Tolerance of young allis shad Alosa alosa (Clupeidae) to oxy-thermic stress

The ecology of the young stages of allis shad Alosa alosa is poorly documented, although they can be exposed to many pressures during their freshwater phase and their downstream migration. When passing through systems such as the Gironde-Garonne-Dordogne watershed (GGD, SW France), they can be subjected to high temperatures and low levels of oxygen (hypoxia). The aim of this work is to assess the tolerance of young Alosa alosa at four ages (c. 10, 30, 60 and 85 days old) by challenging them to different temperatures (18, 22, 26 and 28°C) together with decreasing oxygen saturation levels (from 100% to 30%). Survival of the 10-day-old individuals was not influenced by oxy-thermic conditions, but high stress levels were detected and perhaps this age class was too fragile regarding the constraint of the experimental design. Survival at 30 and at 60 days old was negatively influenced by the highest temperatures tested alone (from 26°C and from 28°C, respectively) but no effect was detected at 85 days old up to 28°C. A combined effect of temperature and oxygen level was highlighted, with heat accelerating survival decrease when associated with oxygen level depletion: essentially, survival was critical (<50%) at 30 days old at temperature ≥22°C together with 30% O₂; at 60 days old, at temperature = 28°C with 30% O₂; at 85 days old, at temperature ≥26°C with ≤40% O₂. Tolerance to oxy-thermic pressures appeared to be greater among the migratory ages (60 and 85 days old) than among the 30-day-old group. Based on environmental data recorded in the GGD system and on our experimental results, an exploratory analysis allowed a discussion of the possible impact of past oxy-thermic conditions on the local population dynamics between 2005 and 2018. The oxy-thermic conditions that may affect Alosa alosa at ages when they migrate downstream (60 and 85 days old) were not frequently recorded in this period, except in cases of extreme episodes of heat together with hypoxia that occurred in some years, in summertime in the turbidity maximum zone of the Gironde estuary (particularly in the year 2006). Interestingly, oxy-thermic conditions that are likely to threaten the 30-day-old individuals occurred more frequently in the lower freshwater parts of the GGD system between the years 2005 and 2018. In the context of climate change, a general increase in temperature is predicted, as well as more frequent and severe hypoxic events, therefore we suggest that local Alosa alosa population recruitment could encounter critical oxy-thermic conditions more frequently in the future if no adaptive management of water resources occurs.     

Estimating regional carbon stocks and spatially covarying edaphic factors using soil maps at three scales

Most estimates of regional and global soil carbon stocks are based on extrapolations of mean soil C contents for broad categories of soil or vegetation types. Uncertainties exist in both the estimates of mean soil C contents and the area over which each mean should be extrapolated. Geographic information systems now permit spatially referenced estimates of soil C at finer scales of resolution than were previously practical. We compared estimates of total soil C stocks of the state of Maine using three methods: (1) multiplying the area of the state by published means of soil C for temperate forests and for Spodosols; (2) calculating areas of inclusions of soil taxa in the 1:5,000,000 FAO/UNESCO Soils Map of the World and multiplying those areas by selected mean carbon contents; and (3) calculating soil C for each soil series and map unit in the 1:250,000 State Soil Geographic Data Base (STATSGO) and summing these estimates for the entire state. The STATSGO estimate of total soil C was between 23% and 49% higher than the common coarse scale extrapolations, primarily because STATSGO included data on Histosols, which cover less than 5% of the area of the state, but which constitute over one-third of the soil C. Spodosols cover about 65% of the state, but contribute less than 39% of the soil C. Estimates of total soil C in Maine based on the FAO map agreed within 8% of the STATSGO estimate for one possible matching of FAO soil taxa with data on soil C, but another plausible matching overestimated soil C stocks. We also compared estimates from the 1:250,000 STATSGO database and from the 1:20,000 Soil Survey Geographic Data Base (SSURGO) for a 7.5 minute quadrangle within the state. SSURGO indicated 13% less total soil C than did STATSGO, largely because the attribute data on depths of soil horizons in SSURGO are more specific for this locality. Despite localized differences, the STATSGO database offers promise of scaling up county soil survey data to regional scales because it includes attribute data and estimates of areal coverage of C-rich inclusions within map units. The spatially referenced data also permit examination of covariation of soil C stocks with soil properties thought to affect stabilization of soil C. Clay content was a poor predictor of soil C in Maine, but drainage class covaried significantly with soil C across the state.     

Genetics and epigenetics of 1q rearrangements in hematological malignancies

Recently, we and others have described a novel class of chromosome aberrations that involves constitutive heterochromatin on human chromosome 1 (cytogenetic band 1q12). These anomalies are particularly frequent in B cell non-Hodgkins lymphoma (NHL) and multiple myeloma (MM) and, remarkably, almost invariably involve partial or total gain of chromosome 1q (including 1q12 heterochromatin) and the formation of novel heterochromatin/euchromatin junctions. This review discusses the pathological significance of these anomalies in light of i) recent integrated gene expression and array comparative genomic hybridisation (aCGH) profiling in MM and ii) increasing evidence of a key role for heterochromatin in the control of normal and pathological gene silencing.     

Cloning and characterization of the rat homologues of the Inhibitor of Apoptosis protein 1, 2, and 3 genes.

Background  

Inhibitor of Apoptosis (IAP) proteins are key intrinsic regulators of apoptosis induced by a variety of triggers. We isolated the rat Inhibitor of Apoptosis genes 1, 2 and 3 and characterized their tissue distribution and expression.     

Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.     

Inhibition of S-phase progression triggered by UVA-induced ROS does not require a functional DNA damage checkpoint response in mammalian cells

Ultraviolet A (UVA) radiation represents more than 90% of the UV spectrum reaching Earth's surface. Exposure to UV light, especially the UVA part, induces the formation of photoexcited states of cellular photosensitizers with subsequent generation of reactive oxygen species (ROS) leading to damages to membrane lipids, proteins and nucleic acids. Although UVA, unlike UVC and UVB, is poorly absorbed by DNA, it inhibits cell cycle progression, especially during S-phase. In the present study, we examined the role of the DNA damage checkpoint response in UVA-induced inhibition of DNA replication. We provide evidence that UVA delays S-phase in a dose dependent manner and that UVA-irradiated S-phase cells accumulate in G2/M. We show that upon UVA irradiation ATM-, ATR- and p38-dependent signalling pathways are activated, and that Chk1 phosphorylation is ATR/Hus1 dependent while Chk2 phosphorylation is ATM dependent. To assess for a role of these pathways in UVA-induced inhibition of DNA replication, we investigated (i) cell cycle progression of BrdU labelled S-phase cells by flow cytometry and (ii) incorporation of [methyl-(3)H]thymidine, as a marker of DNA replication, in ATM, ATR and p38 proficient and deficient cells. We demonstrate that none of these pathways is required to delay DNA replication in response to UVA, thus ruling out a role of the canonical S-phase checkpoint response in this process. On the contrary, scavenging of UVA-induced reactive oxygen species (ROS) by the antioxidant N-acetyl-l-cystein or depletion of vitamins during UVA exposure significantly restores DNA synthesis. We propose that inhibition of DNA replication is due to impaired replication fork progression, rather as a consequence of UVA-induced oxidative damage to protein than to DNA.     

A unique voltage sensor sensitizes the potassium channel AKT2 to phosphoregulation

Among all voltage-gated K+ channels from the model plant Arabidopsis thaliana, the weakly rectifying K+ channel (K(weak) channel) AKT2 displays unique gating properties. AKT2 is exceptionally regulated by phosphorylation: when nonphosphorylated AKT2 behaves as an inward-rectifying potassium channel; phosphorylation of AKT2 abolishes inward rectification by shifting its activation threshold far positive (>200 mV) so that it closes only at voltages positive of +100 mV. In its phosphorylated form, AKT2 is thus locked in the open state in the entire physiological voltage range. To understand the molecular grounds of this unique gating behavior, we generated chimeras between AKT2 and the conventional inward-rectifying channel KAT1. The transfer of the pore from KAT1 to AKT2 altered the permeation properties of the channel. However, the gating properties were unaffected, suggesting that the pore region of AKT2 is not responsible for the unique K(weak) gating. Instead, a lysine residue in S4, highly conserved among all K(weak) channels but absent from other plant K+ channels, was pinpointed in a site-directed mutagenesis approach. Substitution of the lysine by serine or aspartate abolished the "open-lock" characteristic and converted AKT2 into an inward-rectifying channel. Interestingly, phosphoregulation of the mutant AKT2-K197S appeared to be similar to that of the K(in) channel KAT1: as suggested by mimicking the phosphorylated and dephosphorylated states, phosphorylation induced a shift of the activation threshold of AKT2-K197S by about +50 mV. We conclude that the lysine residue K197 sensitizes AKT2 to phosphoregulation. The phosphorylation-induced reduction of the activation energy in AKT2 is approximately 6 kT larger than in the K197S mutant. It is discussed that this hypersensitive response of AKT2 to phosphorylation equips a cell with the versatility to establish a potassium gradient and to make efficient use of it.