Solar influenced late Holocene temperature changes on the northern Tibetan Plateau

Considerable efforts have been made to extend temperature records beyond the instrumental period through proxy reconstructions, in order to further understand the mechanisms of past climate variability. Yet, the global coverage of existing temperature records is still limited, especially for some key regions like the Tibetan Plateau and for earlier times including the Medieval Warm Period (MWP). Here we present decadally-resolved, alkenone-based, temperature records from two lakes on the northern Tibetan Plateau. Characterized by marked temperature variability, our records provide evidence that temperatures during the MWP were slightly higher than the modern period in this region. Further, our temperature reconstructions, within age uncertainty, can be well correlated with solar irradiance changes, suggesting a possible link between solar forcing and natural climate variability, at least on the northern Tibetan Plateau. © 2013 The Author(s).published_or_final_versio

Validity and reliability analysis of the Chinese cancer pain assessment tool

2001-2002 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

High prevalence of plasmid-mediated 16S rRNA methylase gene rmtB among Escherichia coli clinical isolates from a Chinese teaching hospital

<p>Abstract</p> <p>Background</p> <p>Recently, production of 16S rRNA methylases by Gram-negative bacilli has emerged as a novel mechanism for high-level resistance to aminoglycosides by these organisms in a variety of geographic locations. Therefore, the spread of high-level aminoglycoside resistance determinants has become a great concern.</p> <p>Methods</p> <p>Between January 2006 and July 2008, 680 distinct <it>Escherichia coli </it>clinical isolates were collected from a teaching hospital in Wenzhou, China. PCR and DNA sequencing were used to identify 16S rRNA methylase and extended-spectrum β-lactamase (ESBL) genes, including <it>armA </it>and <it>rmtB</it>, and in situ hybridization was performed to determine the location of 16S rRNA methylase genes. Conjugation experiments were subsequently performed to determine whether aminoglycoside resistance was transferable from the <it>E. coli </it>isolates via 16S rRNA methylase-bearing plasmids. Homology of the isolates harboring 16S rRNA methylase genes was determined using pulse-field gel electrophoresis (PFGE).</p> <p>Results</p> <p>Among the 680 <it>E. coli </it>isolates, 357 (52.5%), 346 (50.9%) and 44 (6.5%) isolates were resistant to gentamicin, tobramycin and amikacin, respectively. Thirty-seven of 44 amikacin-resistant isolates harbored 16S rRNA methylase genes, with 36 of 37 harboring the <it>rmtB </it>gene and only one harboring <it>armA</it>. The positive rates of 16S rRNA methylase genes among all isolates and amikacin-resistant isolates were 5.4% (37/680) and 84.1% (37/44), respectively. Thirty-one isolates harboring 16S rRNA methylase genes also produced ESBLs. In addition, high-level aminoglycoside resistance could be transferred by conjugation from four <it>rmtB</it>-positive donors. The plasmids of incompatibility groups IncF, IncK and IncN were detected in 34, 3 and 3 isolates, respectively. Upstream regions of the <it>armA </it>gene contained <it>IS</it>CR1 and <it>tnpU</it>, the latter a putative transposase gene,. Another putative transposase gene, <it>tnpD</it>, was located within a region downstream of <it>armA</it>. Moreover, a transposon, Tn<it>3</it>, was located upstream of the <it>rmtB</it>. Nineteen clonal patterns were obtained by PFGE, with type H representing the prevailing pattern.</p> <p>Conclusion</p> <p>A high prevalence of plasmid-mediated <it>rmtB </it>gene was found among clinical <it>E. coli </it>isolates from a Chinese teaching hospital. Both horizontal gene transfer and clonal spread were responsible for the dissemination of the <it>rmtB </it>gene.</p

SIRT1 associates with eIF2-alpha and regulates the cellular stress response

SIRT1 is a NAD+ dependent protein deacetylase known to increase longevity in model organisms. SIRT1 regulates cellular response to oxidative and/or genotoxic stress by regulating proteins such as p53 and FOXO. The eukaryotic initiation factor-2, eIF2, plays a critical role in the integrated stress response pathway. Under cellular stress, phosphorylation of the alpha subunit of eIF2 is essential for immediate shut-off of translation and activation of stress response genes. Here we demonstrate that SIRT1 interacts with eIF2α. Loss of SIRT1 results in increased phosphorylation of eIF2α. However, the downstream stress induced signaling pathway is compromised in SIRT1-deficient cells, indicated by delayed expression of the downstream target genes CHOP and GADD34 and a slower post-stress translation recovery. Finally, SIRT1 co-immunoprecipitates with mediators of eIF2α dephosphorylation, GADD34 and CreP, suggesting a role for SIRT1 in the negative feedback regulation of eIF2α phosphorylation

Investigation on the Plasma-Induced Emission Properties of Large Area Carbon Nanotube Array Cathodes with Different Morphologies

Large area well-aligned carbon nanotube (CNT) arrays with different morphologies were synthesized by using a chemical vapor deposition. The plasma-induced emission properties of CNT array cathodes with different morphologies were investigated. The ratio of CNT height to CNT-to-CNT distance has considerable effects on their plasma-induced emission properties. As the ratio increases, emission currents of CNT array cathodes decrease due to screening effects. Under the pulse electric field of about 6 V/μm, high-intensity electron beams of 170–180 A/cm2 were emitted from the surface plasma. The production mechanism of the high-intensity electron beams emitted from the CNT arrays was plasma-induced emission. Moreover, the distribution of the electron beams was in situ characterized by the light emission from the surface plasma