HYPOTHETICAL HUMAN IMMUNE GENOME COMPLEX GRADIENT MAY HELP TO EXPLAIN THE CONGENITAL ZIKA SYMDROME CATASTROPHE IN BRAZIL: A NEW THEORY

There are few data considering human genetics as an important risk factor for birth abnormalities related to ZIKV infection during pregnancy, even though sub-Saharan African populations are apparently more resistant to CZS as compared to populations in the Americas. We hypothesized that single nucleotide variants (SNVs), especially in innate immune genes, could make some populations more susceptible to Zika congenital complications than others. Differences in the SNV frequencies among continental populations provide great potential for Machine Learning techniques. We explored a key immune genomic gradient between individuals from Africa, Asia and Latin America, working with complex signatures, using 297 SNVs. We employed a two-step approach. In the first step, decision trees (DTs) were used to extract the most discriminating SNVs among populations. In the second step, machine learning algorithms were used to evaluate the quality of the SNV pool identified in step one for discriminating between individuals from sub-Saharan African and Latin-American populations. Our results suggest that 10 SNVs from 10 genes (CLEC4M, CD58, OAS2, CD80, VEPH1, CTLA4, CD274, CD209, PLAAT4, CREB3L1) were able to discriminate sub-Saharan Africans from Latin American populations using only immune genome data, with an accuracy close to 100%. Moreover, we found that these SNVs form a genome gradient across the three main continental populations. These SNVs are important elements of the innate immune system and in the response against viruses. Our data support the Human Immune Genome Complex Gradient hypothesis as a new theory that may help to explain the CZS catastrophe in Brazil

A guide to the South Plains of Texas

A compilation of essays and articles covering history, agriculture, educational institutions, and legends of the historic South Plains of Texas.[139] leaves ; 152 pdf pages.November 1935.Pictorial illustrations by Bess Hubbard.Mimeographed copy reproduced by the students of Lubbock High School with permission and assistance of the Texas Highway Dept.Plains of Texas / A.W. Evans -- The rock house on Blanco Canyon / R.B. Smith -- The story of the famous Old Yellow House Ranch / Lamb county news -- The T-Bar Ranch / R.B. Smith -- U-Lazy-S Ranch / E. Taylor -- The old Mackenzie Trail / W.L Chittenden -- Mackenzie's Indian campaigns on the Staked Plains / M.L. Cox -- Horse bones / R.G. Carter -- Old Man Singer's store / W.C. Holden -- Letter of long ago describes living conditions in days of first settles / M. Witt -- Shanties and dugouts / The Cattleman -- The legend of the sand hills / J. Mitchell -- Three notable landmarks in Lynn County / F.P. Hill -- Descriptions of South Plains cities and towns / V. Upton -- Elevation, population, and highway mileage maps / M.W. Hobbs -- Roadside divertissement / V. Upton

Identity-by-descent filtering of exome sequence data for disease–gene identification in autosomal recessive disorders

Motivation: Next-generation sequencing and exome-capture technologies are currently revolutionizing the way geneticists screen for disease-causing mutations in rare Mendelian disorders. However, the identification of causal mutations is challenging due to the sheer number of variants that are identified in individual exomes. Although databases such as dbSNP or HapMap can be used to reduce the plethora of candidate genes by filtering out common variants, the remaining set of genes still remains on the order of dozens

Geochemical and mineralogical indicators for aqueous processes in the Columbia Hills of Gusev crater, Mars

Water played a major role in the formation and alteration of rocks and soils in the Columbia Hills. The extent of alteration ranges from moderate to extensive. Five distinct rock compositional classes were identified; the order for degree of alteration is Watchtower = Clovis >Wishstone = Peace > Backstay. The rover’s wheels uncovered one unusual soil (Paso Robles) that is the most S-rich material encountered. Clovis class rocks have compositions similar to Gusev plains soil but with higher Mg, Cl, and Br and lower Ca and Zn; Watchtower and Wishstone classes have high Al, Ti, and P and low Cr and Ni; Peace has high Mg and S and low Al, Na, and K; Backstay basalts have high Na and K compared to plains Adirondack basalts; and Paso Robles soil has high S and P. Some rocks are corundum-normative, indicating that their primary compositions were changed by loss and/or gain of rock-forming elements. Clovis materials consist of magnetite, nanophase ferric-oxides (npOx), hematite, goethite, Ca-phosphates, Ca- and Mg-sulfates, pyroxene, and secondary aluminosilicates. Wishstone and Watchtower rocks consist of Fe-oxides/oxyhydroxides, ilmenite, Ca-phosphate, pyroxene, feldspar, Mg-sulfates, and secondary aluminosilicates. Peace consists of magnetite, npOx, Mg- and Ca-sulfates, pyroxene, olivine, feldspar, apatite, halides, and secondary aluminosilicates. Paso Robles consists of Fe3+-, Mg-, Ca-, and other sulfates, Ca-phosphates, hematite, halite, allophane, and amorphous silica. Columbia Hills outcrops and rocks may have formed by the aqueous alteration of basaltic rocks, volcaniclastic materials, and/or impact ejecta by solutions that were rich in acid-volatile elements

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Origin of acidic surface waters and the evolution of atmospheric chemistry on early Mars

Observations from in situ experiments and planetary orbiters have shown that the sedimentary rocks found at Meridiani Planum, Mars were formed in the presence of acidic surface waters. The water was thought to be brought to the surface by groundwater upwelling, and may represent the last vestiges of the widespread occurrence of liquid water on Mars. However, it is unclear why the surface waters were acidic. Here we use geochemical calculations, constrained by chemical and mineralogical data from the Mars Exploration Rover Opportunity, to show that Fe oxidation and the precipitation of oxidized iron (Fe^(3+)) minerals generate excess acid with respect to the amount of base anions available in the rocks present in outcrop. We suggest that subsurface waters of near-neutral pH and rich in Fe^(2+) were rapidly acidified as iron was oxidized on exposure to O_2 or photo-oxidized by ultraviolet radiation at the martian surface. Temporal variation in surface acidity would have been controlled by the availability of liquid water, and as such, low-pH fluids could be a natural consequence of the aridification of the martian surface. Finally, because iron oxidation at Meridiani would have generated large amounts of gaseous H_2, ultimately derived from the reduction of H_2O, we conclude that surface geochemical processes would have affected the redox state of the early martian atmosphere

Hypoxia, AMPK activation and uterine artery vasoreactivity

This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP270995Genes near adenosine monophosphate-activated protein kinase-α1 (PRKAA1) have been implicated in the greater uterine artery (UtA) blood flow and relative protection from fetal growth restriction seen in altitude-adapted Andean populations. Adenosine monophosphate-activated protein kinase (AMPK) activation vasodilates multiple vessels but whether AMPK is present in UtA or placental tissue and influences UtA vasoreactivity during normal or hypoxic pregnancy remains unknown. We studied isolated UtA and placenta from near-term C57BL/6J mice housed in normoxia (n = 8) or hypoxia (10% oxygen, n = 7-9) from day 14 to day 19, and placentas from non-labouring sea level (n = 3) or 3100 m (n = 3) women. Hypoxia increased AMPK immunostaining in near-term murine UtA and placental tissue. RT-PCR products for AMPK-α1 and -α2 isoforms and liver kinase B1 (LKB1; the upstream kinase activating AMPK) were present in murine and human placenta, and hypoxia increased LKB1 and AMPK-α1 and -α2 expression in the high- compared with low-altitude human placentas. Pharmacological AMPK activation by A769662 caused phenylephrine pre-constricted UtA from normoxic or hypoxic pregnant mice to dilate and this dilatation was partially reversed by the NOS inhibitor l-NAME. Hypoxic pregnancy sufficient to restrict fetal growth markedly augmented the UtA vasodilator effect of AMPK activation in opposition to PE constriction as the result of both NO-dependent and NO-independent mechanisms. We conclude that AMPK is activated during hypoxic pregnancy and that AMPK activation vasodilates the UtA, especially in hypoxic pregnancy. AMPK activation may be playing an adaptive role by limiting cellular energy depletion and helping to maintain utero-placental blood flow in hypoxic pregnancy.Funding for these studies was provided by the Wellcome Trust (084804/2/08/Z) to G.J.B., the British Heart Foundation and the Wellcome Trust to D.A.G., the Biotechnology and Biological Sciences Research Council (BBSRC) to A.L.F., a UK Wellcome Trust Programme Grant (WT081195MA) to A.M.E. and A.D.M., a BBSRC studentship and in vivo skills award to J.S.H., a National Health Medical Research Council and Centre for Trophoblast Research fellowship to A.N.S.-P., and a NIH RO1 grant (HLBI-079647) to L.G.M. along with sabbatical support from Wake Forest University

Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude