On the scalar curvature of constant mean curvature hypersurfaces in space forms

In this paper we study the behavior of the scalar curvature $S$ of a complete hypersurface immersed with constant mean curvature into a Riemannian space form of constant curvature, deriving a sharp estimate for the infimum of $S$. Our results will be an application of a weak Omori-Yau maximum principle due to Pigola, Rigoli and Setti \cite{PRS}.Comment: Final version (August 2009). To appear in Journal of Mathematical Analysis and Applications. Dedicated to Professor Marcos Dajczer on the occasion of his 60th birthda

Role of chondroitin sulfate proteoglycans (CSPGs) in synaptic plasticity and neurotransmission in mammalian spinal cord.

Chronic unilateral hemisection (HX) of the adult rat spinal cord diminishes conduction through intact fibers in the ventrolateral funiculus (VLF) contralateral to HX. Intraspinal injections of Chondroitinase-ABC, known to digest chondroitin sulfate proteoglycans (CSPGs) in the vicinity of injury, prevented this decline of axonal conduction. This was associated with improved locomotor function. We further injected three purified CSPGs into the lateral column of the uninjured cord at T10: NG2 and neurocan, which increase in the vicinity of a spinal injury, and aggrecan, which decreases. Intraspinal injection of NG2 acutely depressed axonal conduction through the injection region in a dose dependent manner. Similar injections of saline, aggrecan, or neurocan had no significant effect. These results identify a novel acute action of CSPGs on axonal conduction in spinal cord, and suggest that antagonism of proteoglycans reverses or prevents the decline of axonal conduction, in addition to stimulating axonal growth

Evaluation of optimal electrode configurations for epidural spinal cord stimulation in cervical spinal cord injured rats

© 2015 Elsevier B.V. Background: Epidural spinal cord stimulation is a promising technique for modulating the level of excitability and reactivation of dormant spinal neuronal circuits after spinal cord injury (SCI). We examined the ability of chronically implanted epidural stimulation electrodes within the cervical spinal cord to (1) directly elicit spinal motor evoked potentials (sMEPs) in forelimb muscles and (2) determine whether these sMEPs can serve as a biomarker of forelimb motor function after SCI. New method: We implanted EMG electrodes in forelimb muscles and epidural stimulation electrodes at C6 and C8 in adult rats. After recovering from a dorsal funiculi crush (C4), rats were tested with different stimulation configurations and current intensities to elicit sMEPs and determined forelimb grip strength. Results: sMEPs were evoked in all muscles tested and their characteristics were dependent on electrode configurations and current intensities. C6(-) stimulation elicited more robust sMEPs than stimulation at C8(-). Stimulating C6 and C8 simultaneously produced better muscle recruitment and higher grip strengths than stimulation at one site. Comparison with existing method(s): Classical method to select the most optimal stimulation configuration is to empirically test each combination individually for every subject and relate to functional improvements. This approach is impractical, requiring extensively long experimental time to determine the more effective stimulation parameters. Our proposed method is fast and physiologically sound. Conclusions: Results suggest that sMEPs from forelimb muscles can be useful biomarkers for identifying optimal parameters for epidural stimulation of the cervical spinal cord after SCI

Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine clinical model of spinal cord injury

Many hundreds of thousands of people around the world are living with the long-term consequences of spinal cord injury and they need effective new therapies. Laboratory research in experimental animals has identified a large number of potentially translatable interventions but transition to the clinic is not straightforward. Further evidence of efficacy in more clinically-relevant lesions is required to gain sufficient confidence to commence human clinical trials. Of the many therapeutic candidates currently available, intraspinally applied chondroitinase ABC has particularly well documented efficacy in experimental animals. In this study we measured the effects of this intervention in a double-blinded randomized controlled trial in a cohort of dogs with naturally-occurring severe chronic spinal cord injuries that model the condition in humans. First, we collected baseline data on a series of outcomes: forelimb-hindlimb coordination (the prespecified primary outcome measure), skin sensitivity along the back, somatosensory evoked and transcranial magnetic motor evoked potentials and cystometry in 60 dogs with thoracolumbar lesions. Dogs were then randomized 1:1 to receive intraspinal injections of heat-stabilized, lipid microtube-embedded chondroitinase ABC or sham injections consisting of needle puncture of the skin. Outcome data were measured at 1, 3 and 6 months after intervention; skin sensitivity was also measured 24 h after injection (or sham). Forelimb-hindlimb coordination was affected by neither time nor chondroitinase treatment alone but there was a significant interaction between these variables such that coordination between forelimb and hindlimb stepping improved during the 6-month follow-up period in the chondroitinase-treated animals by a mean of 23%, but did not change in controls. Three dogs (10%) in the chondroitinase group also recovered the ability to ambulate without assistance. Sensitivity of the dorsal skin increased at 24 h after intervention in both groups but subsequently decreased to normal levels. Cystometry identified a non-significant improvement of bladder compliance at 1 month in the chondroitinase-injected dogs but this did not persist. There were no overall differences between groups in detection of sensory evoked potentials. Our results strongly support a beneficial effect of intraspinal injection of chondroitinase ABC on spinal cord function in this highly clinically-relevant model of chronic severe spinal cord injury. There was no evidence of long-term adverse effects associated with this intervention. We therefore conclude that this study provides strong evidence in support of initiation of clinical trials of chondroitinase ABC in humans with chronic spinal cord injury

TEMPRANILLO is a regulator of juvenility in plants

Many plants are incapable of flowering in inductive daylengths during the early juvenile vegetative phase (JVP). Arabidopsis mutants with reduced expression of TEMPRANILLO (TEM), a repressor of FLOWERING LOCUS T (FT) had a shorter JVP than wild-type plants. Reciprocal changes in mRNA expression of TEM and FT were observed in both Arabidopsis and antirrhinum, which correlated with the length of the JVP. FT expression was induced just prior to the end of the JVP and levels of TEM1 mRNA declined rapidly at the time when FT mRNA levels were shown to increase. TEM orthologs were isolated from antirrhinum (AmTEM) and olive (OeTEM) and were expressed most highly during their juvenile phase. AmTEM functionally complemented AtTEM1 in the tem1 mutant and over-expression of AmTEM prolonged the JVP through repression of FT and CONSTANS (CO). We propose that TEM may have a general role in regulating JVP in herbaceous and woody species

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Insights on the climatic evolution at the pre-Jaramillo to Jaramillo transition in Europe using mineralogical analysis of the Quibas palaeontological site (Early Pleistocene, southern Iberian Peninsula)

© The Authors, 2023. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (for details please see http://creativecommons.org/licenses/by/4.0/), which permits use, copy, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source. This document is the Published version of a Published Work that appeared in final form in Spanish Journal of Palaeontology. To access the final edited and published work see https://doi.org/10.7203/sjp.27562The palaeontological site of Quibas is a karst outcrop with an age between 1.1 and 0.9 Ma (late Early Pleistocene). It represents the unique continuous sequence of terrestrial vertebrates of pre-Jaramillo to Jaramillo age in Europe. It is formed by two main structures: Quibas-Sima (divided into units QS-1 to QS-7) and Quibas-Cueva (QC-1– QC-6). In this work, we analyse the mineralogical composition of the sediments that form the stratigraphic units of Quibas-Sima using X-ray diffraction analysis, electrical conductivity, ion chromatography and optical emission spectrometry, to evaluate climatic trends in the sequence. Preliminary results indicate that there is an increase in the proportions of carbonates, gypsum and halite from QS-2 towards QS-4 and QS-5 (1.07–0.99 Ma), suggesting a progressive decrease in precipitation in south-eastern Iberian Peninsula a million years ago. Our data are consistent with the onset of a glacial phase, which is supported by the progressive disappearance of taxa related to forests and water bodies in Quibas-Sima, such as the flying squirrel Hylopetes sp. and the semiaquatic shrew Neomys sp., in favour of the appearance of taxa linked to open areas such as the Montpellier snake (Malpolon monspessulanus) and the snub-nosed viper (Vipera latastei). El yacimiento paleontológico de Quibas es un afloramiento kárstico con una edad comprendida entre 1,1 y 0,9 Ma (Pleistoceno Inferior tardío). Representa la única secuencia continua de vertebrados terrestres de edad pre-Jaramillo a Jaramillo de Europa. Está formado por dos estructuras principales: Quibas-Sima (dividida en las unidades QS-1 a QS-7) y Quibas-Cueva (QC-1 a QC-6). En este trabajo se estudia la composición mineralógica de los sedimentos que conforman las unidades estratigráficas de QuibasSima, a través e análisis de difracción de rayos X, conductividad eléctrica, cromatografía iónica y espectrometría de emisión óptica por plasma de argón, con el objetivo de evaluar tendencias paleoclimáticas en la secuencia. Los resultados preliminares indican que hay un aumento en las proporciones de carbonatos, yesos y halita desde QS-2 hacia QS-4 y QS-5 (1,07–0,99 Ma), lo que sugiere una progresiva disminución de las precipitaciones en el sureste peninsular hace un millón de años. Los datos son consistentes con el inicio de una fase glaciar, lo cual viene apoyado por la desaparición progresiva en Quibas-Sima de taxones afines a bosques y cursos de agua estables como la ardilla voladora Hylopetes sp. y el musgaño Neomys sp., en favor de la aparición de taxones ligados a espacios abiertos como la culebra bastarda (Malpolon monspessulanus) y la víbora hocicuda (Vipera latastei)

Sub-threshold spinal cord stimulation facilitates spontaneous motor activity in spinal rats

BACKGROUND: Epidural stimulation of the spinal cord can be used to enable stepping on a treadmill (electrical enabling motor control, eEmc) after a complete mid-thoracic spinal cord transection in adult rats. Herein we have studied the effects of eEmc using a sub-threshold intensity of stimulation combined with spontaneous load-bearing proprioception to facilitate hindlimb stepping and standing during daily cage activity in paralyzed rats. METHODS: We hypothesized that eEmc combined with spontaneous cage activity would greatly increase the frequency and level of activation of the locomotor circuits in paralyzed rats. Spontaneous cage activity was recorded using a specially designed swivel connector to record EMG signals and an IR based camcorder to record video. RESULTS AND CONCLUSION: The spinal rats initially were very lethargic in their cages showing little movement. Without eEmc, the rats remained rather inactive with the torso rarely being elevated from the cage floor. When the rats used their forelimbs to move, the hindlimbs were extended and dragged behind with little or no flexion. In contrast, with eEmc the rats were highly active and the hindlimbs showed robust alternating flexion and extension resulting in step-like movements during forelimb-facilitated locomotion and often would stand using the sides of the cages as support. The mean and summed integrated EMG levels in both a hindlimb flexor and extensor muscle were higher with than without eEmc. These data suggest that eEmc, in combination with the associated proprioceptive input, can modulate the spinal networks to significantly amplify the amount and robustness of spontaneous motor activity in paralyzed rats