Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1.

The budding yeast Candida albicans is one of the most significant fungal pathogens worldwide. It proliferates in two distinct cell types: blastopores and filaments. Only cells that are able to transform from one cell type into the other are virulent in mouse disease models. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We now provide evidence that suggests that programmed cell death is cell-type specific in yeast: Filamentous C. albicans cells are more resistant to amphotericin B- and caspofungin-induced programmed cell death than their blastospore counterparts. Finally, our genetic data suggests that this phenomenon is mediated by a protective mechanism involving the yeast metacaspase, MCA1.

Sensory processing disorder in children ages birth-3 years born prematurely: a systematic review.

This systematic review of multidisciplinary literature synthesizes evidence of the prevalence and patterns of sensory processing disorder (SPD) in children ages birth-3 yr born preterm. Forty-five articles including physiological, behavioral, temperament, and SPD research met the inclusion criteria and provided 295 findings related to SPD-130 (44%) positive (evidence of SPD) and 165 (56%) negative (no evidence of SPD). The majority of findings related to sensory modulation disorder (SMD; 43% positive). The most prevalent subcategory of SMD was sensory overresponsivity (82% of findings positive). Evidence of sensory underresponsivity and sensory-seeking SMD, sensory discrimination disorder, and sensory-based motor disorder was limited. This study supports the education of neonatologists, pediatricians, and caregivers about the symptoms and potential consequences of SPD and helps justify the need for follow-up screening for SPD in children ages birth-3 yr born preterm. Research using measures based on sensory processing theory is needed.

SAR of a novel 'Anthranilamide Like' series of VEGFR-2, multi protein kinase inhibitors for the treatment of cancer.

Novel anthranilamides were surprisingly found to exert additional activity on B-RAF. Corresponding thiophene, pyrazole, and thiazole core analogs were prepared as VEGFR-2 inhibitors with c-KIT, and B-RAF activity. Compounds in the phenyl, thiophene, and thiazole series are in vivo active.

Co-translational incorporation of trans-4-hydroxyproline into recombinant proteins in bacteria.

Trans-4-hydroxyproline (Hyp) in eukaryotic proteins arises from post-translational modification of proline residues. Because the modification enzyme is not present in prokaryotes, no natural means exists to incorporate Hyp into proteins synthesized in Escherichia coli. We show here that under appropriate culture conditions Hyp is incorporated co-translationally directly at proline codons in genes expressed in E. coli. The use of Hyp by E. coli protein synthesis machinery under typical culture conditions is not adequate to support protein synthesis; however, intracellular concentrations of Hyp sufficient to compensate for the poor use are achieved in media with hyperosmotic sodium chloride concentrations. Hyp incorporation was demonstrated in several recombinant proteins including human Type I collagen polypeptides. A fragment of the human collagen Type I (alpha1) polypeptide with global Hyp for Pro substitution forms a triple helix. Our results demonstrate a remarkable pliancy in the biosynthetic apparatus of bacteria that may be used more generally to incorporate novel amino acids into recombinant proteins.