Preliminary observations of Dades trout (Salmo multipunctatus) spawning in a High Atlas mountain spring

Ichthyological Research -     

A genetic variant of FcγRIIIa is strongly associatedwith humoral immunity to cyclin B1 in African American patients with prostate cancer

There are significant inter-individual differences in naturally occurring antibody responses to the tumor-associated antigen cyclin B1 in healthy subjects with no history of cancer as well as in patients with multiple types of cancer, but the host genetic factors that might contribute to these differences have not been identified. The aim of the present investigation was to determine whether the variation in endogenous antibody levels to cyclin B1 in patients with prostate cancer was associated with immunoglobulin GM and KM alleles, expressed on the constant regions of γ and κ chains, respectively. We also aimed to determine whether particular Fcgamma receptor (FcγR) genotypes, which have been implicated in the immunobiology of several cancers, contribute to the magnitude of humoral immunity to cyclin B1. DNA samples from 129 Caucasian American (CA) and 76 African American (AA) patients with prostate cancer were genotyped for several GM, KM, and FcγR alleles. Plasma samples from these subjects were also characterized for IgG antibodies to cyclin B1. No significant associations were found between any genetic markers and the level of anticyclin B1 antibodies in CA patients. In AA patients, however, homozygosity for the valine allele at the FcγRIIIa locus was strongly associated with low antibody responsiveness to cyclin B1 (p?=?0.0007). Since immunity to cyclin B1 has been shown to play a protective role, these results may, at least in part, explain the disproportionately higher rate of mortality in AA patients with prostate cancer.     

CEP164C regulates flagellum length in stable flagella

Cilia and flagella are required for cell motility and sensing the external environment and can vary in both length and stability. Stable flagella maintain their length without shortening and lengthening and are proposed to “lock” at the end of growth, but molecular mechanisms for this lock are unknown. We show that CEP164C contributes to the locking mechanism at the base of the flagellum in Trypanosoma brucei. CEP164C localizes to mature basal bodies of fully assembled old flagella, but not to growing new flagella, and basal bodies only acquire CEP164C in the third cell cycle after initial assembly. Depletion of CEP164C leads to dysregulation of flagellum growth, with continued growth of the old flagellum, consistent with defects in a flagellum locking mechanism. Inhibiting cytokinesis results in CEP164C acquisition on the new flagellum once it reaches the old flagellum length. These results provide the first insight into the molecular mechanisms regulating flagella growth in cells that must maintain existing flagella while growing new flagella.     

Ingestion of colostrum from specific cows induces Bovine Neonatal Pancytopenia (BNP) in some calves

Background  

Since 2006, cases of haemorrhagic diathesis in young calves have been observed with a much higher incidence than previously known. The syndrome, now uniformly called Bovine Neonatal Pancytopenia (BNP), is characterized by multiple (external and internal) haemorrhages, thrombocytopenia, leukocytopenia, and bone marrow depletion. Although various infectious and toxicological causes of bleeding disorders in calves have been ruled out, the aetiology of BNP remains unknown. However, field observations have led to the hypothesis that the aetiological principle may be transmitted to calves via colostrum.     

Population Pharmacokinetics of Fixed Dose Combination of Ceftriaxone and Sulbactam in Healthy and Infected Subjects

Increased antibacterial resistance (ABR) and limited drug discovery warrant optimized use of available antibiotics. One option is to rationally combine two antibiotics (fixed dose combination (FDC)) that may delay or prevent emergence of ABR in notorious pathogen. Major concern with FDC is the mutual interaction of its components that might influence their pharmacokinetic (PK) profile, requiring reassessing of whole formulation (adding cost and time). The interaction can be identified by comparing PK profile of a drug present in FDC with its independent entity. An open-label, crossover, single-dose comparative PK study of FDC (ceftriaxone and sulbactam) with their individual reference formulations was performed in 24 healthy adult subjects. No mutual PK interactions between ceftriaxone and sulbactam were observed. Pharmacokinetic data was used to develop a population-PK model to understand between-subject variability (BSV). Pharmacokinetics of ceftriaxone/sulbactam was explained by one and two compartment models, respectively. The subject’s “weight” was identified as a covariate explaining BSV. Both internal and external validations (healthy/infected subjects) were done. The model-derived population-PK parameters of FDC’s active components in infected subjects were similar to literature reported values of individual components. Efficacies of various FDC dosage regimens over a range of minimum inhibitory concentrations (MICs) were assessed by Monte Carlo simulations using population-PK parameters of infected/healthy subjects. In infected subjects, 3 g FDC/24 h can treat bacteria with MIC ≤8 μg/mL, while for MIC 8–32 μg/mL, 3 g FDC/12 h is recommended. Lastly, the developed population-PK model was successfully used to predict drug exposure in pediatric population.     

Western blot analysis of cerebrospinal fluid for detection ofAspergillus antigens

Western-blot immunoassay of cerebrospinal fluid (CSF) specimens of patients with central nervous system (CNS) aspergillosis (3), CNS candidosis (1) and bacterial meningitis (2) was carried out using pooled serum from histopathologically proven deep-seated aspergillosis cases to detect unique antigenic fractions for aspergillosis in CSF. No reactivity was observed in patients with non-fungal meningitis. Four cross-reactive bands (40, 90, 200 and >200 KD) were detectable in CSF from patients with both aspergillosis and candidosis of the CNS. Four additional bands (90–200 KD) were consistently present only in patients with aspergillosis. One prominent band (110 KD) was found only in the patient with aspergillosis who had a fatal outcome and raised the possibility of being a poor prognostic marker.