Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells.

Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients.

An unanticipated architecture of the 750-kDa α6β6 holoenzyme of 3-methylcrotonyl-CoA carboxylase.

3-Methylcrotonyl-CoA carboxylase (MCC), a member of the biotin-dependent carboxylase superfamily, is essential for the metabolism of leucine, and deficient mutations in this enzyme are linked to methylcrotonylglycinuria (MCG) and other serious diseases in humans. MCC has strong sequence conservation with propionyl-CoA carboxylase (PCC), and their holoenzymes are both 750-kilodalton (kDa) α(6)β(6) dodecamers. Therefore the architecture of the MCC holoenzyme is expected to be highly similar to that of PCC.

Image rotation and translation measurement based on double phase-encoded joint transform correlator.

An image rotation and translation measurement technology based on a double phase-encoded joint transform correlator (DPEJTC) is proposed. The reference and the target images are Fourier transformed. Then the magnitude of the Fourier-transformed reference (MFR) and target (MFT) images are multiplied with a high-pass emphasis filter and transformed from Cartesian space into polar space.

Discovery of a novel potent GABA(B) receptor agonist.

Structure-activity studies have led to a discovery of 3-(4-pyridyl)methyl ether derivative 9d that has 25- to 50-fold greater functional potency than R-baclofen at human and rodent GABA(B) receptors in vitro. Mouse hypothermia studies confirm that this compound crosses the blood-brain barrier and is approximately 50-fold more potent after systemic administration.

A pharmacological cocktail for arresting actin dynamics in living cells.

The actin cytoskeleton is regulated by factors that influence polymer assembly, disassembly, and network rearrangement. Drugs that inhibit these events have been used to test the role of actin dynamics in a wide range of cellular processes. Previous methods of arresting actin rearrangements take minutes to act and work well in some contexts, but can lead to significant actin reorganization in cells with rapid actin dynamics, such as neutrophils.

Comparative investigation of parameters for determining the dewaterability of activated sludge.

This paper compared four parameters evaluating the dewaterability of sludge--capillary suction time (CST), specific resistance to filtration (SRF), bound water content, and dry solids content in the centrifuged sludge cake of the different sludge flocs from seven full-scale wastewater treatment plants. The dry solids content correlated with the normalized CST (R2 = 0.7112, p = 0.

Influences of influent carbon source on extracellular polymeric substances (EPS) and physicochemical properties of activated sludge.

It is necessary to understand the bioflocculation, settling and dewatering characteristics in the activated sludge process in order to establish more efficient operational strategies. The influences of carbon source on the extracellular polymeric substances (EPS) and flocculation, settling and dewatering properties of the activated sludge were investigated. Laboratory-scale completely mixed activated sludge processes were used to grow the activated sludge with different carbon sources of starch, glucose and sodium acetate.

Hydrogen-bonding networks and RNA bases revealed by cryo electron microscopy suggest a triggering mechanism for calcium switches.

Helical assemblies such as filamentous viruses, flagella, and F-actin represent an important category of structures in biology. As the first discovered virus, tobacco mosaic virus (TMV) was at the center of virus research. Previously, the structure of TMV was solved at atomic detail by X-ray fiber diffraction but only for its dormant or high-calcium-concentration state, not its low-calcium-concentration state, which is relevant to viral assembly and disassembly inside host cells.

Atomic model of CPV reveals the mechanism used by this single-shelled virus to economically carry out functions conserved in multishelled reoviruses.

Unlike the multishelled viruses in the Reoviridae, cytoplasmic polyhedrosis virus (CPV) is single shelled, yet stable and fully capable of carrying out functions conserved within Reoviridae. Here, we report a 3.1 Å resolution cryo electron microscopy structure of CPV and derive its atomic model, consisting of 60 turret proteins (TPs), 120 each of capsid shell proteins (CSPs) and large protrusion proteins (LPPs).

Access to RNA encapsidated in the nucleocapsid of vesicular stomatitis virus.

The genomic RNA of negative-strand RNA viruses, such as vesicular stomatitis virus (VSV), is completely enwrapped by the nucleocapsid protein (N) in every stage of virus infection. During viral transcription/replication, however, the genomic RNA in the nucleocapsid must be accessible by the virus-encoded RNA-dependent RNA polymerase in order to serve as the template for RNA synthesis. With the VSV nucleocapsid and a nucleocapsid-like particle (NLP) produced in Escherichia coli, we have found that the RNA in the VSV nucleocapsid can be removed by RNase A, in contrast to what was previously reported.

Improved source assessment of Si, Al and related mineral components to PM10 based on a daily sampling procedure.

Samples obtained from an industrialized valley in the East Alpine region were collected daily for a half year and analyzed using X-ray fluorescence to examine the elements Si, Al, Fe, Ca, Mg, Na, K, Zn, P, S and Cl. Some factors affecting the changes of these elements were considered, including time, elemental correlations, weekday, weekend and seasonal changes. Diagnostic analysis provided an insight into a decoupling behavior that occursin siliceous and carbonates minerals.

Cryo-EM model of the bullet-shaped vesicular stomatitis virus.

Vesicular stomatitis virus (VSV) is a bullet-shaped rhabdovirus and a model system of negative-strand RNA viruses. Through direct visualization by means of cryo-electron microscopy, we show that each virion contains two nested, left-handed helices: an outer helix of matrix protein M and an inner helix of nucleoprotein N and RNA. M has a hub domain with four contact sites that link to neighboring M and N subunits, providing rigidity by clamping adjacent turns of the nucleocapsid.

Naphthalene-2,6-dicarb-oxy-lic acid-1-methyl-pyrrolidin-2-one (1/2).

The asymmetric unit of the title compound, C(12)H(8)O(4)·2C(5)H(9)NO, contains one half-mol-ecule of naphthalene-2,6-dicarb-oxy-lic acid (NDA) and one mol-ecule of 1-methyl-pyrrolidin-2-one (NMP): the NDA molecules lie on the crystallographic twofold rotation axes. In the crystal, the components are linked by strong O-H⋯O hydrogen bonds and C-H⋯O inter-actions.

L1 retrotransposition in human neural progenitor cells.

Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo.

Structure of the core editing complex (L-complex) involved in uridine insertion/deletion RNA editing in trypanosomatid mitochondria.

Uridine insertion/deletion RNA editing is a unique form of posttranscriptional RNA processing that occurs in mitochondria of kinetoplastid protists. We have carried out 3D structural analyses of the core editing complex or "L (ligase)-complex" from Leishmania tarentolae mitochondria isolated by the tandem affinity purification procedure (TAP). The purified material, sedimented at 20-25S, migrated in a blue native gel at 1 MDa and exhibited both precleaved and full-cycle gRNA-mediated U-insertion and U-deletion in vitro activities.

Arbaclofen placarbil, a novel R-baclofen prodrug: improved absorption, distribution, metabolism, and elimination properties compared with R-baclofen.

Baclofen is a racemic GABA(B) receptor agonist that has a number of significant pharmacokinetic limitations, including a narrow window of absorption in the upper small intestine and rapid clearance from the blood. Arbaclofen placarbil is a novel transported prodrug of the pharmacologically active R-isomer of baclofen designed to be absorbed throughout the intestine by both passive and active mechanisms via the monocarboxylate type 1 transporter. Arbaclofen placarbil is rapidly converted to R-baclofen in human and animal tissues in vitro.

An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells.

The elucidation of a code for regulated splicing has been a long-standing goal in understanding the control of post-transcriptional gene expression events that are crucial for cell survival, differentiation and development. We decoded functional RNA elements in vivo by constructing an RNA map for the cell type-specific splicing regulator FOX2 (also known as RBM9) via cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells. The map identified a large cohort of specific FOX2 targets, many of which are themselves splicing regulators, and comparison between the FOX2 binding profile and validated splicing events revealed a general rule for FOX2-regulated exon inclusion or skipping in a position-dependent manner.

The effects of Chinese medicines on micro-circulation of nail folds and blood flow velocity of limbs in the patients with arteriosclerotic obliteration.

The effects of Chinese medicines on micro-circulation and blood flow velocity in arteries of the lower limbs were observed in 33 patients with arteriosclerotic obliteration (ASO). The results showed that the integral values of micro-circulation after treatment were obviously higher than those before treatment (P < 0.05 or P < 0.

Selected-control synthesis of PbO2 and Pb3O4 single-crystalline nanorods.

Reaction of Pb(OH)3- with ClO- in the presence of surfactant CTAB under conventional conditions resulted in PbO2 nanorods, whereas the reaction under hydrothermal conditions afforded Pb3O4 nanorods, as confirmed by X-ray powder diffraction and transmission electron microscopy (TEM). Selected area electron diffraction (SEAD) and high-resolution TEM (HRTEM) revealed that both PbO2 and Pb3O4 nanorods are single crystalline. For the formation of Pb3O4 nanorods, it is reasonable that PbO2 slowly decomposes to Pb3O4 under hydrothermal conditions, while retaining the morphology of PbO2.

Stereoselective Solid-Phase Synthesis of a Triaza Tricyclic Ring System: A New Chemotype for Lead Discovery.

Sequential pyrrolidine and hydantoin ring-forming reactions have been applied in the stereoselective solid-phase synthesis of a conformationally constrained, tricyclic triazacyclopenta[c]pentalene scaffold. These novel compounds share the structural complexity characteristic of certain alkaloid natural products and represent a source of chemical diversity that complements more traditional classes of heterocyclic compounds of interest as potential pharmaceutical agents. They are assembled in a 12-step reaction sequence from 4 variable building blocks by combining an intramolecular azomethine ylide cycloaddition reaction with a final cyclative cleavage from resin.