Effective target arrangement in a deterministic scale-free graph

We study the random walk problem on a deterministic scale-free network, in the presence of a set of static, identical targets; due to the strong inhomogeneity of the underlying structure the mean first-passage time (MFPT), meant as a measure of transport efficiency, is expected to depend sensitively on the position of targets. We consider several spatial arrangements for targets and we calculate, mainly rigorously, the related MFPT, where the average is taken over all possible starting points and over all possible paths. For all the cases studied, the MFPT asymptotically scales like N^{theta}, being N the volume of the substrate and theta ranging from (1 - log 2/log3), for central target(s), to 1, for a single peripheral target.Comment: 8 pages, 5 figure

OVOL2 impairs RHO GTPase signaling to restrain mitosis and aggressiveness of Anaplastic Thyroid Cancer

Background: Anaplastic Thyroid Cancer (ATC) is an undifferentiated and aggressive tumor that often originates from well-Differentiated Thyroid Carcinoma (DTC) through a trans-differentiation process. Epithelial-to-Mesenchymal Transition (EMT) is recognized as one of the major players of this process. OVOL2 is a transcription factor (TF) that promotes epithelial differentiation and restrains EMT during embryonic development. OVOL2 loss in some types of cancers is linked to aggressiveness and poor prognosis. Here, we aim to clarify the unexplored role of OVOL2 in ATC. Methods: Gene expression analysis in thyroid cancer patients and cell lines showed that OVOL2 is mainly associated with epithelial features and its expression is deeply impaired in ATC. To assess OVOL2 function, we established an OVOL2-overexpression model in ATC cell lines and evaluated its effects by analyzing gene expression, proliferation, invasion and migration abilities, cell cycle, specific protein localization through immunofluorescence staining. RNA-seq profiling showed that OVOL2 controls a complex network of genes converging on cell cycle and mitosis regulation and Chromatin Immunoprecipitation identified new OVOL2 target genes. Results: Coherently with its reported function, OVOL2 re-expression restrained EMT and aggressiveness in ATC cells. Unexpectedly, we observed that it caused G2/M block, a consequent reduction in cell proliferation and an increase in cell death. This phenotype was associated to generalized abnormalities in the mitotic spindle structure and cytoskeletal organization. By RNA-seq experiments, we showed that many pathways related to cytoskeleton and migration, cell cycle and mitosis are profoundly affected by OVOL2 expression, in particular the RHO-GTPase pathway resulted as the most interesting. We demonstrated that RHO GTPase pathway is the central hub of OVOL2-mediated program in ATC and that OVOL2 transcriptionally inhibits RhoU and RhoJ. Silencing of RhoU recapitulated the OVOL2-driven phenotype pointing to this protein as a crucial target of OVOL2 in ATC. Conclusions: Collectively, these data describe the role of OVOL2 in ATC and uncover a novel function of this TF in inhibiting the RHO GTPase pathway interlacing its effects on EMT, cytoskeleton dynamics and mitosis

CMB Polarization B-mode Delensing with SPTpol and Herschel

We present a demonstration of delensing the observed cosmic microwave background (CMB) B-mode polarization anisotropy. This process of reducing the gravitational-lensing-generated B-mode component will become increasingly important for improving searches for the B modes produced by primordial gravitational waves. In this work, we delens B-mode maps constructed from multi-frequency SPTpol observations of a 90 deg^2 patch of sky by subtracting a B-mode template constructed from two inputs: SPTpol E-mode maps and a lensing potential map estimated from the Herschel 500 μm map of the cosmic infrared background. We find that our delensing procedure reduces the measured B-mode power spectrum by 28% in the multipole range 300 < ℓ < 2300; this is shown to be consistent with expectations from simulations and to be robust against systematics. The null hypothesis of no delensing is rejected at 6.9σ. Furthermore, we build and use a suite of realistic simulations to study the general properties of the delensing process and find that the delensing efficiency achieved in this work is limited primarily by the noise in the lensing potential map. We demonstrate the importance of including realistic experimental non-idealities in the delensing forecasts used to inform instrument and survey-strategy planning of upcoming lower-noise experiments, such as CMB-S4

The maize fused leaves1 (fdl1) gene controls organ separation in the embryo and seedling shoot and promotes coleoptile opening

The fdl1-1 mutation, caused by an Enhancer/Suppressor mutator (En/Spm) element insertion located in the third exon of the gene, identifies a novel gene encoding ZmMYB94, a transcription factor of the R2R3-MYB subfamily. The fdl1 gene was isolated through co-segregation analysis, whereas proof of gene identity was obtained using an RNAi strategy that conferred less severe, but clearly recognizable specific mutant traits on seedlings. Fdl1 is involved in the regulation of cuticle deposition in young seedlings as well as in the establishment of a regular pattern of epicuticular wax deposition on the epidermis of young leaves. Lack of Fdl1 action also correlates with developmental defects, such as delayed germination and seedling growth, abnormal coleoptile opening and presence of curly leaves showing areas of fusion between the coleoptile and the first leaf or between the first and the second leaf. The expression profile of ZmMYB94 mRNA\u2014determined by quantitative RT-PCR\u2014 overlaps the pattern of mutant phenotypic expression and is confined to a narrow developmental window. High expression was observed in the embryo, in the seedling coleoptile and in the first two leaves, whereas RNA level, as well as phenotypic defects, decreases at the third leaf stage. Interestingly several of the Arabidopsis MYB genes most closely related to ZmMYB94 are also involved in the activation of cuticular wax biosynthesis, suggesting deep conservation of regulatory processes related to cuticular wax deposition between monocots and dicots

Adult mesenchymal stem cells for bone and cartilage engineering: effect of scaffold materials

Bone marrow is a useful cell source for skeletal tissue engineering approaches. In vitro differentiation of marrow mesenchymal stem cells (MSCs) to chondrocytes or osteoblasts can be induced by the addition of specific growth factors to the medium. The present study evaluated the behaviour of human MSCs cultured on various scaffolds to determine whether their differentiation can be induced by cell-matrix interactions. MSCs from bone marrow collected from the acetabulum during hip arthroplasty procedures were isolated by cell sorting, expanded and characterised by a flow cytometry system. Cells were grown on three different scaffolds (type I collagen, type I + II collagen and type I collagen + hydroxyapatite membranes) and analysed by histochemistry, immunohistochemistry and spectrophotometry (cell proliferation, alkaline phosphatase activity) at 15 and 30 days. Widely variable cell adhesion and proliferation was observed on the three scaffolds. MSCs grown on type I+II collagen differentiated to cells expressing chondrocyte markers, while those grown on type I collagen + hydroxyapatite differentiated into osteoblast-like cells. The study highlighted that human MSCs grown on different scaffold matrices may display different behaviours in terms of cell proliferation and phenotype expression without growth factor supplementation

Adding pieces to the puzzle of differentiated-to-anaplastic thyroid cancer evolution: the oncogene E2F7

Anaplastic Thyroid Cancer (ATC) is the most aggressive and de-differentiated subtype of thyroid cancer. Many studies hypothesized that ATC derives from Differentiated Thyroid Carcinoma (DTC) through a de-differentiation process triggered by specific molecular events still largely unknown. E2F7 is an atypical member of the E2F family. Known as cell cycle inhibitor and keeper of genomic stability, in specific contexts its function is oncogenic, guiding cancer progression. We performed a meta-analysis on 279 gene expression profiles, from 8 Gene Expression Omnibus patient samples datasets, to explore the causal relationship between DTC and ATC. We defined 3 specific gene signatures describing the evolution from normal thyroid tissue to DTC and ATC and validated them in a cohort of human surgically resected ATCs collected in our Institution. We identified E2F7 as a key player in the DTC-ATC transition and showed in vitro that its down-regulation reduced ATC cells’ aggressiveness features. RNA-seq and ChIP-seq profiling allowed the identification of the E2F7 specific gene program, which is mainly related to cell cycle progression and DNA repair ability. Overall, this study identified a signature describing DTC de-differentiation toward ATC subtype and unveiled an E2F7-dependent transcriptional program supporting this process

CMB Polarization B-mode Delensing with SPTpol and Herschel

We present a demonstration of delensing the observed cosmic microwave background (CMB) B-mode polarization anisotropy. This process of reducing the gravitational-lensing generated B-mode component will become increasingly important for improving searches for the B modes produced by primordial gravitational waves. In this work, we delens B-mode maps constructed from multi-frequency SPTpol observations of a 90 deg$^2$ patch of sky by subtracting a B-mode template constructed from two inputs: SPTpol E-mode maps and a lensing potential map estimated from the $\textit{Herschel}$ $500\,\mu m$ map of the CIB. We find that our delensing procedure reduces the measured B-mode power spectrum by 28% in the multipole range $300 < \ell < 2300$; this is shown to be consistent with expectations from theory and simulations and to be robust against systematics. The null hypothesis of no delensing is rejected at $6.9 \sigma$. Furthermore, we build and use a suite of realistic simulations to study the general properties of the delensing process and find that the delensing efficiency achieved in this work is limited primarily by the noise in the lensing potential map. We demonstrate the importance of including realistic experimental non-idealities in the delensing forecasts used to inform instrument and survey-strategy planning of upcoming lower-noise experiments, such as CMB-S4.Comment: 17 pages, 10 figures. Comments are welcome

Genetic dissection of shoot development in maize

The isolation of genes affecting plant shoot formation is an important prerequisite for understanding the logic of plant development as well as for manipulating plant architecture. To this aim, maize transpositional mutagenesis has been adopted in our laboratory and has led to the isolation of different developmental mutants that are currently under study. Two of them, shootmeristemless (sml) and fused leaves (fdl), are presently described. Their locations, on the long arm of chromosome 10 and chromosome 7 respectively, have been established by traditional B-A translocation mapping and subsequently by linkage analysis with visible, as well as molecular, markers. The sml gene is a recessive mutation affecting shoot apical meristem maintenance and lateral organ formation. Its introgression in different genetic backgrounds has highlighted the epistatic interaction between sml and the unlinked distorted growth (dgr) locus. Seeds homozygous for both sml and dgr loci have a shootless phenotype whereas Dgr/-sml/sml seeds produce plants with altered fillotaxis and abnormal leaf morphogenesis. Microscopy analysis of young dgr primordia will be presented showing that the mutation does not interfere with epidermis formation although cell shape is less regular than in the wild-type. The fdl mutation confers a pleiotropic phenotype to the maize plant, which is specifically confined to the juvenile phase. The lack of a regular coleoptile opening that in normal development occurs after germination, is one of the fdl specific traits that we are presently investigating, for its putative relationship with the programmed cell death (PCD) process. We will present preliminary data on the cloning of the fdl gene along with a description of the strategy we have undertaken for the isolation of novel alleles. They will constitute proof for the gene identity and will provide new genetic material suitable for functional studies