Knowledge of Holocene hydro-climatic conditions in northern China from high temporal resolution stalagmites collected from Lianghua Cave

Our understanding of hydro-climatic dynamics in the East Asian monsoon region during the Holocene was obstructed by very few absolutely dated and high temporally resolved proxy records in northern China. Here we present duplicated carbonate δ18O records of six stalagmites with sub-decadal to multi-decadal temporal resolutions from Lianhua cave to reveal a detailed transition of the East Asian Summer Monsoon (EASM) intensity in northern China from 11.5 thousand years ago (hereafter, ka BP, before 1950 AD). Our composite records show that solar forcing dominated hydro-climatic changes, including an intensified monsoon at the Holocene Optimum from the end of Younger Dryas to 6.5 ka BP, and a subsequent multi-millennial weakening of monsoon intensity, that agree with cave records in central and southern China. However, the EASM has retreated southwards more rapidly than the Indian summer monsoon after ∼6.5 ka BP, resulting in some rapid onset of dry conditions occurring at 4.0 ka BP in northern China, which is ∼2000 years earlier than in central and southern China. This asynchrony may be related to the different regional responses among the coupling of the EASM, Indian summer monsoon, the solar forcing, and the differences in thermal forcing due to complex geographical configurations. In addition, a relative enrichment of 1h in our δ18O data of Lianhua record from 9.5 to 8.1 ka BP shows that the Holocene Optimum was punctuated by a millennial-long weak monsoon interval, which is not registered among previous cave records in central and southern China. The freshwater-induced cold climate conditions in the North Atlantic region could create stronger East Asian winter monsoon and induce a weakened EASM and a southward shift of precipitation band in northern China. Therefore, it shall not be surprised that there are strong heterogeneities among regional hydro-climatic conditions across monsoonal China in the Holocene, given the complex interplay between external and internal forcing mechanisms over the entire Holocene

Asian monsoon dynamics at Dansgaard/Oeschger events 14-8 and Heinrich events 5-4 in northern China

A precisely 230Th-dated stalagmite oxygen isotope (δ18O) record from Dragon Cave,Shanxi Province, northern China, is proposed to reconstruct the millennial-scale changes of the East Asian Summer monsoon (EASM) during the period 53.2-1.3 ka BP (before 1950 AD). Our record shows significant millennial-scale oscillations that match in timing, characteristic, and duration with the Dansgaard/Oeschger (DO)30 events 14-8 and the Heinrich events 5, 4, 2, and 1 (hereafter H5, H4, H2 and H1) in high-latitude regions of the Northern Hemisphere. Especially, the H5 event is well constrained from 48.1 to 46.9 ka BP with ten 230Th dates. Our chronology supports the NGRIP GICC05 timescale from 50 to 38 ka BP. A comprehensive comparison of the Chinese speleothem records from different regions along a north-south transect shows a unique trend towards more negative δ 18O values from 48.0 to 38.0 ka BP, suggesting that an intensified Asian summer monsoon (ASM) across the whole monsoonal China during the interval. We speculate that the joint effect, from both the cooling of the Southern Hemisphere and the enhanced land-sea temperature contrast due to the rising summer insolation, is capable to regulate the low-latitude large-scale atmospheric circulation patterns and exert significant influences on the long-term ASM variations during the middle of Marine Isotope Stage 3

Measurements of Natural Carbonate Rare Earth Elements in Femtogram Quantities by Inductive Coupled Plasma Sector Field Mass Spectrometry

A rapid and precise standard-bracketing method has been developed for measuring femtogram quantity rare earth element (REE) levels in natural carbonate samples by inductively coupled plasma sector field mass spectrometry that does not require chemical separation steps. A desolvation nebulization system was used to effectively reduce polyatomic interference and enhance sensitivity. REE/Ca ratios are calculated directly from the intensities of the ion beams of 46Ca, 139La, 140Ce, 141Pr, 146Nd, 147Sm, 153Eu, 160Gd, 159Tb, 163Dy, 165Ho, 166Er, 169Tm, 172Yb, and 175Lu using external matrix-matched synthetic standards to correct for instrumental ratio drifting and mass discrimination. A routine measurement time of 3 min is typical for one sample containing 20-40 ppm Ca. Replicate measurements made on natural coral and foraminiferal samples with REE/Ca ratios of 2-242 nmol/mol show that external precisions of 1.9-6.5% (2 RSD) can be achieved with only 10-1000 fg of REEs in 10-20 μg of carbonate. We show that different sources for monthly resolved coral ultratrace REE variability can be distinguished using this method. For natural slow growth-rate carbonate materials, such as sclerosponges, tufa, and speleothems, the high sample throughput, high precision, and high temporal resolution REE records that can be produced with this procedure have the potential to provide valuable time-series records to advance our understanding of paleoclimatic and paleoenvironmental dynamics on different time scales

Galantamine plasma concentration and cognitive response in Alzheimer’s disease

Background Galantamine has been approved for the treatment of Alzheimer’s disease (AD). However, there are few studies which have reported the association between cognitive responses and galantamine plasma concentration. The aim of this study was to determine the correlation between galantamine plasma concentration and the subsequent cognitive response following treatment in AD patients. Methods AD sufferers who continuously took 8 mg/d galantamine for at least 6 months without previous exposure to other kinds of AChEI such as donepezil, rivastigmine, or memantine were included in this cohort study. The assessments included the Mini Mental Status Examination (MMSE), Clinical Dementia Rating Scale (CDR) and the Cognitive Assessment Screening Instrument (CASI). Each subdomain of the CASI assessment was conducted at baseline and after 6 months of galantamine. The plasma concentrations of galantamine were measured by capillary electrophoresis after 6 months of the treatment. Logistic regression was performed to adjust for age, gender, apolipoprotein E ε4 genotype status, and baseline score to investigate the association between galantamine plasma concentrations and the cognitive response. Results The total sample consisted of 33 clinically diagnosed AD patients taking galantamine 8 mg/d for 6 months. There was no linear correlation between galantamine concentration and cognitive response in patients. However, 22 patients were responsive to the treatment in the long-term memory domain. In CASI subset domain, concentration improved during the 6 months follow up. Conclusions In the limited samples study, galantamine mostly benefitted the cognitive domain of long-term memory. The benefits were not related to the galantamine plasma concentration. Objective intra-individual evaluation of therapeutic response should be encouraged

The prediction of Alzheimer’s disease through multi-trait genetic modeling

To better capture the polygenic architecture of Alzheimer’s disease (AD), we developed a joint genetic score, MetaGRS. We incorporated genetic variants for AD and 24 other traits from two independent cohorts, NACC (n = 3,174, training set) and UPitt (n = 2,053, validation set). One standard deviation increase in the MetaGRS is associated with about 57% increase in the AD risk [hazard ratio (HR) = 1.577, p = 7.17 E-56], showing little difference from the HR for AD GRS alone (HR = 1.579, p = 1.20E-56), suggesting similar utility of both models. We also conducted APOE-stratified analyses to assess the role of the e4 allele on risk prediction. Similar to that of the combined model, our stratified results did not show a considerable improvement of the MetaGRS. Our study showed that the prediction power of the MetaGRS significantly outperformed that of the reference model without any genetic information, but was effectively equivalent to the prediction power of the AD GRS

Fabrication and Characterization of a Ruthenium Nitride Membrane for Electrochemical pH Sensors

The pH sensing and nonideal characteristics of a ruthenium nitride (RuN) sensing membrane pH sensor were investigated. RuN thin films were deposited from a 99.9% ruthenium target on p-type silicon substrates using radio frequency (r.f.) sputtering with N2 gas. Subsequently, the nanometric structure and surface morphology of RuN thin films were determined. The sensitivity of the RuN sensing membrane pH sensor was 58.03 mV/pH, obtained from ID-VG curves with a current-voltage (I–V) measurement system in standard buffer solutions from pH 1 to pH 13 at room temperature (25 °C). Moreover, the nonideal characteristics of the RuN sensing membrane, such as temperature coefficient, drift with light influence, drift rate and hysteresis width, etc. were also investigated. Finally, the sensing characteristics of the RuN membrane were compared with titanium nitride (TiN), aluminum nitride (AlN) and silicon nitride (Si3N4) membranes

Proteomic analysis of rhein-induced cyt: ER stress mediates cell death in breast cancer cells

Rhein is a natural product purified from herbal plants such as Rheum palmatum, which has been shown to have anti-angiogenesis and anti-tumor metastasis properties. However, the biological effects of rhein on the behavior of breast cancers are not completely elucidated. To evaluate whether rhein might be useful in the treatment of breast cancer and its cytotoxic mechanism, we analyzed the impact of rhein treatment on differential protein expression as well as redox regulation in a non-invasive breast cancer cell line, MCF-7, and an invasive breast cancer cell line, MDA-MB-231, using lysine- and cysteine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF mass spectrometry. This proteomic study revealed that 73 proteins were significantly changed in protein expression; while 9 proteins were significantly altered in thiol reactivity in both MCF-7 and MDA-MB-231 cells. The results also demonstrated that rhein-induced cytotoxicity in breast cancer cells mostly involves dysregulation of cytoskeleton regulation, protein folding, the glycolysis pathway and transcription control. A further study also indicated that rhein promotes misfolding of cellular proteins as well as unbalancing of the cellular redox status leading to ER-stress. Our work shows that the current proteomic strategy offers a high-through-put platform to study the molecular mechanisms of rhein-induced cytotoxicity in breast cancer cells. The identified differentially expressed proteins might be further evaluated as potential targets in breast cancer therapy

Multicentennial to millennial–scale changes in the East Asian summer monsoon during Greenland interstadial 25

A multidecadal-resolved stalagmite δ18O record from two nearby caves, Lianhua and Dragon, in Shanxi Province, northern China, characterizes the detailed East Asian summer monsoon (EASM) intensity changes at 114.6–108.3 ka during Marine Oxygen Isotope Stage 5d. Our record shows an intensification of the EASM at 114.6–109.5 ka, followed by a rapid weakening at 109.5–108.4 ka. The millennial-scale strong monsoonal event appears to be correlated with the warm Greenland interstadial 25 (GI 25), whereas the weak monsoonal event is related to the cold Greenland stadial 25 within dating errors. The GI 25 monsoonal event registered in our record is also documented in various published time series from different regions of China. The lines of evidence indicate that this event occurred over the entirety of monsoonal China and was also broadly antiphase, similar to the corresponding event on a millennial time scale in the South American monsoon territory. In our record, one 700 yr weak monsoon event at 110.7+0.6−0.5 to 110.0+0.8−0.4 ka divides the GI 25 into three substages. These multicentennial to millennial–scale monsoon events correspond to two warm periods and an intervening cold interval for the intra-interstadial climate oscillations within GI 25, thus supporting a persistent coupling of the high- and low-latitude climate systems over the last glacial period

Obliquity pacing of the western Pacific Intertropical Convergence Zone over the past 282,000 years

The Intertropical Convergence Zone (ITCZ) encompasses the heaviest rain belt on the Earth. Few direct long-term records, especially in the Pacific, limit our understanding of long-term natural variability for predicting future ITCZ migration. Here we present a tropical precipitation record from the Southern Hemisphere covering the past 282,000 years, inferred from a marine sedimentary sequence collected off the eastern coast of Papua New Guinea. Unlike the precession paradigm expressed in its East Asian counterpart, our record shows that the western Pacific ITCZ migration was influenced by combined precession and obliquity changes. The obliquity forcing could be primarily delivered by a cross-hemispherical thermal/pressure contrast, resulting from the asymmetric continental configuration between Asia and Australia in a coupled East Asian-Australian circulation system. Our finding suggests that the obliquity forcing may play a more important role in global hydroclimate cycles than previously thought

Mechanism for controlling the monomer–dimer conversion of SARS coronavirus main protease

[[abstract]]The Severe acute respiratory syndrome coronavirus (SARS-CoV) main protease (Mpro) cleaves two virion polyproteins (pp1a and pp1ab); this essential process represents an attractive target for the development of anti-SARS drugs. The functional unit of Mpro is a homodimer and each subunit contains a His41/Cys145 catalytic dyad. Large amounts of biochemical and structural information are available on Mpro; nevertheless, the mechanism by which monomeric Mpro is converted into a dimer during maturation still remains poorly understood. Previous studies have suggested that a C-terminal residue, Arg298, interacts with Ser123 of the other monomer in the dimer, and mutation of Arg298 results in a monomeric structure with a collapsed substrate-binding pocket. Interestingly, the R298A mutant of Mpro shows a reversible substrate-induced dimerization that is essential for catalysis. Here, the conformational change that occurs during substrate-induced dimerization is delineated by X-ray crystallography. A dimer with a mutual orientation of the monomers that differs from that of the wild-type protease is present in the asymmetric unit. The presence of a complete substrate-binding pocket and oxyanion hole in both protomers suggests that they are both catalytically active, while the two domain IIIs show minor reorganization. This structural information offers valuable insights into the molecular mechanism associated with substrate-induced dimerization and has important implications with respect to the maturation of the enzyme.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]電子