Multi‐model Forecasts of the West Texas Intermediate Crude Oil Spot Price

We measure the performance of multi‐model inference (MMI) forecasts compared to predictions made from a single model for crude oil prices. We forecast the West Texas Intermediate (WTI) crude oil spot prices using total OECD petroleum inventory levels, surplus production capacity, the Chicago Board Options Exchange Volatility Index and an implementation of a subset autoregression with exogenous variables (SARX). Coefficient and standard error estimates obtained from SARX determined by conditioning on a single ‘best model’ ignore model uncertainty and result in underestimated standard errors and overestimated coefficients. We find that the MMI forecast outperforms a single‐model forecast for both in‐ and out‐of‐sample datasets over a variety of statistical performance measures, and further find that weighting models according to the Bayesian information criterion generally yields superior results both in and out of sample when compared to the Akaike information criterion. Copyright © 2016 John Wiley & Sons, Ltd.     

The tyrosine phosphatase SHP-1 negatively regulates cytotrophoblast proliferation in first-trimester human placenta by modulating EGFR activation

Insulin-like growth factors (IGFs) influence placental cell (cytotrophoblast) kinetics. We recently reported that the protein tyrosine phosphatase (PTP) SHP-2 positively regulates IGF actions in the placenta. In other systems, the closely related PTP, SHP-1, functions as a negative regulator of signaling events but its role in the placenta is still unknown. We examined the hypothesis that SHP-1 negatively regulates IGF actions in the human placenta. Immunohistochemical (IHC) analysis demonstrated that SHP-1 is abundant in cytotrophoblast. SHP-1 expression was decreased in first-trimester placental explants using siRNA; knockdown did not alter IGF-induced proliferation but it significantly enhanced proliferation in serum-free conditions, revealing that placental growth is endogenously regulated. Candidate regulators were determined by using antibody arrays, Western blotting, and IHC to examine the activation status of multiple receptor tyrosine kinases (RTKs) in SHP-1-depleted explants; amongst the alterations observed was enhanced activation of EGFR, suggesting that SHP-1 may interact with EGFR to inhibit proliferation. The EGFR tyrosine kinase inhibitor PD153035 reversed the elevated proliferation seen in the absence of SHP-1. This study demonstrates a role for SHP-1 in human trophoblast turnover and establishes SHP-1 as a negative regulator of EGFR activation. Targeting placental SHP-1 expression may provide therapeutic benefits in common pregnancy conditions with abnormal trophoblast proliferation.     

Genetic variation in ecophysiological and survival responses to drought in two native grasses: Koeleria macrantha and Elymus elymoides

Genetic variation in ecophysiological and survival responses to drought was studied in 2 northern Arizona native grass species, Koeleria macrantha (Ledeb.) Schult. (prairie Junegrass) and Elymus elymoides (Raf.) Swezey. ssp. elymoides (squirreltail). Low- and high-elevation populations of each species were compared in a greenhouse common garden experiment that included simulated drought. Leaf gas-exchange characteristics were significantly affected by simulated drought and often by population elevation, but gas-exchange responses to drought were similar for high- and low-elevation populations. Compared to high-elevation populations, low-elevation populations of both species had higher net photosynthetic rate and predawn water potential, and for E. elymoides had higher stomatal conductance. Leaf-level water-use efficiency did not differ between populations for either species. Populations also differed significantly in leaf morphological characteristics related to water use. Compared to high-elevation populations, low-elevation populations of both species had smaller leaves. Low-elevation populations of both species survived aboveground longer than high-elevation populations during drought, with a larger difference in K. macrantha than in E. elymoides. These results suggest strong selection for drought adaptation and water use along an elevational and water-availability gradient in native grasses. Se estudió la variación genética en respuestas ecofisiológica y de sobrevivencia a la sequía en dos especies de pasto nativo del norte de Arizona, Koeleria macrantha (Ledeb.) Schult. (“prairie Junegrass”) y Elymus elymoides (Raf.) Swezey. spp. elymoides (“squirreltail”). Se compararon poblaciones de cada especie a elevaciones altas y bajas durante un experimento de jardín común en un invernadero que simulaba condiciones de sequía. Las características relacionadas con el intercambio de gases a nivel de hoja se vieron afectadas significativamente por la sequía simulada y con frecuencia por la elevación de la población, pero la respuesta del intercambio de gases a la sequía fue similar en las poblaciones de alta y baja elevación. En comparación con las poblaciones altas, las poblaciones bajas, en ambas especies, tuvieron una elevada tasa neta de fotosíntesis y un mayor potencial hídrico previo al amanecer; E. elymoides tuvo mayor conductancia estomática. La eficiencia en el uso del agua (EUA) a nivel de hoja no difirió entre poblaciones en ninguna especie. Las poblaciones sí difirieron significativamente en las características de la morfología de la hoja relacionadas con el uso del agua. Comparadas con las poblaciones altas, las poblaciones bajas de ambas especies tuvieron hojas más pequeñas. Durante la sequía, la parte de la planta que estaba encima de la tierra sobrevivió por más tiempo en las poblaciones bajas de ambas especies que en las poblaciones altas, con una mayor diferencia en K. macrantha que en E. elymoides. Estos resultados indican que hay una fuerte selección para la adaptación a la sequía y el uso del agua a lo largo de una gradiente de elevación y de disponibilidad de agua en pastos nativos.     

mTOR signaling in neural stem cells: from basic biology to disease

The mammalian target of rapamycin (mTOR) pathway is a central controller of growth and homeostasis, and, as such, is implicated in disease states where growth is deregulated, namely cancer, metabolic diseases, and hamartoma syndromes like tuberous sclerosis complex (TSC). Accordingly, mTOR is also a pivotal regulator of the homeostasis of several distinct stem cell pools in which it finely tunes the balance between stem cell self-renewal and differentiation. mTOR hyperactivation in neural stem cells (NSCs) has been etiologically linked to the development of TSC-associated neurological lesions, such as brain hamartomas and benign tumors. Animal models generated by deletion of mTOR upstream regulators in different types of NSCs reproduce faithfully some of the TSC neurological alterations. Thus, mTOR dysregulation in NSCs seems to be responsible for the derangement of their homeostasis, thus leading to TSC development. Here we review recent advances in the molecular dissection of the mTOR cascade, its involvement in the maintenance of stem cell compartments, and in particular the implications of mTOR hyperactivation in NSCs in vivo and in vitro.     

Role of Chk1 in the differentiation program of hematopoietic stem cells

Hematopoietic stem cells (HSC) isolated from umbilical cord blood (UCB) were treated with ionizing radiation (IR) and sensitivity and IR induced checkpoints activation were investigated. No difference in the sensitivity and in the activation of DNA damage pathways was observed between CD133+ HSC and cells derived from them after ex vivo expansion. Chk1 protein was very low in freshly isolated CD133+ cells, and undetectable in ex vivo expanded UCB CD133+ cells. Chk1 was expressed only on day 3 of the ex vivo expansion. This pattern of Chk1 expression was corroborated in CD133+ cells isolated from peripheral blood apheresis collected from an healthy donor. Treatment with a specific Chk1 inhibitor resulted in a strong reduction in the percentage of myeloid precursors (CD33+) and an increase in the percentage of lymphoid precursors (CD38+) compared to untreated cells, suggesting a possible role for Chk1 in the differentiation program of UCB CD133+ HSC.     

ATM stabilizes DNA double-strand-break complexes during V(D)J recombination

The ATM (ataxia-telangiectasia mutated) protein kinase mediates early cellular responses to DNA double-strand breaks (DSBs) generated during metabolic processes or by DNA-damaging agents. ATM deficiency leads to ataxia-telangiectasia, a disease marked by lymphopenia, genomic instability and an increased predisposition to lymphoid malignancies with chromosomal translocations involving lymphocyte antigen receptor loci. ATM activates cell-cycle checkpoints and can induce apoptosis in response to DNA DSBs. However, defects in these pathways of the DNA damage response cannot fully account for the phenotypes of ATM deficiency. Here, we show that ATM also functions directly in the repair of chromosomal DNA DSBs by maintaining DNA ends in repair complexes generated during lymphocyte antigen receptor gene assembly. When coupled with the cell-cycle checkpoint and pro-apoptotic activities of ATM, these findings provide a molecular explanation for the increase in lymphoid tumours with translocations involving antigen receptor loci associated with ataxia-telangiectasia.     

Stratified prokaryote network in the oxic-anoxic transition of a deep-sea halocline

The chemical composition of the Bannock basin has been studied in some detail. We recently showed that unusual microbial populations, including a new division of Archaea (MSBL1), inhabit the NaCl-rich hypersaline brine. High salinities tend to reduce biodiversity, but when brines come into contact with fresher water the natural haloclines formed frequently contain gradients of other chemicals, including permutations of electron donors and acceptors, that may enhance microbial diversity, activity and biogeochemical cycling. Here we report a 2.5-m-thick chemocline with a steep NaCl gradient at 3.3 km within the water column betweeen Bannock anoxic hypersaline brine and overlying sea water. The chemocline supports some of the most biomass-rich and active microbial communities in the deep sea, dominated by Bacteria rather than Archaea, and including four major new divisions of Bacteria. Significantly higher metabolic activities were measured in the chemocline than in the overlying sea water and underlying brine; functional analyses indicate that a range of biological processes is likely to occur in the chemocline. Many prokaryotic taxa, including the phylogenetically new groups, were confined to defined salinities, and collectively formed a diverse, sharply stratified, deep-sea ecosystem with sufficient biomass to potentially contribute to organic geological deposits.     

Ecology: mechanisms for consumer diversity

A variety of mechanisms can theoretically produce competitive coexistence in nature, making it hard to identify a single explanation for the maintenance of diversity in any particular system. Based on laboratory experiments with a consumer-resource system of crustacean Daphnia eating algae, Nelson et al. suggest that maintenance of genetic diversity in the consumer populations they studied depends only on the dynamics of the population structure of the consumer. We suggest that the differences in Daphnia genetic diversity that they find for different experimental treatments could equally be explained by a simple, well known mechanism: the number of coexisting competitors cannot exceed the number of shared resources. Here we confirm this possibility by using a simple mathematical model and suggest that more than one mechanism may account for the maintenance of genetic diversity observed by Nelson et al. in their system.