A role for suppressed thermogenesis favoring catch-up fat in the pathophysiology of catch-up growth

Catch-up growth is a risk factor for later obesity, type 2 diabetes, and cardiovascular diseases. We show here that after growth arrest by semistarvation, rats refed the same amount of a low-fat diet as controls show 1) lower energy expenditure due to diminished thermogenesis that favors accelerated fat deposition or catch-up fat and 2) normal glucose tolerance but higher plasma insulin after a glucose load at a time point when their body fat and plasma free fatty acids (FFAs) have not exceeded those of controls. Isocaloric refeeding on a high-fat diet resulted in even lower energy expenditure and thermogenesis and increased fat deposition and led to even higher plasma insulin and elevated plasma glucose after a glucose load. Stepwise regression analysis showed that plasma insulin and insulin-to-glucose ratio after the glucose load are predicted by variations in efficiency of energy use (i.e., in thermogenesis) rather than by the absolute amount of body fat or plasma FFAs. These studies suggest that suppression of thermogenesis per se may have a primary role in the development of hyperinsulinemia and insulin resistance during catch-up growth and underscore a role for suppressed thermogenesis directed specifically at catch-up fat in the link between catch-up growth and chronic metabolic diseases

Carboxy-Terminal Truncation Activates glp-1 Protein to Specify Vulval Fates in Caenorhabditis elegans

The glp-1 and lin-12 genes encode homologous transmembrane proteins that may act as receptors for cell interactions during development. The glp-1 product is required for induction of germ-line proliferation and for embryogenesis. By contrast, lin-12 mediates somatic cell interactions, including those between the precursor cells that form the vulval hypodermis (VPCs). Here we analyse an unusual allele of glp-1, glp-1(q35), which displays a semidominant multivulva phenotype (Muv), as well as the typical recessive, loss-of-function Glp phenotypes (sterility and embryonic lethality). We find that the effects of glp-1(q35) on VPC development mimic those of dominant lin-12 mutations, even in the absence of lin-12 activity. The glp-1(q35) gene bears a nonsense mutation predicted to eliminate the 122 C-terminal amino acids, including a ProGluSerThr (PEST) sequence thought to destabilize proteins. We suggest that the carboxy terminus bears a negative regulatory domain which normally inactivates glp-1 in the VPCs. We propose that inappropriate glp-1(q35) activity can substitute for lin-12 to determine vulval fate, perhaps by driving the VPCs to proliferate

The contribution of Swiss scientists to the assessment of energy metabolism

Although Switzerland is considered a small country, it has its share in discoveries, inventions and developments for the assessment of energy metabolism. This includes seminal contributions to respiratory and metabolic physiology and to devices for measuring energy expenditure by direct and indirect calorimetry in vivo in humans and small animals (as well as in vitro in organs/tissues), for the purpose of evaluating the basic nutritional requirements. A strong momentum came during World War II when it was necessary to evaluate the energy requirements of soldiers protecting the country by assessing their energy expenditure, as well as to determine the nutritional needs of the Swiss civil population in time of war when food rationing was necessary to ensure national neutrality and independence. A further impetus came in the 1970s at the start of the obesity epidemics, toward a better understanding of the metabolic basis of obesity, ranging from the development of whole-body concepts to molecular mechanisms. In a trip down memory lane, this review focuses on some of the earlier leading Swiss scientists who have contributed to a better understanding of the field

Selective inhibition of anti-MAG IgM autoantibody binding to myelin by an antigen-specific glycopolymer.

Anti-myelin-associated glycoprotein (MAG) neuropathy is a disabling autoimmune peripheral neuropathy that is caused by circulating monoclonal IgM autoantibodies directed against the human natural killer-1 (HNK-1) epitope. This carbohydrate epitope is highly expressed on adhesion molecules such as MAG, a glycoprotein present in myelinated nerves. We previously showed the therapeutic potential of the glycopolymer poly(phenyl disodium 3-O-sulfo-β-d-glucopyranuronate)-(1→3)-β-d-galactopyranoside (PPSGG) in selectively neutralizing anti-MAG IgM antibodies in an immunological mouse model and ex vivo with sera from anti-MAG neuropathy patients. PPSGG is composed of a biodegradable backbone that multivalently presents a mimetic of the HNK-1 epitope. In this study, we further explored the pharmacodynamic properties of the glycopolymer and its ability to inhibit the binding of anti-MAG IgM to peripheral nerves. The polymer selectively bound anti-MAG IgM autoantibodies and prevented the binding of patients' anti-MAG IgM antibodies to myelin of non-human primate sciatic nerves. Upon PPSGG treatment, neither activation nor inhibition of human and murine peripheral blood mononuclear cells nor alteration of systemic inflammatory markers was observed in mice or ex vivo in human peripheral blood mononuclear cells. Intravenous injections of PPSGG to mice immunized against the HNK-1 epitope removed anti-MAG IgM antibodies within less than 1 hr, indicating a fast and efficient mechanism of action as compared to a B-cell depletion with anti-CD20. In conclusion, these observations corroborate the therapeutic potential of PPSGG for an antigen-specific treatment of anti-MAG neuropathy. Read the Editorial Highlight for this article on page 465

Nucleologenesis in the Caenorhabditis elegans Embryo

In the Caenorhabditis elegans nematode, the oocyte nucleolus disappears prior to fertilization. We have now investigated the re-formation of the nucleolus in the early embryo of this model organism by immunostaining for fibrillarin and DAO-5, a putative NOLC1/Nopp140 homolog involved in ribosome assembly. We find that labeled nucleoli first appear in somatic cells at around the 8-cell stage, at a time when transcription of the embryonic genome begins. Quantitative analysis of radial positioning showed the nucleolus to be localized at the nuclear periphery in a majority of early embryonic nuclei. At the ultrastructural level, the embryonic nucleolus appears to be composed of a relatively homogenous core surrounded by a crescent-shaped granular structure. Prior to embryonic genome activation, fibrillarin and DAO-5 staining is seen in numerous small nucleoplasmic foci. This staining pattern persists in the germline up to the ∼100-cell stage, until the P4 germ cell divides to give rise to the Z2/Z3 primordial germ cells and embryonic transcription is activated in this lineage. In the ncl-1 mutant, which is characterized by increased transcription of rDNA, DAO-5-labeled nucleoli are already present at the 2-cell stage. Our results suggest a link between the activation of transcription and the initial formation of nucleoli in the C. elegans embryo

Internet of things

Manual of Digital Earth / Editors: Huadong Guo, Michael F. Goodchild, Alessandro Annoni .- Springer, 2020 .- ISBN: 978-981-32-9915-3Digital Earth was born with the aim of replicating the real world within the digital world. Many efforts have been made to observe and sense the Earth, both from space (remote sensing) and by using in situ sensors. Focusing on the latter, advances in Digital Earth have established vital bridges to exploit these sensors and their networks by taking location as a key element. The current era of connectivity envisions that everything is connected to everything. The concept of the Internet of Things(IoT)emergedasaholisticproposaltoenableanecosystemofvaried,heterogeneous networked objects and devices to speak to and interact with each other. To make the IoT ecosystem a reality, it is necessary to understand the electronic components, communication protocols, real-time analysis techniques, and the location of the objects and devices. The IoT ecosystem and the Digital Earth (DE) jointly form interrelated infrastructures for addressing today’s pressing issues and complex challenges. In this chapter, we explore the synergies and frictions in establishing an efficient and permanent collaboration between the two infrastructures, in order to adequately address multidisciplinary and increasingly complex real-world problems. Although there are still some pending issues, the identified synergies generate optimism for a true collaboration between the Internet of Things and the Digital Earth

Geochronological and thermometric evidence of unusually hot fluids in an Alpine fissure of Lauzière granite (Belledonne, Western Alps)

A multi-method investigation into Lauzière granite, located in the external Belledonne massif of the French Alps, reveals unusually hot hydrothermal conditions in vertical open fractures (Alpine-type clefts). The host-rock granite shows sub-vertical mylonitic microstructures and partial retrogression at temperatures of &lt;&thinsp;400&thinsp;∘C during Alpine tectonometamorphism. Novel zircon fission-track (ZFT) data in the granite give ages at 16.3&thinsp;±&thinsp;1.9 and 14.3&thinsp;±&thinsp;1.6&thinsp;Ma, confirming that Alpine metamorphism was high enough to reset the pre-Alpine cooling ages and that the Lauzière granite had already cooled below 240–280&thinsp;∘C and was exhumed to &lt;&thinsp;10&thinsp;km at that time. Novel microthermometric data and chemical compositions of fluid inclusions obtained on millimetric monazite and on quartz crystals from the same cleft indicate early precipitation of monazite from a hot fluid at T&thinsp;&gt;&thinsp;410&thinsp;∘C, followed by a main stage of quartz growth at 300–320&thinsp;∘C and 1.5–2.2&thinsp;kbar. Previous Th-Pb dating of cleft monazite at 12.4&thinsp;±&thinsp;0.1&thinsp;Ma clearly indicates that this hot fluid infiltration took place significantly later than the peak of the Alpine metamorphism. Advective heating due to the hot fluid flow caused resetting of fission tracks in zircon in the cleft hanging wall, with a ZFT age at 10.3&thinsp;±&thinsp;1.0&thinsp;Ma. The results attest to the highly dynamic fluid pathways, allowing the circulation of deep mid-crustal fluids, 150–250&thinsp;∘C hotter than the host rock, which affect the thermal regime only at the wall rock of the Alpine-type cleft. Such advective heating may impact the ZFT data and represent a pitfall for exhumation rate reconstructions in areas affected by hydrothermal fluid flow.</p