Distinct Chemotaxis Protein Paralogs Assemble into Chemoreceptor Signaling Arrays To Coordinate Signaling Output

Most chemotactic motile bacteria possess multiple chemotaxis signaling systems, the functions of which are not well characterized. Chemotaxis signaling is initiated by chemoreceptors that assemble as large arrays, together with chemotaxis coupling proteins (CheW) and histidine kinase proteins (CheA), which form a baseplate with the cytoplasmic tips of receptors. These cell pole-localized arrays mediate sensing, signaling, and signal amplification during chemotaxis responses. Membrane-bound chemoreceptors with different cytoplasmic domain lengths segregate into distinct arrays. Here, we show that a bacterium, Azospirillum brasilense, which utilizes two chemotaxis signaling systems controlling distinct motility parameters, coordinates its chemotactic responses through the production of two separate membrane-bound chemoreceptor arrays by mixing paralogs within chemotaxis baseplates. The polar localization of chemoreceptors of different length classes is maintained in strains that had baseplate signaling proteins from either chemotaxis system but was lost when both systems were deleted. Chemotaxis proteins (CheA and CheW) from each of the chemotaxis signaling systems (Che1 and Che4) could physically interact with one another, and chemoreceptors from both classes present in A. brasilense could interact with Che1 and Che4 proteins. The assembly of paralogs from distinct chemotaxis pathways into baseplates provides a straightforward mechanism for coordinating signaling from distinct pathways, which we predict is not unique to this system given the propensity of chemotaxis systems for horizontal gene transfer

Distinct Chemotaxis Protein Paralogs Assemble into Chemoreceptor Signaling Arrays To Coordinate Signaling Output

Most chemotactic motile bacteria possess multiple chemotaxis signaling systems, the functions of which are not well characterized. Chemotaxis signaling is initiated by chemoreceptors that assemble as large arrays, together with chemotaxis coupling proteins (CheW) and histidine kinase proteins (CheA), which form a base- plate with the cytoplasmic tips of receptors. These cell pole-localized arrays mediate sensing, signaling, and signal amplification during chemotaxis responses. Membrane- bound chemoreceptors with different cytoplasmic domain lengths segregate into distinct arrays. Here, we show that a bacterium, Azospirillum brasilense, which utilizes two chemotaxis signaling systems controlling distinct motility parameters, coordi- nates its chemotactic responses through the production of two separate membrane- bound chemoreceptor arrays by mixing paralogs within chemotaxis baseplates. The polar localization of chemoreceptors of different length classes is maintained in strains that had baseplate signaling proteins from either chemotaxis system but was lost when both systems were deleted. Chemotaxis proteins (CheA and CheW) from each of the chemotaxis signaling systems (Che1 and Che4) could physically interact with one another, and chemoreceptors from both classes present in A. brasilense could interact with Che1 and Che4 proteins. The assembly of paralogs from distinct chemotaxis pathways into baseplates provides a straightforward mechanism for co- ordinating signaling from distinct pathways, which we predict is not unique to this system given the propensity of chemotaxis systems for horizontal gene transfer

Distinct Chemotaxis Protein Paralogs Assemble into Chemoreceptor Signaling Arrays To Coordinate Signaling Output

The assembly of chemotaxis receptors and signaling proteins into polar arrays is universal in motile chemotactic bacteria. Comparative genome analyses indicate that most motile bacteria possess multiple chemotaxis signaling systems, and experimental evidence suggests that signaling from distinct chemotaxis systems is integrated. Here, we identify one such mechanism. We show that paralogs from two chemotaxis systems assemble together into chemoreceptor arrays, forming baseplates comprised of proteins from both chemotaxis systems. These mixed arrays provide a straightforward mechanism for signal integration and coordinated response output from distinct chemotaxis systems. Given that most chemotactic bacteria encode multiple chemotaxis systems and the propensity for these systems to be laterally transferred, this mechanism may be common to ensure chemotaxis signal integration occurs.Most chemotactic motile bacteria possess multiple chemotaxis signaling systems, the functions of which are not well characterized. Chemotaxis signaling is initiated by chemoreceptors that assemble as large arrays, together with chemotaxis coupling proteins (CheW) and histidine kinase proteins (CheA), which form a baseplate with the cytoplasmic tips of receptors. These cell pole-localized arrays mediate sensing, signaling, and signal amplification during chemotaxis responses. Membrane-bound chemoreceptors with different cytoplasmic domain lengths segregate into distinct arrays. Here, we show that a bacterium, Azospirillum brasilense, which utilizes two chemotaxis signaling systems controlling distinct motility parameters, coordinates its chemotactic responses through the production of two separate membrane-bound chemoreceptor arrays by mixing paralogs within chemotaxis baseplates. The polar localization of chemoreceptors of different length classes is maintained in strains that had baseplate signaling proteins from either chemotaxis system but was lost when both systems were deleted. Chemotaxis proteins (CheA and CheW) from each of the chemotaxis signaling systems (Che1 and Che4) could physically interact with one another, and chemoreceptors from both classes present in A. brasilense could interact with Che1 and Che4 proteins. The assembly of paralogs from distinct chemotaxis pathways into baseplates provides a straightforward mechanism for coordinating signaling from distinct pathways, which we predict is not unique to this system given the propensity of chemotaxis systems for horizontal gene transfer

Location as Destiny: Identifying Geospatial Disparities in Radiation Treatment Interruption by Neighborhood, Race, and Insurance

Purpose: Radiation therapy interruption (RTI) worsens cancer outcomes. Our purpose was to benchmark and map RTI across a region in the United States with known cancer outcome disparities. Methods and Materials: All radiation therapy (RT) treatments at our academic center were cataloged. Major RTI was defined as ≥5 unplanned RT appointment cancellations. Univariate and multivariable logistic and linear regression analyses identified associated factors. Major RTI was mapped by patient residence. A 2-sided P value \u3c.0001 was considered statistically significant. Results: Between 2015 and 2017, a total of 3754 patients received RT, of whom 3744 were eligible for analysis: 962 patients (25.8%) had ≥2 RT interruptions and 337 patients (9%) had major RTI. Disparities in major RTI were seen across Medicaid versus commercial/Medicare insurance (22.5% vs 7.2%; P \u3c.0001), low versus high predicted income (13.0% vs 5.9%; P \u3c.0001), Black versus White race (12.0% vs 6.6%; P \u3c.0001), and urban versus suburban treatment location (12.0% vs 6.3%; P \u3c.0001). On multivariable analysis, increased odds of major RTI were seen for Medicaid patients (odds ratio [OR], 3.35; 95% confidence interval [CI], 2.25-5.00; P \u3c.0001) versus those with commercial/Medicare insurance and for head and neck (OR, 3.74; 95% CI, 2.56-5.46; P \u3c.0001), gynecologic (OR, 3.28; 95% CI, 2.09-5.15; P \u3c.0001), and lung cancers (OR, 3.12; 95% CI, 1.96-4.97; P \u3c.0001) compared with breast cancer. Major RTI was mapped to urban, majority Black, low-income neighborhoods and to rural, majority White, low-income regions. Conclusions: Radiation treatment interruption disproportionately affects financially and socially vulnerable patient populations and maps to high-poverty neighborhoods. Geospatial mapping affords an opportunity to correlate RT access on a neighborhood level to inform potential intervention strategies

Initial Impact and Operational Responses to the COVID-19 Pandemic by American Radiation Oncology Practices

Purpose: In February 2020, the COVID-19 pandemic reached the United States. The impact of the pandemic on the US radiation oncology field remains unknown. The American Society for Radiation Oncology surveyed US radiation oncology practice leaders to gauge initial impact and immediate operational responses to the pandemic. Methods and Materials: From April 16 to April 30, 2020, the American Society for Radiation Oncology surveyed US radiation oncology practice leaders by email to gauge initial impact and immediate operational responses to the COVID-19 pandemic. Results: Two hundred twenty-two (43%) of 517 leaders responded from community and academic practices (62% and 34%, respectively), hospital-based and free-standing centers (69% and 29%), and metro and rural locations (88% and 12%). Practices reported treating an average of 1086 patients per year in 2019 (range, 0-7900) with an average daily treatment volume of 70 patients (range, 5-400). All practices reported uninterrupted operation. On average, practices were treating 68% of their typical volume (range, 10%-95%), with 92% implementing planned treatment postponement for lower risk patients. An estimated revenue decrease of 20% or more was experienced by 71% of practices. Confirmed COVID-19 patient cases were treated by 39% of practices. Seventy percent experienced staff shortages. Almost all (98%) practices implemented formal operational procedures to protect patients and staff, although personal protective equipment/infection control supply shortages were reported by 78% of practices. Seventy-four percent used telemedicine for virtual follow-up surveillance, and 15% leveraged telemedicine for on-treatment assessment. Conclusions: The clinical and financial impacts of the COVID-19 pandemic on US radiation oncology were deep and broad. Despite reported shortages in personal protective equipment, declines in revenue, and reduced patient volumes, practices adapted quickly by refining standard processes of care, implementing recommended safety measures, and employing telemedicine to facilitate treatment continuity. Patients with higher risk disease experienced uninterrupted access to care. We plan to continue regular surveying across the lifespan of the pandemic to document the geographic and temporal impact of COVID-19 on the field and its patients

ESTUDO DE COORTE EPIFLORIPA IDOSO: ABORDAGENS METODOLÓGICAS E REPOSIÇÃO DA AMOSTRA DURANTE A ONDA 3 (2017-19)

Objetivo: Descrever o plano amostral, aspectos operacionais e estratégias utilizadas para a reposição da amostra na onda 3 do estudo EpiFloripa Idoso 2017–2019. Métodos: Estudo de coorte, de base populacional, conduzido em Florianópolis/SC, com 1.702 idosos (≥60 anos) na onda 1 (linha de base), 1.197 idosos na onda 2 e 1.335 idosos na onda 3. Os instrumentos de medidas utilizados nas coletas de dados das ondas anteriores foram mantidos na onda 3. Foram acrescidas informações auto reportadas sobre outros fatores de risco à saúde, mensurações de circunferência da panturrilha e testes de avaliação físico-funcionais (mobilidade, força muscular e equilíbrio). Resultados: A taxa de resposta na onda 3 foi de 70,0% (n=1.335) e diferiu significativamente da população avaliada no Censo 2010. Houve predomínio de mulheres (63,8%), 43,7% tinham 70–79 anos e 29,2% completaram 12 anos ou mais de estudo. Ao comparar com as ondas anteriores, não foram observadas diferenças quanto ao status de acompanhamento (entrevistados, perdas/recusas e óbitos), apenas em relação à renda e ao arranjo familiar. Conclusão: As estratégias empregadas no estudo possibilitaram a reposição da amostra e, após 7–10 anos de coleta, a taxa de manutenção daaderência do estudo longitudinal manteve-se satisfatória

ESTUDO DE COORTE EPIFLORIPA IDOSO: ABORDAGENS METODOLÓGICAS E REPOSIÇÃO DA AMOSTRA DURANTE A ONDA 3 (2017-19)

Objetivo: Descrever o plano amostral, aspectos operacionais e estratégias utilizadas para a reposição da amostra na onda 3 do estudo EpiFloripa Idoso 2017–2019. Métodos: Estudo de coorte, de base populacional, conduzido em Florianópolis/SC, com 1.702 idosos (≥60 anos) na onda 1 (linha de base), 1.197 idosos na onda 2 e 1.335 idosos na onda 3. Os instrumentos de medidas utilizados nas coletas de dados das ondas anteriores foram mantidos na onda 3. Foram acrescidas informações auto reportadas sobre outros fatores de risco à saúde, mensurações de circunferência da panturrilha e testes de avaliação físico-funcionais (mobilidade, força muscular e equilíbrio). Resultados: A taxa de resposta na onda 3 foi de 70,0% (n=1.335) e diferiu significativamente da população avaliada no Censo 2010. Houve predomínio de mulheres (63,8%), 43,7% tinham 70–79 anos e 29,2% completaram 12 anos ou mais de estudo. Ao comparar com as ondas anteriores, não foram observadas diferenças quanto ao status de acompanhamento (entrevistados, perdas/recusas e óbitos), apenas em relação à renda e ao arranjo familiar. Conclusão: As estratégias empregadas no estudo possibilitaram a reposição da amostra e, após 7–10 anos de coleta, a taxa de manutenção daaderência do estudo longitudinal manteve-se satisfatória