This paper concerns the influence of the chemical structure on the physical properties of some polysaccharides. Especially, we proposed to discuss the role of the substituents on these properties. In ...some cases, non-carbohydrate substituents play a minor role on rheological properties in the presence of a salt excess as shown on xanthan and succinoglycan. The rheology of aqueous solution of these stereoregular polysaccharides is controlled by the conformation (helical conformation) whose stability is not largely influenced by these substituents. On the other hand, the interaction between galactomannan and xanthan depends on the presence of acetyl substituents on xanthan but also on the xanthan conformation. However, for polymers such as gellan, XM-6 or BEC 1615, complete deacetylation induces the ability to form physical gels in given thermodynamic conditions. The presence of carbohydrate substituents or short side chains was also examined. Especially in the gellan family, the role of position of substitution (position 3 on the glucose unit C or position 6 on the A glucose) was presented. It is concluded that the substituents giving the higher stability for the helical conformation (higher DeltaH and Tm values) also cause a lower salt sensitivity for the helical stability. The role of the substituents on the properties is also described for natural polymers and their chemically or enzymatically modified derivatives.
In this paper, the influence of the conditions of bleaching on initial ground algae is discussed; it is demonstrated that it favours the yield of extraction of purified alginates but that it causes ...chain degradation and a decrease of the M/G ratio. These events are attributed to the sensitivity to hydrolysis of MM and MG osidic linkages. Nevertheless, from all the results it is shown that four of these original algae (except
Sargassum sp. which has a M/G ratio around 1) from Madagascar are rich in guluronic units. Alginates obtained form strong gels in the presence of calcium (1
M CaCl
2) with ratios G′/G″ at 1
Hz larger than 6 (up to 8.6). In few cases, it is shown that bleaching favoured gel formation even if the molecular weight is decreased.
Pertussis toxin (PT) catalyzes ADP-ribosylation of G protein α subunits, thus preventing their role as transducers of external signals targeting metabolic pathways.
In vitro, in human circulating ...lymphocytes insulin at physiological concentrations (5 μU/ml) determines sharp activation of pyruvate dehydrogenase (PDH), the rate limiting enzyme in glucose oxidative breakdown. This study evaluates whether the above-described effects of insulin over PDH are mediated through G proteins. Human circulating lymphocytes (six samples from different donors) were exposed to insulin (5 μU/ml), PT (1–2 μg/ml) or PT-9K, a mutated PT void of catalytic activity (1–10 μg/ml), and to insulin in combination with the two toxins, and then assessed for PDH activity. Plasma membranes from cells incubated with and without PT or PT-9K were subjected to ADP-ribosylation in the presence of
32P NAD
+ and activated PT. In circulating lymphocytes exposed to PT alone, or in combination with insulin, PDH activity falls significantly below basal values (
P < 0.001); PT-9K instead has no effect on basal or on insulin-stimulated PDH activity. ADP-ribosylation of a plasma membrane component with apparent molecular mass (42 kDa) comparable to that of the Gi (inhibitory) protein α subunit takes place in cells exposed to PT but not in those exposed to PT-9K. In human circulating lymphocytes Gi proteins or Gi protein-like components appear to be involved in preserving basal PDH activity as well as in the mechanism by which insulin exerts its control over PDH.
There is an increasing call for local measures to adapt to climate change, based on foresight analyses in collaboration with actors. However, such analyses involve many challenges, particularly ...because the actors concerned may not consider climate change to be an urgent concern. This paper examines the methodological choices made by three research teams in the design and implementation of participatory foresight analyses to explore agricultural and water management options for adaptation to climate change. Case studies were conducted in coastal areas of France, Morocco, and Portugal where the groundwater is intensively used for irrigation, the aquifers are at risk or are currently overexploited, and a serious agricultural crisis is underway. When designing the participatory processes, the researchers had to address four main issues: whether to avoid or prepare dialogue between actors whose relations may be limited or tense; how to select participants and get them involved; how to facilitate discussion of issues that the actors may not initially consider to be of great concern; and finally, how to design and use scenarios. In each case, most of the invited actors responded and met to discuss and evaluate a series of scenarios. Strategies were discussed at different levels, from farming practices to aquifer management. It was shown that such participatory analyses can be implemented in situations which may initially appear to be unfavourable. This was made possible by the flexibility in the methodological choices, in particular the possibility of framing the climate change issue in a broader agenda for discussion with the actors.
The Hypoxia-inducible Factor (HIF) family of transcriptional regulators coordinates the expression of dozens of genes in response to oxygen deprivation. Mammalian development occurs in a hypoxic ...environment and HIF-null mice therefore die in utero due to multiple embryonic and placental defects. Mouse embryonic stem cells do not differentiate into placental cells; therefore, trophoblast stem cells (TSCs) are used to study mouse placental development. Consistent with a requirement for HIF activity during placental development in utero, TSCs derived from HIF-null mice exhibit severe differentiation defects and fail to form trophoblast giant cells (TGCs) in vitro. Interestingly, differentiating TSCs induce HIF activity independent of oxygen tension via unclear mechanisms. Here, we show that altering the extracellular matrix (ECM) composition upon which TSCs are cultured changes their differentiation potential from TGCs to multinucleated syncytiotropholasts (SynTs) and blocks oxygen-independent HIF induction. We further find that modulation of Mitogen Activated Protein Kinase Kinase-1/2 (MAP2K1/2, MEK-1/2) signaling by ECM composition is responsible for this effect. In the absence of ECM-dependent cues, hypoxia-signaling pathways activate this MAPK cascade to drive HIF induction and redirect TSC fate along the TGC lineage. In addition, we show that integrity of the microtubule and actin cytoskeleton is critical for TGC fate determination. HIF-2α ensures TSC cytoskeletal integrity and promotes invasive TGC formation by interacting with c-MYC to induce non-canonical expression of Lim domain kinase 1-an enzyme that regulates microtubule and actin stability, as well as cell invasion. Thus, we find that HIF can integrate positional and metabolic cues from within the TSC niche to regulate placental development by modulating the cellular cytoskeleton via non-canonical gene expression.
Hypoxia-inducible gene domain family member 1A (HIGD1A) is a survival factor induced by hypoxia-inducible factor 1 (HIF-1). HIF-1 regulates many responses to oxygen deprivation, but viable cells ...within hypoxic perinecrotic solid tumor regions frequently lack HIF-1α. HIGD1A is induced in these HIF-deficient extreme environments and interacts with the mitochondrial electron transport chain to repress oxygen consumption, enhance AMPK activity, and lower cellular ROS levels. Importantly, HIGD1A decreases tumor growth but promotes tumor cell survival in vivo. The human Higd1a gene is located on chromosome 3p22.1, where many tumor suppressor genes reside. Consistent with this, the Higd1a gene promoter is differentially methylated in human cancers, preventing its hypoxic induction. However, when hypoxic tumor cells are confronted with glucose deprivation, DNA methyltransferase activity is inhibited, enabling HIGD1A expression, metabolic adaptation, and possible dormancy induction. Our findings therefore reveal important new roles for this family of mitochondrial proteins in cancer biology.
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•HIGD1A protects from glucose deprivation but suppresses tumor growth•HIGD1A interacts with the electron transport chain to decrease respiration•HIGD1A can be induced independent of HIF-1 via differential methylation•HIGD1A may play roles in metabolic regulation of tumor dormancy
Hypoxia-inducible gene domain family member 1A (HIGD1A) is a hypoxia-inducible factor 1 (HIF-1) target found in perinecrotic tumor regions lacking HIF-1 expression. Ameri et al. now find it interacts with the electron transport chain to trigger mitochondrial ROS-dependent AMPK activation and reduces respiration and total ROS to promote survival and suppress growth.
This paper describes the behavior of some polysaccharides with well‐known chemical structures and in which the influence of cooperative secondary interactions play an important role. The roles played ...by hydrophobic and ionic interactions (including ionic selectivity) on polysaccharide conformation and gelation are discussed. Electrostatic attractions are also important in the complexes formed between surfactants and polyelectrolytes of opposite charge. Finally, van der Waals dipolar interactions and particularly hydrogen‐bond formation are examined. The role of hydrogen bonds in solubility, conformation, and especially the local stiffness of polysaccharides, but also in polymer–polymer complexes frequently obtained with polysaccharides, is developed.
Repeat unit for a number polysaccharides.
► Optimization of enzymatic deproteinization for chitin extraction. ► A high level of enzymatic deproteinization 88±5% was recorded. ► Chitin obtained was compared to chitin extracted by alkali ...deproteinization. ► The two chitins were converted to chitosans. ► Acetylation degrees and antibacterial activities of the two chitosans were compared.
Different crude microbial proteases were applied for chitin extraction from shrimp shells. A Box–Behnken design with three variables and three levels was applied in order to approach the prediction of optimal enzyme/substrate ratio, temperature and incubation time on the deproteinization degree with Bacillus mojavensis A21 crude protease. These optimal conditions were: an enzyme/substrate ratio of 7.75U/mg, a temperature of 60°C and an incubation time of 6h allowing to predict 94±4% deproteinization. Experimentally, in these optimized conditions, a deproteinization degree of 88±5% was obtained in good agreement with the prediction and larger than values generally given in literature. The deproteinized shells were then demineralized to obtain chitin which was converted to chitosan by deacetylation and its antibacterial activity against different bacteria was investigated. Results showed that chitosan dissolved at 50mg/ml markedly inhibited the growth of most Gram-negative and Gram-positive bacteria tested.
More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice ...could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.
•PRoXe is an open-source repository of leukemia and lymphoma xenografts•PDXs capture transcriptional, genetic, and phenotypic disease diversity•Randomized phase II-like preclinical drug trials are feasible using PDXs•PDXs facilitate biomarker development and testing of relapsed/refractory disease
Townsend et al. create a large, publicly available repository of leukemia and lymphoma patient-derived xenografts with well-characterized molecular and clinical information, and illustrate the utility of this repository by performing a preclinical in vivo study that mimics randomized human clinical trials.
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