Rôle de la Galectin-3 extra cellulaire dans la migration des cellules B à travers les barrières du système nerveux central dans le contexte de la sclérose en plaques

La sclérose en plaques (SEP) est une maladie inflammatoire chronique du système nerveux central caractérisée par l’infiltration de cellules immunitaires et par la présence de lésions démyélinisantes dans le système nerveux central (SNC) des patients. Un événement clef dans la maladie est la perte d’intégrité des barrières protégeant le système nerveux central (SNC) qui permet la migration des cellules immunitaires, dont les cellules B, vers celui-ci depuis le sang. La migration est contrôlée par différents paramètres dont l’expression de molécules favorisant l’adhésion aux cellules endothéliales constituant les barrières du SNC. Des données protéomiques générées par notre laboratoire nous ont permis d’identifier la galectin-3, une protéine pro-inflammatoire, comme étant potentiellement impliquée dans la migration des cellules B vers le SNC et pouvant influer leur pathogénicité. Les résultats de ce mémoire montrent que chez les donneurs sains la galectin-3 est exprimée à la surface par les cellules B du sang total ainsi que par les cellules B effectrices in vitro. Elle est également présente dans le surnageant de ces dernières. De plus, les cellules galectin-3+ expriment davantage de cytokines pro-inflammatoires que les cellules galectin-3- in vitro. Cependant, la stimulation des cellules B effectrices en présence de galectin-3 exogène induit une diminution temporaire de l’expression de l’IL-6 et de l’IFN-γ. D’autre part, nous avons démontré que la galectin-3 exogène peut se lier à la surface des cellules B toutefois elle n’influence pas leur migration à travers les modèles in vitro des barrières du SNC. Nous avons par la suite mis en évidence que la galectin-3 était présente dans le liquide céphalo-rachidien des patients SEP. De plus la concentration en galectin-3 dans le sérum de ces derniers est plus élevée que celle des donneurs sains. Enfin nous avons démontré que les cellules B des patients SEP exprimaient davantage de galectin-3 à la surface que celles des donneurs sains. Pour conclure, les données ne permettent pas de supporter l’hypothèse selon laquelle la galectin-3 favorise la migration à travers les barrières du SNC. De plus, l’influence de la galectin-3 sur la pathogénicité des cellules B in vitro semble dépendre de sa concentration dans le milieu. Mais l’augmentation de son expression chez les patients suggère une implication dans la SEP.Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), hallmarks of the disease are an important infiltration of immune cells and demyelinating lesions in the CNS of patients. A key event in the disease is CNS barriers’ loss of integrity that allows the migration of immune cells, including B cells, from the blood to the CNS. Migration is regulated by many parameters, among which, the expression of molecules enabling adhesion to the endothelial cells of the CNS barriers. Proteomic data from our lab identified galectin-3, a pro-inflammatory protein, as potentially involved in B cells’ migration toward the CNS. Moreover, galectin-3 could add to B cells pathogenicity. Our results show that healthy donors’ whole blood B cells as well as effector B cells in vitro express galectin-3 on their surface. Moreover, effector B cells are able to secrete galectin-3. In vitro assay revealed that galectin-3+ effector B cells express more pro-inflammatory cytokines than galectin-3- effector B cells. However, a temporary decrease of IL-6 and IFN-γ expression is induced when effector B cells are treated with galectin-3. Furthermore, exogenous galectin-3 can bind to B cells’ surface but it doesn’t influence their migration through in vitro models of the SNC barriers. In addition, we could detect galectin-3 in MS patients’ cerebrospinal fluid (CSF) and serum, the latter showed increased concentration compared to healthy donors’. Moreover, we evidence that MS patients’ B cells express more galectin-3 on the cell surface than healthy donors’. In conclusion, our results don’t support the initial hypothesis that galectin-3 enables B cells’ migration through CNS barriers and galectin-3’s influence on B cells pathogenicity in vitro seems to depend on its concentration. But galectin-3’s increased expression in MS patients suggests that it could be implicated in the disease

Gender and sociocultural factors in animal source foods (ASFs) access and consumption in lower-income households in urban informal settings of Nairobi, Kenya

BACKGROUND: Gender shapes household decision-making and access for nutritious diets, including animal source foods (ASFs) that impact on child health and nutrition status. However, research shows that the poorest households in the urban informal settlements of Nairobi have low ASFs consumption. This study was conducted to explore further from a qualitative perspective the gender, sociocultural factors affecting household ASF consumption this study. METHODS: To explore further on the topic of study, an exploratory qualitative study was carried out to establish the factors that influence access, allocation and consumption of animal source foods (ASFs) by households in urban informal settings of Nairobi. Nineteen focus group discussions with men and women were conducted to enable in-depth exploration of ASFs consumption. RESULTS: Gender influences decision-making of household ASFs dietary intake. Gendered power dynamics prevail with men as breadwinners and household heads often determining the food access and consumption of ASFs. Women are increasingly accessing short-term waged-based incomes in urban informal settings and now play a role in food and nutrition security for their households. This enforces the idea that women's decision-making autonomy is an important aspect of women empowerment, as it relates to women's dietary diversity and subsequently, better household nutritional status. As evidenced in this study, if a woman has bargaining power based on accessing incomes to support their household food needs, she will not jeopardize food security. The mobile digital money platform was key in enabling access to resources to access food. Use of trust to access food on credit and purchasing smaller packaged quantities of food were also enablers to access of food/ASFs

Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures

Inflammatory processes in the brain are orchestrated by microglia and astrocytes in response to activators such as pathogen-associated molecular patterns, danger-associated molecular patterns and some nanostructures. Microglia are the primary immune responders in the brain and initiate responses amplified by astrocytes through intercellular signaling. Intercellular communication between neural cells can be studied in cerebral organoids, co-cultures or in vivo. We used human cerebral organoids and glioblastoma co-cultures to study glia modulation by dendritic polyglycerol sulfate (dPGS). dPGS is an extensively studied nanostructure with inherent anti-inflammatory properties. Under inflammatory conditions, lipocalin-2 levels in astrocytes are markedly increased and indirectly enhanced by soluble factors released from hyperactive microglia. dPGS is an effective anti-inflammatory modulator of these markers. Our results show that dPGS can enter neural cells in cerebral organoids and glial cells in monocultures in a time-dependent manner. dPGS markedly reduces lipocalin-2 abundance in the neural cells. Glioblastoma tumoroids of astrocytic origin respond to activated microglia with enhanced invasiveness, whereas conditioned media from dPGS-treated microglia reduce tumoroid invasiveness. Considering that many nanostructures have only been tested in cancer cells and rodent models, experiments in human 3D cerebral organoids and co-cultures are complementary in vitro models to evaluate nanotherapeutics in the pre-clinical setting. Thoroughly characterized organoids and standardized procedures for their preparation are prerequisites to gain information of translational value in nanomedicine. This study provides data for a well-characterized dendrimer (dPGS) that modulates the activation state of human microglia implicated in brain tumor invasiveness

Consumer perceptions of food safety in animal source foods choice and consumption in Nairobi's informal settlements.

BACKGROUND: Animal-source foods (ASFs) are high-quality nutrient-dense products key to reducing stunting and micronutrient deficiencies. However, their consumption among the poorest households in urban informal settlements is low. Several drivers beyond price, including health considerations have been reported to drive ASF choice and consumption among consumers. This current study explores consumer perceptions of food safety associated with animal source foods (ASFs) consumption in urban informal settlements with a view to unpacking the health considerations driving their choice and consumption. METHODS: Coupled households with children 6-59 months formed the study sample. The Food Environments Working Group (FEWG) Framework of the Agriculture and Nutrition for Health academy (ANH) was used to guide the study which utilized qualitative methods namely, 60 in-depth interviews (IDIs), 19 focus group discussions, and 19 key informant interviews (KIIs) complemented by unstructured observations. Data were transcribed and analysed according to emerging themes. RESULTS: Consumer perceptions of food safety are driven by concerns about food production, processing, handling, storage and the health risks associated with consumption of the ASFs. For all the ASFs, lack of traceability of source, unhygienic environments in which they were sold and health risks around consuming too much or improperly cooked products were key perceptions from the community. To mitigate against food safety risks, consumers used strategies such as boiling the ASFs, purchasing their products from trusted retailers, avoiding vendors in unhygienic environments and reducing the amount and frequency of consumption of ASFs or totally avoiding their consumption. These consumer perceptions are increasingly influencing the ASFs choice and consumption in low-income populations besides other drivers. Notably, given limited incomes that influence their purchasing power and the need for nutritious diets that included ASFs, the dilemma of quality vis-a-vis quantity persists and consumers still accessed and consumed these ASF products to supplement their diets. CONCLUSIONS: To enhance food safety for ASFs, as well as assure consumer access to safe ASFs from informal markets, there is need to contextualize the value chain as informed by consumer perceptions on food safety as these influence their ASFs choice and consumption

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

Gender and sociocultural factors in animal source foods (ASFs) access and consumption in lower-income households in urban informal settings of Nairobi, Kenya

Background Gender shapes household decision-making and access for nutritious diets, including animal source foods (ASFs) that impact on child health and nutrition status. However, research shows that the poorest households in the urban informal settlements of Nairobi have low ASFs consumption. This study was conducted to explore further from a qualitative perspective the gender, sociocultural factors affecting household ASF consumption this study. Methods To explore further on the topic of study, an exploratory qualitative study was carried out to establish the factors that influence access, allocation and consumption of animal source foods (ASFs) by households in urban informal settings of Nairobi. Nineteen focus group discussions with men and women were conducted to enable in-depth exploration of ASFs consumption. Results Gender influences decision-making of household ASFs dietary intake. Gendered power dynamics prevail with men as breadwinners and household heads often determining the food access and consumption of ASFs. Women are increasingly accessing short-term waged-based incomes in urban informal settings and now play a role in food and nutrition security for their households. This enforces the idea that women’s decision-making autonomy is an important aspect of women empowerment, as it relates to women’s dietary diversity and subsequently, better household nutritional status. As evidenced in this study, if a woman has bargaining power based on accessing incomes to support their household food needs, she will not jeopardize food security. The mobile digital money platform was key in enabling access to resources to access food. Use of trust to access food on credit and purchasing smaller packaged quantities of food were also enablers to access of food/ASFs

Consumer perceptions of food safety in animal source foods choice and consumption in Nairobi’s informal settlements

Background Animal-source foods (ASFs) are high-quality nutrient-dense products key to reducing stunting and micronutrient deficiencies. However, their consumption among the poorest households in urban informal settlements is low. Several drivers beyond price, including health considerations have been reported to drive ASF choice and consumption among consumers. This current study explores consumer perceptions of food safety associated with animal source foods (ASFs) consumption in urban informal settlements with a view to unpacking the health considerations driving their choice and consumption. Methods Coupled households with children 6–59 months formed the study sample. The Food Environments Working Group (FEWG) Framework of the Agriculture and Nutrition for Health academy (ANH) was used to guide the study which utilized qualitative methods namely, 60 in-depth interviews (IDIs), 19 focus group discussions, and 19 key informant interviews (KIIs) complemented by unstructured observations. Data were transcribed and analysed according to emerging themes. Results Consumer perceptions of food safety are driven by concerns about food production, processing, handling, storage and the health risks associated with consumption of the ASFs. For all the ASFs, lack of traceability of source, unhygienic environments in which they were sold and health risks around consuming too much or improperly cooked products were key perceptions from the community. To mitigate against food safety risks, consumers used strategies such as boiling the ASFs, purchasing their products from trusted retailers, avoiding vendors in unhygienic environments and reducing the amount and frequency of consumption of ASFs or totally avoiding their consumption. These consumer perceptions are increasingly influencing the ASFs choice and consumption in low-income populations besides other drivers. Notably, given limited incomes that influence their purchasing power and the need for nutritious diets that included ASFs, the dilemma of quality vis-a-vis quantity persists and consumers still accessed and consumed these ASF products to supplement their diets. Conclusions To enhance food safety for ASFs, as well as assure consumer access to safe ASFs from informal markets, there is need to contextualize the value chain as informed by consumer perceptions on food safety as these influence their ASFs choice and consumption

Gender and sociocultural factors in animal source foods (ASFs) access and consumption in lower-income households in urban informal settings of Nairobi, Kenya

Background Gender shapes household decision-making and access for nutritious diets, including animal source foods (ASFs) that impact on child health and nutrition status. However, research shows that the poorest households in the urban informal settlements of Nairobi have low ASFs consumption. This study was conducted to explore further from a qualitative perspective the gender, sociocultural factors affecting household ASF consumption this study. Methods To explore further on the topic of study, an exploratory qualitative study was carried out to establish the factors that influence access, allocation and consumption of animal source foods (ASFs) by households in urban informal settings of Nairobi. Nineteen focus group discussions with men and women were conducted to enable in-depth exploration of ASFs consumption. Results Gender influences decision-making of household ASFs dietary intake. Gendered power dynamics prevail with men as breadwinners and household heads often determining the food access and consumption of ASFs. Women are increasingly accessing short-term waged-based incomes in urban informal settings and now play a role in food and nutrition security for their households. This enforces the idea that women’s decision-making autonomy is an important aspect of women empowerment, as it relates to women’s dietary diversity and subsequently, better household nutritional status. As evidenced in this study, if a woman has bargaining power based on accessing incomes to support their household food needs, she will not jeopardize food security. The mobile digital money platform was key in enabling access to resources to access food. Use of trust to access food on credit and purchasing smaller packaged quantities of food were also enablers to access of food/ASFs

Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures

Inflammatory processes in the brain are orchestrated by microglia and astrocytes in response to activators such as pathogen-associated molecular patterns, danger-associated molecular patterns and some nanostructures. Microglia are the primary immune responders in the brain and initiate responses amplified by astrocytes through intercellular signaling. Intercellular communication between neural cells can be studied in cerebral organoids, co-cultures or in vivo. We used human cerebral organoids and glioblastoma co-cultures to study glia modulation by dendritic polyglycerol sulfate (dPGS). dPGS is an extensively studied nanostructure with inherent anti-inflammatory properties. Under inflammatory conditions, lipocalin-2 levels in astrocytes are markedly increased and indirectly enhanced by soluble factors released from hyperactive microglia. dPGS is an effective anti-inflammatory modulator of these markers. Our results show that dPGS can enter neural cells in cerebral organoids and glial cells in monocultures in a time-dependent manner. dPGS markedly reduces lipocalin-2 abundance in the neural cells. Glioblastoma tumoroids of astrocytic origin respond to activated microglia with enhanced invasiveness, whereas conditioned media from dPGS-treated microglia reduce tumoroid invasiveness. Considering that many nanostructures have only been tested in cancer cells and rodent models, experiments in human 3D cerebral organoids and co-cultures are complementary in vitro models to evaluate nanotherapeutics in the pre-clinical setting. Thoroughly characterized organoids and standardized procedures for their preparation are prerequisites to gain information of translational value in nanomedicine. This study provides data for a well-characterized dendrimer (dPGS) that modulates the activation state of human microglia implicated in brain tumor invasiveness