Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis

Calreticulin (crt) is an ubiquitously expressed and multifunctional Ca2+-binding protein that regulates diverse vital cell functions, including Ca2+ storage in the ER and protein folding. Calreticulin deficiency in mice is lethal in utero due to defects in heart development and function. Herein, we used crt−/− embryonic stem (ES) cells differentiated in vitro into cardiac cells to investigate the molecular mechanisms underlying heart failure of knockout embryos. After 8 d of differentiation, beating areas were prominent in ES-derived wild-type (wt) embryoid bodies (EBs), but not in ES-derived crt−/− EBs, despite normal expression levels of cardiac transcription factors. Crt−/− EBs exhibited a severe decrease in expression and a lack of phosphorylation of ventricular myosin light chain 2 (MLC2v), resulting in an impaired organization of myofibrils. Crt−/− phenotype could be recreated in wt cells by chelating extracellular or cytoplasmic Ca2+ with EGTA or BAPTA, or by inhibiting Ca2+/calmodulin-dependent kinases (CaMKs). An imposed ionomycin-triggered cystolic-free Ca2+ concentration ([Ca2+]c) elevation restored the expression, phosphorylation, and insertion of MLC2v into sarcomeric structures and in turn the myofibrillogenesis. The transcription factor myocyte enhancer factor C2 failed to accumulate into nuclei of crt−/− cardiac cells in the absence of ionomycin-triggered [Ca2+]c increase. We conclude that the absence of calreticulin interferes with myofibril formation. Most importantly, calreticulin deficiency revealed the importance of a Ca2+-dependent checkpoint critical for early events during cardiac myofibrillogenesis

Mineral maturity and crystallinity index are distinct characteristics of bone mineral

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2–4 lm thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis

Antarctic climate, Southern Ocean circulation patterns, and deep water formation during the Eocene

We assess early-to-middle Eocene seawater neodymium (Nd) isotope records from seven Southern Ocean deep-sea drill sites to evaluate the role of Southern Ocean circulation in long-term Cenozoic climate change. Our study sites are strategically located on either side of the Tasman Gateway and are positioned at a range of shallow (Nd(t) = −9.3 ± 1.5). IODP Site U1356 off the coast of Adélie Land, a locus of modern-day Antarctic Bottom Water production, is identified as a site of persistent deep water formation from the early Eocene to the Oligocene. East of the Tasman Gateway an additional local source of intermediate/deep water formation is inferred at ODP Site 277 in the SW Pacific Ocean (εNd(t) = −8.7 ± 1.5). Antarctic-proximal shelf sites (ODP Site 1171 and Site U1356) reveal a pronounced erosional event between 49 and 48 Ma, manifested by ~2 εNd unit negative excursions in seawater chemistry toward the composition of bulk sediments at these sites. This erosional event coincides with the termination of peak global warmth following the Early Eocene Climatic Optimum and is associated with documented cooling across the study region and increased export of Antarctic deep waters, highlighting the complexity and importance of Southern Ocean circulation in the greenhouse climate of the Eocene

A Gigantic Shark from the Lower Cretaceous Duck Creek Formation of Texas

Author Contributions Conceived and designed the experiments: JAF SNS JAD-F. Analyzed the data: JAF SNS. Wrote the paper: JAF SNS. Site data for OMNH V1727 are available by request from the department of vert. paleontology at the (SN)OMNH.Three large lamniform shark vertebrae are described from the Lower Cretaceous of Texas. We interpret these fossils as belonging to a single individual with a calculated total body length of 6.3 m. This large individual compares favorably to another shark specimen from the roughly contemporaneous Kiowa Shale of Kansas. Neither specimen was recovered with associated teeth, making confident identification of the species impossible. However, both formations share a similar shark fauna, with Leptostyrax macrorhiza being the largest of the common lamniform sharks. Regardless of its actual identification, this new specimen provides further evidence that large-bodied lamniform sharks had evolved prior to the Late Cretaceous.Ye

Effect of changes in d18O content of the surface ocean on estimated sea surface in past warm climate.

7 pagesInternational audienceUsing a coupled climate model of intermediate complexity including oxygen 18, CLIMBER-2, we investigate the evolution of the distribution of surface water $^{18}$O composition under warm climate conditions. We then determine the impact of changes of the surface water $^{18}$O distribution on ocean surface temperatures inferred from calcite oxygen 18. Our results show that published temperature reconstructions based on oxygen 18 from calcite are systematically biased by 2° to 4°C in the absence of major oceanic circulation changes and up to 7°C in the presence of major oceanic circulation changes. As the bias introduced is shown to vary with latitude, our work has major implications on past latitudinal temperature gradient reconstructions based on oxygen 18 measurements

Late Cretaceous erosion and chemical weathering record in the offshore Cape Basin: source-to-sink system from Hf Nd isotopes and clay mineralogy.

International audienceSource-to-sink research has often used sediment fluxes as a fundamental parameter when seeking to understand the perturbations caused by tectonics or climate. This parameter is often interpreted only in terms of erosion rates, dismissing the component exerted by chemical weathering. In this study, we characterize sediments from the Deep Surface Drilling Program core 361 (DSDP 361) located in the Cape basin to show the evolution of both, physical erosion and silicate chemical weathering, during the late Cretaceous (100.5–66 Ma) in the source-to-sink system consisting of the South African plateau and the Cape Basin. Transmission Electron Microscopy (TEM) images and trace element analyses indicate that detrital clays predominate within the site and thus reflect variations in surface continental processes. Clay mineralogy shows a predominance of detrital smectite (60–98%) throughout the section. However, an increase in primary clay minerals, in particular illite (20%), indicates a relative enhancement in physical erosion, while an increase in palygorskite (10%) indicates regional climate aridification during the Campanian–Danian interval (ca. 77–62 Ma). Concomitant to this enhancement, we observe both, more radiogenic Hf isotopic compositions and less radiogenic Nd isotopic compositions in the clay fractions (< 2 μm). These variations can be respectively associated to an increase in silicate chemical weathering and the incorporation of unradiogenic material, likely related to the orogenic belts present on the western-south margin of Southern Africa. The regional aridification and the global climate cooling trend observed on δ18O benthic foraminifera records do not appear as suitable mechanisms for the increase in physical erosion and silicate chemical weathering observed. Our results, together with the reported increase in sedimentation rates and the reported tectonic uplift between 80 and 70 Ma, suggest that it is tectonic activity and not climate the main driver in the enhancement of denudation processes. Furthermore, our data suggests that such uplift episode could have impacted the regional climate by causing a rain-shadow effect, with an inland aridification suggested by the increase in palygorskite proportions. The increase in silicate chemical weathering suggested by our new dataset begins in the Campanian (ca. 77 Ma), later than the onset of the global climatic cooling trend that occurs from the Turonian onward. If enhanced weathering of the South African Plateau may not have triggered the recorded climatic cooling, it may still have contributed to maintain cooler conditions in the Campanian-Danian interval

Concise Review: Pluripotent Stem Cell-Derived Cardiac Cells, A Promisingă Cell Source for Therapy of Heart Failure: Where Do We Stand?

International audienceHeart failure is still a major cause of hospitalization and mortality ină developed countries. Many clinical trials have tested the use ofă multipotent stem cells as a cardiac regenerative medicine. The benefită for the patients of this therapeutic intervention has remained limited.ă Herein, we review the pluripotent stem cells as a cell source foră cardiac regeneration. We more specifically address the variousă challenges of this cell therapy approach. We question the cell deliveryă systems, the immune tolerance of allogenic cells, the potentială proarrhythmic effects, various drug mediated interventions to facilitateă cell grafting and, finally, we describe the pathological conditions thată may benefit from such an innovative approach. As members of aă transatlantic consortium of excellence of basic science researchers andă clinicians, we propose some guidelines to be applied to cell types andă modes of delivery in order to translate pluripotent stem cell cardiacă derivatives into safe and effective clinical trials