Boric Acid Disturbs Cell Wall Synthesis in Saccharomyces cerevisiae

Boric acid (BA) has broad antimicrobial activity that makes it a popular treatment for yeast vaginitis in complementary and alternative medicine. In the model yeast S. cerevisiae, BA disturbs the cytoskeleton at the bud neck and impairs the assembly of the septation apparatus. BA treatment causes cells to form irregular septa and leads to the synthesis of irregular cell wall protuberances that extend far into the cytoplasm. The thick, chitin-rich septa that are formed during BA exposure prevent separation of cells after abscission and cause the formation of cell chains and clumps. As a response to the BA insult, cells signal cell wall stress through the Slt2p pathway and increase chitin synthesis, presumably to repair cell wall damage

Inactivation of DltA Modulates Virulence Factor Expression in Streptococcus pyogenes

D-alanylated lipoteichoic acid is a virtually ubiquitous component of gram-positive cell walls. Mutations in the dltABCD operon of numerous species exhibit pleiotropic effects, including reduced virulence, which has been attributed to increased binding of cationic antimicrobial peptides to the more negatively charged cell surface. In this study, we have further investigated the effects that mutating dltA has on virulence factor expression in Streptococcus pyogenes.Isogenic Delta dltA mutants had previously been created in two distinct M1T1 isolates of S. pyogenes. Immunoblots, flow cytometry, and immunofluorescence were used to quantitate M protein levels in these strains, as well as to assess their ability to bind complement. Bacteria were tested for their ability to interact with human PMN and to grow in whole human blood. Message levels for emm, sic, and various regulatory elements were assessed by quantitative RT-PCR. Cell walls of Delta dltA mutants contained much less M protein than cell walls of parent strains and this correlated with reduced levels of emm transcripts, increased deposition of complement, increased association of bacteria with polymorphonuclear leukocytes, and reduced bacterial growth in whole human blood. Transcription of at least one other gene of the mga regulon, sic, which encodes a protein that inactivates antimicrobial peptides, was also dramatically reduced in Delta dltA mutants. Concomitantly, ccpA and rofA were unaffected, while rgg and arcA were up-regulated.This study has identified a novel mechanism for the reduced virulence of dltA mutants of Streptococcus pyogenes in which gene regulatory networks somehow sense and respond to the loss of DltA and lack of D-alanine esterification of lipoteichoic acid. The mechanism remains to be determined, but the data indicate that the status of D-alanine-lipoteichoic acid can significantly influence the expression of at least some streptococcal virulence factors and provide further impetus to targeting the dlt operon of gram-positive pathogens in the search for novel antimicrobial compounds

Psychosocial Needs of Children in Foster Care and the Impact of Sexual Abuse

Children in family foster care, especially those who have experienced sexual abuse, require a safe and nurturing environment in which their psychosocial needs are met. However, there is limited knowledge on how youth prioritize various needs and what impact previous experiences have on these needs. In this study, we asked youth (formerly) in family foster care to indicate their psychosocial needs, and analyzed if youth with a history of sexual abuse have different needs. A Q methodological study was conducted with 44 youth (age 16–28). Fifteen of them reported sexual abuse during their childhood. Using by-person factor analyses, respondents who share similar subjective views were grouped together. Qualitative interpretations of the factors show differences and similarities between and within the two groups, related to help from others, being independent, processing the past, and working toward the future. Although the needs of youth with and without experiences of sexual abuse seem mostly similar, one group of sexually abused youth specifically indicated not wanting an emotional connection to foster parents, but instead a strictly instrumental, professional relationship. This study captured the diverse perspectives of youth themselves, revealing that children in foster care differ with regard to what they consider as (most) important safety, belonging, self-esteem and self-actualization needs

The needs of foster children and how to satisfy them:A systematic review of the literature

Family foster care deeply influences the needs of children and how these are satisfied. To increase our knowledge of foster children’s needs and how these are conceptualized, this paper presents a systematic literature review. Sixty- four empirical articles from six databases were reviewed and categorized (inter-rater agreement K = .78) into four categories: medical, belongingness, psychological and self-actualization needs. The results give a complete overview of needs that are specific to foster children, and what can be implemented to satisfy these needs. This study shows psychological needs are studied more often compared to the other categories, which specially relates to much attention for mental health problems. Furthermore, most articles focus on how to satisfy the needs of foster children and provide no definition or concrete conceptualization of needs. Strikingly, many articles focus on children’s problems instead of their needs, and some even use these terms interchangeably. This review illustrates that future research should employ a proper conceptualization of needs, which could also initiate a shift in thinking about needs instead of problems

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis