p38 MAP kinase regulates the expression of XMyf5 and affects distinct myogenic programs during Xenopus development

AbstractThe p38 MAPK signaling pathway is essential for skeletal muscle differentiation in tissue culture models. We demonstrate a novel role for p38 MAPK in myogenesis during early Xenopus laevis development. Interfering with p38 MAPK causes distinct defects in myogenesis. The initial expression of Myf5 is selectively blocked, while expression of MyoD is unaffected. Expression of a subset of muscle structural genes is reduced. Convergent extension movements are prevented and segmentation of the paraxial mesoderm is delayed, probably due to the failure of cells to withdraw from the cell cycle. Myotubes are properly formed; however, at later stages, they begin to degenerate, and the boundaries between somites disappear. Significant apoptotic cell death occurs in most parts of the somites. The ventral body wall muscle derived from migratory progenitor cells of the ventral somite region is poorly formed. Our data indicate that the developmental defects caused by p38α-knockdown were mediated by the loss of XMyf5 expression. Thus, this study identifies a specific intracellular pathway in which p38 MAPK and Myf5 proteins regulate a distinct myogenic program

The social costs of keystone species collapse : evidence from the decline of vultures in India

The loss of a keystone species can theoretically lead to large social costs because their complex ecosystem interactions may be important for environmental quality. We quantify these effects for the case of vultures in India where they play an important public health role by removing livestock carrion from the environment. The expiration of a patent for a common chemical painkiller led to its increased use in cattle, unexpectedly rendering carcasses fatal to vultures, leading to a catastrophic and near-total population collapse. Using habitat range maps for the affected species, we compare high to low vulture suitability districts before and after the patent for the painkiller expired. We find that, on average, all-cause death rates increased by more than 4%in vulture-suitable districts after the vultures nearly went extinct. We find suggestive evidence that feral dog populations and rabies increased, and that water quality deteriorated in the affected regions. These mechanisms are consistent with the loss of the scavenging function of the vultures. Quantifying the costs of biodiversity losses has critical implications for optimal investments into species conservation and rehabilitation

Heterotrophic and Autotrophic Contribution to Dinitrogen Fixation in the Gulf of Aqaba

We evaluated the seasonal contribution of heterotrophic and autotrophic diazotrophy to the total dinitrogen (N2) fixation in the photic zone of a pelagic station in the northern Gulf of Aqaba, Red Sea. N2 fixation rates were highest during a Trichodesmium bloom in winter (0.7 nmol N l-1 d-1), decreased 7-fold 1 wk later throughout the upper 200 m (~0.1 nmol N l-1) d-1), and were significantly coupled with both primary and bacterial productivity. N2 fixation rates were generally higher in the upper 200 m (~0.4 nmol N l-1) d-1)) during the thermally stratified summer and were correlated solely with bacterial productivity. Experimental enrichment of seawater by phosphorus (P) enhanced bacterial productivity and N2 fixation rates during both seasons by 3- to 5-fold. Moreover, during the stratified season, experimental amendments to seawater applying a combination of the photosynthetic inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea and a mixture of amino acids increased both bacterial productivity and N2 fixation rates. Our findings from the northern Gulf of Aqaba indicate that in the photic zone, a shift occurs in the diazotrophic community from phototrophic and heterotrophic populations in winter, including the cyanobacteria Trichodesmium, to predominantly heterotrophic diazotrophs in summer. These heterotrophic diazotrophs may be both carbon and P limited as illustrated by their response to additions of P and amino acids

Uncoupling Between Dinitrogen Fixation and Primary Productivity in the Eastern Mediterranean Sea

In the nitrogen (N)-impoverished photic zones of many oceanic regions, prokaryotic organisms fixing atmospheric dinitrogen (N2; diazotrophs) supply an essential source of new nitrogen and fuel primary production. We measured dinitrogen fixation and primary productivity (PP) during the thermally stratified summer period in different water regimes of the oligotrophic eastern Mediterranean Sea, including the Cyprus Eddy and the Rhodes Gyre. Low N2 fixation rates were measured (0.8-3.2μmol N m-2 d-1) excluding 10-fold higher rates in the Rhodes Gyre and Cyprus Eddy (~20μmol N m-2 d-1). The corresponding PP increased from east to west (200-2500μmol C m-2 d-1), with relatively higher productivity recorded in the Rhodes Gyre and Cyprus Eddy (2150 and 2300μmol C m-2 d-1, respectively). These measurements demonstrate that N2 fixation in the photic zone of the eastern Mediterranean Sea contributes only negligibly by direct inputs to PP (i.e., cyanobacterial diazotrophs) and is in fact uncoupled from PP. By contrast, N2 fixation is significantly coupled to bacterial productivity and to net heterotrophic areas, suggesting that heterotrophic N2 fixation may in fact be significant in this ultraoligotrophic system. This is further substantiated by the high N2 fixation rates we measured from aphotic depths and by the results of phylogenetic analysis in other studies showing an abundance of heterotrophic diazotrophs

Programming a Ferroptosis-to-Apoptosis Transition Landscape Revealed Ferroptosis Biomarkers and Repressors for Cancer Therapy

Ferroptosis and apoptosis are key cell-death pathways implicated in several human diseases including cancer. Ferroptosis is driven by iron-dependent lipid peroxidation and currently has no characteristic biomarkers or gene signatures. Here a continuous phenotypic gradient between ferroptosis and apoptosis coupled to transcriptomic and metabolomic landscapes is established. The gradual ferroptosis-to-apoptosis transcriptomic landscape is used to generate a unique, unbiased transcriptomic predictor, the Gradient Gene Set (GGS), which classified ferroptosis and apoptosis with high accuracy. Further GGS optimization using multiple ferroptotic and apoptotic datasets revealed highly specific ferroptosis biomarkers, which are robustly validated in vitro and in vivo. A subset of the GGS is associated with poor prognosis in breast cancer patients and PDXs and contains different ferroptosis repressors. Depletion of one representative, PDGFA-assaociated protein 1(PDAP1), is found to suppress basal-like breast tumor growth in a mouse model. Omics and mechanistic studies revealed that ferroptosis is associated with enhanced lysosomal function, glutaminolysis, and the tricarboxylic acid (TCA) cycle, while its transition into apoptosis is attributed to enhanced endoplasmic reticulum(ER)-stress and phosphatidylethanolamine (PE)-to-phosphatidylcholine (PC) metabolic shift. Collectively, this study highlights molecular mechanisms underlying ferroptosis execution, identified a highly predictive ferroptosis gene signature with prognostic value, ferroptosis versus apoptosis biomarkers, and ferroptosis repressors for breast cancer therapy

Chargino contributions to ϵ′/ϵ\epsilon^{\prime}/ \epsilon in the left-right supersymmetric model

We analyze the chargino contributions to the CP violating ratio $\epsilon^{\prime}/\epsilon$ in the left-right supersymmetric model. We study the possibility that these contributions alone can saturate the experimental value of $\epsilon^{\prime}/\epsilon$. We derive conservative bounds on supersymmetric flavor violation parameters in the up squark LL, RR, LR and RL sectors, using the mass insertion approximation. While the LL bounds are found to be consistent with the MSSM values, the LR constraints are new and much stronger.Comment: 14 pages, 1 figure, 2 table

The potential impact of Saharan dust and polluted aerosols on microbial populations in the East Mediterranean Sea, an overview of a mesocosm experimental approach.

Recent estimates of nutrient budgets for the Eastern Mediterranean Sea (EMS) indicate that atmospheric aerosols play a significant role as suppliers of macro- and micro- nutrients to its Low Nutrient Low Chlorophyll water. Here we present the first mesocosm experimental study that examines the overall response of the oligotrophic EMS surface mixed layer (Cretan Sea, May 2012) to two different types of natural aerosol additions, “pure” Saharan dust (SD, 1.6 mg l-1) and mixed aerosols (A - polluted and desert origin, 1 mg l-1). We describe the rationale, the experimental set-up, the chemical characteristics of the ambient water and aerosols and the relative maximal biological impacts that resulted from the added aerosols. The two treatments, run in triplicates (3 m3 each), were compared to control-unamended runs. Leaching of approximately 2.1-2.8 and 2.2-3.7 nmol PO4 and 20-26 and 53-55 nmol NOx was measured per each milligram of SD and A, respectively, representing an addition of approximately 30% of the ambient phosphate concentrations. The nitrate/phosphate ratios added in the A treatment were twice than those added in the SD treatment. Both types of dry aerosols triggered a positive change (25-600% normalized per 1 mg l-1 addition) in most of the rate and state variables that were measured: bacterial abundance (BA), bacterial production (BP), Synechococcus (Syn) abundance, chlorophyll-a (chl-a), primary production (PP) and dinitrogen fixation (N2-fix), with relative changes among them following the sequence BP>PP≈N2-fix>chl-a≈BA≈Syn. Our results show that the ‘polluted’ aerosols triggered a relatively larger biological change compared to the SD amendments (per a similar amount of mass addition), especially regarding BP and PP. We speculate that despite the co-limitation of P and N in the EMS, the additional N released by the A treatment may have triggered the relatively larger response in most of the rate and state variables as compared to SD. An implication of our study is that a warmer atmosphere in the future may increase dust emissions and influence the intensity and length of the already well stratified water column in the EMS and hence the impact of the aerosols as a significant external source of new nutrients

Exact amplitudes in four dimensional non-critical string theories

The large Nc expansion of N=2 supersymmetric Yang-Mills theory with gauge group SU(Nc) has recently been shown to break down at singularities on the moduli space. We conjecture that by taking Nc to infinity and approaching the singularities in a correlated way, all the observables of the theory have a finite universal limit yielding amplitudes in string theories dual to field theories describing the light degrees of freedom. We explicitly calculate the amplitudes corresponding to the Seiberg-Witten period integrals for an A_{n-1} series of multicritical points as well as for other critical points exhibiting a scaling reminiscent of the c=1 matrix model. Our results extend the matrix model approach to non-critical strings in less than one dimension to non-critical strings in four dimensions.Comment: 20 pages; v2: typos correcte