Concentrations of chlorinated pollutants in adipose tissue of yellow-legged gulls (Larus michahellis) from Spain: Role of gender and age.

Concentrations of 7 different polychlorinated biphenyl (PCB) congeners, and eleven organochlorine pesticides (OCPs) and metabolites, including DDTs (dichlorodiphenyltrichloroethane), HCHs (hexachlorocyclohexane isomers), Endosulfan, Endosulfan sulfate, Endrin, Dieldrin and HCB (hexachlorobenzene), were determined in adipose tissue of 57 yellow-legged gulls collected from NW and N Spain. Furthermore, the possible differences due to two endogenous factors, age and gender, were determined. All the analyzed PCBs were detected in over 66% of the samples, with levels of 291.9 (PCB 180), 34.5 (PCB 118), 0.7 (PCB 28), 432.6 (PCB 153), 225.5 (PCB 138), 1.3 (PCB 101) and 0.4 (PCB 52) µg/kg of adipose tissue. With respect to the OCPs and metabolites, only 4,4'-DDE and HCB were detected in more than 50% of the samples, with means of 360.6 and 2.5 µg/kg of adipose tissue, respectively. From all the considered contaminants, only 4,4'-DDE levels presented significant differences depending on the gender, with females showing higher values than males (p < 0.01). Significant differences (p < 0.001) were also found related to age for the levels of PCBs 180, 138, 101, 28 and 153, as well as 4,4'-DDE, with adult levels being higher than those in young birds. The results of the present study constitute a baseline to better assess the environmental impacts of PCB and OCP contamination at other coastal sites for future biomonitoring studies, with particular emphasis on gender- and age-related differences.

Does gender influence the levels of heavy metals in liver of wild boar?

The aim of this study was to determine heavy metal reference levels for risk assessment studies. For this purpose, the levels of lead, cadmium, copper and zinc were determined in liver tissues of wild boars sampled in NW Spain. The mean values were 0.383, 0.326, 23.50 and 56.86mg/kg dried weight, respectively. In general, the levels detected were similar to or lower than the levels reported in literature. This study not only provides a useful baseline for biomonitoring the levels of the analyzed contaminants in wildlife in NW Spain, it also helps to understand the effects of gender on the levels of these elements. Similar to studies performed in other geographical regions, no significant gender-related differences could be detected. Although differences were not significant, the levels of zinc, cadmium and lead were modestly higher in males (55.78, 0.346 and 0.424mg/kg, respectively) compared to females (45.25, 0.305 and 0.341mg/kg). Our results indicate that, although gender did not significantly affect heavy metal uptake and toxicokinetics of contaminants in wild boars, these effects could vary between species, populations, organs, and elements. It is therefore essential to investigate gender-related differences for each species.

Regenerative approaches for the treatment of early OA.

The diagnosis and the prompt treatment of early osteoarthritis (OA) represent vital steps for delaying the onset and progression of fully blown OA, which is the most common form of arthritis, involving more than 10 % of the world's population older than 60 years of age. Nonsurgical treatments such as physiotherapy, anti-inflammatory medications, and other disease-modifying drugs all have modest and short-lasting effect. In this context, the biological approaches have recently gained more and more attention. Growth factors, blood derivatives, such as platelet concentrates, and mesenchymal adult stem cells, either expanded or freshly isolated, are advocated amongst the most promising tool for the treatment of OA, especially in the early phases. Primarily targeted towards focal cartilage defects, these biological agents have indeed recently showed promising results to relieve pain and reduce inflammation in patients with more advanced OA as well, with the final aim to halt the progression of the disease and the need for joint replacement. However, despite of a number of satisfactory in vitro and pre-clinical studies, the evidences are still limited to support their clinical efficacy in OA setting.

Concentrations of Metals, Metalloids, and Chlorinated Pollutants in Blood and Plasma of White Stork (Ciconia ciconia) Nestlings From Spain.

The aim of this study was to determine the levels of different inorganic elements (lead [Pb], mercury [Hg], and arsenic [As]) and persistent chlorinated pollutants (including polychlorinated biphenyls [PCBs] and organochlorine pesticides [OCPs]) in blood and plasma of White stork (Ciconia ciconia) nestlings from northwest (NW) Spain. The concentrations of PCBs were lower than the limit of detection in all samples. The OCPs γ-HCH, 4,4'-DDE, HCB, and endosulfan were detected most frequently in plasma from White stork nestlings. These OCPs were detected in 98, 54, 39, and 37 % of all samples, respectively. However, the concentrations of organic pollutants were lower than the risk thresholds for birds. The mean levels of the inorganic elements Pb, Hg, and As were found to be 36.92 ± 33.48, 16.48 ± 12.87, and 9.813 ± 13.84 µg/L, respectively. These levels were also lower than the risk thresholds for birds. This study not only provides a snapshot of the levels of both inorganic and organic contaminants in wild White storks in NW Spain, it also provides a useful baseline for biomonitoring levels of the measured contaminants in this area.

Non-destructive multibiomarker approach in European quail (Coturnix coturnix coturnix) exposed to the herbicide atrazine.

The effect of orally administered atrazine (25 or 100 mg/kg on days 0, 5, and 10 of the experiment) was studied in European quail (Coturnix coturnix coturnix) on four non-destructive biomarkers: fecal porphyrins, blood glutathione-S-transferase, glutathione reductase, reduced glutathione, and malondialdehyde (MDA). Uroporphyrin I (UPI) and coproporphyrins I and III (CPIII) were the main porphyrins detected in feces. The lowest dose of ATZ caused a significant (P < 0.05) increase in UPI and CPIII at day 5, and the highest dose of ATZ caused an induction of CPI and a significant (P < 0.05) decrease in MDA levels at day 30.

Exact simulation of pigment-protein complexes unveils vibronic renormalization of electronic parameters in ultrafast spectroscopy.

The primary steps of photosynthesis rely on the generation, transport, and trapping of excitons in pigment-protein complexes (PPCs). Generically, PPCs possess highly structured vibrational spectra, combining many discrete intra-pigment modes and a quasi-continuous of protein modes, with vibrational and electronic couplings of comparable strength. The intricacy of the resulting vibronic dynamics poses significant challenges in establishing a quantitative connection between spectroscopic data and underlying microscopic models. Here we show how to address this challenge using numerically exact simulation methods by considering two model systems, namely the water-soluble chlorophyll-binding protein of cauliflower and the special pair of bacterial reaction centers. We demonstrate that the inclusion of the full multi-mode vibronic dynamics in numerical calculations of linear spectra leads to systematic and quantitatively significant corrections to electronic parameter estimation. These multi-mode vibronic effects are shown to be relevant in the longstanding discussion regarding the origin of long-lived oscillations in multidimensional nonlinear spectra.

[Radiosurgery as adjuvant treatment of a recurrent adult medulloblastoma. Ultra-early response]. / Radiocirugía como tratamiento complementario del meduloblastoma recidivadodel adulto: respuesta ultratemprana.

The role of radiosurgery after multimodality treatment of recurrent desmoplastic adult medulloblastoma is analyzed. The ultra-early clinical and pathological response of this tumor to adjunctive radiosurgery is stressed.

Arteriovenous fistula of the vertebral artery in a female infant with hypotonia and cephalocorporal disproportion.

BACKGROUND: Congenital arteriovenous fistulas are exceptional in childhood and imply a therapeutic challenge. CASE REPORT: A 9-month-old female infant was studied for cephalocorporal disproportion, hypotonia, progressive muscular atrophy and hyperreflexia. Computed tomography of the brain and electroencephalography were normal. Electromyographic patterns suggested proximal myopathic involvement. A continuous murmur with systolic reinforcement was audible in the neck. Angioresonance detected intracranial aneurysmal dilatations behind the bulbo-medullary junction and cerebral panangiography evidenced a direct vertebrovertebral fistula with extra- and intra-cranial varices and extreme medullary compression. Occlusion of the afferent vessel to the aneurismal sack was successfully achieved with a mixture of Histoacryl and 75% lipiodol via a microcatheter. CONCLUSION: Clinical signs of an arteriovenous fistula may be atypical. Considerable cephalocorporal disproportion and a bruit in the cervical or retromastoidal regions must suggest its existence. Complete obliteration with endovascular embolization permits somatic and neurological recovery.

Multipactor radiation analysis within a waveguide region based on a frequency-domain representation of the dynamics of charged particles.

A technique for the accurate computation of the electromagnetic fields radiated by a charged particle moving within a parallel-plate waveguide is presented. Based on a transformation of the time-varying current density of the particle into a time-harmonic current density, this technique allows the evaluation of the radiated electromagnetic fields both in the frequency and time domains, as well as in the near- and far-field regions. For this purpose, several accelerated versions of the parallel-plate Green's function in the frequency domain have been considered. The theory has been successfully applied to the multipactor discharge occurring within a two metal-plates region. The proposed formulation has been tested with a particle-in-cell code based on the finite-difference time-domain method, obtaining good agreement.

Effect of long-term exposure to simazine on histopathology, hematological, and biochemical parameters in Cyprinus carpio.

We investigated if residues of simazine in the natural waters would cause histological, hematological, and biochemical alterations in carps from contaminated areas in Badajoz (Spain). Some necrotic foci in kidney and liver, hepatitis, and hepatic steatosis were detected. No changes on measured hematological and biochemical parameters between fish from reference and contaminated ponds were observed. To assess if simazine exposure was the cause of these observations carps were exposed in the laboratory to simazine (45 microg/L) for 90 days. Some results obtained in the field were confirmed in laboratory, such as necrosis in kidney and liver and hepatic steatosis. Globular eosinophilic foci in kidney and a slight decrease of the hematocrit were also detected. These changes were moderate and indicative of an adaptation of the fish to the toxic stress caused by exposure to low simazine concentrations.

Comparative study of esterase activities in different tissues of marine fish species Trachurus trachurus, Merluccius merluccius and Trisopterus luscus.

Pesticides are one of the most frequently anthropogenic xenobiotics detected in water. Among these, the organophosphorus pesticides (OPs) are very widely used in agriculture due to their broad spectrum of activity and their low price, but they also have high potent effects as neurotoxic compounds in non-target organisms. The aim of this study was to evaluate biomarkers acetylcholinesterase (AChE), butyrylcholinesterase (BChE), propionylcholinesterase (PChE) and carboxylesterase (CbE) in the representative Atlantic fish species Trachurus trachurus, Merluccius merluccius and Trisopterus luscus from "Rías Gallegas", a traditional Spanish fishing area. These esterase activities were evaluated in the brain, muscle and liver to determine the most adequate tissue to measure such enzymatic activities. The sensitivity of AChE and CbE activities from different tissues the widely used organophosphorus insecticide chlorpyrifos (CP), and its toxic metabolite (CP-oxon) was also tested. AChE activity was predominant in all tissues of the analysed species (particularly in brain constituting from 78.33%, 89.83% and 88.43% of total ChEs in Trachurus trachurus, Merluccius merluccius and Trisopterus luscus, respectively). Under in vitro exposure, esterases were shown to be highly sensitive to CP and especially to CP-oxon. Moreover, a similar effect observed on AChE and CbE activities could suggest that CbE activity might contribute efficiently against the toxic effects of CP, especially in muscle and the liver. The presence of BChE, PChE and upper CbE activities in muscle and the liver and their OP-sensibilities can be used to study their function in the pesticide biochemical detoxification pathways with a prominent role as a safeguarding mechanism against pesticide toxicity.

Fractal dimension analysis of states of consciousness and unconsciousness using transcranial magnetic stimulation.

BACKGROUND AND OBJECTIVE: Knowing whether a subject is conscious or not is a current challenge with a deep potential clinical impact. Recent theoretical considerations suggest that consciousness is linked to the complexity of distributed interactions within the corticothalamic system. The fractal dimension (FD) is a quantitative parameter that has been extensively used to analyse the complexity of structural and functional patterns of the human brain. In this study we investigate FD to assess whether it can discriminate between consciousness and different states of unconsciousness in healthy individuals. METHODS: We study 69 high-density electroencephalogram (hd-EEG) measurements after transcranial magnetic stimulation (TMS) in 18 healthy subjects progressing from wakefulness to non-rapid eye movement (NREM) sleep and sedation induced by different anaesthetic agents (xenon and propofol). We quantify the integration of thalamocortical networks by calculating the FD of a spatiotemporal voxelization obtained from the locations of all sources that are significantly activated by the perturbation (4DFD). Moreover, we study the temporal evolution of the evoked spatial distributions and compute a measure of the differentiation of the response by means of the Higuchi FD (HFD). Finally, a Fractal Dimension Index (FDI) of perturbational complexity is computed as the product of both quantities: integration FD (4DFD) and differentiation FD (HFD). RESULTS: We found that FDI is significantly lower in sleep and sedation when compared to wakefulness and provides an almost perfect intra-subject discrimination between conscious and unconscious states. CONCLUSIONS: These results support the combination of FD measures of cortical integration and cortical differentiation as a novel paradigm of tracking complex spatiotemporal dynamics in the brain that could provide further insights into the link between complexity and the brain's capacity to sustain consciousness.

Sperm nucleomorphogenesis in the cephalopod Sepia officinalis.

Sperm nucleomorphogenesis in the cephalopod Sepia officinalis is the product of the interaction between perinuclear microtubules and condensing chromatin. This interaction occurs during spermiogenesis and is established through the nuclear membrane. As in other cephalopod species, the perinuclear microtubules are transient structures. In the case of S. officinalis, they begin to appear in the basal area of the early spermatid and progress from there, establishing contact with the external nuclear membrane and follow a defined, but not symmetric, geometry. Thus, the microtubules accumulate preferentially in one area of the nuclear membrane which we refer to here as the "dorsal zone". Later, the microtubules will be eliminated before the mature spermatid migrates to the epidydimis. The chromatin is condensed within the nucleus following a complex pattern, beginning as fibro-granular structures until forming fibres of approximately 45 nm diameter (patterning phases). From this stage on, an increase in the chemical basicity of DNA-interacting proteins is produced, and chromatin fibres coalesce together, being recruited to the dorsal zone of the membrane, where there is a higher density of microtubules. This last step (condensation phases) allows the chromatin fibres to be arranged parallel to the axis of the elongating nucleus, and more importantly, is deduced to cause a lateral compression of the nucleus. This lateral compression is in fact a recruitment of the ventral zone toward the dorsal zone, which brings about an important reduction in nuclear volume. The detailed observations which comprise this work complement previous studies of spermiogenesis of Sepia and other cephalopods, and will help to better understand the process of cellular morphology implicated in the evolution of sperm nuclear shape in this taxonomic group.

Platelet-lymphocyte and neutrophil-lymphocyte ratios are prognostic but not predictive of response to abiraterone acetate in metastatic castration-resistant prostate cancer.

PURPOSE: Recently neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been reported to be inflammatory parameters that confer poorer outcome in metastatic castration-resistant prostate cancer (mCPRPC). However, these ratios have not been analyzed in patients treated with abiraterone acetate. We explored the relationship between different values of PLR and NLR and survival in mCPRCP treated with abiraterone and their possible relation with a prostate specific antigen (PSA) response. METHODS: We retrospectively analyzed 101 patients with mCRPC treated with abiraterone from January of 2012 to November of 2015 in two different hospitals. A cut-off value of 5 for NLR and 150 for PLR were used to compare survival by Kaplan-Meier method. Moreover, an association between these cut-off values and the PSA response was analyzed by a χ 2 test. RESULTS: In the case of NLR, the median DFS were 12, 1 months for NLR <5 and 7 months for NLR ≥5, p = 0.061. The median OS were 23.9 months for NLR <5 and 16.3 months for NLR ≥5, p = 0.046. In the case of PLR, the median DFS were 11.8 months for PLR <150 and 10.6 months for PLR ≥150, p = 0.549. The median OS were 27.4 months for PLR <150 and 15.9 months for PLR ≥150, p = 0.005. It was not observed a correlation between the different cut-off values of PLR or NLR and a PSA response ≥25% (p = 0.31). CONCLUSIONS: It is shown a better prognostic relationship between PLR and NLR low values and OS that is statistically significant in mCPRC patients treated with abiraterone. Furthermore, it was not shown a relation between PLR and NLR values and PSA response.

Quinacrine inhibits the calcium-induced calcium release in heavy sarcoplasmic reticulum vesicles.

Quinacrine is a fluorescence probe useful for studying the effect of local anesthetics. The interaction of quinacrine and sarcoplasmic reticulum membranes measured by fluorescence spectroscopy indicates the presence of a saturable binding site. Typical local anesthetics are able to displace quinacrine bound to heavy sarcoplasmic reticulum membranes. The effectiveness of that displacement decreases in the order dibucaine greater than tetracaine greater than benzocaine greater than lidocaine greater than procaine greater than procainamide, indicating that the size and hydrophobicity of quinacrine are major determinants in the binding process. The use of radioactive tracer and a rapid filtration technique reveals that quinacrine interacts, at lower concentrations, with sarcoplasmic reticulum membranes by blocking the Ca2+-induced Ca2+ release. Higher quinacrine concentrations also affect the Ca2+-pump activity.

Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry.

A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. "Time of addition" experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.

Betulinic acid derivatives: a new class of human immunodeficiency virus type 1 specific inhibitors with a new mode of action.

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.

On the effect of lysophosphatidylcholine, platelet activating factor and other surfactants on calcium permeability in sarcoplasmic reticulum vesicles.

The effect of low concentrations of lysophosphatidylcholine (LPC), platelet-activating factor (PAF) and other surfactants (Triton X-100, C12E8, sodium dodecyl sulfate, sodium cholate and sodium deoxycholate) on membrane permeability of native sarcoplasmic reticulum vesicles and sarcoplasmic reticulum lipid vesicles, has been studied. Triton X-100, C12E8, sodium dodecyl sulfate, sodium cholate and sodium deoxycholate were all able to permeabilize membranes at concentrations of surfactants below their critical micellar concentration (CMC) in both lipid and native vesicles, being the K0.5 of calcium release from native vesicles lower than that from lipid vesicles. The values of these K0.5 were well correlated with the corresponding CMC values for each type of membrane. However, both LPC and PAF behaved in a different way since, although they induced permeabilization of the native vesicles at values of K0.5 close to their CMC, their K0.5 values for permeabilizing vesicles, prepared by using lipids extracted from sarcoplasmic reticulum, were much higher than their corresponding CMC.

Modeling RNA secondary structures. I. Mathematical structural model for predicting RNA secondary structures.

A mathematical model for analyzing the secondary structures of RNA is developed that is based on the connection matrix associated with the planar p-h graph. The classification of the elementary structures allows the introduction of the basis of structural space from which to build the global secondary structure. All admissible solutions belong to the configuration space and can be obtained directly from its basis.

Modeling RNA secondary structures. II. The geometric structural solution for tRNA.

The set of admissible solutions of the configuration space of tRNA molecules is obtained after incorporating further restrictions based on the principles of local stability and homology as well as on geometric and energetic considerations.