Towards robust regional estimates of CO2 sources and sinks using atmospheric transport models

Information about regional carbon sources and sinks can be derived from variations in observed atmospheric CO2 concentrations via inverse modelling with atmospheric tracer transport models. A consensus has not yet been reached regarding the size and distribution of regional carbon fluxes obtained using this approach, partly owing to the use of several different atmospheric transport models. Here we report estimates of surface-atmosphere CO2 fluxes from an intercomparison of atmospheric CO2 inversion models (the TransCom 3 project), which includes 16 transport models and model variants. We find an uptake of CO2 in the southern extratropical ocean less than that estimated from ocean measurements, a result that is not sensitive to transport models or methodological approaches. We also find a northern land carbon sink that is distributed relatively evenly among the continents of the Northern Hemisphere, but these results show some sensitivity to transport differences among models, especially in how they respond to seasonal terrestrial exchange of CO2. Overall, carbon fluxes integrated over latitudinal zones are strongly constrained by observations in the middle to high latitudes. Further significant constraints to our understanding of regional carbon fluxes will therefore require improvements in transport models and expansion of the CO2 observation network within the tropics.     

Heterozygous TGFBR2 mutations in Marfan syndrome

Marfan syndrome is an extracellular matrix disorder with cardinal manifestations in the eye, skeleton and cardiovascular systems associated with defects in the gene encoding fibrillin (FBN1) at 15q21.1 (ref. 1). A second type of the disorder (Marfan syndrome type 2; OMIM 154705) is associated with a second locus, MFS2, at 3p25-p24.2 in a large French family (family MS1). Identification of a 3p24.1 chromosomal breakpoint disrupting the gene encoding TGF-beta receptor 2 (TGFBR2) in a Japanese individual with Marfan syndrome led us to consider TGFBR2 as the gene underlying association with Marfan syndrome at the MSF2 locus. The mutation 1524G-->A in TGFBR2 (causing the synonymous amino acid substitution Q508Q) resulted in abnormal splicing and segregated with MFS2 in family MS1. We identified three other missense mutations in four unrelated probands, which led to loss of function of TGF-beta signaling activity on extracellular matrix formation. These results show that heterozygous mutations in TGFBR2, a putative tumor-suppressor gene implicated in several malignancies, are also associated with inherited connective-tissue disorders.     

Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome

Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. It phenotypically overlaps with Noonan and Costello syndrome, which are caused by mutations in PTPN11 and HRAS, respectively. In 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders.     

TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome

A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations. TGFB2 encodes transforming growth factor (TGF)-β2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-β2 expression and immunostaining. Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-β2 levels leading to a secondary increase in TGF-β2 production in the diseased aorta.     

ING1 and ING2: multifaceted tumor suppressor genes

Inhibitor of Growth 1 (ING1) was identified and characterized as a “candidate” tumor suppressor gene in 1996. Subsequently, four more genes, also characterized as “candidate” tumor suppressor genes, were identified by homology search: ING2, ING3, ING4, and ING5. The ING proteins are characterized by a high homology in their C-terminal domain, which contains a Nuclear Localization Sequence and a Plant HomeoDomain (PHD), which has a high affinity to Histone 3 tri-methylated on lysine 4 (H3K4Me3). The ING proteins have been involved in the control of cell growth, senescence, apoptosis, chromatin remodeling, and DNA repair. Within the ING family, ING1 and ING2 form a subgroup since they are evolutionarily and functionally close. In yeast, only one gene, Pho23, is related to ING1 and ING2 and possesses also a PHD. Recently, the ING1 and ING2 tumor suppressor status has been fully established since several studies have described the loss of ING1 and ING2 protein expression in human tumors and both ING1 and ING2 knockout mice were reported to have spontaneously developed tumors, B cell lymphomas, and soft tissue sarcomas, respectively. In this review, we will describe for the first time what is known about the ING1 and ING2 genes, proteins, their regulations in both human and mice, and their status in human tumors. Furthermore, we explore the current knowledge about identified functions involving ING1 and ING2 in tumor suppression pathways especially in the control of cell cycle and in genome stability.     

Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility

The World Health Organization conservatively estimates that 80 million people suffer from infertility worldwide. Male factors are believed to be responsible for 20-50% of all infertility cases, but microdeletions of the Y chromosome are the only genetic defects altering human spermatogenesis that have been reported repeatedly. We focused our work on infertile men with a normal somatic karyotype but typical spermatozoa mainly characterized by large heads, a variable number of tails and an increased chromosomal content (OMIM 243060). We performed a genome-wide microsatellite scan on ten infertile men presenting this characteristic phenotype. In all of these men, we identified a common region of homozygosity harboring the aurora kinase C gene (AURKC) with a single nucleotide deletion in the AURKC coding sequence. In addition, we show that this founder mutation results in premature termination of translation, yielding a truncated protein that lacks the kinase domain. We conclude that the absence of AURKC causes male infertility owing to the production of large-headed multiflagellar polyploid spermatozoa.     

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders

SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders.     

Fungal lipochitooligosaccharide symbiotic signals in arbuscular mycorrhiza

Arbuscular mycorrhiza (AM) is a root endosymbiosis between plants and glomeromycete fungi. It is the most widespread terrestrial plant symbiosis, improving plant uptake of water and mineral nutrients. Yet, despite its crucial role in land ecosystems, molecular mechanisms leading to its formation are just beginning to be unravelled. Recent evidence suggests that AM fungi produce diffusible symbiotic signals. Here we show that Glomus intraradices secretes symbiotic signals that are a mixture of sulphated and non-sulphated simple lipochitooligosaccharides (LCOs), which stimulate formation of AM in plant species of diverse families (Fabaceae, Asteraceae and Umbelliferae). In the legume Medicago truncatula these signals stimulate root growth and branching by the symbiotic DMI signalling pathway. These findings provide a better understanding of the evolution of signalling mechanisms involved in plant root endosymbioses and will greatly facilitate their molecular dissection. They also open the way to using these natural and very active molecules in agriculture.     

Irregular tropical glacier retreat over the Holocene epoch driven by progressive warming

The causes and timing of tropical glacier fluctuations during the Holocene epoch (10,000 years ago to present) are poorly understood. Yet constraining their sensitivity to changes in climate is important, as these glaciers are both sensitive indicators of climate change and serve as water reservoirs for highland regions. Studies have so far documented extra-tropical glacier fluctuations, but in the tropics, glacier-climate relationships are insufficiently understood. Here we present a (10)Be chronology for the past 11,000?years (11?kyr), using 57 moraines from the Bolivian Telata glacier (in the Cordillera Real mountain range). This chronology indicates that Telata glacier retreated irregularly. A rapid and strong melting from the maximum extent occurred from 10.8?±?0.9 to 8.5?±?0.4?kyr ago, followed by a slower retreat until the Little Ice Age, about 200 years ago. A dramatic increase in the rate of retreat occurred over the twentieth century. A glacier-climate model indicates that, relative to modern climate, annual mean temperature for the Telata glacier region was -3.3?±?0.8 °C cooler at 11?kyr ago and remained -2.1?±?0.8 °C cooler until the end of the Little Ice Age. We suggest that long-term warming of the eastern tropical Pacific and increased atmospheric temperature in response to enhanced austral summer insolation were the main drivers for the long-term Holocene retreat of glaciers in the southern tropics.