Modulation of Cyclic AMP Levels in Fallopian Tube Cells by Natural and Environmental Estrogens

Autocrine/paracrine factors generated in response to 17β-estradiol (E2) within the fallopian tube (FT) facilitate fertilization and early embryo development for implantation. Since cyclic AMP (cAMP) plays a key role in reproduction, regulation of its synthesis by E2 may be of biological/pathophysiological relevance. Herein, we investigated whether cAMP production in FT cells (FTCs) is regulated by E2 and environmental estrogens (EE’s; xenoestrogens and phytoestrogens). Under basal conditions, low levels of extracellular cAMP were detectable in bovine FTCs (epithelial cells and fibroblasts; 1:1 ratio). Treatment of FTCs with forskolin (AC; adenylyl cyclase activator), isoproterenol (β-adrenoceptor agonist) and IBMX (phosphodiesterase (PDE) inhibitor) dramatically (>10 fold) increased cAMP; whereas LRE1 (sAC; soluble AC inhibitor) and 2’,5’-dideoxyadenosine (DDA; transmembrane AC (tmAC)) inhibitor decreased cAMP. Comparable changes in basal and stimulated intracellular cAMP were also observed. Ro-20-1724 (PDE-IV inhibitor), but not milrinone (PDE-III inhibitor) nor mmIBMX (PDE-I inhibitor), augmented forskolin-stimulated cAMP levels, suggesting that PDE-IV dominates in FTCs. E2 increased cAMP levels and CREB phosphorylation in FTCs, and these effects were mimicked by EE’s (genistein, 4-hydroxy-2’,4’,6’-trichlorobiphenyl, 4-hydroxy-2’,4’,6’-dichlorobiphenyl). Moreover, the effects of E2 and EE were blocked by the tmAC inhibitor DDA, but not by the ERα/β antagonist ICI182780. Moreover, BAPTA-AM (intracellular-Ca2+ chelator) abrogated the effects of E2, but not genistein, on cAMP suggesting differential involvement of Ca2+. Treatment with non-permeable E2-BSA induced cAMP levels and CREB-phosphorylation; moreover, the stimulatory effects of E2 and EEs on cAMP were blocked by G15, a G protein-coupled estrogen receptor (GPER) antagonist. E2 and IBMX induced cAMP formation was inhibited by LRE1 and DDA suggesting involvement of both tmAC and sAC. Our results provide the first evidence that in FTCs, E2 and EE’s stimulate cAMP synthesis via GPER. Exposure of the FT to EE’s and PDE inhibitors may result in abnormal non-cyclic induction of cAMP levels which may induce deleterious effects on reproduction

Cell-Cell Interactions and the Regulation of Testis Function

Regulatory interactions have been shown to occur between all the testicular cell types considered. The paracrine factors mediating these interactions generally influence either cellular growth or differentiation. The regulation of cellular growth is essential in the developing testis and is required for the maintenance of spermatogenesis in the adult testis. The rapid rate of germinal cell proliferation and the continuous but slowed growth of the peritubular cells and Leydig cells requires the presence of specific growth factors in the adult. Therefore, cell-cell interactions have evolved that involve growth factors such as IGF, TGF-alpha, TGF-beta and NGF. Other growth factors such as FGF or less characterized components like the seminiferous growth factor (SGF) also may be involved in the paracrine regulation of testis cell growth. An alternate cellular parameter to cell growth to consider is the regulation of cellular function and differentiation. A number of endocrine agents and locally produced paracrine factors have been shown to control and maintain testis cell function and differentiation. Cell-cell interactions mediated by factors such as androgens, POMC peptides, and PModS are all primarily directed at the regulation of cellular differentiation. Therefore, the agents which mediate cell-cell interactions in the testis can generally be categorized into factors that regulate cell growth or those which influence cellular differentiation. The specific cell-cell interactions identified will likely be the first of a large number of cellular interactions yet to be investigated. Although a number of potentially important cell-cell interactions have been identified, future research will require the elucidation of the in vivo physiological significance of these interactions. The existence of different cell types and potential cell-cell interactions in a tissue implies that the actions of an endocrine agent on a tissue will not simply involve a single hormone and single cell. The endocrine regulation of testis function will have effects on cell-cell interactions and be affected by local cell-cell interactions. The ability of LH to influence Leydig cell androgen production promotes a cascade of interactions mediated through several cell types to maintain the process of spermatogenesis. FSH actions on Sertoli cells also promote cell-cell interactions that influence germinal cell development, peritubular myoid cell differentiation and Leydig cell function. Therefore, elucidation of the endocrine regulation of testis function requires an understanding of the local cell-cell interactions in the testis

Headspace Volatile Composition of the Flowers of Caralluma europaea N.E.Br. (Apocynaceae)

The volatile constituents of the flowers of Caralluma (Apteranthes) europaea (Guss.) N.E. Br. (Apocynaceae - Asclepiadoideae) from Lampedusa Island were analyzed by headspace method. The analyses allowed the identification and quantification of 41 compounds. The main components were, among the monoterpenoids, terpinolene (23.3%), a-terpinene (19.1%) and linalool (18.4%), whereas, among the carbonylic compounds the major constituents were heptanal (2.0%), octanoic acid (2.4%) and hexanoic acid (1.7%). It is worth to mention the presence of a nitrogen containing compound, indole (0.8%) and of a sulphur containing compound, dimethylsulphide (t). The compounds found in the flowers of C. europea have been compared with data available in the literature as regard to their odor, presence in other sapromyiophilous taxa, possible role as semiochemicals, and presence in decaying organ matter. 89.3% of total constituents have been described in other sapromyiophilous taxa. Some of the compounds are present in several type of decaying organic matter (excrements, body in decomposition, and spoiled fish, etc). Several volatiles found in C. europea flowers are used as semiochemicals in Hymenoptera, Coleoptera, Diptera, Lepidoptera and other insects. Sixteen volatiles, accounting for 32.4% of the total constituents, are described as attractants of some Diptera families with a biology linked to decaying organic matters. Our data thus confirm that C. europea floral bouquet falls within the sapromyiophilous pollination syndrome

Preferences and skills of Indian public sector teachers

With a sample of 700 future public sector primary teachers in India, a Discrete Choice Experiment is used to measure job preferences, particularly regarding location. General skills are also tested. Urban origin teachers and women are more averse to remote locations than rural origin teachers and men respectively. Women would require a 26-73 percent increase in salary for moving to a remote location. The results suggest that existing caste and gender quotas can be detrimental for hiring skilled teachers willing to work in remote locations. The most preferred location is home, which supports decentralised hiring, although this could compromise skills

Defective spleen function in autoimmune gastrointestinal disorders

Defective spleen function increases susceptibility to bacterial infections which can be prevented by vaccine prophylaxis. Splenic hypofunction can be found in a number of autoimmune disorders; however, no data are available regarding autoimmune atrophic gastritis (AAG), autoimmune enteropathy (AIE) and autoimmune liver disease (AILD). Peripheral blood samples from patients with AAG (n = 40), AIE (n = 3) and AILD (n = 40) were collected. Patients affected by autoimmune disorders already known to be associated with splenic hypofunction, i.e. coeliac disease (CD) and ulcerative colitis (UC), were included as disease controls, while splenectomised patients and healthy subjects were evaluated as positive and negative controls, respectively. Counting of erythrocytes with membrane abnormalities, i.e. pitted red cells, was used as an indicator of spleen function (normal upper limit 4%). Defective splenic function was observed in 22 of the 40 patients with AAG (55.0%), in two of the three patients with AIE (66.6%) and in 35 of the 40 patients with AILD (87.5%). As expected, in untreated CD, refractory CD and UC there was a high prevalence of hyposplenism (43.7%, 88.2% and 54.4%, respectively). Due to the high prevalence of splenic hypofunction, patients with AAG, AILD and AIE should undergo pitted red cell evaluation and, if hyposplenic, they should be candidate to vaccine prophylaxis against encapsulated bacteria

The Tension on dsDNA Bound to ssDNA/RecA Filaments May Play an Important Role in Driving Efficient and Accurate Homology Recognition and Strand Exchange

It is well known that during homology recognition and strand exchange the double stranded DNA (dsDNA) in DNA/RecA filaments is highly extended, but the functional role of the extension has been unclear. We present an analytical model that calculates the distribution of tension in the extended dsDNA during strand exchange. The model suggests that the binding of additional dsDNA base pairs to the DNA/RecA filament alters the tension in dsDNA that was already bound to the filament, resulting in a non-linear increase in the mechanical energy as a function of the number of bound base pairs. This collective mechanical response may promote homology stringency and underlie unexplained experimental results

Acro-cardio-facial syndrome

Acro-cardio-facial syndrome (ACFS) is a rare genetic disorder characterized by split-hand/split-foot malformation (SHFM), facial anomalies, cleft lip/palate, congenital heart defect (CHD), genital anomalies, and mental retardation. Up to now, 9 patients have been described, and most of the reported cases were not surviving the first days or months of age. The spectrum of defects occurring in ACFS is wide, and both interindividual variability and clinical differences among sibs have been reported. The diagnosis is based on clinical criteria, since the genetic mechanism underlying ACFS is still unknown. The differential diagnosis includes other disorders with ectrodactyly, and clefting conditions associated with genital anomalies and heart defects. An autosomal recessive pattern of inheritance has been suggested, based on parental consanguinity and disease's recurrence in sibs in some families. The more appropriate recurrence risk of transmitting the disease for the parents of an affected child seems to be up to one in four. Management of affected patients includes treatment of cardiac, respiratory, and feeding problems by neonatal pediatricians and other specialists. Prognosis of ACFS is poor

Molecular epidemiology and case-control approaches for management of an outbreak of hepatitis A in Liguria, Italy

Introduction and methods. Hepatitis A remains an important public health problem in low endemicity areas, because of the social and economic high burden of cyclical outbreaks. In this study we described an outbreak of HAV infection occurred in the city of Genoa and in its proximity and the viral circulation in the post-epidemic period. In order to identify risk factors associated to the illness and to determine the source of infection and the dynamics of virus evolution, we conducted an epidemiological and molecular investigation by a case-control study and by sequence analysis of high variable regions of the genome. Results. From May to October 2005, 58 HAV hepatitis cases were notified. The case-control study showed that beach establishment attending is strongly associated with HAV hepatitis (OR = 24.5, p-value inf. 0.01), at multivariate analysis. The profile of epidemic curve, the clinical onset of primary cases who occurred in few weeks and the geographic distribution of cases clearly indicated a common exposure to a point source: the outbreak can be probably associated with a contaminated food product dispensed in the affected area. The outbreak has been mainly caused by a single variant, confirming the common exposure to a point source; this variant previously circulated within homosexual man (MSM) network in Northern Europe. During the outbreak and in the following months, different variants originating from Southeast Asia, Southern America and Northern Africa, have co-circulated: all these cases were related to international travel and none of these had determined secondary cases. Discussion. The epidemiological picture of hepatitis A in Liguria is characterized by a wide heterogeneity of circulating HAV strains. This pattern could be associated with the increase of imported cases and transmission within network of persons with similar risk factors. Molecular approach coupled to descriptive and analytical epidemiological studies appeared un-replaceable tools for management and control of HAV outbreaks, because of their capacity to recognize infection origin, transmission patterns and dynamics of virus evolution

The Wicked Machinery of Government: Malta and the Problems of Continuity under the New Model Administration

This is a study focused on the early years of British rule in Malta (1800-1813). It explores the application to the island of the “new model” of colonial government, one based on direct rule from London mediated by the continuation of existing laws and institutions. Systemic deficiencies are identified. These tended to undermine the effectiveness of direct British rule. This study also reveals, in the context of legal and constitutional continuity, unresolved tensions between modernity and tradition. The political stability of the island was damaged and the possibility of continued British possession was threatened