Designing an integrated coastal orientation index: A cross-comparison of Mexican municipalities

To better understand the relation between coastal areas and their influence on social and economic conditions of municipalities, a set of indexes were developed to characterize coastal Mexico with an interdisciplinary approach. The composite of these bio-physical, social and economic indexes is referred to as an “integrated coastal orientation index”. Coastal characteristics should be taken into account in the coastal management policy formulation of a given region, and this index can be used to identify key areas for environmental protection or economic development at a national level. The results suggest that municipalities must manage their coastal jurisdictions, a large and diverse array of coastal space and ecosystems, medium to weak spatial demographics and settlement structures, infrastructure to improve quality of life, an overall low coastal population income, and various coastal activities. Spatial heterogeneity along the littoral zone in the coastal orientation led us to conduct a state analysis. We discuss these values and identify five highly coastal-orientated states in the extremes of the country. The development of this tool could help to pin-point different types of key areas within the regions studied and provide a tool to guide regional priorities. As an example, using a combination of extreme values of bio-physical, social and economic indexes was used to identify specific municipalities as candidates for environmental protection and others as areas where development can continue. Choices of indexes are discussed, and the relative importance given to each component of the coastal orientation (rather bio-physical, social and/or economic) will define the course of the coast's development and its sustainability.     

Structure of human complement C8, a precursor to membrane attack

Complement component C8 plays a pivotal role in the formation of the membrane attack complex (MAC), an important antibacterial immune effector. C8 initiates membrane penetration and coordinates MAC pore formation. High-resolution structures of C8 subunits have provided some insight into the function of the C8 heterotrimer; however, there is no structural information describing how the intersubunit organization facilitates MAC assembly. We have determined the structure of C8 by electron microscopy and fitted the C8α-MACPF (membrane attack complex/perforin)-C8γ co-crystal structure and a homology model for C8β-MACPF into the density. Here, we demonstrate that both the C8γ protrusion and the C8α-MACPF region that inserts into the membrane upon activation are accessible.     

Modulation of diorganoyl dichalcogenides reactivity by non-bonded nitrogen interactions

The study was designed to explore the biochemical influence of non bonding nitrogen interactions (N?Se/S) on organochalcogens potency. Approximately five and six times higher thiol peroxidase (TPx) like activity was observed for compound (C)-2 than C-1 and C-3, respectively. C-2 also displayed significantly (p < 0.05) higher activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and deoxyribose degradation assays. All compounds, except C-4 and C-6 significantly inhibited Fe (II) and sodium nitroprusside (SNP) induced thiobarbituric acid reactive species (TBARS) production in rat’s brain, liver and kidney preparations with highest activity observed for C-2. The highest C-2 activity was attributed to the presence of non-bonded nitrogen interactions which were absent in C-1 and blocked with butoxycarbonyl (BOC group) in C-3. The same structural activity analogy was extended to organosulfur compounds and it was observed that compound with non-bonding nitrogen interactions, i.e. C-5 has significantly (p < 0.05) higher TPx like activity than C-6 and C-4. C-5 at the highest tested concentration significantly (p < 0.05) protected against Fe (II) and SNP induced TBARS formation in rat’s brain, kidney and liver preparations but did not display activity in DPPH and deoxyribose degradation assays. This study confirms the influence of not only N?Se interaction but also for the first time the effect of non bonded N?S interactions on organochalcogens potency. C-2 (with the highest activity) was also tested in vivo and was administered at three different doses, i.e. 15, 30 and 50 mg/kg to get an exact idea about its interaction with thiol containing molecules (NPSH) and enzyme α-ALA-D (sulfhydryl containing enzyme). Oxidative stress parameters, i.e. free radical concentration by dichlorofluoreseein (DCF) assay, TBARS, ascorbic acid level, hepatic (ALT and AST) and renal (urea and creatinine) toxicity markers were also estimated to get an insight about its possible toxicological profile. Our data indicates that C-2 has higher TPx and Antioxidant activity and importantly, C2 did not induce toxicity even when tested at relatively high doses, indicating that its pharmacological properties should be further explored in models of diseases associated with oxidative stress.     

Functional interactions of DNA topoisomerases with a human replication origin

The human DNA replication origin, located in the lamin B2 gene, interacts with the DNA topoisomerases I and II in a cell cycle-modulated manner. The topoisomerases interact in vivo and in vitro with precise bonds ahead of the start sites of bidirectional replication, within the pre-replicative complex region; topoisomerase I is bound in M, early G1 and G1/S border and topoisomerase II in M and the middle of G1. The Orc2 protein competes for the same sites of the origin bound by either topoisomerase in different moments of the cell cycle; furthermore, it interacts on the DNA with topoisomerase II during the assembly of the pre-replicative complex and with DNA-bound topoisomerase I at the G1/S border. Inhibition of topoisomerase I activity abolishes origin firing. Thus, the two topoisomerases are closely associated with the replicative complexes, and DNA topology plays an essential functional role in origin activation.     

Unilateral sectioning of the superior ovarian nerve of rats with polycystic ovarian syndrome restores ovulation in the innervated ovary

The present study tested the hypothesis that if polycystic ovary syndrome (PCOS) results from activating the noradrenergic outflow to the ovary, unilaterally sectioning the superior ovarian nerve (SON) will result in ovulation by the denervated ovary, and the restoration of progesterone (P4), testosterone (T) and estradiol (E2) normal serum level. A single 2 mg dose of estradiol valerate (EV) to adult rats results in the development of a syndrome similar to the human PCOS. Ten-day old rats were injected with EV or vehicle solution (Vh) and were submitted to sham surgery, unilateral or bilateral sectioning of the SON at 24-days of age. The animals were sacrificed at 90 to 92 days of age, when they presented vaginal estrus preceded by a pro-estrus smear. In EV-treated animals, unilateral sectioning of the SON restored ovulation by the innervated ovary and unilateral or bilateral sectioning of the SON normalized testosterone and estradiol levels. These results suggest that aside from an increase in ovarian noradrenergic tone in the ovaries, in the pathogenesis of the PCOS participate other neural influences arriving to the ovaries via the SON, regulating spontaneous ovulation. Changes in P4, T and E2 serum levels induced by EV treatment seem to be controlled by neural signals arising from the abdominal wall and other signals arriving to the ovaries through the SON, and presents asymmetry.     

Growth hormone restores aged diaphragm myosin composition and performance after chronic undernutrition.

The effects of growth hormone (GH) on diaphragm muscle myosin heavy chain (MHC) composition and mechanical performance were investigated in Fischer 344 male rats aged to senescence (24.5 mo of age). Chronic undernutrition (UN), refeeding (RF), and RF+GH were compared with ad libitum feeding by using a model of UN that produced a 50% decrease in body weight over a 12-mo period. The effect of aging was assessed by comparing MHC composition of ad libitum-fed rats at 12 and 24.5 mo of age. At senescence, significant decreases in slow type I (-23%) and fast type IIA (-31%) MHC had occurred with aging. Conversely, UN over this aging period increased types I (32-73%) and IIA (22-23%) MHC and decreased fast types IIB (32-54%) and IIX (30-31%) MHC. RF and RF+GH reversed these shifts back toward control values. At senescence, maximal specific force, maximal velocity, and specific power capacity were not different across treatment groups. During repetitive isotonic contraction trials, the diaphragms of UN rats maintained power production over time (54% of initial power at 60 s), whereas the power production of diaphragms of ad libitum-fed rats fell to 0% (P < 0.05). In comparison with UN rats, the diaphragms of RF and RF+GH rats produced 23 (not significant) and 11% (P < 0.05) of initial power, respectively, suggesting that RF+GH treatment restored performance characteristics after UN. We conclude that RF+GH can reverse alterations in MHC composition and mechanical performance produced by chronic UN in the aged rat diaphragm.     

Binding study of semotiadil and levosemotiadil with alpha(1)-acid glycoprotein using high-performance frontal analysis.

High-performance frontal analysis (HPFA) was used to investigate the binding properties of human alpha(1)-acid glycoprotein (AGP) with semotiadil ((R)-isomer, Ca-channel blocker) and its antipode levosemotiadil ((S)-isomer, Ca- and Na-channel blockers). An on-line HPLC system consisting of a HPFA column, an extraction column, and an analytical HPLC column was used to determine the unbound concentrations of these enantiomers, and the experimental data were subsequently subjected to the Scatchard analyses to estimate their binding parameters. The binding affinity of the (R)-isomer (K = 3.17 x 10(7) M, n = 0.74) is approximately 1.2 times stronger than that of (S)-isomer (K = 2.59 x 10(7) M, n = 0.74). An enantioselective competitive binding study indicated that both enantiomers are bound at the same site on AGP molecules.     

Senescence in European Middle Pleistocene hominids: The Atapuerca evidence

The mandibular specimens AT-250 and AT-793 (individual IV) and AT-888 (individual XXI) from the Atapuerca Middle Pleistocene sample show a combination of traits interpreted as evidence of senescence. In order to explore age-related mandibular changes relevant to the interpretation of the Atapuerca hominids, the sample of known age and sex from Spitalfields (London) and the Neolithic sample from Abu Hureyra (Syria) were used as a baseline. Results obtained indicate that the occurrence of an enlarged and posteriorly located mental foramen, in association with high alveolar resorption in AT-250 and AT-888, support the hypothesis of senescence in individuals IV and XXI from the Atapuerca sample. The findings suggest that European Middle Pleistocene populations lived long enough to reach senescence. The age at death for Middle Pleistocene hominids and Neanderthals has previously been estimated at around 40–45 years in the oldest specimens. The appearance of senescence processes before this age is indicative of higher rates of morphological aging in the clade which gave rise to Neanderthals. The anatomical significance of ageing features when considered in the context of craniofacial remodelling can help in the understanding of the taxonomic status of these morphological traits.     

Evidence for immune responses to a self-antigen in lung transplantation: role of type V collagen-specific T cells in the pathogenesis of lung allograft rejection

We have reported that lung allograft rejection involves an immune response to a native protein in the lung, type V collagen (col(V)), and that col(V)-induced oral tolerance prevented acute and chronic rejection. In support of these findings col(V) fragments were detected in allografts during rejection, but not in normal lungs. The purpose of the current study was to isolate and characterize col(V)-specific allograft-infiltrating T cells and to determine their contribution to the rejection response in vivo. Two col(V)-specific T cell lines, LT1 and LT3, were isolated from F344 (RT1(lv1)) rat lung allografts during rejection that occurred after transplantation into WKY (RT1(l)) recipients. Both cell lines, but not normal lung lymphocytes, proliferated in response to col(V). Neither LT1 nor LT3 proliferated in response to alloantigens. LT1 and LT3 were CD4(+)CD25(-) and produced IFN-gamma in response to col(V). Compared with normal CD4(+) T cells, both cell lines expressed a limited V-beta TCR repertoire. Each cell strongly expressed V-beta 9 and 16, but differed in expression of other V-betas. Adoptive transfer of each cell line did not induce pathology in lungs of normal WKY rats. In contrast, adoptive transfer of LT1, but not LT3, caused marked peribronchiolar and perivascular inflammation in isograft (WKY) lungs and abrogated col(V)-induced oral tolerance to allograft (F344) lungs. Collectively, these data show that lung allograft rejection involves both allo- and autoimmune responses, and graft destruction that occurs during the rejection response may expose allograft-infiltrating T cells to potentially antigenic epitopes in col(V).     

Effect of Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Application in Achilles-Tendon Injury in an Animal Model

Background: Achilles-tendon rupture prevails as a common tendon pathology. Adipose-derived mesenchymal stem cells (ADMSCs) are multipotent stem cells derived from adipose tissue with attractive regeneration properties; thus, their application in tendinopathies could be beneficial. Methods: Male rabbit ADMSCs were obtained from the falciform ligament according to previously established methods. After tenotomy and suture of the Achilles tendon, 1 × 10⁶ flow-cytometry-characterized male ADMSCs were injected in four female New Zealand white rabbits in the experimental group (ADMSC group), whereas four rabbits were left untreated (lesion group). Confirmation of ADMSC presence in the injured site after 12 weeks was performed with quantitative sex-determining region Y (SRY)-gene RT-PCR. At Week 12, histochemical analysis was performed to evaluate tissue regeneration along with quantitative RT-PCR of collagen I and collagen III mRNA. Results: Presence of male ADMSCs was confirmed at Week 12. No statistically significant differences were found in the histochemical analysis; however, statistically significant differences between ADMSC and lesion group expression of collagen I and collagen III were evidenced, with 36.6% and 24.1% GAPDH-normalized mean expression, respectively, for collagen I (p < 0.05) and 26.3% and 11.9% GAPDH-normalized mean expression, respectively, for collagen III (p < 0.05). The expression ratio between the ADMSC and lesion group was 1.5 and 2.2 for collagen I and collagen III, respectively. Conclusion: Our results make an important contribution to the understanding and effect of ADMSCs in Achilles-tendon rupture.