Temporal response of endogenous neural progenitor cells following injury to the adult rat spinal cord

© 2016 Mao, Mathews and Gorrie. A pool of endogenous neural progenitor cells (NPCs) found in the ependymal layer and the sub-ependymal area of the spinal cord are reported to upregulate Nestin in response to traumatic spinal cord injury (SCI). These cells could potentially be manipulated within a critical time period offering an innovative approach to the repair of SCI. However, little is known about the temporal response of endogenous NPCs following SCI. This study used a mild contusion injury in rat spinal cord and immunehistochemistry to determine the temporal response of ependymal NPCs following injury and their correlation to astrocyte activation at the lesion edge. The results from the study demonstrated that Nestin staining intensity at the central canal peaked at 24 h post-injury and then gradually declined over time. Reactive astrocytes double labeled by Nestin and glial fibrillary acidic protein (GFAP) were found at the lesion edge and commenced to form the glial scar from 1 week after injury. We conclude that the critical time period for manipulating endogenous NPCs following a spinal cod injury in rats is between 24 h when Nestin expression in ependymal cells is increased and 1 week when astrocytes are activated in large numbers

Functional impairment of reading in patients with dry eye

BACKGROUND/AIMS: To evaluate the impact of dry eye on reading performance. METHODS: Out-loud and silent reading in patients with clinically significant dry eye (n=41) and controls (n=50) was evaluated using standardised texts. Dry eye measures included tear film break-up time, Schirmer's test and corneal epithelial staining. Symptoms were assessed by the Ocular Surface Disease Index (OSDI). RESULTS: The dry eye group had a greater proportion of women as compared with the control group but did not differ in age, race, education level or visual acuity (p≥0.05 for all). Out-loud reading speed averaged 148 words per minute (wpm) in dry eye subjects and 163 wpm in controls (p=0.006). Prolonged silent reading speed averaged 199 wpm in dry eye subjects versus 226 wpm in controls (p=0.03). In multivariable regression models, out-loud and sustained silent reading speeds were 10 wpm (95% CI −20 to −1 wpm, p=0.039) and 14% (95% CI −25% to −2%, p=0.032) slower, respectively, in dry eye subjects as compared with controls. Greater corneal staining was associated with slower out-loud (−2 wpm/1 unit increase in staining score, 95% CI =−3 to −0.3 wpm) and silent (−2%, 95% CI −4 to −0.6 wpm) reading speeds (p<0.02 for both). Significant interactions were found between OSDI score and word-specific features (longer and less commonly used words) on out-loud reading speed (p<0.05 for both). CONCLUSIONS: Dry eye is associated with slower out-loud and silent reading speeds, providing direct evidence regarding the functional impact of dry eye. Reading speed represents a measurable clinical finding that correlates directly with dry eye severity

Near-field examination of perovskite-based superlenses and superlens-enhanced probe-object coupling

A planar slab of negative index material works as a superlens with sub-diffraction-limited imaging resolution, since propagating waves are focused and, moreover, evanescent waves are reconstructed in the image plane. Here, we demonstrate a superlens for electric evanescent fields with low losses using perovskites in the mid-infrared regime. The combination of near-field microscopy with a tunable free-electron laser allows us to address precisely the polariton modes, which are critical for super-resolution imaging. We spectrally study the lateral and vertical distributions of evanescent waves around the image plane of such a lens, and achieve imaging resolution of wavelength/14 at the superlensing wavelength. Interestingly, at certain distances between the probe and sample surface, we observe a maximum of these evanescent fields. Comparisons with numerical simulations indicate that this maximum originates from an enhanced coupling between probe and object, which might be applicable for multifunctional circuits, infrared spectroscopy, and thermal sensors.Comment: 20 pages, 6 figures, published as open access article in Nature Communications (see http://www.nature.com/ncomms/

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Differences in the cellular response to acute spinal cord injury between developing and mature rats highlights the potential significance of the inflmmatory response

© 2017 Sutherland, Mathews, Mao, Nguyen and Gorrie. There exists a trend for a better functional recovery from spinal cord injury (SCI) in younger patients compared to adults, which is also reported for animal studies; however, the reasons for this are yet to be elucidated. The post injury tissue microenvironment is a complex milieu of cells and signals that interact on multiple levels. Inflammation has been shown to play a significant role in this post injury microenvironment. Endogenous neural progenitor cells (NPC), in the ependymal layer of the central canal, have also been shown to respond and migrate to the lesion site. This study used a mild contusion injury model to compare adult (9 week), juvenile (5 week) and infant (P7) Sprague-Dawley rats at 24 h, 1, 2, and 6 weeks post-injury (n = 108). The innate cells of the inflammatory response were examined using counts of ED1/IBA1 labeled cells. This found a decreased inflammatory response in the infants, compared to the adult and juvenile animals, demonstrated by a decreased neutrophil infiltration and macrophage and microglial activation at all 4 time points. Two other prominent cellular contributors to the post-injury microenvironment, the reactive astrocytes, which eventually form the glial scar, and the NPC were quantitated using GFAP and Nestin immunohistochemistry. After SCI in all 3 ages there was an obvious increase in Nestin staining in the ependymal layer, with long basal processes extending into the parenchyma. This was consistent between age groups early post injury then deviated at 2 weeks. The GFAP results also showed stark differences between the mature and infant animals. These results point to significant differences in the inflammatory response between infants and adults that may contribute to the better recovery indicated by other researchers, as well as differences in the overall injury progression and cellular responses. This may have important consequences if we are able to mirror and manipulate this response in patients of all ages; however much greater exploration in this area is required

Circumstellar discs: What will be next?

This prospective chapter gives our view on the evolution of the study of circumstellar discs within the next 20 years from both observational and theoretical sides. We first present the expected improvements in our knowledge of protoplanetary discs as for their masses, sizes, chemistry, the presence of planets as well as the evolutionary processes shaping these discs. We then explore the older debris disc stage and explain what will be learnt concerning their birth, the intrinsic links between these discs and planets, the hot dust and the gas detected around main sequence stars as well as discs around white dwarfs.Comment: invited review; comments welcome (32 pages

Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.Obsessive Compulsive FoundationTourette Syndrome AssociationAnxiety Disorders Association of AmericaAmerican Academy of Child and Adolescent Psychiatr

To VBAC or Not to VBAC

Catherine Spong discusses new research in PLoS Medicine that sheds more light on the risks of uterine rupture for women attempting a trial of labor following previous cesarean section

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

BACKGROUND: Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. METHODS: In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3–6 months (when below the threshold) or every 9–12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. FINDINGS: 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86–1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95–1·22) for threshold 200 and 1·03 (0·96–1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17–3·43) for threshold 200 and 1·24 (0·89–1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (−25·5 to 26·3) cells per μL for threshold 200 and −3·5 (−16·0 to 8·9) cells per μL for threshold 350. INTERPRETATION: Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. FUNDING National Institutes of Health

Entrepreneurial-intention constraint model: A comparative analysis among post-graduate management students in India, Singapore and Malaysia

YesAlthough literature on entrepreneurship has increasingly focused on intention-based models, not much emphasis has been laid on understanding the combined effect of contextual and situational factors along with support of university environment on the formation of entrepreneurial intention among students. In an effort to make up for this shortfall, by taking Theory of Planned Behavior as basic framework, the present study seeks to understand the influence of three of the most important factors, viz. (a) endogenous barriers, (b) exogenous environment, and (c) university environment and support on the entrepreneurial intention among management students. The study sample consisted of 1,097 students, wherein 526 students were from India, 252 from Singapore, and 319 were from Malaysia. The results indicates that along with positive attitude and perceived behavioral control that directly influences entrepreneurial intention, university environment and support and exogenous environment also have an indirect but significant impact on shaping of entrepreneurial intention among students. With this, it was found that exogenous environment was found to have a negative relationship with both attitude towards behavior and perceived behavioral control for all three countries.The full-text of this article will be released for public view at the end of the publisher embargo on 2 Jun 2018