Late Quaternary paleoclimatic and geomorphological evolution at the interface between the Menyuan basin and the Qilian Mountains, northeastern Tibetan Plateau

The Tibetan Plateau is regarded as an amplifier and driver of environmental change in adjacent regions because of its extent and high altitude. However, reliable age control for paleoenvironmental information on the plateau is limited. OSL appears to be a valid method to constrain the age of deposits of glacial and fluvial origin, soils and periglacial structures in the Menyuan basin on the northeastern Tibetan Plateau. Dating results show glaciers advanced extensively to the foot of the Qilian mountains at ~. 21. ka, in agreement with the timing of the global Last Glacial Maximum (LGM) recorded in Northern Hemisphere ice cores. Comparison with results from the eastern Tibetan Plateau suggests that the factor controlling glacial advance in both regions was decreased temperature, not monsoon-related precipitation increase. The areas of the Menyuan basin occupied by glacio-fluvial deposits experienced continuous permafrost during the LGM, indicated by large cryoturbation features, interpreted to indicate that the mean annual temperature was ≥. 7. °C lower than at present. Glacio-fluvial systems in the Menyuan basin aggraded and terraces formed during cold periods (penultimate glaciation, LGM, and possibly the Younger Dryas) as a response to increased glacial sediment production and meltwater runoff then. © 2013 University of Washington

Constitutive IP₃ signaling underlies the sensitivity of B-cell cancers to the Bcl-2/IP₃ receptor disruptor BIRD-2

Anti-apoptotic Bcl-2 proteins are upregulated in different cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), enabling survival by inhibiting pro-apoptotic Bcl-2-family members and inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-mediated Ca2+-signaling. A peptide tool (Bcl-2/IP3R Disruptor-2; BIRD-2) was developed to abrogate the interaction of Bcl-2 with IP3Rs by targeting Bcl-2′s BH4 domain. BIRD-2 triggers cell death in primary CLL cells and in DLBCL cell lines. Particularly, DLBCL cells with high levels of IP3R2 were sensitive to BIRD-2. Here, we report that BIRD-2-induced cell death in DLBCL cells does not only depend on high IP3R2-expression levels, but also on constitutive IP3 signaling, downstream of the tonically active B-cell receptor. The basal Ca2+ level in SU-DHL-4 DLBCL cells was significantly elevated due to the constitutive IP3 production. This constitutive IP3 signaling fulfilled a pro-survival role, since inhibition of phospholipase C (PLC) using U73122 (2.5 µM) caused cell death in SU-DHL-4 cells. Milder inhibition of IP3 signaling using a lower U73122 concentration (1 µM) or expression of an IP3 sponge suppressed both BIRD-2-induced Ca2+ elevation and apoptosis in SU-DHL-4 cells. Basal PLC/IP3 signaling also fulfilled a pro-survival role in other DLBCL cell lines, including Karpas 422, RI-1 and SU-DHL-6 cells, whereas PLC inhibition protected these cells against BIRD-2-evoked apoptosis. Finally, U73122 treatment also suppressed BIRD-2-induced cell death in primary CLL, both in unsupported systems and in co-cultures with CD40L-expressing fibroblasts. Thus, constitutive IP3 signaling in lymphoma and leukemia cells is not only important for cancer cell survival, but also represents a vulnerability, rendering cancer cells dependent on Bcl-2 to limit IP3R activity. BIRD-2 seems to switch constitutive IP3 signaling from pro-survival into pro-death, presenting a plausible therapeutic strategy

A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42

Introduction: The ability to identify individuals at increased genetic risk for Alzheimer's disease (AD) may streamline biomarker and drug trials and aid clinical and personal decision making. Methods: We evaluated the discriminative ability of a genetic risk score (GRS) covering 22 published genetic risk loci forADin 1162 Flanders-BelgianADpatients and 1019 controls and assessed correlations with family history, onset age, and cerebrospinal fluid (CSF) biomarkers (A beta(1-42), T-Tau, P-Tau(181P)). Results: A GRS including all single nucleotide polymorphisms (SNPs) and age-specific APOE epsilon 4 weights reached area under the curve (AUC) 0.70, which increased to AUC 0.78 for patients with familial predisposition. Risk of AD increased with GRS (odds ratio, 2.32 (95% confidence interval 2.08-2.58 per unit; P < 1.0e(-15)). Onset age and CSF Ab1-42 decreased with increasing GRS (P-onset_age 5 9.0e(-11); P-A beta = 8.9e(-7)). Discussion: The discriminative ability of this 22-SNP GRS is still limited, but these data illustrate that incorporation of age-specific weights improves discriminative ability. GRS-phenotype correlations highlight the feasibility of identifying individuals at highest susceptibility. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association

A comprehensive study of three different portable XRF scanners to assess the soil geochemistry of an extensive sample dataset

The assessment of soil elemental concentrations nowadays mainly occurs through conventional laboratory analyses. However, proximal soil sensing (PSS) techniques such as X-ray fluorescence (XRF) spectrometry are proving to reduce analysis time and costs, and thus offer a worthy alternative to laboratory analyses. Moreover, XRF scanners are non-destructive and can be directly employed in the field. Although the use of XRF for soil elemental analysis is becoming widely accepted, most previous studies were limited to one scanner, a few samples, a few elements, or a non-diverse sample database. Here, an extensive and diverse soil database was used to compare the performance of three different XRF scanners with results obtained through conventional laboratory analyses. Scanners were used in benchtop mode with built-in soil calibrations to measure the concentrations of 15 elements. Although in many samples Cu, S, P, and Mg concentrations were up to 6, 12, 13, and 5 times overestimated by XRF, and empirical recalibration is recommended, all scanners produced acceptable results, even for lighter elements. Unexpectedly, XRF performance did not seem to depend on soil characteristics such as CaCO3 content. While performances will be worse when expanding to the field, our results show that XRF can easily be applied by non-experts to measure soil elemental concentrations reliably in widely different environments

Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32)

The BCR-ABL1 fusion kinase is frequently associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia but is rare in T-cell acute lymphoblastic leukemia (T-ALL). We recently identified NUP214-ABL1 as a variant ABL1 fusion gene in 6% of T-ALL patients. Here we describe the identification of another ABL1 fusion, EML1-ABL1, in a T-ALL patient with a cryptic t(9;14)(q34;q32) associated with deletion of CDKN2A (p16) and expression of TLX1 (HOX11). Echinoderm microtubule-associated protein-like 1-Abelson 1 (EML1-ABL1) is a constitutively phosphorylated tyrosine kinase that transforms Ba/F3 cells to growth factor-independent growth through activation of survival and proliferation pathways, including extracellular signal-related kinase 1/2 (Erk1/2), signal transducers and activators of transcription 5 (Stat5), and Lyn kinase. Deletion of the coiled-coil domain of EML1 abrogated the transforming properties of the fusion kinase. EML1-ABL1 and breakpoint cluster region (BCR)-ABL1 were equally sensitive to the tyrosine kinase inhibitor imatinib. These data further demonstrate the involvement of ABL1 fusions in the pathogenesis of T-ALL and identify EML1-ABL1 as a novel therapeutic target of imatinib

High-resolution in vivo imaging of xylem-transported CO2 in leaves based on real-time 11C-tracing

Plant studies using the short-lived isotope C-11 to label photosynthate via atmospheric carbon dioxide (CO2), have greatly advanced our knowledge about the allocation of recent photosynthate from leaves to sinks. However, a second source for photosynthesis is CO2 in the transpiration stream, coming from respiration in plant tissues. Here, we use in vivo tracing of xylem-transported (CO2)-C-11 to increase our knowledge on whole plant carbon cycling.We developed a newmethod for in vivo tracing of xylem-transported CO2 in excised poplar leaves using C-11 in combination with positron emission tomography (PET) and autoradiography. To show the applicability of both measurement techniques in visualizing and quantifying CO2 transport dynamics, we administered the tracer via the cut petiole and manipulated the transport by excluding light or preventing transpiration. Irrespective of manipulation, some tracer was found in main and secondary veins, little of it was fixed in minor veins or mesophyll, while most of it diffused out the leaf. Transpiration, phloem loading and CO2 recycling were identified as mechanisms that could be responsible for the transport of internal CO2. Both C-11-PET and autoradiography can be successfully applied to study xylem-transported CO2, toward better understanding of leaf and plant carbon cycling, and its importance in different growing conditions

Embryotransplantatie bij het paard: onmisbaar in de moderne fokkerij

Nowadays, a valuable competition mare can produce offspring without interrupting its sport career which is made possible by a technique called embryo transfer. The valuable mare is inseminated and an embryo is flushed seven days later. The early embryo is then transferred to the uterus of a recipient mare that carries the pregnancy to term. In 50% of the cases, flushing of the donor mare results in an embryo. After transfer, an average of 70% of the recipient mares become pregnant. These percentages are influenced by several factors related to both the donor and recipient mares