (1978) Existence of optimal simple policies for discounted-cost inventory and cash management in continuous time. Oper Res 26(4):620–636da Costa Moraes MB, Nagano MS, Sobreiro VA (2015) Stochastic cash flow management models: a literature review since the 1980s. In: Guarnieri P (ed) Decision models in engineering and management. Springer, Berlin, pp 11–28de Avila Pacheco JV, Morabito R (2011) Application of network flow models for the cash management of an agribusiness company. Comput Ind Eng 61(3):848–857Golden B, Liberatore M, Lieberman C (1979) Models and solution techniques for cash flow management. Comput Oper Res 6(1):13–20Gormley FM, Meade N (2007) The utility of cash flow forecasts in the management of corporate cash balances. Eur J Oper Res 182(2):923–935Gregory G (1976) Cash flow models: a review. Omega 4(6):643–656Makridakis S, Wheelwright SC, Hyndman RJ (2008) Forecasting methods and applications. Wiley, New YorkRighetto GM, Morabito R, Alem D (2016) A robust optimization approach for cash flow management in stationery companies. Comput Ind Eng 99:137–152Salas-Molina F (2017) Risk-sensitive control of cash management systems. Oper Res. https://doi.org/10.1007/s12351-017-0371-0Salas-Molina F, Pla-Santamaria D, Rodriguez-Aguilar JA (2018) A multi-objective approach to the cash management problem. Ann Oper Res 267(1):515–529Srinivasan V, Kim YH (1986) Deterministic cash flow management: state of the art and research directions. Omega 14(2):145–166Valiente G (2013) Algorithms on trees and graphs. Springer, Berli

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis