Lifetime Smoking History and Cause-Specific Mortality in a Cohort Study with 43 Years of Follow-Up

BackgroundIn general, smoking increases the risk of mortality. However, it is less clear how the relative risk varies by cause of death. The exact impact of changes in smoking habits throughout life on different mortality risks is less studied.MethodsWe studied the impact of baseline and lifetime smoking habits, and duration of smoking on the risk of all-cause mortality, mortality of cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), any cancer and of the four most common types of cancer (lung, colorectal, prostate, and breast cancer) in a cohort study (Vlagtwedde-Vlaardingen 1965–1990, with a follow-up on mortality status until 2009, n = 8,645). We used Cox regression models adjusted for age, BMI, sex, and place of residence. Since previous studies suggested a potential effect modification of sex, we additionally stratified by sex and tested for interactions. In addition, to determine which cause of death carried the highest risk we performed competing-risk analyses on mortality due to CVD, cancer, COPD and other causes.ResultsCurrent smoking (light, moderate, and heavy cigarette smoking) and lifetime persistent smoking were associated with an increased risk of all-cause, CVD, COPD, any cancer, and lung cancer mortality. Higher numbers of pack years at baseline were associated with an increased risk of all-cause, CVD, COPD, any cancer, lung, colorectal, and prostate cancer mortality. Males who were lifetime persistent pipe/cigar smokers had a higher risk of lung cancer [HR (95% CI) = 7.72 (1.72–34.75)] as well as all-cause and any cancer mortality. A longer duration of smoking was associated with a higher risk of COPD, any and lung cancer [HR (95% CI) = 1.06 (1.00–1.12), 1.03 (1.00–1.06) and 1.10 (1.03–1.17) respectively], but not with other mortality causes. The competing risk analyses showed that ex- and current smokers had a higher risk of cancer, CVD, and COPD mortality compared to all other mortality causes. In addition, heavy smokers had a higher risk for COPD mortality compared to cancer, and CVD mortality.ConclusionOur study indicates that lifetime numbers of cigarettes smoked and the duration of smoking have different impacts for different causes of mortality. Moreover, our findings emphasize the importance of smoking-related competing risks when studying the smoking-related cancer mortality in a general population and that smoking cessation immediately effectively reduces the risk of all-cause and any cancer mortality.     

Recombinational repair is critical for survival of Escherichia coli exposed to nitric oxide

Nitric oxide (NO(.)) is critical to numerous biological processes, including signal transduction and macrophage-mediated immunity. In this study, we have explored the biological effects of NO(.)-induced DNA damage on Escherichia coli. The relative importance of base excision repair, nucleotide excision repair (NER), and recombinational repair in preventing NO(.)-induced toxicity was determined. E. coli strains lacking either NER or DNA glycosylases (including those that repair alkylation damage [alkA tag strain], oxidative damage [fpg nei nth strain], and deaminated cytosine [ung strain]) showed essentially wild-type levels of NO(.) resistance. However, apyrimidinic/apurinic (AP) endonuclease-deficient cells (xth nfo strain) were very sensitive to killing by NO(.), which indicates that normal processing of abasic sites is critical for defense against NO(.). In addition, recA mutant cells were exquisitely sensitive to NO(.)-induced killing. Both SOS-deficient (lexA3) and Holliday junction resolvase-deficient (ruvC) cells were very sensitive to NO(.), indicating that both SOS and recombinational repair play important roles in defense against NO(.). Furthermore, strains specifically lacking double-strand end repair (recBCD strains) were very sensitive to NO(.), which suggests that NO(.) exposure leads to the formation of double-strand ends. One consequence of these double-strand ends is that NO(.) induces homologous recombination at a genetically engineered substrate. Taken together, it is now clear that, in addition to the known point mutagenic effects of NO(.), it is also important to consider recombination events among the spectrum of genetic changes that NO(. ) can induce. Furthermore, the importance of recombinational repair for cellular survival of NO(.) exposure reveals a potential susceptibility factor for invading microbes.     

Biochemical activities of Iranian Mentha piperita L. and Myrtus communis L. essential oils

GC-MS analysis of essential oils of Iranian Mentha piperita and Myrtus communis extracted by hydrodistillation lead to identification of 26 and 32 compounds, respectively. The oils had good to excellent antimicrobial activities against Escherichia coli, Staphylococcus aureus and Candida albicans with the oil of M. piperita being more active. The findings suggest feasibility of application of M. piperita oil in treatment of the infections caused by C. albicans and E. coli. D-values on exposure to M. piperita and Myrtus communis oils were (2.14 and 2.8min), (1.4 and 12.8min) and (4.3 and 8.6min) for E. coli, S. aureus and C. albicans , respectively. The oils were screened for their possible antioxidant activities by two complementary test systems, namely DPPH free radical scavenging and beta-carotene/linoleic acid systems. M. piperirta oil exerted greater antioxidant activity than that of M. communis. Phytochemical and phytobiological characteristics of these oils may lead to extraction and production of active compounds in single or combined forms with useful applications.     

Small-scale spatial structure within patterns of seed dispersal

A large proportion of dispersing propagules land near their maternal plant, even in species that have evolved structures which enhance dispersal. For these propagules, their post-dispersal spatial pattern is likely to reflect the overall shape and scale of the parental plant canopy and, especially in poorly dispersing species, aggregation of propagules on the plant prior to dispersal. Localised patterns within seed shadows are also likely to be affected by secondary movement after dispersal, leading to either more or less small-scale aggregation, depending on the mechanism. Our general aim was to study the small-scale spatial structure within patterns of seed dispersal of Raphanus raphanistrum L. to generate hypotheses about the sequence of processes and events leading to the spatial pattern of dispersal in this species. More specifically, we determined the sizes of small-scale structures within the seed shadows on the ground after dispersal and the extent to which these match the sizes of pre-dispersal aggregations within the parental canopy. Variation in plant size and shape was provided by four levels of inter-specific competition resulting from differing wheat crop densities. Positions of propagules were determined using a three-dimensional digitizer, and the data for each plant were analysed using point pattern analysis. Not surprisingly, larger plants, growing at lower plant density, had larger seed shadows, showing an overall influence of maternal plant size. The pattern of propagules exhibited significant small-scale aggregates, with similar sizes on the plant and on the ground. There was no evidence that aggregation size was greater on the ground or increased with time, but the strength of the aggregation increased with length of time on the ground.     

Influence of temperature on life-table parameters of Stethorus gilvifrons (Mulsant) (Coleoptera: Coccinellidae) fed on Tetranychus urticae Koch

The influence of temperature on life-table parameters, fecundity and survivorship of the predatory ladybird, Stethorus gilvifrons , fed on Tetranychus urticae was determined at seven constant temperatures of 15°C, 20°C, 25°C, 28°C, 30°C, 35°C and 40°C. No development was observed at 40°C, thus being regarded as the threshold for the development of S. gilvifrons . The results indicate a significant decrease in male and female longevity with increasing temperature from 15°C to 35°C. The longest and shortest longevity were 18.40 and 12.75 days for males and 17.40 and 8.80 days for females, respectively. The intrinsic rate of natural increase ( r _m ) and the net reproductive rate ( R ₀) of S. gilvifrons linearly increased with increasing temperatures from 15°C to 35°C, while the mean generation time ( T ) and doubling time (DT) decreased linearly within this temperature range. The highest values of r _m (0.240 females/female/day) and R ₀ (59.27 females/female) and the lowest mean generation time (17.01 days) and DT (2.88 days) were recorded at 35°C. The maximum (185.50 eggs) and minimum (25.50 eggs) measurement of total fecundity was also recorded at 35°C and 15°C, respectively. The results indicate that temperature greatly affected fecundity, survivorship and life-table parameters of S. gilvifrons , and that 35°C is a suitable temperature for population growth of this predator.     

Curcumin: A new candidate for retinal disease therapy?

The retina is the neural portion and light-sensitive layer of the eye, which has been observed in most of the vertebrates. The retina is composed of light-sensitive cells that absorb light and convert it into neural signals. These signals are sent to the brain for visual recognition. It has been shown that many pathogenesis conditions, including inflammation, angiogenesis, oxidative stress, and imbalanced histone modifications in the retina are associated with initiation and progression of retinal diseases (ie, glaucoma, diabetic retinopathy, and age-related macular degeneration). Currently available treatments include laser surgery, freezing, stem-cell therapy, shrinking abnormal blood vessels. It has some limitations, such as invasive methods, high costs, and many side effects. Hence, finding a new therapeutic platform for stopping or slowing of the disease progression is required. Curcumin is a natural product, which is associated with a wide range of properties, such as antioxidant, anti-inflammatory, antiangiogenic, and antitumor activates. It exerts therapeutic effects via activation/inhibition cellular and molecular targets involved in various diseases, such as retinal diseases. Increasing evidence revealed that curcumin can be used as a therapeutic option in the treatment of different retinal diseases. Here, we summarized various clinical and preclinical studies that used curcumin as a therapeutic agent in the treatment of retinal disorders.     

Synthesis and evaluation of arylalkoxy- and biarylalkoxy-phenylamide and phenylimidazoles as potent and selective sphingosine-1-phosphate receptor subtype-1 agonists

In pursuit of potent and selective sphingosine-1-phosphate receptor agonists, we have utilized previously reported phenylamide and phenylimidazole scaffolds to explore extensive side-chain modifications to generate new molecular entities. A number of designed molecules demonstrate good selectivity and excellent in vitro and in vivo potency in both mouse and rat models. Oral administration of the lead molecule 11c (PPI-4667) demonstrated potent and dose-responsive lymphopenia.     

Ultrastructure and osmoregulatory function of the kidney in larvae of the Persian sturgeon Acipenser persicus

The localization of Na(+) , K(+) -ATPase (NKA) and the ultrastructural features of kidney were examined in larvae of the Persian sturgeon Acipenser persicus (L 31-41 mm total length and 182·3-417·3 mg). Investigations were conducted through light and electron microscopy and through immunofluorescence for NKA detection. The kidney nephrons consisted of a large glomerulus and tubules (neck, proximal, distal and collecting), which connected to the ureters. Posteriorly, ureters extended and joined together into a thin-walled ureter terminal sac. Ultrastructurally, the glomerular cells (podocytes) possessed distinctive pedicels that extended to the basal membrane. The proximal tubule (PT) showed two different cells. The cells lining the anterior part of PT possessed apical tall microvilli (c. 2·7 μm), a sub-apical tubular system, a basal nucleus and dense granules. Posteriorly in the cells, the sub-apical tubular system and granules were absent and round mitochondria associated with basolateral infoldings were found; the apical microvilli were reduced. Distal and collecting tubular cells showed the typical features of osmoregulatory cells, i.e. well-developed basolateral infoldings associated with numerous mitochondria. No immunofluorescence of NKA was detected in the glomeruli. A weak immunostaining was observed at the basolateral side of the cells lining the neck and PT. A strong immunostaining of NKA was observed in the entire cells of the distal tubules, collecting tubules and in some isolated cells of the ureters. In all immunostained cells, the basolateral region showed a much higher fluorescence and nuclei were immunonegative. In conclusion, the epithelial cells of kidney tubules had morphological and enzymatic features of ionocytes, particularly in the distal and collecting tubules. Thus, the kidney of A. persicus larvae possesses active ion exchange capabilities and, beside its implication in excretion, participates in osmoregulation.     

CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells

Background

A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.

Methods/Findings

We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.

Conclusions/Significance

The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.