In budding yeast, acetylation of histone H3 lysine 56 (H3-K56) is catalyzed by the Rtt109-Vps75 histone acetyltransferase (HAT) complex, with Rtt109 being the catalytic subunit, and histone chaperone ...Asf1 is required for this modification. Cells lacking Rtt109 are susceptible to perturbations in DNA replication. However, how Asf1 regulates acetylation of H3-K56 and how loss of H3-K56 acetylation affects DNA replication are unclear. We show that at low concentrations the Rtt109-Vps75 HAT complex acetylates H3-K56 in vitro when H3/H4 is complexed with Asf1, but not H3/H4 tetramers, recapitulating the in vivo requirement of Asf1 for H3-K56 acetylation using recombinant proteins. Moreover, the Rtt109-Vps75 complex interacts with Asf1-H3/H4 but not Asf1. In vivo, the Rtt109-Asf1 interaction is also dependent on the ability of Asf1 to bind H3/H4. Furthermore, the Rtt109 homolog in Schizosaccharomyces pombe (SpRtt109) also displayed an Asf1-dependent H3-K56 HAT activity in vitro. These results indicate that Asf1 regulates H3-K56 acetylation by presenting histones H3 and H4 to Rtt109-Vps575 for acetylation, and this mechanism is likely to be conserved. Finally, we have shown that cells lacking Rtt109 or expressing H3-K56 mutants exhibited significant reduction in the association of three proteins with stalled DNA replication forks and hyper-recombination of replication forks stalled at replication fork barriers of the ribosomal DNA locus compared with wild-type cells. Taken together, these studies provide novel insight into the role of Asf1 in the regulation of H3-K56 acetylation and the function of this modification in DNA replication.
Glioblastomas are the most common and most lethal primary brain tumor. Recent studies implicate an important role for a restricted population of neoplastic cells (glioma stem cells (GSCs)) in glioma ...maintenance and recurrence. We now demonstrate that GSCs preferentially express two interleukin 6 (IL6) receptors: IL6 receptor alpha (IL6Rα) and glycoprotein 130 (gp130). Targeting IL6Rα or IL6 ligand expression in GSCs with the use of short hairpin RNAs (shRNAs) significantly reduces growth and neurosphere formation capacity while increasing apoptosis. Perturbation of IL6 signaling in GSCs attenuates signal transducers and activators of transcription three (STAT3) activation, and small molecule inhibitors of STAT3 potently induce GSC apoptosis. These data indicate that STAT3 is a downstream mediator of prosurvival IL6 signals in GSCs. Targeting of IL6Rα or IL6 expression in GSCs increases the survival of mice bearing intracranial human glioma xenografts. IL6 is clinically significant because elevated IL6 ligand and receptor expression are associated with poor glioma patient survival. The potential utility of anti‐IL6 therapies is demonstrated by decreased growth of subcutaneous human GSC‐derived xenografts treated with IL6 antibody. Together, our data indicate that IL6 signaling contributes to glioma malignancy through the promotion of GSC growth and survival, and that targeting IL6 may offer benefit for glioma patients. STEM CELLS 2009;27:2393–2404
GABA-ergic interneurons provide diverse inhibitions that are essential for the operation of neuronal circuits in the neocortex. However, the mechanisms that control the functional organization of ...neocortical interneurons remain largely unknown. Here we show that developmental origins influence fine-scale synapse formation and microcircuit assembly of neocortical interneurons. Spatially clustered neocortical interneurons originating from low-titre retrovirus-infected radial glial progenitors in the embryonic medial ganglionic eminence and preoptic area preferentially develop electrical, but not chemical, synapses with each other. This lineage-related electrical coupling forms predominantly between the same interneuron subtype over an extended postnatal period and across a range of distances, and promotes action potential generation and synchronous firing. Interestingly, this selective electrical coupling relates to a coordinated inhibitory chemical synapse formation between sparsely labelled interneurons in clusters and the same nearby excitatory neurons. These results suggest a link between the lineage relationship of neocortical interneurons and their precise functional organization.
To investigate the application and effectiveness of self-made spring plate in surgical treatment of acetabular posterior wall fracturejavascript:void(0)s.
Between June 2013 and June 2017, 38 patients ...with acetabular posterior wall fractures were treated. There were 27 males and 11 females with an average age of 53 years (range, 28-68 years). The injury caused by traffic accident in 18 cases, falling from height in 15 cases, and tumble in 5 cases. There were 4 cases of simple posterior wall fracture, 18 cases of posterior wall fracture with posterior dislocation of hip joint, 10 cases of posterior wall fracture with posterior column fracture, and 6 cases of posterior wall fracture with transverse fracture. The time from injury to admission was 1-4 days (mean, 2.5 days). The time from injury to operation was 4-8 days (mean, 5 days). After fracture reduction via the Kocher-Langenbeck approach (35 cases) or the combined ilioinguinal approach (3 cases), the spring plate was used to press the posterior wall fractur
Background: Tai Chi is an increasingly utilized aerobic rehabilitation exercise in the field of cardiovascular disease (CVD). However, there remains debate regarding its effects on physiological ...function and mental health in patients with coronary heart disease (CHD). This study aims to investigate the impact of Tai Chi-based rehabilitation exercises on physical and psychological health outcomes for CHD patients. Methods: By collecting data from 12 databases up to December 2022, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of Tai Chi on the physical function and psychological health among CHD patients. Results: We analyzed twenty qualified studies involving 2095 patients. Meta-analyses revealed that compared with conventional therapy groups, those who participated in Tai Chi-based interventions demonstrated significant improvements in physical function as measured by six-minute walk test (6MWT) mean difference (MD) = 56.40, 95% confidence interval (CI) (38.50, 74.29), p < 0.01, maximal oxygen consumption (VO2 max) standardized mean difference (SMD) = 0. 57, 95% CI (0.12, 1.03), p = 0.01, New York Heart Association (NYHA) class relative risk (RR) = 1.34, 95% CI (1.18, 1.53), p < 0.01 and physical health components (PHC) SMD = 1.23, 95% CI (0.76, 1.69), p < 0.01. Additionally, Tai Chi participants showed greater improvement than control groups across various psychological parameters including anxiety scales SMD = –0.80, 95% CI (–1.33, –0.28), p = 0.003, depression scales SMD = –0.77, 95% CI (–1.32, –0.23), p = 0.005 and mental health components (MHC) SMD = 1.27, 95% CI (0.76, –1.78), p < 0.01. The GRADEpro (Grade Guideline Development Tool) indicated evidence levels ranging from very low to moderate. Conclusions: The present meta-analysis demonstrates that mind-body rehabilitation exercises based on Tai Chi can improve both physical and psychological health outcomes for CHD patients. These findings suggest that this exercise pattern may be a potential option for cardiovascular rehabilitation. PROSPERO Registration: The protocol for this systematic review and meta-analysis has been registered with PROSPERO International Prospective Systematic Reviews (No: CRD42022370021, http://www.crd.york.ac.uk/PROSPERO).
We used pollen and grain-size data from a peat bog in Xiansan, Fujian Province, southeastern China, to reconstruct a high-resolution record of vegetation change, climatic dynamics, and human impact ...over the last 1330 cal BP. During 1330–1200 cal BP, we infer the existence of a swamp bog with dense cypress forests, based on dominant Cupressaceae pollen, suggesting cold and dry conditions during this early period. Fine-grained sediment and higher percentages of wetland pollen and fern spores suggest intermittent-lake conditions, indicating a wet Medieval Warm Period (MWP; 1200–730 cal BP). The increase in coniferous forest and montane shrub-meadow pollen indicate a cold and dry climate during the early to mid-Little Ice Age (LIA; 730–370 cal BP), but coarse-grained sediments associated with more abundant wetland taxa pollen indicate a shallower intermittent-lake landscape, reflecting relatively humid periods during 620–560 cal BP and 400–450 cal BP. During the last 370 cal BP, a rapid increase in the secondary forest component and a gradual decrease in the pollen-inferred floristic diversity index suggest that the natural vegetation was converted to secondary vegetation, as a result of severe anthropogenic disturbance in the montane region of Fujian Province. The reconstructed regional precipitation trend prior to this period was mainly correlated with East Asian summer monsoon (EASM) intensity, which is related to variation in solar irradiation.
Size-differentiated REE characteristics can serve as more effective source tracers for aeolian sediments, allowing for a better the exact source(s) of the Ili loess.
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...•Size-differentiated REE can act as improved provenance tracers for aeolian sediment.•REE of the <2μm particle is sensitive indicators to identify distant dust in the Ili Basin.•REE of coarse fraction is effective to track proximal dust and regional circulations.
Aeolian loess in the Ili Basin is an important geological archive for studying the changes in paleoclimate and sources of dust particles. Size-differentiated rare earth elements (REE) may help to distinguish potential dust sources. This study investigates the size-differentiated REE characteristics from three sites including the Zhaosu loess and the Kekdala desert sediments from the Ili Basin, and the Chaona loess from the Chinese Loess Plateau (CLP). Our results show that the patterns of variation of the REE characteristics in different size fractions can act as improved source tracers for aeolian sediments. Moreover, the REE characteristics of the <2μm particles are sensitive indicators for distinguishing dust particles transported over long distances in the semi-arid areas with limited pedogenesis such as the Ili Basin. However, it should be interpreted cautiously in the CLP due to the post-depositional chemical weathering. The REE characteristics of coarse fractions are effective tracers for tracking changes in proximal dust sources and regional boundary level circulations. Our study has implications for identifying the exact source(s) of the Ili loess, which is helpful to understand paleoclimate changes and westerly circulation patterns in Central Asia.
The hippocampus, as part of the cerebral cortex, is essential for memory formation and spatial navigation. Although it has been extensively studied, especially as a model system for neurophysiology, ...the cellular processes involved in constructing and organizing the hippocampus remain largely unclear. Here, we show that clonally related excitatory neurons in the developing hippocampus are progressively organized into discrete horizontal, but not vertical, clusters in the stratum pyramidale, as revealed by both cell-type-specific retroviral labeling and mosaic analysis with double markers (MADM). Moreover, distinct from those in the neocortex, sister excitatory neurons in the cornu ammonis 1 region of the hippocampus rarely develop electrical or chemical synapses with each other. Instead, they preferentially receive common synaptic input from nearby fast-spiking (FS), but not non-FS, interneurons and exhibit synchronous synaptic activity. These results suggest that shared inhibitory input may specify horizontally clustered sister excitatory neurons as functional units in the hippocampus.
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•Clonally related pyramidal neurons form horizontal clusters in the hippocampus•Sister pyramidal neurons do not preferentially develop synapses with each other•Sister pyramidal neurons exhibit synchronous synaptic activity•Sister pyramidal neurons receive common inputs from nearby FS interneurons
Clonally related excitatory neurons in the hippocampus are progressively organized into discrete horizontal clusters and preferentially receive common synaptic inputs from nearby fast-spiking interneurons and exhibit synchronous activity.
We present a new 230Th-dated absolute chronology of Asian summer monsoon (ASM) variability from 113.5 to 86.6 kyr BP (before 1950 AD). This integrated multidecadally resolved record, based on 1435 ...oxygen isotope data and 46 230Th dates with 2-sigma errors as low as ±0.3 kyr from three stalagmites collected in Sanxing Cave, southwestern China, can be a new reference for calibrating paleoclimate proxy sequences. The Sanxing δ18O record follows the 23 kyr precessional cycle of insolation and is punctuated by prominent millennial-scale oscillations of the Chinese Interstadials (CIS) 25 to 22, corresponding to Greenland Interstadials (GIS) 25 to 22. The onset of CIS 25, 24, 23 and 22 is dated to 113.1 ± 0.4, 108.1 ± 0.3, 103.7 ± 0.3 and 91.4 ± 0.6 kyr BP in the Sanxing record, respectively. The end of CIS 24 and CIS 22 is constrained to 105.5 ± 0.4 and 87.7 ± 0.3 kyr BP, respectively. A centennial-scale precursor event at 104.1 ± 0.3 kyr BP preceding CIS 23 is clearly registered. These events in the Sanxing record are synchronous with those identified in stalagmites from the European Alps (NALPS), except for the onset of GIS 25 and the end of GIS 22, and differ by up to 2.3 kyr from the corresponding ones in Greenland ice core records. The high degree of similarity of the δ18O records between Sanxing Cave and Greenland supports a Northern Hemisphere forcing of the ASM. The anti-phase relationship of δ18O records between Sanxing stalagmites and Antarctic ice cores suggests an additional ASM linkage to the Southern Hemisphere.
•A record of multidecadally resolved Asian monsoon variability between 113.5 and 86.6 kyr BP.•The first-time identification of GIS 23 precursor event in a continental archive of the Asian monsoon.•Precisely dated stalagmite δ18O provide a promising reference for calibrating paleoclimate proxy sequences.
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