DNA sequences can hybridize with each other in a predictable and a programmable manner to form linear and branched double-stranded (ds) helical structures. This ability makes DNA an excellent building block for preparation of nanostructures of defined shapes and sizes. For example, surface patterns and complex 2D and even 3D objects have been obtained by self-assembly of DNA strands.[1] To make dsDNA conductive, it has been coated with metals, metal oxides, or metal sulfides. For example, a number of methods for the complete coverage of DNA with Au 0 , Pd 0 , Pt 0 , Ag 0 , Cu 0 , and CdS have been reported. [2,3] However, less is known about the controlled modification of pre-selected sections of DNA. The first example of the selective coating of DNA with metal was reported by Braun and co-workers.[4] In particular, they protected a portion of l DNA with a RecA protein/ ssDNA complex. This step was followed by metallization of the unprotected DNA by sequential reduction of Ag + and Au 3+ . Finally, the RecA protein was degraded, exposing the protected region of l DNA for further manipulations. This method provided two stretches of conducting DNA wires that are interrupted by a circa 1 mm-long stretch of nonconductive DNA. However, as RecA-induced homologous recombination is efficient only with long DNA sections, this approach is limited to construction of rather large molecular objects (>1 mm).Chemical synthesis of dsDNA containing metal ions between coordinating base pairs has been reported. [5] By the variation of the number of such base pairs, the length of the metal-containing stretches within the DNA can be varied.[5] It still remains to be experimentally confirmed that the metal ion/DNA complexes obtained are conductive and, therefore, applicable as conducting wires.Herein we describe a method for selective metallization of ds regions of DNA with copper(0) (Figure 1). ssDNA overhangs present in the duplexes could potentially be used as addressable anchors for preparation of functional devices based on metallized dsDNA. We prepared a simple device of this type containing two metallized dsDNA connected by a non-metallized rigid linker.

Removal of toxic substances from the blood depends on patent connections between the kidney, ureters and bladder that are established when the ureter is transposed from its original insertion site in the male genital tract to the bladder. This transposition is thought to occur as the trigone forms from the common nephric duct and incorporates into the bladder. Here we re-examine this model in the context of normal and abnormal development. We show that the common nephric duct does not differentiate into the trigone but instead undergoes apoptosis, a crucial step for ureter transposition controlled by vitamin A-induced signals from the primitive bladder. Ureter abnormalities occur in 1-2% of the human population and can cause obstruction and end-stage renal disease. These studies provide an explanation for ureter defects underlying some forms of obstruction in humans and redefine the current model of ureter maturation.

Racemates often have lower solubility than enantiopure compounds, and mixing of enantiomers can enhance aggregation propensity of peptides. Amyloid β (Aβ) 42 is an aggregation-prone peptide, believed to play a key role in Alzheimer’s Disease. Soluble Aβ42 aggregation intermediates (oligomers) have emerged as particularly neurotoxic. We hypothesized that addition of mirror image (D-) Aβ42 should reduce the concentration of toxic oligomers formed by natural (L-) Aβ42. We synthesized L- and D-Aβ42 and found their equimolar mixing to lead to accelerated fibril formation. Confocal microscopy with fluorescently labeled analogs of the enantiomers showed their co-localization in racemic fibrils. Reflecting enhanced fibril formation propensity, racemic Aβ42 was less prone to form soluble oligomers. This resulted in protection of cells from toxicity of L-Aβ42 at concentrations ranging up to 50 µM. In summary, mixing of Aβ42 enantiomers induces accelerated formation of non-toxic fibrils.

Background Pelvic floor disorders including urinary incontinence (UI) and pelvic organ prolapse (POP) are common conditions; however, most women with these symptoms do not seek care. Failure to seek care may be related to misconceptions about these conditions. The aim of this study was to assess the baseline knowledge of UI and POP among adult women presenting to primary care clinics, as well as factors associated with knowledge levels. Methods A survey with questions from previously validated UI and POP knowledge questionnaires (PIKQ-UI and PIKQ-POP, respectively) was self-administered to a cross-sectional group of adult female patients presenting to three primary care clinics: geriatric, community-based, and hospital-based. Participants’ demographics and medical histories were compared using ANOVA or Kruskal-Wallis for continuous variables and Chi-square test or Fisher’s exact test for categorical variables. In order to compare various covariates with knowledge non-proficiency on PIKQ-UI and PIKQ-POP scales, unadjusted and adjusted ORs with 95% CIs were calculated using bivariate analysis and multivariate logistic regression, respectively. Results Of 346 participants, knowledge non-proficiency was similar and consistent across clinic sites and reached 72.0% for UI and 53.6% for POP. On multivariate analysis, lower educational attainment, being unaware of UI or POP as medical conditions, and having no history of care-seeking for these conditions were significantly associated with knowledge non-proficiency on UI, POP, or both. Conclusions Knowledge non-proficiency for UI and POP is common among women presenting for primary care. For UI, healthcare providers should assess patients’ actual understanding of the disease, especially among those with lower educational attainment, to eliminate any possible misconceptions. For POP, the focus should be on increasing awareness of this disease, as many women may have not previously heard of this condition. Simple strategies may increase knowledge in these areas and change care-seeking behaviors. Study registration None.

Racemic mixtures frequently display properties that are different from those associated with their enantiopure counterparts, and are often characterized by higher propensity to form aggregates. Our previous research established that mixing of the enantiomers of Alzheimer amyloid β (Aβ) 42 peptides is an effective strategy to induce an oligomer‐to‐fibril conversion, which puts Aβ42 into a substantially less toxic state. Here, new insights into this chiral inactivation effect are presented. In addition to the commonly used Thioflavin T fibril formation assays, the use of the less aggregation‐prone Aβ40 system allowed us to monitor peptide aggregation by NMR. Whereas enantiopure peptide was well soluble under the chosen experimental conditions and showed no sign of precipitation, addition of one equivalent of the mirror‐image peptide triggered an instant and rapid aggregation, observable through the attenuation of the NMR signal. The racemic Aβ40 fibrils were found by transmission electron microscopy to be distinct in morphology, exhibiting a ~2‐fold narrowing as compared with their enantiopure counterparts.