bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel pre-clinical model for CDKL5 Deficiency Disorder
Authors: Serrano Rita J. , Lee Clara , Bryson-Richardson Robert J. , Sztal Tamar E. 
Published: April 2021

AbstractCyclin-dependent kinase-like-5 (CDKL5) Deficiency Disorder (CDD) is a severe X-linked neurodegenerative disease characterized by early-onset epileptic seizures, low muscle tone, progressive intellectual disability, severe motor function and visual impairment. CDD affects approximately 1 in 60,000 live births with many patients dying by early adulthood. For many patients, quality of life is significantly reduced due to the severity of their neurological symptoms and functional impairment. There are no effective therapies for CDD with current treatments focusing on improving symptoms rather than addressing the underlying causes of the disorder. Zebrafish offer a number of unique advantages for high-throughput pre-clinical evaluation of potential therapies for human neurological diseases including CDD. In particular, the large number of zebrafish that can be produced, together with the possibilities forin vivoimaging and genetic manipulation, allows for the detailed assessment of disease pathogenesis and therapeutic discovery. We have characterised a loss of function zebrafish model for CDD, containing a nonsense mutation incdkl5.cdkl5mutant zebrafish display defects in neuronal patterning, microcephaly, and reduced muscle function caused by impaired muscle innervation. This study provides a powerful vertebrate model to investigate CDD disease pathophysiology and allow high-throughput screening for effective therapies.
Knockdown ofPHYTOENE DESATURASEin the field dodder,Cuscuta campestris, by Virus-Induced Gene Silencing
Authors: Dyer Steven , Weir Ryan , Manesiotis Panagiotis , Dalzell Johnathan J. 
Published: April 2021

AbstractCuscuta campestrisis a globally distributed obligate holoparasitic plant, and economically important crop pest. There is an urgent need for safe and effective new herbicides to controlCuscutaspp. PHYTOENE DESATURASE (PDS) is a biosynthetic enzyme within the carotenoid synthesis pathway, which is a target for several commercially available herbicides. The low transpiration rate ofC. campestrisresults in sub-optimal translocation of PDS-targeting herbicides throughout the parasite, and resistance to these herbicides, and others, should be anticipated. Here we demonstrate that RNA interference (RNAi) can effectively reduce the expression ofPDSinC. campestris. Virus Induced Gene Silencing (VIGS) is capable of inducingPDSknockdown inC. campestris, when Tobacco Rattle Virus (TRV) is used to deliver aPDS-specific sequence through the host plantArabidopsis thaliana. This leads to a reduction in the accumulation of beta carotene, which is synthesised from phytoene, and significantly reduced growth ofC. campestris. We hypothesise that secondary amplification and spread ofPDSdouble-stranded RNA withinC. campestrismay circumvent the translocation limitations of other xylem and phloem-spread PDS-specific herbicides. These data demonstrate for the first time that VIGS can be used for reverse genetics interrogation of theC. campestrisgenome.
Noise-augmented directional clustering of genetic association data identifies distinct mechanisms underlying obesity
Authors: Grant Andrew J. , Gill Dipender , Kirk Paul D. W. , Burgess Stephen 
Published: April 2021

AbstractClustering genetic variants based on their associations with different traits can provide insight into their underlying biological mechanisms. Existing clustering approaches typically group variants based on the similarity of their association estimates for various traits. We present a new procedure for clustering variants based on their proportional associations with different traits, which is more reflective of the underlying mechanisms to which they relate. The method is based on a mixture model approach for directional clustering and includes a noise cluster that provides robustness to outliers. The procedure performs well across a range of simulation scenarios. In an applied setting, clustering genetic variants associated with body mass index generates groups reflective of distinct biological pathways. Mendelian randomization analyses support that the clusters vary in their effect on coronary heart disease, including one cluster that represents elevated body mass index with a favourable metabolic profile and reduced coronary heart disease risk. Analysis of the biological pathways underlying this cluster identifies inflammation as playing a key role in mediating the effects of increased body mass index on coronary heart disease.
Evolution of quantitative trait locus hotspots in yeast species
Authors: Peltier Emilien , Bibi-Triki Sabrina , Dutreux Fabien , Caradec Claudia , Friedrich Anne , Llorente Bertrand , Schacherer Joseph 
Published: April 2021

AbstractDissecting the genetic basis of complex trait remains a real challenge. The budding yeastSaccharomyces cerevisiaehas become a model organism for studying quantitative traits, successfully increasing our knowledge in many aspects. However, the exploration of the genotype-phenotype relationship in non-model yeast species could provide a deeper insight into the genetic basis of complex traits. Here, we have studied this relationship in theLachancea waltiispecies which diverged from theS. cerevisiaelineage prior to the whole-genome duplication. By performing linkage mapping analyses in this species, we identified 86 quantitative trait loci (QTL) affecting growth fitness in a large number of conditions. The distribution of these loci across the genome has revealed two major QTL hotspots. A first hotspot corresponds to a general fitness QTL, impacting a wide range of conditions. By contrast, the second hotspot highlighted a fitness trade-off with a disadvantageous allele for drug-free conditions which proved to be advantageous in the presence of several drugs. Finally, the comparison of the detected QTL inL. waltiiwith those which had been previously identified for the same traits in a closely related species,Lachancea kluyveri, clearly revealed the absence of interspecific conservation of these loci. Altogether, our results expand our knowledge on the variation of the QTL landscape across different yeast species.
Alternative transmission patterns in independently acquired nutritional co-symbionts of Dictyopharidae planthoppers
Authors: Michalik Anna , Franco Diego C. , Kobiałka Michał , Szklarzewicz Teresa , Stroiński Adam , Łukasik Piotr 
Published: April 2021

AbstractSap-sucking hemipterans host specialized, heritable microorganisms that supplement their unbalanced diet with essential nutrients. These microbes show unusual features that provide a unique perspective on the evolution of life but have not been systematically studied. Here, we combine microscopy with high-throughput sequencing to revisit 80-year-old reports on the diversity of symbiont transmission modes in a broadly distributed planthopper family Dictyopharidae. We show that in all species examined, the ancestral nutritional endosymbiontsSulciaandVidaniaare complemented by co-primary symbionts, eitherArsenophonusorSodalis, acquired several times independently by different host lineages. Like in other obligate sap-feeders, the ancestral symbionts produce essential amino acids, whereas co-primary symbionts contribute to the biosynthesis of B vitamins. These symbionts reside within separate bacteriomes within the abdominal cavity, although in females,Vidaniaalso occupies bacteriocytes in the rectal organ. Notably, the symbionts are transmitted from mothers to offspring in two alternative ways. In most examined species, all nutritional symbionts simultaneously infect the posterior end of the full-grown (vitellogenic) oocytes and next gather in their perivitelline space. In contrast, in other species,Sodaliscolonizes the cytoplasm of the anterior pole of young (previtellogenic) oocytes forming a cluster separate from the “symbiont ball” formed by late-invadingSulciaandVidania. Our data add to evidence on frequent replacements of gammaproteobacterial symbionts combined with the relative functional stability of the nutritional functions during the evolution of sap-feeding insects, and show how newly-arriving microbes may utilize different strategies to establish long-term heritable symbiosis.Significance statementSup-sucking hemipterans host ancient heritable microorganisms that supplement their unbalanced diet with essential nutrients, and which have repeatedly been complemented or replaced by other microorganisms. They need to be reliably transmitted to subsequent generations through the reproductive system, and often they end up using the same route as the ancient symbionts. We show for the first time that in a single family of planthoppers, the complementing symbionts that have established infections independently utilize different transmission strategies, one of them novel, with the transmission of different microbes separated spatially and temporarily. These data show how newly-arriving microbes may utilize different strategies to establish long-term heritable symbiosis.
Uncertainty in population estimates: a meta-analysis for petrels
Authors: Bird Jeremy P. , Woodworth Bradley K. , Fuller Richard A. , Shaw Justine D. S. 
Published: April 2021

ABSTRACTPopulation estimates are commonly generated and used in conservation science. All estimates carry inherent uncertainty, but little attention has been given to when and how this uncertainty limits their use. This requires an understanding of the specific purposes for which population estimates are intended, an assessment of the level of uncertainty each purpose can tolerate, and information on current uncertainty.We conducted a review and meta-analysis for a widespread group of seabirds, the petrels, to better understand how and why population estimates are being used. Globally petrels are highly threatened, and aspects of their ecology make them difficult to survey, introducing high levels of uncertainty into population estimates.We found that by far the most common intended use of population estimates was to inform status and trend assessments, while less common uses were trialling methods to improve estimates, and assessing threat impacts and conservation outcomes.The mean coefficient of variation for published estimates was 0.17 (SD = 0.14), with no evidence that uncertainty has been reduced through time. As a consequence of this high uncertainty, when we simulated declines equivalent to thresholds commonly used to trigger management, only 5% of studies could detect significant differences between population estimates collected 10 years apart for populations declining at a rate of 30% over three generations.Reporting of uncertainty was variable with no dispersion statistics reported with 38% of population estimates and most not reporting key underlying parameters: nest numbers/density and nest occupancy. We also found no correlation between population estimates and either island size, body size or species threat status—potential predictors of uncertainty.Synthesis and applications—Key recommendations for managers are to be mindful of uncertainty in past population estimates if aiming to collect contemporary estimates for comparison, to report uncertainty clearly for new estimates, and to give careful consideration to whether a proposed estimate is likely to achieve the requisite level of certainty for the investment in its generation to be warranted. We recommend a practitioner-based Value of Information assessment to confirm where there is value in reducing uncertainty.
Immersive virtual prism adaptation therapy with depth-sensing camera: A feasibility study with functional near-infrared spectroscopy in healthy adults
Authors: Cho Sungmin , Kim Won-Seok , Park Jihong , Lee Seung Hyun , Lee Jongseung , Han Cheol E. , Paik Nam-Jong 
Published: April 2021

AbstractUnilateral spatial neglect (USN) is common after stroke and associated with poor functional recovery. Prism adaptation (PA) is one of the most supported modality able to ameliorate USN but underapplied due to several issues. Using immersive virtual reality and depth-sensing camera, we developed the virtual prism adaptation therapy (VPAT) to overcome the limitations in conventional PA. In this study, we investigated whether VPAT can induce behavioral adaptations and which cortical area is most significantly activated. Fourteen healthy subjects participated in this study. The experiment consisted of four sequential phases (pre-VAPT, VPAT-10°, VPAT-20°, and post-VPAT) with functional near-infrared spectroscopy recordings. Each phase consisted of alternating target pointing and resting (or clicking) blocks. To find out the most significantly activated area during pointing in different phases (VPAT-10°, VPAT-20°, and Post-VPAT) in contrast to pointing during the pre-VPAT phase, we analyzed changes in oxyhemoglobin concentration during pointing. The pointing errors of the virtual hand deviated to the right-side during early pointing blocks in the VPAT-10° and VPAT-20° phases. There was a left-side deviation of the real hand to the target in the post-VPAT phase. The most significantly activated channels were all located in the right hemisphere, and possible corresponding cortical areas included the dorsolateral prefrontal cortex and frontal eye field. In conclusion, VPAT may induce behavioral adaptation with modulation of the dorsal attentional network. Future clinical trials using multiple sessions of a high degree of rightward deviation VPAT over a more extended period are required in stroke patients with unilateral spatial neglect.
Raman imaging and statistical methods for analysis various type of human brain tumor
Authors: Kopec M. , Błaszczyk M. , Radek M. , Abramczyk H. 
Published: April 2021

AbstractSpectroscopic methods provide information on the spatial localization of biochemical components based on the analysis of vibrational spectra. Raman spectroscopy and Raman imaging can be used to analyze various types of human brain tissue. The objective of this study is employment of Raman spectroscopy and Raman imaging to evaluate the Raman biomarkers to distinguish tumor types. We have demonstrated that bands characteristic for carotenoids (1156 cm−1, 1520 cm−1), proteins (1004 cm−1), fatty acids (1444 cm−1, 1655 cm−1) and cytochrome (1585 cm−1) can be used as universal biomarkers to distinguish aggressiveness in human brain tumor. The sensitivity and specificity obtained from PLS-DA have been over 85%. Only for pituitary adenoma the specificity is lower and takes equal 46%. The presented results confirm the potential applications of vibrational spectroscopy methods in oncological diagnostics.
Quantitative analysis of spore shapes improves identification of fungi
Authors: Ordynets Alexander , Keßler Sarah , Langer Ewald 
Published: April 2021

AbstractMorphology of organisms is an important source of evidence for biodiversity assessment, taxonomic decisions, and understanding of evolution. Shape information about zoological and botanical objects is often treated quantitatively and in this form improves species identification. In studies of fungi, quantitative shape analysis was almost ignored. The disseminated propagules of fungi, the spores, are crucial for their taxonomy – currently in the form of linear measurements or subjectively defined shape categories. It remains unclear how much quantifying spore shape information can improve species identification. In this study, we tested the hypothesis that shape, as a richer source of information, overperforms size when performing automated identification of fungal species. We used the fungi of the genusSubulicystidium(Agaricomycetes, Basidiomycota) as a study object. We analysed 2D spore shape data via elliptic Fourier and Principal Component analyses. With flexible discriminant analysis, we achieved a slightly higher species identification success rate for shape predictors (61.5%) than for size predictors (59.1%). However, we achieved the highest rate for a combination of both (64.7%). We conclude that quantifying fungal spore shapes is worth the effort. We provide an open access protocol which, we hope, will stimulate a broader use of quantitative shape analysis in fungal taxonomy. We also discuss the challenges of such analyses that are specific to fungal spores.
Treatment of canine visceral leishmaniasis with Milteforan™inducesLeishmania infantumresistance to miltefosine and amphotericin B
Authors: Gonçalves Gustavo , Campos Monique Paiva , Gonçalves Alessandra Silva , Soares Medeiros Lia Carolina , Figueiredo Fabiano Borges 
Published: April 2021

AbstractVisceral leishmaniasis (VL) is the most severe form of leishmaniasis and is caused byLeishmania infantumin the Americas. Since the use of Milteforam™ was authorized to treat canine visceral leishmaniasis (CVL) in Brazil in 2017, there has also been fear of the emergence of parasites resistant to this drug and, through cross-resistance mechanisms, to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are determining factors for parasite virulence. In this context, this study aims to analyze the impact of treating a dog with Milteforan™ on the generation of parasites resistant to miltefosine, meglumine antimoniate, and amphotericin B. To this end,in vitrosusceptibility tests were conducted against these drugs with T0 (parasites isolated from the dog before treatment with Milteforan™), T1 (after one course of treatment), and T2 (after two courses of treatment) isolates. The rates of cell proliferation, infectivity, and metacyclogenesis of the isolates were also evaluated. The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. A trend increase in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. Therefore, treatment of CVL with Milteforan™ induces resistance to miltefosine and amphotericin B as well as changes in parasite fitness, and may have an impact on animal and human public health.
Quest for the Allmitey: Potential ofPronematus ubiquitus(Acari: Iolinidae) as a biocontrol agent againstTetranychus urticaeandTetranychus evansi(Acari: Tetranychidae) on tomato (Solanum lycopersicumL.)
Authors: Van de Velde Viktor , Duarte Marcus V. A. , Benavente Alfredo , Vangansbeke Dominiek , Wäckers Felix , De Clercq Patrick 
Published: April 2021

AbstractThe spider mitesTetranychus evansiBaker & Pritchard andTetranychus urticaeKoch (Acari: Tetranychidae) are key tomato pests worldwide. Biological control of spider mites using phytoseiid predatory mites remains challenging. The glandular trichomes on the tomato leaves and stem severely hamper the movement and establishment of the predatory mites. As a result, smaller predatory mites, able to thrive under the sticky heads of the glandular trichomes, have gained much interest. As some iolinid predatory mites were reported to feed on spider mites, we investigated the potential ofPronematus ubiquitusMcGregor to control bothT. urticaeandT. evansion tomato plants. On whole tomato plants,P. ubiquituswas able to suppress populations ofT. urticae, but not ofT. evansi. Based on the marginal number of spider mites killed in laboratory trials, the observed biocontrol effect on full tomato plants might not be due to direct predation but to a plant-mediated indirect impact. The oviposition ofT. urticaewas found to be significantly lower on tomato leaflets pre-exposed toP. ubiquitusas compared to non-exposed leaflets. The oviposition rate ofT. evansiwas not affected by previous exposure of the tomato host plant toP. ubiquitus. We demonstrated thatP. ubiquitusreduces the population growth ofT. urticaeon tomato plants. Further large-scale field trials need to confirm the findings of the present study.
A Positive Regulatory Feedback Loop Between EKLF/ KLF1 and TAL1/SCL Sustaining the Erythropoiesis
Authors: Hung Chun-Hao , Huang Yu-Szu , Lee Tung-Liang , Yang Kang-Chung , Shyu Yu-Chiau , Wen Shau-Ching , Lu Mu-Jie , Yuan Shinsheng , Shen Che-Kun James 
Published: April 2021

AbstractThe erythroid Krüppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and promoter-based ChIP-chip assay of E14.5 fetal liver cells from wild type (WT) and EKLF-knockout (Eklf−/−) mouse embryos, we have identified the pathways and direct target genes activated or repressed by EKLF. This genome-wide study together with molecular/cellular analysis of mouse erythroleukemic cells (MEL) indicate that among the downstream direct target genes of EKLF isTal1/Scl.Tal1/Sclencodes another DNA-binding hematopoietic transcription factor TAL1/SCL known to be anEklfactivator and essential for definitive erythroid differentiation. Further identification of the authenticTallgene promoter in combination within vivogenomic footprinting approach and DNA reporter assay demonstrate that EKLF activatesTallgene through binding to a specific CACCC motif located in its promoter. These data establish the existence of a previously unknow positive regulatory feedback loop between two DNA-binding hematopoietic transcription factors that sustains the mammalian erythropoiesis.
Natural variations in reproductive timing of brood size and X-chromosome nondisjunction inCaenorhabditis elegans
Authors: Lim Jiseon , Kim Jun , Lee Junho 
Published: April 2021

AbstractReproductive timing underlies self-sperm production and X-chromosome nondisjunction rate inCaenorhabditis elegans. These traits can be measured as brood size and male-production rate, and brood size decreases and male-production rate increases as worms age. These phenotypic changes occur simultaneously; however, whether these changes share common underlying genetic architectures still remains unclear. To enhance our understanding of reproductive timing inC. elegans, we measured and compared these two reproductive timing-related traits of 96 wild strains during early, late and total reproductive periods. We found that the two traits exhibited natural phenotypic variation with few outliers and a similar reproductive timing pattern as previous reports. The brood size and the male-production rate were not genetically correlated, implying that they might have different genetic architectures and that meiosis quality can be maintained despite increased progeny-production in the late reproductive period caused by more self-sperm. We also identified loci and candidate genetic variants significantly associated with male-production rate in the late and total reproductive periods. Our results provide an insight into life history traits in wildC. elegansstrains.