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Rac GTPases act as master switches to coordinate multiple interweaved signaling pathways. A major function for Rac GTPases is to control neurite development by influencing downstream effector molecules and pathways. In Caenorhabditis elegans, the Rac proteins CED-10, RAC-2 and MIG-2 act in parallel to control axon outgrowth and guidance. Here, we have identified a single glycine residue in the CED-10/Rac1 Switch 1 region that confers a non-redundant function in axon outgrowth but not guidance. Mutation of this glycine to glutamic acid (G30E) reduces GTP binding and inhibits axon outgrowth but does not affect other canonical CED-10 functions. This demonstrates previously unappreciated domain-specific functions within the CED-10 protein. Further, we reveal that when CED-10 function is diminished, the adaptor protein NAB-1 (Neurabin) and its interacting partner SYD-1 (Rho-GAP-like protein) can act as inhibitors of axon outgrowth. Together, we reveal that specific domains and residues within Rac GTPases can confer context-dependent functions during animal development. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) with exogenous protoporphyrin IX (PpIX) or endogenous PpIX derived from 5-aminolevulinic acid (ALA) has been carried out to produce apoptotic effects on macrophages, indicating a potential treatment methodology for atherosclerosis. Our previous studies have found that mitochondria damage by reactive oxygen species (ROS) plays a major role in the SDT-induced apoptosis. This study aimed at investigating the potential involvement of the mitochondrial 18 kDa translocator protein (TSPO) and ROS in the pro-apoptotic effects of SDT on THP-1 macrophages. THP-1 macrophages were divided into control and SDT groups, and went through pretreatment of the specific TSPO ligand PK11195 and ROS scavengers N-Acetyl Cysteine (NAC), then compared with groups without pretreatment. Application of PK11195 reduced intracellular accumulation of endogenous PpIX. PK11195 and NAC reduced the generation of intracellular ROS and oxidation of cardiolipin induced by SDT, respectively. PK11195 and NAC also reduced SDT-induced mitochondrial membrane potential (ΔΨm) loss, the translocation of cytochrome c and cell apoptosis. PpIX accumulation, ROS generation and cell apoptosis were also attenuated by siTSPO. Our findings indicate the pivotal role of TSPO and ROS in SDT-induced cardiolipin oxidation, ΔΨm collapse, cytochrome c translocation and apoptosis in THP-1 macrophages. [ABSTRACT FROM AUTHOR]

In this paper, based on our previous multi-pattern uniform resource locator (URL) binary-matching algorithm called HEM, we propose an improved multi-pattern matching algorithm called MH that is based on hash tables and binary tables. The MH algorithm can be applied to the fields of network security, data analysis, load balancing, cloud robotic communications, and so on—all of which require string matching from a fixed starting position. Our approach effectively solves the performance problems of the classical multi-pattern matching algorithms. This paper explores ways to improve string matching performance under the HTTP protocol by using a hash method combined with a binary method that transforms the symbol-space matching problem into a digital-space numerical-size comparison and hashing problem. The MH approach has a fast matching speed, requires little memory, performs better than both the classical algorithms and HEM for matching fields in an HTTP stream, and it has great promise for use in real-world applications. [ABSTRACT FROM AUTHOR]

Exact prediction of Hemorrhagic fever with renal syndrome (HFRS) epidemics must improve to establish effective preventive measures in China. A Seasonal Autoregressive Integrated Moving Average (SARIMA) model was applied to establish a highly predictive model of HFRS. Meteorological factors were considered external variables through a cross correlation analysis. Then, these factors were included in the SARIMA model to determine if they could improve the predictive ability of HFRS epidemics in the region. The optimal univariate SARIMA model was identified as (0,0,2)(1,1,1)12. The R2 of the prediction of HFRS cases from January 2014 to December 2014 was 0.857, and the Root mean square error (RMSE) was 2.708. However, the inclusion of meteorological variables as external regressors did not significantly improve the SARIMA model. This result is likely because seasonal variations in meteorological variables were included in the seasonal characteristics of the HFRS itself. [ABSTRACT FROM AUTHOR]

Human beings are inevitably exposed to ubiquitous phthalate esters (PAEs). Processed, packaged foods are popular nowadays, in which emulsifiers are frequently added as food additives. It is unclear how emulsifiers affect the bioavailability of ingested PAEs contaminants and their toxicities. The purposes of our study were to explore whether food emulsifier Glycerin Monostearate (GMS) could increase the internal exposure levels of six priority controlled PAEs and affect their reproductive toxicities when male rats are exposed to PAEs mixture (MIXPs). The male rats were exposed to MIXPs by gavage for thirty days in combination with or without given GMS. Phthalate monoesters (MPAEs), primary metabolites of PAEs, in rat urine were used as biomarkers to predict the internal exposure levels of the six PAEs, and their concentrations were determined using UPLC-MS. The reproductive toxicity was evaluated using serum testosterone levels test and histopathology of testes. Results showed that compared to PAEs exposure alone, the internal exposure levels of PAEs increased by 30%-49% in the presence of GMS. PAEs exposure led to the reduction of testosterone level by 23.4%-42.1% in the presence and absence of GMS, respectively, compared to the baseline. Testosterone levels in MIXPs+GMS and DEHP+GMS group were decreased by 9.1% and 13.6%, respectively, compared with MIXPs and DEHP group. Histopathology showed that injuries of testis (deciduous spermatids) were observed, and GMS exacerbated the injuries. The results indicated food emulsifiers chronically taken up might increase safety risks of food PAEs contaminants. [ABSTRACT FROM AUTHOR]

Background and Purpose: The conflicting findings of previous morphological and hemodynamic studies on intracranial aneurysm rupture may be caused by the relatively small sample sizes and the variation in location of the patient-specific aneurysm models. We aimed to determine the discriminators for aneurysm rupture status by focusing on only posterior communicating artery (PCoA) aneurysms. Materials and Methods: In 129 PCoA aneurysms (85 ruptured, 44 unruptured), clinical, morphological and hemodynamic characteristics were compared between the ruptured and unruptured cases. Multivariate logistic regression analysis was performed to determine the discriminators for rupture status of PCoA aneurysms. Results: While univariate analyses showed that the size of aneurysm dome, aspect ratio (AR), size ratio (SR), dome-to-neck ratio (DN), inflow angle (IA), normalized wall shear stress (NWSS) and percentage of low wall shear stress area (LSA) were significantly associated with PCoA aneurysm rupture status. With multivariate analyses, significance was only retained for higher IA (OR = 1.539, p < 0.001) and LSA (OR = 1.393, p = 0.041). Conclusions: Hemodynamics and morphology were related to rupture status of intracranial aneurysms. Higher IA and LSA were identified as discriminators for rupture status of PCoA aneurysms. [ABSTRACT FROM AUTHOR]

Background: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) which can be severe and cause death in approximately 10% of cases. Up to now, six randomized controlled trials (RCTs) have been found relevant to the effect of allopurinol on prevention of Post-ERCP pancreatitis (PEP). However, these results remained controversial. Objective: To conduct a meta-analysis with RCTs published in full text to determine the effectiveness of prophylactic allopurinol of different dosages and administration time in the incidence and severity of PEP. Methods: Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library from databases inception to May 2014. RCTs comparing the effect of allopurinol with placebo on prevention of PEP were included. Statistical heterogeneity was quantitatively evaluated byχ2 test with the significance set P<0.10 or I2>50%. Results: Six RCTs consisting of 1974 participants were eventually included. The incidences of PEP in allopurinol group and placebo group were 8.4%(83/986) and 9.9%(98/988) respectively. Meta-analysis showed no evident prevention effect of allopurinol on the incidence of PEP (RR 0.75, 95%CI 0.39–1.42) with significant heterogeneity (I2 = 70.4%, P = 0.005). When studies were stratified according to the dosages and administration time of allopurinol they applied, there was still no evident prevention effect of allopurinol on mild, moderate or severe PEP. However, statistically substantial heterogeneity was presented in the subgroup of moderate PEP when the effect of high dose of allopurinol was analyzed (Imoderate2 = 82.3%, Pmoderate = 0.018). Statistically significant heterogeneity was also observed in subgroup of mild PEP, when the effect of long adminstration time of allopurinol was investigated (Imild2 = 62.8%, Pmild = 0.068). Conclusion: The prophylactic use of allopurinol in different dosages and administration time had no effect in preventing incidence and severity of PEP. [ABSTRACT FROM AUTHOR]