Molecular dialogue between the human gut microbiota and the host: a Lactobacillus and Bifidobacterium perspective

The human gut represents a highly complex ecosystem, which is densely colonized by a myriad of microorganisms that influence the physiology, immune function and health status of the host. Among the many members of the human gut microbiota, there are microorganisms that have co-evolved with their host and that are believed to exert health-promoting or probiotic effects. Probiotic bacteria isolated from the gut and other environments are commercially exploited, and although there is a growing list of health benefits provided by the consumption of such probiotics, their precise mechanisms of action have essentially remained elusive. Genomics approaches have provided exciting new opportunities for the identification of probiotic effector molecules that elicit specific responses to influence the physiology and immune function of their human host. In this review, we describe the current understanding of the intriguing relationships that exist between the human gut and key members of the gut microbiota such as bifidobacteria and lactobacilli, discussed here as prototypical groups of probiotic microorganisms.     

The Importance of Being Timely

Policymakers want to know about real‐time economy performance. However, closely watched macroeconomic time series produced by national statistics offices are published infrequently, with a time lag and subject to revision. Such issues create uncertainty in tracking economic developments, a by‐product of which is to raise the value of business and consumer surveys. Although providing less granularity than official data series, the surveys are released in a timelier manner and are subject to little revision. Using real‐time data sourced from the Deutsche Bundesbank, the OECD and the Office for National Statistics, an assessment of the role that the popular and widely used Purchasing Managers' Index (PMI) play in reducing forecasting errors in a simple ‘nowcasting’ framework is undertaken. The empirical exercise is conducted for five developed economies and also covers the period of the Great Recession. The conclusion is clear: timing matters. Copyright © 2015 John Wiley & Sons, Ltd.     

Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency

Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.     

Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis

The genetic association of the major histocompatibility complex (MHC) to rheumatoid arthritis risk has commonly been attributed to alleles in HLA-DRB1. However, debate persists about the identity of the causal variants in HLA-DRB1 and the presence of independent effects elsewhere in the MHC. Using existing genome-wide SNP data in 5,018 individuals with seropositive rheumatoid arthritis (cases) and 14,974 unaffected controls, we imputed and tested classical alleles and amino acid polymorphisms in HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1 and HLA-DRB1, as well as 3,117 SNPs across the MHC. Conditional and haplotype analyses identified that three amino acid positions (11, 71 and 74) in HLA-DRβ1 and single-amino-acid polymorphisms in HLA-B (at position 9) and HLA-DPβ1 (at position 9), which are all located in peptide-binding grooves, almost completely explain the MHC association to rheumatoid arthritis risk. This study shows how imputation of functional variation from large reference panels can help fine map association signals in the MHC.     

Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis

The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases.     

Heat-shock protein 60 translocates to the surface of apoptotic cells and differentiated megakaryocytes and stimulates phagocytosis

Heat-shock protein 60 (Hsp60) is a highly conserved stress protein which has chaperone functions in prokaryotes and mammalian cells. Hsp60 is associated with the mitochondria and the plasma membrane through phosphorylation by protein kinase A, and is incorporated into lipid membranes as a protein-folding chaperone. Its diverse intracellular chaperone functions include the secretion of proteins where it maintains the conformation of precursors and facilitates their translocation through the plasma membrane. We report here that Hsp60 is concentrated in apoptotic membrane blebs and translocates to the surface of cells undergoing apoptosis. Hsp60 is also enriched in platelets derived from terminally differentiated megakaryocytes and expressed at the surface of senescent platelets. Furthermore, the exposure of monocytic U937 cells to Hsp60 enhanced their phagocytic activity. Our results suggests that externalized Hsp60 in apoptotic cells and senescent platelets influences events subsequent to apoptosis, such as the clearance of apoptotic cells by phagocytes.     

Predation of adult razorback sucker and bonytail by striped bass in Lake Mohave, Arizona–Nevada

We report 2 separate records from sport-fish anglers in Lake Mohave, Arizona–Nevada, that document the presence of endangered razorback sucker Xyrauchen texanus and bonytail Gila elegans in stomach contents of large (13+ kg) nonnative striped bass Morone saxatilis. These records suggest that striped bass, since their first appearance in Lake Mohave nearly 3 decades ago, may have played a role in population declines of the other 2 species. Current native-fish stocking programs at Lake Mohave continue to face significant obstacles to achieving population recoveries because all life stages of repatriated individuals, including mature adults, are vulnerable to predation.     

Pollinator preferences for yellow, orange, and red flowers of Mimulus verbenaceus and M. Cardinalis

Red. orange, and yellow morphs of Mimulus verbenaceus and M. cardinalis were field tested for pollinator preferences. The species are closely similar except that M. verbenaceus flowers have partially reflexed corolla lobes, whereas M. cardinalis flowers have fully reflexed corolla lobes. On the basis of over 6000 bumblebee and hummingbird visits, highly significant ( p Mimulus verbenaceus and M. cardinalis .     

First North American record of Cichlasoma managuense (Pisces: Cichlidae)

An established population of a neotropical cichlid fish, Cichlasoma managuense , was found in a spring pool in the Virgin River basin, Utah. Presence of this predatory species poses an additional threat to the native fish fauna of the Virgin River, which already has suffered multiple impacts of water development and introduced fishes.     

Stick nests on a building and transmission towers used for nesting by large falcons in Utah

Large falcons (genus Falco ) do not build their own nests and, in North America at least, usually nest on high cliffs. Occasionally they nest in abandoned stick nests built by another large bird on the cliff. In Asia and particularly South Africa, they sometimes nest in stick nests on electrical transmission towers. This use of electric transmission towers was recently (1980) reported for the Prairie Falcon ( Falco mexicanus ) in North America but is unknown, except for 1 anocdotically documented use of an ""electric-power pole"" at the turn of century in California, for the Peregrine Falcon ( Falco peregrines ) in North America. Here we report such nesting of the peregrine in North America and additional tower nestings of the Prairie Falcon.