ABSTRACT
The causes and conditions of displacement often increase the vulnerability of migrant and refugee populations to food insecurity, alongside other material hardships. We aimed to examine the multidimensional aspects and patterns of food insecurity and other material hardships in a cross-sectional sample of 6221 Venezuelan refugees and migrants in urban Colombia using a latent class analysis. Using multinomial and logistic regression models, we investigated the demographic and migratory experiences associated with identified classes and how class membership is associated with multiple health outcomes among Venezuelan refugees and migrants, respectively. Approximately two thirds of the sample was comprised cisgender women, and the participants had a median age of 32 years (IQR: 26-41). Four heterogeneous classes of food insecurity and material hardships emerged: Class 1-low food insecurity and material hardship; Class 2-high food insecurity and material hardship; Class 3-high income hardship with insufficient food intake; and Class 4-income hardship with food affordability challenges. Class 2 reflected the most severe food insecurity and material hardships and had the highest class membership; Venezuelans with an irregular migration status were almost 1.5 times more likely to belong to this class. Food insecurity and material hardship class membership was independently associated with self-rated health, mental health symptoms, and recent violence victimization and marginally associated with infectious disease outcomes (laboratory-confirmed HIV and/or syphilis infection). Social safety nets, social protection, and other interventions that reduce and prevent material hardships and food insecurity among refugees and migrants, alongside the host community, may improve public health, support development, and reduce healthcare costs. In the long term, regularization and social policies for migrants aimed at enhancing refugees' and migrants' social and economic inclusion may contribute to improving food security in this population.
Subject(s)
Refugees , South American People , Transients and Migrants , Adult , Female , Humans , Colombia , Cross-Sectional Studies , Latent Class Analysis , MaleABSTRACT
INTRODUCTION: Equitable access to vaccines for migrants and refugees is necessary to ensure their right to health and to achieve public health goals of reducing vaccine-preventable illness. Public health policies require regulatory frameworks and communication to effect uptake of effective vaccines among the target population. In Colombia, the National COVID-19 Vaccination Plan implicitly included Venezuelan refugees and migrants; however, initial communication of the policy indicated that vaccine availability was restricted to people with regular migration status. We estimated the impact of a public announcement, which clarified access for refugees and migrants, on vaccination coverage among Venezuelans living in Colombia. METHODS: Between 30 July 2021 and 5 February 2022, 6221 adult Venezuelans participated in a cross-sectional, population-based health survey. We used a comparative cross-sectional time-series analysis to estimate the effect of the October 2021 announcement on the average biweekly change in COVID-19 vaccine coverage of Venezuelans with regular and irregular migration status. RESULTS: 71% of Venezuelans had an irregular status. The baseline (preannouncement) vaccine coverage was lower among people with an irregular status but increased at similar rates as those with a regular status. After the announcement, there was a level change of 14.49% (95% CI: 1.57 to 27.42, p=0.03) in vaccination rates among individuals with irregular migration status with a 4.61% increase in vaccination rate per biweekly period (95% CI: 1.71 to 7.51, p=0.004). By February 2022, there was a 26.2% relative increase in vaccinations among individuals with irregular migration status compared with what was expected without the announcement. CONCLUSION: While there was no policy change, communication clarifying the policy drastically reduced vaccination inequalities across migration status. Lessons can be translated from the COVID-19 pandemic into more effective global, regional and local public health emergency preparedness and response to displacement.
Subject(s)
COVID-19 Vaccines , COVID-19 , Refugees , South American People , Transients and Migrants , Adult , Humans , Colombia/epidemiology , Communication , COVID-19/prevention & control , Cross-Sectional Studies , Health Policy , Pandemics , VaccinationABSTRACT
Background: Population-based estimates of syphilis prevalence are critical to informing public health response. We aimed to measure syphilis prevalence among Venezuelan refugees and migrants in Colombia to inform public health programming. Methods: Between July 2021 and February 2022, we surveyed 6221 adult Venezuelan refugees and migrants in four cities in Colombia using respondent-driven sampling (RDS). Participants completed a survey and dual-rapid HIV/treponemal syphilis screening. Confirmatory laboratory-based rapid plasma reagin testing was conducted on whole blood samples. Active syphilis infection was defined as RPR titer ≥ 1:8 and no self-reported syphilis treatment. We used multivariable regression models to identify associations with active syphilis infection among subgroups by gender and history of pregnancy (cisgender men n = 2123, cisgender women n = 4044, transgender/nonbinary people n = 47, pregnant women n = 150). Findings: Population (RDS-weighted) prevalence of laboratory-confirmed syphilis was 5.1% (95% CI: 4.6-5.6). Syphilis prevalence was 5.8% (weighted) among men; lifetime sexually transmitted infections (STI) diagnosis, same-sex relationships, HIV infection, and partner number were independently associated with syphilis infection. Syphilis prevalence was 4.6% (weighted) in women; correlates of infection included: lifetime STI diagnosis, food insecurity, current engagement in sex work, current pregnancy, any unsafe night in Colombia, irregular migration status, and no healthcare utilization in Colombia. 14.9% (unweighted) of transgender participants had syphilis infection; correlates of infection included partner number and HIV infection. The prevalence of syphilis was 9.0% (weighted) among pregnant women, which was associated with lifetime STI diagnosis. Interpretation: Syphilis among Venezuelans in Colombia is high. Correlates of infection are distinct among demographic groups, spanning sexual and social vulnerabilities, suggesting tailored public health strategies. Funding: US President's Emergency Plan for AIDS Relief through the U.S. Centers for Disease Control and Prevention.
ABSTRACT
BACKGROUND: Venezuela has experienced substantial human displacement since 2015. To inform HIV programmes and treatment distribution, we aimed to estimate HIV prevalence and associated indicators among migrants and refugees from Venezuela residing in Colombia, the largest receiving country. METHODS: We conducted a biobehavioural, cross-sectional survey using respondent-driven sampling among Venezuelan people aged 18 years or older who had arrived in Colombia since 2015 and resided in four cities (ie, Bogotá, Soacha, Soledad, and Barranquilla). Participants completed sociobehavioural questionnaires and rapid HIV and syphilis screening with laboratory-based confirmatory testing, CD4 cell counts, and viral load quantification. Policies related to migration status affect access to insurance and HIV services in Colombia, as in many receiving countries, so we provided legal assistance and navigation support to participants with HIV for sustained access to treatment. Population-based estimates were weighted for the complex sampling design. Penalised multivariable logistic regression analysis was used to identify correlates of viral suppression (HIV-1 RNA <1000 copies per mL). FINDINGS: Between July 30, 2021, and Feb 5, 2022, 6506 participants were recruited through respondent-driven sampling, of whom 6221 were enrolled. 4046 (65·1%) of 6217 were cisgender women, 2124 (34·2%) of 6217 were cisgender men, and 47 (0·8%) of 6217 were transgender or non-binary people. 71 (1·1%) of all 6221 participants had laboratory-confirmed HIV infection, resulting in a weighted population HIV prevalence of 0·9% (95% CI 0·6-1·4). Among participants living with HIV, 34 (47·9%) of 71 had been previously diagnosed with HIV and 25 (35·7%) of 70 had viral suppression. Individuals with irregular migration status compared with individuals with regular migration status (adjusted odds ratio 0·3, 95% CI 0·1-0·9) and with a most recent HIV test in Colombia compared with a most recent test in Venezuela (0·2, 0·1-0·8) were less likely to have suppressed viral loads. INTERPRETATION: HIV prevalence among migrants and refugees from Venezuela in Colombia suggests the HIV epidemic is close to being generalised, which could be addressed by the inclusion of migrants and refugees from Venezuela in local HIV services, improved access to and navigation support for HIV testing and care, and coordination with humanitarian programmes. There is an association between migration status and viral suppression, conferring both clinical and epidemiological implications. Therefore, legal support and access to insurance might lead to early detection of HIV and timely treatment for people with irregular migration status. FUNDING: US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
Subject(s)
HIV Infections , Refugees , Transients and Migrants , Male , Humans , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/epidemiology , Cross-Sectional Studies , Colombia/epidemiology , Venezuela/epidemiology , Continuity of Patient CareABSTRACT
Background: Colombia hosts a large number of Venezuelan migrants and refugees who are uniquely vulnerable and have been markedly impacted by the COVID-19 pandemic. It is necessary to understand their experiences to inform future policy decisions both in Colombia and during disease outbreaks in other humanitarian contexts in the future. As part of a larger study focused on HIV among Venezuelans residing in Colombia, qualitative interviews were conducted to understand this population's experiences and access to healthcare. Methods: Interviews were conducted with Venezuelan migrants and refugees as well as stakeholders such as care providers, humanitarian workers, and government officials. Interviews were recorded, transcribed, and coded using thematic content analysis. Select quotes were translated and edited for length and/or clarity. Results: Venezuelan migrants and refugees reported high levels of housing instability, job instability, increased barriers to accessing healthcare, and complications in engaging in the HIV care continuum, among other impacts of the COVID-19 pandemic. Stakeholders reported complications in provision of care and obtaining medicines, difficulty maintaining contact with patients, increased discrimination and xenophobia targeting Venezuelan migrants and refugees, increased housing instability among Venezuelan migrants and refugees, and other impacts as a result of the COVID-19 pandemic. Conclusions: This study demonstrates the unique impacts of the COVID-19 pandemic among Venezuelans residing in Colombia by both compounding extant vulnerabilities and introducing new challenges, such as high rates of eviction. Colombia has enacted increasingly inclusive migration policies for Venezuelan refugees and migrants within the country; findings from this study underscore the necessity for such policies both in and outside of the Colombian context.
ABSTRACT
Innexins facilitate cell-cell communication by forming gap junctions or nonjunctional hemichannels, which play important roles in metabolic, chemical, ionic, and electrical coupling. The lack of knowledge regarding the evolution and role of these channels in ctenophores (comb jellies), the likely sister group to the rest of animals, represents a substantial gap in our understanding of the evolution of intercellular communication in animals. Here, we identify and phylogenetically characterize the complete set of innexins of four ctenophores: Mnemiopsis leidyi, Hormiphora californensis, Pleurobrachia bachei, and Beroe ovata. Our phylogenetic analyses suggest that ctenophore innexins diversified independently from those of other animals and were established early in the emergence of ctenophores. We identified a four-innexin genomic cluster, which was present in the last common ancestor of these four species and has been largely maintained in these lineages. Evidence from correlated spatial and temporal gene expression of the M. leidyi innexin cluster suggests that this cluster has been maintained due to constraints related to gene regulation. We describe the basic electrophysiological properties of putative ctenophore hemichannels from muscle cells using intracellular recording techniques, showing substantial overlap with the properties of bilaterian innexin channels. Together, our results suggest that the last common ancestor of animals had gap junctional channels also capable of forming functional innexin hemichannels, and that innexin genes have independently evolved in major lineages throughout Metazoa.
Subject(s)
Ctenophora , Animals , Ctenophora/genetics , Phylogeny , Signal Transduction , Genome , Cell Communication/physiologyABSTRACT
ABSTRACT: The Nursing First Program was established to provide students in an associate of science in nursing program at a downstate New York community college a seamless transition into the registered nurse to baccalaureate program of a nearby university while promoting academic performance and professional excellence. Selected students attend mandatory seminars designed to provide academic support and a sense of camaraderie, with the aim of ensuring success in both programs. Initial outcomes indicate that the program inspired participants to reach their highest potential, academically and professionally. Nursing First scholars have excelled as newly employed registered nurses and as students in the university program.
Subject(s)
Education, Nursing, Baccalaureate , Nurses , Students, Nursing , Humans , Students , New YorkABSTRACT
BACKGROUND: Epidemiologic research among migrant populations is limited by logistical, methodological, and ethical challenges, but it is necessary for informing public health and humanitarian programming. OBJECTIVE: We describe a methodology to estimate HIV prevalence among Venezuelan migrants in Colombia. METHODS: Respondent-driven sampling, a nonprobability sampling method, was selected for attributes of reaching highly networked populations without sampling frames and analytic methods that permit estimation of population parameters. Respondent-driven sampling was modified to permit electronic referral of peers via SMS text messaging and WhatsApp. Participants complete sociobehavioral surveys and rapid HIV and syphilis screening tests with confirmatory testing. HIV treatment is not available for migrants who have entered Colombia through irregular pathways; thus, medicolegal services integrated into posttest counseling provide staff lawyers and legal assistance to participants diagnosed with HIV or syphilis for sustained access to treatment through the national health system. Case finding is integrated into respondent-driven sampling to allow partner referral. This study is implemented by a local community-based organization providing HIV support services and related legal services for Venezuelans in Colombia. RESULTS: Data collection was launched in 4 cities in July and August 2021. As of November 2021, 3105 of the target 6100 participants were enrolled, with enrollment expected to end by February/March 2022. CONCLUSIONS: Tailored methods that combine community-led efforts with innovations in sampling and linkage to care can aid in advancing health research for migrant and displaced populations. Worldwide trends in displacement and migration underscore the value of improved methods for translation to humanitarian and public health programming. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36026.
ABSTRACT
The Saccharomyces cerevisiae protein Slk19 has been shown to localize to kinetochores throughout mitosis and to the spindle midzone in anaphase. However, Slk19 clearly also has an important role for spindle formation and stabilization in prometaphase and metaphase, albeit this role is unresolved. Here we show that Slk19's localization to metaphase spindles in vivo and to microtubules (MTs) in vitro depends on the MT cross-linking protein Ase1 and the MT cross-linking and stabilizing protein Stu1. By analyzing a slk19 mutant that specifically fails to localize to spindles and MTs, we surprisingly found that the presence of Slk19 amplified the amount of Ase1 strongly and that of Stu1 moderately at the metaphase spindle in vivo and at MTs in vitro. Furthermore, Slk19 markedly enhanced the cross-linking of MTs in vitro when added together with Ase1 or Stu1. We therefore suggest that Slk19 recruits additional Ase1 and Stu1 to the interpolar MTs (ipMTs) of metaphase spindles and thus increases their cross-linking and stabilization. This is in agreement with our observation that cells with defective Slk19 localization exhibit shorter metaphase spindles, an increased number of unaligned nuclear MTs, and most likely reduced ipMT overlaps.
Subject(s)
Microtubule-Associated Proteins/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Cell Cycle/physiology , Cell Nucleus/metabolism , Kinetochores/metabolism , Metaphase/physiology , Microtubule-Associated Proteins/physiology , Microtubules/metabolism , Mitosis/physiology , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/physiology , Spindle Apparatus/metabolismABSTRACT
Kinetochores that are not attached to microtubules prevent chromosome missegregation via the spindle assembly checkpoint. We show that they also promote their own capturing. Similar to what governs the localization of spindle assembly checkpoint proteins, the phosphorylation of Spc105 by Mps1 allows unattached kinetochores to sequester Stu1 in cooperation with Slk19. The withdrawal of Stu1, a CLASP essential for spindle integrity, from microtubules and attached kinetochores disrupts the organization of the spindle and thus allows the enhanced formation of dynamic random microtubules that span the nucleus and are ideal to capture unattached kinetochores. The enhanced formation of nuclear random microtubules does not occur if Stu1 sequestering to unattached kinetochores fails and the spindle remains uncompromised. Consequently, these cells exhibit a severely decreased capturing efficiency. After the capturing event, Stu1 is relocated to the capturing microtubule and prevents precocious microtubule depolymerization as long as kinetochores are laterally or incompletely end-on attached.
Subject(s)
Kinetochores/metabolism , Microtubule-Associated Proteins/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/metabolism , Microtubule-Associated Proteins/genetics , Mitosis , Multigene Family , Protein Binding , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics , Spindle Apparatus/genetics , Spindle Apparatus/metabolismABSTRACT
Professional confidence is an essential trait for new graduate nurses to possess in order to provide quality patient care in today's complex hospital setting. However, many new graduates are entering the workforce without it and this remains to be explored. This study describes how new graduate nurses accounted for their lack of professional confidence upon entry into professional practice and how it developed during their first year of practice in the hospital setting. Two face-to-face, individual interviews of 12 participants were utilized to capture the lived experiences of new graduate nurses to gain an understanding of this phenomenon. After manual content analysis seven themes emerged: communication is huge, making mistakes, disconnect between school and practice, independence, relationship building, positive feedback is important, and gaining experience. The findings indicate that the development of professional confidence is a dynamic process that occurs throughout the first year of practice. New graduate nurses must experience both positive and negative circumstances in order to move toward the attainment of professional confidence. Knowing this, nurse educators in academia as well as in the hospital setting may better support the development of professional confidence both before and during the first year of practice.
Subject(s)
Nurses/psychology , Nurses/standards , Professional Competence , Self Efficacy , Adult , Education, Nursing, Graduate/trends , Female , Humans , Male , Middle Aged , Qualitative ResearchABSTRACT
Cytoplasmic linker-associated proteins (CLASPs) are proposed to function in cell division based on their ability to bind tubulin via arrayed tumor overexpressed gene (TOG)-like (TOGL) domains. Structure predictions suggest that CLASPs have at least two TOGL domains. We show that only TOGL2 of Saccharomyces cerevisiae CLASP Stu1 binds to tubulin and is required for polymerization of spindle microtubules (MTs) in vivo. In contrast, TOGL1 recruits Stu1 to kinetochores (KTs), where it is essential for the stability and tension-dependent regulation of KT MTs. Stu1 is also recruited to spindle MTs by different mechanisms depending on the mitotic phase: in metaphase, Stu1 binds directly to the MT lattice, whereas in anaphase, it is localized indirectly to the spindle midzone. In both phases, the activity of TOGL2 is essential for interpolar MT stability, whereas TOGL1 is not involved. Thus, the two TOGL domains of yeast CLASP have different activities and execute distinct mitotic functions.
Subject(s)
Kinetochores/metabolism , Microtubule-Associated Proteins/metabolism , Microtubules/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Dimerization , Metaphase/physiology , Microtubule-Associated Proteins/chemistry , Microtubule-Associated Proteins/genetics , Protein Binding/physiology , Protein Structure, Tertiary/physiology , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/genetics , Spindle Apparatus/metabolism , Tubulin/metabolismABSTRACT
Esta investigación tuvo como objetivo establecer la presencia y grado de relación que existe entre dos factores cognitivos disfuncionales: Creencias Irracionales y Esquemas Maladaptativos Tempranos (EMT), en un grupo de homosexuales masculinos de la ciudad de Santa Marta, Colombia. Se utilizó un tipo de investigación correlacional en una muestra de 196 homosexuales masculinos, de 25 a 40 años de edad, con una media de 28,2 años, quienes fueron seleccionados mediante el procedimiento de "bola de nieve", pues se desconocía la población total. Se aplicaron dos Pruebas: el IBT (Irracional Beliefs Test), de Jones, R. G. (1968); el Young Schema Questionnaire Long Form - 2nd edition (YSQ-L2), de Young (1990), validado para población colombiana (Castrillón, Chaves, Ferrer, Londoño, Maestre, Marín & Schnitter, 2005); y una entrevista diseñada por los autores a cuatro de ellos. Se tomó como significativas aquellas creencias que prevalecieron sobre el 50% de la población. No se halló presencia significativa de creencias irracionales, y la creencia influencia del pasado fue la que más se aproximó al 50%, con un 44% en el límite superior. Se hallaron dos EMT que prevalecen: entrampamiento (43%) e inhibición emocional (35%). Se estableció que la creencia irracional mayoritaria y los dos EMT encontrados no se asocian. Se concluye que personas o hechos del pasado que han sido importantes o determinantes para definir su orientación sexual no lo atan necesariamente a ellas, pueden buscar su felicidad y apoyo en otros grupos, como en la comunidad gay que frecuentan. Estos resultados son similares a los hallados por otros estudios relacionados. Se sugiere seguir investigando con otras variables y pruebas.
This research aimed to establish the presence and degree of relationship between two dysfunctional cognitive factors: Irrational Beliefs and early maladaptive schemas (EMT), in a group of gay men in the city of Santa Marta, Colombia. We used a correlational research type in a sample of 196 gay men, 25 to 40 years old, with a mean of 28.2 years, who were selected by the method of "snowball" because it was unaware of the total population. We applied two tests: the IBT (Irrational Beliefs Test), Jones, R. G. (1968), the Young Schema Questionnaire Long Form -Second Edition (YSQ-L2), Young (1990), validated for the Colombian population (Castrillón, Chaves, Ferrer, Londoño, Master, Marin, and Schnitter, 2005) and, Interview by authors designed four. Was taken as significant those beliefs that prevailed on 50% of the population. We found no significant presence of irrational beliefs, still the influence of the past belief that more approached 50%, with 44% at the upper limit. We found two prevailing EMT: entrapment (43%) and emotional inhibition (35%). It was established that the majority irrational belief and the two EMT found, not associated. We conclude that people or past events that have been important or crucial to define their sexual orientation does not necessarily tied to them, they can pursue happiness and support from other groups, such as frequenting gay community, according to the interview. These results are similar to those found for other related studies. We suggest further research with other variables and tests.
ABSTRACT
Mentoring is important for the recruitment and retention of qualified nurse faculty, their ongoing career development, and leadership development. However, what are current best practices of mentoring? The purpose of this paper is to provide an overview of a model for excellence in establishing a formal mentoring program for academic nurse educators. Six themes for establishing a formal mentoring program are presented, highlighting best practices in mentoring as culled from experience and the literature. Themes reflect aims to achieve appropriately matched dyads, establish clear mentorship purpose and goals, solidify the dyad relationship, advocate for and guide the protégé, integrate the protégé into the academic culture, and mobilize institutional resources for mentoring support. Attending to the six themes will help mentors achieve important protégé outcomes, such as orientation to the educator role, integration into the academic community, development of teaching, scholarship, and service skills, as well as leadership development. The model is intended to be generalizable for faculty teaching in a variety of academic nursing institution types and sizes. Mentoring that integrates the six themes assists faculty members to better navigate the academic environment and more easily transition to new roles and responsibilities.
ABSTRACT
Cranberries, high in polyphenols, have been associated with several cardiovascular health benefits, although limited clinical trials have been reported to validate these findings. We tested the hypothesis that commercially available low-energy cranberry juice (Ocean Spray Cranberries, Inc, Lakeville-Middleboro, Mass) will decrease surrogate risk factors of cardiovascular disease, such as lipid oxidation, inflammation, and dyslipidemia, in subjects with metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, participants identified with metabolic syndrome (n = 15-16/group) were assigned to 1 of 2 groups: cranberry juice (480 mL/day) or placebo (480 mL/day) for 8 weeks. Anthropometrics, blood pressure measurements, dietary analyses, and fasting blood draws were conducted at screen and 8 weeks of the study. Cranberry juice significantly increased plasma antioxidant capacity (1.5 ± 0.6 to 2.2 ± 0.4 µmol/L [means ± SD], P < .05) and decreased oxidized low-density lipoprotein and malondialdehyde (120.4 ± 31.0 to 80.4 ± 34.6 U/L and 3.4 ± 1.1 to 1.7 ± 0.7 µmol/L, respectively [means ± SD], P < .05) at 8 weeks vs placebo. However, cranberry juice consumption caused no significant improvements in blood pressure, glucose and lipid profiles, C-reactive protein, and interleukin-6. No changes in these parameters were noted in the placebo group. In conclusion, low-energy cranberry juice (2 cups/day) significantly reduces lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome.
Subject(s)
Antioxidants/administration & dosage , Beverages , Lipid Peroxidation/drug effects , Metabolic Syndrome/drug therapy , Phytotherapy , Vaccinium macrocarpon/chemistry , Adult , Antioxidants/analysis , Biomarkers , C-Reactive Protein/analysis , Double-Blind Method , Female , Fruit/chemistry , Humans , Interleukin-6/analysis , Lipoproteins, LDL/blood , Malondialdehyde/blood , Middle Aged , Risk FactorsABSTRACT
The Saccharomyces cerevisiae CLASP (CLIP-associated protein) Stu1 is essential for the establishment and maintenance of the mitotic spindle. Furthermore, Stu1 localizes to kinetochores. Here we show that, in prometaphase, Stu1 assembles in an Ndc80-dependent manner exclusively at kinetochores that are not attached to microtubules. Stu1 relocates to microtubules when a captured kinetochore reaches a spindle pole. This relocation does not depend on kinetochore biorientation, but requires a functional DASH complex. Stu1 at detached kinetochores facilitates kinetochore capturing. Furthermore, since most of the nuclear Stu1 is sequestered by one or a few detached kinetochores, the presence of detached kinetochores prevents Stu1 from localizing the spindle, and therefore from stabilizing the spindle. Thus, the sequestering of Stu1 by detached kinetochores serves as a checkpoint that keeps spindle poles in close proximity until all kinetochores are captured. This is likely to facilitate kinetochore biorientation. In agreement with the findings described above, a kinetochore mutant (okp1-52) that fails to release Stu1 from the kinetochore displays a severe spindle defect upon spindle pole body separation, and this defect can be rescued by destroying the okp1-52 kinetochore.
Subject(s)
Kinetochores/metabolism , Microtubule-Associated Proteins/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/metabolism , Spindle Apparatus/metabolism , Microtubule-Associated Proteins/genetics , Mutation , Protein Binding , Protein Structure, Tertiary , Protein Transport/physiology , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/geneticsABSTRACT
The protein kinase Mps1 is, among others, essential for the spindle assembly checkpoint (SAC). We found that Saccharomyces cerevisiae Mps1 interacts physically with the N-terminal domain of Ndc80 (Ndc80(1-257)), a constituent of the Ndc80 kinetochore complex. Furthermore, Mps1 effectively phosphorylates Ndc80(1-257) in vitro and facilitates Ndc80 phosphorylation in vivo. Mutating 14 of the phosphorylation sites to alanine results in compromised checkpoint signalling upon nocodazole treatment of mutants. Mutating the identical sites to aspartate (to simulate constitutive phosphorylation) causes a metaphase arrest with wild-type-like bipolar kinetochore-microtubule attachment. This arrest is due to a constitutively active SAC and consequently the inviable aspartate mutant can be rescued by disrupting SAC signalling. Therefore, we conclude that a putative Mps1-dependent phosphorylation of Ndc80 is important for SAC activation at kinetochores.
Subject(s)
Cell Cycle/physiology , Nuclear Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein-Tyrosine Kinases/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Spindle Apparatus/metabolism , Alanine/metabolism , Amino Acid Sequence , Animals , Aspartic Acid/metabolism , Aurora Kinases , Genes, cdc , Intracellular Signaling Peptides and Proteins , Kinetochores/metabolism , Microtubules/metabolism , Molecular Sequence Data , Nuclear Proteins/genetics , Phosphorylation , Protein Kinases/genetics , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Protein-Tyrosine Kinases/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics , Signal Transduction/physiologyABSTRACT
Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management. Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy. An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly. Adherence to therapy is multifactorial and involves both the patient and the primary care provider. The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma. While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient's selection of both the device and the regimen. Patient's health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy. This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence.
Subject(s)
Medication Adherence , Pulmonary Disease, Chronic Obstructive/drug therapy , Economics, Pharmaceutical , Health Behavior , Hospitalization , Humans , Metered Dose Inhalers , Patient Education as Topic , Patient Satisfaction , Pulmonary Disease, Chronic Obstructive/physiopathology , Quality of LifeABSTRACT
A critical aspect of mitosis is the interaction of the kinetochore with spindle microtubules. Fission yeast Mal3 is a member of the EB1 family of microtubule plus-end binding proteins, which have been implicated in this process. However, the Mal3 interaction partner at the kinetochore had not been identified. Here, we show that the mal3 mutant phenotype can be suppressed by the presence of extra Spc7, an essential kinetochore protein associated with the central centromere region. Mal3 and Spc7 interact physically as both proteins can be coimmunoprecipitated. Overexpression of a Spc7 variant severely compromises kinetochore-microtubule interaction, indicating that the Spc7 protein plays a role in this process. Spc7 function seems to be conserved because, Spc105, a Saccharomyces cerevisiae homolog of Spc7, identified by mass spectrometry as a component of the conserved Ndc80 complex, can rescue mal3 mutant strains.
Subject(s)
Chromosomal Proteins, Non-Histone/metabolism , Kinetochores/metabolism , Microtubule-Associated Proteins/metabolism , Schizosaccharomyces pombe Proteins/metabolism , Schizosaccharomyces/cytology , Schizosaccharomyces/metabolism , Spindle Apparatus/metabolism , Centromere/chemistry , Centromere/metabolism , Chromosomal Proteins, Non-Histone/genetics , Gene Expression , Immunoprecipitation , Kinetochores/chemistry , Microtubule-Associated Proteins/genetics , Microtubules/metabolism , Mitosis , Mutation/genetics , Phenotype , Protein Binding , Schizosaccharomyces/genetics , Schizosaccharomyces pombe Proteins/genetics , ran GTP-Binding Protein/genetics , ran GTP-Binding Protein/metabolismABSTRACT
Tests were conducted by a Task Force on Disinfectant Test Methods that was appointed to investigate controversies regarding the accuracy of AOAC test methods for disinfectants as presented in AOAC's Official Methods of Analysis, Chapter 6. The general principles for new and improved AOAC tests are discussed, and a disinfectant test using microbes labeled onto a polyester fiber surface is described. The quantitative test measures the survival of test microbes as a function of exposure time as well as the exposure conditions required to kill 6 log10 of the test microbes. The time required was similar to that for the kinetics of the kill of Bacillus subtilis-labeled cylinders as tested by methods of the AOAC Sporicidal Test 966.04.