Phosphine-Stabilized Pnictinidenes.

The reaction of the intramolecular germylene-phosphine Lewis pair (o-PPh )C H GeAr* (1) with Group 15 element trichlorides ECl (E=P, As, Sb) was investigated. After oxidative addition, the resulting compounds (o-PPh )C H (Ar*)Ge(Cl)ECl (2: E=P, 3: E=As, 4: E=Sb) were reduced by using sodium metal or LiHBEt . The molecular structures of the phosphine-stabilized phosphinidene (o-PPh )C H (Ar*)Ge(Cl)P (5), arsinidene (o-PPh )C H (Ar*)Ge(Cl)As (6) and stibinidene (o-PPh )C H (Ar*)Ge(Cl)Sb (7) are presented; they feature a two-coordinate low-valent Group 15 element.

Phosphine-Stabilized Germasilenylidene: Source for a Silicon-Atom Transfer.

A phosphine-stabilized germasilenylidene is synthesized following the pathway of SiCl oxidative addition at a germylene-phosphine Lewis pair. Low-temperature reduction using {(Nacnac)Mg} resulted in a chlorosilylene intermediate and finally a molecule exhibiting a Ge═Si: motif. Inside the chelating phosphine-germylene, a low-valent silicon atom is stabilized and was transferred to diazabutadiene to give N-heterocyclic silylenes.

Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a rare hematopoietic disease characterized by a block in red cell differentiation. Most DBA cases are caused by mutations in ribosomal proteins and characterized by higher than normal activity of the tumor suppressor p53. Higher p53 activity is thought to contribute to DBA phenotypes by inducing apoptosis during red blood cell differentiation.

Germaborenes: Borylene Transfer Agents for the Synthesis of Iminoboranes.

Halide and phenyl substituted germaborenes were shown to react with azides at room temperature and transfer a borylene moiety to give iminoboranes. This iminoborane synthesis based on a borylene transfer route was investigated computationally in the case of the phenyl substituted germaborene.

Ge=B π-Bonding: Synthesis and Reversible [2+2] Cycloaddition of Germaborenes.

Phosphine-stabilized germaborenes featuring an unprecedented Ge=B double bond with short B⋅⋅⋅Ge contacts of 1.886(2) (4) and 1.895(3) Å (5) were synthesized starting from an intramolecular germylene-phosphine Lewis pair (1).

A zone-plate-based two-color spectrometer for indirect X-ray absorption spectroscopy.

X-ray absorption spectroscopy (XAS) is a powerful element-specific technique that allows the study of structural and chemical properties of matter. Often an indirect method is used to access the X-ray absorption (XA). This work demonstrates a new XAS implementation that is based on off-axis transmission Fresnel zone plates to obtain the XA spectrum of LaSrMnO by analysis of three emission lines simultaneously at the detector, namely the O 2p-1s, Mn 3s-2p and Mn 3d-2p transitions.

Transmission zone plates as analyzers for efficient parallel 2D RIXS-mapping.

We have implemented and successfully tested an off-axis transmission Fresnel zone plate as spectral analyzer for resonant inelastic X-ray scattering (RIXS). The imaging capabilities of zone plates allow for advanced two-dimensional (2D) mapping applications. By varying the photon energy along a line focus on the sample, we were able to simultaneously record the emission spectra over a range of excitation energies.

Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with mutations.

Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines.

L-Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q- syndrome in a TP53-independent way.

Haploinsufficiency of ribosomal proteins (RPs) and upregulation of the tumour suppressor TP53 have been shown to be the common basis for the anaemia observed in Diamond Blackfan anaemia and 5q- myelodysplastic syndrome. We previously demonstrated that treatment with L-Leucine resulted in a marked improvement in anaemia in disease models. To determine if the L-Leucine effect was Tp53-dependent, we used antisense MOs to rps19 and rps14 in zebrafish; expression of tp53 and its downstream target cdkn1a remained elevated following L-leucine treatment.

Ultrafast dynamical study of pyrene-N,N-dimethylaniline (PyDMA) as an organic molecular diode in solid state.

Femtosecond optical pump-probe spectroscopy has been employed for studying the directly linked electron donor-acceptor system pyrene-N,N-dimethylaniline (PyDMA) in solid state. This DMA-pyrene derivative discussed is being applied as a molecular diode system switching on an ultrafast time scale. Our ultrafast solid-state studies reveal a complex photochemistry of this molecular crystal system.

The emerging importance of ribosomal dysfunction in the pathogenesis of hematologic disorders.

More than a decade has passed since the initial identification of ribosomal protein gene mutations in patients with Diamond-Blackfan anemia (DBA), a hematologic disorder that became the founding member of a class of diseases known as ribosomopathies. In these diseases, genetic abnormalities that result in defective ribosome biogenesis cause strikingly tissue-specific phenotypes in patients, specifically bone marrow failure, craniofacial abnormalities and skeletal defects. Several animal models and numerous in vitro studies have demonstrated that the p53 pathway is central to the ribosomopathy phenotype.

Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency.

NOTCH1 pathway activation contributes to the pathogenesis of over 60% of T-cell acute lymphoblastic leukemia (T-ALL). While Notch is thought to exert the majority of its effects through transcriptional activation of Myc, it also likely has independent roles in T-ALL malignancy. Here, we utilized a zebrafish transgenic model of T-ALL, where Notch does not induce Myc transcription, to identify a novel Notch gene expression signature that is also found in human T-ALL and is regulated independently of Myc.

Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity resulting in significant morbidity and mortality. The pathology of BPD is multifactorial and leads to alveolar simplification and distal lung injury. Previous studies have shown a beneficial effect of systemic treatment with bone marrow-derived mesenchymal stromal cells (MSCs) and MSC-conditioned media (MSC-CM) leading to amelioration of the lung parenchymal and vascular injury in vivo in the hyperoxia murine model of BPD.

Characterization of the cell of origin for small cell lung cancer.

Small cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer that affects more than 200,000 people worldwide every year with a very high mortality rate. Here, we used a mouse genetics approach to characterize the cell of origin for SCLC; in this mouse model, tumors are initiated by the deletion of the Rb and p53 tumor suppressor genes in the lung epithelium of adult mice. We found that mouse SCLCs often arise in the lung epithelium, where neuroendocrine cells are located, and that the majority of early lesions were composed of proliferating neuroendocrine cells.

Commentary: Sca-1 and Cells of the Lung: A matter of Different Sorts.

In two separate articles published in this issue, Teisanu et al. and McQualter et al. report the use of flow cytometry and cell sorting to identify putative bronchiolar stem cells that are low in expression for the cell surface marker Sca-1 yet negative for CD34, and a mesenchymal, fibroblastic progenitor cell population from the lung that is positive for Sca-1, respectively.

Stem cell biology in the lung and lung cancers: using pulmonary context and classic approaches.

Classic stem cell biology approaches tailored specifically with lung biology in mind are needed to bring the field of lung stem cell biology up to speed with that in other tissues. The infrequent cellular turnover, the diversity of cell types, and the necessity of daily cell function in this organ must be considered in stem cell studies. Previous work has created a base from which to explore transplantation, label retention, and more sophisticated lineage-tracing schemes to identify and characterize stem cell populations in the normal lung.

Experimental characterization and Monte Carlo simulation of Si(Li) detector efficiency by radioactive sources and PIXE.

This work relates to the study and characterization of the response function of an X-ray spectrometry system. The intrinsic efficiency of a Si(Li) detector has been simulated with the Monte Carlo codes MCNP and GEANT4 in the photon energy range of 2.6-59.