Embryonic Stem Cell-Derived L1 Overexpressing Neural Aggregates Enhance Recovery after Spinal Cord Injury in Mice

An obstacle to early stem cell transplantation into the acutely injured spinal cord is poor survival of transplanted cells. Transplantation of embryonic stem cells as substrate adherent embryonic stem cell-derived neural aggregates (SENAs) consisting mainly of neurons and radial glial cells has been shown to enhance survival of grafted cells in the injured mouse brain. In the attempt to promote the beneficial function of these SENAs, murine embryonic stem cells constitutively overexpressing the neural cell adhesion molecule L1 which favors axonal growth and survival of grafted and imperiled cells in the inhibitory environment of the adult mammalian central nervous system were differentiated into SENAs and transplanted into the spinal cord three days after compression lesion. Mice transplanted with L1 overexpressing SENAs showed improved locomotor function when compared to mice injected with wild-type SENAs. L1 overexpressing SENAs showed an increased number of surviving cells, enhanced neuronal differentiation and reduced glial differentiation after transplantation when compared to SENAs not engineered to overexpress L1. Furthermore, L1 overexpressing SENAs rescued imperiled host motoneurons and parvalbumin-positive interneurons and increased numbers of catecholaminergic nerve fibers distal to the lesion. In addition to encouraging the use of embryonic stem cells for early therapy after spinal cord injury L1 overexpression in the microenvironment of the lesioned spinal cord is a novel finding in its functions that would make it more attractive for pre-clinical studies in spinal cord regeneration and most likely other diseases of the nervous system

Light-evoked Somatosensory Perception of Transgenic Rats That Express Channelrhodopsin-2 in Dorsal Root Ganglion Cells

In vertebrate somatosensory systems, each mode of touch-pressure, temperature or pain is sensed by sensory endings of different dorsal root ganglion (DRG) neurons, which conducted to the specific cortical loci as nerve impulses. Therefore, direct electrical stimulation of the peripheral nerve endings causes an erroneous sensation to be conducted by the nerve. We have recently generated several transgenic lines of rat in which channelrhodopsin-2 (ChR2) transgene is driven by the Thy-1.2 promoter. In one of them, W-TChR2V4, some neurons were endowed with photosensitivity by the introduction of the ChR2 gene, coding an algal photoreceptor molecule. The DRG neurons expressing ChR2 were immunohistochemically identified using specific antibodies to the markers of mechanoreceptive or nociceptive neurons. Their peripheral nerve endings in the plantar skin as well as the central endings in the spinal cord were also examined. We identified that ChR2 is expressed in a certain population of large neurons in the DRG of W-TChR2V4. On the basis of their morphology and molecular markers, these neurons were classified as mechanoreceptive but not nociceptive. ChR2 was also distributed in their peripheral sensory nerve endings, some of which were closely associated with CK20-positive cells to form Merkel cell-neurite complexes or with S-100-positive cells to form structures like Meissner's corpuscles. These nerve endings are thus suggested to be involved in the sensing of touch. Each W-TChR2V4 rat showed a sensory-evoked behavior in response to blue LED flashes on the plantar skin. It is thus suggested that each rat acquired an unusual sensory modality of sensing blue light through the skin as touch-pressure. This light-evoked somatosensory perception should facilitate study of how the complex tactile sense emerges in the brain

Chondroitin sulfates and their binding molecules in the central nervous system

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases

Urban-agricultural water appropriation: the Hyderabad, India case

With the urbanisation drive comes steady growth in urban water demand. Although in the past this new demand could often be met by tapping unclaimed water sources, this option is increasingly untenable in many regions where little if any unclaimed water remains. The result is that urban water capture, and the appropriation of associated physical and institutional infrastructure, now often implies conflict with other existing uses and users. While the urbanisation process has been studied in great depth, the processes and, critically, impacts of urban water capture and appropriation are not well researched or understood. This paper undertakes a critical examination of the specific case of Hyderabad, one of India's fastest growing cities, to shed light more generally on the process of water capture by cities and the resultant impacts on pre-existing claims, particularly agriculture. It does this by examining the history and institutional response to Hyderabad's urban-rural water contest; how the results of that contest are reflected in surface and groundwater hydrology; and the eventual impacts on agriculture. The findings show that the magnitude, and sometimes even direction, of impact from urban water transfer vary in space and time and depend on location-specific rainfall patterns, the nature of existing water infrastructure and institutions, and farmers' adaptive capacities and options, notably recourse to groundwater. Broader consideration of the specific findings provides insights into policy mechanisms to reduce the possible negative impacts from the global, and seemingly inexorable, flow of water to the world's growing cities

Urban-agricultural water appropriation: the Hyderabad, India case

With the urbanisation drive comes steady growth in urban water demand. Although in the past this new demand could often be met by tapping unclaimed water sources, this option is increasingly untenable in many regions where little if any unclaimed water remains. The result is that urban water capture, and the appropriation of associated physical and institutional infrastructure, now often implies conflict with other existing uses and users. While the urbanisation process has been studied in great depth, the processes and, critically, impacts of urban water capture and appropriation are not well researched or understood. This paper undertakes a critical examination of the specific case of Hyderabad, one of India's fastest growing cities, to shed light more generally on the process of water capture by cities and the resultant impacts on pre-existing claims, particularly agriculture. It does this by examining the history and institutional response to Hyderabad's urban-rural water contest; how the results of that contest are reflected in surface and groundwater hydrology; and the eventual impacts on agriculture. The findings show that the magnitude, and sometimes even direction, of impact from urban water transfer vary in space and time and depend on location-specific rainfall patterns, the nature of existing water infrastructure and institutions, and farmers' adaptive capacities and options, notably recourse to groundwater. Broader consideration of the specific findings provides insights into policy mechanisms to reduce the possible negative impacts from the global, and seemingly inexorable, flow of water to the world's growing cities

A preliminary randomized controlled trial of contingency management for alcohol use reduction using a transdermal alcohol sensor

Aims: We tested the efficacy of daily contingent reinforcement for reducing alcohol use compared with (yoked) non-contingent reinforcement (NR) using a transdermal alcohol sensor to detect alcohol use. Design: Pilot randomized controlled design with 1 baseline week, 3 intervention weeks and 1-month follow-up. Setting: New England, USA. Participants: Heavy drinking adults (46.7% female) not seeking treatment were randomized to (1) an escalating schedule of cash reinforcement (CR; n = 15) for days on which alcohol was neither reported nor detected or (2) yoked NR (n = 15). Intervention and comparator: Reinforcement for CR participants started at $5 and increased$2 every subsequent day on which alcohol was not detected or reported, to a maximum of $17. Participants received no reinforcement for days on which alcohol use was detected or reported, and the reinforcer value was re-set to$5 the day after a drinking day. NR participants were yoked to the daily reinforcer value of an individual in the CR condition, in order of enrollment. Paired participants in CR and NR therefore received the same amount of money, but the amount for the NR participant was not behavior-related. Measurements: The primary outcome was percentage of days without sensor-detected drinking. Secondary outcomes were number of consecutive days with no detected drinking, peak transdermal alcohol concentration (TAC), self-reported drinks per week and drinking below NIH low-risk guidelines. Findings: Controlling for baseline, CR had a higher percentage of days with no drinking detected (54.3%) than NR (31.2%) during intervention weeks [P = 0.05, Cohen\u27s d = 0.74; 95% confidence interval (CI) = 0.007–1.47]. The longest period of consecutive days with no drinking detected was 8.0 for CR versus 2.9 for NR (P = 0.03, d = 0.85; 95% CI = 0.08–1.61). Peak TAC during intervention showed a non-significant group difference (P = 0.20; d = 0.48; 95% CI = 0.00–1.18); a similar result was found for drinks per week (P = 0.12; d = 0.59; 95% CI = 0.00–1.30). Four times more participants in CR drank below NIH low-risk drinking guidelines during intervention than did participants in NR: 31.1 versus 7.1% (P = 0.07; d = 0.71; 95% CI = –0.04 to 1.46). At 1-month follow-up, the highest number of consecutive days without drinking (self-report) did not differ significantly between conditions (P = 0.26), but showed a medium effect size (d = 0.44; 95% CI = −0.32 to 1.18). Conclusions: Cash incentives linked to a transdermal alcohol sensor can reduce heavy alcohol consumption while the incentives are in operation

Using the internet to access key populations in ecological momentary assessment research: comparing adherence, reactivity, and erratic responding across those enrolled remotely versus in-person.

Ecological momentary assessment (EMA) is a set of longitudinal methods that researchers can use to understand complex processes (e.g., health, behavior, emotion) in “high resolution.” Although technology has made EMA data collection easier, concerns remain about the consistency and quality of data collected from participants who are enrolled and followed online. In this study, we used EMA data from a larger study on HIV-risk behavior among men who have sex with men (MSM) to explore whether several indicators of data consistency/quality differed across those who elected to enroll in-person and those enrolled online. One hundred MSM (age 18–54) completed a 30-day EMA study. Forty-five of these participants chose to enroll online. There were no statistically significant differences in response rates for any survey type (e.g., daily diary [DD], experience sampling [ES], event-contingent [EC]) across participants who enrolled in-person versus online. DD and ES survey response rates were consistent across the study and did not differ between groups. EC response rates fell sharply across the study, but this pattern was also consistent across groups. Participants’ responses on the DD were generally consistent with a poststudy follow-up Timeline Followback (TLFB) with some underreporting on the TLFB, but this pattern was consistent across both groups. In this sample of well-educated, mostly White MSM recruited from urban areas, EMA data collected from participants followed online was as consistent, reliable, and valid as data collected from participants followed in-person. These findings yield important insights about best practices for EMA studies with cautions regarding generalizability. (PsycInfo Database Record (c) 2020 APA, all rights reserved