Identification of non-dot/icm suppressors of the Legionella pneumophila △dotL lethality phenotype

Legionella pneumophila, a causative agent of bacterial pneumonia, survives inside phagocytic cells by avoiding rapid targeting to the lysosome. This bacterium utilizes a type IVB secretion system, encoded by the dot/icm genes, to replicate inside host cells. DotL, a critical component of the Dot/Icm secretion apparatus, functions as the type IV coupling protein. In contrast to most dot/icm genes, which are dispensable for growth on bacteriological media, dotL is required for the viability of wild-type L. pneumophila. Previously we reported that ΔdotL lethality could be suppressed by inactivation of the Dot/Icm complex via mutations in other dot/icm genes. Here we report the isolation of non-dot/icm suppressors of this phenotype. These ΔdotL suppressors include insertions that disrupt the function of the L. pneumophila homologs of cpxR, djlA, lysS, and two novel open reading frames, lpg0742 and lpg1594, that we have named ldsA and ldsB for lethality of ΔdotL suppressor. In addition to suppressing ΔdotL lethality, inactivation of these genes in a wild-type strain background causes a range of defects in L. pneumophila virulence traits, including intracellular growth, implicating these factors in the proper function of the Dot/Icm complex. Consistent with previous data showing a role for the cpx system in regulating expression of several dot/icm genes, the cpxR insertion mutant produced decreased levels of three Dot/Icm proteins, DotA, IcmV, and IcmW. The remaining four suppressors did not affect the steady-state levels of any Dot/Icm protein and are likely to represent the first identified factors necessary for assembly and/or activation of the Dot/Icm secretion complex

The role of strength-related factors on psychological readiness for return to sport following anterior cruciate ligament (ACL) reconstruction

Psychological readiness following anterior cruciate ligament reconstruction (ACLR) correlates with different return to sport outcomes. However, the relationship between strength and power and psychological readiness remains unexplored. The aim of this study was to investigate the relationship between anterior cruciate ligament return to sport after injury (ACL-RSI) scores and various hamstrings and quadriceps strength and power variables. Twelve participants (20.7 ± 2.5 years old; 174.2 ± 7.5 cm; 70.2 ± 8.5 kg; 18.2 ± 8.3% of body fat) who had an ACLR nine months or more before the study completed the ACL-RSI questionnaire and isokinetic strength testing of the hamstrings and quadriceps (60°·s−1 and 180°·s−1). Based on ACL-RSI scores, they were divided into “cases” and “controls”, deemed not psychologically ready and psychologically ready to return to previous sport performance (PILOS), respectively. The main findings are that quadriceps’ and hamstrings’ rate of torque development (RTD) and time since surgery were determinants of psychological readiness following ACLR. Furthermore, compared to controls, cases showed significantly lower quadriceps torque at angles close to full knee extension (40 deg and 30 deg from extension). They also showed lower RTD than controls, but no difference in peak torque. These results suggest that physiotherapists should facilitate athletes’ return to sport (RTS) by focusing on the restoration of RTD and strength at angles close to full knee extension

Biological and anthropogenic predictors of metal concentration in the Eurasian otter, a sentinel of freshwater ecosystems

Toxic metals have been linked to a range of adverse health effects in freshwater organisms. However, for higher vertebrates, there is little understanding of the large-scale drivers of exposure. We quantified toxic metal/semi-metal concentrations in a sentinel freshwater top predator, the Eurasian otter (Lutra lutra), across England and Wales, and determined how this varied with key natural and anthropogenic factors. We related liver concentrations in 278 otters that died between 2006 and 2017 to habitat biogeochemistry, proximity to point source contamination and to biological characteristics (length, sex, condition). Evidence for any positive association with putative anthropogenic sources (mining, human population, known discharges) was weak or lacking in nearly all cases, with the exception of a positive association between lead and human population density. Despite concerns that burgeoning use of nanosilver in consumer products might increase silver concentrations in waste waters, there was no increase over time. Spatial variation in soil/sediment pH, precipitation, and soil calcium oxide are indicated as significant predictors of metal concentrations in otters (higher cadmium and silver in areas with lower pH and higher rainfall, and higher chromium and lead in areas of lower calcium oxide). Liver chromium and nickel concentrations declined significantly over time (Cr 0.030 ± 1.2 to 0.015 ± 1.3 μg/g dry weight, Ni 0.0038 ± 1.2 to 0.00068 ± 1.5 μg/g, between 2006–2009 and 2014–2017), but other metals showed no temporal change. Biotic associations were important, with age related accumulation indicated for mercury and cadmium (as well as interactions with body condition). Our results suggest that larger-scale geochemical and hydrological processes are important in determining metal exposure in otters, and we provide an indication of risk factors that may be of relevance for freshwater vertebrates in other countries with well-developed water pollution management

A comparative analysis of early child health and development services and outcomes in countries with different redistributive policies

Background: The social environment is a fundamental determinant of early child development and, in turn, early child development is a determinant of health, well-being, and learning skills across the life course. Redistributive policies aimed at reducing social inequalities, such as a welfare state and labour market policies, have shown a positive association with selected health indicators. In this study, we investigated the influence of redistributive policies specifically on the social environment of early child development in five countries with different political traditions. The objective of this analysis was to highlight similarities and differences in social and health services between the countries and their associations with other health outcomes that can inform better global early child development policies and improve early child health and development. Methods: Four social determinants of early child development were selected to provide a cross-section of key time periods in a child's life from prenatal to kindergarten. They included: 1) prenatal care, 2) maternal leave, 3) child health care, and 4) child care and early childhood education. We searched international databases and reports (e.g. Organization for Economic Cooperation and Development, World Bank, and UNICEF) to obtain information about early child development policies, services and outcomes. Results: Although a comparative analysis cannot claim causation, our analysis suggests that redistributive policies aimed at reducing social inequalities are associated with a positive influence on the social determinants of early child development. Generous redistributive policies are associated with a higher maternal leave allowance and pay and more preventive child healthcare visits. A decreasing trend in infant mortality, low birth weight rate, and under five mortality rate were observed with an increase in redistributive policies. No clear influence of redistributive policies was observed on breastfeeding and immunization rates. In the analysis of child care and early education, the lack of uniform measures of early child development outcomes was apparent. Conclusions: This paper provides further support for an association between redistributive policies and early child health and development outcomes, along with the organization of early child health and development services

Elevated PGC-1α Activity Sustains Mitochondrial Biogenesis and Muscle Function without Extending Survival in a Mouse Model of Inherited ALS

SummaryThe transcriptional coactivator PGC-1α induces multiple effects on muscle, including increased mitochondrial mass and activity. Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, adult-onset neurodegenerative disorder characterized by selective loss of motor neurons and skeletal muscle degeneration. An early event is thought to be denervation-induced muscle atrophy accompanied by alterations in mitochondrial activity and morphology within muscle. We now report that elevation of PGC-1α levels in muscles of mice that develop fatal paralysis from an ALS-causing SOD1 mutant elevates PGC-1α-dependent pathways throughout disease course. Mitochondrial biogenesis and activity are maintained through end-stage disease, accompanied by retention of muscle function, delayed muscle atrophy, and significantly improved muscle endurance even at late disease stages. However, survival was not extended. Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1α activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS

Pediatric heart transplantation: Improving results in high-risk patients

AbstractObjectives: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. Methods and results: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05). Conclusions: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation. (J Thorac Cardiovasc Surg 2001;121:782-91

Spatial reasoning in early childhood

This document is about how children develop spatial reasoning in early childhood (birth to 7 years) and how practitioners working with young children can support this. Spatial reasoning is a vital and often overlooked aspect of mathematics. So this toolkit, which is informed by extensive review of research in this areas, will support practitioners to enhance children's early mathematical learning. For the full Spatial Reasoning toolkit: https://earlymaths.org/spatial-reasoning

word~river literary review (2009)

wordriver is a literary journal dedicated to the poetry, short fiction and creative nonfiction of adjuncts and part-time instructors teaching in our universities, colleges, and community colleges. Our premier issue was published in Spring 2009. We are always looking for work that demonstrates the creativity and craft of adjunct/part-time instructors in English and other disciplines. We reserve first publication rights and onetime anthology publication rights for all work published. We define adjunct instructors as anyone teaching part-time or full-time under a semester or yearly contract, nationwide and in any discipline. Graduate students teaching under part-time contracts during the summer or who have used up their teaching assistant time and are teaching with adjunct contracts for the remainder of their graduate program also are eligible.https://digitalscholarship.unlv.edu/word_river/1002/thumbnail.jp