Selection shapes the landscape of functional variation in wild house mice.

BACKGROUND: Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. RESULTS: Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. CONCLUSIONS: Overall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases

Population and subspecies diversity at mouse centromere satellites.

BACKGROUND: Mammalian centromeres are satellite-rich chromatin domains that execute conserved roles in kinetochore assembly and chromosome segregation. Centromere satellites evolve rapidly between species, but little is known about population-level diversity across these loci. RESULTS: We developed a k-mer based method to quantify centromere copy number and sequence variation from whole genome sequencing data. We applied this method to diverse inbred and wild house mouse (Mus musculus) genomes to profile diversity across the core centromere (minor) satellite and the pericentromeric (major) satellite repeat. We show that minor satellite copy number varies more than 10-fold among inbred mouse strains, whereas major satellite copy numbers span a 3-fold range. In contrast to widely held assumptions about the homogeneity of mouse centromere repeats, we uncover marked satellite sequence heterogeneity within single genomes, with diversity levels across the minor satellite exceeding those at the major satellite. Analyses in wild-caught mice implicate subspecies and population origin as significant determinants of variation in satellite copy number and satellite heterogeneity. Intriguingly, we also find that wild-caught mice harbor dramatically reduced minor satellite copy number and elevated satellite sequence heterogeneity compared to inbred strains, suggesting that inbreeding may reshape centromere architecture in pronounced ways. CONCLUSION: Taken together, our results highlight the power of k-mer based approaches for probing variation across repetitive regions, provide an initial portrait of centromere variation across Mus musculus, and lay the groundwork for future functional studies on the consequences of natural genetic variation at these essential chromatin domains

Root morphology and mycotrophy of Disperis neilgherrensis (Orchidaceae) from Western Ghats, southern India

Por primera vez se examinó la morfología radicular y la microtrofia de Disperis neilgherrensis Wight., provenientes de los Ghats occi- dentales, India meridional. El sistema radicula es disperso, consis- tiendo en una raices blancas delgadas de 0,28 ± 0,11 mm, que par- ten de un rizoma marrón. Las raíces están cubiertas por pelos radi- culares (19,2 ± 1,5 por mm de raíz) de 161,80 ± 12,68 μm de largo y 4,55 ± 1,17 μm de ancho. Las celulas corticales contenían es- tructuras fúngicas típicas de micorrizas orquidoides (OM) y arbus- culares (AM). En contraste, los rizomas sólo presentan estructuras OM. La colonización OM se caracteriza por presentar ovillos man- chados claros u obscuros, con hifas regularmente septadas de diá- metros variados. La colonización AM se caracteriza por ovillos hifa- les intracelulares no septados, arbúsculos y vesículas intracelula- res. El porcentaje de longitud con colonización OM fue de 56,51% para raíces y 73,64% para rizomas, mientras que la longitud de raíz con colonización AM fue de 30,23%. En tipo de AM en D. neil- gherrensis corresponde al tipo Paris

Development, testing and plant trails of single reagent system for coal flotation

Flotation is an important means of upgrading the fine fraction of raw coal, typically particles finer than 0.5 mm. Due to increased use of highly mechanized mining techniques large quantities of fines (< 0.5 mm) are being generated. These fines presently account for approximately 20–30% of the total plant feed. More than 140 million tones of fine coals are beneficiated by flotation worldwide annually. In coal flotation, reagents are required to enhance the hydrophobicity of coal surface. In addition to hydrophobic character, the selectivity, proper froth structure, stability and less sensitive to water chemistry are important. Water insoluble hydrocarbons are widely used as collectors in coal flotation. These collectors are basically non-polar oils like diesel, kerosene, etc. along with some frothers. Thus, it is necessary to add collector and frother separately in coal flotation. It is generally accepted that in coal flotation a single reagent system is more advantageous than the present practice of two reagent system. National Metallurgical Laboratory is involved in the flotation of coal fines using alternative single collector systems to developed specially replace fuel oils and frothers. For this purpose NML has entered into an agreement with M/s Somu Organo-Chem Pvt. Ltd. (SOCPL) Bangalore, a leading reagent manufacturer. Under this collaboration M/s SOCPL developed reagents and NML evaluated their selectivity index and application in coal flotation. Among many reagents developed and evaluated one best reagent was selected and full scale plant trails were conducted. The paper deals with the results obtained with several reagents in the laboratory and the plant trails

Measuring childhood socioeconomic position in health research:Development and validation of childhood socioeconomic position questionnaire using mixed method approach

Background: There is no single best indicator to assess the childhood socioeconomic position (CSEP) in public health research. The aim of the study is to develop and validate a new questionnaire, with adequate psychometric properties, to measure the childhood SEP of the young adults. Methods: The first phase consisted of a qualitative phase to identify the variables to measure childhood SEP through the in-depth interviews among 15 young adults (18-45 years) of rural Kerala. The second phase was a quantitative phase to validate the questionnaire through a cross sectional survey among 200 young adults of Kerala. We did content validity, reliability tests and construct validity by using exploratory factor analysis of the questionnaire to demonstrate its psychometric properties. Results: The qualitative analysis reported 26 variables spread across 5 domains to measure the CSEP. Finally, the questionnaire has 11 questions with 3 domains named as value added through paternity, maternal occupation-related factors and parental education. The questionnaire has good reliability (Cronbach's α=0.88) also. Conclusion: We have developed a reliable and valid questionnaire to measure the childhood SEP of younger adults and can be used in various public health research

Comparative analysis of cyanobacterial superoxide dismutases to discriminate canonical forms

<p>Abstract</p> <p>Background</p> <p>Superoxide dismutases (SOD) are ubiquitous metalloenzymes that catalyze the disproportion of superoxide to peroxide and molecular oxygen through alternate oxidation and reduction of their metal ions. In general, SODs are classified into four forms by their catalytic metals namely; FeSOD, MnSOD, Cu/ZnSOD and NiSOD. In addition, a cambialistic form that uses Fe/Mn in its active site also exists. Cyanobacteria, the oxygen evolving photosynthetic prokaryotes, produce reactive oxygen species that can damage cellular components leading to cell death. Thus, the co-evolution of an antioxidant system was necessary for the survival of photosynthetic organisms with SOD as the initial enzyme evolved to alleviate the toxic effect. Cyanobacteria represent the first oxygenic photoautotrophs and their SOD sequences available in the databases lack clear annotation. Hence, the present study focuses on structure and sequence pattern of subsets of cyanobacterial superoxide dismutases.</p> <p>Result</p> <p>The sequence conservation and structural analysis of Fe (<it>Thermosynechococcus elongatus </it>BP1) and MnSOD (<it>Anabaena </it>sp. PCC7120) reveal the sharing of N and C terminal domains. At the C terminal domain, the metal binding motif in cyanoprokaryotes is DVWEHAYY while it is D-X-[WF]-E-H-[STA]-[FY]-[FY] in other pro- and eukaryotes. The cyanobacterial FeSOD differs from MnSOD at least in three ways <it>viz</it>. (i) FeSOD has a metal specific signature F184X₃A188Q189_.......T280_......F/Y303 while, in Mn it is R184X₃G188G189_......G280......W303, (ii) aspartate ligand forms a hydrogen bond from the active site with the outer sphere residue of W243 in Fe where as it is Q262 in MnSOD; and (iii) two unique lysine residues at positions 201 and 255 with a photosynthetic role, found only in FeSOD. Further, most of the cyanobacterial Mn metalloforms have a specific transmembrane hydrophobic pocket that distinguishes FeSOD from Mn isoform. Cyanobacterial Cu/ZnSOD has a copper domain and two different signatures G-F-H-[ILV]-H-x-[NGT]-[GPDA]-[SQK]-C and G-[GA]-G-G-[AEG]-R-[FIL]-[AG]-C-G, while Ni isoform has an nickel containing SOD domain containing a Ni-hook HCDGPCVYDPA.</p> <p>Conclusion</p> <p>The present analysis unravels the ambiguity among cyanobacterial SOD isoforms. NiSOD is the only SOD found in lower forms; whereas, Fe and Mn occupy the higher orders of cyanobacteria. In conclusion, cyanobacteria harbor either Ni alone or a combination of Fe and Ni or Fe and Mn as their catalytic active metal while Cu/Zn is rare.</p

Eco Friendly and Cost-Effective Reagent for Coal Flotation

Conventionally, diesel in combination with a frother is used widely in flotation of coal fines. With the continuous price escalation of petroleum products and their negative impact on environment, attempts were made to formulate an eco-friendly single reagent to replace diesel-frother system without affecting the flotation performance. Laboratory flotation tests were carried out, on a coking coal sample from eastern India, that analyzed 25.67% ash and 53.97% fixed carbon using a series of reagents developed. Among them, the performance of Sokem 590C derived from a vegetable oil was found to be encouraging. Concentrate assaying 11.77% ash and 66.40% fixed carbon was obtained with yield of 56.57%. Moreover, the reagent is biodegradable and eco friendly. Based on favorable kinetics and encouraging test results, plant trials were conducted at a coal preparation plant and the superiority of this reagent was demonstrated

Single reagent for coal flotation

Froth flotation is widely used for the beneficiation of fine coal and collectors are important for the effective separation in flotation. Conventionally, diesel in combination with a commercial frother is used in most of the coal washeries. With the escalating costs of petroleum products and their negative impact on environment, attempts were made to formulate an eco-friendly single reagent to replace diesel-frother system without hindering the flotation process performance. NML-Madras Centre in collaboration with M/s Somu Organo Chem Pvt Ltd, has been working on the formulation and evaluation of flotation reagents. Laboratory flotation tests were carried out using series of single reagents on a coking coal sample from Jharia region in the eastern part of India with an ash content of 24.9%. The best among the single reagents, Sokem 590C, yielded a float of 56.57% at 13.97% ash in the bench scale laboratory test. Based on encouraging results of flotation tests and kinetics studies, plant trials were conducted at a coal preparation plant in eastern India. The results of plant trials using this single reagent, Sokem 590C, are highly encouraging and economical as compared to diesel-frother system and this single reagent is non-petroleum based and biodegradable

A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients with Acquired Brain Injury

OBJECTIVES: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury. DESIGN: A single center prospective observational study. SETTING: Pediatric and cardiac ICUs at a single tertiary care, academic center. PATIENTS: Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were collected from the extracorporeal membrane oxygenation circuit at day 1 (10-23 hr), day 3, and day 7 of extracorporeal membrane oxygenation. Flow cytometry quantified circulating innate and adaptive immune cells, and CNS-directed autoreactivity was detected using an in vitro recall response assay. Disruption of cerebral autoregulation was determined using continuous bedside near-infrared spectroscopy and acquired brain injury confirmed by MRI. Extracorporeal membrane oxygenation patients with acquired brain injury (n = 9) presented with a 10-fold increase in interleukin-8 over extracorporeal membrane oxygenation patients without brain injury (p \u3c 0.01). Furthermore, brain injury within extracorporeal membrane oxygenation patients potentiated an inflammatory phenotype in adaptive immune cells and selective autoreactivity to brain peptides in circulating B cell and cytotoxic T cell populations. Correlation analysis revealed a significant relationship between adaptive immune responses of extracorporeal membrane oxygenation patients with acquired brain injury and loss of cerebral autoregulation. CONCLUSIONS: We show that pediatric extracorporeal membrane oxygenation patients with acquired brain injury exhibit an induction of pro-inflammatory cell signaling, a robust activation of adaptive immune cells, and CNS-targeting adaptive immune responses. As these patients experience developmental delays for years after extracorporeal membrane oxygenation, it is critical to identify and characterize adaptive immune cell mechanisms that target the developing CNS

Single reagent for graphite flotation

Generally, diesel and frother are used as reagents in graphite flotation. With the escalating cost of petroleum products and their negative impact on environment, attempts are made to formulate an eco-friendly single reagent to replace the diesel-frother system without affecting the flotation performance. CSIR-NML Madras Centre in collaboration with M/s Somu Organo Chem Pvt Ltd., India, has worked out the formulation and evaluation of single reagent on a low grade graphite ore sourced from eastern India. The petrography studies indicate that the ore primarily consists of quartz and graphite with minor quantity of mica and analyzing 87.85% ash content. The ore is crushed in stages followed by primary coarse wet grinding to 242 µm (d80). Rougher flotation is carried out in Denver flotation cell with a view to eliminate gangue as much as possible in the form of primary tailings with minimal loss of carbon. Regrinding of rougher concentrate to 216 µm (d80) is opted to improve the liberation of graphite values. This approach involving a primary coarse grinding and regrinding of rougher float followed by multi-stage cleaning using this single reagent is found to yield better recovery and grade when compared with that of the dual reagent system. A final concentrate of 12.03% weight recovery with 3.22% ash could be achieved. Based on encouraging laboratory studies using the single reagent, plant trials were carried out. From the cost benefit analysis, this single reagent proves to be an economically viable in place of diesel-frother for processing low grade graphite