High Expression of Pitx-2 in the ICAT-deficient Metanephros Leads to Developmental Arrest

ICAT (Inhibitor of β-catenin and T cell factor) inhibits the interaction between β-catenin and TCF/LEF transcription factor and serves as a negative regulator of Wnt signaling. In a subset of ICAT knockout mice, significant delay in the ureteric bud branching and renal agenesis are observed. In order to examine the process of this developmental defect, molecular changes were analyzed in fetal ICAT–/– kidneys with a focus on Wnt-signaling associated factors. The protein level of active β-catenin was elevated in ICAT–/– kidneys. DNA microarray and immunohistochemical analyses revealed that the expression of a Wnt target gene Pitx-2 was enhanced in ICAT–/– kidneys. There was no genotypic difference in the expression level of another Wnt target gene, c-Ret. These results suggest that the enhancement of Pitx-2 expression induced by activated Wnt signaling leads to delays in ureteric bud branching and subsequent renal agenesis. In the ICAT–/– kidneys which developed to E18.5 without any apparent defect, renal glomeruli, convoluted tubules and collecting ducts were decreased in density and showed abnormal structure. ICAT may be required for various developmental stages during renal development

Reconstructing the primordial power spectrum from the CMB

We propose a straightforward and model independent methodology for characterizing the sensitivity of CMB and other experiments to wiggles, irregularities, and features in the primordial power spectrum. Assuming that the primordial cosmological perturbations are adiabatic, we present a function space generalization of the usual Fisher matrix formalism, applied to a CMB experiment resembling Planck with and without ancillary data. This work is closely related to other work on recovering the inflationary potential and exploring specific models of non-minimal, or perhaps baroque, primordial power spectra. The approach adopted here, however, most directly expresses what the data is really telling us. We explore in detail the structure of the available information and quantify exactly what features can be reconstructed and at what statistical significance.Comment: 43 pages Revtex, 23 figure

The role of information and communications technology in real-time monitoring for quality WASH infrastructure

The risk of inefficiencies in quality of WASH infrastructure construction is higher in places where monitoring is less or absent or when monitoring is only limited to persons directly involved with the business processes and transactions. To address system deficiencies and constraints in the monitoring of latrine construction in WASH in schools’ project, CRS Ghana explored innovative technology solutions that allow access to quick, cost-effective quality data on progress of construction activities. The solution involves the use of Tablets, GPS, Iformbuilder Platform and BarTender software to develop a simple system to track and certify construction results in real-time. This approach prevents construction defects, supports cost-effective delivery of quality infrastructure, promotes transparency and allows decision making on payments, contracts and WASH programming

Signatures of heavy Majorana neutrinos and HERA's isolated lepton events

The graph of neutrinoless double beta decay is applied to HERA and generalized to final states with any two charged leptons. Considered is the case in which one of the two escapes typical identification criteria and the case when a produced tau decays hadronically. Both possibilities give one isolated lepton with high transverse momentum, hadronic activity and an imbalance in transverse momentum. We examine the kinematical properties of these events and compare them with the high p_T isolated leptons reported by the H1 collaboration. Their positive charged muon events can be explained by the ``double beta'' process and we discuss possibilities for the precise determination which original final state produced the single isolated lepton. To confirm our hypothesis one should search in the data for high pseudorapidity and/or low p_T leptons or for additional separated jets.Comment: 19 pages with 14 figures, minor change

`Standard' Cosmological model & beyond with CMB

Observational Cosmology has indeed made very rapid progress in the past decade. The ability to quantify the universe has largely improved due to observational constraints coming from structure formation Measurements of CMB anisotropy and, more recently, polarization have played a very important role. Besides precise determination of various parameters of the `standard' cosmological model, observations have also established some important basic tenets that underlie models of cosmology and structure formation in the universe -- `acausally' correlated initial perturbations in a flat, statistically isotropic universe, adiabatic nature of primordial density perturbations. These are consistent with the expectation of the paradigm of inflation and the generic prediction of the simplest realization of inflationary scenario in the early universe. Further, gravitational instability is the established mechanism for structure formation from these initial perturbations. The signature of primordial perturbations observed as the CMB anisotropy and polarization is the most compelling evidence for new, possibly fundamental, physics in the early universe. The community is now looking beyond the estimation of parameters of a working `standard' model of cosmology for subtle, characteristic signatures from early universe physics.Comment: 16 pages, 6 figures, Plenary talk, Proc. of GR-19, Mexico City, Mexico (Jul 5-9, 2010). To appear in a special issue in Class. Q. Gra

l W nu production at CLIC: a window to TeV scale non-decoupled neutrinos

We discuss single heavy neutrino production e+ e- -> N nu -> l W nu, l = e, mu, tau, at a future high energy collider like CLIC, with a centre of mass energy of 3 TeV. This process could allow to detect heavy neutrinos with masses of 1-2 TeV if their coupling to the electron V_eN is in the range 0.004-0.01. We study the dependence of the limits on the heavy neutrino mass and emphasise the crucial role of lepton flavour in the discovery of a positive signal at CLIC energy. We present strategies to determine heavy neutrino properties once they are discovered, namely their Dirac or Majorana character and the size and chirality of their charged current couplings. Conversely, if no signal is found, the bound V_eN < 0.002-0.006 would be set for masses of 1-2 TeV, improving the present limit up to a factor of 30. We also extend previous work examining in detail the flavour and mass dependence of the corresponding limits at ILC, as well as the determination of heavy neutrino properties if they are discovered at this collider.Comment: LaTeX 32 pages. Added comments and references. Matches version to appear in JHE

Cosmology with CMB anisotropy

Measurements of CMB anisotropy and, more recently, polarization have played a very important role allowing precise determination of various parameters of the `standard' cosmological model. The expectation of the paradigm of inflation and the generic prediction of the simplest realization of inflationary scenario in the early universe have also been established -- `acausally' correlated initial perturbations in a flat, statistically isotropic universe, adiabatic nature of primordial density perturbations. Direct evidence for gravitational instability mechanism for structure formation from primordial perturbations has been established. In the next decade, future experiments promise to strengthen these deductions and uncover the remaining crucial signature of inflation -- the primordial gravitational wave background.Comment: Plenary talk at the IXth. International Workshop on High Energy Physics Phenomenology (WHEPP-9), Institute of Physics, Bhubaneshwar, India. Jan 3-14, 2006; To appear in the Proceedings to be published in Pramana; 12 pages, 2 figure

Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia

Background: Loss of adenomatous polyposis coli (APC) gene function results in constitutive activation of the canonical Wnt pathway and represents the main initiating and rate-limiting event in colorectal tumorigenesis. APC is likely to participate in a wide spectrum of biological functions via its different functional domains and is abundantly expressed in the brain as well as in peripheral tissues. However, the neuronal function of APC is poorly understood. To investigate the functional role of Apc in the central nervous system, we analyzed the neurological phenotypes of Apc 1638T/1638T mice, which carry a targeted deletion of the 3′ terminal third of Apc that does not affect Wnt signaling. Results: A series of behavioral tests revealed a working memory deficit, increased locomotor activity, reduced anxiety-related behavior, and mildly decreased social interaction in Apc 1638T/1638T mice. Apc 1638T/1638T mice showed abnormal morphology of the dendritic spines and impaired long-term potentiation of synaptic transmission in the hippocampal CA1 region. Moreover, Apc 1638T/1638T mice showed abnormal dopamine and serotonin distribution in the brain. Some of these behavioral and neuronal phenotypes are related to symptoms and endophenotypes of schizophrenia. Conclusions: Our results demonstrate that the C-terminus of the Apc tumor suppressor plays a critical role in cognitive and neuropsychiatric functioning. This finding suggests a potential functional link between the C-terminus of APC and pathologies of the central nervous system

The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity