Effects of temperature and rainfall variation on population structure and sexual dimorphism across the geographical range of a dioecious species

The effects of climate (precipitation and temperature) on sexual dimorphism and population structure were analysed along a broad-scale environmental gradient covering the distributional range of the endemic dioecious species Corema album, along the west coast of the Iberian Peninsula. We aimed to assess distribution constraints and sex-related differences in demography and size associated with higher reproductive investment in females. Nine populations were chosen from across the geographic range of C. album and ten 10 × 10 m plots were established (10 m apart) along a 200-m transect. All male, female and non-reproductive shrubs were quantified within each plot and plant size, photosynthetic layer, height, sex ratio, population density and structure, and spatial segregation of sexes, under environmental conditions ranging from temperate to Mediterranean climate, were recorded and analysed. Increased aridity was related to lower population density and less structured populations, indicating an effect of higher temperature and lower precipitation on regeneration. Sexual dimorphism was influenced by climate, with size differences between sexes varying with aridity. However, demographic differences between sexes reflected in sex ratio deviations or the occurrence of spatial segregation were unrelated to any climatic variable, suggesting the existence of compensatory mechanisms that may counterbalance the higher reproductive effort of female plants. The results show the vulnerability of this endemic species to the increase in aridity expected in the southernmost limit of the biogeographical area due to global climate change, and demonstrate the importance of broad scale studies in the assessment of sexual dimorphism.     

Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: a basis for tumor-promoting interactions

The chemokines RANTES (CCL5) and MCP-1 (CCL2) were suggested to contribute, independently, to breast malignancy. In the present study, we asked if the two chemokines are jointly expressed in clinical samples of breast cancer patients, and do they interact in breast tumor cells. We found that RANTES and MCP-1 were expressed by breast tumor cells in primary tumors of Ductal Carcinoma In Situ and of Invasive Ductal Carcinoma, but minimally in normal breast epithelial duct cells. The chemokines were also detected in metastases and pleural effusions. Novel findings showed that co-expression of RANTES and MCP-1 in the same tumor was associated with more advanced stages of disease, suggesting that breast tumors "benefit" from interactions between the two chemokines. Accordingly, MCP-1 significantly promoted the release of RANTES from endogenous pre-made vesicles, in an active process that depended on calcium from intracellular and extracellular sources, and on intracellular transport of RANTES towards exocytosis. Our findings show a chemokine-triggered release of stored pro-malignancy chemokine from breast tumor cells. These observations support a major tumor-promoting role for co-expression of the chemokines in breast malignancy, and agree with the significant association of joint RANTES and MCP-1 expression with advanced stages of breast cancer.     

STAG2 and Rad21 mammalian mitotic cohesins are implicated in meiosis

STAG/SA proteins are specific cohesin complex subunits that maintain sister chromatid cohesion in mitosis and meiosis. Two members of this family, STAG1/SA1 and STAG2/SA2,double dagger are classified as mitotic cohesins, as they are found in human somatic cells and in Xenopus laevis as components of the cohesin(SA1) and cohesin(SA2) complexes, in which the shared subunits are Rad21/SCC1, SMC1 and SMC3 proteins. A recently reported third family member, STAG3, is germinal cell-specific and is a subunit of the meiotic cohesin complex. To date, the meiosis-specific cohesin complex has been considered to be responsible for sister chromatid cohesion during meiosis. We studied replacement of the mitotic by the meiotic cohesin complex during mouse germinal cell maturation, and we show that mammalian STAG2 and Rad21 are also involved in several meiosis stages. Immunofluorescence results suggest that a cohesin complex containing Rad21 and STAG2 cooperates with a STAG3-specific complex to maintain sister chromatid cohesion during the diplotene stage of meiosis.     

Synthesis and biological properties of chimeric interferon-alpha2b peptides

We have previously reported the antiproliferative activity of synthetic sequences 29-35 and 122-139 of the interferon-alpha2b (IFN-alpha2b), both probably representing a common receptor recognition domain. In the search of new peptidic agonists, we designed and synthesized the linear peptide (Gly)2-122-137-Gly138-Gly29-30-35-(Gly)2, in which Gly residues replaced the 138 and 29 Cys bound through a disulfide bridge in the native cytokine. Additionally, a cyclic analog was obtained by reaction of the N- and C-terminal ends of the linear fragment. Thus, the distance that separates residues 122 and 35 in the crystalline structure of the IFN-alpha2b was maintained through a (Gly)4 bridge. When the influence of chimeric peptides on the proliferation of WISH cells was studied, it was shown that both derivatives significantly diminished cell growth. A more evident inhibitory effect on (125)I-IFN-alpha2b binding to WISH cell-membrane receptors was observed for both peptides. Results indicated that chimeric IFN-alpha2b peptides behaved as partial agonists of the IFN-alpha2b molecule and may be of interest for drug design purposes.     

Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

In Leishmania amazonensis, kinetoplastid membrane protein-11 (KMP-11) expression increases during meta-cyclogenesis and is higher in amastigotes than in promastigotes, suggesting a role for this protein in the infection of the mammalian host. We show that the addition of KMP-11 exacerbates L. amazonensis infection in peritoneal macrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducing nitric oxide (NO) production. The doses of KMP-11, the IL-10 levels and the intracellular amastigote loads were strongly, positively and significantly correlated. The increase in parasite load induced by KMP-11 was inhibited by anti-KMP-11 or anti-IL-10 neutralising antibodies, but not by isotype controls. The neutralising antibodies, but not the isotype controls, were also able to significantly decrease the parasite load in macrophages cultured without the addition of KMP-11, demonstrating that KMP-11-induced exacerbation of the infection is not dependent on the addition of exogenous KMP-11 and that the protein naturally expressed by the parasite is able to promote it. In this study, the exacerbating effect of KMP-11 on macrophage infection with Leishmania is for the first time demonstrated, implicating it as a virulence factor in L. amazonensis. The stimulation of IL-10 production and arginase activity and the inhibition of NO synthesis are likely involved in this effect.     

The dynamics of tent‐roosts in the palm Sabal mauritiiformis and their use by bats in a montane dry forest

Tent‐making bats modify leaves to build refuges. Leaf modification involves energetic and defense costs that should be balanced by the benefits of tent‐roosting. The alteration of the leaf's vascular system reduces the tent's life expectancy, so to obtain a benefit, bats are expected to use tents regularly as long as they remain functional and not modify more leaves than necessary. Over 2 yr, we documented the dynamics of tent construction and use by Uroderma convexum and other bat species in the palm Sabal mauritiiformis in a Colombian transitional dry forest. We also assessed tent condition and compared it to nonmodified leaves of approximately the same age in focal palms. Probability of tent use by U. convexum varied between 57 percent during a reproductive period and 4 percent outside of this period. Bats cut the main vein of folioles, partially affecting water transport in the leaf. However, there were no differences between tents and nonmodified leaves in deterioration scores or deterioration rates over 1 yr. During 2 yr, 48 tents were lost for different causes, but this loss was balanced by the construction of 51 new tents. Thus, bats maintained an excess of usable tents. Palm leaves are long‐lived and seem preadapted to sustain damage and remain viable, particularly in species growing in dry environments. We present several hypotheses to explain the advantage of maintaining a tent surplus.     

FMR1 CGG repeat distribution and linked microsatellite-SNP haplotypes in normal Mexican Mestizo and indigenous populations

The (CGG)n repeat size distribution in the FMR1 gene was studied in healthy individuals: 80 X chromosomes of Mexican Mestizos from Mexico City and 33 X chromosomes of Mexican Amerindians from three indigenous communities (Purepechas, Nahuas, and Tzeltales), along with alleles and haplotypes defined by two microsatellite polymorphic markers (DXS548 and FRAXAC1) and two single nucleotide polymorphisms (FMRA and FMRB). Genetic frequencies of Mestizo and Amerindian subpopulations were statistically similar in almost all cases and thus were considered one population for comparisons with other populations. Sixteen (CGG)n alleles in the 17-38 size range were observed, and the most common were the 25 (38.0%), 26 (28.3%), and 24 (12.3%) repeat alleles. This pattern differs from most other populations reported, but a closer relation to Amerindian, European, and African populations was found, as expected from the historical admixture that gave rise to Mexican Mestizos. The results of the CA repeats analysis at DXS548-FRAXAC1 were restricted to nine haplotypes, of which haplotypes 7-4 (52.2%), 8-4 (23.8%), and 7-3 (11.5%) were predominant. The modal haplotype 7-4, instead of the nearly universal haplotype 7-3, had been reported exclusively in Eastern Asian populations. Likewise, only seven different FRAXAC1-FMRA-FMRB haplotypes were observed, including five novel haplotypes (3TA, 4TA, 3 - A, 4 - A, and 5 - A), compared with Caucasians. Of these, haplotypes - A (78.7%) and 3 - A (13.2%) were the most common in the Mexican population. These data suggest a singular but relatively low genetic diversity at FMR1 in the studied Mexican populations that may be related to the recent origin of Mestizos and the low admixture rate of Amerindians.     

Effect of C282Y Genotype on Self-Reported Musculoskeletal Complications in Hereditary Hemochromatosis

Objective

Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype.

Methods

A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status.

Results

In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2–5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1–12.1]).

Conclusion

Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.     

Insulin and Non-esterified Fatty Acid Metabolism in Asymptomatic Diabetics and Atherosclerotic Subjects

Glucose, insulin and non-esterified fatty acid (NEFA) metabolism was studied in 18 patients (mean age 49) with ischemic heart disease (IHD) who did not have any concurrent disorder known to affect glucose tolerance.Significant hyperglycemia and hyperinsulinemia were observed in the IHD patients after oral glucose. The serum NEFA declined to a lower level in IHD patients than in normal subjects who received glucose.In response to hypoglycemia following the oral administration of sodium tolbutamide the serum NEFA in IHD patients rose to a higher level in the rebound phase than in normal subjects. This rise was preceded by a sharp decline in the concentration of circulating insulin.In 72% of the patients (IHD sub-group) the blood glucose values after oral glucose satisfied the criteria for the diagnosis of diabetes mellitus. The metabolic changes following oral glucose in the IHD sub-group and in asymptomatic diabetics (AD), free of clinical atherosclerosis and with similar impairment in glucose tolerance, were compared. Despite insignificantly lower insulin concentrations, the AD showed a significantly lesser fall in circulating NEFA than did the patients in the IHD sub-group. After oral sodium tolbutamide the IHD sub-group patients showed a greater insulin response and a greater rebound increase in circulating NEFA than did the AD.These differences in response to oral glucose and to sodium tolbutamide suggest that the pathogenesis of the impaired glucose tolerance in IHD may be different from that responsible for abnormal carbohydrate tolerance in asymptomatic diabetics without evident atherosclerosis. The abnormalities demonstrated in glucose, insulin and NEFA metabolism may play a role in the genesis of the hyperlipoproteinemia and atherosclerosis of IHD. One possible mechanism leading to hyperlipoproteinemia in ischemic heart disease compatible with the data is discussed.