Gene‐Centric Metagenome Analysis Reveals Gene Clusters for Carbon Monoxide Conversion and Validates Isolation of a Clostridial Acetogen for C2 Chemical Production

Syngas fermentation is largely dependent on acetogens that occur in various anaerobic environmental samples including soil, sediment, and feces. Here the authors report the metagenomic isolation of acetogens for C2 chemical production from syngas. Screening acetogens for C2 chemical production typically involves detecting the presence of the Wood‐Ljungdahl Pathway for carbon monoxide conversion. The authors collect samples from river‐bed sediments potentially having conditions suitable for carbon monoxide‐converting anaerobes, and enrich the samples under carbon monoxide selection pressure. Changes in the microbial community during the experimental procedure are investigated using both amplicon and shotgun metagenome sequencing. Combined next‐generation sequencing techniques enabl in situ tracking of the major acetogenic bacterial group and lead to the discovery of a 16 kb of gene cluster for WLP. The authors isolat an acetogenic clostridial strain from the enrichment culture (strain H21‐9). The functional activity of H21‐9 is confirmed by its high level of production of C2 chemicals from carbon monoxide (77.4 mM acetate and 2.5 mM of ethanol). This approach of incorporating experimental enrichment with metagenomic analysis can facilitate the discovery of novel strains from environmental habitats by tracking target strains during the screening process, combined with validation of their functional activity.     

Mesocestoides corti (syn. vogae, cestoda): characterization of genes encoding cysteine-rich secreted proteins (CRISP)

With the aim of identifying genes involved in development and parasite adaptation in cestodes, four coding sequences were isolated from the cyclophyllidean Mesocestoides corti larval stage (tetrathyridium). Genes showed significant similarity to the cysteine-rich secreted protein (CRISP) encoding genes, a large family that includes stage and tissue-specific genes from diverse organisms, many associated with crucial biological processes. The full-length McCrisp2 cDNA encodes a predicted protein of 202 residues in length, containing 10 cysteines and a putative signal peptide. The expression level of McCrisp2 was estimated by Real-time PCR, relative to GAPDH, showing an increase of 75% in segmented worms compared to tetrathyridia. By in situ hybridization, McCrisp2 expression was localized mainly at the larvae apical region of tetrathyridia and in the proglottids of segmented worms. Taken together our results suggest a possible role for M. corti CRISP proteins as ES products, potentially involved in differentiation processes as proposed for homologs in other organisms.     

Exceptionally preserved North American Paleogene metatherians: adaptations and discovery of a major gap in the opossum fossil record

A major gap in our knowledge of the evolution of marsupial mammals concerns the Paleogene of the northern continents, a critical time and place to link the early history of metatherians in Asia and North America with the more recent diversification in South America and Australia. We studied new exceptionally well-preserved partial skeletons of the Early Oligocene fossil Herpetotherium from the White River Formation in Wyoming, which allowed us to test the relationships of this taxon and examine its adaptations. Herpetotheriidae, with a fossil record extending from the Cretaceous to the Miocene, has traditionally been allied with opossums (Didelphidae) based on fragmentary material, mainly dentitions. Analysis of the new material reveals that several aspects of the cranial and postcranial anatomy, some of which suggests a terrestrial lifestyle, distinguish Herpetotherium from opossums. We found that Herpetotherium is the sister group to the crown group Marsupialia and is not a stem didelphid. Combination of the new palaeontological data with molecular divergence estimates, suggests the presence of a long undocumented gap in the fossil record of opossums extending some 45Myr from the Early Miocene to the Cretaceous.     

Micropearls and other intracellular inclusions of amorphous calcium carbonate: an unsuspected biomineralization capacity shared by diverse microorganisms

An unsuspected biomineralization process, which produces intracellular inclusions of amorphous calcium carbonate (ACC), was recently discovered in unicellular eukaryotes. These mineral inclusions, called micropearls, can be highly enriched with other alkaline-earth metals (AEM) such as Sr and Ba. Similar intracellular inclusions of ACC have also been observed in prokaryotic organisms. These comparable biomineralization processes involving phylogenetically distant microorganisms are not entirely understood yet. This review gives a broad vision of the topic in order to establish a basis for discussion on the possible molecular processes behind the formation of the inclusions, their physiological role, the impact of these microorganisms on the geochemical cycles of AEM and their evolutionary relationship. Finally, some insights are provided to guide future research.     

The Response to Stimulation in Neurons and Astrocytes

Neurochemical Research - The brain uses mainly glucose as fuel with an index of glucose to oxygen utilization close to 6, the maximal index if all glucose was completely oxidized. However, this...     

Gestational jet lag predisposes to later-life skeletal and cardiac disease

Circadian rhythm disturbance (CRD) increases the risk of disease, e.g. metabolic syndrome, cardiovascular disease, and cancer. In the present study, we investigated later life adverse health effects triggered by repeated jet lag during gestation. Pregnant mice were subjected to a regular light-dark cycle (CTRL) or to a repeated delay (DEL) or advance (ADV) jet lag protocol. Both DEL and ADV offspring showed reduced weight gain. ADV offspring had an increased circadian period, and an altered response to a jet lag was observed in both DEL and ADV offspring. Analysis of the bones of adult male ADV offspring revealed reduced cortical bone mass and strength. Strikingly, analysis of the heart identified structural abnormalities and impaired heart function. Finally, DNA methylation analysis revealed hypermethylation of miR17-92 cluster and differential methylation within circadian clock genes, which correlated with altered gene expression. We show that developmental CRD affects the circadian system and predisposes to non-communicable disease in adult life.     

Functional Phenotype of Synovial Monocytes Modulating Inflammatory T-Cell Responses in Rheumatoid Arthritis (RA)

Monocytes function as crucial innate effectors in the pathogenesis of chronic inflammatory diseases, including autoimmunity, as well as in the inflammatory response against infectious pathogens. Human monocytes are heterogeneous and can be classified into three distinct subsets based on CD14 and CD16 expression. Although accumulating evidence suggests distinct functions of monocyte subsets in inflammatory conditions, their pathogenic roles in autoimmune diseases remain unclear. Thus, we investigated the phenotypic and functional characteristics of monocytes derived from synovial fluid and peripheral blood in RA patients in order to explore the pathogenic roles of these cells. In RA patients, CD14⁺CD16⁺, but not CD14^dimCD16⁺, monocytes are predominantly expanded in synovial fluid and, to a lesser degree, in peripheral blood. Expression of co-signaling molecules of the B7 family, specifically CD80 and CD276, was markedly elevated on synovial monocytes, while peripheral monocytes of RA and healthy controls did not express these molecules without stimulation. To explore how synovial monocytes might gain these unique properties in the inflammatory milieu of the synovial fluid, peripheral monocytes were exposed to various stimuli. CD16 expression on CD14⁺ monocytes was clearly induced by TGF-β, although co-treatment with IL-1β, TNF-α, or IL-6 did not result in any additive effects. In contrast, TLR stimulation with LPS or zymosan significantly downregulated CD16 expression such that the CD14⁺CD16⁺ monocyte subset could not be identified. Furthermore, treatment of monocytes with IFN-γ resulted in the induction of CD80 and HLA-DR expression even in the presence of TGF-β. An in vitro assay clearly showed that synovial monocytes possess the unique capability to promote Th1 as well as Th17 responses of autologous peripheral CD4 memory T cells. Our findings suggest that the cytokine milieu of the synovial fluid shapes the unique features of synovial monocytes as well as their cardinal role in shaping inflammatory T-cell responses in RA.     

Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer's disease

The redox co‐factor nicotinamide adenine dinucleotide (NAD) declines with age, and NAD deficits are specifically associated with dysfunctional energy metabolism in late‐onset Alzheimer''s disease (LOAD). Nicotinamide riboside (NR), a dietary NAD precursor, has been suggested to ameliorate the aging process or neurodegeneration. We assessed whether NR with or without caffeine, which increases nicotinamide mononucleotide transferase subtype 2 (NMNAT2), an essential enzyme in NAD production, modulates bioenergetic functions in LOAD. In LOAD patients—and young or old control individuals—derived dermal fibroblasts as well as in induced pluripotent stem cell‐differentiated neural progenitors and astrocytes, NR and caffeine cell type‐specifically increased the NAD pool, transiently enhanced mitochondrial respiration or glycolysis and altered the expression of genes in the NAD synthesis or consumption pathways. However, continued treatment led to reversed bioenergetic effects. Importantly, NR and caffeine did not alter the characteristics of a previously documented inherent LOAD‐associated bioenergetic phenotype. Thus, although NR and caffeine can partially restore diminished NAD availability, increasing NAD alone may not be sufficient to boost or restore energy metabolism in brain aging or alter aberrant energy management in LOAD. Nicotinamide riboside might still be of value in combination with other agents in preventive or therapeutic intervention strategies to address the aging process or age‐associated dementia.     

Differences in nutritional status between rural and urban Yucatec Maya children: The importance of early life conditions

Early-life conditions shape childhood growth and are affected by urbanization and the nutritional transition. To investigate how early-life conditions (across the “first” and “second” 1000 days) are associated with rural and urban children's nutritional status, we analyzed anthropometric data from Maya children in Yucatan, Mexico. We collected weight, height and triceps skinfold measures, then computed body mass and fat mass indices (BMI/FMI), in a cross-sectional sample of 6-year-olds (urban n = 72, rural n = 66). Demographic, socioeconomic and early-life variables (birthweight/mode, rural/urban residence, household crowding) were collected by maternal interview. We statistically analyzed rural-urban differences in demographic, socioeconomic, early-life, and anthropometric variables, then created linear mixed models to evaluate associations between early-life variables and child anthropometric outcomes. Two-way interactions were tested between early-life variables and child sex, and between early-life variables and rural-urban residence. Results showed that rural children were shorter-statured, with lower overweight/obesity and cesarean delivery rates, compared to urban children. Household crowding was a negative predictor of anthropometric outcomes; the strongest effect was in boys and in urban children. Birthweight positively predicted anthropometric outcomes, especially weight/BMI. Birth mode was positively (not statistically) associated with any anthropometric outcome. Cesarean delivery was more common in boys than in girls, and predicted increased height in urban boys. In conclusion, urbanization and household crowding were the most powerful predictors of Maya 6-year-old anthropometry. The negative effects of crowding may disproportionately affect Maya boys versus girls and urban versus rural children. Early-life conditions shape Maya children's nutritional status both in the “first” and “second” 1000 days.