Regulation of stem cell self-renewal versus differentiation is critical for embryonic development and adult tissue homeostasis. Drosophila larval neuroblasts divide asymmetrically to self-renew, and ...are a model system for studying stem cell self-renewal. Here we identify three mutations showing increased brain neuroblast numbers that map to the aurora-A gene, which encodes a conserved kinase implicated in human cancer. Clonal analysis and time-lapse imaging in aurora-A mutants show single neuroblasts generate multiple neuroblasts (ectopic self-renewal). This phenotype is due to two independent neuroblast defects: abnormal atypical protein kinase C (aPKC)/Numb cortical polarity and failure to align the mitotic spindle with the cortical polarity axis. numb mutant clones have ectopic neuroblasts, and Numb overexpression partially suppresses aurora-A neuroblast overgrowth (but not spindle misalignment). Conversely, mutations that disrupt spindle alignment but not cortical polarity have increased neuroblasts. We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal.
Parasitic interactions are often part of complex networks of interspecific relationships that have evolved in biological communities. Despite many years of work on the evolution of parasitism, the ...likelihood that sister taxa of parasites can co-evolve with their hosts to specifically infect two related lineages, even when those hosts occur sympatrically, is still unclear. Furthermore, when these specific interactions occur, the molecular and physiological basis of this specificity is still largely unknown. The presence of these specific parasitic relationships can now be tested using molecular markers such as DNA sequence variation. Here we test for specific parasitic relationships in an emerging host-parasite model, the stickleback-Schistocephalus system. Threespine and ninespine stickleback fish are intermediate hosts for Schistocephalus cestode parasites that are phenotypically very similar and have nearly identical life cycles through plankton, stickleback, and avian hosts. We analyzed over 2000 base pairs of COX1 and NADH1 mitochondrial DNA sequences in 48 Schistocephalus individuals collected from threespine and ninespine stickleback hosts from disparate geographic regions distributed across the Northern Hemisphere. Our data strongly support the presence of two distinct clades of Schistocephalus, each of which exclusively infects either threespine or ninespine stickleback. These clades most likely represent different species that diverged soon after the speciation of their stickleback hosts. In addition, genetic structuring exists among Schistocephalus taken from threespine stickleback hosts from Alaska, Oregon and Wales, although it is much less than the divergence between hosts. Our findings emphasize that biological communities may be even more complex than they first appear, and beg the question of what are the ecological, physiological, and genetic factors that maintain the specificity of the Schistocephalus parasites and their stickleback hosts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dendrites often exhibit structural changes in response to local inputs. Although mechanisms that pattern and maintain dendritic arbors are becoming clearer, processes regulating regrowth, during ...context-dependent plasticity or after injury, remain poorly understood. We found that a class of Drosophila sensory neurons, through complete pruning and regeneration, can elaborate two distinct dendritic trees, innervating independent sensory fields. An expression screen identified Cysteine proteinase-1 (Cp1) as a critical regulator of this process. Unlike known ecdysone effectors, Cp1-mutant ddaC neurons pruned larval dendrites normally but failed to regrow adult dendrites. Cp1 expression was upregulated/concentrated in the nucleus during metamorphosis, controlling production of a truncated Cut homeodomain transcription factor. This truncated Cut, but not the full-length protein, allowed Cp1-mutant ddaC neurons to regenerate higher-order adult dendrites. These results identify a molecular pathway needed for dendrite regrowth after pruning, which allows the same neuron to innervate distinct sensory fields.
Display omitted
•Drosophila ddaC sensory neurons elaborate 2 distinct dendritic trees via remodeling•Expression screen identifies protease Cp1 as a key regulator of dendrite regeneration•Cp1 controls production of distinct Cut protein isoform, needed for dendrite regrowth•Induced by hormone, Cp1 ties extracellular cues to dendritic/sensory field plasticity
Dendrites are the primary antennas for information input to neurons. Their territory for individual neurons represents a "receptive or sensory field" and is important for conveying the precision of information gathered. But when this sensory field changes due to experience or injury, how does a neuron innervate a new sensory field? Does it reuse a developmental program first employed to grow dendrites, or does it call up a new one? In this study, Kuo and colleagues show that, surprisingly, it is both.
Over the past 20 years, the education system in Guyana has significantly improved. Despite this improvement, students with disabilities in Guyana still face higher rates of poverty, lack of access to ...schools, and a lack of teachers who are trained in how to best meet their needs. Guyana has tried to address these problems with the drafting of legislation and policies such as the Persons With Disabilities Act of 2010 and the SEN Inclusion Policy. While progress has been made, there is still a need for additional efforts related to the education of individuals with disabilities in Guyana before their full potential is realized. This column presents a brief historical background and summary of current practices related to the identification, educational placements, and provision of educational services and supports for students with disabilities in Guyana. Additional needs and future recommendations are also included.
Drosophila neuroblasts are a model system for studying stem cell self-renewal and the establishment of cortical polarity. Larval neuroblasts generate a large apical self-renewing neuroblast, and a ...small basal cell that differentiates. We performed a genetic screen to identify regulators of neuroblast self-renewal, and identified a mutation in sgt1 (suppressor-of-G2-allele-of-skp1) that had fewer neuroblasts. We found that sgt1 neuroblasts have two polarity phenotypes: failure to establish apical cortical polarity at prophase, and lack of cortical Scribble localization throughout the cell cycle. Apical cortical polarity was partially restored at metaphase by a microtubule-induced cortical polarity pathway. Double mutants lacking Sgt1 and Pins (a microtubule-induced polarity pathway component) resulted in neuroblasts without detectable cortical polarity and formation of “neuroblast tumors.” Mutants in hsp83 (encoding the predicted Sgt1-binding protein Hsp90), LKB1, or AMPKα all show similar prophase apical cortical polarity defects (but no Scribble phenotype), and activated AMPKα rescued the sgt1 mutant phenotype. We propose that an Sgt1/Hsp90–LKB1–AMPK pathway acts redundantly with a microtubule-induced polarity pathway to generate neuroblast cortical polarity, and the absence of neuroblast cortical polarity can produce neuroblast tumors.
► We used a novel sequence-capture genomic method to identify sgt1. ► Sgt1 is required for Bazooka localization in neuroblasts. ► Sgt1 is required for Scribble localization in neuroblasts. ► Sgt1 acts at the top of an Hsp90–LKB1–AMPK polarity pathway.
This study compared the effectiveness of static picture prompting to video prompting when used as precursors for teaching daily living and motor skills to three individuals with autism spectrum ...disorders. The video prompting intervention was delivered on an iPad. Participants learned three out of six different tasks, which included throwing a ball overhand, walking backward, performing jumping jacks, washing a mirror, cutting a banana, and brushing teeth. The effects of the instructional methods were compared and assessed using an alternating treatment design. Results show that video prompting and static pictures are both effective in teaching correct independent skill responses to children with ASD. Although one participant showed greater gains on one of the three tasks using static pictures, video prompting resulted in overall faster acquisition.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning.
Methods
Twenty histologic ...features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis OA patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes.
Results
Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C‐reactive protein (CRP) levels were significantly correlated with the severity of pain in the high inflammatory subgroup but not in the others.
Conclusion
Gene expression analysis of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels were used to generate a histologic scoring algorithm in which the histologic scores were found to be associated with parameters of systemic inflammation, including the erythrocyte sedimentation rate, CRP level, and autoantibody levels. Comparison of gene expression patterns to clinical features revealed a potentially clinically important distinction: mechanisms of pain may differ in patients with different synovial subtypes.
During atherogenesis, cholesterol precipitates into cholesterol crystals (CC) in the vessel wall, which trigger plaque inflammation by activating the NACHT, LRR and PYD domains-containing protein 3 ...(NLRP3) inflammasome. We investigated the relationship between CC, complement and NLRP3 in patients with cardiovascular disease.
We analysed plasma, peripheral blood mononuclear cells (PBMC) and carotid plaques from patients with advanced atherosclerosis applying ELISAs, multiplex cytokine assay, qPCR, immunohistochemistry, and gene profiling.
Transcripts of interleukin (IL)-1beta(β) and NLRP3 were increased and correlated in PBMC from patients with acute coronary syndrome (ACS). Priming of these cells with complement factor 5a (C5a) and tumour necrosis factor (TNF) before incubation with CC resulted in increased IL-1β protein when compared to healthy controls. As opposed to healthy controls, systemic complement was significantly increased in patients with stable angina pectoris or ACS. In carotid plaques, complement C1q and C5b-9 complex accumulated around CC-clefts, and complement receptors C5aR1, C5aR2 and C3aR1 were higher in carotid plaques compared to control arteries. Priming human carotid plaques with C5a followed by CC incubation resulted in pronounced release of IL-1β, IL-18 and IL-1α. Additionally, mRNA profiling demonstrated that C5a and TNF priming followed by CC incubation upregulated plaque expression of NLRP3 inflammasome components.
We demonstrate that CC are important local- and systemic complement activators, and we reveal that the interaction between CC and complement could exert its effect by activating the NLRP3 inflammasome, thus promoting the progression of atherosclerosis.
Background
The measurement of physical fitness has a history that dates back nearly 200 years. Recently, there has been an increase in international research and surveillance on physical fitness ...creating a need for setting international priorities that could help guide future efforts.
Objective
This study aimed to produce a list of the top 10 international priorities for research and surveillance on physical fitness among children and adolescents.
Methods
Using a twin-panel Delphi method, two independent panels consisting of 46 international experts were identified (panel 1 = 28, panel 2 = 18). The panel participants were asked to list up to five priorities for research or surveillance (round 1), and then rated the items from their own panel on a 5-point Likert scale of importance (round 2). In round 3, experts were asked to rate the priorities identified by the other panel.
Results
There was strong between-panel agreement (panel 1:
r
s
= 0.76,
p
< 0.01; panel 2:
r
s
= 0.77,
p
< 0.01) in the priorities identified. The list of the final top 10 priorities included (i) “conduct longitudinal studies to assess changes in fitness and associations with health”. This was followed by (ii) “use fitness surveillance to inform decision making”, and (iii) “implement regular and consistent international/national fitness surveys using common measures”.
Conclusions
The priorities identified in this study provide guidance for future international collaborations and research efforts on the physical fitness of children and adolescents over the next decade and beyond.
Laboratory cultures of two 'biosynthetically talented' bacterial strains harvested from tropical and temperate Pacific Ocean sediment habitats were examined for the production of new natural ...products. Cultures of the tropical
strain RJA3005, harvested from a PNG marine sediment, produced salinorcinol (
) and salinacetamide (
), which had previously been reported as products of engineered and mutated strains of
, but had not been found before as natural products. An
.
strain RJA4486, harvested from marine sediment collected in the temperate ocean waters off British Columbia, produced the new aminoquinone polyketide salinisporamine (
). Natural products
,
, and
are putative shunt products of the widely distributed rifamycin biosynthetic pathway.
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