Culture Environment-Induced Pluripotency of SACK-Expanded Tissue Stem Cells

Previous efforts to improve the efficiency of cellular reprogramming for the generation of induced pluripotent stem cells (iPSCs) have focused mainly on transcription factors and small molecule combinations. Here, we report the results of our focus instead on the phenotype of the cells targeted for reprogramming. We find that adult mouse pancreatic tissue stem cells derived by the method of suppression of asymmetric cell kinetics (SACK) acquire increased potency simply by culture under conditions for the production and maintenance of pluripotent stem cells. Moreover, supplementation with the SACK agent xanthine, which promotes symmetric self-renewal, significantly increases the efficiency and degree of acquisition of pluripotency properties. In transplantation analyses, clonal reprogrammed pancreatic stem cells produce slow-growing tumors with tissue derivative of all three embryonic germ layers. This acquisition of pluripotency, without transduction with exogenous transcription factors, supports the concept that tissue stem cells are predisposed to cellular reprogramming, particularly when symmetrically self-renewing

RECRUDESCENCE OF ONCHOCERCIASIS IN THE COMOÉ VALLEY IN SOUTHWEST BURKINA FASO.

: Onchocerciasis control by vector control was instigated in southwest Burkina Faso in January 1969 by ORSTOM/OCCGE, and continued until operations were taken over by the WHO Onchocerciasis Control Programme (OCP) in February 1975, which itself ceased operations in the area in 1989 when onchocerciasis was judged to have been reduced to insignificant levels. Initially (1969-1975) vector immigration maintained unacceptably high levels of transmission, but OCP was much larger than the preceding campaign and in 1975 the Annual Transmission Potential (ATP) dropped below 100 at all sites in the Comoé river valley except Folonzo, which continued to be subject to reinvasion, along with the whole of the Léraba river valley. However, after the southern extension of the OCP in 1979, ATPs dropped below 100 everywhere in the Comoé basin (including the Léraba valley), and further dropped to insignificant levels after the western extension of the OCP in 1985. Thus transmission dropped more quickly in the Comoé river valley than the Léraba river valley (which had been subject to vector reinvasion), and this was also reflected in prevalence of microfilaraemia in the human population. After 1986 prevalence was less than 5% in all villages in the Comoé river valley (except for two, which subsequently dropped to 0% and 3.7% by 1999). However, in 2001 (12 years after the cessation of vector control) the prevalence in one village in the Comoé river valley had increased to 39.6%, and two more had increased above 5% by 2007. New epidemiological surveys in 2011 and 2012 showed that in 13 out of 30 villages in the Comoé river valley prevalence of microfilaraemia was above 5%, although this was not observed in the Léraba river valley where prevalence remained low. This is the first documented case of recrudescence of onchocerciasis in the old OCP area, and the reasons are not clear. It is possible that there has been immigration of parasites with humans or vectors from areas where there has been a shorter period of control, or that control has been less effective. It is possible that in spite of very low levels of transmission the local parasite population was never reduced to a level below the transmission breakpoint, or that there has been a local recrudescence due to stochastic population effects. In any case it is clear that the distribution of ivermectin against lymphatic filariasis in the area since 2004 has failed to prevent the recrudescence of onchocerciasis, and the Burkina Faso Programme National de Lutte contre l'Onchocercose (PNLO - Ministere de la Santé) has instigated a programme of Community Directed Treatment with Ivermectin specifically aimed at onchocerciasis in accordance with the strategy developed by APOC and recommended to governments by OCP when it was dissolved in 2002.<br/

Lowbush blueberry fruit yield and growth response to inorganic and organic N-fertilization when competing with two common weed species

Inorganic N fertilizers are commonly used in commercial blueberry fields; however, this form of N can favor increased weed species’ growth, which can ultimately reduce the benefits of fertilization. We hypothesized that chipped ramial wood (CRW) compost is an effective alternative organic fertilizer for blueberry plants when weeds are present, as ericaceous shrub species are generally more efficient in utilizing organic N than herbaceous weed species. In this study, we measured the growth, fruit yield, and foliar N response of lowbush blueberry (Vaccinium angustifolium Aiton) to an application of 45 kg N ha-1 in the form of organic (CRW) or inorganic N (ammonium sulfate) in two areas of a commercial field colonized by either poverty oat grass (Danthonia spicata (L.) Beauv.) or sweet fern (Comptonia peregrina (L.) Coult.). We also assessed the impact of the fertilization treatments on litter decomposition rates. Contrary to our hypothesis, we found no significant increase in blueberry fruit yield or growth using CRW. By contrast, inorganic N-fertilization increased fruit yield by 70%. The effect was higher in the area colonized by D. spicata (+83%) than by C. peregrina (+45%). Blueberry fruit yield was on average twice higher in the area of the field having D. spicata than C. peregrina, suggesting a stronger competition with the latter. However, the increase in D. spicata density from 0–1 to >25 plants m-2 reduced fruit production by three-fold and strongly impacted vegetative growth in both fertilized and unfertilized plots. The impact of increased C. peregrina density was comparatively much lower, especially on vegetative growth, which was much higher in the area having C. peregrina. These patterns are likely due to a lower competition for N uptake with C. peregrina as this species can derive N from the atmosphere. Interestingly, the higher fruit yield in the area colonized by D. spicata occurred even in plots where the weeds were nearly absent (density of 0–1 plant m-2), revealing the influence of unidentified variables on blueberry fruit yield. We hypothesized that this difference resulted from over-optimal foliar N concentrations in the area colonized by C. peregrina as suggested by the significantly higher foliar N concentrations and by the negative correlation between foliar N concentrations and fruit yields in this area. The possibility of an influence of C. peregrina on flowering and pollination success, as well as of unidentified local site conditions is discussed. The tested N-fertilization treatments did not affect foliar N concentrations or litter decomposition rates. Overall, our results show that ammonium sulfate is very effective at increasing fruit yields but that both fruit yields and the efficiency of the N-fertilization treatment are decreased by increased D. spicata density, especially above 25 plants m-2. Although CRW did not significantly enhance fruit yields in the short term, this fertilizer may have a long-term beneficial effect

Retroperitoneal Transdiaphragmatic Robotic-Assisted Laparoscopic Resection of a Left Thoracolumbar Neurofibroma

ObjectiveRobotic technology has been used in a variety of surgical procedures for its 3D magnification and precision. Minimally invasive techniques have already become common in neurosurgery; however, robotic-assisted procedures in neurosurgery are still a relatively new frontier. This report describes the first use of robotic technology to resect a left thoracolumbar neurofibroma.Case reportA 19-year-old male with a family history of neurofibromatosis was diagnosed with a suspected 3-cm x 4-cm neurofibroma in the T12-L1 left paraspinal area. His only complaint was back pain requiring narcotic analgesics. He had no other findings on physical examination or laboratory/radiologic workup.MethodsAfter consulting urologic robotic surgeons, it was agreed to use the da Vinci robot (Intuitive Surgical, Sunnyvale, CA) for the resection of this mass. Following retroperitoneal laparoscopic access, the urologic surgeons opened the diaphragm and began the initial mobilization of the mass laparoscopically. The robot was docked, and the neurosurgeon operated the robot at the console to resect the mass from its nerve origin. There were no complications, and the mass, a confirmed neurofibroma, was completely removed. The patient was discharged on postoperative day 2; his back pain resolved, requiring no analgesia by the end of the first postoperative week.ConclusionThis case provides early evidence that robotic assistance can be successfully used for the resection of a paraspinal neurofibroma

Detection of subthreshold pulses in neurons with channel noise

Neurons are subject to various kinds of noise. In addition to synaptic noise, the stochastic opening and closing of ion channels represents an intrinsic source of noise that affects the signal processing properties of the neuron. In this paper, we studied the response of a stochastic Hodgkin-Huxley neuron to transient input subthreshold pulses. It was found that the average response time decreases but variance increases as the amplitude of channel noise increases. In the case of single pulse detection, we show that channel noise enables one neuron to detect the subthreshold signals and an optimal membrane area (or channel noise intensity) exists for a single neuron to achieve optimal performance. However, the detection ability of a single neuron is limited by large errors. Here, we test a simple neuronal network that can enhance the pulse detecting abilities of neurons and find dozens of neurons can perfectly detect subthreshold pulses. The phenomenon of intrinsic stochastic resonance is also found both at the level of single neurons and at the level of networks. At the network level, the detection ability of networks can be optimized for the number of neurons comprising the network.Comment: 14 pages, 9 figure

ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons

BACKGROUND: ASIC3, the most sensitive of the acid-sensing ion channels, depolarizes certain rat sensory neurons when lactic acid appears in the extracellular medium. Two functions have been proposed for it: 1) ASIC3 might trigger ischemic pain in heart and muscle; 2) it might contribute to some forms of touch mechanosensation. Here, we used immunocytochemistry, retrograde labelling, and electrophysiology to ask whether the distribution of ASIC3 in rat sensory neurons is consistent with either of these hypotheses. RESULTS: Less than half (40%) of dorsal root ganglion sensory neurons react with anti-ASIC3, and the population is heterogeneous. They vary widely in cell diameter and express different growth factor receptors: 68% express TrkA, the receptor for nerve growth factor, and 25% express TrkC, the NT3 growth factor receptor. Consistent with a role in muscle nociception, small (<25 μm) sensory neurons that innervate muscle are more likely to express ASIC3 than those that innervate skin (51% of small muscle afferents vs. 28% of small skin afferents). Over 80% of ASIC3+ muscle afferents co-express CGRP (a vasodilatory peptide). Remarkably few (9%) ASIC3+ cells express P2X3 receptors (an ATP-gated ion channel), whereas 31% express TRPV1 (the noxious heat and capsaicin-activated ion channel also known as VR1). ASIC3+/CGRP+ sensory nerve endings were observed on muscle arterioles, the blood vessels that control vascular resistance; like the cell bodies, the endings are P2X3- and can be TRPV1+. The TrkC+/ASIC3+ cell bodies are uniformly large, possibly consistent with non-nociceptive mechanosensation. They are not proprioceptors because they fail two other tests: ASIC3+ cells do not express parvalbumin and they are absent from the mesencephalic trigeminal nucleus. CONCLUSION: Our data indicates that: 1) ASIC3 is expressed in a restricted population of nociceptors and probably in some non-nociceptors; 2) co-expression of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a class of sensory neurons, some of which innervate blood vessels. We suggest that these latter afferents may be muscle metaboreceptors, neurons that sense the metabolic state of muscle and can trigger pain when there is insufficient oxygen

Development of integrated ecological standards of sustainable forest management at an operational scale

Within Canada, and internationally, an increasing demand that forests be managed to maintain all resources has led to the development of criteria and indicators of sustainable forest management. There is, however, a lack of understanding, at an operational scale, how to evaluate and compare forest management activities to ensure the sustainability of all resources. For example, nationally, many of the existing indicators are too broad to be used directly at a local scale of forest management; provincially, regulations are often too prescriptive and rigid to allow for adaptive management; and forest certification programs, often based largely on public or stake-holder opinion instead of scientific understanding, may be too local in nature to permit a comparison of operations across a biome. At an operational scale indicators must be relevant to forest activities and ecologically integrated. In order to aid decision-makers in the adaptive management necessary for sustainable forest management, two types of indicators are identified: those that are prescriptive to aid in planning forest management and those that are evaluative to be used in monitoring and suggesting improvements. An integrated approach to developing standards based on an ecosystem management paradigm is outlined for the boreal forest where the variability inherent in natural systems is used to define the limits within which forest management is ecologically sustainable. Sustainability thresholds are thus defined by ecosystem response after natural disturbances. For this exercise, standards are proposed for biodiversity, forest productivity via regeneration, soil conservation and aquatic resources. For each of these standards, planning indicators are developed for managing forest conditions while forest values are evaluated by environmental indicators, thus leading to a continuous cycle of improvement. Approaches to developing critical thresholds and corresponding prescriptions are also outlined. In all cases, the scale of evaluation is clearly related to the landscape (or FMU) level while the stand level is used for measurement purposes. In this view the forest should be managed as a whole even though forest interventions are usually undertaken at the stand level