Maritime-oriented foragers during the Late Pleistocene on the eastern costa del sol (Southeast Iberia): Cueva Victoria (Málaga, Spain).

The Mediterranean coast of Spain is marked by several clusters of Palaeolithic sites: to the south of the Pyrenees, in the area around the Ebro River, in the central part, and on the south coast, one of the southernmost regions in Europe. The number of sites is small compared with northern Iberia, but like that region, the Palaeolithic occupations are accompanied by several rock art ensembles. The archaeological material (both biotic and abiotic resources) and radiocarbon dates presented here were obtained during archaeological fieldwork of professor J. Fortea in the Late Pleistocene deposits in Cueva Victoria, located near the modern coastline and about 150 km north of the Strait of Gibraltar. In the three occupation phases, marine resources were acquired by shell-fishing (focusing almost exclusively on the clam Ruditapes decussatus), fishing, and the use of beached marine mammals. This contrasts with the limited data about the exploitation of terrestrial resources by hunting and gathering animals and plants. The study is completed by the study of artefacts (lithic and bone industry and objects of adornment) that help to understand the subsistence strategies of the cave occupants and enable a comparison with other groups inhabiting the Mediterranean coasts of the Iberian Peninsula during Greenland Interstadial 1, between ca. 15.1 and 13.6 cal BP.

Type I conventional dendritic cells relate to disease severity in virus-induced asthma exacerbations.

RATIONALE: Rhinoviruses are the major precipitant of asthma exacerbations and individuals with asthma experience more severe/prolonged rhinovirus infections. Concurrent viral infection and allergen exposure synergistically increase exacerbation risk. Although dendritic cells orchestrate immune responses to both virus and allergen, little is known about their role in viral asthma exacerbations. OBJECTIVES: To characterize dendritic cell populations present in the lower airways, and to assess whether their numbers are altered in asthma compared to healthy subjects prior to infection and during rhinovirus-16 infection. METHODS: Moderately-severe atopic asthmatic patients and healthy controls were experimentally infected with rhinovirus-16. Bronchoalveolar lavage was collected at baseline, day 3 and day 8 post infection and dendritic cells isolated using fluorescence activated cell sorting. MEASUREMENTS AND MAIN RESULTS: Numbers of type I conventional dendritic cells, which cross prime CD8+ T helper cells and produce innate interferons, were significantly reduced in the lower airways of asthma patients compared to healthy controls at baseline. This reduction was associated serum IgE at baseline and with reduced numbers of CD8+ T helper cells and with increased viral replication, airway eosinophils and reduced lung function during infection. IgE receptor expression on lower airway plasmacytoid dendritic cells was significantly increased in asthma, consistent with a reduced capacity to produce innate interferons. CONCLUSIONS: Reduced numbers of anti-viral type I conventional dendritic cells in asthma are associated with adverse outcomes during rhinovirus infection. This, with increased FcεR1α expression on lower airway plasmacytoid DCs could mediate the more permissive respiratory viral infection observed in asthma patients.

Relación entre medidas radiológicas y morfología de cadera en individuos con parálisis cerebral: serie de casos / Relationship between radiological measurements and hip morphology in subjects with cerebral palsy: case series

Introducción En la parálisis cerebral (PC) existen distintos procesos y tensiones musculares que afectan al desarrollo biomecánico de la articulación coxofemoral. El trabajo muestra las proporciones existentes entre medidas radiológicas referidas a musculatura periarticular de la cadera en relación con la morfología ósea. Materiales y métodos Estudio descriptivo, observacional y transversal de 14 individuos con PC pertenecientes a los niveles IV y V de la Gross Motor Function Classification System (28 caderas) de edades comprendidas entre los 6 y los 10 años. Se llevaron a cabo medidas radiológicas referidas a glúteo mediano, glúteo menor, cuadrado crural y pectíneo. También se valoraron el porcentaje de migración de Reimers y el ángulo cervicodiafisario de cada una de las caderas. Resultados Se comprueba una relación directa entre las distancias referidas a glúteo mediano y glúteo menor respecto a la realizada para el pectíneo e inversa de todas ellas respecto al cuadrado crural. El ángulo cervicodiafisario presentó relación inversa respecto a las proporciones para el cuadrado crural, tanto en proporción al glúteo mediano como en proporción al pectíneo. Discusión En la población de este estudio existe asociación entre una adecuada longitud de la musculatura pelvitrocantérea respecto a la aductora y abductora, y ángulos cervicodiafisarios cercanos a la normalidad, y son negativas medidas de acortamiento del cuadrado crural. Nivel de evidencia clínica Nivel IV.

Background In cerebral palsy (CP), there are different processes and muscle forces that affect the biomechanical developmental behaviour of the hip joint. This study aims to present the differences between radiological measurements as regards peri-articular hip musculature and the bone morphology. Materials and methods Descriptive, observational and cross-sectional study of 14 individuals, aged between 6 and 10 years, with CP at levels IV and V of the Gross Motor Function Classification System (28 hips). Radiological measurements were performed on the gluteus medius, gluteus minimus, quadratus femoris, and pectineus. Reimer's migration percentage and neck-shaft angle for each of the hips were also evaluated. Results A direct relationship was observed between distances as regards the gluteus medius and minimus, with respect to pectineus, and an inverse one of all with respect to quadratus femoris. The neck shaft angle showed an inverse relationship with the proportions for the quadratus femoris, both in proportion to the gluteus medius and pectineus. Discussion In the studied population, there is an association between an adequate length of the pelvic-trochanteric musculature with respect to the abductor and adductor and near-normal neck shaft angles, with measurements of shortening of the quadratus femoris being negative. Evidence level IV.

Functional and structural recovery of the injured spinal cord in rats treated with gonadotropin-releasing hormone.

Several studies have shown that gonadotropin-releasing hormone (GnRH) have extra-pituitary roles, including neurotrophic effects. This study was to evaluate the effects of GnRH treatment on the spinal cord injury (SCI) of rats. Ovariectomized rats were divided into: sham SCI surgery (Sham), SCI treated with saline solution (SCI + SS), and SCI treated with GnRH (SCI + GnRH). The SCI was induced by compression. One day after the lesion, SCI + GnRH group was injected with GnRH (60 µg/kg/twice/day; i.m.) for 15 days and the other groups with saline solution. To kinematic gait analysis, length and velocity of the stride were measured. In spinal cord, axonal morphometry and spared white and gray matter were analyzed by histochemistry. Protein expression of spinophilin was evaluated by western blot. The results showed that, 5 weeks after the injury, the group of animals treated with GnRH, significantly increased the length and velocity of the stride compared to SCI + SS group and they were similar to Sham group. In spinal cord, GnRH treatment increased the number and caliber of nerve axons and in the case of white matter, spared tissue was significantly higher than those animals treated with saline solution. The expression of spinophilin in spinal cord of SCI + GnRH group was slightly increased with respect to those not treated. In conclusion, GnRH treatment improves recovery of gait and decreases histopathological damage in the injured spinal cord of rat. These findings suggest that GnRH acts as a neurotrophic factor and can be used as a potential therapeutic agent for treatment of SCI.

Multichannel detrended fluctuation analysis reveals synchronized patterns of spontaneous spinal activity in anesthetized cats.

The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA-α mean = 1.04[Formula: see text]0.09) or simultaneously from several lumbar segments (mDFA-α mean = 1.01[Formula: see text]0.06), where α = 0.5 indicates randomness while α = 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA-[Formula: see text] = 0.992 as compared to initial conditions mDFA-α = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA-α = 0.924). In contrast to the classical methods, such as correlation and coherence quantification that define a relation between two sets of data, the mDFA method properly reveals the synchronization of multiple groups of neurons in several segments of the spinal cord. This method is envisaged as a useful tool to characterize the structure of higher order ensembles of cord dorsum spontaneous potentials after spinal cord or peripheral nerve lesions.

6-Hydroxydopamine lesion in thalamic reticular nucleus reduces anxiety behaviour in the rat.

We have studied the effect of the lesion of the dopaminergic innervation of the thalamic reticular nucleus (TRn) on anxiety and motor behaviour. The lesion of the dopamine innervation was produced by the injection of 6-hydroxydopamine into the dorsal part of the thalamic reticular nucleus. The lesion decreased the number of TH (+) cells of the pars compacta of substantia nigra by 33%, without modifying the number of TH (+) cells in ventral tegmental area. The lesion increased the time spent by the rats on the open arms of the elevated plus maze and decreased the duration of burying in the shock-probe test. Both results suggest reduced anxiety. The loss of the dopamine innervation to the TRn decreased the number of rearings but did not significantly affect total motor activity, gait or motor coordination, as evidenced by rotarod performance. These findings suggest that dopamine in the TRn plays a role in fear-related behaviour.

Differential development of body equilibrium among littermates in the newborn rabbit.

Interest is growing among psychobiologists and behavioral ecologists in the role of sibling relations in shaping individual development and life histories. In litters of domestic rabbits Oryctolagus cuniculus the heaviest pups at birth are more likely to survive the critical first postnatal week, they compete more effectively with littermates for milk and well-insulated positions in the litter huddle, and are the heaviest at weaning. Here we report that high birth weight pups are also better able to maintain body equilibrium. Testing pups' ability to maintain equilibrium when placed on a 15 degrees ramp for 2 min each day during the first postnatal week, we found that pups showed a continual daily improvement in their ability to maintain balance while moving on the ramp, rarely lost balance by postnatal day 8, and that heavier pups could maintain balance better and earlier than their lighter littermates. Better ability to maintain body equilibrium, however achieved, may help explain heavier pups' advantage in competing for vital resources such as milk and in gaining access to better-insulated positions in the litter huddle. It also provides further support for the usefulness of birth weight, not only as an absolute measure but also relative to the weight of other littermates, as a predictor of different developmental trajectories, behavioral and physiological, among same-age siblings in this mammal.

Differences in morphology and contractility of the bulbospongiosus and pubococcygeus muscles in nulliparous and multiparous rabbits.

In women, birth trauma can result in altered anatomy of supporting structures of the pelvic floor and in the development of urinary incontinence. The goal of this study was to investigate the association between parturition and the morphology and function of perineal and pelvic muscles in the female rabbit. In ten nulliparous and ten multiparous same-age females, we investigated morphological, histological (n = 5 females/group), and contractile characteristics (n = 5 females/group) of the perineal bulbospongiosus (Bsm) and the pelvic pubococcygeus (Pcm) muscles. Bsm and Pcm muscles of multiparous females were significantly lighter, they had a smaller cross-sectional fiber area, and developed significantly lower twitch and tetanic tension force in response to electrical stimulation than muscles of nulliparous females. In female rabbits, multiparity is associated with potentially pathological changes in the morphological and functional characteristics of these perineal and pelvic muscles, possibly as a result of stretching during parturition.

Functional and morphological effects of repeated sodium arsenite exposure on rat peripheral sensory nerves.

Exposure to inorganic arsenic (iAs) is known to result in peripheral neuropathy. To better understand the functional and morphological consequences of iAs exposure, we examined the electrophysiological and histological characteristics of the sensory sural nerves in adult Male Wistar rats following 30 days of sodium arsenite administration by gavage (10 mg/kg body weight/day). Arsenic (As) levels in the peripheral nerves of exposed animals were about 150 times greater than those in controls. Lipid peroxidation was also increased in iAs-exposed animals. Compound action potentials (CAPs) evoked in iAs-exposed nerves were characterized by a slower conduction velocity ( approximately 26%). iAs-exposed nerves also showed a trend towards a decreased CAP area ( approximately 35%). These electrophysiological changes were consistent with histological alterations such as a approximately 56% decrease in myelin thickness. In addition, the perimeter and transverse area of axons were reduced to 29% and 45% of control, respectively. Our results suggest that accumulation of As produced by iAs exposure induces oxidative damage, severe demyelination, and other morphological alterations in axons of peripheral nerves. These changes may, in turn, induce changes in the generation and propagation of action potentials in peripheral nerves, leading to decreased transmission of information from peripheral sensory organs to the central nervous system.

Absence of linear correlation between fluctuations in area of simultaneous recorded monosynaptic responses and Hoffmann's reflexes in the rat.

In this study we analyze the possible relationship between fluctuations in area of monosynaptic reflex responses (MSR) and Hoffmann's reflex (H reflexes) in the plantar closed loop pathway of the anesthetized rat. These reflexes were evoked by low-frequency stimuli applied to the sciatic nerve or lateral plantar nerve and then concurrently recorded on the distal tibial nerve or lateral plantar nerve, respectively as well as the lateral plantar muscles in the foot of the anesthetized rat. From trial to trial, H reflexes showed higher variability in area than MSR, whether the latter was recorded in the distal tibial nerve (n=8 experiments) or in the lateral plantar nerve (n=5 experiments). No linear correlation was found between changes in area of concurrently evoked MSR and H reflexes (r(MSR-H,n=8)=0.11+/-0.03 and r(MSR-H,n=5)=0.08+/-0.09, respectively). These findings suggest that trial-to-trial fluctuations in area of H reflexes may involve interaction of several sources of variation, among others to MSR variability (due to pre-, and post-synaptic factors influencing the excitability of spinal motoneurons) in combination with those related to peripheral mechanisms, such as trial to trial activation of a different number of muscle fibers, either by the probabilistic transmitter release from neuromuscular junctions, by activation of motor units of variable size or to fluctuations in excitability of muscle fibers.

Neurotensin polyplex as an efficient carrier for delivering the human GDNF gene into nigral dopamine neurons of hemiparkinsonian rats.

Recently we showed that the neurotensin polyplex is a nanoparticle carrier system that targets reporter genes in nigral dopamine neurons in vivo. Herein, we report its first practical application in experimental parkinsonism, which consisted of transfecting dopamine neurons with the gene coding for human glial cell line-derived neurotrophic factor (hGDNF). Hemiparkinsonism was induced in rats by a single dose of 6-hydroxydopamine (30 microg) into the ventrolateral part of the striatum. We showed that transfection of the hGDNF gene into the substantia nigra of rats 1 week after the neurotoxin injection produced biochemical, anatomical, and functional recovery from hemiparkinsonism. RT-PCR analysis showed mRNA expression of exogenous hGDNF in the transfected substantia nigra. Western blot analysis verified transgene expression by recognizing the flag epitope added at the C-terminus of the hGDNF polypeptide, which was found mainly in dopamine neurons by double immunofluorescence techniques. These data indicate that the neurotensin polyplex holds great promise for the neuroprotective therapy of Parkinson disease.

Lipid oxidative damage and distribution of inorganic arsenic and its metabolites in the rat nervous system after arsenite exposure: influence of alpha tocopherol supplementation.

Inorganic arsenic (iAs) exposure causes peripheral neuropathy. Oxidative effects caused by iAs exposure in peripheral nerves have been incompletely characterized. This study analyzed arsenic and lipid oxidative damage in the brain, spinal cord, and sciatic and sensory sural nerves following arsenite exposure. This study also explored whether alpha tocopherol (alpha-TOC) administration mitigates arsenite-induced oxidative damage. Thiobarbituric acid-reactive substance (TBARS) levels and distributions of iAs and its metabolites were evaluated in male Wistar rats following 30d of sodium arsenite exposure (10mg/kg bodyweight (bw)/d, by gavage). A second group also received alpha-TOC (125mg/kg bw/d, by gavage) during the final 20d of arsenite administration. Arsenite exposure caused increased TBARS levels within each region of the nervous system; oxidative stress was most pronounced in the sural and sciatic nerves. In addition there was a positive quadratic relationship between TBARS levels and the concentration of arsenicals found in the nervous system (r(2)=0.878, p<0.001). Dimethylarsenic was the predominant metabolite of iAs found. Animals alpha-TOC-treated had a 1.7-5.2-fold reduction in TBARS levels when compared with rats that received iAs alone. These results suggest that oxidative damage may be the main mechanism of toxicity induced by exposure of the peripheral nervous system to arsenite and that such damage could be attenuated by alpha-TOC-supplementation.

Biophysical characteristics of neurotensin polyplex for in vitro and in vivo gene transfection.

Previously we improved the neurotensin (NT)-polyplex by the coupling of HA2 fusogenic peptide (FP) and Vp1 SV40 karyophilic peptide (KP). We now report the proportion of [(125)I]-NT, [(3)H]-FP, and poly-l-lysine (PLL) in the NT-polyplex, and some of its biophysical properties. We concluded that the most efficient NT-polyplex comprised 1 NT, 4 FP, and 2 PLL molecules. Electrophoresis revealed that high acidity is detrimental for NT-polyplex stability. Electron microscopy and electrophoresis studies showed that 6 muM KP and 1% serum condensed the plasmid DNA (pDNA) before the appearance of toroid structures. Four plasmids were used to evaluate the transfection efficiency. In vitro, maximum expression was produced at molar ratios (pDNA : [(125)I]-NT-[(3)H]-FP-PLL conjugate) of 1:34 for pEGFP-N1 and 1:27 for pECFP-Nuc. Cotransfection of those plasmids was attained at their optimum molar ratios. In vivo, maximum expression of the pDAT-BDNF-flag in dopamine neurons was produced at a 1:45 molar ratio, whereas that of pDAT-EGFP was at 1:20. The NT-polyplex in the presence of 1 muM SR-48692, an NT-receptor specific antagonist, and untargeted polyplex did not cause transfection in vivo demonstrating the specificity of gene transfer via NT-receptor endocytosis. This information is essential for synthesizing an efficient NT-polyplex that can provide a useful tool for specific gene transfection.