Uncovering hidden treasures: establishing the discipline of Indian manuscriptology

A recent IIAS workshop brought together esteemed scholars to look at the production, distribution and collection of Sanskrit manuscripts in Ancient South India

Separating ventricular activity in thoracic EIT using 4D image-based FEM simulations

One challenge in central hemodynamic monitoring based on electrical impedance tomography (EIT) is to robustly detect ventricular signal components and the corresponding EIT image region without external monitoring information. Current stimulation and voltage measurement of EIT were simulated with finite element porcine torso models in presence of a multitude ofthoracic blood volume shifts. The simulated measurement data was examined for linear dependence on changes in stroke volume. Based onthe results the EIT measurement information regardingstroke volume changesis sparse

PHLPP1 counter-regulates STAT1-mediated inflammatory signaling.

Inflammation is an essential aspect of innate immunity but also contributes to diverse human diseases. Although much is known about the kinases that control inflammatory signaling, less is known about the opposing phosphatases. Here we report that deletion of the gene encoding PH domain Leucine-rich repeat Protein Phosphatase 1 (PHLPP1) protects mice from lethal lipopolysaccharide (LPS) challenge and live Escherichia coli infection. Investigation of PHLPP1 function in macrophages reveals that it controls the magnitude and duration of inflammatory signaling by dephosphorylating the transcription factor STAT1 on Ser727 to inhibit its activity, reduce its promoter residency, and reduce the expression of target genes involved in innate immunity and cytokine signaling. This previously undescribed function of PHLPP1 depends on a bipartite nuclear localization signal in its unique N-terminal extension. Our data support a model in which nuclear PHLPP1 dephosphorylates STAT1 to control the magnitude and duration of inflammatory signaling in macrophages

Influences of physical oceanographic processes on chlorophyll distributions in coastal and estuarine waters of the South Atlantic Bight

Coastal and estuarine waters of the South Atlantic Bight are highly productive, with primary production of 600-700 gC/m2/y. While controls and fate of this production are conceptually well understood, the importance of meteorology and physical circulation processes on phytoplankton has not received equivalent attention. Here, we describe the effects of wind stress and tidal currents on temporal and spatial distributions of phytoplankton biomass represented as chlorophyll a (chl a). Moored instruments were deployed and shipboard sampling was conducted in the North Edisto estuary (South Carolina) and adjacent inner shelf waters during four, two-week field studies in May and August 1993, and June and September 1994. Local wind regimes induced upwelling- and downwelling-favorable conditions which strengthened or reduced vertical density stratification in the coastal frontal zone, respectively, and shifted the location of the front. Chl a in shelf waters was more or less homogenous independent of the wind regime, while chl a on the estuary delta was generally vertically stratified. Within the estuary, chl a concentrations were positively correlated with the alongshore component of wind stress; chl a was not correlated with the weaker cross-shelf component of wind stress. Highest chl a occurred during strong downwelling-favorable events. The quick response time to wind forcing (6-12 hrs) implied a direct effect on chl a distributions and not a stimulation of growth processes. The source of the elevated chl a in response to wind forcing was apparently resuspension of settled and epibenthic algal cells. Tidal currents also influenced the vertical distribution and concentration of chl a. Time series sampling on the estuary delta showed that, with increasing velocity of ebb and flood tide currents, the relative contributions of pennate and centric diatoms with attached detritus and sand grains also increased, indicating that tidal resuspension of settled and epibenthic microalgae also occurred. Vertical stratification of chl a (highest concentrations near the bottom) began to degrade upon mixing by tidal currents with velocities as low as 10 cm/sec. Homogenization of 5-7 m water columns was fully achieved at velocities of 20-30 cm/sec. The data document the direct and comparatively immediate (timescales of minuteshours) impact of tidal and wind energy on concentrations and distribution patterns of phytoplankton in coastal and estuarine waters of the South Atlantic Bight

Research and demonstration updates: ISU Rhodes Research Farm and PFI on-farm cooperator data

A recently completed study compared the economic return of hooped buildings versus conventional facilities. Factors considered included pig growth rate, feed efficiency, developing growth function, distrib-qtion of growth, production costs and returns, and rate of return on investment

WHO scientific update on trans fatty acids: Summary and conclusions

The purpose of the WHO scientific review on trans fatty acids (TFAs) was to examine the evidence generated since the 1993 Joint FAO/WHO Expert Consultation on Fats and Oils in Human Nutrition, and to inform member countries on the health consequences of TFAs consumption that have emerged since the last report was released. The new information was deemed sufficient to recommend the need to significantly reduce or to virtually eliminate industrially produced TFA from the food supply in agreement with the implementation of the 2004 WHO Global Strategy on Diet, Physical Activity and Health. This goal has been accomplished in some countries and cities, by the virtual elimination of partially hydrogenated vegetable oils in the human food supply, replacing them with healthy cis-unsaturated fatty acids. The document provides the evidence base to promote discussion between the international scientific community related to nutrition and health as well as between agriculturalists, food producers, relevant health professionals, national and international food regulatory agencies, civil society and the private sector to achieve the stated goal.Facultad de Ciencias Médica

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Pleckstrin homology domain leucine-rich repeat protein phosphatases set the amplitude of receptor tyrosine kinase output

Growth factor receptor levels are aberrantly high in diverse cancers, driving the proliferation and survival of tumor cells. Understanding the molecular basis for this aberrant elevation has profound clinical implications. Here we show that the pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) suppresses receptor tyrosine kinase (RTK) signaling output by a previously unidentified epigenetic mechanism unrelated to its previously described function as the hydrophobic motif phosphatase for the protein kinase AKT, protein kinase C, and S6 kinase. Specifically, we show that nuclear-localized PHLPP suppresses histone phosphorylation and acetylation, in turn suppressing the transcription of diverse growth factor receptors, including the EGF receptor. These data uncover a much broader role for PHLPP in regulation of growth factor signaling beyond its direct inactivation of AKT: By suppressing RTK levels, PHLPP dampens the downstream signaling output of two major oncogenic pathways, the PI3 kinase/AKT and the Rat sarcoma (RAS)/ERK pathways. Our data are consistent with a model in which PHLPP modifies the histone code to control the transcription of RTKs

Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages

Mechanisms by which members of the AP-1 family of transcription factors play non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, here we investigate the molecular functions and genome-wide DNA binding patterns of AP-1 family members in primary and immortalized mouse macrophages. ChIP-sequencing shows overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yields dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions are confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif