The dangers of ambidexterity: The origins of handedness

Handedness remains an enigmatic phenomenon. There is no definitive explanation as to why man should have single rather than dual handedness. Intuitively it would seem advantageous in almost every context to have the benefit of equally dextrous hands. Either in context of warfare or hunting, using two hands equally as effectively would appear to be a favourable adaptation over single dexterity. No satisfactory explanation has been offered as to why and how single-handedness evolved.     

Prenatal diagnosis: update on invasive versus noninvasive fetal diagnostic testing from maternal blood

The modern obstetrics care includes noninvasive prenatal diagnosis testing such as first trimester screening performed between 11 and 14 weeks' gestation and second trimester screening performed between 15 and 20 weeks. In these screening tests, biochemical markers are measured in the maternal blood with or without ultrasound for fetal nuchal translucency with reported accuracy of up to 90%. Invasive procedures, including amniocentesis or chorionic villi sampling, are used to achieve over 99% accuracy. During these procedures direct fetal material is examined and, therefore, these tests are highly accurate with the caveat of a small risk for pregnancy loss. Much research now focuses on other noninvasive highly accurate and risk-free tests that will identify fetal material in the maternal blood. Fetal cells and fetal DNA/RNA provide fetal information but are hard to find in an overwhelming background of maternal cells and in the absence of specific fetal cell markers. The most experience has been accumulated with fetal rhesus and fetal sex determination from maternal blood, with an accuracy of up to 100% by using gene sequences that are absent from maternal blood. Although not clinically applicable yet, fetal cells, fetal DNA/RNA and fetal proteomics in combination with cutting edge technology are described to prenatally diagnose aneuploidies and single-gene disorders.     

Targeting the PI3K and MAPK pathways to treat Kaposi's-sarcoma-associated herpes virus infection and pathogenesis

Cells require the ability to appropriately respond to signals in their extracellular environment. To initiate, inhibit and control these processes, the cell has developed a complex network of signaling cascades. The phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways regulate several responses including mitosis, apoptosis, motility, proliferation, differentiation and many others. It is not surprising, therefore, that many viruses target the PI3K and MAPK pathways as a means to manipulate cellular function. Recently, Kaposi's sarcoma-associated herpes virus (KSHV) has been added to the list. KSHV manipulates the PI3K and MAPK pathways to control such divergent processes as cell survival, cellular migration, immune responses, and to control its own reactivation and lytic replication. Manipulation of the PI3K and MAPK pathways also plays a role in malignant transformation. Here, the authors review the potential to target the PI3K and MAPK signaling pathways to inhibit KSHV infection and pathogenesis.     

The clinical utility of fetal cell sorting to determine prenatally fetal E/e or e/e Rh genotype from peripheral maternal blood

OBJECTIVE: This study was undertaken to determine the fetal E/e or e/e Rh genotype prenatally from peripheral maternal blood by examining sorted fetal cells from alloimmunized and nonalloimmunized pregnancies. STUDY DESIGN: Eighteen maternal peripheral venous blood samples were obtained before amniocentesis from 15 pregnant women who were homozygous for the e allele. Five were not alloimmunized and 10 were alloimmunized. The mononuclear cell layer was isolated from the maternal blood and enriched for fetal nucleated red blood cells by flow cytometry with monoclonal antibodies to CD36 or CD71 and to glycophorin A. Eight samples were treated with CD45 monoclonal antibody-coated magnetic beads before they were sorted to deplete the maternal sample of leukocytes (CD45(+) cells). We defined the positive fetal cell fractions as the monoclonal antibody positive-sorted cells derived from the maternal samples. These included sorted cells that were CD36(+)/glycophorin A(+), CD71(+)/glycophorin A(+) and CD45(-) cells that were sorted to become CD45(-)/CD36(+)/glycophorin A(+) or CD45(-)/CD71(+)/glycophorin A(+). The negative fractions were the cells that were negative for either CD36/glycophorin A or CD71/glycophorin A or were the CD45(+) cells. Deoxyribonucleic acid was isolated from all fractions and amplified by polymerase chain reaction with allele-specific primers for the E or e Rh genes. Gel electrophoresis was performed to detect fetal E/e or e/e Rh genotype. The fetal E/e or e/e Rh genotype was confirmed by serologic and deoxyribonucleic acid testing. The accuracy of E/e or e/e Rh genotype determination from the positive cell fractions was compared with that of E/e or e/e Rh genotype determination from the negative fractions. RESULTS: Fetal E/e or e/e Rh genotype was determined correctly in 17 of 18 of the fetal cell enriched positive fractions (94%). Fetal E/e or e/e Rh genotype was determined correctly in 11 of 14 of the maternal samples in the negative unselected cell fractions (79%). Fetal E/e or e/e Rh genotype was determined correctly in 15 of 16 sample fractions that underwent magnetic bead separation with CD45 and were subsequently sorted into positive and negative fractions (94%). Fetal E/e or e/e Rh genotype was determined correctly in 13 of 13 of the samples obtained from the alloimmunized pregnancies (100%). CONCLUSIONS: The use of monoclonal antibodies for cell sorting or for magnetic separation predicted fetal E/e or e/e Rh genotype from peripheral maternal blood correctly in as many as 100% of alloimmunized pregnancies. Thus noninvasive fetal E/e or e/e Rh genotyping can be performed by polymerase chain reaction amplification of the rare fetal cells in maternal blood. The correct prediction of fetal E/e or e/e Rh genotype from the cell population not selected by the monoclonal antibodies suggests that there are fetal cell types other than fetal nucleated erythrocytes that can also be used as a source of fetal deoxyribonucleic acid for noninvasive genetic diagnosis. Improved technology may provide methods less laborious than cell sorting to accurately determine fetal Rh type from different fetal cell types that circulate in maternal blood.     

Cigarette smoke concentrate inhibits Kaposi's sarcoma-associated herpesvirus infection

Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS), primary effusion lymphoma(PEL), multicentric Castleman disease, and other tumors. Progression of KS is dictated by an aberrant production of inflammatory cytokines and increase in KSHV infection of cells. In this study, we analyzed the effect of cigarette smoke concentrate (CSC) on KSHV infection of human foreskin fibroblasts (HFF) using real time quantitative RT-PCR. Our results demonstrated that the CSC-treated cells supported 50% lower infection of KSHV when compared to the untreated cells. Radiolabeled-binding assays indicated that CSC inhibited KSHV infection of cells at a post attachment stage of entry. Taken together, we report for the first time the ability of CSC to specifically inhibit KSHV infection of cells.