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Introduction: Stress is associated with increased risk of stroke and poor prognosis, but the mechanisms through which stress may alter stroke outcome remain elusive. Stress compromises neuronal survival and neuroinflammation following an ischemic attack. Post-ischemic inflammatory response involves the activation of microglia, which can be polarized from a harmful M1 phenotype which expresses pro-inflammatory cytokines, to a protective M2 phenotype which releases neurotrophic factors. We hypothesize that progesterone (PROG) will improve global ischemia outcome by modulating microglial polarization in stressed ischemic animals. Methods: Adult male rats were exposed to social defeat stress over 8 consecutive days. Then, rats were subjected to 8 min of global ischemia by the four-vessel occlusion model. PROG (8 mg/Kg/b.w.) was administered by intraperitoneal injection at 2 h post-ischemia followed by subcutaneous injections at 6 h and once every 24 h post-injury for 5 days, and then 2 days with progressively halved dosages. Animals were sacrificed at 7 days post-ischemia. Neuronal loss was assessed by Nissl staining, M1/M2 polarization markers were assessed by immunofluorescence, and pro-inflammatory cytokine and growth factor expression were assessed by western blot. Results: Results revealed extensive neuronal loss and exacerbated microglial activation in hippocampal CA1 region of stressed ischemic rats. Remarkably, both M1 and M2 markers increased. PROG treatment attenuated neuronal loss, robustly reduced M1/M2 markers and significantly increased brain-derived neurotrophic factor expression in the stressed ischemic hippocampus. Conclusion: Our data demonstrate that PROG can modulate neuroinflammation after global ischemic injury by changing microglial phenotype in certain vulnerable brain areas like the hippocampus. These findings support the therapeutic potential of PROG for treating global ischemia with comorbid stress.

The potential impacts of CO2 leakage from a natural subsurface reservoir on soil and water quality were studied. Field measurements of soil pore CO2 concentrations and visual inspection of plants at Mammoth Mountain, CA, allowed the demarcation of tree-kill and non-tree-kill zones, with CO2 concentrations100,000 ppm and ∼ 1,000 ppm, respectively. Soils collected from six sites along a transect stretching from the center of the tree-kill zone to an equidistant point into the non-tree-kill zone were analyzed for surface area and organic carbon content. Batch and column leaching tests were conducted to determine the extent of weathering induced by the presence of CO2 in the aqueous solution. Soils deep into the tree-kill area exhibited significantly higher surface areas (10.67 m(2)/g vs 2.53 m(2)/g) and lower organic carbon content (9,550 mg/kg vs 35,550 mg/kg). Batch results indicated that lower pH values (∼ 2) released higher concentrations of Mg, Si, Fe, and As, while, for soils in the tree-kill zone, longer-term batch results indicated higher releases at the higher pH of 5.5. Column experiments were used to compare the effects of pH adjusted using HCl vs CO2. For pore volumes (PV)100, CO2 enhanced trace element release. For 100PV10,000 concentrations of elements in the two systems were equivalent and steady. At PV10,000, after a drop in pH in the CO2 system, larger amounts of Fe and As were released, suggesting a CO2-induced dissolution of Fe-silicates/clays and/or reductive dissolution of Fe(3+) that releases Fe-bound arsenic. The specific role of pore water-dissolved CO2 on the release of trace elements is hitherto unknown. However, interactions of pore-water CO2 and the minerals in the Mammoth Mountain soils can cause the release of environmental pollutants.

The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥200mg/kg, and involving granular cell damage at doses of 400mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system.

Hay tres procesos politicos que interactuan en algunos paises de America Latina: el giro a la izquierda, la generacion de movimientos constituyentes impulsados por dichos gobiernos, y un cada vez mas relevante papel de los derechos humanos (DH) en la formulacion de politica publica (PP). Daremos cuenta de la convergencia de estos procesos situandonos en el ultimo: la PP con perspectiva de DH (PPDH). La constitucionalizacion de los derechos humanos es un tema extensamente trabajado; sin embargo, la vinculacion de este con la politica publica es un ambito de analisis relativamente nuevo, aunque fundamental para entender las brechas entre el cumplimiento y el ejercicio de los derechos humanos. Nos preguntamos: ?cual es la relacion entre las constituciones emitidas por los gobiernos del giro a la izquierda y la formulacion de PPDH? Se esperaria que el papel que tomaron los DH en las nuevas constituciones tuviera un impacto sostenido en la formulacion de la PP; no obstante, esto no es necesariamente asi. Si bien hay interaccion entre las constituciones y las PP, hay dos aspectos interesantes por subrayar: el proceso de resignificacion, en el caso ecuatoriano, y la segunda vuelta institucional, en el caso venezolano. Public policies with a human rights perspective in the shift to the left. From rupture to the second round in Venezuela and Ecuador Abstract There are three processes that interact in certain countries in Latin America: the shift to the left, movements to develop new constitutions driven by left wing governments , and the increasingly relevant role played by human rights in the development of public policy. We will make evident these interactions by analyzing this last point: public policy with a human rights perspective (PPHR). The inclusion of human rights in constitutions is something that has been thoroughly analyzed; yet the link of this inclusion with pubic policy is an area that is relatively new despite it being key in understanding the gaps between the fulfillment and enjoyment of human rights. We ask: what is the relationship between constitutions issued by left wing governments and the development of PPHR? One would expect that the role played by human rights in new constitutions would have a sustained impact in the development of PP. This is not necessarily the case: although there is interaction between constitutions and PP, there are two interesting aspects to highlight: the rebranding in the case of Ecuador and the second round in the case of Venezuela.

exico Abstract. Purpose: To assess the long-term neuroprotective effects of progesterone (P4) and allopregnanolone (ALLO) on functional and morphological parameters of the integrity of the hippocampus, after global cerebral ischemia. Methods: Adult male Sprague-Dawley rats were subjected to a transient severe (20 min) forebrain ischemia (Isch) episode and treated with P4 or ALLO (8 mg/kg i.v.) or its vehicle, at 20 min, 2, 6, 24, 48 and 72 h after ischemia. Rats subjected to Sham procedures, and intact rats were included as non-ischemic controls. Three months after ischemia, both the functional (spatial learning and memory, and reference and working memory), and the morphological integrity (dimensions of the hippocampal formation, thickness of the CA1 subfield, and pyramidal neur on population) of the hippocampus and the medial prefrontal cortex (mPFC) were determined. Results: Treatment with P4 or ALLO significantly reduced the impairment in spatial lear ning and memory, as well as in reference and working memory, and prevented the narrowing of the hippocampus, otherwise induced by ischemia. This better performance of P4- and ALLO-treated rats than vehicle (Veh) -treated rats, occurred in spite of a loss of pyramidal neurons in the CA1, CA2, CA3 and hilus subfields of the Ammon's horn (remaining neurons: Isch+Veh: 21.0, 35.6, 44.1, and 40.3%; Isch+P4: 19.9, 32.2, 41.1, and 32.5%; Isch+ALLO: 25.5, 62.0, 73.7, and 56.7%), and non-significant changes in the mPFC, as compared to the Inta ct group (100%). Conclusions: Performance of P4- or ALLO-treated rats in learning and memory tests suggests that these steroids promoted neural conditions accounting for adequate functioning long after ischemia, in spite of the loss of hippocampal pyramidal neurons.

El ácido oxolínico tienen una gran actividad antimicrobiana por lo que se usa en el tratamiento de infecciones del tracto urinario. La formación de complejos de ácido oxolínico con g-ciclodextrina se estudió por medio de espectroscopía UV-VIS. El ácido oxolínico forma complejos de inclusión (1:1) con g-ciclodextrina en medio ácido y básico.

The establishment of silent chromatin requires passage through S-phase, but not DNA replication per se. Nevertheless, many proteins that affect silencing are bona fide DNA replication factors. It is not clear if mutations in these replication factors affect silencing directly or indirectly via deregulation of S-phase or DNA replication. Consequently, the relationship between DNA replication and silencing remains an issue of debate. Here we analyze the effect of mutations in DNA replication factors (mcm5-461, mcm5-1, orc2-1, orc5-1, cdc45-1, cdc6-1, and cdc7-1) on the silencing of a group of reporter constructs, which contain different combinations of “natural” subtelomeric elements. We show that the mcm5-461, mcm5-1, and orc2-1 mutations affect silencing through subtelomeric ARS consensus sequences (ACS), while cdc6-1 affects silencing independently of ACS. orc5-1, cdc45-1, and cdc7-1 affect silencing through ACS, but also show ACS-independent effects. We also demonstrate that isolated nontelomeric ACS do not recapitulate the same effects when inserted in the telomere. We propose a model that defines the modes of action of MCM5 and CDC6 in silencing.

We hypothesized that some children with idiopathic short stature in Chile might bear heterozygous mutations of the GH receptor. We selected 26 patients (3 females, 23 males) from 112 patients who consulted for idiopathic short stature at the University of Chile. Their chronological age was 8.3 ± 1.9, and bone age was 6.1± 1.0 yr. Their height was −3.0 ± 0.7 sds; IGF-I, −1.2 ± 1.1 sd; IGF binding protein 3, −0.7 ± 2.0 SDS; and GH binding protein, 0.4 ± 0.8 SDS. Patients were admitted, and blood samples were obtained every 20 min to determine GH concentrations overnight. Coding sequences and intron-exon boundaries of exons 2–10 of GH receptor gene were amplified by PCR and subsequently analyzed through single-strand conformational analysis. Mean serum GH concentration, over 12-h, was 0.20 ± 0.08 nm; pulse amplitude, 0.40 ± 0.15 nm; number of peaks, 5.8 ±1.5 peaks/12 h; peak value of GH during the 12-h sampling, 1.03 ± 0.53 nm; and area under the curve, 151.4 ± 56.1 nm/12 h. There were positive correlations between mean GH vs. area under the curve (P < 0.001) and GH peak (P < 0.01). The single-strand conformational analysis of the GH receptor gene showed abnormal migration for exon 6 in 9 patients and for exon 10 in 9 patients, which (by sequence analysis) corresponded to 2 polymorphisms of the GH receptor gene: an A-to-G transition in third position of codon 168 in exon 6 and a C-to-A transversion in the first position of codon 526 in exon 10. We further sequenced all coding exons and intron-exon boundaries in the most affected patients (nos. 6, 9, 11, 14, 15, 16, and 23). This analysis revealed a C-to-T transition in codon 161 of exon 6 in patient 23, which results in an amino acid change (Arg to Cys) in an heterozygous form in the patient and his father. In conclusion, the results of our study suggest that, in Chilean patients with idiopathic short stature, GH receptor gene mutations are uncommon, although we cannot exclude mutations that were missed by single-strand conformational analysis or mutations within introns or in the promoter regions of the GH receptor gene.

In this study, the effects of progesterone (P4) on the immunoreactivity to the neurite growth inhibitor Nogo-A, its receptor (Ng-R), and its effector Rho-A in the rat hippocampus, in association with parameters of spatial learning and memory following global cerebral ischemia, were assessed. Adult male rats were subjected to global cerebral ischemia (15 min), and treated with P4 or its vehicle at 15 min, 2, 6, 24, 48 and 72 h of reperfusion. Immunoreactivity to Nogo-A, Ng-R, and Rho-A was evaluated at 24 h, 72 h or 7 d, or at 14 d of reperfusion after rats were tested in the Morris Water Maze (MWM). Global cerebral ischemia induced an increase in Nogo-A, Ng-R, and Rho-A immunoreactivities in the cell bodies of CA1 pyramidal neurons at 24h after global cerebral ischemia, peaking at 72 h, and persisting 14 d later. In addition, at 72 h, a strong immunoreactivity was observed in the hippocampal layers where dendritic arborizations of CA1 pyramidal neurons are located. Treatment with P4 reduced Nogo-A, Ng-R, and Rho-A immunoreactivities in CA1, particularly at 72 h of reperfusion. These effects of P4 were consistent with the parameters of a more efficient spatial learning and memory in the MWM, as compared to vehicle-treated rats. Overall results suggest the reduction of neurite growth inhibitory molecules Nogo-A, Ng-R, and Rho-A, as a part of the restorative effects of progesterone possibly allowing the plastic phenomena to occur, able to support the functional preservation of the hippocampus following global cerebral ischemia.

Delayed death of hippocampal CA1 pyramidal neurons following global cerebral ischemia/reperfusion may be mediated, in part, by caspase-3 activation resulting in DNA fragmentation. Progesterone (P4) is known to exert neuroprotective effects in several models of brain injury. This study was designed to assess the effect of P4 on caspase-3 levels and activation, and DNA fragmentation in the hippocampus following global cerebral ischemia/reperfusion. Adult male Sprague-Dawley rats were subjected to global ischemia by the four-vessel occlusion model. P4 (8 mg/kg), or its vehicle were administered i.v. at 15 min, 2, 6, 24, 48 and 70 h of reperfusion. Remaining pyramidal neurons were assesed by the Nissl staining technique, caspase-3 levels and activation by immunohistochemistry and an in situ activity assay, and DNA fragmentation by the TUNEL method. Post-ischemic progesterone treatment significantly reduced the ischemia/reperfusion-induced increase in caspase-3 levels and activation at 72 h, and DNA fragmentation and CA1 neuronal loss at 7 days. Present results suggest the reduction of caspase-3 levels/activation, and DNA fragmentation, as a part of the neuroprotective effects of progesterone against global cerebral ischemia/reperfusion injury.

GCN5 encodes one of the non-essential Histone Acetyl Transferases in Saccharomyces cerevisiae. Extensive evidence has indicated that GCN5 is a key regulator of gene expression and could also be involved in transcriptional elongation, DNA repair and centromere maintenance. Here we show that the deletion of GCN5 decreases the stability of mini-chromosomes; that the tethering of Gcn5p to a crippled origin of replication stimulates its activity; that high dosage of GCN5 suppresses conditional phenotypes caused by mutant alleles of bona fide replication factors, orc2-1, orc5-1 and mcm5-461. Furthermore, Gcn5p physically associates with origins of DNA replication, while its deletion leads to localized condensation of chromatin at origins. Finally, Deltagcn5 cells display a deficiency in the assembly of pre-replicative complexes. We propose that GCN5 acts as a positive regulator of DNA replication by counteracting the inhibitory effect of Histone Deacetylases.

Among a hypothetical cohort of 11-18-year-old females, we used a probabilistic decision tree model to estimate the number of pregnant adolescent females potentially receiving contraindicated vaccines during well child exams, and to determine the impact of two different pregnancy screening strategies on pregnancy detection rates, vaccine administration and pregnancy detection-associated costs. We found that under current practice conditions, the majority (95-99%) of adolescent pregnancies are likely missed during well child exams, allowing the opportunity to administer contraindicated vaccines. A strategy to test everyone detected the highest proportion of pregnancies, but at a substantial financial cost (USD 12,270,037-USD 19,430,607). Testing was more efficient for older adolescents, but both testing strategies were associated with a significant number of false positive test results (41-98%), regardless of age. These results suggest that systematic pregnancy screening strategies would be effective for preventing pregnant adolescents from receiving contraindicated vaccines, but may not be worth the potentially high financial and psychological costs.