Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B.

UnlabelledNitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis.ImportanceBacterial nitric oxide (NO) signaling via heme-nitric oxide/oxygen binding (H-NOX) proteins regulates biofilm formation, playing an important role in protecting bacteria from oxidative stress and other environmental stresses. Biofilms are also an important part of symbiosis, allowing the organism to remain in a nutrient-rich environment. In this study, we show that in Silicibacter sp. strain TrichCH4B, NO mediates symbiosis with the alga Trichodesmium erythraeum, a major marine diazotroph. In addition, Silicibacter sp. TrichCH4B is the first characterized bacteria to harbor both the NOS and H-NOX proteins, making it uniquely capable of both synthesizing and sensing NO, analogous to mammalian NO signaling. Our study expands current understanding of the role of NO in bacterial signaling, providing a novel role for NO in bacterial communication and symbiosis

Clonal Chromosome Anomalies Affecting Fli1 Mimic Inherited Thrombocytopenia Of The Paris-Trousseau Type

Introduction: The thrombocytopenia of the Paris-Trousseau (TCPT) type is a contiguous gene syndrome characterized by mild bleeding tendency, variable thrombocytopenia (THC), abnormal giant alpha-granules in platelets and dysmegakaryopoiesis: it derives from a constitutional deletion of chromosome 11 leading to the loss of FLI1, a transcription factor involved in megakaryocyte differentiation and maturation. Case report: A women with an acquired, isolated THC developing over 10 yr showed morphological features typical of TCPT in platelets and bone marrow (BM). Twenty years after the onset of THC, the other hematological parameters are still normal and the patient is well. Results: Clonal hemopoiesis was shown and chromosome analyses performed on BM revealed a clone with 45 chromosomes and a complex unbalanced translocation involving chromosomes 2, 3, and 11. The anomaly was present in the majority of bone marrow cells but only in a few peripheral blood elements. A microarray-based comparative genomic hybridization defined the deleted region of chromosome 11 including the FLI1 locus that was missing. Conclusion: Although our patient presented with nearly all the characteristics of TCPT, her illness was acquired instead of being inherited and the most appropriate diagnosis is that of the unilineage dysplasia 'refractory THC.' This observation suggests that appropriate cytogenetic investigations should be always considered in patients with acquired THC of unknown origin

Comparative genomic hybridization on microarray (a-CGH) in constitutional and acquired mosaicism may detect as low as 8% abnormal cells

Abstract. Background: The results of cytogenetic investigations on unbalanced chromosome anomalies, both constitutional and acquired, were largely improved by comparative genomic hybridization on microarray (a-CGH), but in mosaicism the ability of a-CGH to reliably detect imbalances is not yet well established. This problem of sensitivity is even more relevant in acquired mosaicism in neoplastic diseases, where cells carrying acquired imbalances coexist with normal cells, in particular when the proportion of abnormal cells may be low. We constructed a synthetic mosaicism by mixing the DNA of three patients carrying altogether seven chromosome imbalances with normal sex-matched DNA. Dilutions were prepared mimicking 5%, 6%, 7%, 8%, 10% and 15% levels of mosaicism. Oligomer-based a-CGH (244 K whole-genome system) was applied on the patients' DNA and customized slides designed around the regions of imbalance were used for the synthetic mosaics. Results and conclusions. The a-CGH on the synthetic mosaics proved to be able to detect as low as 8% abnormal cells in the tissue examined. Although in our experiment some regions of imbalances escaped to be revealed at this level, and were detected only at 10-15% level, it should be remarked that these ones were the smallest analyzed, and that the imbalances recurrent as clonal anomalies in cancer and leukaemia are similar in size to those revealed at 8% level

Preventing corona effects: multi-phosphonic acid poly(ethylene glycol) copolymers for stable stealth iron oxide nanoparticles

When disperse in biological fluids, engineered nanoparticles are selectively coated with proteins, resulting in the formation of a protein corona. It is suggested that the protein corona is critical in regulating the conditions of entry into the cytoplasm of living cells. Recent reports describe this phenomenon as ubiquitous and independent of the nature of the particle. For nanomedicine applications however, there is a need to design advanced and cost-effective coatings that are resistant to protein adsorption and that increase the biodistribution in vivo. In this study, phosphonic acid poly(ethylene glycol) copolymers were synthesized and used to coat iron oxide particles. The copolymer composition was optimized to provide simple and scalable protocols as well as long-term stability in culture media. It is shown that polymers with multiple phosphonic acid functionalities and PEG chains outperform other types of coating, including ligands, polyelectrolytes and carboxylic acid functionalized PEG. PEGylated particles exhibit moreover exceptional low cellular uptake, of the order of 100 femtograms of iron per cell. The present approach demonstrates that the surface chemistry of engineered particles is a key parameter in the interactions with cells. It also opens up new avenues for the efficient functionalization of inorganic surfaces.Comment: 21 page, 7 figures,Biomacromolecules 201

Deletion of chromosome 20 in bone marrow of patients with Shwachman-Diamond syndrome, loss of the EIF6 gene and benign prognosis

Shwachman-Diamond Syndrome (SDS; On-line Mendelian Inheritance in Man database number 260400) is an autosomal recessive disorder caused by mutations in the SBDS gene in at least 90% of cases (Boocock et al, 2003). It is characterized by exocrine pancreatic insufficiency, skeletal anomalies, and bone marrow failure with variable severity of neutropenia, thrombocytopenia and anaemia (Rothbaum et al, 2002). Acquired clonal chromosome anomalies are commonly found in the bone marrow (BM), being an isochromosome for the long arms of a 7, i(7)(q10), and a deletion of the long arms of a 20, del(20)(q11), the most frequent. The relationship between these chromosome changes and the risk of patients with SDS to develop myelodysplastic syndromes and acute myeloid leukaemia (MDS/AML) has been discussed (Dror, 2005). This risk increases with the age (Shimamura, 2006), and we have also shown that the acquisition of BM clonal anomalies is age-related (Maserati et al, 2009)

Different loss of material in recurrent chromosome 20 interstitial deletions in Shwachman-Diamond syndrome and in myeloid neoplasms

Abstract BACKGROUND: An interstitial deletion of the long arms of chromosome 20, del(20)(q), is frequent in the bone marrow (BM) of patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), and it is recurrent in the BM of patients with Shwachman-Diamond syndrome (SDS), who have a 30-40% risk of developing MDS and AML. RESULTS: We report the results obtained by microarray-based comparative genomic hybridization (a-CGH) in six patients with SDS, and we compare the loss of chromosome 20 material with one patient with MDS, and with data on 92 informative patients with MDS/AML/MPN and del(20)(q) collected from the literature. CONCLUSIONS: The chromosome material lost in MDS/AML/MPN is highly variable with no identifiable common deleted regions, whereas in SDS the loss is more uniform: in 3/6 patients it was almost identical, and the breakpoints that we defined are probably common to most patients from the literature. In some SDS patients less material may be lost, due to different distal breakpoints, but the proximal breakpoint is in the same region, always leading to the loss of the EIF6 gene, an event which was related to a lower risk of MDS/AML in comparison with other patients

Estratégia de maximização de sucesso de perseguição e fuga nos contextos de caça entre golfinhos Sotalia guianensis (Van Bénedén, 1864) e peixes no povoado de Pipa, RN

Estratégia de maximização de sucesso de perseguição e fuga nos contextos de caça entre golfinhos Sotalia guianensis (Van Bénedén, 1864) e peixes no povoado de Pipa, RN</htm

Installation of ECR2 at LNS and Preliminary tests

The source ECR2 has been built in 1998 by Pantechnik, according to the design suggested by LNS Ion Source Group. This design entails some improvements with respect to a standard CAPRICE-type source: a) the magnetic field (up to 1.6 T axial, 1.1 T radial) allows to operate the source at 14 GHz in High B mode and at 18 GHz; b) two frequency heating can be used; c) an aluminum made plasma chamber is used in place of the stainless steel one. The main features of ECR2 along with a review of the preliminary tests will be outlined. Typical currents for fully stripped nitrogen are about 25 emA; for the heaviest ions, 1 emA of Kr28+ and 10 emA of Ta27+ have been measured. The installation at LNS has been completed recently and the details will be given

Spectral analysis and domain truncation for Maxwell's equations

We analyse how the spectrum of the anisotropic Maxwell system with bounded conductivity σ on a Lipschitz domain Ω is approximated by domain truncation. First we prove a new non-convex enclosure for the spectrum of the Maxwell system, with weak assumptions on the geometry of Ω and none on the behaviour of the coefficients at infinity. We also establish a simple criterion for non-accumulation of eigenvalues at as well as resolvent estimates. For asymptotically constant coefficients, we describe the essential spectrum and show that spectral pollution may occur only in the essential numerical range of the quadratic pencil , acting on divergence-free vector fields. Further, every isolated spectral point of the Maxwell system lying outside and outside the part of the essential spectrum on is approximated by spectral points of the Maxwell system on the truncated domains. Our analysis is based on two new abstract results on the (limiting) essential spectrum of polynomial pencils and triangular block operator matrices, which are of general interest. We believe our strategy of proof could be used to establish domain truncation spectral exactness for more general classes of non-self-adjoint differential operators and systems with non-constant coefficients

Estratégia de maximização de sucesso de perseguição e fuga nos contextos de caça entre golfinhos Sotalia guianensis (Van Bénedén, 1864) e peixes no povoado de Pipa, RN

Estratégia de maximização de sucesso de perseguição e fuga nos contextos de caça entre golfinhos Sotalia guianensis (Van Bénedén, 1864) e peixes no povoado de Pipa, RN </htm