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1.
Food Nutr Bull ; 44(2_suppl): S94-S108, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37850928

RESUMEN

Reduction of wasting, or low weight-for-height, is a critical target for the Zero Hunger Sustainable Development Goal, yet robust evidence establishing continuous seasonal patterns of wasting is presently lacking. The current consensus of greatest hunger during the preharvest period is based on survey designs and analytical methods, which discretize time frame into preharvest/postharvest, dry/wet, or lean/plenty seasons. We present a spatiotemporally nuanced study of acute malnutrition seasonality in African drylands using a 15-year data set of Standardized Monitoring and Assessment of Relief and Transition surveys (n = 412,370). Climatological similarity was ensured by selecting subnational survey regions with 1 rainy season and by spatially matching each survey to aridity and livelihood zones. Harmonic logit regression models indicate 2 peaks of wasting during the calendar year. Greatest wasting prevalence is estimated in April to May, coincident with the primary peak of temperature. A secondary peak of wasting is observed in August to October, coinciding with the primary peak of rainfall and secondary peak of temperature. This pattern is retained across aridity and livelihood zones and is sensitive to temperature, precipitation, and vegetation. Improved subnational estimation of acute malnutrition seasonality can thus assist decision makers and practitioners in data-sparse settings and facilitate global progress toward Zero Hunger.


Plain language titleFifteen Years of Rapid Assessment Surveys Indicate Seasonal Variability in Prevalence of Acute Malnutrition Among Children Younger Than 5 Years in African DrylandsPlain language summaryWasting or low weight-for-height is a key indicator of short-term or acute malnutrition. The timing of highest wasting prevalence, particularly among children younger than 5 years, is of interest for humanitarian efforts to reduce hunger. Current knowledge about this timing derives from survey designs, which discretize continuous time into preharvest/postharvest, dry/wet, or lean/plenty seasons. Instead of this categorical approach, we utilize harmonic regressions that allow for modeling of continuous time in our analysis of 15 years of Standardized Monitoring and Assessment of Relief and Transition surveys. Surveys conducted in parts of North Africa with 1 rainy season (unimodal regions) were selected for similar climate, and survey locations were further subdivided by aridity and livelihood zones. The seasonal pattern of extreme wasting prevalence in each group was modeled using survey data for a total of 412,370 children. We identified 2 periods of highest wasting prevalence in April to May and August to October. The April to May peak occurs during highest temperatures, and the August to October peak occurs during periods of highest rainfall and warmer temperatures in the study area. These findings can inform the timing of nutrition programs in unimodal dryland regions and guide future quantitative models of acute malnutrition seasonality.


Asunto(s)
Desnutrición , Humanos , Lactante , Desnutrición/epidemiología , Estaciones del Año , Prevalencia
2.
Food Nutr Bull ; 44(2_suppl): S69-S82, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37850926

RESUMEN

BACKGROUND: Chad suffers from protracted hunger, facing high food insecurity (Integrated Food Security Phase Classification 3 and above), and acute malnutrition levels that surpass the emergency threshold (15% global acute malnutrition) yearly. The Food Security Sector, with European Union support, leads an inclusive effort to increase synergy between humanitarian, development, and peace-building actors to understand and address drivers of hunger. OBJECTIVE: To understand the spatial distribution of child wasting and household food insecurity and systemic drivers (conflict, livelihoods, vegetation, cultural norms) as well as better understand the relationship between child wasting and household food insecurity in Kanem and Bahr el Ghazal (BeG) region, Chad, with the goal of improving nexus programming and targeting. METHODS: A cross-sectional randomized cluster survey was conducted in August 2021 in Kanem and BeG across 86 villages, reaching 7002 households and 6136 children. Data were collected on child anthropometry, household food security, and livelihoods. Using mixed methods, primary data were triangulated with secondary geospatial data on vegetation index and conflicts as well as qualitative interviews with local actors. Analysis was conducted using comparison tests, linear and logistic crude, and adjusted models, as well as looking at the design effect as a measure of clustering of outcomes at the community level. RESULTS: The geospatial distribution of hunger indicators shows child wasting and food insecurity are highly clustered. However, communities with a high prevalence of child wasting were not those with the highest levels of food insecurity, indicating different pathways. Clustering of food insecurity and child wasting is due to basic drivers of conflict, health, and seasonal access to natural resources. CONCLUSIONS: The high levels of food insecurity and child wasting are each concentrated in specific survey clusters and are not necessarily connected. They result from different causal pathways at the community level linked to the systemic drivers of the rule of access to natural resources, environmental seasonality, and livelihoods. This suggests a greater need for an integrated humanitarian, development, and peace-building interventions to address the persistent high prevalence of food insecurity and child wasting. It also suggests that these community-level and systemic drivers require greater consideration from the start in research design and data collection.


Plain language titleUnderstanding Linkages Between Household Food Insecurity, Child Malnutrition, and Their Respective Clustered Drivers in ChadPlain language summaryChad experiences emergency levels of household food insecurity and child malnutrition. To address this issue, the United Nations Food and Agricultural Organization has undertaken a collaborative effort to enhance cooperation among humanitarian, development, and peace-building actors. The objective of this study was to examine how child malnutrition, food insecurity, and their drivers cluster across communities in Kanem and Bahr El Ghazal to improve response planning and targeting. The study collected data in August 2021 on malnutrition, food security, livelihoods, vegetation, and conflict and carried out interviews with local informants. In total, the research covers 86 villages, 7,002 households, and 6,136 children. The research shows that the 2 measures of hunger, child malnutrition and food insecurity, are highly clustered, affecting some communities more than others. However, villages with a high prevalence of child acute malnutrition did not have the highest levels of food insecurity, suggesting different community-level drivers. The clustering of food insecurity and malnutrition at the village level was linked to the diversity of livelihoods, the experience of conflict, health, and seasonal limitations in accessing natural resources. These findings are crucial for informing the targeting and design of integrated humanitarian, development, and peace programs. Taking a systemic approach and fostering strong coordination across interventions to address the drivers of food insecurity and malnutrition holds great potential for tackling hunger in Chad.


Asunto(s)
Abastecimiento de Alimentos , Desnutrición , Niño , Humanos , Estudios Transversales , Chad/epidemiología , Desnutrición/epidemiología , Análisis por Conglomerados , Inseguridad Alimentaria
3.
Food Nutr Bull ; 44(2_suppl): S109-S118, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37850930

RESUMEN

BACKGROUND: Understanding seasonal patterns in nutritional status is critical for achieving and tracking global nutrition goals. However, the majority of nutrition seasonality research design draws on 2 or 3 within-year time points based on existing assumptions of seasonality, missing a more nuanced pattern. OBJECTIVE: We aimed to identify the intra-year variability of childhood wasting, severe wasting, and weight-for-height z-scores (WHZ) in a dryland single wet-season context and illustrate an analytical approach for improving analysis of the seasonality of nutritional status. METHODS: To quantify the intra-year variability in nutritional status, we use data from a 23-month panel study (May 2018 to March 2020) following 231 children (6-59 months of age) in eastern Chad. We apply a mixed-effects harmonic regression with child- and village-level fixed effects on the odds of being wasted, severely wasted, and on WHZ, testing for multiple and nonsymmetrical seasonal peaks, adjusted for child sex and age. We triangulate our findings using climate data on temperature, vegetation, and precipitation. RESULTS: We identify 2 annual peaks of wasting and severe wasting. Wasting peaks at 14.7% (confidence interval [CI], 11.8-18.2) at the end of the dry season, while the smaller peak corresponds to the start of the harvest period at 13.4% (CI, 10.7-16.6). The odds of being wasted decline during the rainy season to 11.8% (CI, 9.4-14.7), with the lowest prevalence of 8.8% (CI, 6.9-11.1) occurring during the start of the dry season. In addition, a 1°C monthly increase in temperature is significantly associated with a 5% (CI, 1.4-8.7) and 12% (CI, 3.0-20.3) increase in the odds that a child is wasted and severely wasted, respectively. CONCLUSIONS: Intra-year variability of child wasting is far more complex and nuanced than identified by the literature, with 2 peaks, as opposed to 1, likely corresponding to different seasonal drivers, such as food insecurity, disease, water contamination, and care practices at different times of year. Better seasonality analysis can go a long way in improving the timing and content of programming with the goal of reducing child wasting.


Plain language titleTwo Seasonal Peaks of Acute Malnutrition in ChadPlain language summaryUnderstanding seasonal patterns in nutrition is crucial for achieving and monitoring global nutrition goals. However, most research on nutrition seasonality relies on only a few time points within a year, which oversimplifies the true pattern. In our study conducted in Chad, a dryland environment with a single rainy season, we examined various indicators of acute malnutrition, including severe acute malnutrition. We analyzed 23 months of data from 231 children aged 6 to 59 months, considering factors such as sex, age, monthly rainfall, temperature, and vegetation. Our findings revealed 2 peaks of acute malnutrition, challenging the prevailing notion of a single peak identified in existing literature. The first, larger peak occurred at the onset of the rainy season, followed by a decline and then a second peak just before the harvest period. This pattern aligned with temperature variations rather than rainfall. The complex and nuanced seasonal patterns we observed suggest that different factors such as food insecurity, disease, water contamination, and care practices may contribute to acute malnutrition at different times of the year. Improved analysis of seasonality can significantly enhance the timing and effectiveness of interventions aimed at reducing child wasting.


Asunto(s)
Estado Nutricional , Humanos , Lactante , Chad/epidemiología , Estaciones del Año , Prevalencia
4.
J Public Health Policy ; 44(2): 196-210, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37081136

RESUMEN

Experience of serious violations of International Humanitarian Law (IHL) results in complex physical disability and psychosocial trauma amplifying poverty and multi-generational trauma and impeding long-term recovery. We use data from a representative sample of victims in the case Prosecutor V. Dominic Ongwen brought before the International Criminal Court. Thirteen years after the 2004 massacre, the victims were significantly worse off than the general war-affected population that did not experience serious violations of IHL. The differences in health and wellbeing persisted for individuals and their households, including children born after the massacre. The victims have significantly lower availability of appropriate health services and medications, including significantly greater distance to travel to these services. These findings call attention to the needs of people having experienced IHL violations, for provision of physical and emotional trauma care to allow for recovery, and better understanding of the short- and long-term impacts of IHL violations.


Asunto(s)
Altruismo , Políticas , Niño , Humanos , Uganda
5.
Food Nutr Bull ; 44(2_suppl): S124-S126, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37021371
6.
BMC Nutr ; 8(1): 90, 2022 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-36002905

RESUMEN

BACKGROUND: The Community-Based Management of Acute Malnutrition (CMAM) model transformed the treatment of severe acute malnutrition (SAM) by shifting treatment from inpatient facilities to the community. Evidence shows that while CMAM programs are effective in the initial recovery from SAM, recovery is not sustained for some children requiring them to receive treatment repeatedly. This indicates a potential gap in the model, yet little evidence is available on the incidence of relapse, the determinants of the phenomena, or its financial implications on program delivery. METHODS: This study is a multi-country prospective cohort study following "post-SAM" children (defined as children following anthropometric recovery from SAM through treatment in CMAM) and matched community controls (defined as children not previously experiencing acute malnutrition (AM)) monthly for six months. The aim is to assess the burden and determinants of relapse to SAM. This study design enables the quantification of relapse among post-SAM children, but also to determine the relative risk for, and excess burden of, AM between post-SAM children and their matched community controls. Individual -, household-, and community-level information will be analyzed to identify potential risk-factors for relapse, with a focus on associations between water, sanitation, and hygiene (WASH) related exposures, and post-discharge outcomes. The study combines a microbiological assessment of post-SAM children's drinking water, food, stool via rectal swabs, dried blood spots (DBS), and assess for indicators of enteric pathogens and immune function, to explore different exposures and potential associations with treatment and post-treatment outcomes. DISCUSSION: This study is the first of its kind to systematically track children after recovery from SAM in CMAM programs using uniform methods across multiple countries. The design allows the use of results to: 1) facilitate understandings of the burden of relapse; 2) identify risk factors for relapse and 3) elucidate financial costs associated with relapse in CMAM programs. This protocol's publication aims to support similar studies and evaluations of CMAM programs and provides opportunities for comparability of an evidence-based set of indicators for relapse to SAM.

7.
Trials ; 23(1): 244, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35365180

RESUMEN

OBJECTIVE: To implement and measure the effects of a multi-level multi-sectoral social behavior change (SBC) intervention in Agago District of Northern Uganda and to determine the potential for scale-up. INTERVENTION: Compare the Nutrition Impact and Positive Practice (NIPP) approach to a NIPP+ approach. The NIPP approach involves nutrition education and SBC, whereas the NIPP+ adds agricultural inputs, training, and tools to support improved farm and water quality practices. The intervention effect will be measured through lower levels of aflatoxin in grain, lower water contamination, and improved knowledge on nutrition and health. DESIGN: This is a three-arm cluster-randomized controlled superiority trial (cRCT). The study arms include the following: group 1: NIPP; group 2: NIPP+, and group 3: control. Groups 1 and 2 will receive a 12-week intervention (NIPP or NIPP+) with active monitoring and longitudinal follow-up at 2, 6, and 12 months post-intervention. Additionally, an in-depth process and performance evaluation of each intervention arm will be undertaken using quantitative and qualitative methods. A total of 60 clusters from 5 subcounties of the Agago district will be randomly selected, and 15 households per cluster will be recruited using specific inclusion/exclusion criteria for a total of 900 households (300/arm). Respondents for the qualitative portion will be purposely selected. ANALYSIS: We will collect data from all participants at 3 time points: baseline, endline, and 12 months post-intervention. The analysis will utilize intent-to-treat (ITT) using the initial randomization of the treatment arms to determine the overall impact of having the NIPP vs. NIPP+ vs. control. Mixed effects models will be used to determine the role of time-variant and invariant individual household, and community characteristics, as well as measures of exposure and integration on key outcome indicators. A difference-in-difference analysis (baseline/endline, baseline/12 months post-intervention, endline/12 months post-intervention) will also be used to triangulate findings. TRIAL REGISTRATION: NCT04209569 . One Nutrition in Complex Environments (ONCE) Registered 24 December 2019.


Asunto(s)
Terapia Nutricional , Estado Nutricional , Composición Familiar , Educación en Salud , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Uganda
8.
Adv Nutr ; 13(3): 748-757, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35254406

RESUMEN

The rapid expansion of food and nutrition information requires new ways of data sharing and dissemination. Interactive platforms integrating data portals and visualization dashboards have been effectively utilized to describe, monitor, and track information related to food and nutrition; however, a comprehensive evaluation of emerging interactive systems is lacking. We conducted a systematic review on publicly available dashboards using a set of 48 evaluation metrics for data integrity, completeness, granularity, visualization quality, and interactivity based on 4 major principles: evidence, efficiency, emphasis, and ethics. We evaluated 13 dashboards, summarized their characteristics, strengths, and limitations, and provided guidelines for developing nutrition dashboards. We applied mixed effects models to summarize evaluation results adjusted for interrater variability. The proposed metrics and evaluation principles help to improve data standardization and harmonization, dashboard performance and usability, broaden information and knowledge sharing among researchers, practitioners, and decision makers in the field of food and nutrition, and accelerate data literacy and communication.

9.
Artículo en Inglés | MEDLINE | ID: mdl-33668508

RESUMEN

Seasonality is a critical source of vulnerability across most human activities and natural processes, including the underlying and immediate drivers of acute malnutrition. However, while there is general agreement that acute malnutrition is highly variable within and across years, the evidence base is limited, resulting in an overreliance on assumptions of seasonal peaks. We review the design and analysis of 24 studies exploring the seasonality of nutrition outcomes in Africa's drylands, providing a summary of approaches and their advantages and disadvantages. Over half of the studies rely on two to four time points within the year and/or the inclusion of time as a categorical variable in the analysis. While such approaches simplify interpretation, they do not correspond to the climatic variability characteristic of drylands or the relationship between climatic variability and human activities. To better ground our understanding of the seasonality of acute malnutrition in a robust evidence base, we offer recommendations for study design and analysis, including drawing on participatory methods to identify community perceptions of seasonality, use of longitudinal data and panel analysis with approaches borrowed from the field of infectious diseases, and linking oscillations in nutrition data with climatic data.


Asunto(s)
Enfermedades Transmisibles , Desnutrición , Humanos , Desnutrición/epidemiología , Estado Nutricional , Estaciones del Año
10.
Matern Child Nutr ; 17(2): e13103, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33145931

RESUMEN

Progress on the nutrition Sustainable Development Goals has been slow. More attention is needed on the 'sustainable' part, focused on impact lasting beyond programme implementation. To determine sustained impact of a multisectoral nutrition intervention that provided water, sanitation, hygiene, livelihood, health and nutrition support (2013-2015) in eastern Chad, we utilize longitudinal household data collected 2 years (2017) after the intervention ended. Between 2013 and 2015, children (6-59 months) in the multisectoral intervention were less likely to be severely wasted, underweight and had a higher weight-for-height z-score (WHZ) compared with the control. To measure sustained programme impact, we use data on six nutrition indicators from 517 children between 2015 and 2017. We ran three models: a generalized linear model on cross-sectional child cohorts; a mixed-effects model on household panel data; and a mixed-effects model on child panel data. For children who were born during the programme, we saw significant improvement in underweight, weight for age z-scores (WAZs) and height-for-age z-scores (HAZs). Boys 6-23 months born after the end of the programme, on the other hand, were significantly more likely to be underweight or wasted and had lower WHZ and WAZ compared with boys born during the programme and girls born during and after the programme. Corresponding to the literature from sub-Saharan Africa, boys appear to be more vulnerable to malnutrition, which might be why they are more sensitive to programme cessation. Future monitoring, evaluations and research need to consider impact sustainability and that it might not be homogeneous across age and gender.


Asunto(s)
Trastornos de la Nutrición del Niño , Desnutrición , África del Sur del Sahara , Niño , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Desnutrición/epidemiología , Estado Nutricional , Saneamiento
11.
Artículo en Inglés | MEDLINE | ID: mdl-32365830

RESUMEN

Interventions tackling multiple drivers of child malnutrition have potential, yet the evidence is limited and draws on different analysis and nutrition outcomes, reducing comparability. To better understand the advantages and disadvantages of three different analytical approaches on seven common nutrition indicators, we use panel data (2012, 2014, 2015) on 1420 households from a randomized control study of a multi-sectoral intervention in Chad. We compare program impact using three types of analysis: a cross-sectional analysis of non-matched children; a panel analysis on longitudinal outcomes following the worst-off child in the household; and a panel analysis on longitudinal outcomes of matched children. We find that the sensitivity of the nutrition outcomes to program impact increases with each subsequent analytical approach, despite the reduction in sample size, as the analysis is able to control for more non-measured child and household characteristics. In the matched child panel analysis, the odds of a child being severely wasted were 76% lower (CI: 0.59-0.86, p = 0.001), the odds of being underweight were 33% lower (CI: 0.15-0.48, p = 0.012), and weight-for-height z-score was 0.19 standard deviations higher (CI: 0.09-0.28, p = 0.022) in the treatment versus control group. The study provides evidence for multi-sectoral interventions to tackle acute malnutrition and recommends the best practice analytical approach.


Asunto(s)
Trastornos de la Nutrición del Niño , Estado Nutricional , Niño , Preescolar , Estudios Transversales , Composición Familiar , Femenino , Humanos , Lactante , Ensayos Clínicos Controlados Aleatorios como Asunto , Delgadez
12.
Disasters ; 42 Suppl 1: S61-S78, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29281138

RESUMEN

Girls and women who bear children owing to wartime sexual violence committed by armed actors face challenges in gaining acceptance on return to their families and societies. This study analyses the lives of women survivors and their children born of wartime sexual violence in Uganda. It draws on a population-based survey of 1,844 households in the Acholi and Lango sub-regions of northern Uganda, as well as on in-depth qualitative interviews conducted in 2014 and 2015 with 67 purposefully selected women survivors of wartime sexual violence. The study finds that: stigma is linked to broader gender discriminatory sociocultural norms and practices and changes under different circumstances; women's economic agency is essential to reducing stigma; households with members who suffered war-related sexual violence experienced significantly higher rates of violence post conflict than did other households; and the passage of time is less of a determining factor in their acceptance and reintegration than previously thought.


Asunto(s)
Delitos Sexuales , Estigma Social , Sobrevivientes/psicología , Crímenes de Guerra , Adulto , Niño , Femenino , Identidad de Género , Humanos , Relaciones Interpersonales , Embarazo , Investigación Cualitativa , Normas Sociales , Sobrevivientes/estadística & datos numéricos , Uganda , Adulto Joven
13.
Food Nutr Bull ; 38(1): 115-127, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27932595

RESUMEN

BACKGROUND: The causes of acute malnutrition are complex and time and geography variant and need to be better understood in order to both design more effective nutrition programs and evaluate them. The findings reported here are part of an evaluation of a 4-year multisectoral nutrition program led by Concern Worldwide in the Sila Region of eastern Chad. OBJECTIVE: To present evidence and learning about the relationships between acute malnutrition and potential drivers in Sila, Chad. METHODS: Quantitative household-level data from a clustered randomized control trial were collected in November/December 2014. The survey was complemented with water quality testing and qualitative data collected in February and March 2013 and 2014. RESULTS: Households who reported not regularly cleaning the container used for transporting water for household consumption were almost twice as likely to have a malnourished child. Households living in villages with larger concentrations of cattle and having more livestock sharing the same water source as for human consumption were significantly more likely to have a malnourished child. However, cleaning the water container mediated the negative impact of living in a village with a large cattle concentration on wasting. CONCLUSION: These results demonstrate that hygiene practices and livestock water management are correlated with acute malnutrition in Sila, Chad. These findings provide a hypothesis for a possible pathogen driving acute malnutrition rates- Cryptosporidium-as part of a complex water chain, whereby the source of infection may be mitigated by hygiene behaviors with important implications for humanitarian programs.

14.
Dev Dyn ; 234(1): 190-200, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16059908

RESUMEN

The 37-kd laminin receptor precursor (LR) was first identified as a 67-kd protein that binds laminin with high affinity. We have recently isolated the Xenopus laevis LR as an in vitro substrate of matrix metalloproteinase stromelysin-3 (ST3), which is highly upregulated during intestinal metamorphosis in Xenopus laevis. Here, we show that LR is expressed in the intestinal epithelium of premetamorphic tadpoles. During intestinal metamorphosis, LR is downregulated in the apoptotic epithelium and concurrently upregulated in the connective tissue but with little expression in the developing adult epithelium. Toward the end of metamorphosis, as adult epithelial cells differentiate, they begin to express LR. Furthermore, LR is cleaved during intestinal remodeling when ST3 is highly expressed or in premetamorphic intestine of transgenic tadpoles overexpressing ST3. These results suggest that LR plays a role in cell fate determination and tissue morphogenesis, in part through its cleavage by ST3. Interestingly, high levels of LR are known to be expressed in tumor cells, which are often surrounded by fibroblasts expressing ST3, suggesting that LR cleavage by ST3 plays a role in both physiological and pathological processes.


Asunto(s)
Intestinos/crecimiento & desarrollo , Metaloproteinasa 11 de la Matriz/fisiología , Receptores de Laminina/metabolismo , Secuencia de Aminoácidos , Animales , Larva/crecimiento & desarrollo , Metaloproteinasa 11 de la Matriz/genética , Datos de Secuencia Molecular , Especificidad de Órganos , Xenopus laevis
15.
Cell Res ; 15(3): 150-9, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15780176

RESUMEN

The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. However, like other MMPs, the molecular basis of ST3 function in vivo remains unclear due to the lack of information on its physiological substrates. Furthermore, ST3 has only weak activities toward all tested ECM proteins. Using thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we demonstrated previously that ST3 is important for apoptosis and tissue morphogenesis during intestinal remodeling. Here, we used yeast two-hybrid screen with mRNAs from metamorphosing tadpoles to identify potential substrate of ST3 during development. We thus isolated the 37 kd laminin receptor precursor (LR). We showed that LR binds to ST3 in vitro and can be cleaved by ST3 at two sites, distinct from where other MMPs cleave. Through peptide sequencing, we determined that the two cleavage sites are in the extracellular domain between the transmembrane domain and laminin binding sequence. Furthermore, we demonstrated that these cleavage sites are conserved in human LR. These results together with high levels of human LR and ST3 expression in carcinomas suggest that LR is a likely in vivo substrate of ST3 and that its cleavage by ST3 may alter cell-extracellular matrix interaction, thus, playing a role in mediating the effects of ST3 on cell fate and behavior observed during development and pathogenesis.


Asunto(s)
Metaloendopeptidasas/química , Receptores de Laminina/química , Secuencia de Aminoácidos , Animales , Sitios de Unión , Clonación Molecular , Secuencia Conservada , Humanos , Larva , Metaloproteinasa 11 de la Matriz , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Técnicas del Sistema de Dos Híbridos , Xenopus laevis
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