The FAM deubiquitylating enzyme localizes to multiple points of protein trafficking in epithelia, where it associates with E-cadherin and β-catenin

Ubiquitylation is a necessary step in the endocytosis and lysosomal trafficking of many plasma membrane proteins and can also influence protein trafficking in the biosynthetic pathway. Although a molecular understanding of ubiquitylation in these processes is beginning to emerge, very little is known about the role deubiquitylation may play. Fat Facets in mouse (FAM) is substrate-specific deubiquitylating enzyme highly expressed in epithelia where it interacts with its substrate, β-catenin. Here we show, in the polarized intestinal epithelial cell line T84, FAM localized to multiple points of protein trafficking. FAM interacted with β-catenin and E-cadherin in T84 cells but only in subconfluent cultures. FAM extensively colocalized with β-catenin in cytoplasmic puncta but not at sites of cell-cell contact as well as immunoprecipitating with β-catenin and E-cadherin from a higher molecular weight complex (~500 kDa). At confluence FAM neither colocalized with, nor immunoprecipitated, β-catenin or E-cadherin, which were predominantly in a larger molecular weight complex (~2 MDa) at the cell surface. Overexpression of FAM in MCF-7 epithelial cells resulted in increased β-catenin levels, which localized to the plasma membrane. Expression of E-cadherin in L-cell fibroblasts resulted in the relocalization of FAM from the Golgi to cytoplasmic puncta. These data strongly suggest that FAM associates with E-cadherin and β-catenin during trafficking to the plasma membrane.

Combinatorial design of key distribution mechanisms for wireless sensor networks

Key distribution is one of the most challenging security issues in wireless sensor networks where sensor nodes are randomly scattered over a hostile territory. In such a sensor deployment scenario, there will be no prior knowledge of post deployment configuration. For security solutions requiring pair wise keys, it is impossible to decide how to distribute key pairs to sensor nodes before the deployment. Existing approaches to this problem are to assign more than one key, namely a key-chain, to each node. Key-chains are randomly drawn from a key-pool. Either two neighbouring nodes have a key in common in their key-chains, or there is a path, called key-path, among these two nodes where each pair of neighbouring nodes on this path has a key in common. Problem in such a solution is to decide on the key-chain size and key-pool size so that every pair of nodes can establish a session key directly or through a path with high probability. The size of the key-path is the key factor for the efficiency of the design. This paper presents novel, deterministic and hybrid approaches based on Combinatorial Design for key distribution. In particular, several block design techniques are considered for generating the key-chains and the key-pools. Comparison to probabilistic schemes shows that our combinatorial approach produces better connectivity with smaller key-chain sizes.

On the prediction of simultaneous inbreeding coefficients at multiple loci

A new deterministic method for predicting simultaneous inbreeding coefficients at three and four loci is presented. The method involves calculating the conditional probability of IBD (identical by descent) at one locus given IBD at other loci, and multiplying this probability by the prior probability of the latter loci being simultaneously IBD. The conditional probability is obtained applying a novel regression model, and the prior probability from the theory of digenic measures of Weir and Cockerham. The model was validated for a finite monoecious population mating at random, with a constant effective population size, and with or without selfing, and also for an infinite population with a constant intermediate proportion of selfing. We assumed discrete generations. Deterministic predictions were very accurate when compared with simulation results, and robust to alternative forms of implementation. These simultaneous inbreeding coefficients were more sensitive to changes in effective population size than in marker spacing. Extensions to predict simultaneous inbreeding coefficients at more than four loci are now possible.

Investigation of an inducible nitric oxide synthase gene (NOS2A) polymorphism in a multiple sclerosis population

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting most commonly the Caucasian population. Nitric oxide (NO) is a biological signaling and effector molecule and is especially important during inflammation. Inducible nitric oxide synthase (iNOS) is one of the three enzymes responsible for generating NO. It has been reported that there is an excessive production of NO in MS concordant with an increased expression of iNOS in MS lesions. This study investigated the role of a bi-allelic tetranucleotide polymorphism located in the promoter region of the human iNOS (NOS2A) gene in MS susceptibility. A group of MS patients (n = 101) were genotyped and compared to an age- and sex-matched group of healthy controls (n = 101). The MS group was subdivided into three subtypes, namely relapsing-remitting MS (RR-MS), secondary-progressive MS (SP-MS) and primary-progressive MS (PP-MS). Results of a chi-squared analysis and a Fisher's exact test revealed that allele and genotype distributions between cases and controls were not significantly different for the total population (chi(2) = 3.4, P(genotype) = 0.15; chi(2) = 3.4, P(allele) = 0.082) and for each subtype of MS (P > 0.05). This suggests that there is no direct association of this iNOS gene variant with MS susceptibility.

Transitions in taste in Vietnam and the diaspora

This paper argues that food and styles of eating have become the predominant markers of social change for the Vietnamese in both Vietnam and in the diaspora. In post-socialist Vietnam the transition to a market economy has allowed for a huge growth in the number of restaurants and cafes, and in the north, a return to an earlier style of cooking. The intense interest and emphasis on food as embodied pleasure has meant that it has come to stand for the transition away from a heavily state-controlled economy. The new configurations of family and friendship are being framed by newly available ways of ‘eating out’, which are both a means of social display and distinction as well as an indicator of the tensions between reform and festivity within an authoritarian nation-state struggling to define itself in a globalising world. At the same time as food in Vietnam is undergoing rapid transformation so too has the Vietnamese diaspora enerationally changed its eating patterns. Although there as been a focus in the literature on food in the diaspora that emphasises the nostalgic and recuperative elements of ‘migrant food’, I argue that food is the prime mechanism of intercultural engagement for each diasporic generation. For older Vietnamese, Vietnamese restaurants and barbecues have been the sites of interplay between cultural tradition’ and innovation, and between Australianness and Vietnameseness, and these interstitial places continue to be important for younger Vietnamese. Within this established framework of cross-cultural interaction, for Vietnamese youth, the social settings of ‘ethnic food’, eaten at home and shared with family, have been grafted onto a sociality of eating fast food. This melding together of both invention and convention, of transgression and ordinariness provides the background against which young people from migrant backgrounds are reinvigorating the social spaces of food consumption and in the process both e-enchanting and destabilising the notion of migrant food.

Clinico-pathological and biological prognostic factors in pleural malignant mesothelioma

In the UK mortality from malignant mesothelioma (MM) is likely to more than double over the next 20 years and despite advances in surgery, chemotherapy and radiation treatment the overall prognosis for patients remains poor. A number of scoring systems based on assessment of clinicopathological features of patients with the disease have been developed but the search continues for further prognostic indicators. Angiogenesis, tumour necrosis (TN), epidermal growth factor receptor (EGFR) expression, cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) have been linked with poor prognosis in some types of solid tumour and their relevance as prognostic factors in malignant mesothelioma is examined in this paper. © 2004 Elsevier Ireland Ltd. All rights reserved.

Postoperative chemotherapy for non-small cell lung cancer : a systematic review and meta-analysis

Background Postoperative chemotherapy is currently not recommended for resected non-small cell lung cancer in many countries and centers. Recently, results of several large randomized clinical trials were reported with conflicting evidence. Accordingly, we sought to determine whether postoperative chemotherapy is associated with improved survival compared with that after surgical intervention alone. Methods Randomized clinical trials with cisplatin- or uracil plus ftorafur-containing regimens were included and evaluated separately. A systematic review that included randomized clinical trials performed before 1995 was identified and found to be of adequate quality. Further randomized controlled trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trials Register from 1995 through 2004. In addition, the reference lists of articles and conference abstracts were searched. The logarithm of the hazard ratio and its standard error were calculated, and a fixed-effect model was used to combine the estimates. Results There were 7200 patients enrolled in 19 trials included in the analyses. An overall estimate of 13% relative reduction in mortality (95% confidence interval, 7%-19%) was found. There was 11% relative reduction in mortality associated with postoperative cisplatin (95% confidence interval, 4%-18%; P = .004) and 17% associated with uracil plus ftorafur (95% confidence interval, 5%-27%; P = .006) compared with that after surgical intervention alone. This means that there would be an additional survivor at 5 years for 25 patients treated with cisplatin or for 30 patients treated with uracil plus ftorafur. Conclusions Postoperative chemotherapy is associated with improved survival compared with that after surgical intervention alone. Selected patients with completely resected non-small cell lung cancer should be offered chemotherapy. Copyright © 2004 by The American Association for Thoracic Surgery.

Phase II trial of Oxaliplatin and 5-Fluorouracil/Leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy

Objective To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial. Methods Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 ≥ 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m 2) was given on day 1, and 5-Fluorouracil (370 mg/m 2) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle. Results Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months. Conclusion Oxaliplatin and 5-Fluorouracil/ Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer. © 2004 Elsevier Inc. All rights reserved.

Intranasal immunization with C. muridarum major outer membrane protein (MOMP) and cholera toxin elicits local production of neutralising IgA in the prostate

Successful control of sexually transmitted diseases (STDs) through vaccination will require the development of vaccine strategies that target protective immunity to both the female and male reproductive tracts (MRT). In the male, the immune privileged nature of the male reproductive tract provides a barrier to entry of serum immunoglobulins into the male reproductive ducts, thereby preventing the induction of protective immunity using conventional injectable vaccination techniques. In this study we investigated the potential of intranasal (IN) immunization to elicit anti-chlamydial immunity in BALB/c male mice. Intranasal immunization with Chlamydia muridarum major outer membrane protein (MOMP) admixed with cholera toxin (CT) resulted in high levels of MOMP-specific IgA in prostatic fluids (PF) and MOMP-specific IgA-secreting cells in the prostate. Prostatic fluid IgA inhibited in vitro infection of McCoy cells with C. muridarum. Using RT-PCR we also show that mRNA for the polymeric immunoglobulin receptor (PIgR), which transports IgA across mucosal epithelia, is expressed only in the prostate but not in other regions of the male reproductive ducts upstream of the prostate. These data suggest that using intranasal immunization to target IgA to the prostate may protect males against STDs while at the same time maintaining the state of immune privilege within the MRT.

The human topoisomerase I damage response plays a role in apoptosis

Previous studies have shown that human topoisomerase I cleavage complexes form as a response to various DNA damages in vivo, the so called human topoisomerase I “damage response”. It was suggested that this damage response may play a role in DNA repair as well as in apoptosis, but only very few investigations have been done and the significance of the damage response still remains unclear. Here we demonstrate that human topoisomerase I cleavage complexes induced by high doses of UV irradiation are highly stable for up to 48 h. Furthermore, we show that human topoisomerase I cleavage complexes correlate with apoptosis. However, at low UV doses the cleavage complex level was very low and the complexes were repaired. Surprisingly, we found that high levels of stable cleavage complexes were not only found in UV-irradiated cells but also in untreated cells that underwent apoptosis. A possible role of human topoisomerase I in apoptosis is discussed.

Motor Accident Insurance Act 1994 - reasonable excuse for delay in giving notice under s37

The decisions in Perdis v The Nominal Defendant [2003] QCA 555, Miller v the Nominal Defendant [2003] QCA 558 and Piper v the Nominal Defendant [2003] QCA 557 were handed down contemporaneously by the Queensland Court of Appeal on December 15 2003. They consider important issues as to the construction of key provisions of the Motor Accident Insurance Act 1994 (Qld)

The implicit structure of positive characteristics

The implicit structure of positive character traits was examined in two studies of 190 and 100 undergraduates. Participants judged the pairwise covariation or semantic similarity of 42 positive characteristics using a sorting or a rating task. Characteristics were drawn from a new classification of strengths and virtues, the Five-Factor Model, and a taxonomy of values. Participants showed consistent patterns of perceived association among the characteristics across the study conditions. Multidimensional scaling yielded three consistent dimensions underlying these judgments (“warmth vs. self-control,” “vivacity vs. decency,” and “wisdom vs. power”). Cluster analyses yielded six consistent groupings—“self-control,” “love,” “wisdom,” “drive,” “vivacity,” and “collaboration”—that corresponded only moderately to the virtue classification. All three taxonomies were systematically related to this implicit structure, but none captured it satisfactorily on its own. Revisions to positive psychology’s classification of strengths are proposed.

Composition of chemical attractants affects trap catches of the Australian sheep blowfly, lucilia cuprina, and other blowflies

Numbers of Lucilia cuprina (Australian sheep blowfly), Chrysomya spp., and Calliphora spp. blowflies caught on sticky traps baited with various synthetic attractants or a standard liver/sodium sulfide attractant in western Queensland were recorded. Numbers of each genus collected were influenced by the composition of the chemical attractants. Attractant mixtures based on 2-mercaptoethanol, indole, butanoic/pentanoic acid, and a sodium sulfide solution gave 5- to 20-fold higher L. cuprina catches than the liver standard. These blends attracted similar numbers of Chrysomya spp. (0.85–2.7× ) and fewer Calliphora spp. (0.02–0.2× ) compared to the liver standard. These synthetic attractants were more effective and selective for L. cuprina than the standard liver/sodium sulfide attractant, and they can be packaged in controlled-release dispensers to generate constant, prolonged release of the attractant.

Assessment of quality defects in macadamia kernels using NIR spectroscopy

Spectral data were collected of intact and ground kernels using 3 instruments (using Si-PbS, Si, and InGaAs detectors), operating over different areas of the spectrum (between 400 and 2500 nm) and employing transmittance, interactance, and reflectance sample presentation strategies. Kernels were assessed on the basis of oil and water content, and with respect to the defect categories of insect damage, rancidity, discoloration, mould growth, germination, and decomposition. Predictive model performance statistics for oil content models were acceptable on all instruments (R2 > 0.98; RMSECV < 2.5%, which is similar to reference analysis error), although that for the instrument employing reflectance optics was inferior to models developed for the instruments employing transmission optics. The spectral positions for calibration coefficients were consistent with absorbance due to the third overtones of CH2 stretching. Calibration models for moisture content in ground samples were acceptable on all instruments (R2 > 0.97; RMSECV < 0.2%), whereas calibration models for intact kernels were relatively poor. Calibration coefficients were more highly weighted around 1360, 740 and 840 nm, consistent with absorbance due to overtones of O-H stretching and combination. Intact kernels with brown centres or rancidity could be discriminated from each other and from sound kernels using principal component analysis. Part kernels affected by insect damage, discoloration, mould growth, germination, and decomposition could be discriminated from sound kernels. However, discrimination among these defect categories was not distinct and could not be validated on an independent set. It is concluded that there is good potential for a low cost Si photodiode array instrument to be employed to identify some quality defects of intact macadamia kernels and to quantify oil and moisture content of kernels in the process laboratory and for oil content in-line. Further work is required to examine the robustness of predictive models across different populations, including growing districts, cultivars and times of harvest.