Heme Stabilization of α-Synuclein Oligomers during Amyloid Fibril Formation.

α-Synuclein (αSyn), which forms amyloid fibrils, is linked to the neuronal pathology of Parkinson's disease, as it is the major fibrillar component of Lewy bodies, the inclusions that are characteristic of the disease. Oligomeric structures, common to many neurodegenerative disease-related proteins, may in fact be the primary toxic species, while the amyloid fibrils exist either as a less toxic dead-end species or even as a beneficial mechanism for clearing damaged proteins. To alter the progression of the aggregation and gain insights into the prefibrillar structures, we determined the effect of heme on αSyn oligomerization by several different techniques, including native (nondenaturing) polyacrylamide gel electrophoresis, thioflavin T fluorescence, transmission electron microscopy, atomic force microscopy, circular dichroism, and membrane permeation using a calcein release assay.

Peptide-Metal Organic Framework Swimmers that Direct the Motion toward Chemical Targets.

Highly efficient and robust chemical motors are expected for the application in microbots that can selectively swim toward targets and accomplish their tasks in sensing, labeling, and delivering. However, one of major issues for such development is that current artificial swimmers have difficulty controlling their directional motion toward targets like bacterial chemotaxis. To program synthetic motors with sensing capability for the target-directed motion, we need to develop swimmers whose motions are sensitive to chemical gradients in environments.

From Sexual Assault to Sexual Risk: A Relational Pathway?

Among women and gay and bisexual men, sexual assault is associated with increased rates of sexual risk behavior and negative sexual health outcomes. Although the mechanisms of these effects are potentially myriad, the current analyses examine the role of perceived partner pressure for condomless sex in mediating the association between adult sexual assault (ASA) and recent anal or vaginal sex without a condom. In a sample of 205 young adult women and gay and bisexual men, ASA was indirectly associated with condomless anal and/or vaginal sex via perceptions of partner pressure for condomless sex, χ(1) = 5.

Equations of motion for rays in a Snell's law medium.

The equations of motion for a ray in a Snell's law medium with a varying index of refraction are derived. A stratified medium is considered. Explicit expressions are given for the velocity and acceleration components of the ray.

Derivation of T cells in vitro from mouse embryonic stem cells.

The OP9/OP9-DL1 co-culture system has become a well-established method for deriving differentiated blood cell types from embryonic and hematopoietic progenitors of both mouse and human origin. It is now used to address a growing variety of complex genetic, cellular and molecular questions related to hematopoiesis, and is at the cutting edge of efforts to translate these basic findings to therapeutic applications. The procedures are straightforward and routinely yield robust results.

Sample limited characterization of a novel disulfide-rich venom peptide toxin from terebrid marine snail Terebra variegata.

Disulfide-rich peptide toxins found in the secretions of venomous organisms such as snakes, spiders, scorpions, leeches, and marine snails are highly efficient and effective tools for novel therapeutic drug development. Venom peptide toxins have been used extensively to characterize ion channels in the nervous system and platelet aggregation in haemostatic systems. A significant hurdle in characterizing disulfide-rich peptide toxins from venomous animals is obtaining significant quantities needed for sequence and structural analyses.

Adapting in vitro embryonic stem cell differentiation to the study of locus control regions.

Numerous locus control region (LCR) activities have been discovered in gene loci important to immune cell development and function. LCRs are a distinct class of cis-acting gene regulatory elements that appear to contain all the DNA sequence information required to establish an independently and predictably regulated gene expression program at any genomic site in native chromatin of a whole animal. As such, LCR-regulated transgenic reporter systems provide invaluable opportunities to investigate the mechanisms of gene regulatory DNA action during development.

Deadenylation and its regulation in eukaryotic cells.

Messenger RNA deadenylation is a process that allows rapid regulation of gene expression in response to different cellular conditions. The change of the mRNA poly(A) tail length by the activation of deadenylation might regulate gene expression by affecting mRNA stability, mRNA transport, or translation initiation. Activation of deadenylation processes are highly regulated and associated with different cellular conditions such as cancer, development, mRNA surveillance, DNA damage response, and cell differentiation.

Regulating the ubiquitin/proteasome pathway via cAMP-signaling: neuroprotective potential.

The cAMP-signaling pathway has been under intensive investigation for decades. It is a wonder that such a small simple molecule like cAMP can modulate a vast number of diverse processes in different types of cells. The ubiquitous involvement of cAMP-signaling in a variety of cellular events requires tight spatial and temporal control of its generation, propagation, compartmentalization, and elimination.

Negative regulation of 26S proteasome stability via calpain-mediated cleavage of Rpn10 subunit upon mitochondrial dysfunction in neurons.

Proteasomal and mitochondrial dysfunctions are implicated in chronic neurodegenerative diseases. To investigate the impact of mitochondrial impairment on the proteasome, we treated rat cerebral cortical neurons with oligomycin, antimycin, or rotenone, which inhibit different elements of the electron transport chain. Firstly, we observed a reduction in ubiquitinated proteins and E1 activity.

Positive and negative feedback loops in the p53 and mRNA 3' processing pathways.

Although the p53 network has been intensively studied, genetic analyses long hinted at the existence of components that remained elusive. Recent studies have shown regulation of p53 at the mRNA level mediated via both the 5' and the 3' untranslated regions and affecting the stability and translation efficiency of the p53 mRNA. Here, we provide evidence of a feedback loop between p53 and the poly(A)-specific ribonuclease (PARN), in which PARN deadenylase keeps p53 levels low in nonstress conditions by destabilizing p53 mRNA, and the UV-induced increase in p53 activates PARN deadenylase, regulating gene expression during DNA damage response in a transactivation-independent manner.

cAMP stimulates the ubiquitin/proteasome pathway in rat spinal cord neurons.

Proteasome impairment and accumulation of ubiquitinated proteins are implicated in neurodegeneration associated with different forms of spinal cord injury. We show herein that elevating cAMP in rat spinal cord neurons increases 26S proteasome activity in a protein kinase A-dependent manner. Treating spinal cord neurons with dibutyryl-cAMP (db-cAMP) also raised the levels of various components of the UPP including proteasome subunits Rpt6 and β5, polyubiquitin shuttling factor p62/sequestosome1, E3 ligase CHIP, AAA-ATPase p97 and the ubiquitin gene ubB.

Coordination between proteasome impairment and caspase activation leading to TAU pathology: neuroprotection by cAMP.

Neurofibrillary tangles (NFTs) are hallmarks of Alzheimer's disease (AD). The main component of NFTs is TAU, a highly soluble microtubule-associated protein. However, when TAU is cleaved at Asp421 by caspases it becomes prone to aggregation leading to NFTs.

The prevalence of peripheral arterial disease (PAD) and PAD risk factors among different ethnic groups in the US population.

The National Health and Nutrition Examination Survey (NHANES) 2003-2004 data set was utilized to examine and compare trends and differences in PAD-related risk factor variables among 5 different ethnic/racial groups. The sample included individuals 40 years and older with PAD and of the ethnic/racial groups: Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, and Other/Multiracial. Two demographic variables (age and gender) and 4 PAD-risk factors (hypertension [HTN], systolic blood pressure [SBP], and diastolic blood pressure [DBP]), dyslipidemia, high-density lipoprotein [HDL] and low-density lipoprotein [LDL], diabetes, and cigarette smoking) were examined for each group.

Facile synthesis of a flexible tethered porphyrin dimer that preferentially complexes fullerene C70.

A simple, high yield, two-step synthesis yields a porphyrin dimer linked by a flexible dithiol tether that preferentially binds fullerene C(70) over C(60) in toluene solution. The complex forms stable aggregates when cast on glass.

Comparison of identical and functional Igh alleles reveals a nonessential role for Eμ in somatic hypermutation and class-switch recombination.

Somatic hypermutation (SHM), coupled with Ag selection, provides a mechanism for generating Abs with high affinity for invading pathogens. Class-switch recombination (CSR) ensures that these Abs attain pathogen-appropriate effector functions. Although the enzyme critical to both processes, activation-induced cytidine deaminase, has been identified, it remains unclear which cis-elements within the Ig loci are responsible for recruiting activation-induced cytidine deaminase and promoting its activity.

A tale of two obesCities: the role of municipal governance in reducing childhood obesity in New York City and London.

As rates of childhood obesity and overweight rise around the world, researchers and policy makers seek new ways to reverse these trends. Given the concentration of the world's population, income inequalities, unhealthy diets, and patterns of physical activity in cities, urban areas bear a disproportionate burden of obesity. To address these issues, in 2008, researchers from the City University of New York and London Metropolitan University created the Municipal Responses to Childhood Obesity Collaborative.

Kinetic analysis of the interaction of b/HLH/Z transcription factors Myc, Max, and Mad with cognate DNA.

Myc, Mad, and Max proteins belong to the basic helix-loop-helix leucine zipper family of transcription factors. They bind to a specific hexanucleotide element of DNA, the E-box (CACGTG). To be biologically active, Myc and Mad require dimerization with Max.

Kinetic mechanism for the binding of eIF4F and tobacco Etch virus internal ribosome entry site rna: effects of eIF4B and poly(A)-binding protein.

The wheat germ eukaryotic translation initiation factor (eIF) 4F binds tightly to the mRNA internal ribosome entry site (IRES) of tobacco etch virus (TEV) to promote translation initiation. When eIF4F is limiting, TEV is preferentially translated compared with host cell mRNA. To gain insight into the dynamic process of protein synthesis initiation and the mechanism of binding, the kinetics of eIF4F binding to TEV IRES were examined.

Clinical examination tools for lateropulsion or pusher syndrome following stroke: a systematic review of the literature.

Objective: To examine the clinimetric properties and clinical applicability of published tools for 'quantifying' the degree of lateropulsion or pusher syndrome following stroke.

Data Sources: Search through electronic databases (MEDLINE, EMBASE, CINAHL, Science Citation Index) with the terms lateropulsion, pushing, pusher syndrome, validity, reliability, internal consistency, responsiveness, sensitivity, specificity, posture and stroke. Databases were searched from their inception to October 2008.

Self-organized porphyrinic materials.

The self-assembly and self-organization of porphyrins and related macrocycles enables the bottom-up fabrication of photonic materials for fundamental studies of the photophysics of these materials and for diverse applications. This rapidly developing field encompasses a broad range of disciplines including molecular design and synthesis, materials formation and characterization, and the design and evaluation of devices. Since the self-assembly of porphyrins by electrostatic interactions in the late 1980s to the present, there has been an ever increasing degree of sophistication in the design of porphyrins that self-assemble into discrete arrays or self-organize into polymeric systems.

Fabrication of metal nanoparticles using toroidal plasmid DNA as a sacrificial mold.

A new method for synthesizing gold, nickel, and cobalt metal nanoparticles at room temperature from metal salts employing plasmid DNA in a toroidal topology as a sacrificial mold is presented. The diameter of the toroidal DNA drives the formation and size of the nanoparticle, and UV light initiates the oxidation of the DNA and concomitant reduction of the DNA bound metal ions. The nanoparticles were characterized by atomic force microscopy (AFM), transmission electron microscopy (TEM), and electron diffraction (ED).

A role for the IgH intronic enhancer E mu in enforcing allelic exclusion.

The intronic enhancer (E mu) of the immunoglobulin heavy chain (IgH) locus is critical for V region gene assembly. To determine E mu's subsequent functions, we created an Igh allele with assembled V(H) gene but with E mu removed. In mice homozygous for this E mu-deficient allele, B cell development was normal and indistinguishable from that of mice with the same V(H) knockin and E mu intact.

Low concentrations of a non-hydrolysable tetra-S-glycosylated porphyrin and low light induces apoptosis in human breast cancer cells via stress of the endoplasmic reticulum.

A water-soluble tetra-S-glycosylated porphyrin (P-Glu(4)) is absorbed by MDA-MB-231 human breast cancer cells whereupon irradiation with visible light causes necrosis or apoptosis depending on the concentration of the porphyrin and the power of the light. With the same amount of light irradiation power (9.4 W m(-2)), at 10-20 microM concentrations necrosis is predominantly observed, while at <10 microM concentrations, apoptosis is the principal cause of cell death.

Electrostatic self-organization of robust porphyrin-polyoxometalate films.

Strategies to create thin films using layer-by-layer methods use oppositely charged polymeric polyelectrolytes for both or at least one component to beneficially exploit multitopic electrostatic interactions between the deposited layers with opposite charges. In contrast, the electrostatic deposition of tetracationic 5,10,15,20-tetrakis(1'-methyl-4'-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP(4+)) with tetraanionic polyoxometalates such as EuPW(11)O(39)(4-) or SiW(12)O(40)(4-) onto charged substrates, such as mica, or polar substrates, such as glass and indium-tin oxide (ITO), demonstrates that the use of polymeric components is not a priori necessary. The use of molecules in sequential dipping approaches requires a careful balance in the interaction energies between the oppositely charged molecules, as demonstrated by the observation that a tetraanionic porphyrin such as 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin does not form layers with TMPyP(4+).