Impact of Intrapartum Antibiotic Prophylaxis on Offspring Microbiota.

Infants are born into a world filled with microbes and must adapt without undue immune response while exploiting the microbiota's ability to produce otherwise unavailable nutrients. The process by which humans and microbes establish this relationship has only recently begun to be studied with the aid of genomic methods. Nearly half of all pregnant women receive antibiotics during gestation to prevent maternal and neonatal infection. Though this has been largely successful in reducing early-onset sepsis, we have yet to understand the long-term consequences of antibiotic administration during gestation to developing infants. Studies involving antibiotic use in infants suggest that dysbiosis during this period is associated with increased obesity, allergy, autoimmunity, and chronic diseases in adulthood, however, research around the limited doses of intravenous antibiotics used for intrapartum prophylaxis is limited. In this mini review, we focused on the state of the science regarding the effects of intrapartum antibiotic prophylaxis on the newborn microbial colonization process. Although, the literature indicates that there is wide variety in the specific bacteria that colonize infants from birth, limited parenteral antibiotic administration prior to delivery consistently affects the microbiota of infants by decreasing bacteria in the phylum Bacteroidetes and increasing bacteria in the phylum Proteobacteria, thus altering the normal pattern of colonization that infants experience. Delivery by cesarean section and formula feeding magnify and prolong this effect. Our mini review shows that the impact of intravenous antibiotic administration during gestation has on early colonization, growth, or immune programming in the developing offspring has not been well studied in human or animal models.

The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4.

The dual-specific kinase DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A) is the mammalian orthologue of the Drosophila minibrain (MNB) protein kinase and executes diverse roles in neuronal development and adult brain physiology. DYRK1A is overexpressed in Down syndrome (DS) and has recently been implicated in several neurodegenerative diseases. In an attempt to elucidate the molecular basis of its involvement in cognitive and neurodegeneration processes, we searched for novel proteins interacting with the kinase domain of DYRK1A in the adult mouse brain and identified septin 4 (SEPT4, also known as Pnutl2/CDCrel-2). SEPT4 is a member of the group III septin family of guanosine triphosphate hydrolases (GTPases), which has previously been found in neurofibrillary tangles of Alzheimer disease brains and in alpha-synuclein-positive cytoplasmic inclusions in Parkinson disease brains. In transfected mammalian cells, DYRK1A specifically interacts with and phosphorylates SEPT4. Phosphorylation of SEPT4 by DYRK1A was inhibited by harmine, which has recently been identified as the most specific inhibitor of DYRK1A. In support of a physiological relation in the brain, we found that Dyrk1A and Sept4 are co-expressed and co-localized in neocortical neurons. These findings suggest that SEPT4 is a substrate of DYRK1A kinase and thus provide a possible link for the involvement of DYRK1A in neurodegenerative processes and in DS neuropathologies.

Conditional transgenesis and recombination to study the molecular mechanisms of brain plasticity and memory.

In the postgenomic era, a primary focus of mouse genetics is to elucidate the role of individual genes in vivo. However, in the nervous system, studying the contribution of specific genes to brain functions is difficult because the brain is a highly complex organ with multiple neuroanatomical structures, orchestrating virtually every function in the body. Further, higher-order brain functions such as learning and memory simultaneously recruit several signaling cascades in different subcellular compartments and have highly fine-tuned spatial and temporal components. Conditional transgenic and gene targeting methodologies, however, now offer valuable tools with improved spatial and temporal resolution for appropriate studies of these functions. This chapter provides an overview of these tools and describes how they have helped gain better understanding of the role of candidate genes such as the NMDA receptor, the protein kinase CaMKIIIalpha, the protein phosphatases calcineurin and PP1, or the transcription factor CREB, in the processes of learning and memory. This review illustrates the broad and innovative applicability of these methodologies to the study of brain plasticity and cognitive functions.

Deimos: an obstacle to the solar wind.

Two isolated solar wind disturbances about 5 minutes in duration were detected aboard the Russian spacecraft Phobos-2 upon its crossing the wake of the martian moon Deimos about 15,000 kilometers downstream from the moon on 1 February 1989. These plasma and magnetic events are interpreted as the inbound and outbound crossings of a Mach cone that is formed as a result of an effective interaction of the solar wind with Deimos. Possible mechanisms such as remanent magnetization, cometary type interaction caused by heavy ion or charged dust production, and unipolar induction resulting from the finite conductivity of the body are discussed. Although none of the present models is fully satisfactory, neutral gas emission through water loss by Deimos at a rate of about 10(23) molecules per second, combined with a charged dust coma, is favored.

A magnetohydrodynamic model of solar wind interaction with asteroid gaspra.

The solar wind response to a small-sized magnetized body is modeled on the basis of a two-dimensional magnetohydrodynamic (MHD) plasma description including Hall current corrections (Hall-MHD model). Basic features of the magnetic signatures observed near Galileo's closest approach to asteroid Gaspra are reproduced, assuming Gaspra's magnetic dipole momentto be of the order of 10(14) ampere.meters squared and tilted to the solar wind flow direction at an angle of about 45 degrees .