Cortico-cerebral development in the gray short-tailed opossum Monodelphis domestica

The marsupial South-American short-tailed opossum, Monodelphis domestica, is an appealing animal model for developmental studies on cortico-cerebral development, since the opossum cortex mainly develops after birth and newborns are particularly suitable for early ex-utero micro-surgical manipulations of this structure and the entire CNS. Opossum have been also largely employed as an ideal substrate for regenerative studies, since the pup is able to regenerate connections between neurons of the cerebral cortex and spinal cord upon experimental trauma. Moreover, branching from the common mammal ancestor about 180 My ago, Marsupials might provide a valuable tool for tracing evolutionary origins of key traits peculiar to the eutherian central nervous system (CNS). Until recently, the cortico-cerebral marsupial development has been prevalently investigated by methods of classical histology, but several features of Monodelphis corticogenesis were still unknown. By taking advantage of molecular tools set up for developmental studies in Placentals and availability of Monodelphis domestica genomic sequence, we tried to fill gaps in our knowledge of opossum corticogenesis, studying in particular: origin of cortical neurons, their laminar differentiation and their migration profiles, from their birthplaces to their final layer positions. We found many similarities between marsupial and placental corticogenesis, as for neuron generation, their laminar diversification and \u201cinside-out\u201d migration. This allowed us to establish a comparative time-table of mouse and opossum corticogenesis. One major difference emerged from our study. In the opossum, projection neurons are mainly born from apical progenitors and a basal proliferative compartment is hardly detectable

Cortico-cerebral histogenesis in the opossum Monodelphis domestica: generation of a hexalaminar neocortex in the absence of a basal proliferative compartment

<p>Abstract</p> <p>Background</p> <p>The metatherian <it>Monodelphis domestica</it>, commonly known as the South-American short-tailed opossum, is an appealing animal model for developmental studies on cortico-cerebral development. Given its phylogenetic position, it can help in tracing evolutionary origins of key traits peculiar to the eutherian central nervous system. The capability of its pup to regenerate damaged cortico-spinal connections makes it an ideal substrate for regenerative studies. Recent sequencing of its genome and the <it>ex utero </it>accessibility of its developing cerebral cortex further enhance its experimental interest. However, at the moment, a comprehensive cellular and molecular characterization of its cortical development is missing.</p> <p>Results</p> <p>A systematic analysis of opossum cortico-cerebral development was performed, including: origin of cortical neurons; migration of these neurons from their birthplaces to their final layer destinations; and molecular differentiation of distinct neocortical laminae.</p> <p>We observed that opossum projection neurons and interneurons are generated by pallial and subpallial precursors, respectively, similar to rodents. A six-layered cortex with a eutherian-like molecular profile is laid down, according to the inside-out rule. However, neocortical projection neurons are generated by apical neural precursors and almost no basal progenitors may be found in the neuronogenic neopallial primordium. In the opossum neocortex, <it>Tbr2</it>, the hallmark of eutherian basal progenitors, is transiently expressed by postmitotic progenies of apical precursors prior to the activation of more mature neuronal markers.</p> <p>Conclusions</p> <p>The neocortical developmental program predates Eutheria-Methatheria branching. However, in metatherians, unlike eutherians, a basal proliferative compartment is not needed for the formation of a six-layered neuronal blueprint.</p

Factors Influencing Household Uptake of Improved Solid Fuel Stoves in Low- and Middle-Income Countries: A Qualitative Systematic Review

Household burning of solid fuels in traditional stoves is detrimental to health, the environment and development. A range of improved solid fuel stoves (IS) are available but little is known about successful approaches to dissemination. This qualitative systematic review aimed to identify factors that influence household uptake of IS in low- and middle-income countries. Extensive searches were carried out and studies were screened and extracted using established systematic review methods. Fourteen qualitative studies from Asia, Africa and Latin-America met the inclusion criteria. Thematic synthesis was used to synthesise data and findings are presented under seven framework domains. Findings relate to user and stakeholder perceptions and highlight the importance of cost, good stove design, fuel and time savings, health benefits, being able to cook traditional dishes and cleanliness in relation to uptake. Creating demand, appropriate approaches to business, and community involvement, are also discussed. Achieving and sustaining uptake is complex and requires consideration of a broad range of factors, which operate at household, community, regional and national levels. Initiatives aimed at IS scale up should include quantitative evaluations of effectiveness, supplemented with qualitative studies to assess factors affecting uptake, with an equity focus

Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

The evidence from post-mortem biochemical studies conducted on cortisol and catecholamines suggest that analysis of the adrenal gland could provide useful information about its role in human pathophysiology and the stress response. Authors designed an immunohistochemical study on the expression of the adrenal β2-adrenergic receptor (β2-AR), a receptor with high-affinity for catecholamines, with the aim to show which zones it is expressed in and how its expression differs in relation to the cause of death. The immunohistochemical study was performed on adrenal glands obtained from 48 forensic autopsies of subjects that died as a result of different pathogenic mechanisms using a mouse monoclonal β2-AR antibody. The results show that immunoreactivity for β2-AR was observed in all adrenal zones. Furthermore, immunoreactivity for β2-AR has shown variation in the localization and intensity of different patterns in relation to the original cause of death. To the best of our knowledge, this is the first study that demonstrates β2-AR expression in the human cortex and provides suggestions on the possible involvement of β2-AR in human cortex hormonal stimulation. In conclusion, the authors provide a possible explanation for the observed differences in expression in relation to the cause of death

Factors Influencing Household Uptake of Improved Solid Fuel Stoves in Low- and Middle-Income Countries: A Qualitative Systematic Review

Household burning of solid fuels in traditional stoves is detrimental to health, the environment and development. A range of improved solid fuel stoves ( IS) are available but little is known about successful approaches to dissemination. This qualitative systematic review aimed to identify factors that influence household uptake of IS in low- and middle-income countries. Extensive searches were carried out and studies were screened and extracted using established systematic review methods. Fourteen qualitative studies from Asia, Africa and Latin-America met the inclusion criteria. Thematic synthesis was used to synthesise data and findings are presented under seven framework domains. Findings relate to user and stakeholder perceptions and highlight the importance of cost, good stove design, fuel and time savings, health benefits, being able to cook traditional dishes and cleanliness in relation to uptake. Creating demand, appropriate approaches to business, and community involvement, are also discussed. Achieving and sustaining uptake is complex and requires consideration of a broad range of factors, which operate at household, community, regional and national levels. Initiatives aimed at IS scale up should include quantitative evaluations of effectiveness, supplemented with qualitative studies to assess factors affecting uptake, with an equity focus

Drivers of the Adoption and Exclusive Use of Clean Fuel for Cooking in Sub-Saharan Africa: Learnings and Policy Considerations from Cameroon

Household air pollution (HAP) caused by the combustion of solid fuels for cooking and heating is responsible for almost 5% of the global burden of disease. In response, the World Health Organisation (WHO) has recommended the urgent need to scale the adoption of clean fuels, such as liquefied petroleum gas (LPG), in low and middle-income countries (LMICs). To understand the drivers of the adoption and exclusive use of LPG for cooking, we analysed representative survey data from 3343 peri-urban and rural households in Southwest Cameroon. Surveys used standardised tools to collect information on fuel use, socio-demographic and household characteristics and use of LPG for clean cooking. Most households reported LPG to be clean (95%) and efficient (88%), but many also perceived it to be expensive (69%) and unsafe (64%). Positive perceptions about LPG's safety (OR = 2.49, 95% CI = 2.04, 3.05), cooking speed (OR = 4.31, 95% CI = 2.62, 7.10), affordability (OR = 1.7, 95% CI = 1.38, 2.09), availability (OR = 2.17, 95% CI = 1.72, 2.73), and its ability to cook most dishes (OR = 3.79, 95% CI = 2.87, 5.01), were significantly associated with exclusive LPG use. Socio-economic status (higher education) and household wealth (higher income) were also associated with a greater likelihood of LPG adoption. Effective strategies to raise awareness around safe use of LPG and interventions to address financial barriers are needed to scale wider adoption and sustained use of LPG for clean cooking, displacing reliance on polluting solid fuels

Shaping substrate selectivity in a broad-spectrum metallo-β-lactamase

Metallo-β-lactamases (MBLs) are the major group of carbapenemases produced by bacterial pathogens. The design of MBL inhibitors has been limited by, among other issues, incomplete knowledge about how these enzymes modulate substrate recognition. While most MBLs are broad-spectrum enzymes, B2 MBLs are exclusive carbapenemases. This narrower substrate profile has been attributed to a sequence insertion present in B2 enzymes that limits accessibility to the active site. In this work, we evaluate the role of sequence insertions naturally occurring in the B2 enzyme Sfh-I and in the broad-spectrum B1 enzyme SPM-1. We engineered a chimeric protein in which the sequence insertion of SPM-1 was replaced by the one present in Sfh-I. The chimeric variant is a selective cephalosporinase, revealing that the substrate profile of MBLs can be further tuned depending on the protein context. These results also show that the stable scaffold of MBLs allows a modular engineering much richer than the one observed in nature.Fil: González, Lisandro J.. Instituto de Biologia Molecular y Celular de Rosario; ArgentinaFil: Stival, Cintia Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Puzzolo, Juan Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Moreno, Diego M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Aguilar Vila, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin