612 research outputs found

    Bearing the brunt: The social impact of the Belt and Road Initiative’s infrastructure projects on the local communities in Myanmar

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    Since its unveiling in October 2013 by Chinese President Xi Jinping, the bulk of research on the Chinese Belt and Road Initiative (BRI) has dealt with the development of Chinese-sponsored and Chinese-built physical infrastructures, its economic consequences, such as the inflow of foreign direct investments (FDIs) into partner countries, often developing ones, and its geopolitical implications. Due to its unique geographical location on the eastern coast of the Bay of Bengal connecting the Chinese landlocked province of Yunnan with the Indian Ocean, Myanmar has long been playing a pivotal role in the BRI. Although recognizing how the BRI can positively impact Myanmar’s economic growth, this work moves away from the modernist understanding of infrastructures and, in line with the so-called “infrastructural turn”, acknowledges the negative societal externalities that infrastructural development inadvertently brings about. Taking a bottom-up approach and building on Mark Overland and Vakulchuk (2020), this study argues that the Chinese physical infrastructures’ construction phase and everyday functioning have been entailing negative social impacts and that these have been disproportionately born by the Myanmar local communities, especially land-dependent ones, whose lives and livelihoods were disrupted. To assess these negative social impacts, the article introduces interrelated concepts of infrastructural violence (Rodgers and O’Neill 2013) and infrastructural harm (Kallianos Dunlap, and Dalakoglou 2023). The latter will be applied to two BRI-funded infrastructure projects in Myanmar, namely the Myanmar-China Oil and Gas Pipelines and the Kyaukphyu Special Economic Zone (KP SEZ). The analysis shows that in both cases no sufficient compensation was provided to the affected local communities and ultimately makes a case for the development of non-exploitative infrastructures benefitting Myanmar’s overall population in the future

    The impact of inflation on heterogeneous groups of households: an application to Italy

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    This paper explores the determinants of the heterogeneity in the expenditure behaviours of the Italian households, using the Households Expenditure Survey provided by the Italian National Institute of Statistics (ISTAT) for the year 2005. We assume that differences among consumers are associated with differences in their economic and socio-demographic characteristics (such as gender, employment status and age of the householder, number of household components, presence of under 18 years old components), and we look for those characteristics that better differentiate groups of households according to their purchasing patterns. We apply a nonparametric discriminant analysis based on the various expenditure budget components, and detect the most discrĂŹminating partitions of families. The technique allows us also to identify the specific goods of consumption that significantly differ across the groups identified by the best partitions. We then study the different effects of the price dynamics on subgroups of households, and propose consumer price indices specific for the optimal households groups

    Collagen and non-collagenous proteins molecular crosstalk in the pathophysiology of osteoporosis.

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    Abstract Collagenous and non-collagenous proteins (NCPs) in the extracellular matrix, as well as the coupling mechanisms between osteoclasts and osteoblasts, work together to ensure normal bone metabolism. Each protein plays one or more critical roles in bone metabolism, sometimes even contradictory, thus affecting the final mechanical, physical and chemical properties of bone tissue. Anomalies in the amount and structure of one or more of these proteins can cause abnormalities in bone formation and resorption, which consequently leads to malformations and defects, such as osteoporosis (OP). The connections between key proteins involved in matrix formation and resorption are far from being elucidated. In this review, we resume knowledge on the crosstalk between collagen type I and selected NCPs (Transforming Growth Factor-ÎČ, Insulin-like Growth Factor-1, Decorin, Osteonectin, Osteopontin, Bone Sialoprotein and Osteocalcin) of bone matrix, focusing on their possible involvement and role in OP. The different elements of this network can be pharmacologically targeted or used for the design/development of innovative regenerative strategies to modulate a feedback loop in bone remodelling

    A drug-induced microscopic colitis in an older woman: a case report

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    We presented a case of a 87-year-old woman hospitalized for chronic watery diarrhea, affected by multimorbidities. After excluding other caus-es of diarrhea by biohumoral and microbiological tests, endoscopy was performed without revealing any macroscopic abnormalities, but, at histological examination of random biopsies, the characteristic features of collagenous colitis were found. Lansoprazolo and sertraline, chronically taken by the patient, was discontinued, and budesonide was started with prompt clinical improvement. Collagenous colitis is a rare cause of chronic diarrhea in advanced age, but it should be suspected in patients with polypharmacotherapy, after an accurate differential diagnosis

    Analysis of multiple protein detection methods in human osteoporotic bone extracellular matrix: From literature to practice

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    The punctual analysis of bone Extracellular Matrix (ECM) proteins represents a pivotal point for medical research in bone diseases like osteoporosis. Studies in this field, historically done to appreciate bone biology, were mainly conducted on animal samples and, up to today, only a few studies on protein detection in human bone are present. The challenges in bone ECM protein extraction and quantitation protocols are related to both the separation of proteins from the mineral content (i.e. hydroxyapatite) and the difficulty of avoiding protein denaturation during the extraction processes. The aim of the present work was to define appropriate protocol(s) for bone ECM protein extraction that could be applied to investigate both normal and pathological conditions. We compared and optimised some of the most used protocols present in the literature, modifying the protein precipitation method, the buffer used for resuspension and/or the volume of reagent used. Bradford and BCA assays and Western Blotting were used to evaluate the variations in the total protein recovery and the amount of selected proteins (Type I Collagen, TGF-ÎČ, IGF-1, Decorin, Osteopontin, Bone Sialoprotein-2 and Osteocalcin). Collectively, we were capable to draw-up two single-extract protocols with optimal recovery and ideal protein content, that can be used for a detailed analysis of ECM proteins in pathological bone samples. Time-consuming multi-extract procedures, optimised in their precipitation methods, are however crucial for a precise detection of specific proteins, like osteocalcin. As the matter of fact, also the demineralization processes, commonly suggested and performed in several protocols, could hinder an accurate protein detection, thus inherently affecting the study of a pathological bone ECM. This study represents a starting point for the definition of appropriate strategies in the study of bone extracellular matrix proteins involved in the onset and maintenance of bone diseases, as well as a tool for the development of customized scaffolds capable to modulate a proper feedback loop in bone remodelling, altered in case of diseases like osteoporosis

    Cis and trans effects differentially contribute to the evolution of promoters and enhancers

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    Background Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects are caused by genetic variants located on the same DNA molecule as the target gene, trans effects are due to genetic variants that affect diffusible elements. Previous studies have mostly assessed the impact of cis and trans effects at the gene level. However, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we use massively parallel reporter assays to directly measure the transcriptional outputs of thousands of individual regulatory elements in embryonic stem cells and measure cis and trans effects between human and mouse. Results Our approach reveals that cis effects are widespread across transcribed regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we find that trans effects are rare but stronger in enhancers than promoters and are associated with a subset of transcription factors that are differentially expressed between human and mouse. While we find that cis-trans compensation is common within promoters, we do not see evidence of widespread cis-trans compensation at enhancers. Cis-trans compensation is inversely correlated with enhancer redundancy, suggesting that such compensation may often occur across multiple enhancers. Conclusions Our results highlight differences in the mode of evolution between promoters and enhancers in complex mammalian genomes and indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.K.M. was a National Science Foundation Graduate Research Fellow under grant no. DGE1144152 during the majority of the project. M.M. was a Gilead Fellow of the Life Sciences Research Foundation during part of the project and is currently supported by the Spanish Ministry of Science and Innovation with a Ramon y Cajal grant (RYC-2017-22249). J.L.R. is an HHMI faculty scholar.Peer ReviewedPostprint (published version

    Biofabrication of bundles of poly(lactic acid)-collagen blends mimicking the fascicles of the human Achille tendon

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    Electrospinning is a promising technique for the production of scaffolds aimed at the regeneration of soft tissues. The aim of this work was to develop electrospun bundles mimicking the architecture and mechanical properties of the fascicles of the human Achille tendon. Two different blends of poly(L-lactic acid) (PLLA) and collagen (Coll) were tested, PLLA/Coll-75/25 and PLLA/Coll-50/50, and compared with bundles of pure PLLA. First, a complete physico-chemical characterization was performed on non-woven mats made of randomly arranged fibers. The presence of collagen in the fibers was assessed by thermogravimetric analysis, differential scanning calorimetry and water contact angle measurements. The collagen release in phosphate buffer solution (PBS) was evaluated for 14 days: results showed that collagen loss was about 50% for PLLA/Coll-75/25 and 70% for PLLA/Coll-50/50. In the bundles, the individual fibers had a diameter of 0.48 ±0.14 Όm (PLLA), 0.31 ±0.09 Όm (PLLA/Coll-75/25), 0.33 ±0.08 Όm (PLLA/Coll-50/50), whereas bundle diameter was in the range 300-500 Όm for all samples. Monotonic tensile tests were performed to measure the mechanical properties of PLLA bundles (as-spun) and of PLLA/Coll-75/25 and PLLA/Coll-50/50 bundles (as-spun, and after 48 h, 7 days and 14 days in PBS). The most promising material was the PLLA/Coll-75/25 blend with a Young modulus of 98.6 ±12.4 MPa (as-spun) and 205.1 ±73.0 MPa (after 14 days in PBS). Its failure stress was 14.2 ±0.7 MPa (as-spun) and 6.8 ±0.6 MPa (after 14 days in PBS). Pure PLLA withstood slightly lower stress than the PLLA/Coll-75/25 while PLLA/Coll-50/50 had a brittle behavior. Human-derived tenocytes were used for cellular tests. A good cell adhesion and viability after 14 day culture was observed. This study has therefore demonstrated the feasibility of fabricating electrospun bundles with multiscale structure and mechanical properties similar to the human tendon

    Study of the Adhesion of the Human Gut Microbiota on Electrospun Structures

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    Although the adhesion of bacteria on surfaces is a widely studied process, to date, most of the works focus on a single species of microorganisms and are aimed at evaluating the antimicrobial properties of biomaterials. Here, we describe how a complex microbial community, i.e., the human gut microbiota, adheres to a surface to form stable biofilms. Two electrospun structures made of natural, i.e., gelatin, and synthetic, i.e., polycaprolactone, polymers were used to study their ability to both promote the adhesion of the human gut microbiota and support microbial growth in vitro. Due to the different wettabilities of the two surfaces, a mucin coating was also added to the structures to decouple the effect of bulk and surface properties on microbial adhesion. The developed biofilm was quantified and monitored using live/dead imaging and scanning electron microscopy. The results indicated that the electrospun gelatin structure without the mucin coating was the optimal choice for developing a 3D in vitro model of the human gut microbiota

    Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency

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    Although many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we developed a clustering approach to infer mechanisms of action of lncRNA hits based on a variety of genomic features. We subsequently identified and validated FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and methodology described herein can be adapted to discover and characterize novel regulators of differentiation into any lineage
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