Electrical spin injection and detection in Germanium using three terminal geometry

In this letter, we report on successful electrical spin injection and detection in \textit{n}-type germanium-on-insulator (GOI) using a Co/Py/Al$_{2}$O$_{3}$ spin injector and 3-terminal non-local measurements. We observe an enhanced spin accumulation signal of the order of 1 meV consistent with the sequential tunneling process via interface states in the vicinity of the Al$_{2}$O$_{3}$/Ge interface. This spin signal is further observable up to 220 K. Moreover, the presence of a strong \textit{inverted} Hanle effect points at the influence of random fields arising from interface roughness on the injected spins.Comment: 4 pages, 3 figure

Electrical and thermal spin accumulation in germanium

In this letter, we first show electrical spin injection in the germanium conduction band at room temperature and modulate the spin signal by applying a gate voltage to the channel. The corresponding signal modulation agrees well with the predictions of spin diffusion models. Then by setting a temperature gradient between germanium and the ferromagnet, we create a thermal spin accumulation in germanium without any tunnel charge current. We show that temperature gradients yield larger spin accumulations than pure electrical spin injection but, due to competing microscopic effects, the thermal spin accumulation in germanium remains surprisingly almost unchanged under the application of a gate voltage to the channel.Comment: 7 pages, 3 figure

Crossover from spin accumulation into interface states to spin injection in the germanium conduction band

Electrical spin injection into semiconductors paves the way for exploring new phenomena in the area of spin physics and new generations of spintronic devices. However the exact role of interface states in spin injection mechanism from a magnetic tunnel junction into a semiconductor is still under debate. In this letter, we demonstrate a clear transition from spin accumulation into interface states to spin injection in the conduction band of $n$-Ge. We observe spin signal amplification at low temperature due to spin accumulation into interface states followed by a clear transition towards spin injection in the conduction band from 200 K up to room temperature. In this regime, the spin signal is reduced down to a value compatible with spin diffusion model. More interestingly, we demonstrate in this regime a significant modulation of the spin signal by spin pumping generated by ferromagnetic resonance and also by applying a back-gate voltage which are clear manifestations of spin current and accumulation in the germanium conduction band.Comment: 5 pages, 4 figure

Pocket Size Ultra-Sound versus Cardiac Auscultation in Diagnosing Cardiac Valve Pathologies: A Prospective Cohort

Background: Pocket-size ultrasound devices are used to perform focused ultrasound studies (POCUS). We compared valve malfunction diagnosis rate by cardiac auscultation to POCUS (insonation), both conducted by medical students. Methods: A prospective cohort study was conducted among subjects with and without clinically relevant valve dysfunction. Inclusion criteria for subjects with a clinically relevant valve dysfunction was based on the presence of at least one moderate severity valve pathology identified by echocardiography. Three final-year medical students examined the patients. Each subject underwent auscultation and a POCUS using a pocket-size ultrasound machine. Sensitivity and specificity were calculated. Results: The study included 56 patients. In 18 patients (32%) no valve pathology was found. Nineteen patients (34%) had at least two valvular pathologies. Sixty valve lesions were present in the entire cohort. Students' sensitivity for detecting any valve lesion was 32% and 64% for auscultation and insonation, respectively, and specificity was similar. The sensitivity for diagnosing mitral regurgitation, mitral stenosis, and aortic regurgitation rose significantly by using POCUS compared to auscultation alone. When using POCUS, students identified valvular pathologies in 22 cases (39%) from the patients with at least two valve dysfunctions, and none when using auscultation. Conclusions: Final-year medical students' competency to detect valve dysfunction by performing cardiac auscultation is poor. Cardiac ultrasound-focused training significantly improved medical students' sensitivity for diagnosing a variety of valve pathologies

Q&A: ChIP-seq technologies and the study of gene regulation

10.1186/1741-7007-8-56BMC Biology85

Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al

Assigning roles to DNA regulatory motifs using comparative genomics

Motivation: Transcription factors (TFs) are crucial during the lifetime of the cell. Their functional roles are defined by the genes they regulate. Uncovering these roles not only sheds light on the TF at hand but puts it into the context of the complete regulatory network

Rb regulates fate choice and lineage commitment in vivo

February 1, 2011Mutation of the retinoblastoma gene (RB1) tumour suppressor occurs in one-third of all human tumours and is particularly associated with retinoblastoma and osteosarcoma[superscript 1]. Numerous functions have been ascribed to the product of the human RB1 gene, the retinoblastoma protein (pRb). The best known is pRb’s ability to promote cell-cycle exit through inhibition of the E2F transcription factors and the transcriptional repression of genes encoding cell-cycle regulators[superscript 1]. In addition, pRb has been shown in vitro to regulate several transcription factors that are master differentiation inducers[superscript 2]. Depending on the differentiation factor and cellular context, pRb can either suppress or promote their transcriptional activity. For example, pRb binds to Runx2 and potentiates its ability to promote osteogenic differentiation in vitro[superscript 3]. In contrast, pRb acts with E2F to suppress peroxisome proliferator-activated receptor γ subunit (PPAR-γ), the master activator of adipogenesis[superscript 4, 5]. Because osteoblasts and adipocytes can both arise from mesenchymal stem cells, these observations suggest that pRb might play a role in the choice between these two fates. However, so far, there is no evidence for this in vivo. Here we use mouse models to address this hypothesis in mesenchymal tissue development and tumorigenesis. Our data show that Rb status plays a key role in establishing fate choice between bone and brown adipose tissue in vivo.National Cancer Institute (U.S.) (Grant)National Institutes of Health (U.S.) (Grant

Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene

Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state