Delayed diagnosis of Townes‑Brocks syndrome with multicystic kidneys and renal failure caused by a novel SALL1 nonsense mutation: A case report

Townes‑Brocks syndrome (TBS) is a rare autosomal dominant congenital anomaly syndrome characterized by the triad of anorectal, hand and external ear malformations. Kidney involvement is less common and may progress to end‑stage renal failure (ESRF) early in life. The present study reports the case of a male patient presenting with multiple bilateral cortical kidney cysts at the age of 4 years, at which time the kidneys were of normal size and function. A clinical diagnosis of autosomal recessive polycystic kidney disease was made initially as the patient's parents are clinically healthy. However, the consideration of extra‑renal involvements (imperforate anus at birth, preaxial polydactyly and dysplastic right ear) following the progression of the patient to ESRF at the age of 16 years, led to the diagnosis of TBS. This prompted sequencing of the SALL1 gene, which identified a novel heterozygous nonsense mutation in the mutational ‘hotspot’ of exon 2 (c.874C>T, p.Q292X), and this mutation was not detected in healthy controls. The current case highlights that TBS may present with normal sized, cystic kidneys in childhood, while recognition of extra‑renal features of cystic kidney diseases, such as TBS, and genetic testing may facilitate the correct diagnosis and transmission mode. Reaching a correct diagnosis of as TBS is important since this condition has a 50% rate of transmission to offspring and can progress to ESRF early in life

Electronic measurement and control of spin transport in Silicon

The electron spin lifetime and diffusion length are transport parameters that define the scale of coherence in spintronic devices and circuits. Since these parameters are many orders of magnitude larger in semiconductors than in metals, semiconductors could be the most suitable for spintronics. Thus far, spin transport has only been measured in direct-bandgap semiconductors or in combination with magnetic semiconductors, excluding a wide range of non-magnetic semiconductors with indirect bandgaps. Most notable in this group is silicon (Si), which (in addition to its market entrenchment in electronics) has long been predicted a superior semiconductor for spintronics with enhanced lifetime and diffusion length due to low spin-orbit scattering and lattice inversion symmetry. Despite its exciting promise, a demonstration of coherent spin transport in Si has remained elusive, because most experiments focused on magnetoresistive devices; these methods fail because of universal impedance mismatch obstacles, and are obscured by Lorentz magnetoresistance and Hall effects. Here we demonstrate conduction band spin transport across 10 microns undoped Si, by using spin-dependent ballistic hot-electron filtering through ferromagnetic thin films for both spin-injection and detection. Not based on magnetoresistance, the hot electron spin-injection and detection avoids impedance mismatch issues and prevents interference from parasitic effects. The clean collector current thus shows independent magnetic and electrical control of spin precession and confirms spin coherent drift in the conduction band of silicon.Comment: Single PDF file with 4 Figure

Prostate transglutaminase (TGase-4) antagonizes the anti-tumour action of MDA-7/IL-24 in prostate cancer

Background Transglutamiase-4 (TGase-4), also known as prostate transglutaminase, belongs to the TGase family and is uniquely expressed in the prostate gland. The functions of this interesting protein are not clearly defined. In the present study, we have investigated an unexpected link between TGase-4 and the melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24), a cytokine known to regulate the growth and apoptosis of certain cancer and immune cells. Methods Frozen sections of normal and malignant human prostate tissues and human prostate cancer (PCa) cell lines PC-3 and CA-HPV-10, cell lines expressing low and high levels of TGase-4, and recombinant MDA-7/IL-24 (rhMDA-7/IL-24) were used. Expression construct for human TGase-4 was generated using a mammalian expression vector with full length human TGase-4 isolated from normal human prostate tissues. PC-3 cells were transfected with expression construct or control plasmid. Stably transfected cells for control transfection and TGase-4 over expression were created. Similarly, expression of TGase-4 in CA-HPV-10 cells were knocked down by way of ribozyme transgenes. Single and double immunofluorescence microscopy was used for localization and co-localization of TGase-4 and MDA-7/IL-24 in PCa tissues and cells with antibodies to TGase-4; MDA-7/IL-24; IL-20alpha; IL-20beta and IL-22R. Cell-matrix adhesion, attachment and migration were by electric cell substrate impedance sensing and growth by in vitro cell growth assay. A panel of small molecule inhibitors, including Akt, was used to determine signal pathways involving TGase-4 and MDA-7/IL-24. Results We initially noted that MDA-7 resulted in inhibition of cell adhesion, growth and migration of human PCa PC-3 cells which did not express TGase-4. However, after the cells over-expressed TGase-4 by way of transfection, the TGase-4 expressing cells lost their adhesion, growth and migratory inhibitory response to MDA-7. On the other hand, CA-HPV-10 cells, a cell type naturally expressing high levels of TGase-4, had a contrasting response to MDA-7 when compared with PC-3 cells. Inhibitor to Akt reversed the inhibitory effect of MDA-7, only in PC-3 control cells, but not the TGase-4 expressing PC-3 cells. In human prostate tissues, TGase-4 was found to have a good degree of co-localization with one of the MDA-7 receptor complexes, IL-20Ra. Conclusion The presence of TGase-4 has a biological impact on a prostate cancer cell's response to MDA-7. TGase-4, via mechanism(s) yet to be identified, blocked the action of MDA-7 in prostate cancer cells. This has an important implication when considering the use of MDA-7 as a potential anticancer cytokine in prostate cancer therapies

Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure.

Endothelial dysfunction is a critical factor in many cardiovascular diseases, including hypertension. Although lipid signaling has been implicated in endothelial dysfunction and cardiovascular disease, specific molecular mechanisms are poorly understood. Here we report that Nogo-B, a membrane protein of the endoplasmic reticulum, regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Nogo-B inhibits serine palmitoyltransferase, the rate-limiting enzyme of the de novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine 1-phosphate and autocrine, G protein-coupled receptor-dependent signaling by this metabolite. Mice lacking Nogo-B either systemically or specifically in endothelial cells are hypotensive, resistant to angiotensin II-induced hypertension and have preserved endothelial function and nitric oxide release. In mice that lack Nogo-B, pharmacological inhibition of serine palmitoyltransferase with myriocin reinstates endothelial dysfunction and angiotensin II-induced hypertension. Our study identifies Nogo-B as a key inhibitor of local sphingolipid synthesis and shows that autocrine sphingolipid signaling within the endothelium is critical for vascular function and blood pressure homeostasis

Staircase Quantum Dots Configuration in Nanowires for Optimized Thermoelectric Power

The performance of thermoelectric energy harvesters can be improved by nanostructures that exploit inelastic transport processes. One prototype is the three-terminal hopping thermoelectric device where electron hopping between quantum-dots are driven by hot phonons. Such three-terminal hopping thermoelectric devices have potential in achieving high efficiency or power via inelastic transport and without relying on heavy-elements or toxic compounds. We show in this work how output power of the device can be optimized via tuning the number and energy configuration of the quantum-dots embedded in parallel nanowires. We find that the staircase energy configuration with constant energy-step can improve the power factor over a serial connection of a single pair of quantum-dots. Moreover, for a fixed energy-step, there is an optimal length for the nanowire. Similarly for a fixed number of quantum-dots there is an optimal energy-step for the output power. Our results are important for future developments of high-performance nanostructured thermoelectric devices

Electromagnetic form factor of pion from N_f=2+1 dynamical flavor QCD

We present a calculation of the electromagnetic form factor of the pion in $N_f=2+1$ flavor lattice QCD. Calculations are made on the PACS-CS gauge field configurations generated using Iwasaki gauge action and Wilson-clover quark action on a $32^3\times64$ lattice volume with the lattice spacing estimated as $a=0.0907(13)$ fm at the physical point. Measurements of the form factor are made using the technique of partially twisted boundary condition to reach small momentum transfer as well as periodic boundary condition with integer momenta. Additional improvements including random wall source techniques and a judicious choice of momenta carried by the incoming and outgoing quarks are employed for error reduction. Analyzing the form factor data for the pion mass at $M_\pi \approx 411$ MeV and 296 MeV, we find that the NNLO SU(2) chiral perturbation theory fit yields $=0.441 \pm 0.046 {\rm fm}^2$ for the pion charge radius at the physical pion mass. Albeit the error is quite large, this is consistent with the experimental value of $0.452\pm 0.011 {\rm fm}^2$. Below $M_\pi\approx 300$ MeV, we find that statistical fluctuations in the pion two- and three-point functions become too large to extract statistically meaningful averages on a $32^3$ spatial volume. We carry out a sample calculation on a $64^4$ lattice with the quark masses close to the physical point, which suggests that form factor calculations at the physical point become feasible by enlarging lattice sizes to $M_\pi L\approx 4$.Comment: 28 pages, 14 figure

Extremely long quasiparticle spin lifetimes in superconducting aluminium using MgO tunnel spin injectors

There has been an intense search in recent years for long-lived spin-polarized carriers for spintronic and quantum-computing devices. Here we report that spin polarized quasi-particles in superconducting aluminum layers have surprisingly long spin-lifetimes, nearly a million times longer than in their normal state. The lifetime is determined from the suppression of the aluminum's superconductivity resulting from the accumulation of spin polarized carriers in the aluminum layer using tunnel spin injectors. A Hanle effect, observed in the presence of small in-plane orthogonal fields, is shown to be quantitatively consistent with the presence of long-lived spin polarized quasi-particles. Our experiments show that the superconducting state can be significantly modified by small electric currents, much smaller than the critical current, which is potentially useful for devices involving superconducting qubits

Composition of gut microbiota in infants in China and global comparison

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Metal-insulator transition in vanadium dioxide nanobeams: probing sub-domain properties of strongly correlated materials

Many strongly correlated electronic materials, including high-temperature superconductors, colossal magnetoresistance and metal-insulator-transition (MIT) materials, are inhomogeneous on a microscopic scale as a result of domain structure or compositional variations. An important potential advantage of nanoscale samples is that they exhibit the homogeneous properties, which can differ greatly from those of the bulk. We demonstrate this principle using vanadium dioxide, which has domain structure associated with its dramatic MIT at 68 degrees C. Our studies of single-domain vanadium dioxide nanobeams reveal new aspects of this famous MIT, including supercooling of the metallic phase by 50 degrees C; an activation energy in the insulating phase consistent with the optical gap; and a connection between the transition and the equilibrium carrier density in the insulating phase. Our devices also provide a nanomechanical method of determining the transition temperature, enable measurements on individual metal-insulator interphase walls, and allow general investigations of a phase transition in quasi-one-dimensional geometry.Comment: 9 pages, 3 figures, original submitted in June 200

HSP60 as a Target of Anti-Ergotypic Regulatory T Cells

The 60 kDa heat shock protein (HSP60) has been reported to influence T-cell responses in two ways: as a ligand of toll-like receptor 2 signalling and as an antigen. Here we describe a new mechanism of T-cell immuno-regulation focused on HSP60: HSP60 is up-regulated and presented by activated T cells (HSP60 is an ergotope) to regulatory (anti-ergotypic) T cells. Presentation of HSP60 by activated T cells was found to be MHC-restricted and dependent on accessory molecules - CD28, CD80 and CD86. Anti-ergotypic T cells responded to T-cell HSP60 by proliferation and secreted IFNγ and TGFβ1. In vitro, the anti-ergotypic T cells inhibited IFNγ production by their activated T-cell targets. In vivo, adoptive transfer of an anti-ergotypic HSP60-specific T-cell line led to decreased secretion of IFNγ by arthritogenic T cells and ameliorated adjuvant arthritis (AA). Thus, the presentation of HSP60 by activated T cells turns them into targets for anti-ergotypic regulatory T cells specific for HSP60. However, the direct interaction between the anti-ergotypic T regulators (anti-HSP60) and the activated T cells also down-regulated the regulators. Thus, by functioning as an ergotope, HSP60 can control both the effector T cells and the regulatory HSP60-specific T cells that control them