Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis.

The regulation of the proliferation and polarity of neural progenitors is crucial for the development of the brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator of both proliferation and polarity, yet the functional relevance of its signaling for the unique features of human corticogenesis remains to be elucidated. We harnessed human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Single-cell transcriptome profiling revealed a direct impact on early neurogenesis and uncovered a selective role of GSK3 in the regulation of glutamatergic lineages and outer radial glia output. Our dissection of the GSK3-dependent transcriptional network in human corticogenesis underscores the robustness of the programs determining neuronal identity independent of tissue architecture.

Environmental assessment of the entire pork value chain in Catalonia - A strategy to work towards Circular Economy.

Pork industry in Catalonia plays a foremost and representative role in the Spanish pork sector. Beyond the economic benefits, conventional practices in the pork industry also imply a number of environmental impacts that need to be dealt with. In this context, the environmental performance of traditional linear pork chain in Catalonia was evaluated through a LCA approach. The outcomes of the analysis showed that both fodder production and transport activities were identified as the critical stages of the system. Accordingly, alternative schemes based on circular economy principles were proposed and potential environmental credits were estimated. Within this framework, comparative results highlighted the advantages of moving towards a closing loop production system, where resource efficiency and waste valorisation were prioritised over final disposal options.

Carbon and water footprint of pork supply chain in Catalonia: From feed to final products.

A systematic tool to assess the Carbon Footprint (CF) and Water Footprint (WF) of pork production companies was developed and applied to representative Catalan companies. To do so, a cradle-to-gate environmental assessment was carried out by means of the LCA methodology, taking into account all the stages involved in the pork chain, from feed production to the processing of final products, ready for distribution. In this approach, the environmental results are reported based on eight different functional units (FUs) according to the main pork products obtained. With the aim of ensuring the reliability of the results and facilitating the comparison with other available reports, the Product Category Rules (PCR) for Catalan pork sector were also defined as a basis for calculations. The characterization results show fodder production as the main contributor to the global environmental burdens, with contributions higher than 76% regardless the environmental indicator or the life cycle stage considered, which is in agreement with other published data. In contrast, the results in terms of CF and WF lay above the range of values reported elsewhere. However, major discrepancies are mainly due to the differences in the co-products allocation criteria. In this sense, economic/physical allocation and/or system expansion have been mostly considered in literature. In contrast, no allocation was considered appropriate in this study, according to the characteristics of the industries and products under assessment; thus, the major impacts fall on the main product, which derives on comparatively higher environmental burdens. Finally, due to the relevance of fodder production in the overall impact assessment results, strategies to reduce greenhouse gases (GHG) emissions as well as water use associated to this stage were proposed in the pork supply chain.

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-X(L).

Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and pro-dopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-X(L) induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-X(L) anticipates and enhances DAn generation.