Mining the Conserved Transcriptional Response to Phytophthora Infection for Factors Beyond the Known PR Genes

Oomycetes of the genus Phytophthora are devastating plant pathogens that affect many commercially important plants. Considerable efforts have been made to investigate the transcriptional response of individual plant species to phytophthora infection, often showing a concerted upregulation of pathogen-response (PR) gene families, which are also induced upon infection by fungi and other biotic and even non-biotic stressors. By integrating four transcriptomics datasets derived from three different plants (arabidopsis, soybean, cocoa), a core set of upregulated sequence clusters was derived, which represents a conserved multi-species response to phytophthora infections. We annotated more than 300 common induced gene clusters and subjected them to bioinformatical analysis. Besides the expected PR genes, several novel gene families without known links to biotic stress were found to be strongly induced in all tested datasets. Among the most prominent response genes are two families of putatively secreted peptides and a family of predicted mitochondrial complex-IV associated proteins. Interestingly, the latter sequences are related to the mammalian NDUFA4 family, which also contains members with constitutive and pathogen-induced expression. This recurrent functional diversification points toward an important role of complex IV regulation within the biotic defense response in multiple kingdoms.

Aging and interferon gamma response drive the phenotype of neutrophils in the inflamed joint

Objectives: Neutrophils are typically the most abundant leukocyte in arthritic synovial fluid. We sought to understand changes that occur in neutrophils as they migrate from blood to joint. Methods: We performed RNA sequencing of neutrophils from healthy human blood, arthritic blood, and arthritic synovial fluid, comparing transcriptional signatures with those from murine K/BxN serum transfer arthritis. We employed mass cytometry to quantify protein expression and sought to reproduce the synovial fluid phenotype ex vivo in cultured healthy blood neutrophils. Results: Blood neutrophils from healthy donors and patients with active arthritis exhibited largely similar transcriptional signatures. By contrast, synovial fluid neutrophils exhibited more than 1,600 differentially expressed genes. Gene signatures identified a prominent response to interferon gamma (IFNγ), as well as to tumor necrosis factor, interleukin 6, and hypoxia, in both humans and mice. Mass cytometry also found healthy and arthritic donor blood neutrophils largely indistinguishable but revealed a range of neutrophil phenotypes in synovial fluid defined by downregulation of CXCR1 and upregulation of FcγRI, HLA-DR, PD-L1, ICAM-1 and CXCR4. Reproduction of key elements of this signature in cultured blood neutrophils required both IFNγ and prolonged culture. Conclusions: Circulating neutrophils from arthritis patients resemble those from healthy controls, but joint fluid cells exhibit a network of changes, conserved across species, that implicate IFNγ response and aging as complementary drivers of the synovial neutrophil phenotype.

FACT-mediated maintenance of chromatin integrity during transcription is essential for viability of mammalian stem cells

Replication and transcription machineries access DNA through unwrapping it from histone core. Preservation of nucleosome structure during replication is a focus of intensive research, while maintenance of nucleosomes during transcription is less studied. Histone chaperone FACT is involved in transcription elongation, although whether it opens nucleosomes for polymerase or protects core histones from loss during passage of polymerase is still unclear. We used conditional knockout model of Ssrp1, subunit of FACT complex, to deplete FACT in mice and monitored consequences of FACT loss to establish the functional relevance of FACT in mammals. FACT loss was lethal for mice at all ages due to failure of hematopoietic and intestinal tissues. In these tissues, only the progenitors completely vanished upon FACT loss, while number of some other cell types were changed up and down. Using isolated stem cells of several tissues we showed that FACT loss was toxic only for stem cells, but not for cells which were differentiated in vitro. Chromatin accessibility in stem cells was increased genome wide upon FACT depletion in transcription dependent manner. The most prominent response to the loss of chromatin integrity upon FACT depletion in cells was activation of interferon signaling, followed by accumulation of immune cells in sensitive organs. Thus, in undifferentiated mammalian cells FACT keeps chromatin stable during transcription elongation and this function of FACT is essential for viability of stem cells.

Sanctioning Genocide: To What Effect?

Although economic sanctions have become a prominent response to mass atrocity, there has been relatively little scholarship assessing the impact of economic sanctions on genocidal violence. This article examines whether and how economic sanctions are associated with both the magnitude and the duration of state-led genocide. We analyze 39 genocides that occurred between 1955 and 2005. Results indicate that economic sanctions are not significantly associated with decreased magnitude or duration of genocide. These findings contribute to theory regarding the impact of sanctions on state behavior and hold significance for policy decisions in the face of genocide.

Pharmacognostic, Physicochemical and Anti-Oxidant Screening of Solenostemma Argel’s Leaf Extract

The present work deals with the identification of new approach towards the lead generation in medicinal chemistry and authenticating the reports present on the use of this Sudanese medicinal plant Solenostemma argel in the tribal region of Sudan. The pharmacognostic screening showed its physical and chemical composition with identification of active ingredients. The antioxidant activity was carried out by DPPH and nitric oxide scavenging method. In which ethanolic leaf extract showed prominent response which may be due to the promising presence of flavonoids and related poly phenolic compounds in it

EFFECT OF PROTEASE SUPPLEMENTATION ON THE PERFORMANCE AND DIGESTIBILITY OF BROILERS

Premise of the study was to validate the growth promoting eff ect of protease on the performance and to explore its digestion enhancer eff ect in broiler chicks. For this purpose 4 commercial diets were divided into two types (low and high density) and were enriched with protease using a completely randomized design with 4 replicates per diet having 10 chicks each having totaled 200 poultry broiler chickens (day-old). Until 14 days, no eff ects were observed on chicks however at day 14; little variations were observed on weight gain, feed intake and FCR (feed conversion ratio) among the enzyme enriched diets. At day 28, prominent response of protease supplementation in low protein was procured. The chicks gained 10.06 and 8.0 % more weight on CFP1 than CFG1 and CFG2, respectively. Similar response in FCR was observed and was found to be 0.20 and 0.15 points better on CFP1 than on CFG1 and CFG2, respectively. However, CFP2 failed to show protease effi cacy declining the weight gain by 23.01 % while the FCR by 0.49 points as compared with CFP1. This suggested that the nature of feed ingredients in the diets is important for obtaining maximum benefi t of protease supplementation. The overall performance indicated signifi cant response to enzyme supplemented diets. Among the low protein diets CP digestibility remained unchanged but they were diff erent in sparing AME (apparent metabolizable energy) for chicks. The CFP2 spared 98.21 kcal/Kg more AME than CFP1. However, this increased AME values did not help to boost the performance and was attributed to the widening ratio between CP and AME. These results demonstrated that the overall growth response of chicks was improved on low protein diet enriched with protease. It showed higher CP digestibility and AME values than good quality diets. However, the inconsistent results observed within the two types of diets revealed that the nature of diets might have infl uenced the effi cacy of protease. Key words: Broilers, digestibility, protease, FCR, Feed intake.

Chitosan Oligosaccharide Addition to Buddhist Pine (Podocarpus macrophyllus (Thunb) Sweet) under Drought: Reponses in Ecophysiology and δ13C Abundance

Climate warming induces the necessity to increase the drought resistance of shade-obligate juvenile trees in sub-tropical forests. Chitosan oligosaccharide (COS) is a biopolymer derived from the marine resource that has attracted accumulative attention to induce and promote a plant’s resistance to abiotic stress. Buddhist pine (Podocarpus mascrophyllus (Thunb)Sweet) seedlings were cultured as the model material whose natural distribution in sub-tropical areas of China has suffered severe summer drought events in the last 113 years. A split-block design was conducted with a simulated drought event (drought vs. irrigated control), the COS addition, and two samplings at the ends of drought and re-watered treatments. The COS addition increased the resistance to drought by inducing a starch allocation towards roots where δ13C abundance and antioxidant enzyme activities were upregulated. The COS addition can promote biomass allocation to roots and increase the number of new roots. The COS addition to drought-treated Buddhist pine seedlings resulted in robust diameter growth. Therefore, COS is an available polymer to promote the resistance of Buddhist pine to drought. More work is suggested to clarify the dose of COS addition that can induce a prominent response of biomass accumulation and carbohydrate metabolism.

A previously identified apoptosis inhibitor iASPP confers resistance to chemotherapeutic drugs by suppressing senescence in cancer cells

Cellular senescence is terminal cell cycle arrest that represents a prominent response to numerous anticancer therapies. The oncogene inhibitor of the apoptosis-stimulating protein of p53 (iASPP) plays essential roles in regulating cellular drug response by inhibiting apoptosis. However, whether or not it regulates chemotherapy-induced senescence (TIS) in cancer cells remains unclear. Here, using two commonly used cancer cell lines, HCT 116 and MCF-7, along with the xenograft mouse model, we found that iASPP inhibits senescence and also influences the senescence-associated secretory phenotype (SASP), which confers anticancer drug resistance independently of apoptosis. Mechanistically, iASPP is transcriptionally elevated by the p65 subunit of NF-κB in senescent cells and then translocates to the nucleus, where it binds p53 and NF-κBp65. This binding inhibits their transcriptional activities toward p21 and the key SASP factors interleukin (IL)-6/IL-8, respectively, and subsequently prevents senescence. Of note, we observed that iASPP knockdown sensitizes apoptosis-resistant cancers to doxorubicin treatment by promoting senescence both in vitro and in vivo. We conclude that iASPP integrates the NF-κBp65- and p53-signaling pathways and thereby regulates cell fate in response to TIS, leading to chemotherapy resistance. These findings suggest that iASPP inhibition might be a strategy that could help restore senescence in cancer cells and improve outcomes of chemotherapy-based therapies.