Tumors of the same histologic type often comprise clinically and molecularly distinct subgroups; however, the etiology of these subgroups is unknown. Here, we report that histologically identical, but genetically distinct, ependymomas exhibit patterns of gene expression that recapitulate those of radial glia cells in the corresponding region of the central nervous system. Cancer stem cells isolated from ependymomas displayed a radial glia phenotype and formed tumors when orthotopically transplanted in mice. These findings identify restricted populations of radial glia cells as candidate stem cells of the different subgroups of ependymoma, and they support a general hypothesis that subgroups of the same histologic tumor type are generated by different populations of progenitor cells in the tissues of origin.

We examined the interobserver reliability of local progressive disease (L-PD) determination using two major radiological response evaluation criteria systems (Response evaluation Criteria in Solid Tumors (RECIST) and the European and American Osteosarcoma Study (EURAMOS)) in patients diagnosed with localized osteosarcoma (OS). Additionally, we describe the outcomes of patients determined to experience L-PD.

Visual prostheses such as the Argus II provide partial vision for individuals with limited or no light perception. However, their effectiveness in daily life situations is limited by scene complexity and variability. We investigated whether additional image processing techniques could improve mobility performance in everyday indoor environments. A mobile system connected to the Argus II provided thermal or distance-filtered video stimulation. Four participants used the thermal camera to locate a person and the distance filter to navigate a hallway with obstacles. The thermal camera allowed for finding a target person in 99% of trials, while unfiltered video led to confusion with other objects and a success rate of only 55% ([Formula: see text]). Similarly, the distance filter enabled participants to detect and avoid 88% of obstacles by removing background clutter, whereas unfiltered video resulted in a detection rate of only 10% ([Formula: see text]). For any given elapsed time, the success rate with filtered video was higher than with unfiltered video. After 90 s, participants' success rate reached above 50% with filtered video and 24% and 3% with normal camera in the first and second tasks, respectively. Despite individual variations, all participants showed significant improvement when using the thermal and distance filters compared to unfiltered video. Adding a thermal and distance filter to a visual prosthesis system can enhance the performance of mobility activities by removing clutter in the background, showing people and warm objects with the thermal camera, or nearby obstacles with the distance filter.

Cancer stem cells are remarkably similar to normal stem cells: both self-renew, are multipotent and express common surface markers, for example, prominin 1 (PROM1, also called CD133). What remains unclear is whether cancer stem cells are the direct progeny of mutated stem cells or more mature cells that reacquire stem cell properties during tumour formation. Answering this question will require knowledge of whether normal stem cells are susceptible to cancer-causing mutations; however, this has proved difficult to test because the identity of most adult tissue stem cells is not known. Here, using an inducible Cre, nuclear LacZ reporter allele knocked into the Prom1 locus (Prom1(C-L)), we show that Prom1 is expressed in a variety of developing and adult tissues. Lineage-tracing studies of adult Prom1(+/C-L) mice containing the Rosa26-YFP reporter allele showed that Prom1(+) cells are located at the base of crypts in the small intestine, co-express Lgr5 (ref. 2), generate the entire intestinal epithelium, and are therefore the small intestinal stem cell. Prom1 was reported recently to mark cancer stem cells of human intestinal tumours that arise frequently as a consequence of aberrant wingless (Wnt) signalling. Activation of endogenous Wnt signalling in Prom1(+/C-L) mice containing a Cre-dependent mutant allele of beta-catenin (Ctnnb1(lox(ex3))) resulted in a gross disruption of crypt architecture and a disproportionate expansion of Prom1(+) cells at the crypt base. Lineage tracing demonstrated that the progeny of these cells replaced the mucosa of the entire small intestine with neoplastic tissue that was characterized by focal high-grade intraepithelial neoplasia and crypt adenoma formation. Although all neoplastic cells arose from Prom1(+) cells in these mice, only 7% of tumour cells retained Prom1 expression. Our data indicate that Prom1 marks stem cells in the adult small intestine that are susceptible to transformation into tumours retaining a fraction of mutant Prom1(+) tumour cells.

Cassava mosaic geminiviruses (CMGs) and cassava brown streak viruses (CBSVs) cause the highest yield losses in cassava production in Africa. In particular, cassava brown streak disease (CBSD) is and continues to be a significant constraint to optimal cassava production in Eastern and Southern Africa. While CBSD has not been reported in West Africa, its recent rapid spread and damage to cassava productivity in Eastern, and Southern Africa is alarming. The aim of this study was to evaluate Nigerian cassava genotypes in order to determine their responses to CBSD, in the event that it invades Nigeria, the world's largest cassava producer. The study gathered information on whether useful CBSD resistance alleles are present in the elite Nigerian cassava accessions. A total of 1,980 full-sib cassava seedlings from 106 families were assessed in the field at the seedling stage for a year. A subset of 569 clones were selected and assessed for another year at the clonal stage in Namulonge, central Uganda, a known hotspot for CBSD screening. Results indicated that foliar and root incidences and severities varied significantly (p ≤ 0.01, p ≤ 0.001) except for CBSD foliar incidence at 6 months (CBSD6i ). Highest and lowest plot-based heritability estimates for CBSD were registered for CBSD root severity (CBSD rs ) (0.71) and CBSD6i (0.5). Positive and highly significant correlations were noted between CBSD root incidence (CBSD ri ) and CBSD rs (r = 0.90***). Significant positive correlations were also noted between CBSD foliar severity at 3 months (CBSD3s ) and CBSD foliar incidence at 6 months (CBSD6i ) (r = 0.77***), CBSD3s and CBSD rs (r = 0.35***). Fresh root weight (Fresh RW ) negatively correlated with CBSD ri and CBSD rs , respectively (r = -0.21*** and r = -0.22***). Similarly, CBSD3s correlated negatively with cassava mosaic disease severity at 3 (CMD3s ) and 6 months (CMD6s ), respectively (r = -0.25*** and r = -0.21***). Fifteen clones were selected using a non-weighted summation selection index for further screening. In conclusion, results revealed that the elite Nigerian accessions exhibited significant susceptibility to CBSD within 2 years of evaluation period. It is expected that this information will aid future breeding decisions for the improvement of CBSD resistance among the Nigerian cassava varieties.

Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.

Heterosis-exploiting breeding schemes are currently under consideration as a means of accelerating genetic gains in sweetpotato (Ipomoea batatas) breeding. This study was aimed at establishing heterotic gains, fitness costs and transgressive segregation associated with sweetpotato weevil (SPW) resistance in a partial diallel cross of sweetpotato. A total of 1896 clones were tested at two sites, for two seasons each in Uganda. Data on weevil severity (WED), weevil incidence (WI), storage root yield (SRY) and dry matter content (DM) were obtained. Best linear unbiased predictors (BLUPs) for each clone across environments were used to estimate heterotic gains and for regression analyses to establish relationships between key traits. In general, low mid-parent heterotic gains were detected with the highest favorable levels recorded for SRY (14.7%) and WED (- 7.9%). About 25% of the crosses exhibited desirable and significant mid-parent heterosis for weevil resistance. Over 16% of the clones displayed superior transgressive segregation, with the highest percentages recorded for SRY (21%) and WED (18%). A yield penalty of 10% was observed to be associated with SPW resistance whereas no decline in DM was detected in relation to the same. Chances of improving sweetpotato through exploiting heterosis in controlled crosses using parents of mostly similar background are somewhat minimal, as revealed by the low heterotic gains. The yield penalty detected due to SPW resistance suggests that a trade-off may be necessary between maximizing yields and developing weevil-resistant cultivars if the current needs for this crop are to be met in weevil-prone areas.

Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS). Subgroup-specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumours to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus (that encodes Cdkn2a and b). The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs. Notably, activation of Ephb2 signalling in these, but not other, NSCs generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human supratentorial tumour. Further, comparative analysis of matched mouse and human tumours revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup-specific driver mutations with cellular compartments to model and interrogate cancer subgroups.

Cancers are believed to arise from cancer stem cells (CSCs), but it is not known if these cells remain dependent upon the niche microenvironments that regulate normal stem cells. We show that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain these cells in a stem cell-like state. Increasing the number of endothelial cells or blood vessels in orthotopic brain tumor xenografts expanded the fraction of self-renewing cells and accelerated the initiation and growth of tumors. Conversely, depletion of blood vessels from xenografts ablated self-renewing cells from tumors and arrested tumor growth. We propose that brain CSCs are maintained within vascular niches that are important targets for therapeutic approaches.

This study investigated the phenotypic variation of continuous storage root formation and bulking (CSRFAB) growth patterns underlying the development of sweetpotato genotypes for identification of potential varieties adapted to piecemeal harvesting for small scale farmers. The research was conducted between September 2016 and August 2017 in Uganda. Genotypes from two distinct sweetpotato genepool populations (Population Uganda A and Population Uganda B) comprising 130 genotypes, previously separated using 31 simple sequence repeat (SSR) markers were used. Measurements (4 harvest times with 4 plants each) were repeated on genotypes in a randomized complete block design with 2 replications in 2 locations for 2 seasons. We developed a scoring scale of 1 to 9 and used it to compare growth changes between consecutive harvests. Data analysis was done using residual or restricted maximum likelihood (REML). Data showed a non-linear growth pattern within and between locations, seasons, and genotypes for most traits. Some genotypes displayed early initiation and increase of bulking, while others showed late initiation. Broad sense heritability of CSRFAB was low due to large GxE interactions but higher in other traits  probably due to high genetic influence and the effectiveness of the methodology. A high level of reproducibility (89%) was observed comparing 2016B and 2017A seasons (A and B are first and second season, respectively) at the National Crops Resources Research Institute (NaCRRI), Namulonge, Uganda. Choosing CSRFAB genotypes can more than double the sweetpotato production (average maximum yield of 13.1 t/ha for discontinuous storage root formation and bulking (DSRFAB) versus 28.6 t/ha for CSRFAB, demonstrating the importance of this underresearched component of storage root yield.

At present, Argus II is the only retinal prosthesis approved by the US Food and Drug Administration that induces visual percepts in people who are blind from end-stage outer retinal degenerations such as retinitis pigmentosa. It has been shown to work well in sparse, high-contrast settings, but in daily practice visual performance with the device is likely to be hampered by the cognitive load presented by a cluttered real-world environment. In this study, we investigated the effect of a stereo-disparity-based distance-filtering system on four experienced Argus II users for a range of tasks: object localization, depth discrimination, orientation and size discrimination, and people detection and direction of motion.