Dynamic and complex microclimate responses to warming and grazing manipulations

Synthesis efforts that identify patterns of ecosystem response to a suite of warming manipulations can make important contributions to climate change science. However, cross‐study comparisons are impeded by the paucity of detailed analyses of how passive warming and other manipulations affect microclimate. Here we document the independent and combined effects of a common passive warming manipulation, open‐top chambers (OTCs), and a simulated widespread land use, clipping, on microclimate on the Tibetan Plateau. OTCs consistently elevated growing season averaged mean daily air temperature by 1.0–2.0°C, maximum daily air temperature by 2.1–7.3°C and the diurnal air temperature range by 1.9–6.5°C, with mixed effects on minimum daily air temperature, and mean daily soil temperature and moisture. These OTC effects on microclimate differ from reported effects of a common active warming method, infrared heating, which has more consistent effects on soil than on air temperature. There were significant interannual and intragrowing season differences in OTC effects on microclimate. For example, while OTCs had mixed effects on growing season averaged soil temperatures, OTCs consistently elevated soil temperature by approximately 1.0°C early in the growing season. Nonadditive interactions between OTCs and clipping were also present: OTCs in clipped plots generally elevated air and soil temperatures more than OTCs in nonclipped plots. Moreover, site factors dynamically interacted with microclimate and with the efficacy of the OTC manipulations. These findings highlight the need to understand differential microclimate effects between warming methods, within warming method across ecosystem sites, within warming method crossed with other treatments, and within sites over various timescales. Methods, sites and scales are potential explanatory variables and covariables in climate warming experiments. Consideration of this variability among and between experimental warming studies will lead to greater understanding and better prediction of ecosystem response to anthropogenic climate warming.     

Hematopoietic chimerism monitoring based on STRs: quantitative platform performance on sequential samples.

Hematopoietic stem cell transplantation (HSCT) creates a donor-recipient cellular chimerism in the patient, which is quantitatively assayed from peripheral blood based on STR-DNA. Since chimerism values often vary across a patient's samples, it is important to determine to what extent this variability reflects technical aspects of platform performance. This issue is systematically assessed in the current study for the first time. Using the SGM Plus multiplex PCR kit and ABI platform, the longitudinal performance of STR markers was quantitatively evaluated in two chimeric models with true values, and in patient samples (n >500 marker loci). Computation of percent chimerism for each marker, and mean (sample) percent chimerism, standard deviation, and coefficient of variance was performed by our ChimerTrack utility. In chimeric models with known values, individual markers exhibited an accuracy (observed/true) of 88-98%; replication precision was 92-100% true, with a mean error of 2%. Fragment size calling was greater than 99% accurate and precise. Patient results were comparable for markers, relaive to sample means. One source of technical variability in chimerism estimation was allelic differential amplification efficiency. The latter was influenced by signal amplitude, dye label, marker size, and allelic size interval. It can be concluded that long-term chimeric tracking is routinely feasible using this platform in conjunction with ChimerTrack software. Importantly, mean percent chimerism, for any sample, should closely approximate the true chimeric status, with a technical accuracy of 98%. Guidelines are presented for selecting an optimized marker profile.     

Physical Frailty and Body Composition in Obese Elderly Men and Women

Objective: To evaluate the prevalence of frailty and interrelationships among body composition, physical function, and quality of life in community‐dwelling obese elderly (OE) persons. Research Methods and Procedures: Fifty‐two OE, 52 nonobese frail, and 52 nonobese nonfrail subjects, matched for age and sex, were studied. Subjective and objective measures of functional status were evaluated by using the physical performance test, exercise stress test, lower extremity (LE) strength, gait speed, static and dynamic balance, functional status questionnaires, and health‐related quality‐of‐life questionnaire (Medical Outcomes Short Form). Body composition was evaluated by using DXA, and muscle quality was evaluated by determining the ratio of LE strength to LE lean mass. Results: Among OE subjects, 96% met our standard criteria for mild to moderate frailty. Compared with the nonobese nonfrail group, the OE and nonobese frail groups had lower and similar scores in physical performance test, peak aerobic power, and functional status questionnaire, and exhibited similar impairments in strength, walking speed, balance, and health‐related quality of life. Although absolute fat‐free mass (FFM) was greater, the percentage body weight as FFM and muscle quality was lower in the OE group than in the other two groups. Discussion: Physical frailty, which predisposes to loss of independence, is common in community‐living OE men and women. Physical frailty in OE subjects was associated with low percentage FFM, poor muscle quality, and decreased quality of life. These findings suggest that weight loss therapy may be particularly important in OE persons to improve physical function, in addition to improving the medical complications associated with obesity.     

CD200: a putative therapeutic target in cancer

CD200 was recently described as a new prognosis factor in multiple myeloma and acute myeloid leukemia. CD200 is a membrane glycoprotein that imparts an immunoregulatory signal through CD200R, leading to the suppression of T-cell-mediated immune responses. We investigated the expression of CD200 in cancer using publicly available gene expression data. CD200 gene expression in normal or malignant human tissues or cell lines was obtained from the Oncomine Cancer Microarray database, Amazonia database and the ITTACA database. We found significant overexpression of CD200 in renal carcinoma, head and neck carcinoma, testicular cancer, malignant mesothelioma, colon carcinoma, MGUS/smoldering myeloma, and in chronic lymphocytic leukemia compared to their normal cells or their tissue counterparts. Moreover, we show that CD200 expression is associated with tumor progression in various cancers. Taken together, these data suggest that CD200 is a potential therapeutic target and prognostic factor for a large array of malignancies.     

Predicting the clinical lethality of osteogenesis imperfecta from collagen glycine mutations

Osteogenesis imperfecta (OI), or brittle bone disease, often results from missense mutation of one of the conserved glycine residues present in the repeating Gly-X-Y sequence characterizing the triple-helical region of type I collagen. A composite model was developed for predicting the clinical lethality resulting from glycine mutations in the alpha1 chain of type I collagen. The lethality of mutations in which bulky amino acids are substituted for glycine is predicted by their position relative to the N-terminal end of the triple helix. The effect of a Gly --> Ser mutation is modeled by the relative thermostability of the Gly-X-Y triplet on the carboxy side of the triplet containing the substitution. This model also predicts the lethality of Gly --> Ser and Gly --> Cys mutations in the alpha2 chain of type I collagen. The model was validated with an independent test set of six novel Gly --> Ser mutations. The hypothesis derived from the model of an asymmetric interaction between a Gly --> Ser mutation and its neighboring residues was tested experimentally using collagen-like peptides. Consistent with the prediction, a significant decrease in stability, calorimetric enthalpy, and folding time was observed for a peptide with a low-stability triplet C-terminal to the mutation compared to a similar peptide with the low-stability triplet on the N-terminal side. The computational and experimental results together relate the position-specific effects of Gly --> Ser mutations to the local structural stability of collagen and lend insight into the etiology of OI.     

Identification of Brucella spp. genes involved in intracellular trafficking

After uptake by host cells, the pathogen Brucella transits through early endosomes, evades phago–lysosome fusion and replicates in a compartment associated with the endoplasmic reticulum (ER). The molecular mechanisms underlying these processes are still poorly understood. To identify new bacterial factors involved in these processes, a library of 1800 Brucella melitensis 16M mini-Tn 5catkm mutants was screened for intracellular survival and multiplication in HeLa cells and J774A.1 macrophages. Thirteen mutants were identified as defective for their intracellular survival in both cell types. In 12 of them, the transposon had inserted in the virB operon, which encodes a type IV-related secretion system. The preponderance of virB mutants demonstrates the importance of this secretion apparatus in the intracellular multiplication of B. melitensis . We also examined the intracellular fate of three virB mutants ( virB2 , virB4 and virB9 ) in HeLa cells by immunofluorescence. The three VirB proteins are not necessary for penetration and the inhibition of phago–lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane-bound vacuole expressing the late endosomal marker, LAMP1, and the sec61β protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER.     

Identification of genomic regions that affect grain-mould incidence and other traits of agronomic importance in sorghum

Grain-mould is a major problem in grain sorghum utilization as mouldy grain has a reduced quality due to the deterioration of the endosperm and reduced embryo viability. Here, our objective was to use genome mapping to improve knowledge of genetic variation and co-variation for grain-mould incidence and other inter-related agronomic traits. Grain-mould incidence, kernel-milling hardness, grain density, plant height, panicle peduncle length, foliar-disease incidence, and plant color were measured on 125 F₅ genotypes derived from a cross of Sureño and RTx430. Quantitative trait loci were detected by means of 130 mapped markers (44 microsatellites, 85 AFLPs, one morphological-trait locus) distributed among ten linkage groups covering 970 cM. One to five QTLs affected each trait, with the exception of grain density for which no QTLs were detected. Grain-mould incidence was affected by five QTLs each accounting for between 10 and 23% of the phenotypic variance. The effects and relative positions of QTLs for grain-mould incidence were in accordance with the QTL distribution of several inter-related agronomic traits (e.g., plant height, peduncle length) and with the correlation between these phenotypic traits and grain-mould incidence. The detection of QTLs for grain-mould incidence was dependent on the environment, which is consistent with heritibility estimates that show strong environmental and genotype × environment effects. Several genomic regions affected multiple traits including one region that affected grain-mould incidence, plant height, panicle peduncle length, and grain-milling hardness, and a second region that influenced grain-mould (in four environments) and plant height. One genomic region, which harbors loci for plant color, influenced the severity of foliar disease symptoms and the incidence of grain-mould in one environment. Collectively QTLs detected in the present population explained between 10% and 55% of the phenotypic variance observed for a given trait.