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result(s) for
"Miller, Troy K."
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Legume Alternative Oxidase Isoforms Show Differential Sensitivity to Pyruvate Activation
by
Miller, Troy K.
,
Day, David A.
,
Sweetman, Crystal
in
activation
,
Alternative oxidase
,
Cotyledons
2022
Alternative oxidase (AOX) is an important component of the plant respiratory pathway, enabling a route for electrons that bypasses the energy-conserving, ROS-producing complexes of the mitochondrial electron transport chain. Plants contain numerous isoforms of AOX, classified as either AOX1 or AOX2. AOX1 isoforms have received the most attention due to their importance in stress responses across a wide range of species. However, the propensity for at least one isoform of AOX2 to accumulate to very high levels in photosynthetic tissues of all legumes studied to date, suggests that this isoform has specialized roles, but we know little of its properties. Previous studies with sub-mitochondrial particles of soybean cotyledons and roots indicated that differential expression of GmAOX1, GmAOX2A, and GmAOX2D across tissues might confer different activation kinetics with pyruvate. We have investigated this using recombinantly expressed isoforms of soybean AOX in a previously described bacterial system ( Selinski et al., 2016 , Physiologia Plantarum 157, 264-279). Pyruvate activation kinetics were similar between the two GmAOX2 isoforms but differed substantially from those of GmAOX1, suggesting that selective expression of AOX1 and 2 could determine the level of AOX activity. However, this alone cannot completely explain the differences seen in sub-mitochondrial particles isolated from different legume tissues and possible reasons for this are discussed.
Journal Article
Salt-induced expression of intracellular vesicle trafficking genes, CaRab-GTP, and their association with Na+ accumulation in leaves of chickpea (Cicer arietinum L.)
by
Miller, Troy K.
,
Khassanova, Gulmira
,
Sweetman, Crystal
in
Abiotic stress
,
Accumulation
,
Agriculture
2020
Background
Chickpea is an important legume and is moderately tolerant to salinity stress during the growing season. However, the level and mechanisms for salinity tolerance can vary among accessions and cultivars. A large family of
CaRab
-GTP genes, previously identified in chickpea, is homologous to intracellular vesicle trafficking superfamily genes that play essential roles in response to salinity stress in plants.
Results
To determine which of the gene family members are involved in the chickpea salt response, plants from six selected chickpea accessions (Genesis 836, Hattrick, ICC12726, Rupali, Slasher and Yubileiny) were exposed to salinity stress and expression profiles resolved for the major
CaRab
-GTP gene clades after 5, 9 and 15 days of salt exposure. Gene clade expression profiles (using degenerate primers targeting all members of each clade) were tested for their relationship to salinity tolerance measures, namely plant biomass and Na
+
accumulation. Transcripts representing 11 out of the 13
CaRab
clades could be detected by RT-PCR, but only six (
CaRabA2
,
−B
,
−C
,
−D
,
−E
and −
H
) could be quantified using qRT-PCR due to low expression levels or poor amplification efficiency of the degenerate primers for clades containing several gene members. Expression profiles of three gene clades,
CaRabB
,
−D
and
−E
, were very similar across all six chickpea accessions, showing a strongly coordinated network. Salt-induced enhancement of
CaRabA2
expression at 15 days showed a very strong positive correlation (R
2
= 0.905) with Na
+
accumulation in leaves. However, salinity tolerance estimated as relative plant biomass production compared to controls, did not correlate with Na
+
accumulation in leaves, nor with expression profiles of any of the investigated
CaRab
-GTP genes.
Conclusion
A coordinated network of
CaRab-GTP
genes, which are likely involved in intracellular trafficking, are important for the salinity stress response of chickpea plants.
Journal Article
Identification of Alternative Mitochondrial Electron Transport Pathway Components in Chickpea Indicates a Differential Response to Salinity Stress between Cultivars
by
Miller, Troy K.
,
Sweetman, Crystal
,
Booth, Nicholas J.
in
Calcium - metabolism
,
Cicer - genetics
,
Cicer - physiology
2020
All plants contain an alternative electron transport pathway (AP) in their mitochondria, consisting of the alternative oxidase (AOX) and type 2 NAD(P)H dehydrogenase (ND) families, that are thought to play a role in controlling oxidative stress responses at the cellular level. These alternative electron transport components have been extensively studied in plants like Arabidopsis and stress inducible isoforms identified, but we know very little about them in the important crop plant chickpea. Here we identify AP components in chickpea (Cicer arietinum) and explore their response to stress at the transcript level. Based on sequence similarity with the functionally characterized proteins of Arabidopsis thaliana, five putative internal (matrix)-facing NAD(P)H dehydrogenases (CaNDA1-4 and CaNDC1) and four putative external (inter-membrane space)-facing NAD(P)H dehydrogenases (CaNDB1-4) were identified in chickpea. The corresponding activities were demonstrated for the first time in purified mitochondria of chickpea leaves and roots. Oxidation of matrix NADH generated from malate or glycine in the presence of the Complex I inhibitor rotenone was high compared to other plant species, as was oxidation of exogenous NAD(P)H. In leaf mitochondria, external NADH oxidation was stimulated by exogenous calcium and external NADPH oxidation was essentially calcium dependent. However, in roots these activities were low and largely calcium independent. A salinity experiment with six chickpea cultivars was used to identify salt-responsive alternative oxidase and NAD(P)H dehydrogenase gene transcripts in leaves from a three-point time series. An analysis of the Na:K ratio and Na content separated these cultivars into high and low Na accumulators. In the high Na accumulators, there was a significant up-regulation of CaAOX1, CaNDB2, CaNDB4, CaNDA3 and CaNDC1 in leaf tissue under long term stress, suggesting the formation of a stress-modified form of the mitochondrial electron transport chain (mETC) in leaves of these cultivars. In particular, stress-induced expression of the CaNDB2 gene showed a striking positive correlation with that of CaAOX1 across all genotypes and time points. The coordinated salinity-induced up-regulation of CaAOX1 and CaNDB2 suggests that the mitochondrial alternative pathway of respiration is an important facet of the stress response in chickpea, in high Na accumulators in particular, despite high capacities for both of these activities in leaf mitochondria of non-stressed chickpeas.
Journal Article
Israel's God and Rebecca's Children
by
David B. Capes, April D. DeConick, Helen K. Bond, Troy A. Miller
in
Christianity
,
Church history
,
Communities
2011,2007
Israel's God and Rebecca's Children is a collection of essays written as a tribute to the lasting scholarship and friendship of Larry Hurtado (University of Edinburgh) and Alan Segal (Barnard College), two scholars who have contributed significantly to the contemporary understanding of Second Temple and Rabbinic Judaism and early Christianity. Their colleagues and friends examine a wide range of topics that have been the focus of Hurtado and Segal's research, including Christology, community, Jewish-Christian relations, soteriology and the development of early Christianity. Together these essays reconceptualize Christology and community in Judaism and Christianity and provide valuable insights into the issues of community and identity.
Diversity in trap color and height increases species richness of bark and woodboring beetles detected in multiple funnel traps
2025
Early detection of non-native, potentially invasive bark beetles and woodboring beetles (BBWB) (Coleoptera: Buprestidae, Cerambycidae, Disteniidae; Curculionidae: Scolytinae) inadvertently introduced to new habitats via global trade is a critical issue for regulatory agencies in numerous countries. We conducted trapping experiments to evaluate the effects of trap color (black vs. green vs. purple) and trap height (canopy vs. understory) on detection of BBWB in Canada, Poland, USA, and China, using Fluon-treated 12-unit multiple-funnel traps. Each trap was baited with the same pheromone and ethanol lures known to attract several species of BBWB. We predicted BBWB species composition would differ between vertical strata and among trap colors, and that the number of BBWB species detected would increase with greater diversity of trapping methods, i.e., by using more than one color of trap and by placing traps in both the canopy and understory. Our prediction was partially supported, i.e., placing one color of trap in the understory and a different colored trap in the canopy detected more species than did a single trap color placed in either the understory or canopy. However, the combinations of trap height and colors that detected the most species varied among sites. The community of BBWB species captured in traps was significantly affected by trap height and trap color at all sites, with the strongest patterns in the data from Poland and the USA. Black and purple traps caught similar communities of BBWB species in the canopy and understory, but green traps caught a different species assemblage in the canopy in Poland and the USA. Effects of trap height and color on species richness were consistent across all four sites within the subfamilies Agrilinae (more species captured in green canopy traps than any other trap height-color combination), Chrysochroinae (more species captured in purple canopy traps than any trap height-color combination) and Scolytinae (more species captured in the understory than the canopy and no effect of trap color), but varied significantly among sites within Cerambycidae subfamilies. None of the species accumulation curves reached an asymptote for any trap color-height combination at any site, indicating that 8–9 traps per site were not sufficient to detect all BBWB species present. Thus, increasing the number of traps deployed per site will increase the BBWB species richness captured and the chances of detecting non-native species that may be present.
Journal Article
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans
by
Oluoch, Herold
,
Ahmed, Rafi
,
Bennouna, Soumaya
in
Adolescent
,
Adult
,
Antibodies, Viral - blood
2009
A major challenge for vaccinologists is to understand vaccine immunogenicity. Pulendran and colleagues use systems biology to determine gene 'signatures' that predict CD8
+
T cell and antibody responses to the yellow fever vaccine.
A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4—an orchestrator of the integrated stress response—that correlated with and predicted YF-17D CD8
+
T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor
TNFRS17
, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.
Journal Article
Integrated genomic characterization of oesophageal carcinoma
by
Wilson, Richard K
,
Gulley, Margaret L
,
Moore, Richard A
in
631/67/1504/1477
,
631/67/69
,
Adenocarcinoma - classification
2017
Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of
CCND1
and
SOX2
and/or
TP63
, whereas
ERBB2, VEGFA
and
GATA4
and
GATA6
were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.
The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.
Complexity in oesophageal carcinomas
The Cancer Genome Atlas Research Network reports integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus. They identify genomic and molecular features that differentiate oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. They find that the genomic profiles of oesophageal adenocarcinomas are more similar to those for gastric adenocarcinoma, suggesting that these might be classified together. Separate consideration of adenocarcinoma and squamous cell carcinoma—and further molecular characterization of these cancers—may be helpful in clinical trials and for developing targeted drug therapies.
Journal Article
Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey
2020
Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.
Journal Article
56 Classification Accuracy of InformantReport on the Dementia Severity Rating Scale (DSRS) for Identifying Examinee-Generated Performance and Symptom Invalidity
by
Miller, Brian I
,
Choudhury, Tabina K
,
Webber, Troy A
in
Accuracy
,
Assessment/Psychometrics/Methods (Adult)
,
Classification
2023
Objective:Assessment of response validity is essential to neuropsychological assessment. Although informant report of examinee functioning has previously been associated with examinee-generated performance and cognitive symptom invalidity (PVT; SVT-C), empirically-derived guidelines for interpreting informantreport validity are lacking. This study sought to assess the classification accuracy of a widely used informant-report measure, the Dementia Severity Rating Scale (DSRS), for discriminating examinee-generated PVT and SVT-C.Participants and Methods:Data were collected from 145 examinee-informant dyads who completed neuropsychological batteries as part of a routine workup in an epilepsy monitoring unit. PVT status was determined by below-threshold performances on >2 indicators (Test of Memory Malingering, Wechsler Digit Span Age Corrected Scaled Score, Word Memory Test). SVT-C status was determined by above-threshold responses on both the Minnesota Multiphasic Personality Inventory-2-Restructured Form Response Bias Scale (MMPI-2-RF RBS) and Structured Inventory of Malingered Symptomatology Amnestic Disorders subscale (SIMS-AM). After assessing demographic and relational covariance via t-test and chi square analyses, receiver operator characteristic curves were derived to assess the classification accuracy of the DSRS for discriminating examinee PVT and SVT-C status.Results:DSRS total score demonstrated acceptable accuracy in classifying PVT status (AUC = .77), with cut scores of >21 and >15 yielding .93-.82 specificity and .44-.63 sensitivity. The DSRS also classified SVT-C status with acceptable accuracy (AUC = .71), with the aforementioned cut scores exhibiting .90-.78 specificity and .50-.64 sensitivity. The DSRS also classified SVT-C status using only one indicator (i.e., MMPI-2-RF RBS or SIMS-AM) with acceptable accuracy (AUC = .71-.72), with the aforementioned cut scores exhibiting .92 specificity and .37-.42 sensitivity.Conclusions:The DSRS can be used to classify examinee-generated PVT and SVT-C on an epilepsy monitoring unit. Results provide empirically-derived psychometric guidelines for interpreting informant-report response validity that are clinically useful and lay the groundwork for future investigations of informant-report response validity.
Journal Article
Timely intervention and control of a novel coronavirus (COVID-19) outbreak at a large skilled nursing facility—San Francisco, California, 2020
2021
To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission.
This cohort study was conducted during March 22-May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California.
Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.
Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages.
Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.
Journal Article