is a noted human and animal pathogen. Despite decades of research on this important bacterium, there are still many unanswered questions regarding the pathogenic mechanisms it uses to infect the ...mammalian host. This can be attributed to it possessing a plethora of virulence factors and complex virulence factor and metabolic regulation. PurR, the purine biosynthesis regulator, was recently also shown to regulate virulence factors in
, and mutations in
result in derepression of fibronectin binding proteins (FnBPs) and extracellular toxins, required for a so-called hypervirulent phenotype. Here, we show that hypervirulent strains containing
mutations can be attenuated with the addition of purine biosynthesis mutations, implicating the necessity for
purine biosynthesis in this phenotype and indicating that
in the mammalian host experiences purine limitation. Using cell culture, we showed that while
mutants are not altered in epithelial cell binding, compared to that of wild-type (WT)
,
mutants have enhanced invasion of these nonprofessional phagocytes, consistent with the requirement of FnBPs for invasion of these cells. This correlates with
mutants having increased transcription of
genes, resulting in higher levels of surface-exposed FnBPs to promote invasion. These data provide important contributions to our understanding of how the pathogenesis of
is affected by sensing of purine levels during infection of the mammalian host.
Understanding host pathogen interactions is paramount to the development of novel antimicrobials. An important facet of this pursuit is the accurate characterization of pathogen replication within ...infected host cells. Here we describe the use of a fluorescence-based proliferation assay to identify intracellular populations of replicating bacteria at the subcellular level. Using
as a model Gram-positive bacterial pathogen and macrophages as a model host phagocyte, we demonstrate this assay can be used to reliably identify individual phagocytes that contain replicating bacteria. Furthermore, we demonstrate this assay is compatible with additional cellular probes that enable characterization of cellular compartments in which replicating bacteria reside. Finally, we demonstrate that this assay facilitates the investigation of both Gram-negative and Gram-positive bacteria within host cells.
One year after participating in the Research-based, Developmentally Informed (REDI) intervention or "usual practice" Head Start, the learning and behavioral outcomes of 356 children (17% Hispanic, ...25% African American; 54% girls; M age = 4.59 years at initial assessment) were assessed. In addition, their 202 kindergarten classrooms were evaluated on quality of teacher–student interactions, emphasis on reading instruction, and school-level student achievement. Hierarchical linear analyses revealed that the REDI intervention promoted kindergarten phonemic decoding skills, learning engagement, and competent social problem-solving skills, and reduced aggressive–disruptive behavior. Intervention effects on social competence and inattention were moderated by kindergarten context, with effects strongest when children entered schools with low student achievement. Implications are discussed for developmental models of school readiness and early educational programs.
Accurate estimates of manure excretion are needed for planning manure storage facilities and for nutrient management. Data sets from metabolism studies conducted at several universities were compiled ...and evaluated for excretion of total manure, N, P, and K. Animal groups included calves weighing up to 204kg, heifers weighing between 274 and 613kg, nonlactating cows, and lactating cows. Regression equations were developed to predict excretion of total manure, total dry matter, N, P, and K. Predictors used in the regression equations for lactating cows included milk yield, percentages of protein and fat in milk, dietary concentrations of crude protein and neutral detergent fiber, and intakes of nutrients. The regression equations provide improved predictions of excretion and enable more accurate planning of manure storage and nutrients to be managed at the farm level.
This study applied an algorithm developed to identify schizophrenia spectrum disorder patients with probable decrements between estimated premorbid and current cognitive ability (Keefe et al., 2005). ...Cognitive trajectories and associated functional status were examined in patients and control participants.
Patients with schizophrenia or schizoaffective disorder (n = 139) and control participants (n = 63) completed measures of verbal and working memory, processing speed, verbal fluency, reading ability and non-verbal reasoning. A predicted cognitive composite score was generated using control participants' parental education and reading scores, consistent with methods in Keefe et al. (2005), and compared to current performance. Three performance trajectory profiles were identified: decrement, stable, and increment. Functionality and clinical status were assessed with the Multidimensional Scale of Independent Functioning (MSIF) and the Positive and Negative Syndrome Scale (PANSS).
Approximately 60% (n = 83) of patients demonstrated a decrement trajectory, 16% (n = 22) demonstrated an increment trajectory, and 24% (n = 34) demonstrated a stable trajectory. Patients with decrement profiles were significantly more symptomatic (negative) and functionally impaired (MSIF) than those with increment profiles. Patients with increment and normal-range performance profiles remained functionally deficient relative to controls.
Schizophrenia and schizoaffective patients meeting psychometric criteria for cognitive decline relative to estimated premorbid levels are common in the outpatient population but may occur less frequently than earlier estimates suggest. Minorities with stable and improved performance profiles also exist, show clinical and functional advantage relative to more typical patients, but underperform healthy controls.
Brain development has largely been studied through unimodal analysis of neuroimaging data, providing independent results for structural and functional data. However, structure clearly impacts ...function and vice versa, pointing to the need for performing multimodal data collection and analysis to improve our understanding of brain development, and to further inform models of typical and atypical brain development across the lifespan. Ultimately, such models should also incorporate genetic and epigenetic mechanisms underlying brain structure and function, although currently this area is poorly specified. To this end, we are reporting here a multi-site, multi-modal dataset that captures cognitive function, brain structure and function, and genetic and epigenetic measures to better quantify the factors that influence brain development in children originally aged 9–14 years. Data collection for the Developmental Chronnecto-Genomics (Dev-CoG) study (http://devcog.mrn.org/) includes cognitive, emotional, and social performance scales, structural and functional MRI, diffusion MRI, magnetoencephalography (MEG), and saliva collection for DNA analysis of single nucleotide polymorphisms (SNPs) and DNA methylation patterns. Across two sites (The Mind Research Network and the University of Nebraska Medical Center), data from over 200 participants were collected and these children were re-tested annually for at least 3 years. The data collection protocol, sample demographics, and data quality measures for the dataset are presented here. The sample will be made freely available through the collaborative informatics and neuroimaging suite (COINS) database at the conclusion of the study.
Climate change research is advancing to more complex and more comprehensive studies that include long-term experiments, multiple life-history stages, multi-population, and multi-trait approaches. We ...used a population of the barnacle Balanus improvisus known to be sensitive to short-term acidification to determine its potential for long-term acclimation to acidification. We reared laboratory-bred individuals (as singles or pairs), and field-collected assemblages of barnacles, at pH 8.1 and 7.5 (≈ 400 and 1600 μatm pCO2 respectively) for up to 16 months. Acidification caused strong mortality and reduced growth rates. Acidification suppressed respiration rates and induced a higher feeding activity of barnacles after 6 months, but this suppression of respiration rate was absent after 15 months. Laboratory-bred barnacles developed mature gonads only when they were held in pairs, but nonetheless failed to produce fertilized embryos. Field-collected barnacles reared in the laboratory for 8 months at the same pH's developed mature gonads, but only those in pH 8.1 produced viable embryos and larvae. Because survivors of long-term acidification were not capable of reproducing, this demonstrates that B. improvisus can only partially acclimate to long-term acidification. This represents a clear and significant bottleneck in the ontogeny of this barnacle population that may limit its potential to persist in a future ocean.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Siderophores, iron-scavenging small molecules, are fundamental to bacterial nutrient metal acquisition and enable pathogens to overcome challenges imposed by nutritional immunity. Multimodal imaging ...mass spectrometry allows visualization of host−pathogen iron competition, by mapping siderophores within infected tissue. We have observed heterogeneous distributions of Staphylococcus aureus siderophores across infectious foci, challenging the paradigm that the vertebrate host is a uniformly iron-depleted environment to invading microbes.
Limiting feeding time has been a concept used in growing and nonlactating ruminant animals with good success, especially in improving feed efficiency while maintaining normal rumen function and fiber ...digestibility. This study evaluated the physiological and productive responses of cows fed a total mixed ration (TMR) available for 24 or 19 h/d with or without access to additional long hay. Eight multiparous Holstein cows were used in a replicated 4 × 4 Latin square design with 21-d periods. Rations were formulated to mimic a TMR used in the Parmigiano Reggiano cheese production area of Italy, consisting of all dry and nonfermented components. Intakes were reduced by 2.49 kg/d in cows with restricted TMR access and 1.16 kg/d without supplemental hay. Rumen characteristics were similar for all groups with improvements in energy-corrected milk. The results show that once cows adapted to diet changes, few differences were observed when offering TMR continuously or with limited access. Energy-corrected milk feed efficiency was improved in cows having access to feed 19 versus 24 h/d. In addition, the presence of long hay during the TMR restriction offered the optimal conditions for ruminal function and pH stability, yet no effects were observed on body weight change. A Latin square with 21-d periods could have a carry-over effect on energy storage, and mobilization of fat reserves might be able to mask negative energy balance during restriction. Restricted feeding could be used as a strategy to manage feed availability according to cow production and metabolic condition, to maximize the use of nutrient resources, reducing the cost of milk production and improving the cows' welfare and health.
PDF
