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1.
Plant Genome ; 17(1): e20418, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38093595

ABSTRACT

Greenbug [Schizaphis graminum (Rondani)] is a major insect pest that significantly affects barley production worldwide. The identification of novel greenbug resistance genes is crucial for sustainable barley production and global food security. To identify greenbug resistance genes from a US breeding line PI 499276 and a Chinese cultivar PI 566459, two F6:7 recombinant inbred line (RIL) populations developed from crosses Weskan × PI 499276 and Weskan × PI 566459 were phenotyped for responses to greenbug biotype E and genotyped using genotyping-by-sequencing (GBS). Linkage analysis using single nucleotide polymorphism and kompetitive allele-specific polymorphism (KASP) markers delimited the greenbug resistance genes from PI 499276 and PI 566459 to a 1.2 Mb genomic region between 666.5 and 667.7 Mb on the long arm of chromosome 3H in the Morex Hordeum vulgare r1 reference sequence. Allelism tests based on responses of four F2 populations to greenbug biotype E indicated that the greenbug resistance gene in PI 499276 and PI 566459 is either allelic or very close to Rsg1. Given that PI 499276 and PI 566459 shared the same unique resistance pattern to a set of 14 greenbug biotypes, which is different from those of other Rsg1 alleles, they carry a new Rsg1 allele. The greenbug resistance genes in Post 90, PI 499276/PI 566459, and WBDC 336 were designated as Rsg1.a1, Rsg1.a2, and Rsg1.a3, respectively. KASP markers KASP-Rsg1a3-1, KASP-Rsg1a3-2, and KASP160 can be used to tag Rsg1.a2 in barley breeding.


Subject(s)
Hordeum , Hordeum/genetics , Alleles , Plant Breeding , Phenotype , Genotype
2.
Curr Protoc ; 3(12): e940, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38050642

ABSTRACT

In a living cell, proteins interact to assemble both transient and constant molecular complexes, which transfer signals/information around internal pathways. Modern proteomic techniques can identify the constituent components of these complexes, but more detailed analysis demands a network approach linking the molecules together and analyzing the emergent architectural properties. The Bioconductor package BioNAR combines a selection of existing R protocols for network analysis with newly designed original methodological features to support step-by-step analysis of biological/biomedical . Critically, BioNAR supports a pipeline approach whereby many networks and iterative analyses can be performed. Here we present a network analysis pipeline that starts from initiating a network model from a list of components/proteins and their interactions through to identifying its functional components based solely on network topology. We demonstrate that BioNAR can help users achieve a number of network analysis goals that are difficult to achieve anywhere else. This includes how users can choose the optimal clustering algorithm from a range of options based on independent annotation enrichment, and predict a protein's influence within and across multiple subcomplexes in the network and estimate the co-occurrence or linkage between metadata at the network level (e.g., diseases and functions across the network, identifying the clusters whose components are likely to share common function and mechanisms). The package is freely available in Bioconductor release 3.17: https://bioconductor.org/packages/3.17/bioc/html/BioNAR.html. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Creating and annotating the network Support Protocol 1: Installing BioNAR from RStudio Support Protocol 2: Building the sample network from synaptome.db Basic Protocol 2: Network properties and centrality Basic Protocol 3: Network communities Basic protocol 4: Choosing the optimal clustering algorithm based on the enrichment with annotation terms Basic Protocol 5: Influencing network components and bridgeness Basic Protocol 6: Co-occurrence of the annotations.


Subject(s)
Proteomics , Software , Algorithms , Proteins
3.
PLoS One ; 18(12): e0295848, 2023.
Article in English | MEDLINE | ID: mdl-38109382

ABSTRACT

Hikers and hillwalkers typically use the gradient in the direction of travel (walking slope) as the main variable in established methods for predicting walking time (via the walking speed) along a route. Research into fell-running has suggested further variables which may improve speed algorithms in this context; the gradient of the terrain (hill slope) and the level of terrain obstruction. Recent improvements in data availability, as well as widespread use of GPS tracking now make it possible to explore these variables in a walking speed model at a sufficient scale to test statistical significance. We tested various established models used to predict walking speed against public GPS data from almost 88,000 km of UK walking / hiking tracks. Tracks were filtered to remove breaks and non-walking sections. A new generalised linear model (GLM) was then used to predict walking speeds. Key differences between the GLM and established rules were that the GLM considered the gradient of the terrain (hill slope) irrespective of walking slope, as well as the terrain type and level of terrain obstruction in off-road travel. All of these factors were shown to be highly significant, and this is supported by a lower root-mean-square-error compared to existing functions. We also observed an increase in RMSE between the GLM and established methods as hill slope increases, further supporting the importance of this variable.


Subject(s)
Running , Walking , Walking Speed , Linear Models , Algorithms , Biomechanical Phenomena
4.
Phys Rev Lett ; 131(4): 041002, 2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37566836

ABSTRACT

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.

5.
Front Behav Neurosci ; 17: 1148172, 2023.
Article in English | MEDLINE | ID: mdl-37035623

ABSTRACT

Monitoring the activity of mice within their home cage is proving to be a powerful tool for revealing subtle and early-onset phenotypes in mouse models. Video-tracking, in particular, lends itself to automated machine-learning technologies that have the potential to improve the manual annotations carried out by humans. This type of recording and analysis is particularly powerful in objective phenotyping, monitoring behaviors with no experimenter intervention. Automated home-cage testing allows the recording of non-evoked voluntary behaviors, which do not require any contact with the animal or exposure to specialist equipment. By avoiding stress deriving from handling, this approach, on the one hand, increases the welfare of experimental animals and, on the other hand, increases the reliability of results excluding confounding effects of stress on behavior. In this study, we show that the monitoring of climbing on the wire cage lid of a standard individually ventilated cage (IVC) yields reproducible data reflecting complex phenotypes of individual mouse inbred strains and of a widely used model of neurodegeneration, the N171-82Q mouse model of Huntington's disease (HD). Measurements in the home-cage environment allowed for the collection of comprehensive motor activity data, which revealed sexual dimorphism, daily biphasic changes, and aging-related decrease in healthy C57BL/6J mice. Furthermore, home-cage recording of climbing allowed early detection of motor impairment in the N171-82Q HD mouse model. Integrating cage-floor activity with cage-lid activity (climbing) has the potential to greatly enhance the characterization of mouse strains, detecting early and subtle signs of disease and increasing reproducibility in preclinical studies.

6.
Nat Commun ; 14(1): 1602, 2023 03 23.
Article in English | MEDLINE | ID: mdl-36959177

ABSTRACT

Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes, play key roles in fundamental cellular processes, including the sensing and transduction of mechanical cues. Here, we investigate systems-level changes in the integrin adhesome in patient-derived cutaneous squamous cell carcinoma cells and identify the actin regulatory protein Mena as a key node in the adhesion complex network. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope. Moreover, Mena potentiates the interactions of nesprin-2 with the actin cytoskeleton and the nuclear lamina. CRISPR-mediated Mena depletion causes altered nuclear morphology, reduces tyrosine phosphorylation of the nuclear membrane protein emerin and downregulates expression of the immunomodulatory gene PTX3 via the recruitment of its enhancer to the nuclear periphery. We uncover an unexpected role for Mena at the nuclear membrane, where it controls nuclear architecture, chromatin repositioning and gene expression. Our findings identify an adhesion protein that regulates gene transcription via direct signalling across the nuclear envelope.


Subject(s)
Carcinoma, Squamous Cell , Skin Neoplasms , Humans , Actins/genetics , Actins/metabolism , Carcinoma, Squamous Cell/metabolism , Cell Nucleus/metabolism , Gene Expression , Integrins/metabolism , Microfilament Proteins/metabolism , Nuclear Envelope/metabolism , Nuclear Lamina/metabolism , Skin Neoplasms/metabolism
7.
Front Physiol ; 14: 1076533, 2023.
Article in English | MEDLINE | ID: mdl-36776967

ABSTRACT

As a model organism, Drosophila is uniquely placed to contribute to our understanding of how brains control complex behavior. Not only does it have complex adaptive behaviors, but also a uniquely powerful genetic toolkit, increasingly complete dense connectomic maps of the central nervous system and a rapidly growing set of transcriptomic profiles of cell types. But this also poses a challenge: Given the massive amounts of available data, how are researchers to Find, Access, Integrate and Reuse (FAIR) relevant data in order to develop an integrated anatomical and molecular picture of circuits, inform hypothesis generation, and find reagents for experiments to test these hypotheses? The Virtual Fly Brain (virtualflybrain.org) web application & API provide a solution to this problem, using FAIR principles to integrate 3D images of neurons and brain regions, connectomics, transcriptomics and reagent expression data covering the whole CNS in both larva and adult. Users can search for neurons, neuroanatomy and reagents by name, location, or connectivity, via text search, clicking on 3D images, search-by-image, and queries by type (e.g., dopaminergic neuron) or properties (e.g., synaptic input in the antennal lobe). Returned results include cross-registered 3D images that can be explored in linked 2D and 3D browsers or downloaded under open licenses, and extensive descriptions of cell types and regions curated from the literature. These solutions are potentially extensible to cover similar atlasing and data integration challenges in vertebrates.

8.
Plant Genome ; 16(1): e20287, 2023 03.
Article in English | MEDLINE | ID: mdl-36479942

ABSTRACT

Greenbug (Schizaphis graminum Rondani) is a pest that poses a serious threat to cereal production worldwide. Yield losses caused by greenbug are predicted to increase because of global warming. To date, only a few barley (Hordeum vulgare L.) greenbug resistance genes have been reported and new genes are urgently needed because of the continuous occurrence of novel greenbug biotypes. PI 565676, a landrace collected from Henan province of China, exhibits high resistance to several predominant greenbug biotypes. An F6:7 recombinant inbred line (RIL) population derived from the cross PI 565676 × 'Weskan' was evaluated for response to greenbug biotypes E and F using a standard aphid assay protocol, and a randomized complete block design with two replicates was adopted. The RIL population was genotyped using single-nucleotide polymorphisms (SNPs) markers generated by genotyping-by-sequencing (GBS). Gene mapping placed the greenbug resistance gene in PI 565676, designated Rsg3, to an interval of 93,140 bp between 667,558,306 and 667,651,446 bp on the long arm of chromosome 3H. Four high-confidence genes were annotated in this region with one encoding a leucine-rich repeat-containing protein. An allelism test indicated that Rsg3 is independent of the Rsg1 locus, with estimated recombination frequency of 12.85 ± 0.20% and genetic distance of 13.14 ± 0.21 cM between the two loci. Therefore, Rsg3 represents a new locus for greenbug resistance. Two SNPs flanking Rsg3 were converted to Kompetitive Allele Specific PCR (KASP) markers, which can be used to tag Rsg3 in barley breeding.


Subject(s)
Aphids , Hordeum , Animals , Alleles , Aphids/genetics , Chromosome Mapping , Genotype , Hordeum/genetics , Plant Breeding
9.
Rev Sci Instrum ; 93(11): 113534, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36461490

ABSTRACT

Charged particle spectrometry is a critical diagnostic to study inertial-confinement-fusion plasmas and high energy density plasmas. The OMEGA Laser Facility has two fixed magnetic charged particle spectrometers (CPSs) to measure MeV-ions. In situ calibration of these spectrometers was carried out using 241Am and 226Ra alpha emitters. The alpha emission spectrum from the sources was measured independently using surface-barrier detectors (SBDs). The energy dispersion and broadening of the CPS systems were determined by comparing the CPS measured alpha spectrum to that of the SBD. The calibration method significantly constrains the energy dispersion, which was previously obtained through the measurement of charged particle fusion products. Overall, a small shift of 100 keV was observed between previous and the calibration done in this work.

10.
Genomics ; 114(4): 110408, 2022 07.
Article in English | MEDLINE | ID: mdl-35716823

ABSTRACT

Since 2013, the sorghum aphid (SA), Melanaphis sorghi (Theobald), has been a serious pest that hampers all types of sorghum production in the U.S. Known sorghum aphid resistance in sorghum is limited to a few genetic regions on SBI-06. In this study, a subset of the Sorghum Association Panel (SAP) was used along with some additional lines to identify genomic regions that confer sorghum aphid resistance. SAP lines were grown in the field and visually evaluated for SA resistance during the growing seasons of 2019 and 2020 in Tifton, GA. In 2020, the SAP accessions were also evaluated for SA resistance in the field using drone-based high throughput phenotyping (HTP). Flowering time was recorded in the field to confirm that our methods were sufficient for identifying known quantitative trait loci (QTL). This study combined phenotypic data from field-based visual ratings and reflectance data to identify genome-wide associated (GWAS) marker-trait associations (MTA) using genotyping-by-sequencing (GBS) data. Several MTAs were identified for SA-related traits across the genome, with a few common markers that were consistently identified on SBI-08 and SBI-10 for aphid count and plant damage, as well as loci for reflectance-based traits on SBI-02, SBI-03, and SBI-05. Candidate genes encoding leucine-rich repeats (LRR), Avr proteins, lipoxygenases (LOXs), calmodulins (CAM) dependent protein kinase, WRKY transcription factors, flavonoid biosynthesis genes, and 12-oxo-phytodienoic acid reductase were identified near SNPs that had significant associations with different SA traits. In this study, flowering time-related genes were also identified as a positive control for the methods. The total phenotypic variation explained by significant SNPs across SA-scored traits, reflectance data, and flowering time ranged from 6 to 61%, while the heritability value ranged from 4 to 69%. This study identified three new sources of resistant lines to sorghum aphid. These results supported the existing literature, and also revealed several new loci. Markers identified in this study will support marker-assisted breeding for sorghum aphid resistance.


Subject(s)
Aphids , Sorghum , Animals , Aphids/genetics , Edible Grain/genetics , Genome-Wide Association Study , Genotype , Phenotype , Plant Breeding , Polymorphism, Single Nucleotide , Sorghum/genetics
11.
Nature ; 2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35488057
12.
BMC Public Health ; 22(1): 849, 2022 04 28.
Article in English | MEDLINE | ID: mdl-35484587

ABSTRACT

BACKGROUND: As of 2019, men who have sex with men (MSM) in Canada are ineligible to donate blood if they have had oral or anal sex with another man in the last 3 months. Deferral policies targeting MSM are largely interpreted as unjust by gay, bisexual, and other men who have sex with men (GBMSM) - shaping their desire to donate blood and engage with blood operators. This mixed methods study explores interest in blood donation among GBMSM as well as willingness (and eligibility) to donate under four different deferral policies. METHODS: We surveyed 447 GBMSM who were recruited from the Ontario-wide #iCruise study. Participants were asked whether they were interested in blood donation and if they were willing to donate under each of our four deferral policies. We also completed interviews with 31 of these GBMSM. Participants were asked to describe their feelings about blood donation, their views on our different deferral policies, the impact of a policy change, as well as other means of redress. RESULTS: Most participants (69%) indicated that they were interested in donating blood. Despite this, an interpretation of the MSM deferral policy as discriminatory was common among all participants. Our mixed methods findings indicate that, among those who were interested in blood donation, the adoption of one of the alternative policies presented in this study (specifically Policy 2 or Policy 3) would significantly increase the number of participants willing to donate and be viewed as "a step in the right direction." However, many participants who were not interested in blood donation argued that a gender-neutral deferral policy would need to be implemented for them to donate. Participants recommended that blood operators consider efforts to repair relations with GBMSM beyond policy change, including pop-up clinics in predominantly queer areas and diversity sensitivity training for staff. CONCLUSION: We argue that the most impactful policy shift would be the implementation of an individual risk-based deferral policy that is applied to all donors regardless of sexual orientation or gender identity. However, given MSM's historical exclusion from blood donations, blood operators should pair this policy shift with community relationship-building efforts.


Subject(s)
Sexual and Gender Minorities , Blood Donors , Female , Gender Identity , Homosexuality, Male , Humans , Male , Ontario , Policy , Sexual Behavior
13.
Mult Scler Relat Disord ; 57: 103330, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35158444

ABSTRACT

OBJECTIVE: This study compared traditional statistical methods to different predictive analytics methods on the endpoint of multiple sclerosis (MS) relapse. STUDY SETTING: This is a secondary data analysis on four different MS Centers based on the third year of data, July 2019-June 2020. STUDY DESIGN: The parent study is a two-part, 3-year clinical quality improvement prospective study that started in June 2017 and concluded in June 2020, and utilizes a prospective stepped-wedge randomized design. Binary logistic regression was compared with other machine learning models, specifically ridge, least absolute shrinkage and selection operator (LASSO), and random forest. DATA COLLECTION: This study used electronic health record data extracted at the individual level and 'rolled up' to the system and population level. Inclusion criteria included participants aged 18 years or older, with MS presenting to any of the four centers, who entered the study in any quarter. Exclusion criteria included cases with missing or incorrectly input data and those who refused to participate in the study. PRINCIPAL FINDINGS: When comparing relapse indices across models, random forest significantly outperformed logistic regression and other machine learning algorithms (ΔperfA =27.1%, ΔperfM =27.5%). However, for ΔperfF, logistic regression and random forest performed relatively the same. Ridge and LASSO outperformed logistic regression (ΔperfM1 =0.9%, ΔperfM2 =9.4%, ΔperfF2=25.8%, respectively). CONCLUSION: Multiple sclerosis is a complex and costly chronic ("3C") condition that currently has no cure. In a condition like MS, which has an unpredictable course, the use of predictive analytics could help health systems learn better, faster, and to improve more effectively and predict rather than react to emerging health needs for people with MS. Comparing the predictability of relapse across various models with a predictive analytics framework can potentially change how we manage MS care.


Subject(s)
Multiple Sclerosis , Adolescent , Humans , Logistic Models , Machine Learning , Multiple Sclerosis/diagnosis , Multiple Sclerosis/epidemiology , Multiple Sclerosis/therapy , Prospective Studies , Recurrence
14.
Sci Adv ; 8(6): eabj4633, 2022 Feb 11.
Article in English | MEDLINE | ID: mdl-35138897

ABSTRACT

Rapid environmental change can lead to population extinction or evolutionary rescue. The global staple crop sorghum (Sorghum bicolor) has recently been threatened by a global outbreak of an aggressive new biotype of sugarcane aphid (SCA; Melanaphis sacchari). We characterized genomic signatures of adaptation in a Haitian breeding population that had rapidly adapted to SCA infestation, conducting evolutionary population genomics analyses on 296 Haitian lines versus 767 global accessions. Genome scans and geographic analyses suggest that SCA adaptation has been conferred by a globally rare East African allele of RMES1, which spread to breeding programs in Africa, Asia, and the Americas. De novo genome sequencing revealed potential causative variants at RMES1. Markers developed from the RMES1 sweep predicted resistance in eight independent commercial and public breeding programs. These findings demonstrate the value of evolutionary genomics to develop adaptive trait technology and highlight the benefits of global germplasm exchange to facilitate evolutionary rescue.

15.
Planta ; 255(2): 38, 2022 Jan 14.
Article in English | MEDLINE | ID: mdl-35031833

ABSTRACT

MAIN CONCLUSION: Three known sugarcane aphid-resistant pollinator parents were sterilized in A3 cytoplasmic male sterility and were confirmed in this study to be resistant to sugarcane aphid allowing for the development of sugarcane aphid-resistant forage hybrids. We utilized A3 cytoplasmic male sterility and converted known sugarcane aphid-resistant sorghum TX 2783, and newly released R. LBK1 (Reg. No. GP-865, PI 687244) and R. LBK2 (Reg. No. GP-866, PI 687245) into A3 sterility to determine if the sterile counterparts would also equally express tolerance and or antibiosis to sugarcane aphid. Free-choice flat screen trials and life-table demographic studies were utilized and compared to know susceptible/fertile entries KS 585, and TX 7000, and known resistant/fertile entries TX 2783 and DKS 37-07. The R. LBK1 fertile entry was more tolerant than the known susceptible entries KS 585 and TX 7000, but was not as resistant as the other resistant entries, sustaining a damage rating of 6.0 across two different screen trials. The sterile A3 R. LBK2 showed a greater tolerance and expressed higher levels of antibiosis during aphid reproductive studies when compared to the known resistant and fertile TX 2783. All other fertile (R. LBK2, TX2783) and the A3 male sterile counterparts (A3 R. LBK2, A3 TX2783) were very similar in expression of high levels of tolerance and exhibited statistically similar damage ratings of 3.3-4.3 when exposed to sugarcane aphids. No entry, either fertile or sterile, was as tolerant as DKS 37-07, a known resistant commercial hybrid. Other plant measurements including percent loss in chlorophyll content, difference in plant height, and number of true leaves for sugarcane aphid infested versus non-infested were very consistent and highly correlated with damage ratings. Antibiosis was also exhibited in both fertile and sterile versions of the resistant lines. There was a 2 × reduction in fecundity between the R. LBK1 fertile and its sterile A3 R. LBK1 when compared to the susceptible KS 585 and TX 7000; however, the remaining fertile and sterile entries had 3.8 × to 5.8 × decrease in fecundity when compared to the susceptible KS 585 and TX 7000. Other measurements in life-table statistics such as nymphs produced/female/d, and the intrinsic rates of increased were significantly lower for all fertile and sterile lines, showing that antibiosis significantly affected sugarcane aphid reproduction. In conclusion, the A3 cytoplasmic male sterility shows consistency for maintaining the single dominant trait SCA-resistant trait of TX 2783 for expressing both antibiosis and tolerance, and great utility in the development of sugarcane aphid-resistant forage sorghums.


Subject(s)
Aphids , Plant Infertility , Sorghum , Animals , Edible Grain , Sorghum/genetics
16.
Occup Med (Lond) ; 72(1): 35-42, 2022 01 13.
Article in English | MEDLINE | ID: mdl-34729600

ABSTRACT

BACKGROUND: Health care workers (HCWs) have been recognized as being at higher risk for coronavirus disease 2019 (COVID-19) infection; however, relevant factors and magnitude have not been clearly elucidated. AIM: This study was aimed to describe COVID-19 infections among hospital employees at a large tertiary care hospital located in Ontario, Canada from March to July 2020, towards better understanding potential risk factors. METHODS: Data on all HCWs with either a positive COVID test or a high-risk exposure from March to July 2020 were analyzed. HCWs with positive COVID test results and high-risk exposures were described. Those who developed COVID-19 following high-risk exposure were compared to those who did not. Data were also analyzed to determine trends over time. RESULTS: Over the period of observation, 193 staff (2% of total working staff) had a positive COVID-19 test. Incidence of HCW infections closely followed community incidence. Overall, 31% of COVID-19 cases were deemed occupationally acquired. Of these, 41% were acquired from a patient, with the remainder (59%) from fellow staff. Over the same period, 204 staff were identified as having a high-risk exposure. The majority of exposures (55%) were patient-associated, with the remaining (45%) resulting from staff-to-staff contact. Overall, 13% went on to develop COVID-19. Of these cases, 58% were patient-associated and 42% were a result of staff-to-staff transmission. CONCLUSIONS: HCWs are at risk for work-related COVID-19. Given the number of infections attributed to staff-staff transmission, greater attention could be paid to implementing prevention measures in non-clinical areas.


Subject(s)
COVID-19 , Health Personnel , Humans , Ontario/epidemiology , Personnel, Hospital , Risk Factors , SARS-CoV-2
17.
Br J Dermatol ; 186(4): 694-704, 2022 04.
Article in English | MEDLINE | ID: mdl-34773645

ABSTRACT

BACKGROUND: For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis. OBJECTIVES: The aim of the present study was to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)-ß signalling to the loss of AMBRA1 in the epidermis overlying the primary tumour and disruption of epidermal integrity. METHODS: Immunohistochemistry was used to analyse AMBRA1 and TGF-ß2 in a cohort of 109 AJCC all-stage melanomas, and TGF-ß2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analysed in a cohort of 42 melanomas, with TGF-ß2 signalling evaluated in primary keratinocytes. RESULTS: Increased tumoral TGF-ß2 was significantly associated with loss of peritumoral AMBRA1 (P < 0·05), ulceration (P < 0·001), AMLo high-risk status (P < 0·05) and metastasis (P < 0·01). TGF-ß2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes (P < 0·05). Importantly, we show loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression (P < 0·05), parakeratosis (P < 0·01) and cleft formation in the dermoepidermal junction (P < 0·05). CONCLUSIONS: Collectively, these data suggest a paracrine mechanism whereby TGF-ß2 causes loss of AMBRA1 overlying high-risk AJCC early-stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumour ulceration.


Subject(s)
Melanoma , Skin Neoplasms , Transforming Growth Factor beta2/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Epidermis/metabolism , Humans , Melanoma/pathology , Skin Neoplasms/pathology , Transforming Growth Factor beta/metabolism , Transforming Growth Factors/metabolism
18.
J Intellect Disabil Res ; 66(3): 213-224, 2022 03.
Article in English | MEDLINE | ID: mdl-34796573

ABSTRACT

BACKGROUND: Knowledge regarding neuropsychological training in Rett syndrome (RS) is scarce. The aim of this study was to assess the outcome and the duration of the effect of cognitive stimulation on topographic electroencephalography (EEG) data in RS. METHODS: Twenty female children diagnosed with RS were included in the analysis. Girls with RS conducted a cognitive task using an eye-tracker designed to evaluate access and choice skills. EEG data were acquired during the experimental procedure including two 10-min baseline stages before and after the task. Topographical changes of several EEG spectral markers including absolute and relative powers, Brain Symmetry Index and entropy were assessed. RESULTS: Topographic significance probability maps suggested statistical decreases on delta activity and increases on beta rhythm associated with the cognitive task. Entropy increased during and after the task, likely related to more complex brain activity. A significant positive interaction was obtained between Brain Symmetry Index and age showing that the improvement of interhemispheric symmetry was higher in younger girls (5-10 years). CONCLUSIONS: According to our findings, significant alterations of brain rhythms were observed during and after cognitive stimulation, suggesting that cognitive stimulation may have effects on brain activity beyond the stimulation period. Finally, our promising results also showed an increase brain symmetry that was especially relevant for the younger group. This could suggest an interaction of the eye-tracking cognitive task; however, further studies in this field are needed to assess the relation between brain asymmetries and age.


Subject(s)
Cognitive Behavioral Therapy , Rett Syndrome , Brain , Child , Child, Preschool , Cognition , Electroencephalography/methods , Female , Humans
19.
Bioinform Adv ; 2(1): vbac086, 2022.
Article in English | MEDLINE | ID: mdl-36699346

ABSTRACT

Summary: The neuronal synapse is underpinned by a large and diverse proteome but the molecular evidence is spread across many primary datasets. These data were recently curated into a single dataset describing a landscape of ∼8000 proteins found in studies of mammalian synapses. Here, we describe programmatic access to the dataset via the R/Bioconductor package Synaptome.db, which enables convenient and in-depth data analysis from within the Bioconductor environment. Synaptome.db allows users to obtain the respective gene information, e.g. subcellular localization, brain region, gene ontology, disease association and construct custom protein-protein interaction network models for gene sets and entire subcellular compartments. Availability and implementation: The package Synaptome.db is part of Bioconductor since release 3.14, https://bioconductor.org/packages/release/data/annotation/html/synaptome.db.html, it is open source and available under the Artistic license 2.0. The development version is maintained on GitHub (https://github.com/lptolik/synaptome.db). Full documentation including examples is provided in the form of vignettes on the package webpage. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

20.
J Econ Entomol ; 114(6): 2277-2289, 2021 12 06.
Article in English | MEDLINE | ID: mdl-34447985

ABSTRACT

Studies were conducted with ozone gas fumigation under vacuum as a methyl bromide alternative against life stages of coffee berry borer (CBB) Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae), and the urediniospores of coffee leaf rust (CLR), Hemileia vastatrix Berkeley & Broome (Basidiomycota: Pucciniales) in green coffee, Coffea spp. L. Fumigation with 10,000 ppm O3 gas under -25.4 mm Hg vacuum1 at 13.0 ± 3.0°C for 6.0 h killed all CBB larvae, pupae, and adults, but did not kill all CBB eggs (~15% survival). Mortality of CLR urediniospores was 100% within the first hour of the 6-h fumigation. Ozone fumigation had no adverse effects on coffee quality. Results indicated that CBB adult hitchhikers may be the only target life stage of quarantine concern, and additional studies focused on this stage. CBB adult survival and reproduction decreased significantly at moisture contents ≤20%, and F1 generation survival did not occur in green coffee at moisture contents ≤15%. As the international standard for green coffee moisture content is 9-12%, adult CBB should not survive or reproduce in exported dry green coffee. Standard industry processing of harvested coffee cherries to the green coffee stage using either mechanical- or sun-drying eliminated CBB infestations from the field. A systems approach is recommended for exporting green coffee to control CBB and CLR that includes eliminating CBB life stages with standard processing methods, reducing moisture content to 9-12% to prevent egg deposition, survival or reproduction, and O3 fumigation to ensure quarantine security against potential CBB adult hitchhikers.


Subject(s)
Basidiomycota , Coffea , Ozone , Weevils , Animals , Coffee , Fumigation , Hawaii , Plant Diseases , Risk Assessment , Vacuum
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