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Advances in high-throughput DNA sequencing technologies have determined an explosion in the number of sequenced bacterial genomes. Comparative sequence analysis frequently reveals evidences of homologous recombination occurring with different mechanisms and rates in different species, but the large-scale use of computational methods to identify recombination events is hampered by their high computational costs. Here, we propose a new method to identify recombination events in large datasets of whole genome sequences. Using a filtering procedure of the gene conservation profiles of a test genome against a panel of strains, this algorithm identifies sets of contiguous genes acquired by homologous recombination. The locations of the recombination breakpoints are determined using a statistical test that is able to account for the differences in the natural rate of evolution between different genes. The algorithm was tested on a dataset of 75 genomes of Staphylococcus aureus and 50 genomes comprising different streptococcal species, and was able to detect intra-species recombination events in S. aureus and in Streptococcus pneumoniae. Furthermore, we found evidences of an inter-species exchange of genetic material between S. pneumoniae and Streptococcus mitis, a closely related commensal species that colonizes the same ecological niche. The method has been implemented in an R package, Reco, which is freely available from supplementary material, and provides a rapid screening tool to investigate recombination on a genome-wide scale from sequence data.

Receptor tyrosine kinase signaling cooperates with WNT/β-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/β-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent of the PI3K/AKT pathway. Instead, this phenotype depends on ERK MAP kinase-mediated phosphorylation of WNT co-receptor LRP6 at Ser1490 and Thr1572 during its Golgi network-based maturation process. This phosphorylation dramatically increases the cellular response to WNT. Moreover, FGFR2, FGFR3, EGFR and TRKA directly phosphorylate β-catenin at Tyr142, which is known to increase cytoplasmic β-catenin concentration via release of β-catenin from membranous cadherin complexes. We conclude that signaling via ERK/LRP6 pathway and direct β-catenin phosphorylation at Tyr142 represent two mechanisms used by various receptor tyrosine kinase systems to activate canonical WNT signaling.

Acinetobacter baumannii is an increasingly multidrug-resistant (MDR) cause of hospital-acquired infections, often associated with limited therapeutic options. We investigated A. baumannii isolates at a New York hospital to characterize genetic relatedness.Thirty A. baumannii isolates from geographically-dispersed nursing units within the hospital were studied. Isolate relatedness was assessed by repetitive sequence polymerase chain reaction (rep-PCR). The presence and characteristics of integrons were assessed by PCR. Metabolomic profiles of a subset of a prevalent strain isolates and sporadic isolates were characterized and compared.We detected a hospital-wide group of closely related carbapenem resistant MDR A. baumannii isolates. Compared with sporadic isolates, the prevalent strain isolates were more likely to be MDR (p = 0.001). Isolates from the prevalent strain carried a novel Class I integron sequence. Metabolomic profiles of selected prevalent strain isolates and sporadic isolates were similar.The A. baumannii population at our hospital represents a prevalent strain of related MDR isolates that contain a novel integron cassette. Prevalent strain and sporadic isolates did not segregate by metabolomic profiles. Further study of environmental, host, and bacterial factors associated with the persistence of prevalent endemic A. baumannii strains is needed to develop effective prevention strategies.

The monoclonal antibodies cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), are licensed for the treatment of KRAS wild-type metastatic colorectal cancer (mCRC). Such ‘molecular restriction’ derived from post-hoc analyses of randomized trials and from other retrospective series all indicate how tumors bearing KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations are resistant to EGFR inhibition. Even if highly sensitive for nonresponse, KRAS testing is not very specific. In fact, a limited but still considerable proportion of KRAS wild-type patients rapidly progress on treatment with an EGFR inhibitor. New potential molecular determinants of benefit from such treatment are under investigation and may further refine the selection of patients. Pharmacogenomic analyses and translational studies are also ongoing for exploring the field of acquired resistance to anti-EGFRs, since all patients eventually progress. New biological data are awaited for optimizing the use of molecular agents in colorectal cancer and for identifying promising targets that could allow to better understand and, potentially, overcome mechanisms of primary or secondary resistance to EGFR inhibitors.

BACKGROUND:Aggregates formed between leukocytes and platelets in the circulation lead to release of tissue factor (TF)-bearing microparticles contributing to a prothrombotic state. As enterohemorrhagic Escherichia coli (EHEC) may cause hemolytic uremic syndrome (HUS), in which microthrombi cause tissue damage, this study investigated whether the interaction between blood cells and EHEC virulence factors Shiga toxin (Stx) and lipopolysaccharide (LPS) led to release of TF. METHODOLOGY/PRINCIPAL FINDINGS:The interaction between Stx or LPS and blood cells induced platelet-leukocyte aggregate formation and tissue factor (TF) release, as detected by flow cytometry in whole blood. O157LPS was more potent than other LPS serotypes. Aggregates formed mainly between monocytes and platelets and less so between neutrophils and platelets. Stimulated blood cells in complex expressed activation markers, and microparticles were released. Microparticles originated mainly from platelets and monocytes and expressed TF. TF-expressing microparticles, and functional TF in plasma, increased when blood cells were simultaneously exposed to the EHEC virulence factors and high shear stress. Stx and LPS in combination had a more pronounced effect on platelet-monocyte aggregate formation, and TF expression on these aggregates, than each virulence factor alone. Whole blood and plasma from HUS patients (n = 4) were analyzed. All patients had an increase in leukocyte-platelet aggregates, mainly between monocytes and platelets, on which TF was expressed during the acute phase of disease. Patients also exhibited an increase in microparticles, mainly originating from platelets and monocytes, bearing surface-bound TF, and functional TF was detected in their plasma. Blood cell aggregates, microparticles, and TF decreased upon recovery. CONCLUSIONS/SIGNIFICANCE:By triggering TF release in the circulation, Stx and LPS can induce a prothrombotic state contributing to the pathogenesis of HUS.

BACKGROUND: The impact of the pneumococcal conjugate vaccine (PCV-7) on antibiotic resistance among pneumococcal strains causing invasive pneumococcal disease (IPD) has varied in different locales in the United States. We assessed trends in IPD including trends for IPD caused by penicillin non-susceptible strains before and after licensure of PCV-7 and the impact of the 2008 susceptibility breakpoints for penicillin on the epidemiology of resistance. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective review of IPD cases at Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University Medical Center. Subjects were < or = 18 years of age with Streptococcus pneumoniae isolated from sterile body sites from January 1995-December 2006. The rate of IPD from 1995-1999 versus 2002-2006 significantly decreased from 4.1 (CI(95) 3.4, 4.8) to 1.7 (CI(95) 1.3, 2.2) per 1,000 admissions. Using the breakpoints in place during the study period, the proportion of penicillin non-susceptible strains increased from 27% to 49% in the pre- vs. post-PCV-7 era, respectively (p = 0.001), although the rate of IPD caused by non-susceptible strains did not change from 1995-1999 (1.1 per 1,000 admissions, CI(95) 0.8, 1.5) when compared with 2002-2006 (0.8 per 1,000 admissions, CI(95) 0.6, 1.2). In the multivariate logistic regression model controlling for the effects of age, strains causing IPD in the post-PCV-7 era were significantly more likely to be penicillin non-susceptible compared with strains in the pre-PCV-7 era (OR 2.46, CI(95) 1.37, 4.40). However, using the 2008 breakpoints for penicillin, only 8% of strains were non-susceptible in the post-PCV-7 era. CONCLUSIONS/SIGNIFICANCE: To date, there are few reports that document an increase in the relative proportion of penicillin non-susceptible strains of pneumococci causing IPD following the introduction of PCV-7. Active surveillance of pneumococcal serotypes and antibiotic resistance using the new penicillin breakpoints is imperative to assess potential changes in the epidemiology of IPD.

Activating mutations in FGFR3 tyrosine kinase cause several forms of human skeletal dysplasia. Although the mechanisms of FGFR3 action in cartilage are not completely understood, it is believed that the STAT1 transcription factor plays a central role in pathogenic FGFR3 signaling. Here, we analyzed STAT1 activation by the N540K, G380R, R248C, Y373C, K650M and K650E-FGFR3 mutants associated with skeletal dysplasias. In a cell-free kinase assay, only K650M and K650E-FGFR3 caused activatory STAT1(Y701) phosphorylation. Similarly, in RCS chondrocytes, HeLa, and 293T cellular environments, only K650M and K650E-FGFR3 caused strong STAT1 activation. Other FGFR3 mutants caused weak (HeLa) or no activation (293T and RCS). This contrasted with ERK MAP kinase activation, which was strongly induced by all six mutants and correlated with the inhibition of proliferation in RCS chondrocytes. Thus the ability to activate STAT1 appears restricted to the K650M and K650E-FGFR3 mutants, which however account for only a small minority of the FGFR3-related skeletal dysplasia cases. Other pathways such as ERK should therefore be considered as central to pathological FGFR3 signaling in cartilage.

Out of early research, Cisco Systems (1999) have built an impressive foundation that advocates for reusable learning objects (RLOs). As the need for online methods for delivering both formal and informal educational content has increased, the prospect of greater influence through carefully constructed RLOs has grown. RLOs are any digital resource that can be used and reused to enhance online learning. RLOs typically are small, discrete, self-contained digital objects that may be sequenced, combined, and used within a variety of instructional activities. RLOs have been implemented in nursing, pharmacy, and physician assistant programs. However, there is a lack of literature regarding RLOs in occupational therapy education. An attitudinal survey was administered to occupational therapy students after they had used an RLO focused on goal writing. Student preferences toward RLO content, instructional design, and eLearning were generally positive. Nearly three-quarters of the students who responded to the survey indicated that the RLO presented was beneficial. All respondents noted that they would use the RLO for future occupational therapy courses. It is argued that incorporating RLOs offers a cost-effective, efficient learning tool, and also adds credibility to the given curriculum program as being innovative with instructing occupational-therapy related concepts.

Categorizing Event Sequences Using Regular Expressions

Categorizing Event Sequences Using Regular Expressions

Both long- and short-term consequences should be considered when examining the effects of fire on the foraging behavior of caribou. Post-fire increases in protein content, digestibility, and availability of E. vaginatum make burned tussock tundra an attractive feeding area for caribou in late winter. These benefits are likely short-lived, however. Lowered availability of lichens and increased relative frequency of bryophytes will persist for a much longer period.

What does the issue of sexual violence against women have to do with Equity and Trusts law? Most students and scholars of the subject would say “very little”. In this paper I argue, on the contrary that the issue of gendered violence does indeed arise in this subject-area but it is usually rendered invisible by an overly narrow view of what counts as appropriate legal scholarship and pedagogy. The aim of this paper is a modest one: it is to take one narrowly defined “legal” method — case analysis — and turn it on its head so that it forms the basis of a critical, context-sensitive pedagogy which makes space for an exploration of the issue of sexual violence within this subject-area. By employing what I call “critical case analysis” in three doctrinal areas of Equity and Trusts law — undue influence, unconscionable dealing and fiduciary relationships — I hope to show that issues of sexual violence do arise in this subject; that these issues are often omitted or inadequately dealt with by courts and traditional scholars; and that critical case analysis can be a useful pedagogical tool in our classrooms for exposing and exploring such issues.

Using Oreochromis niloticus (L.), commonly known as tilapia, as a model, this study evaluated the exposure of trace metal and their risk assessment on human health. In addition, the status of amino acids, fatty acids, vital elements, and their benefits is also studied. Estimating the nutrient composition of fish muscle is necessary to ensure that it meets the requirements for human health, food regulations, and commercial specifications. The species examined contained appreciable concentrations of amino acids, fatty acid content, and minerals, suggesting that the fish species could be a good source of protein, fat, and minerals. Hazardous heavy metals were found to be lower compared to their corresponding maximum tolerable limits. The order of trace metals is Zn (22,709 µg/kg) > Fe (19,878 µg/kg) > Cu (1261 µg /kg) > Mn (1228 µg/kg) > Cr (474 µg/kg) > Ni (152 µg/kg) As (318 µg /kg) > Pb (281 µg/kg) > Co (24 µg /kg) > Cd (13 µg/kg) > Hg (5 µg/kg); a number of health-related indices, including estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI), as well as carcinogenic risk (CR) indices for adult and children, were calculated to evaluate the human health hazard of the heavy metals. The THQ and HI of heavy metals for tilapia are lower than 1, posing a non-carcinogenic threat to human health due to the biomagnifications of these deadly poisonous metals. Principal component, cluster, and correlation analyses delineated the common probabilistic sources of metal contamination origin and significant inter-parameter associations. Although no human health risks for the consumption of tilapia was found, more attention must be paid for the monitoring of Oreochromis niloticus before entering the market., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The objective was to assess the chemical composition, cholesterol, fatty acid (FAs), and amino acid (AAs) profiles of buffalo cheese, butter, and ghee., Materials and Methods: Buffalo milk (raw) was collected from the Bangladesh Agricultural University (BAU) Dairy Farm, BAU, Mymensingh-2202, Bangladesh. Cheese, butter, and ghee were prepared at the Dairy Chemistry and Technology Laboratory, Department of Dairy Science, BAU, Mymensingh, Bangladesh, and subjected to subsequent analyses. The gross nutritional composition and AAs profile of milk were analyzed prior to the manufacture of cheese, butter, and ghee. The gross nutritional composition of milk and dairy products was analyzed by applying an automated milk analyzer and the Association of Agricultural Chemists techniques, respectively. The cholesterol, FAs, and AAs contents of cheese, butter, and ghee were determined by the Bangladesh Council for Scientific and Industrial Research, Dhaka, Bangladesh. Furthermore, atherogenic and thrombogenic indices were also calculated using reference equations., Results: The results indicated that the buffalo milk is a good source of first-rate nutrients (dry matter: 16.50%, fat: 7.50%, protein: 3.75%). Findings indicated that the butter was significantly rich with ( p < 0.05) total solids and fat where higher ( p > 0.05) protein, carbohydrate, and minerals were found in cheese. The saponification, Reichert-Meissl, Polenski, and Kirschner values of buffalo ghee were found to be 225, 30, 1.2, and 25, respectively. A significant ( p < 0.05) variation was found in the cholesterol content of buffalo cheese, butter, and ghee. Butter and ghee had 40.14 and 39.57 mg more cholesterol, respectively, than cheese. The results revealed identical FA profiles except for C24:0 among the three dairy products where the major FA compositions were C4:0, C14:0, C16:0, and C18:0 and C18:1 cis-9. The atherogenicity index and thrombogenicity index of cheese, butter, and ghee were statistically similar ( p > 0.05). Butter was found with the most conducive anti-atherogenic and anti-thrombogenic characteristics due to lower saturated and higher polyunsaturated FAs. However, all the AAs concentrations were statistically higher ( p < 0.05) in cheese than in butter and ghee., Conclusion: To conclude, buffalo cheese is superior to butter and ghee as regards nutrient density, but consumers can choose other foods based on their choice., Competing Interests: The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright: © Journal of Advanced Veterinary and Animal Research.)

Objective: This study investigated and compared the chemical composition, cholesterol content, fatty acid (FA), and amino acid (AA) profiles of doi and rasomalai made from buffalo milk., Materials and Methods: Bangladesh Agricultural University Dairy Farm, Mymensingh-2202, Bangladesh was the source of raw buffalo milk. Then, doi and rasomalai were produced and analyzed. Prior to the production of doi and rasomalai, the gross composition and AAs of milk were evaluated. Milk and dairy products were evaluated for gross composition using an automated milk analyzer and the Association of Agricultural Chemists techniques, respectively. At the Bangladesh Council for Scientific and Industrial Research, Dhaka, Bangladesh, the cholesterol, FA, and AA levels of doi and rasomalai were determined. Additionally, atherogenic and thrombogenic indices were determined using established equations., Results: The results indicated that the majority of the proximate components were significantly greater ( p < 0.05) in rasomalai than in doi. Rasomalai had 3.64 mg more cholesterol ( p > 0.05) than doi. The FA profile was identical across doi and rasomalai with the exception of oleic acid (C18:1 cis -9), which was 1.50% greater ( p < 0.05) in rasomalai. The atherogenicity index was found to be statistically higher in doi than in rasomalai ( p > 0.05). Similarly, the thrombogenic index was found to be significantly higher ( p > 0.05) in doi (1.98) when compared to the rasomalai (1.92). The concentrations of all AAs were found to be quantitatively higher in doi than in rasomalai ( p > 0.05)., Conclusion: The conclusion is that buffalo milk rasomalai appears to have a higher nutritional density than buffalo milk doi., Competing Interests: No objections have been raised by the authors in regard to publishing of this paper., (Copyright: © Journal of Advanced Veterinary and Animal Research.)