Genome-wide mapping reveals single-origin chromosome replication in Leishmania, a eukaryotic microbe

Background DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features of DNA replication are true of all eukaryotes, we describe genome-wide origin mapping in the parasite Leishmania. Results Origin mapping in Leishmania suggests a striking divergence in origin usage relative to characterized eukaryotes, since each chromosome appears to be replicated from a single origin. By comparing two species of Leishmania, we find evidence that such origin singularity is maintained in the face of chromosome fusion or fission events during evolution. Mapping Leishmania origins suggests that all origins fire with equal efficiency, and that the genomic sites occupied by origins differ from related non-origins sites. Finally, we provide evidence that origin location in Leishmania displays striking conservation with Trypanosoma brucei, despite the latter parasite replicating its chromosomes from multiple, variable strength origins. Conclusions The demonstration of chromosome replication for a single origin in Leishmania, a microbial eukaryote, has implications for the evolution of origin multiplicity and associated controls, and may explain the pervasive aneuploidy that characterizes Leishmania chromosome architecture

Behavior of Wild Pigs toward Conspecific Carcasses: Implications for Disease Transmission in a Hot, Semiarid Climate

Wild pigs (Sus scrofa) are a prolific, invasive species in the United States of America and act as vectors for many pathogens. An emerging pathogen of concern to the USA is African swine fever (ASF), a deadly viral disease affecting swine that is endemic to Africa and has spread to parts of Europe, Asia, and the Caribbean. ASF affects both wild and domesticated pigs and can be transmitted via several avenues, including interactions between and consumption of dead pigs by their live conspecifics. As wild pigs are considered a serious threat in the transmission of ASF, understanding the behavior of wild pigs towards their dead conspecifics is imperative when considering the transmission of ASF and other diseases in the USA. We placed camera traps at a sample of wild pig carcasses dispatched during four aerial shooting events between November, 2020, and June, 2022, at East Foundation’s San Antonio Viejo Ranch, South Texas. We recorded visitation events to carcasses by live wild pigs and recorded their behavior. Furthermore, we assessed daily carcass decomposition rates by visiting carcass sites without cameras. We found no evidence of cannibalism and recorded live wild pig visitations to only 33% of carcasses before advanced stages of decomposition were reached. Carcass decomposition was rapid (2.5 to 3 days), regardless of season, and the time to the first visitation and investigation of carcasses by live conspecifics was quicker than has been recorded in Europe. We posit that active scavenger guilds at our study site, coupled with high temperatures, result in the rapid decomposition of wild pig carcasses, which reduces opportunities for live wild pigs to interact with them when compared to milder climates. We suggest additional research investigating the persistence of ASF in hot, arid climates and the interactions between live pigs and the skeletonized remains of conspecifics

Change in hematologic indices over time in pediatric inflammatory bowel disease treated with azathioprin

Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood cell (WBC) indices reflecting efficacy or toxicity. Understanding the interactions between bone marrow stem cells and azathioprine could highlight abnormal response patterns as forerunners for hematologic malignancies. This study gives a statistical description of factors influencing the relationship between MCV and WBC in children with inflammatory bowel disease treated with azathioprine. We found that leukopenia preceded macrocytosis. Macrocytosis is therefore not a good predictor of leukopenia. Further studies will be necessary to determine the subgroup of patients at increased risk of malignancies based on bone marrow response. © 2010 Soman et al., publisher and licensee Adis Data Information BV

Change in hematologic indices over time in pediatric inflammatory bowel disease treated with azathioprine

Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood cell (WBC) indices reflecting efficacy or toxicity. Understanding the interactions between bone marrow stem cells and azathioprine could highlight abnormal response patterns as forerunners for hematologic malig-nancies. This study gives a statistical description of factors influencing the relationship between MCV and WBC in children with inflammatory bowel disease treated with azathioprine. We found that leukopenia preceded macro¬cytosis. Macrocytosis is therefore not a good predictor of leukopenia. Further studies will be necessary to determine the subgroup of patients at increased risk of malignancies based on bone marrow response

The Effects of Distraction and a Brief Intervention on Auditory and Visual-Spatial Working Memory in College Students with Attention Deficit Hyperactivity Disorder

Two studies addressed how young adult college students with attention deficit hyperactivity disorder (ADHD) (n = 44) compare to their nonaffected peers (n = 42) on tests of auditory and visual–spatial working memory (WM), are vulnerable to auditory and visual distractions, and are affected by a simple intervention. Students with ADHD demonstrated worse auditory WM than did controls. A near significant trend indicated that auditory distractions interfered with the visual WM of both groups and that, whereas controls were also vulnerable to visual distractions, visual distractions improved visualWM in the ADHD group. The intervention was ineffective. Limited correlations emerged between self-reported ADHD symptoms and objective test performances; students with ADHD who perceived themselves as more symptomatic often had better WM and were less vulnerable to distractions than their ADHD peers

Isolated IgG2 deficiency is an independent risk factor for exacerbations in bronchiectasis

BACKGROUND: Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is not known. AIM: To analyse if bronchiectasis patients with isolated IgG2 deficiency at risk of recurrent exacerbations and/or hospitalization? Do patients with IgG2 deficiency have worse disease progression? DESIGN AND METHODS: This is a retrospective study (2015–20) exploring independent risk factors for recurrent exacerbations (3 or more per year) and/or hospitalization with bronchiectasis exacerbations using multivariable models using binary logistic regression. There was no patient with IgG deficiency, IgG 1, 3 or 4 deficiency, or IgA or IgM deficiency included. In this model, the authors included: serum IgG2 level; lung function; body mass index; MRC breathlessness scale; age; sex; number of bronchiectatic lobes; bacterial colonization; comorbidities; and the use of long-term immunosuppressant drugs or antibiotics for more than 28 days. Analysing 2-year longitudinal data, one-way ANOVA and Mann–Whitney U-test were used to compare bronchiectasis severity between patients with different IgG2 levels. RESULTS: Serum IgG2 levels (4.45 g/l) (P = 0.003, 0.013). CONCLUSION: Reduced IgG2 levels were an independent predictor for bronchiectasis exacerbations and have increased disease progression

Quantifying defence cascade responses as indicators of pig affect and welfare using computer vision methods

Publishe

A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation

The KRAS GTPase plays a critical role in the control of cellular growth. The activity of KRAS is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and also post-translational modification. Lysine 104 in KRAS can be modified by ubiquitylation and acetylation, but the role of this residue in intrinsic KRAS function has not been well characterized. We find that lysine 104 is important for GEF recognition, because mutations at this position impaired GEF-mediated nucleotide exchange. Because the KRAS K104Q mutant has recently been employed as an acetylation mimetic, we conducted a series of studies to evaluate its in vitro and cell-based properties. Herein, we found that KRAS K104Q exhibited defects in both GEF-mediated exchange and GAP-mediated GTP hydrolysis, consistent with NMR-detected structural perturbations in localized regions of KRAS important for recognition of these regulatory proteins. Despite the partial defect in both GEF and GAP regulation, KRAS K104Q did not alter steady-state GTP-bound levels or the ability of the oncogenic KRAS G12V mutant to cause morphologic transformation of NIH 3T3 mouse fibroblasts and of WT KRAS to rescue the growth defect of mouse embryonic fibroblasts deficient in all Ras genes. We conclude that the KRAS K104Q mutant retains both WT and mutant KRAS function, probably due to offsetting defects in recognition of factors that up-regulate (GEF) and down-regulate (GAP) RAS activity

Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV – RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity