Postural stability is a fundamental aspect of motor ability that allows individuals to sustain and maintain the desired physical position of one’s body. The present study examined postural stability ...in average-IQ adolescents and adults with Autism Spectrum Disorder (ASD). Twenty-six individuals with ASD and 26 age-and-IQ-matched individuals with typical development stood on one leg or two legs with eyes opened or closed on a Wii balance board. Results indicated significant group differences in postural stability during one-legged standing, but there were no significant group differences during two-legged standing. This suggests that static balance during more complex standing postures is impaired in average-IQ individuals with ASD. Further, current ASD symptoms were related to postural stability during two-legged standing in individuals with ASD. Future directions and clinical implications are discussed.
Although a causal association remains to be determined, epidemiologic evidence suggests an association between hearing loss and increased risk of dementia. If we determine the association is causal, ...opportunity for targeted intervention for hearing loss may play a fundamental role in dementia prevention. In this discussion, we summarize current research on the association between hearing loss and dementia and review potential casual mechanisms behind the association (e.g., sensory-deprivation hypothesis, information-degradation hypothesis, common cause). We emphasize key areas of research which might best inform our investigation of this potential casual association. These selected research priorities include examination of the causal mechanism, measurement of co-existing hearing loss and cognitive impairment and determination of any bias in testing, potential for managing hearing loss for prevention of dementia and cognitive decline, or the potential to reduce dementia-related symptoms through the management of hearing loss. Addressing these research gaps and how results are then translated for clinical use may prove paramount for dementia prevention, management, and overall health of older adults.
Orthologous relationships form the basis of most comparative genomic and metagenomic studies and are essential for proper phylogenetic and functional analyses. The third version of the eggNOG ...database (http://eggnog.embl.de) contains non-supervised orthologous groups constructed from 1133 organisms, doubling the number of genes with orthology assignment compared to eggNOG v2. The new release is the result of a number of improvements and expansions: (i) the underlying homology searches are now based on the SIMAP database; (ii) the orthologous groups have been extended to 41 levels of selected taxonomic ranges enabling much more fine-grained orthology assignments; and (iii) the newly designed web page is considerably faster with more functionality. In total, eggNOG v3 contains 721 801 orthologous groups, encompassing a total of 4 396 591 genes. Additionally, we updated 4873 and 4850 original COGs and KOGs, respectively, to include all 1133 organisms. At the universal level, covering all three domains of life, 101 208 orthologous groups are available, while the others are applicable at 40 more limited taxonomic ranges. Each group is amended by multiple sequence alignments and maximum-likelihood trees and broad functional descriptions are provided for 450 904 orthologous groups (62.5%).
Research on memory in autism spectrum disorder (ASD) finds increased difficulty encoding contextual associations in episodic memory and suggests executive dysfunction (e.g., selective attention, ...cognitive flexibility) and deficient metacognitive monitoring as potential contributing factors. Findings from our lab suggest that age-related impairments in selective attention contribute to those in context memory accuracy and older adults tended to show dependence in context memory accuracy between relevant and irrelevant context details (i.e., hyper-binding). Using an aging framework, we tested the effects of selective attention on context memory in a sample of 23 adults with ASD and 23 typically developed adults. Participants studied grayscale objects flanked by two types of contexts (color, scene) on opposing sides and were told to attend to only one object-context relationship, ignoring the other context. At test, participants made object and context recognition decisions and judgment of confidence decisions allowing for an evaluation of context memory performance, hyper-binding, and metacognitive performance for context judgments in a single task. Results showed that adults with ASD performed similarly to typically developed adults on all measures. These findings suggest that context memory performance is not always disrupted in adults with ASD, even when demands on selective attention are high. We discuss the need for continued research to evaluate episodic memory in a wider variety of adults with ASD.
A fusion protein comprising factor IX and the dimeric Fc domain of IgG1 has a half-life that is five times as long as that of native factor IX, allowing prophylactic injections to be spaced as far as ...2 weeks apart while maintaining levels of factor IX that are sufficient to prevent bleeding.
In patients with severe hemophilia B, recurrent bleeding leads to painful hemarthroses, disabling hemophilic arthropathy, and other sequelae.
1
,
2
Prophylactic replacement of coagulation factor IX is associated with improved clinical outcomes
3
–
7
; however, the relatively short half-lives of currently available factor IX products necessitate frequent intravenous injections (two or three times weekly) to maintain protective levels (at or above 1 IU per deciliter).
8
,
9
The frequency of injections is a considerable burden, cited by patients as a key deterrent to undertaking prophylactic treatment.
10
Various strategies to reduce this burden and improve the treatment of hemophilia B are under investigation, . . .
Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin combined with paclitaxel. Although this regimen is initially effective in a ...high percentage of cases, unfortunately within few months of initial treatment, tumor relapse occurs because of platinum-resistance. This is attributed to chemo-resistance of cancer stem cells (CSCs). Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs. Treatment of nude mice bearing orthotopic ovarian tumors generated by injecting human ovarian epithelial cancer cell line (A2780) with WFA and cisplatin (WFA) alone or in combination resulted in a 70 to 80% reduction in tumor growth and complete inhibition of metastasis to other organs compared to untreated controls. Histochemical and Western blot analysis of the tumors revealed that inclusion of WFA (2 mg/kg) resulted in a highly significant elimination of cells expressing CSC markers - CD44, CD24, CD34, CD117 and Oct4 and downregulation of Notch1, Hes1 and Hey1 genes. In contrast treatment of mice with CIS alone (6 mg/kg) had opposite effect on those cells. Increase in cells expressing CSC markers and Notch1 signaling pathway in tumors exposed to CIS may explain recurrence of cancer in patients treated with carboplatin and paclitaxel. Since, WFA alone or in combination with CIS eliminates putative CSCs, we conclude that WFA in combination with CIS may present more efficacious therapy for ovarian cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The distribution, systematics and ecology of Bactrocera tryoni, the Queensland fruit fly, are reviewed. Bactrocera tryoni is a member of the B. tryoni complex of species, which currently includes ...four named species, viz. B. tryoni ssp., B. neohumeralis, B. melas and B. aquilonis. The species status of B. melas and B. aquilonis is unclear (they may be junior synonyms of B. tryoni) and their validity, or otherwise, needs to be confirmed as a matter of urgency. While Queensland fruit fly is regarded as a tropical species, it cannot be assumed that its distribution will spread further south under climate change scenarios. Increasing aridity and hot dry summers, as well as more complex, indirect interactions resulting from elevated CO₂, make predicting the future distribution and abundance of B. tryoni difficult. The ecology of B. tryoni is reviewed with respect to current control approaches (with the exception of sterile insect technique (SIT) which is covered in a companion paper). We conclude that there are major gaps in the knowledge required to implement most noninsecticide-based management approaches. Priority areas for future research include host-plant interactions, protein and cue-lure foraging and use, spatial dynamics, development of new monitoring tools, investigating the use of natural enemies and better integration of fruit flies into general horticultural IPM systems.
No adeno-associated virus (AAV) capsid has been described in the literature to exhibit a primary oligodendrocyte tropism when a constitutive promoter drives gene expression, which is a significant ...barrier for efficient in vivo oligodendrocyte gene transfer. The vast majority of AAV vectors, such as AAV1, 2, 5, 6, 8 or 9, exhibit a dominant neuronal tropism in the central nervous system. However, a novel AAV capsid (Olig001) generated using capsid shuffling and directed evolution was recovered after rat intravenous delivery and subsequent capsid clone rescue, which exhibited a >95% tropism for striatal oligodendrocytes after rat intracranial infusion where a constitutive promoter drove gene expression. Olig001 contains a chimeric mixture of AAV1, 2, 6, 8 and 9, but unlike these parental serotypes after intravenous administration Olig001 has very low affinity for peripheral organs, especially the liver. Furthermore, in mixed glial cell cultures, Olig001 exhibits a 9-fold greater binding when compared with AAV8. This novel oligodendrocyte-preferring AAV vector exhibits characteristics that are a marked departure from previously described AAV serotypes.
Abstract
The coastal areas of Vanuatu are under a multitude of threats stemming from commercialization, human development, and climate change.
Atyphella
Olliff is a genus of firefly that includes ...species endemic to these coastal areas and will need protection. The research that has already been conducted was affected by accessibility due to the remote nature of the islands which left numerous knowledge gaps caused by a lack of distributional data (e.g., Wallacean shortfall). Species distribution models (SDM) are a powerful tool that allow for the modeling of the broader distribution of a taxon, even with limited distributional data available. SDMs assist in filling the knowledge gap by predicting potential areas that could contain the species of interest, making targeted collecting and conservation efforts more feasible when time, resources, and accessibility are major limiting factors. Here a MaxEnt prediction was used to direct field collecting and we now provide an updated predictive distribution for this endemic firefly genus. The original model was validated with additional fieldwork, ultimately expanding the known range with additional locations first identified using MaxEnt. A bias analysis was also conducted, providing insight into the effect that developments such as roads and settlements have on collecting and therefore the SDM, ultimately allowing for a more critical assessment of the overall model. After demonstrating the accuracy of the original model, this new updated SDM can be used to identify specific areas that will need to be the target of future conservation efforts by local government officials.
Current factor VIII (FVIII) products display a half-life (t1/2) of ∼ 8-12 hours, requiring frequent intravenous injections for prophylaxis and treatment of patients with hemophilia A. rFVIIIFc is a ...recombinant fusion protein composed of a single molecule of FVIII covalently linked to the Fc domain of human IgG1 to extend circulating rFVIII t1/2. This first-in-human study in previously treated subjects with severe hemophilia A investigated safety and pharmacokinetics of rFVIIIFc. Sixteen subjects received a single dose of rFVIII at 25 or 65 IU/kg followed by an equal dose of rFVIIIFc. Most adverse events were unrelated to study drug. None of the study subjects developed anti-rFVIIIFc antibodies or inhibitors. Across dose levels, compared with rFVIII, rFVIIIFc showed 1.54- to 1.70-fold longer elimination t1/2, 1.49- to 1.56-fold lower clearance, and 1.48- to 1.56-fold higher total systemic exposure. rFVIII and rFVIIIFc had comparable dose-dependent peak plasma concentrations and recoveries. Time to 1% FVIII activity above baseline was ∼ 1.53- to 1.68-fold longer than rFVIII across dose levels. Each subject showed prolonged exposure to rFVIIIFc relative to rFVIII. Thus, rFVIIIFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia A. This trial was registered at www.clinicaltrials.gov as NCT01027377.
PDF
