Cenozoic epeirogeny of the Indian peninsula

Peninsular India is a cratonic region with asymmetric relief manifest by eastward tilting from the 1.5 km high Western Ghats escarpment toward the flood-plains of eastward-draining rivers. Oceanic residual depth measurements on either side of India show that this west-east asymmetry is broader scale, occurring over distances of >2,000 km. Admittance analysis of free-air gravity and topography shows that the elastic thickness is 10 ± 3 km, suggesting that regional uplift is not solely caused by flexural loading. To investigate how Indian physiography is generated, we have jointly inverted 530 river profiles to determine rock uplift rate as a function of space and time. Key erosional parameters are calibrated using independent geologic constraints (e.g. emergent marine deposits, elevated paleosurfaces, uplifted lignite deposits). Our results suggest that regional tilt grew at rates of up to 0.1 mm a‾¹ between 25 Ma and the present day. Neogene uplift initiated in the south and propagated northward along the western margin. This calculated history is corroborated by low-temperature ther- mochronologic observations, by sedimentary flux of clastic deposits into the Krishna- Godavari delta, and by sequence stratigraphic architecture along adjacent rifted margins. Onset of regional uplift predates intensification of the Indian monsoon at 8 Ma, suggesting that rock uplift rather than climatic change is responsible for modern-day relief. A positive correlation between residual depth measure- ments and shear wave velocities beneath the lithosphere suggests that regional uplift is generated and maintained by temperature anomalies of ±100 ⁰C within a 200 ± 25 km thick asthenospheric channel

Reassessing the Thermal Structure of Oceanic Lithosphere With Revised Global Inventories of Basement Depths and Heat Flow Measurements

Half-space cooling and plate models of varying complexity have been proposed to account for changes in basement depth and heat flow as a function of lithospheric age in the oceanic realm. Here, we revisit this well-known problem by exploiting a revised and augmented database of 2028 measurements of depth to oceanic basement, corrected for sedimentary loading and variable crustal thickness, and 3597 corrected heat flow measurements. Joint inverse modeling of both databases shows that the half-space cooling model yields a mid-oceanic axial temperature that is >100°C hotter than permitted by petrologic constraints. It also fails to produce the observed flattening at old ages. Then, we investigate a suite of increasingly complex plate models and conclude that the optimal model requires incorporation of experimentally determined temperature- and pressure-dependent conductivity, expansivity and specific heat capacity, as well as a low conductivity crustal layer. This revised model has a mantle potential temperature of 1300 ± 50°C, which honors independent geochemical constraints and has an initial ridge depth of 2.6 ± 0.3 km with a plate thickness of 135 ± 30 km. It predicts that the maximum depth of intraplate earthquakes is bounded by the 700°C isothermal contour, consistent with laboratory creep experiments on olivine aggregates. Estimates of the lithosphere-asthenosphere boundary derived from studies of azimuthal anisotropy coincide with the 1175 ± 50°C isotherm. The model can be used to isolate residual depth and gravity anomalies generated by flexural and sub-plate convective processes.Natural Environment Research Council PhD Studentshi

Neural development features: Spatio-temporal development of the Caenorhabditis elegans neuronal network

The nematode Caenorhabditis elegans, with information on neural connectivity, three-dimensional position and cell linage provides a unique system for understanding the development of neural networks. Although C. elegans has been widely studied in the past, we present the first statistical study from a developmental perspective, with findings that raise interesting suggestions on the establishment of long-distance connections and network hubs. Here, we analyze the neuro-development for temporal and spatial features, using birth times of neurons and their three-dimensional positions. Comparisons of growth in C. elegans with random spatial network growth highlight two findings relevant to neural network development. First, most neurons which are linked by long-distance connections are born around the same time and early on, suggesting the possibility of early contact or interaction between connected neurons during development. Second, early-born neurons are more highly connected (tendency to form hubs) than later born neurons. This indicates that the longer time frame available to them might underlie high connectivity. Both outcomes are not observed for random connection formation. The study finds that around one-third of electrically coupled long-range connections are late forming, raising the question of what mechanisms are involved in ensuring their accuracy, particularly in light of the extremely invariant connectivity observed in C. elegans. In conclusion, the sequence of neural network development highlights the possibility of early contact or interaction in securing long-distance and high-degree connectivity

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Long-term declines in ADLs, IADLs, and mobility among older Medicare beneficiaries

<p>Abstract</p> <p>Background</p> <p>Most prior studies have focused on short-term (≤ 2 years) functional declines. But those studies cannot address aging effects inasmuch as all participants have aged the same amount. Therefore, the authors studied the extent of long-term functional decline in older Medicare beneficiaries who were followed for varying time lengths, and the authors also identified the risk factors associated with those declines.</p> <p>Methods</p> <p>The analytic sample included 5,871 self- or proxy-respondents who had complete baseline and follow-up survey data that could be linked to their Medicare claims for 1993-2007. Functional status was assessed using activities of daily living (ADLs), instrumental ADLs (IADLs), and mobility limitations, with declines defined as the development of two of more new difficulties. Multiple logistic regression analysis was used to focus on the associations involving respondent status, health lifestyle, continuity of care, managed care status, health shocks, and terminal drop.</p> <p>Results</p> <p>The average amount of time between the first and final interviews was 8.0 years. Declines were observed for 36.6% on ADL abilities, 32.3% on IADL abilities, and 30.9% on mobility abilities. Functional decline was more likely to occur when proxy-reports were used, and the effects of baseline function on decline were reduced when proxy-reports were used. Engaging in vigorous physical activity consistently and substantially protected against functional decline, whereas obesity, cigarette smoking, and alcohol consumption were only associated with mobility declines. Post-baseline hospitalizations were the most robust predictors of functional decline, exhibiting a dose-response effect such that the greater the average annual number of hospital episodes, the greater the likelihood of functional status decline. Participants whose final interview preceded their death by one year or less had substantially greater odds of functional status decline.</p> <p>Conclusions</p> <p>Both the additive and interactive (with functional status) effects of respondent status should be taken into consideration whenever proxy-reports are used. Encouraging exercise could broadly reduce the risk of functional decline across all three outcomes, although interventions encouraging weight reduction and smoking cessation would only affect mobility declines. Reducing hospitalization and re-hospitalization rates could also broadly reduce the risk of functional decline across all three outcomes.</p

Immigrant community integration in world cities

As a consequence of the accelerated globalization process, today major cities all over the world are characterized by an increasing multiculturalism. The integration of immigrant communities may be affected by social polarization and spatial segregation. How are these dynamics evolving over time? To what extent the different policies launched to tackle these problems are working? These are critical questions traditionally addressed by studies based on surveys and census data. Such sources are safe to avoid spurious biases, but the data collection becomes an intensive and rather expensive work. Here, we conduct a comprehensive study on immigrant integration in 53 world cities by introducing an innovative approach: an analysis of the spatio-temporal communication patterns of immigrant and local communities based on language detection in Twitter and on novel metrics of spatial integration. We quantify the "Power of Integration" of cities --their capacity to spatially integrate diverse cultures-- and characterize the relations between different cultures when acting as hosts or immigrants.Comment: 13 pages, 5 figures + Appendi

CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

A deeply branching thermophilic bacterium with an ancient acetyl-CoA pathway dominates a subsurface ecosystem

<div><p>A nearly complete genome sequence of <em>Candidatus</em> ‘Acetothermum autotrophicum’, a presently uncultivated bacterium in candidate division OP1, was revealed by metagenomic analysis of a subsurface thermophilic microbial mat community. Phylogenetic analysis based on the concatenated sequences of proteins common among 367 prokaryotes suggests that <em>Ca.</em> ‘A. autotrophicum’ is one of the earliest diverging bacterial lineages. It possesses a folate-dependent Wood-Ljungdahl (acetyl-CoA) pathway of CO₂ fixation, is predicted to have an acetogenic lifestyle, and possesses the newly discovered archaeal-autotrophic type of bifunctional fructose 1,6-bisphosphate aldolase/phosphatase. A phylogenetic analysis of the core gene cluster of the acethyl-CoA pathway, shared by acetogens, methanogens, some sulfur- and iron-reducers and dechlorinators, supports the hypothesis that the core gene cluster of <em>Ca.</em> ‘A. autotrophicum’ is a particularly ancient bacterial pathway. The habitat, physiology and phylogenetic position of <em>Ca.</em> ‘A. autotrophicum’ support the view that the first bacterial and archaeal lineages were H₂-dependent acetogens and methanogenes living in hydrothermal environments.</p> </div

Age-related differences in the cloacal microbiota of a wild bird species

Background: Gastrointestinal bacteria play a central role in the health of animals. The bacteria that individuals acquire as they age may therefore have profound consequences for their future fitness. However, changes in microbial community structure with host age remain poorly understood. We characterised the cloacal bacteria assemblages of chicks and adults in a natural population of black-legged kittiwakes (Rissa tridactyla), using molecular methods. Results: We show that the kittiwake cloaca hosts a diverse assemblage of bacteria. A greater number of total bacterial OTUs (operational taxonomic units) were identified in chicks than adults, and chicks appeared to host a greater number of OTUs that were only isolated from single individuals. In contrast, the number of bacteria identified per individual was higher in adults than chicks, while older chicks hosted more OTUs than younger chicks. Finally, chicks and adults shared only seven OTUs, resulting in pronounced differences in microbial assemblages. This result is surprising given that adults regurgitate food to chicks and share the same nesting environment. Conclusions: Our findings suggest that chick gastrointestinal tracts are colonised by many transient species and that bacterial assemblages gradually transition to a more stable adult state. Phenotypic differences between chicks and adults may lead to these strong differences in bacterial communities. These data provide the framework for future studies targeting the causes and consequences of variation in bacterial assemblages in wild birds

Functional compensation of glutathione S-transferase M1 (GSTM1) null by another GST superfamily member,GSTM2

The gene for glutathione-S-transferase (GST) M1 (GSTM1), a member of the GST-superfamily, is widely studied in cancer risk with regard to the homozygous deletion of the gene (GSTM1 null), leading to a lack of corresponding enzymatic activity. Many of these studies have reported inconsistent findings regarding its association with cancer risk. Therefore, we employed in silico, in vitro, and in vivo approaches to investigate whether the absence of a functional GSTM1 enzyme in a null variant can be compensated for by other family members. Through the in silico approach, we identified maximum structural homology between GSTM1 and GSTM2. Total plasma GST enzymatic activity was similar in recruited individuals, irrespective of their GSTM1 genotype (positive/null). Furthermore, expression profiling using real-time PCR, western blotting, and GSTM2 overexpression following transient knockdown of GSTM1 in HeLa cells confirmed that the absence of GSTM1 activity can be compensated for by the overexpression of GSTM