Epidemiology of Non-small Cell Lung Cancer in Asian Americans: Incidence Patterns Among Six Subgroups by Nativity

BackgroundDifferences in the epidemiology of lung cancer between Asians and non-Hispanic whites have brought to light the relative influences of genetic and environmental factors on lung cancer risk. We set out to describe the epidemiology of non-small cell lung cancer (NSCLC) among Asians living in California, and to explore the effects of acculturation on lung cancer risk by comparing lung cancer rates between U.S.-born and foreign-born Asians.MethodsAge-adjusted incidence rates of NSCLC were calculated for Chinese, Filipino, Japanese, Korean, Vietnamese, and South Asians in California between 1988 and 2003 using data from the California Cancer Registry. Incidence rates were calculated and stratified by sex and nativity. We analyzed population-based tobacco smoking prevalence data to determine whether differences in rates were associated with prevalence of tobacco smoking.ResultsAsians have overall lower incidence rates of NSCLC compared with whites (29.8 and 57.7 per 100,000, respectively). South Asians have markedly low rates of NSCLC (12.0 per 100,000). Foreign-born Asian men and women have an approximately 35% higher rate of NSCLC than U.S.-born Asian men and women. The incidence pattern by nativity is consistent with the population prevalence of smoking among Asian men; however, among women, the prevalence of smoking is higher among U.S.-born, which is counter to their incidence patterns.ConclusionsForeign-born Asians have a higher rate of NSCLC than U.S.-born Asians, which may be due to environmental tobacco smoke or nontobacco exposures among women. South Asians have a remarkably low rate of NSCLC that approaches white levels among the U.S.-born. More studies with individual-level survey data are needed to identify the specific environmental factors associated with differential lung cancer risk occurring with acculturation among Asians

Display of a β-mannanase and a chitosanase on the cell surface of Lactobacillus plantarum towards the development of whole-cell biocatalysts

BACKGROUND: Lactobacillus plantarum is considered as a potential cell factory because of its GRAS (generally recognized as safe) status and long history of use in food applications. Its possible applications include in situ delivery of proteins to a host, based on its ability to persist at mucosal surfaces of the human intestine, and the production of food-related enzymes. By displaying different enzymes on the surface of L. plantarum cells these could be used as whole-cell biocatalysts for the production of oligosaccharides. In this present study, we aimed to express and display a mannanase and a chitosanase on the cell surface of L. plantarum. RESULTS: ManB, a mannanase from Bacillus licheniformis DSM13, and CsnA, a chitosanase from Bacillus subtilis ATCC 23857 were fused to different anchoring motifs of L. plantarum for covalent attachment to the cell surface, either via an N-terminal lipoprotein anchor (Lp_1261) or a C-terminal cell wall anchor (Lp_2578), and the resulting fusion proteins were expressed in L. plantarum WCFS1. The localization of the recombinant proteins on the bacterial cell surface was confirmed by flow cytometry and immunofluorescence microscopy. The highest mannanase and chitosanase activities obtained for displaying L. plantarum cells were 890 U and 1360 U g dry cell weight, respectively. In reactions with chitosan and galactomannans, L. plantarum CsnA- and ManB-displaying cells produced chito- and manno-oligosaccharides, respectively, as analyzed by high performance anion exchange chromatography (HPAEC) and mass spectrometry (MS). Surface-displayed ManB is able to break down galactomannan (LBG) into smaller manno-oligosaccharides, which can support growth of L. plantarum. CONCLUSION: This study shows that mannanolytic and chitinolytic enzymes can be anchored to the cell surface of L. plantarum in active forms. L. plantarum chitosanase- and mannanase-displaying cells should be of interest for the production of potentially ‘prebiotic’ oligosaccharides. This approach, with the enzyme of interest being displayed on the cell surface of a food-grade organism, may also be applied in production processes relevant for food industry

PGC-1 alpha Signaling Increases GABA(A) Receptor Subunit alpha 2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1 alpha expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of gamma-aminobutyric acid (GABA) type A receptor-alpha 2 subunit (GABAR alpha 2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1 alpha in neurons. Along with this, GABAR alpha 2 expression was enhanced in the hippocampus of the PGC-1 alpha Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABAR alpha 2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1 alpha Tg mice compared with controls. To study whether drugs acting on PPAR gamma can affect GABAR alpha 2, we employed pioglitazone that elevated GABAR alpha 2 expression in primary cultured neurons. Similar results were obtained using the specific PPAR gamma agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1 alpha regulates GABAR alpha 2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABAR alpha 2 expression via the PPAR gamma/PGC-1 alpha system.Peer reviewe

Breast, cervical, and colorectal cancer screening rates amongst female Cambodian, Somali, and Vietnamese immigrants in the USA

<p>Abstract</p> <p>Introduction</p> <p>Minority women, particularly immigrants, have lower cancer screening rates than Caucasian women, but little else is known about cancer screening among immigrant women. Our objective was to assess breast, cervical, and colorectal cancer screening rates among immigrant women from Cambodia, Somalia, and Vietnam and explore screening barriers.</p> <p>Methods</p> <p>We measured screening rates by systematic chart review (N = 100) and qualitatively explored screening barriers via face-to-face questionnaire (N = 15) of women aged 50–75 from Cambodia, Somalia, and Vietnam attending a general medicine clinic (Portland, Maine, USA).</p> <p>Results</p> <p><it>Chart Review </it>– Somali women were at higher risk of being unscreened for breast, cervical, and colorectal cancer compared with Cambodian and Vietnamese women. A longer period of US residency was associated with being screened for colorectal cancer. We observed a 7% (OR 1.07, 95% CI 1.01–1.13, p = 0.01) increase in the odds that a woman would undergo a fecal occult blood test for each additional year in the US, and a 39% increase in the odds of a woman being screened by colonoscopy or flexible sigmoidoscopy for every five years of additional US residence (OR 1.39, 95% CI 1.21–1.61, p = 0.02). We did not observe statistically significant relationships between odds of being screened by mammography, clinical breast exam or papanicolaou test according to years in the US. <it>Questionnaire </it>– We identified several barriers to breast, cervical, and colorectal cancer screening, including discomfort with exams conducted by male physicians.</p> <p>Discussion</p> <p>Somali women were less likely to be screened for breast, cervical, and colorectal cancer than Cambodian and Vietnamese women in this population, and uptake of colorectal cancer screening is associated with years of residency in this country. Future efforts to improve equity in cancer screening among immigrants may require both provider and community education.</p

Potential effects of oilseed rape expressing oryzacystatin-1 (OC-1) and of purified insecticidal proteins on larvae of the solitary bee Osmia bicornis

Despite their importance as pollinators in crops and wild plants, solitary bees have not previously been included in non-target testing of insect-resistant transgenic crop plants. Larvae of many solitary bees feed almost exclusively on pollen and thus could be highly exposed to transgene products expressed in the pollen. The potential effects of pollen from oilseed rape expressing the cysteine protease inhibitor oryzacystatin-1 (OC-1) were investigated on larvae of the solitary bee Osmia bicornis (= O. rufa). Furthermore, recombinant OC-1 (rOC-1), the Bt toxin Cry1Ab and the snowdrop lectin Galanthus nivalis agglutinin (GNA) were evaluated for effects on the life history parameters of this important pollinator. Pollen provisions from transgenic OC-1 oilseed rape did not affect overall development. Similarly, high doses of rOC-1 and Cry1Ab as well as a low dose of GNA failed to cause any significant effects. However, a high dose of GNA (0.1%) in the larval diet resulted in significantly increased development time and reduced efficiency in conversion of pollen food into larval body weight. Our results suggest that OC-1 and Cry1Ab expressing transgenic crops would pose a negligible risk for O. bicornis larvae, whereas GNA expressing plants could cause detrimental effects, but only if bees were exposed to high levels of the protein. The described bioassay with bee brood is not only suitable for early tier non-target tests of transgenic plants, but also has broader applicability to other crop protection products

Establishing induced pluripotent stem cell lines from two dominant optic atrophy patients with distinct OPA1 mutations and clinical pathologies

Dominant optic atrophy (DOA) is an inherited disease that leads to the loss of retinal ganglion cells (RGCs), the projection neurons that relay visual information from the retina to the brain through the optic nerve. The majority of DOA cases can be attributed to mutations in optic atrophy 1 (OPA1), a nuclear gene encoding a mitochondrial-targeted protein that plays important roles in maintaining mitochondrial structure, dynamics, and bioenergetics. Although OPA1 is ubiquitously expressed in all human tissues, RGCs appear to be the primary cell type affected by OPA1 mutations. DOA has not been extensively studied in human RGCs due to the general unavailability of retinal tissues. However, recent advances in stem cell biology have made it possible to produce human RGCs from pluripotent stem cells (PSCs). To aid in establishing DOA disease models based on human PSC-derived RGCs, we have generated iPSC lines from two DOA patients who carry distinct OPA1 mutations and present very different disease symptoms. Studies using these OPA1 mutant RGCs can be correlated with clinical features in the patients to provide insights into DOA disease mechanisms

Miles to go (mtgo) encodes FNDC3 proteins that interact with the chaperonin subunit CCT3 and are required for NMJ branching and growth in Drosophila.

Analysis of mutants that affect formation and function of the Drosophila larval neuromuscular junction (NMJ) has provided valuable insight into genes required for neuronal branching and synaptic growth. We report that NMJ development in Drosophila requires both the Drosophila ortholog of FNDC3 genes; CG42389 (herein referred to as miles to go; mtgo), and CCT3, which encodes a chaperonin complex subunit. Loss of mtgo function causes late pupal lethality with most animals unable to escape the pupal case, while rare escapers exhibit an ataxic gait and reduced lifespan. NMJs in mtgo mutant larvae have dramatically reduced branching and growth and fewer synaptic boutons compared with control animals. Mutant larvae show normal locomotion but display an abnormal self-righting response and chemosensory deficits that suggest additional functions of mtgo within the nervous system. The pharate lethality in mtgo mutants can be rescued by both low-level pan- and neuronal-, but not muscle-specific expression of a mtgo transgene, supporting a neuronal-intrinsic requirement for mtgo in NMJ development. Mtgo encodes three similar proteins whose domain structure is most closely related to the vertebrate intracellular cytosolic membrane-anchored fibronectin type-III domain-containing protein 3 (FNDC3) protein family. Mtgo physically and genetically interacts with Drosophila CCT3, which encodes a subunit of the TRiC/CCT chaperonin complex required for maturation of actin, tubulin and other substrates. Drosophila larvae heterozygous for a mutation in CCT3 that reduces binding between CCT3 and MTGO also show abnormal NMJ development similar to that observed in mtgo null mutants. Hence, the intracellular FNDC3-ortholog MTGO and CCT3 can form a macromolecular complex, and are both required for NMJ development in Drosophila

Nonmuscle myosins II-B and Va are components of detergentresistant membrane skeletons derived from mouse forebrain

Myosins are actin-based molecular motors that may have specialized trafficking and contractile functions in cytoskeletal compartments that lack microtubules. The postsynaptic excitatory synapse is one such specialization, yet little is known about the spatial organization of myosin motor proteins in the mature brain. We used a proteomics approach to determine if class II and class V myosin isoforms are associated with Triton X-100-resistant membranes isolated from mouse forebrain. Two nonmuscle myosin isoforms (II-B and Va), were identified as components of lipid raft fractions that also contained typical membrane skeletal proteins such as non-erythrocyte spectrins, actin, alpha-actinin-2 and tubulin subunits. Other raft-associated proteins included lipid raft markers, proteins involved in cell adhesion and membrane dynamics, receptors and channels including glutamate receptor subunits, scaffolding and regulatory proteins. Myosin II-B and Va were also present in standard postsynaptic density (PSD) fractions, however retention of myosin II-B was strongly influenced by ATP status. If homogenates were supplemented with ATP, myosin II-B could be extracted from PSD I whereas myosin Va and other postsynaptic proteins were resistant to extraction. In summary, both myosin isoforms are components of a raft-associated membrane skeleton and are likely detected in standard PSD fractions as a result of their intrinsic ability to form actomyosin. Myosin IIB, however, is loosely or more peripherally associated with the PSD than myosin Va, which appears to be a core PSD protein.Keywords: lipid raft, mass spectrometry, actin cytoskeleton, proteomics, postsynaptic density, myosin II, myosin