Sinorhizobium Meliloti, A Bacterium Lacking The Autoinducer-2 (AI-2) Synthase, Responds To AI-2 Supplied By Other Bacteria

Many bacterial species respond to the quorum-sensing signal autoinducer-2 (AI-2) by regulating different niche-specific genes. Here, we show that Sinorhizobium meliloti, a plant symbiont lacking the gene for the AI-2 synthase, while not capable of producing AI-2 can nonetheless respond to AI-2 produced by other species. We demonstrate that S. meliloti has a periplasmic binding protein that binds AI-2. The crystal structure of this protein (here named SmlsrB) with its ligand reveals that it binds (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran (R-THMF), the identical AI-2 isomer recognized by LsrB of Salmonella typhimurium. The gene encoding SmlsrB is in an operon with orthologues of the lsr genes required for AI-2 internalization in enteric bacteria. Accordingly, S. meliloti internalizes exogenous AI-2, and mutants in this operon are defective in AI-2 internalization. S. meliloti does not gain a metabolic benefit from internalizing AI-2, suggesting that AI-2 functions as a signal in S. meliloti. Furthermore, S. meliloti can completely eliminate the AI-2 secreted by Erwinia carotovora, a plant pathogen shown to use AI-2 to regulate virulence. Our findings suggest that S. meliloti is capable of \u27eavesdropping\u27 on the AI-2 signalling of other species and interfering with AI-2-regulated behaviours such as virulence

Lepton-Flavour Violation in Ordinary and Supersymmetric Grand Unified Theories

By an explicit calculation we show that in ordinary SU(5) logarithmic divergence in the amplitude of $\mu \to e\gamma$ cancels among diagrams and remaining finite part is suppressed by at least $1/M_{GUT}^2$. In SUSY SU(5), when the effect of flavour changing wave function renormalization is taken into account such logarithmic correction disappears, provided a condition is met among SUSY breaking masses. In SUGRA-inspired SUSY GUT the remaining logarithmic effect is argued not to be taken as a prediction of the theory.Comment: 8 pages, LaTeX209 file, using axodraw.st

Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics.

The vitamin B12 family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, but only 37% are predicted to synthesize cobamides de novo. The distribution of cobamide biosynthesis and use vary at the phylum level. While 57% of Actinobacteria are predicted to biosynthesize cobamides, only 0.6% of Bacteroidetes have the complete pathway, yet 96% of species in this phylum have cobamide-dependent enzymes. The form of cobamide produced by the bacteria could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. Bacteria with a partial cobamide biosynthesis pathway include those in a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor salvaging as examples of nutritional dependencies in bacteria

Youth of West Cameroon are at high risk of developing IDD due to low dietary iodine and high dietary thiocyanate.

Objectives: Hypothyroidism in utero leading to mental retardation is highly prevalent and recurrent in developing countries where iodine deficiency and thiocyanate overload are combined. So, to explore and identify human population's risks for developing iodine deficiency disorders and their endemicity in Western Cameroon, with the aim to prevent this deficiency and to fight again it, urinary iodine and thiocyanate levels were determined. Methods: The district of Bamougoum in Western Cameroon was selected for closer study due to its geographic location predisposing for iodine deficiency disorders (IDD). A comprehensive sampling strategy included 24-h urine samples collected over three days from 120 school-aged children. Urinary iodine and thiocyanate levels were measured by colorimetric methods. Results: Twenty one percent of boys between the ages 3 and 19 were classified as iodine deficient. The prevalence of thiocyanate overload in the same population was found to be 20%. Conclusion: Presence of endemic iodine deficiency and excessive thiocyanate in the population indicates that the region is at risk of iodine deficiency disorder. A multifactorial approach that includes improvement of diet, increasing iodine and minimizing goitrogen substances intake, soil and crop improvement and an iodine supplementation program may help alleviate IDD in the affected area studied. African Health Sciences Vol. 8 (4) 2008: pp. 227-23

Role of Human-Induced Pluripotent Stem Cell-Derived Spinal Cord Astrocytes in the Functional Maturation of Motor Neurons in a Multielectrode Array System

The ability to generate human-induced pluripotent stem cell (hiPSC)-derived neural cells displaying region-specific phenotypes is of particular interest for modeling central nervous system biology in vitro. We describe a unique method by which spinal cord hiPSC-derived astrocytes (hiPSC-A) are cultured with spinal cord hiPSC-derived motor neurons (hiPSC-MN) in a multielectrode array (MEA) system to record electrophysiological activity over time. We show that hiPSC-A enhance hiPSC-MN electrophysiological maturation in a time-dependent fashion. The sequence of plating, density, and age in which hiPSC-A are cocultured with MN, but not their respective hiPSC line origin, are factors that influence neuronal electrophysiology. When compared to coculture with mouse primary spinal cord astrocytes, we observe an earlier and more robust electrophysiological maturation in the fully human cultures, suggesting that the human origin is relevant to the recapitulation of astrocyte/motor neuron crosstalk. Finally, we test pharmacological compounds on our MEA platform and observe changes in electrophysiological activity, which confirm hiPSC-MN maturation. These findings are supported by immunocytochemistry and real-time PCR studies in parallel cultures demonstrating human astrocyte mediated changes in the structural maturation and protein expression profiles of the neurons. Interestingly, this relationship is reciprocal and coculture with neurons influences astrocyte maturation as well. Taken together, these data indicate that in a human in vitro spinal cord culture system, astrocytes support hiPSC-MN maturation in a time-dependent and species-specific manner and suggest a closer approximation of in vivo conditions

Raman Scattering Study of Ba-doped C60 with t1g States

Raman spectra are reported for Ba doped fullerides, BaxC60(x=3,4,and 6). The lowest frequency Hg modes split into five components for Ba4C60 and Ba6C60 even at room temperature, allowing us a quantitative analysis based on the electron-phonon couping theory. For the superconducting Ba4C60, the density of states at the Fermi energy was derived as 7 eV-1, while the total value of electron-phonon coupling \lambda was found to be 1.0, which is comparable to that of K3C60. The tangential Ag(2) mode, which is known as a sensitive probe for the degree of charge transfer on C60 molecule, shows a remarkable shift depending on the Ba concentration, being roughly consistent with the full charge transfer from Ba to C60. An effect of hybridization between Ba and C60 \pi orbitals is also discussed.Comment: 15 pages, 6 figures submitted to Phys. Rev. B (December 1,1998

Naturally occurring cobalamin (B12) analogs can function as cofactors for human methylmalonyl-CoA mutase

Cobalamin, commonly known as vitamin B12, is an essential micronutrient for humans because of its role as an enzyme cofactor. Cobalamin is one of over a dozen structurally related compounds - cobamides - that are found in certain foods and are produced by microorganisms in the human gut. Very little is known about how different cobamides affect B12-dependent metabolism in human cells. Here, we test in vitro how diverse cobamide cofactors affect the function of methylmalonyl-CoA mutase (MMUT), one of two cobalamin-dependent enzymes in humans. We find that, although cobalamin is the most effective cofactor for MMUT, multiple cobamides support MMUT function with differences in binding affinity (Kd), binding kinetics (kon), and concentration dependence during catalysis (KM, app). Additionally, we find that six disease-associated MMUT variants that cause cobalamin-responsive impairments in enzymatic activity also respond to other cobamides, with the extent of catalytic rescue dependent on the identity of the cobamide. Our studies challenge the exclusive focus on cobalamin in the context of human physiology, indicate that diverse cobamides can support the function of a human enzyme, and suggest future directions that will improve our understanding of the roles of different cobamides in human biology. Keywords: Cobalamin; Cobamide; MMUT; Methylmalonic aciduria; Methylmalonyl-CoA mutase; Vitamin B(12)

The M 31 double nucleus probed with OASIS and HST. A natural m=1 mode?

We present observations with the adaptive optics assisted integral field spectrograph OASIS of the M 31 double nucleus at a spatial resolution better than 0.5 arcsec FWHM. These data are used to derive the two-dimensional stellar kinematics within the central 2 arcsec. Archival WFPC2/HST images are revisited to perform a photometric decomposition of the nuclear region. We also present STIS/HST kinematics obtained from the archive. The luminosity distribution of the central region is well separated into the respective contributions of the bulge, the nucleus including P1 and P2, and the so-called UV peak. We then show that the axis joining P1 and P2, the two local surface brightness maxima, does not coincide with the kinematic major-axis, which is also the major-axis of the nuclear isophotes (excluding P1). We also confirm that the velocity dispersion peak is offset by ~ 0.2 arcsec from the UV peak, assumed to mark the location of the supermassive black hole. The newly reduced STIS/HST velocity and dispersion profiles are then compared to OASIS and other published kinematics. We find significant offsets with previously published data. Simple parametric models are then built to successfully reconcile all the available kinematics. We finally interpret the observations using new N-body simulations. The nearly keplerian nuclear disk of M31 is subject to a natural m=1 mode, with a very slow pattern speed (3 km/s/pc for M_BH = 7 10^7~\Msun), that can be maintained during more than a thousand dynamical times. The resulting morphology and kinematics of the mode can reproduce the M~31 nuclear-disk photometry and mean stellar velocity, including the observed asymmetries. It requires a central mass concentration and a cold disk system representing between 20 and 40% of its mass. Abridged..Comment: 21 pages. accepted for publication in A&

Evolution of central pattern generators for the control of a five-link bipedal walking mechanism

Central pattern generators (CPGs), with a basis is neurophysiological studies, are a type of neural network for the generation of rhythmic motion. While CPGs are being increasingly used in robot control, most applications are hand-tuned for a specific task and it is acknowledged in the field that generic methods and design principles for creating individual networks for a given task are lacking. This study presents an approach where the connectivity and oscillatory parameters of a CPG network are determined by an evolutionary algorithm with fitness evaluations in a realistic simulation with accurate physics. We apply this technique to a five-link planar walking mechanism to demonstrate its feasibility and performance. In addition, to see whether results from simulation can be acceptably transferred to real robot hardware, the best evolved CPG network is also tested on a real mechanism. Our results also confirm that the biologically inspired CPG model is well suited for legged locomotion, since a diverse manifestation of networks have been observed to succeed in fitness simulations during evolution.Comment: 11 pages, 9 figures; substantial revision of content, organization, and quantitative result

Role of the Small GTPase Rho3 in Golgi/Endosome Trafficking through Functional Interaction with Adaptin in Fission Yeast

BACKGROUND: We had previously identified the mutant allele of apm1(+) that encodes a homolog of the mammalian µ1A subunit of the clathrin-associated adaptor protein-1 (AP-1) complex, and we demonstrated the role of Apm1 in Golgi/endosome trafficking, secretion, and vacuole fusion in fission yeast. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we isolated rho3(+), which encodes a Rho-family small GTPase, an important regulator of exocystosis, as a multicopy-suppressor of the temperature-sensitive growth of the apm1-1 mutant cells. Overexpression of Rho3 suppressed the Cl(-) sensitivity and immunosuppressant sensitivity of the apm1-1 mutant cells. Overexpression of Rho3 also suppressed the fragmentation of vacuoles, and the accumulation of v-SNARE Syb1 in Golgi/endosomes and partially suppressed the defective secretion associated with apm1-deletion cells. Notably, electron microscopic observation of the rho3-deletion cells revealed the accumulation of abnormal Golgi-like structures, vacuole fragmentation, and accumulation of secretory vesicles; these phenotypes were very similar to those of the apm1-deletion cells. Furthermore, the rho3-deletion cells and apm1-deletion cells showed very similar phenotypic characteristics, including the sensitivity to the immunosuppressant FK506, the cell wall-damaging agent micafungin, Cl(-), and valproic acid. Green fluorescent protein (GFP)-Rho3 was localized at Golgi/endosomes as well as the plasma membrane and division site. Finally, Rho3 was shown to form a complex with Apm1 as well as with other subunits of the clathrin-associated AP-1 complex in a GTP- and effector domain-dependent manner. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings reveal a novel role of Rho3 in the regulation of Golgi/endosome trafficking and suggest that clathrin-associated adaptor protein-1 and Rho3 co-ordinate in intracellular transport in fission yeast. To the best of our knowledge, this study provides the first evidence of a direct link between the small GTPase Rho and the clathrin-associated adaptor protein-1 in membrane trafficking