Biomedical subjects

Zheng Zhou

Publications and source records attributed to Zheng Zhou.

At least 19 recordsLinked to original sources

PubMed2026

Biomarker Analysis from Patients with Metastatic PDAC Treated with TGFβ Antibody NIS793 plus Abraxane + Gemcitabine versus Abraxane + Gemcitabine Alone in a Phase II, Open-Label, Randomized Study.

PURPOSE: Transforming growth factor β (TGFβ) plays a dual role in cancer, acting as a tumor suppressor early in the disease but promoting progression and immune evasion when dysregulated. In pancreatic ductal adenocarcinoma (PDAC), TGFβ-driven desmoplasia fosters chemoresistance and immunosuppression, limiting therapeutic efficacy. NIS793, a fully human mAb targeting TGFβ, demonstrated antifibrotic and immunomodulatory activity in preclinical models and early-phase trials. PATIENTS AND METHODS: We conducted a randomized, open-label, phase II study in treatment-naïve patients with metastatic PDAC (mPDAC) to evaluate NIS793 ± spartalizumab (anti-PD-1) combined with nab-paclitaxel (or Abraxane)/gemcitabine (ABRA/GEM) versus ABRA/GEM alone. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), safety, pharmacokinetics, and biomarker analyses. Exploratory assessments included paired tumor RNA sequencing, cell-free DNA profiling, and plasma proteomics. RESULTS: NIS793 demonstrated target engagement and suppression of TGFβ signaling, confirmed by transcriptomic and proteomic analyses. Stromal remodeling was evident, with significant downregulation of cancer-associated fibroblast markers (Acta2, Fap) and collagen-related signatures. Despite proof of mechanism, clinical efficacy was not observed: Median PFS and OS were comparable or numerically worse in the NIS793 arm versus control (HR for OS in NIS793 + ABRA/GEM vs. ABRA/GEM: 1.32; 95% confidence interval, 0.84-2.07). The safety profile was manageable, with no unexpected toxicities. Biomarker data revealed increased expression of neutrophil-related genes after treatment, suggesting potential induction of tumor-promoting inflammation. CONCLUSIONS: NIS793 effectively inhibited TGFβ signaling and led to stromal remodeling but failed to improve outcomes in mPDAC. These findings highlight the complexity of TGFβ biology and caution against its blockade in combination with chemotherapy for PDAC. Future strategies should consider context-dependent effects of TGFβ inhibition.

Humans↗

PubMed2026

Multi-omics integrative analysis provides insight into potential molecular responses to sustained high water flow in common carp (Cyprinus carpio) cultured in recirculating aquaculture.

To investigate the potential molecular responses by which water flow intensity affects the growth of common carp (Cyprinus carpio) in a recirculating aquaculture system (RAS), a control group (CG, actual water velocity 0.3 cm/s) and three sustained flow treatment groups were established, including a low-flow group (LF, 1 body length per second, bl/s), a medium-flow group (MF, 2 bl/s), and a high-flow group (HF, 3 bl/s). After 12 weeks of culture in the RAS, growth performance was compared among groups under different flow intensities. The best-performing group and the control group were then selected for the determination of intestinal digestive enzyme activities, as well as transcriptomic and whole-genome bisulfite sequencing analyses of muscle tissue. The results showed that the specific growth rate and feed intake of the HF group were significantly higher than those of the other groups (P < 0.05), whereas no significant difference in feed conversion ratio was observed among groups. Compared with the CG group, lipase activity was significantly higher in the HF group (P < 0.05), while α-amylase and trypsin activities showed increasing trends without significant differences. RNA-seq identified a total of 273 differentially expressed genes, including 72 upregulated genes and 201 downregulated genes in the HF group relative to the CG group. These genes were mainly enriched in glycolysis, pyruvate metabolism, ATP metabolism, the pentose phosphate pathway, the insulin signaling pathway, the PPAR signaling pathway, and the adipocytokine signaling pathway, indicating that sustained high water flow induced a muscle transcriptional response characterized by remodeling of energy metabolism and substrate utilization. Whole-genome bisulfite sequencing analysis showed that DNA methylation in common carp muscle occurred predominantly in the CpG context. Differentially methylated regions between the HF and CG groups were mainly distributed in transcription-related regulatory regions, including promoters, CpG islands, and CpG island shores. In promoter regions, the number of hypermethylated regions in the HF group relative to the CG group was markedly higher than that of hypomethylated regions. Integrated analysis further identified two candidate genes showing both promoter differential methylation and differential expression, namely LOC109094644 and bcorl1, suggesting that adaptation to high water flow may involve IGF-related growth regulation and remodeling of upstream transcriptional programs. The qPCR results were consistent with the transcriptomic data. Taken together, within the tested range, a sustained water flow of 3 bl/s was more conducive to the growth of common carp in the RAS, which may be associated with enhanced lipid digestion and utilization, remodeling of the muscle energy metabolic network, changes in promoter methylation, and the coordinated regulation of key candidate genes. This study provides a theoretical basis for clarifying the exercise adaptation mechanism of common carp in recirculating aquaculture and for optimizing flow velocity parameters.

Animals↗

PubMed2026

Triple primary synchronous liver cancer in one patient: the first case report and origin speculation through bioinformatics.

INTRODUCTION: A diagnosis of multiple primary liver tumors is extremely rare. Preoperative diagnosis based on imaging findings is difficult. Moreover, the clinical benefits of treatment strategies for multiple liver cancers remain unclear. Here, we report a case of three synchronous primary liver tumors with three distinct pathological types-hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC‑CCA)-in a single patient. Bioinformatics analysis supported at least two clonal origins, with cHCC‑CCA and ICC sharing a common lineage based on identical HBV integration sites. CASE PRESENTATION: A 63-year-old female with a history of hepatitis B for several years presented with three lesions in hepatic segment VIII. Multiphase magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid revealed a diagnosis of multiple lesions, namely, cHCC‑CCA, with multiple intrahepatic metastases. The AFP level was normal, while the CA 19 - 9 level was mildly elevated (normal range ≤ 30.00 U/ml). Hepatectomy was performed, and postoperative assessment confirmed that the large lesion was cHCC‑CCA. However, the small lesions close to the large lesion were HCC and ICC. Gene testing revealed distinct mutational profiles among the three tumors. Similar gene mutations were detected in cHCC‑CCA and ICC. We also found that gene fragments of hepatitis B virus-C (HBV-C) were inserted into the genomes of ICC and cHCC‑CCA rather than that of HCC. The genomic integration site of HBV-C in cHCC‑CCA and ICC was the same. CONCLUSION: We report an extremely rare case of three synchronous primary liver tumors with three distinct pathological types (HCC, ICC, and cHCC‑CCA) in a single patient. Bioinformatics analysis supported at least two clonal origins, with cHCC‑CCA and ICC sharing a common lineage based on identical HBV integration sites. Hepatectomy represents a potential radical strategy for the treatment of multiple PLCs.

Humans↗

PubMed2026

Identification and evaluation of glutamine-related gene characteristics based on multi-omics to predict the prognosis of patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), a prevalent malignancy of the gastrointestinal tract, ranks among the leading causes of cancer-related morbidity and mortality. Its clinical course is marked by high fatality and poor prognosis. Elucidating the mechanisms underlying CRC initiation and recurrence is therefore critical for identifying novel therapeutic targets. METHODS: This study incorporated two datasets, TCGA-CRC and GSE17537. A total of 84 glutamine metabolism-related genes (GMRGs) were identified, and differential expression analysis was conducted using the TCGA-CRC dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to determine gene modules most strongly associated with GMRG scores. Single-cell RNA sequencing (scRNA-seq) was utilized to characterize key cellular clusters and to identify differentially expressed genes (DEGs) between high and low glutamine metabolism (GM) groups. Overlapping GMRGs were visualized using the ggVennDiagram package in R. A CRC risk prediction model was developed through Cox proportional hazards and LASSO regression analyses, with performance evaluated by ROC curves. Cell type enrichment across 64 immune and stromal populations was assessed via xCell, and intergroup differences were tested using the Wilcoxon rank-sum test. TIDE scores were used to estimate immunotherapy responsiveness, while oncoPredict facilitated drug sensitivity profiling. PCOLCE2 expression in CRC was validated by RT-qPCR and Western blotting. Its functional role was examined through CCK-8 assays, invasion and migration tests, flow cytometry, and glutamate quantification. RESULTS: ScRNA-seq analysis identified two key cell populations and 437 DEGs associated with GM status. WGCNA pinpointed the MEgreen module as most significantly correlated with GMRG scores, encompassing 1075 genes. Integration of DEGs, module genes, and GM-related DEGs yielded 60 candidate genes for downstream analysis. A GMRG-based prognostic model comprising six genes (SRPX, CXCL1, GPX3, PCOLCE2, CLU, SEMA3E) demonstrated strong predictive performance. Prognostic gene expression correlated with immune and stromal infiltration patterns, as indicated by Spearman correlation analysis. The high-risk group exhibited diminished predicted response to immunotherapy (TIDE scores). Drug sensitivity analysis identified four compounds—Dasatinib-51, WH-4-023-56, TWS-119-366, and LDN-193189-478—with elevated efficacy in high-risk CRC cases. PCOLCE2 expression was significantly reduced in CRC tissues. Functional assays revealed that PCOLCE2 knockdown did not substantially affect cell proliferation but significantly impaired invasion and migration in CRC cells, increased apoptosis, and suppressed both glutamine uptake and glutamate production—highlighting its oncogenic role. CONCLUSION: Six GMRGs—SRPX, CXCL1, GPX3, PCOLCE2, CLU, and SEMA3E—were identified as key components of a robust prognostic model for CRC. These findings offer valuable insights into CRC pathogenesis and potential therapeutic strategies. Notably, this study provides the first evidence implicating PCOLCE2 as a tumor-promoting factor in CRC.

Glutamine↗

PubMed2024

Genome evolution of the ancient hexaploid Platanus × acerifolia (London planetree).

Whole-genome duplication (WGD; i.e., polyploidy) and chromosomal rearrangement (i.e., genome shuffling) significantly influence genome structure and organization. Many polyploids show extensive genome shuffling relative to their pre-WGD ancestors. No reference genome is currently available for Platanaceae (Proteales), one of the sister groups to the core eudicots. Moreover, Platanus × acerifolia (London planetree; Platanaceae) is a widely used street tree. Given the pivotal phylogenetic position of Platanus and its 2-y flowering transition, understanding its flowering-time regulatory mechanism has significant evolutionary implications; however, the impact of Platanus genome evolution on flowering-time genes remains unknown. Here, we assembled a high-quality, chromosome-level reference genome for P. × acerifolia using a phylogeny-based subgenome phasing method. Comparative genomic analyses revealed that P. × acerifolia (2n = 42) is an ancient hexaploid with three subgenomes resulting from two sequential WGD events; Platanus does not seem to share any WGD with other Proteales or with core eudicots. Each P. × acerifolia subgenome is highly similar in structure and content to the reconstructed pre-WGD ancestral eudicot genome without chromosomal rearrangements. The P. × acerifolia genome exhibits karyotypic stasis and gene sub-/neo-functionalization and lacks subgenome dominance. The copy number of flowering-time genes in P. × acerifolia has undergone an expansion compared to other noncore eudicots, mainly via the WGD events. Sub-/neo-functionalization of duplicated genes provided the genetic basis underlying the unique flowering-time regulation in P. × acerifolia. The P. × acerifolia reference genome will greatly expand understanding of the evolution of genome organization, genetic diversity, and flowering-time regulation in angiosperms.

Polyploidy↗

PubMed2007

Population and structure determination of hidden folding intermediates by native-state hydrogen exchange-directed protein engineering and nuclear magnetic resonance.

Structural characterization of folding intermediates has been one of the important steps toward understanding the mechanism of protein folding. However, it has been very difficult to obtain high-resolution structures of folding intermediates. Such results have become available only very recently. Here, we review a procedure that uses the native-state amide hydrogen exchange-directed protein engineering method to populate partially unfolded intermediates and multidimensional NMR to solve the high-resolution structures of the intermediates.

Models, Molecular↗

PubMed2006

Cooperation between engulfment receptors: the case of ABCA1 and MEGF10.

The engulfment of dying cells is a specialized form of phagocytosis that is extremely conserved across evolution. In the worm, it is genetically controlled by two parallel pathways, which are only partially reconstituted in mammals. We focused on the recapitulation of the CED-1 defined pathway in mammalian systems. We first explored and validated MEGF10, a novel receptor bearing striking structural similarities to CED-1, as a bona fide functional ortholog in mammals and hence progressed toward the analysis of molecular interactions along the corresponding pathway. We ascertained that, in a system of forced expression by transfection, MEGF10 function can be modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7. Indeed, the coexpression of either a functional or a mutant ABCA1 exerted a transdominant positive or negative modulation on the MEGF10-dependent engulfment. The combined use of biochemical and biophysical approaches indicated that this functional cooperation relies on the alternate association of these receptors with a common partner, endogenously expressed in our cell system. We provide the first working model structuring in mammals the CED-1 dependent pathway.

ATP Binding Cassette Transporter 1↗

PubMed2006

Detection of a hidden folding intermediate in the focal adhesion target domain: Implications for its function and folding.

The focal adhesion target (FAT) domain of focal adhesion kinase has a four-helix bundle structure. Based on a hydrogen exchange-constrained computer simulation study and some indirect experimental results, it has been suggested that a partially unfolded state of the FAT domain with the N-terminal helix unfolded plays an important role in its biological function. Here, using a native-state hydrogen exchange method, we directly detected an intermediate with the N-terminal helix unfolded in a mutant (Y925E) of the FAT domain. In addition, kinetic folding studies on the FAT domain suggest that this intermediate exists on the native side of the rate-limiting transition state for folding. These results provide more direct evidence of the existence of the proposed intermediate and help to understand the folding mechanism of small single domain proteins.

Circular Dichroism↗

PubMed2006

The folding pathway of T4 lysozyme: an on-pathway hidden folding intermediate.

T4 lysozyme has two easily distinguishable but energetically coupled domains: the N and C-terminal domains. In earlier studies, an amide hydrogen/deuterium exchange pulse-labeling experiment detected a stable submillisecond intermediate that accumulates before the rate-limiting transition state. It involves the formation of structures in both the N and C-terminal regions. However, a native-state hydrogen exchange experiment subsequently detected an equilibrium intermediate that only involves the formation of the C-terminal domain. Here, using stopped-flow circular dichroism and fluorescence, amide hydrogen exchange-folding competition, and protein engineering methods, we re-examined the folding pathway of T4-lysozyme. We found no evidence for the existence of a stable folding intermediate before the rate-limiting transition state at neutral pH. In addition, using native-state hydrogen exchange-directed protein engineering, we created a mimic of the equilibrium intermediate. We found that the intermediate mimic folds with the same rate as the wild-type protein, suggesting that the equilibrium intermediate is an on-pathway intermediate that exists after the rate-limiting transition state.

Bacteriophage T4↗

PubMed2006

Mixed macromolecular crowding accelerates the refolding of rabbit muscle creatine kinase: implications for protein folding in physiological environments.

The effects of four single macromolecular crowding agents, Ficoll 70, dextran 70, polyethylene glycol (PEG) 2000, and calf thymus DNA (CT DNA), and three mixed crowding agents containing both CT DNA and polysaccharide (or PEG 2000) on the refolding of guanidine hydrochloride-denatured rabbit muscle creatine kinase (MM-CK) have been examined by activity assay. When the total concentration of the mixed crowding agent is 100 g/l, in which the weight ratio of CT DNA to Ficoll 70 is 1:9, the refolding yield of MM-CK after refolding for 3 h under these conditions increases 23% compared with that in the presence of 10 g/l CT DNA, 18% compared with 100 g/l Ficoll 70, and 19% compared with that in the absence of crowding agents. A remarkable increase in the refolding yield of MM-CK by a mixed crowding agent containing CT DNA and dextran 70 (or PEG 2000) is also observed. Further folding kinetics analyses show that these three mixed crowding agents remarkably accelerate the refolding of MM-CK, compared with single crowding agents. Aggregation of MM-CK in the presence of any of the three mixed crowding agents is less serious than that in the presence of a single crowding agent at the same concentration but more serious than that in the absence of crowding agents. Both the refolding yield and the refolding rate of MM-CK in mixtures of these agents are increased relative to the individual agents by themselves, indicating that mixed macromolecular crowding agents are more favorable to MM-CK folding and can be used to reflect the physiological environment more accurately than single crowding agents.

Animals↗

PubMed2006

Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair.

The Rad23/Rad4 nucleotide excision repair (NER) protein complex functions at an early stage of the NER reaction, possibly promoting the recognition of damaged DNA. Here we show that Rad4 protein is ubiquitinated and degraded in response to ultraviolet (UV) radiation, and identify a novel cullin-based E3 ubiquitin ligase required for this process. We also show that this novel ubiquitin ligase is required for optimal NER. Our results demonstrate that optimal NER correlates with the ubiquitination of Rad4 following UV radiation, but not its subsequent degradation. Furthermore, we show that the ubiquitin-proteasome pathway (UPP) regulates NER via two distinct mechanisms. The first occurs independently of de novo protein synthesis, and requires Rad23 and a nonproteolytic function of the 19S regulatory complex of the 26S proteasome. The second requires de novo protein synthesis, and relies on the activity of the newly identified E3 ubiquitin ligase. These studies reveal that, following UV radiation, NER is mediated by nonproteolytic activities of the UPP, via the ubiquitin-like domain of Rad23 and UV radiation-induced ubiquitination of Rad4.

DNA Repair↗

PubMed2006

Probing the transition state ensemble of a protein folding reaction by pressure-dependent NMR relaxation dispersion.

The F61A/A90G mutant of a redesigned form of apocytochrome b562 folds by an apparent two-state mechanism. We have used the pressure dependence of 15N NMR relaxation dispersion rate profiles to study the changes in volumetric parameters that accompany the folding reaction of this protein at 45 degrees C. The experiments were performed under conditions where the folding/unfolding equilibrium could be studied at each pressure without addition of denaturants. The exquisite sensitivity of the methodology to small changes in folding/unfolding rates facilitated the use of relatively low-pressure values (between 1 and 270 bar) so that pressure-induced changes to the unfolded state ensemble could be minimized. A volume change for unfolding of -81 mL/mol is measured (at 1 bar), a factor of 1.4 larger (in absolute value) than the volume difference between the transition state ensemble (TSE) and the unfolded state. Notably, the changes in the free energy difference between folded and unfolded states and in the activation free energy for folding were not linear with pressure. Thus, the difference in the isothermal compressibility upon unfolding (-0.11 mL mol(-1) bar(-1)) and, for the first time, the compressibility of the TSE relative to the unfolded state (0.15 mL mol(-1) bar(-1)) could be calculated. The results argue for a TSE that is collapsed but loosely packed relative to the folded state and significantly hydrated, suggesting that the release of water occurs after the rate-limiting step in protein folding. The notion of a collapsed and hydrated TSE is consistent with expectations based on earlier temperature-dependent folding studies, showing that the barrier to folding at 45 degrees C is entropic (Choy, W. Y.; Zhou, Z.; Bai, Y.; Kay, L. E. J. Am. Chem. Soc. 2005, 127, 5066-5072).

Cytochromes b↗

PubMed2006

Regulation of osteoclast function and bone mass by RAGE.

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily that has multiple ligands and is implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative disorders, and inflammatory responses. However, the role of RAGE in normal physiology is largely undefined. Here, we present evidence for a role of RAGE in osteoclast maturation and function, which has consequences for bone remodeling. Mice lacking RAGE had increased bone mass and bone mineral density and decreased bone resorptive activity in vivo. In vitro-differentiated RAGE-deficient osteoclasts exhibited disrupted actin ring and sealing zone structures, impaired maturation, and reduced bone resorptive activity. Impaired signaling downstream of alphavbeta3 integrin was observed in RAGE(-/-) bone marrow macrophages and precursors of OCs. These results demonstrate a role for RAGE in osteoclast actin cytoskeletal reorganization, adhesion, and function, and suggest that the osteosclerotic-like phenotype observed in RAGE knockout mice is due to a defect in osteoclast function.

Actins↗

PubMed2006

15N NMR spin relaxation dispersion study of the molecular crowding effects on protein folding under native conditions.

The effects of macromolecular crowding on protein stability and folding kinetics have been studied using the recently developed 15N spin relaxation dispersion technique. By applying this method to a redesigned apocytochrome b562, the kinetics and thermodynamics of the protein folding processes in both the presence and the absence of crowding agents have been characterized. The result indicates that, even under the mild crowded environments (in the presence of 85 mg/mL of PEG 20K), the folding rate of the protein can speed up significantly while the unfolded rate remains unchanged within experimental error.

Cytochrome b Group↗

PubMed2006

A HIPAA-compliant architecture for securing clinical images.

The Health Insurance Portability and Accountability Act (HIPAA, instituted April 2003) Security Standards mandate health institutions to protect health information against unauthorized use or disclosure. One approach to addressing this mandate is by utilizing user access control and generating audit trails of the various authorized as well as unauthorized user access of health data. Although most current clinical image systems [e.g., picture archiving and communication system (PACS)] have components that generate log files for application debugging purposes, there is a lack of methodology to obtain and synthesize the pertinent data from the large volumes of log data generated by these multiple components within a PACS. We have designed a HIPAA-compliant architecture specifically for tracking and auditing the image workflow of clinical imaging systems such as PACS. As an initial first step, we developed HIPAA-compliant auditing system (H-CAS) based on parts of this HIPAA-compliant architecture. H-CAS was implemented within a test-bed PACS simulator located in the Image Processing and Informatics lab at the University of Southern California. Evaluation scenarios were developed where different user types performed legal and illegal access of PACS image data within each of the different components in the PACS simulator. Results were based on whether the scenarios of unauthorized access were correctly identified and documented as well as on normal operational activity. Integration and implementation pitfalls were also noted and included.

California↗

PubMed2006

Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention.

BACKGROUND: The relative efficacy of different statins for long-term cardiovascular prevention remains largely undetermined. METHODS: Using adjusted indirect comparison, we compared 3 statins (pravastatin, simvastatin, and atorvastatin) based on published randomized placebo-controlled trials for long-term cardiovascular prevention. A systematic literature search between 1980 and 2004 was conducted. Randomized placebo-controlled trials of the 3 statins, which studied cardiovascular diseases or death as the outcome, enrolled > or = 1000 participants, and had > or = 1-year follow-up, were included. Trials were grouped according to the statin under study. A pooled relative risk (RR) was derived from each set of trials using a random-effects model. Adjusted indirect comparisons using pooled RRs were made between statins with regard to prespecified clinical outcomes. RESULTS: Eight placebo-controlled trials met the inclusion criteria, including 4 pravastatin trials (n = 25,572), 2 simvastatin trials (n = 24,980), and 2 atorvastatin trials (n = 13,143). All trials had a similar degree of lipid reduction. Graphical and statistical assessments showed minimal heterogeneity in the trials' effect sizes. Adjusted indirect comparisons did not reveal a statistically significant difference between statins in reducing fatal coronary heart disease and nonfatal myocardial infarctions (simvastatin vs pravastatin: RR 0.93 [95% CI 0.84-1.03]; atorvastatin vs simvastatin: RR 0.84 [95% CI 0.66-1.08]; atorvastatin vs pravastatin: RR 0.79 [95% CI 0.61-1.02]). We were unable to detect differences either in outcomes for fatal and nonfatal strokes, all cardiovascular deaths, and all-cause mortality. CONCLUSION: Evidence from published statin randomized placebo-controlled trials suggests that pravastatin, simvastatin, and atorvastatin, when used at their standard dosages, show no statistically significant difference in their effect on long-term cardiovascular prevention.

Atorvastatin↗

PubMed2006

C. elegans Dynamin mediates the signaling of phagocytic receptor CED-1 for the engulfment and degradation of apoptotic cells.

Dynamins are large GTPases that act in multiple vesicular trafficking events. We identified 14 loss-of-function alleles of the C. elegans dynamin gene, dyn-1, that are defective in the removal of apoptotic cells. dyn-1 functions in engulfing cells to control the internalization and degradation of apoptotic cells. dyn-1 acts in the genetic pathway composed of ced-7 (ABC transporter), ced-1 (phagocytic receptor), and ced-6 (CED-1's adaptor). DYN-1 transiently accumulates to the surface of pseudopods in a manner dependent on ced-1, ced-6, and ced-7, but not on ced-5, ced-10, or ced-12. Abnormal vesicle structures accumulate in engulfing cells upon dyn-1 inactivation. dyn-1 and ced-1 mutations block the recruitment of intracellular vesicles to pseudopods and phagosomes. We propose that DYN-1 mediates the signaling of the CED-1 pathway by organizing an intracellular vesicle pool and promoting vesicle delivery to phagocytic cups and phagosomes to support pseudopod extension and apoptotic cell degradation.

Alleles↗

PubMed2006

Dissociative experiences in China.

The Dissociative Experiences Scale was administered to a non-clinical sample in Shanghai, China (N = 618) and the results were compared with a previous sample of the general population from Winnipeg, Canada (N = 1055). The Dissociative Disorders Interview Schedule was administered to the 618 Chinese participants and results were compared with those of the Canadian participants (N = 502). In addition, both measures were administered to a sample of Chinese psychiatric inpatients (N = 423) and outpatients (N = 304). Rates of childhood trauma and dissociation were far lower in the Chinese non-clinical sample than in the two Chinese psychiatric patient groups, and far lower than in the Canadian general population. Among the 618 respondents in the Chinese non-clinical sample, no childhood sexual abuse was reported and only one person reported childhood physical abuse. These rates of childhood abuse were far lower than in other non-clinical samples from China; for example, rates were 16.7% for sexual abuse of girls and 10.5% for sexual abuse of boys in a previous study. Among the more traumatized Chinese psychiatric patients, and among the Canadian respondents, dissociative experiences were much more common than in the Chinese general population. The data provide a base frequency for dissociation in non-clinical samples reporting little or no childhood physical and sexual abuse.

Adult↗