1. P-glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATPdependent ... more 1. P-glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATPdependent transporter activity. It has been suggested that P-glycoprotein may also function as a volume-regulated chloride channel or chloride channel regulator. To assess the chloride channel function of P-glycoprotein, we examined swelling-activated chloride conductances in Xenopusoocytes injected with human MDR1 cRNA. 2. Functional expression of P-glycoprotein in Xenopus oocytes was confirmed using Western blot analysis and by assessing transport of the P-glycoprotein substrate, calcein AM. 3. Endogenous, swelling-activated chloride conductances were virtually absent by the time P-glycoprotein expression was confirmed. Thus, this expression system afforded the advantage of assessing putative MDR1-associated chloride currents in the absence of background currents. 4. The currents activated by hypotonic shock (50 %) in both MDR1-injected and control (waterinjected) oocytes were not significantly different. The swelling response was due in part to the activation of a potassium-selective conductance which could be inhibited by barium. No chloride-selective currents were activated by hypotonic shock in the presence or absence of barium. Therefore, we conclude that P-glycoprotein expression does not produce a swellingactivated chloride conductance in the Xenopus oocyte expression system.
Analysis of the gut microbiome in beef cattle and its association with feed intake, growth, and e... more Analysis of the gut microbiome in beef cattle and its association with feed intake, growth, and efficiency
1. P‐glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATP‐dependent... more 1. P‐glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATP‐dependent transporter activity. It has been suggested that P‐glycoprotein may also function as a volume‐regulated chloride channel or chloride channel regulator. To assess the chloride channel function of P‐glycoprotein, we examined swelling‐activated chloride conductances in Xenopus oocytes injected with human MDR1 cRNA. 2. Functional expression of P‐glycoprotein in Xenopus oocytes was confirmed using Western blot analysis and by assessing transport of the P‐glycoprotein substrate, calcein AM. 3. Endogenous, swelling‐activated chloride conductances were virtually absent by the time P‐glycoprotein expression was confirmed. Thus, this expression system afforded the advantage of assessing putative MDR1‐associated chloride currents in the absence of background currents. 4. The currents activated by hypotonic shock (50%) in both MDR1‐injected and control (water‐injected) oocytes were not significantl...
Collaborating scientists and storytellers successfully built a university-based science-in-action... more Collaborating scientists and storytellers successfully built a university-based science-in-action video storytelling model to test the research question: Can university scientists increase their relatability and public engagement through science-in-action video storytelling? Developed over 14 years, this science storytelling model produced more than a dozen high-visibility narratives that translated science to the public and featured scientists, primarily environmental and climate scientists, who are described in audience surveys as relatable people. This collaborative model, based on long-term trusting partnerships between scientists and video storytellers, documented scientists as they conducted their research and together created narratives intended to humanize scientists as authentic people on journeys of discovery. Unlike traditional documentary filmmaking or journalism, the participatory nature of this translational science model involved scientists in the shared making of nar...
This working paper contains findings from an October 2013 online U.S. national survey on public p... more This working paper contains findings from an October 2013 online U.S. national survey on public perceptions of labeling of genetically modified (GM) foods.
Changing institutional culture to be more diverse and inclusive within the biomedical academic co... more Changing institutional culture to be more diverse and inclusive within the biomedical academic community is difficult for many reasons. Herein we present evidence that a collaborative model involving multiple institutions of higher education can initiate and execute individual institutional change directed at enhancing diversity and inclusion at the postdoctoral researcher (postdoc) and junior faculty level by implementing evidence-based mentoring practices. A higher education consortium, the Big Ten Academic Alliance, invited individual member institutions to send participants to one of two types of annual mentor training: 1) "Mentoring-Up" training for postdocs, a majority of whom were from underrepresented groups; 2) Mentor Facilitator training-a train-the-trainer model-for faculty and senior leadership. From 2016 to 2019, 102 postdocs and 160 senior faculty and administrative leaders participated. Postdocs reported improvements in their mentoring proficiency (87%) and improved relationships with their PIs (71%). 29% of postdoc respondents transitioned to faculty positions, and 85% of these were underrepresented and 75% were female. 59 out of the 120 faculty and administrators (49%) trained in the first three years provided mentor training on their campuses to over 3000 undergraduate and graduate students, postdocs and faculty within the project period. We conclude that early stage biomedical professionals as well as individual institutions of higher education benefited significantly from this collaborative mentee/mentor training model
African indigenous vegetables (AIVs) have recently received wide attention for their contribution... more African indigenous vegetables (AIVs) have recently received wide attention for their contribution toward food and nutrition security. Promoting the production and consumption of AIVs is likely to mitigate food insecurity and alleviate malnutrition in the African region. To document and analyze existing patterns of AIV production in Zambia, farmers were surveyed in person using a structured questionnaire. A total of 300 farmers were selected from Lusaka (50), Katete (50), Chipata (75), Lundazi (75), and Petauke (75). Analysis of the survey results using logit model identified that those who farm less than 10 acres of farming land, were concerned about nutrition quality of AIVs, reported that price of farm produce is fixed by buyers, were registered as a member of any community group or association, received training related to nutrition and health, saved money for unexpected expenses, and were single are more likely than other farmers to produce AIVs for home consumption. Whereas, th...
The R domain of cystic fibrosis transmembrane conductance regulator (CFTR) connects the two halve... more The R domain of cystic fibrosis transmembrane conductance regulator (CFTR) connects the two halves of the protein, each of which possess a transmembranespanning domain and a nucleotide binding domain. Phosphorylation of serine residues, which reside mostly within the C-terminal two-thirds of the R domain, is required for nucleotide-dependent activation of CFTR chloride channel activity. The N terminus of the R domain is also likely to be important in CFTR function, since this region is highly conserved among CFTRs of different species and exhibits sequence similarity with the "linker region" of the related protein, P-glycoprotein. To date, however, the role of this region in CFTR channel function remains unknown. In this paper, we report the effects of five disease-causing mutations within the N terminus of the CFTR-R domain. All five mutants exhibit defective protein processing in mammalian HEK-293 cells, suggesting that they are mislocalized and fail to reach the cell surface. However, in the Xenopus oocyte, three mutants reached the plasma membrane. One of these mutants, L619S, exhibits no detectable function, whereas the other two, D614G and I618T, exhibit partial activity as chloride channels. Single channel analysis of these latter two mutants revealed that they possess defective rates of channel opening, consistent with the hypothesis that the N terminus of the R domain participates in ATP-dependent channel gating. These findings support recent structural models that include this region within extended boundaries of the first nucleotide binding domain.
Genetically modified food created by microorganisms and genetically modified animals and fish are... more Genetically modified food created by microorganisms and genetically modified animals and fish are beyond the scope of this article.
IntroductionNutrition security continues to worsen in sub-Saharan Africa. Current research is lim... more IntroductionNutrition security continues to worsen in sub-Saharan Africa. Current research is limited on how seasonality may influence the impact of nutrition, culinary, and production interventions on food security, diet quality, and consumption of African Indigenous Vegetables (AIV); a culturally accepted source of micro-and-macronutrients that are easily produced due to their adaptation to the local environment. The objective of this study was to evaluate the programmatic impact of AIV interventions on nutrition security among smallholder farmers.MethodsIn a randomized control trial, five target counties in Western Kenya were randomly assigned to one of four treatments: (1) control; (2) production intervention (PI); (3) nutrition and culinary intervention (NCI); and (4) NCI and PI (NCI/PI). After the counties were randomly assigned to a treatment, 503 smallholder farmers (18–65 years) were selected from participatory farmer groups. The PI consisted of five agricultural production...
The prevalence of micronutrient deficiencies continues to remain alarmingly high in subSaharan Af... more The prevalence of micronutrient deficiencies continues to remain alarmingly high in subSaharan Africa. One potential solution to undernutrition is to promote the consumption of African Indigenous Vegetables (AIVs) that are rich in vitamin A, iron, zinc and other healthpromoting phytochemicals. However, due to limited advances in agronomic practices, seed development, available improved varieties, and access to these indigenous plants in the marketplace, work was needed to drive AIVs into the formal marketplace to meet consumer demand. This paper summarizes the research and activities of a diverse group of stakeholders and researchers who came together to improve research, management, production, distribution, and consumption of nutritious AIVs in Eastern Simon et al.: Improving Income and Nutrition of Smallholder Farmers in Eastern
are interrelated disciplines that underpin a shared understanding of the functional prerequisites... more are interrelated disciplines that underpin a shared understanding of the functional prerequisites of health, sustainable vitality and wellbeing. All of these are based on recognition that health interconnects species across the planet, and they offer ways to more effectively tackle complex real-world challenges. Herein we present a bibliometric analysis to document usage of a subset of such terms by journals over time. We also provide examples of parasitic and vector-borne diseases, including malaria, toxoplasmosis, baylisascariasis, and Lyme disease. These and many other diseases have persisted, emerged or re-emerged, and caused great harm to human and animal populations in developed and low income, biodiverse nations around the world, largely because of societal drivers that undermined natural processes of disease prevention and control, which had developed through co-evolution over millennia. Shortcomings in addressing drivers has arisen from a lack or coordinated efforts among researchers, health stewards, societies at large, and governments. Fortunately, specialists collaborating under transdisciplinary and socio-ecological health umbrellas are increasingly integrating established and new techniques for disease modeling, prediction, diagnosis, treatment, control, and prevention. Such approaches often emphasize conservation of biodiversity for health protection, and they provide novel opportunities to increase the efficiency and probability of success.
This is the author's manuscript for a work that has been accepted for publication. Changes result... more This is the author's manuscript for a work that has been accepted for publication. Changes resulting from the publishing process, such as copyediting, final layout, and pagination, may not be reflected in this document. The publisher takes permanent responsibility for the work. Content and layout follow publisher's submission requirements.
The electron-microscopic technique for immunogold labelling of thawed cryosectioned material (K.T... more The electron-microscopic technique for immunogold labelling of thawed cryosectioned material (K.T. Tokuyasu, 1989, Histochem J 21: 163-171) has been adapted for use with isolated chloroplasts. Percollpurified pea (Pisum Sativum L. cv Feltham First) chloroplasts were fixed in a buffered glutaraldehyde solution and then infiltrated with a buffered solution of 10% polyvinylpyrrolidone in 2.07 M sucrose prior to freezing in liquid nitrogen and sectioning in an ultracryomicrotome. Sections were thawed, immunolabelled, and stained with ammonium molybdate in methyl cellulose on Formvar/carbon-coated Cu or Cu/Pd electron-microscope grids. Cryosectioning gave excellent structural preservation and retained antigenicity. The effectiveness of this technique in localizing proteins to their specific chloroplast compartment was assayed using antibodies raised against: (i) the large subunit of ribulose-l,5-bisphosphate carboxylase/oxygenase (Rubisco), a stromal protein, (ii) the chloroplast ATP synthase (CF1), a peripheral thylakoid protein, and (iii) different envelope membrane proteins. Antibodies raised against three members of the chloroplastic outer envelope protein (OEP) import machinery, a 34-kDa protein (OEP34 or IAP34), the channel-forming 75-kDa protein (OEP75 or IAP75), and the 86-kDa precursor protein receptor (OEP86 or IAP86) were tested for their localization. The previous localization of OEP86,
1. P-glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATPdependent ... more 1. P-glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATPdependent transporter activity. It has been suggested that P-glycoprotein may also function as a volume-regulated chloride channel or chloride channel regulator. To assess the chloride channel function of P-glycoprotein, we examined swelling-activated chloride conductances in Xenopusoocytes injected with human MDR1 cRNA. 2. Functional expression of P-glycoprotein in Xenopus oocytes was confirmed using Western blot analysis and by assessing transport of the P-glycoprotein substrate, calcein AM. 3. Endogenous, swelling-activated chloride conductances were virtually absent by the time P-glycoprotein expression was confirmed. Thus, this expression system afforded the advantage of assessing putative MDR1-associated chloride currents in the absence of background currents. 4. The currents activated by hypotonic shock (50 %) in both MDR1-injected and control (waterinjected) oocytes were not significantly different. The swelling response was due in part to the activation of a potassium-selective conductance which could be inhibited by barium. No chloride-selective currents were activated by hypotonic shock in the presence or absence of barium. Therefore, we conclude that P-glycoprotein expression does not produce a swellingactivated chloride conductance in the Xenopus oocyte expression system.
Analysis of the gut microbiome in beef cattle and its association with feed intake, growth, and e... more Analysis of the gut microbiome in beef cattle and its association with feed intake, growth, and efficiency
1. P‐glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATP‐dependent... more 1. P‐glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATP‐dependent transporter activity. It has been suggested that P‐glycoprotein may also function as a volume‐regulated chloride channel or chloride channel regulator. To assess the chloride channel function of P‐glycoprotein, we examined swelling‐activated chloride conductances in Xenopus oocytes injected with human MDR1 cRNA. 2. Functional expression of P‐glycoprotein in Xenopus oocytes was confirmed using Western blot analysis and by assessing transport of the P‐glycoprotein substrate, calcein AM. 3. Endogenous, swelling‐activated chloride conductances were virtually absent by the time P‐glycoprotein expression was confirmed. Thus, this expression system afforded the advantage of assessing putative MDR1‐associated chloride currents in the absence of background currents. 4. The currents activated by hypotonic shock (50%) in both MDR1‐injected and control (water‐injected) oocytes were not significantl...
Collaborating scientists and storytellers successfully built a university-based science-in-action... more Collaborating scientists and storytellers successfully built a university-based science-in-action video storytelling model to test the research question: Can university scientists increase their relatability and public engagement through science-in-action video storytelling? Developed over 14 years, this science storytelling model produced more than a dozen high-visibility narratives that translated science to the public and featured scientists, primarily environmental and climate scientists, who are described in audience surveys as relatable people. This collaborative model, based on long-term trusting partnerships between scientists and video storytellers, documented scientists as they conducted their research and together created narratives intended to humanize scientists as authentic people on journeys of discovery. Unlike traditional documentary filmmaking or journalism, the participatory nature of this translational science model involved scientists in the shared making of nar...
This working paper contains findings from an October 2013 online U.S. national survey on public p... more This working paper contains findings from an October 2013 online U.S. national survey on public perceptions of labeling of genetically modified (GM) foods.
Changing institutional culture to be more diverse and inclusive within the biomedical academic co... more Changing institutional culture to be more diverse and inclusive within the biomedical academic community is difficult for many reasons. Herein we present evidence that a collaborative model involving multiple institutions of higher education can initiate and execute individual institutional change directed at enhancing diversity and inclusion at the postdoctoral researcher (postdoc) and junior faculty level by implementing evidence-based mentoring practices. A higher education consortium, the Big Ten Academic Alliance, invited individual member institutions to send participants to one of two types of annual mentor training: 1) "Mentoring-Up" training for postdocs, a majority of whom were from underrepresented groups; 2) Mentor Facilitator training-a train-the-trainer model-for faculty and senior leadership. From 2016 to 2019, 102 postdocs and 160 senior faculty and administrative leaders participated. Postdocs reported improvements in their mentoring proficiency (87%) and improved relationships with their PIs (71%). 29% of postdoc respondents transitioned to faculty positions, and 85% of these were underrepresented and 75% were female. 59 out of the 120 faculty and administrators (49%) trained in the first three years provided mentor training on their campuses to over 3000 undergraduate and graduate students, postdocs and faculty within the project period. We conclude that early stage biomedical professionals as well as individual institutions of higher education benefited significantly from this collaborative mentee/mentor training model
African indigenous vegetables (AIVs) have recently received wide attention for their contribution... more African indigenous vegetables (AIVs) have recently received wide attention for their contribution toward food and nutrition security. Promoting the production and consumption of AIVs is likely to mitigate food insecurity and alleviate malnutrition in the African region. To document and analyze existing patterns of AIV production in Zambia, farmers were surveyed in person using a structured questionnaire. A total of 300 farmers were selected from Lusaka (50), Katete (50), Chipata (75), Lundazi (75), and Petauke (75). Analysis of the survey results using logit model identified that those who farm less than 10 acres of farming land, were concerned about nutrition quality of AIVs, reported that price of farm produce is fixed by buyers, were registered as a member of any community group or association, received training related to nutrition and health, saved money for unexpected expenses, and were single are more likely than other farmers to produce AIVs for home consumption. Whereas, th...
The R domain of cystic fibrosis transmembrane conductance regulator (CFTR) connects the two halve... more The R domain of cystic fibrosis transmembrane conductance regulator (CFTR) connects the two halves of the protein, each of which possess a transmembranespanning domain and a nucleotide binding domain. Phosphorylation of serine residues, which reside mostly within the C-terminal two-thirds of the R domain, is required for nucleotide-dependent activation of CFTR chloride channel activity. The N terminus of the R domain is also likely to be important in CFTR function, since this region is highly conserved among CFTRs of different species and exhibits sequence similarity with the "linker region" of the related protein, P-glycoprotein. To date, however, the role of this region in CFTR channel function remains unknown. In this paper, we report the effects of five disease-causing mutations within the N terminus of the CFTR-R domain. All five mutants exhibit defective protein processing in mammalian HEK-293 cells, suggesting that they are mislocalized and fail to reach the cell surface. However, in the Xenopus oocyte, three mutants reached the plasma membrane. One of these mutants, L619S, exhibits no detectable function, whereas the other two, D614G and I618T, exhibit partial activity as chloride channels. Single channel analysis of these latter two mutants revealed that they possess defective rates of channel opening, consistent with the hypothesis that the N terminus of the R domain participates in ATP-dependent channel gating. These findings support recent structural models that include this region within extended boundaries of the first nucleotide binding domain.
Genetically modified food created by microorganisms and genetically modified animals and fish are... more Genetically modified food created by microorganisms and genetically modified animals and fish are beyond the scope of this article.
IntroductionNutrition security continues to worsen in sub-Saharan Africa. Current research is lim... more IntroductionNutrition security continues to worsen in sub-Saharan Africa. Current research is limited on how seasonality may influence the impact of nutrition, culinary, and production interventions on food security, diet quality, and consumption of African Indigenous Vegetables (AIV); a culturally accepted source of micro-and-macronutrients that are easily produced due to their adaptation to the local environment. The objective of this study was to evaluate the programmatic impact of AIV interventions on nutrition security among smallholder farmers.MethodsIn a randomized control trial, five target counties in Western Kenya were randomly assigned to one of four treatments: (1) control; (2) production intervention (PI); (3) nutrition and culinary intervention (NCI); and (4) NCI and PI (NCI/PI). After the counties were randomly assigned to a treatment, 503 smallholder farmers (18–65 years) were selected from participatory farmer groups. The PI consisted of five agricultural production...
The prevalence of micronutrient deficiencies continues to remain alarmingly high in subSaharan Af... more The prevalence of micronutrient deficiencies continues to remain alarmingly high in subSaharan Africa. One potential solution to undernutrition is to promote the consumption of African Indigenous Vegetables (AIVs) that are rich in vitamin A, iron, zinc and other healthpromoting phytochemicals. However, due to limited advances in agronomic practices, seed development, available improved varieties, and access to these indigenous plants in the marketplace, work was needed to drive AIVs into the formal marketplace to meet consumer demand. This paper summarizes the research and activities of a diverse group of stakeholders and researchers who came together to improve research, management, production, distribution, and consumption of nutritious AIVs in Eastern Simon et al.: Improving Income and Nutrition of Smallholder Farmers in Eastern
are interrelated disciplines that underpin a shared understanding of the functional prerequisites... more are interrelated disciplines that underpin a shared understanding of the functional prerequisites of health, sustainable vitality and wellbeing. All of these are based on recognition that health interconnects species across the planet, and they offer ways to more effectively tackle complex real-world challenges. Herein we present a bibliometric analysis to document usage of a subset of such terms by journals over time. We also provide examples of parasitic and vector-borne diseases, including malaria, toxoplasmosis, baylisascariasis, and Lyme disease. These and many other diseases have persisted, emerged or re-emerged, and caused great harm to human and animal populations in developed and low income, biodiverse nations around the world, largely because of societal drivers that undermined natural processes of disease prevention and control, which had developed through co-evolution over millennia. Shortcomings in addressing drivers has arisen from a lack or coordinated efforts among researchers, health stewards, societies at large, and governments. Fortunately, specialists collaborating under transdisciplinary and socio-ecological health umbrellas are increasingly integrating established and new techniques for disease modeling, prediction, diagnosis, treatment, control, and prevention. Such approaches often emphasize conservation of biodiversity for health protection, and they provide novel opportunities to increase the efficiency and probability of success.
This is the author's manuscript for a work that has been accepted for publication. Changes result... more This is the author's manuscript for a work that has been accepted for publication. Changes resulting from the publishing process, such as copyediting, final layout, and pagination, may not be reflected in this document. The publisher takes permanent responsibility for the work. Content and layout follow publisher's submission requirements.
The electron-microscopic technique for immunogold labelling of thawed cryosectioned material (K.T... more The electron-microscopic technique for immunogold labelling of thawed cryosectioned material (K.T. Tokuyasu, 1989, Histochem J 21: 163-171) has been adapted for use with isolated chloroplasts. Percollpurified pea (Pisum Sativum L. cv Feltham First) chloroplasts were fixed in a buffered glutaraldehyde solution and then infiltrated with a buffered solution of 10% polyvinylpyrrolidone in 2.07 M sucrose prior to freezing in liquid nitrogen and sectioning in an ultracryomicrotome. Sections were thawed, immunolabelled, and stained with ammonium molybdate in methyl cellulose on Formvar/carbon-coated Cu or Cu/Pd electron-microscope grids. Cryosectioning gave excellent structural preservation and retained antigenicity. The effectiveness of this technique in localizing proteins to their specific chloroplast compartment was assayed using antibodies raised against: (i) the large subunit of ribulose-l,5-bisphosphate carboxylase/oxygenase (Rubisco), a stromal protein, (ii) the chloroplast ATP synthase (CF1), a peripheral thylakoid protein, and (iii) different envelope membrane proteins. Antibodies raised against three members of the chloroplastic outer envelope protein (OEP) import machinery, a 34-kDa protein (OEP34 or IAP34), the channel-forming 75-kDa protein (OEP75 or IAP75), and the 86-kDa precursor protein receptor (OEP86 or IAP86) were tested for their localization. The previous localization of OEP86,
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