Seasonality of marriages in sardinian pastoral and agricultural communities in the nineteenth century

The study of marriage seasonality of populations with different socioeconomic backgrounds may contribute to the better understanding their reproductive behaviours. This study analyses the monthly distribution of marriages in the 19th century in four agricultural villages and four pastoral villages on the island of Sardinia (Italy). The data were derived from 7340 marriage acts (3571 for the four agricultural villages and 3769 for the four pastoral villages). The aim is to ascertain whether the Sardinian agricultural and pastoral communities followed the matrimonial models reported for contemporary Italy and Europe and whether there was a change in the monthly distribution of marriages between the two halves of the 19th century. The results suggest that the marriage seasonality of the Sardinian farmers and shepherds was very similar to the patterns shown in the 19th century by Italian and European agricultural and pastoral communities. The Sardinian farmers preferred to marry in autumn-winter, while the Sardinian shepherds had a very high concentration of marriages in summer-autumn. Both communities avoided marriages in the Advent and Easter periods and in the month of May (dedicated to the Virgin Mary), and the farmers also in August (also dedicated to the Virgin Mary). Despite a certain seasonal stability, there was a significant change in the monthly distribution of marriages between the two halves of the 19th century in both the agricultural and pastoral communities, probably due to a series of laws that transformed the centuries-old socioeconomic system of Sardinia in the second half of the century.     

Candidate genes and sensory functions in health and irritable bowel syndrome

Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including alpha2A (C-1291G), alpha2C (Del 332-325), GNbeta3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GNbeta3 was associated only with fasting GV; we did not detect associations between alpha2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GNbeta3 with fasting GV may explain, in part, the reported association of GNbeta3 with dyspepsia.     

Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation

Cannabinoid agonist inhibits gastrointestinal motility. The endocannabinoid, anandamide, is inactivated by fatty acid amide hydrolase (FAAH). A single nucleotide polymorphism in the human FAAH gene (C385A) reduces FAAH expression. Our aim was to evaluate associations between FAAH genotype variation and symptom phenotype, gastric emptying and volume, colonic transit, and rectal sensation in patients with functional gastrointestinal disorders (FGID). 482 FGID patients [Rome II positive, 159 constipation disorders, 184 diarrhea disorders (D-IBS), 86 mixed bowel function (M-IBS), 20 chronic abdominal pain (CAP), 33 functional dyspepsia], and 252 healthy volunteers (HV) underwent questionnaires and studies of phenotype and genotype from 2000 to 2007: 250 gastric emptying, 210 fasting and postprandial gastric volume, 152 colonic transit, and 123 rectal sensation. All had FAAH genotype [CC vs. polymorphic (CA/AA)] determined by TaqMan. FAAH genotype distribution of FGID patients and HV did not deviate from Hardy-Weinberg equilibrium. There was a significant association of FAAH genotype with FGID phenotype (overall chi(2), P = 0.011) and with specific individual phenotypes (P = 0.048). Thus FAAH CA/AA increases the odds (relative to HV) for D-IBS (P = 0.008), M-IBS (P = 0.012), and, possibly, CAP (P = 0.055). There was a significant association of FAAH CA/AA genotype with accelerated colonic transit in D-IBS (P = 0.037). There was no association of FAAH genotype with rectal sensation thresholds or ratings. The association of genetic variation in metabolism of endocannabinoids with symptom phenotype in D-IBS and M-IBS and with faster colonic transit in D-IBS supports the hypothesis that cannabinoid mechanisms may play a role in the control of colonic motility in humans and deserve further study.     

Synthesis and cytotoxic activity of heterocyclic ring-substituted betulinic acid derivatives

A new series of betulinic acid derivatives have been synthesized by introducing heterocyclic ring between C-2 and C-3 positions of betulinic acid. Further modifications were also carried out by reduction of C-20(29) unsaturated bond and substitution of C-28 carboxyl group by ester and amide linkage to enhance the selectivity. Compound 11 resulted in IC(50) of 2.44, 2.5, and 2.7 microg/ml on MIAPaCa, PA-1, and SW620 cancer cell lines, respectively. Compound 38 resulted in IC(50) of 0.67 microg/ml on MIAPaCa cell line.     

Phylogeny of the Brachytheciaceae (Bryophyta) based on morphology and sequence level data

Brachytheciaceae is often considered a taxonomically difficult group of mosses. For example, morphological variation has led to difficulty in generic delimitation. We used DNA sequence data (chloroplast psbT‐H and trnL‐F and nuclear ITS2) together with morphology (63 characters) to examine the relationships within this family. The combined unaligned length of the DNA sequences used in the phylogenetic analyses varied between 1277 and 1343 bp. For phylogeny reconstruction we performed direct optimization, as implemented in POY. Analyses were performed with three different gap costs and the morphological data partition was weighted both: (1) equal to gap cost, and (2) with a weight of one. The utility of sensitivity analysis has recently been cast into doubt; hence in this study it was performed only to explore the effects of weighting on homology statements and topologies and to enable more detailed comparisons between earlier studies utilizing the direct optimization method. The wide sequence length variation of non‐coding ITS2 sequences resulted in character optimizations (i.e., “alignments”) of very different lengths when various gap costs were applied. Despite this variation, the topologies of equally parsimonious trees remained fairly stable. The inclusion of several outgroups, instead of only one, was observed to increase the congruence between data sets and to slightly increase the resolution. An inversion event in the 9 bp loop region in the chloroplast psbT‐N spacer in mosses has been postulated to include only uninformative variation, thus possibly negatively impacting the phylogeny reconstruction. Despite this inversion, its variation within Brachytheciaceae was clearly congruent with information from other sources, but inclusion of these 9 bp in the analysis had only a minor effect on the phylogenetic results. In the most parsimonious topology, which was obtained with equal weighting of all data, Meteoriaceae and Brachytheciaceae were resolved as monophyletic sister groups, which had recently been suggested based on a few shared morphological characters. Our study revealed some new generic relationships within the Brachytheciaceae, which are discussed in light of the morphological characters traditionally used for generic delimitation.     

Allelopathic effects of the Baltic cyanobacteria Nodularia spumdigena, Aphanizomenon flos-aquae and Anabaena lemmermannii on algal monocultures

Allelopathy, the release of extracellular compounds that inhibit the growth of other microorganisms, may be one factor contributing to the formation and/or maintenance of cyanobacterial blooms. We investigated the allelopathic effects of three cyanobacterial species (Nodularia spumigena, Aphanizomenon flos-aquae and Anabaena lemmermannii) that frequently form mass-occurrences in the Baltic Sea. We exposed monocultures of three phytoplankton species (Thalassiosira weissflogii, Rhodomonas sp. and Prymnesium parvum) to cell-free filtrates of the three cyanobacteria, and quantified allelopathic effects with cell counts. We also investigated the role of the growth phase of cyanobacteria in their allelopathy, by comparing the effects of an exponential and a stationary phase culture of N. spumigena. All tested cyanobacteria inhibited the growth of Rhodomonas sp., but none of them affected P. parvum. The effects on T. weissflogii were more variable, and they were amplified by repeated filtrate additions compared to a single filtrate addition. N. spumigena was more allelopathic in exponential than in stationary growth phase, whereas the culture filtrate was more hepatotoxic in stationary phase. Hepatotoxins were thus probably not involved in the allelopathic effects, which is also indicated by the allelopathic properties of the non-toxic A. flos-aquae and A. lemmermannii. The results demonstrate that the common Baltic cyanobacteria affect some coexisting phytoplankton species negatively. Allelopathy may therefore play a role in interspecific competition and contribute to cyanobacterial bloom maintenance.     

Origin and evolution of the northern hemisphere disjunction in the moss genus Homalothecium (Brachytheciaceae)

Competing hypotheses that rely either on a stepping-stone dispersal via the North Atlantic or the Bering land bridges, or more recent transoceanic dispersal, have been proposed to explain the disjunct distribution of Mediterranean flora in southern Europe and western North America. These hypotheses were tested with molecular dating using a phylogeny of the moss genus Homalothecium based on ITS, atpB-rbcL, and rpl16 sequence data. The monophyly of two main lineages in Western Palearctic (Europe, central Asia and north Africa) and North America is consistent with the ancient vicariance hypothesis. The monophyly of Madeiran H. sericeum accessions supports the recognition of the Macaronesian endemic H. mandonii. A range of absolute rates of molecular evolution documented in land plants was used as probabilistic calibration prior by a Bayesian inference implementing a relaxed-clock model to derive ages for the nodes of interest. Our age estimates for the divergence of the American and Western Palearctic Homalothecium clade (5.7 Ma, IC 3.52-8.26) and the origin of H. mandonii (2.52 Myr IC 0.86-8.25) are not compatible with the ancient vicariance hypothesis. Age estimates suggests that species distributions result from rare instances of dispersal and subsequent sympatric diversification. The calibrated phylogeny indicates that Homalothecium has undergone a fast radiation during the last 4 Myr, which is consistent with the low levels of morphological divergence among sibling species.     

Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function

Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over a life span. By genotyping 362,129 SNPs in 4,300 Sardinians, we identified a strong association (p = 1.3 x 10(-11)) between alleles of rs4704397 and circulating TSH levels; each additional copy of the minor A allele was associated with an increase of 0.13 muIU/ml in TSH. The single-nucleotide polymorphism (SNP) is located in intron 1 of PDE8B, encoding a high-affinity cAMP-specific phosphodiesterase. The association was replicated in 4,158 individuals, including additional Sardinians and two genetically distant cohorts from Tuscany and the Old Order Amish (overall p value = 1.9 x 10(-20)). In addition to association of TSH levels with SNPs in PDE8B, our genome scan provided evidence for association with PDE10A and several biologically interesting candidates in a focused analysis of 24 genes. In particular, we found evidence for association of TSH levels with SNPs in the THRB (rs1505287, p = 7.3 x 10(-5)), GNAQ (rs10512065, p = 2.0 x 10(-4)), TG (rs2252696, p = 2.2 x 10(-3)), POU1F1 (rs1976324, p = 3.9 x 10(-3)), PDE4D (rs27178, p = 8.3 x 10(-3)), and TSHR (rs4903957, p = 8.6 x 10(-3)) loci. Overall, the results suggest a primary effect of PDE8B variants on cAMP levels in the thyroid. This would affect production of T4 and T3 and feedback to alter TSH release by the pituitary. PDE8B may thus provide a candidate target for the treatment of thyroid dysfunction.     

Dynamic association of human insulin receptor with lipid rafts in cells lacking caveolae

Cholesterol-sphingolipid rich plasma membrane domains, known as rafts, have emerged as important regulators of signal transduction. The adipocyte insulin receptor (IR) is localized to and signals via caveolae that are formed by polymerization of caveolins. Caveolin binds to IR and stimulates signalling. We report that, in liver-derived cells lacking caveolae, autophosphorylation of the endogenous IR is dependent on raft lipids, being compromised by acute cyclodextrin-mediated cholesterol depletion or by antibody clustering of glycosphingolipids. Moreover, we provide evidence that IR becomes recruited to detergent-resistant domains upon ligand binding and that clustering of GM2 ganglioside inhibits IR signalling apparently by excluding the ligand-bound IR from these domains. Our results indicate that, in cells derived from liver, an important insulin target tissue, caveolae are not required for insulin signalling. Rather, the dynamic recruitment of the ligand-bound IR into rafts may serve to regulate interactions in the initiation of the IR signalling cascade.     

Vitamin C enhances differentiation of a continuous keratinocyte cell line (REK) into epidermis with normal stratum corneum ultrastructure and functional permeability barrier

A continuous rat epidermal cell line (rat epidermal keratinocyte; REK) formed a morphologically well-organized epidermis in the absence of feeder cells when grown for 3 weeks on a collagen gel in culture inserts at an air-liquid interface, and developed a permeability barrier resembling that of human skin. By 2 weeks, an orthokeratinized epidermis evolved with the suprabasal layers exhibiting the differentiation markers keratin 10, involucrin, and filaggrin. Granular cells with keratohyalin granules and lamellar bodies, and corneocytes with cornified envelopes and tightly packed keratin filaments were present. Morphologically, vitamin C supplementation of the culture further enhanced the normal wavy pattern of the stratum corneum, the number of keratohyalin granules present, and the quantity and organization of intercellular lipid lamellae in the interstices of the stratum corneum. The morphological enhancements observed with vitamin C correlated with improved epidermal barrier function, as indicated by reduction of the permeation rates of tritiated corticosterone and mannitol, and transepidermal water loss, with values close to those of human skin. Moreover, filaggrin mRNA was increased by vitamin C, and western blots confirmed higher levels of profilaggrin and filaggrin, suggesting that vitamin C also influences keratinocyte differentiation in aspects other than the synthesis and organization of barrier lipids. The unique REK cell line in organotypic culture thus provides an easily maintained and reproducible model for studies on epidermal differentiation and transepidermal permeation.