Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs

We explore the possibility of characterizing sperm cells without the need to stain them using spectral and fluorescence lifetime analyses after multi-photon excitation in an insect model. The autofluorescence emission spectrum of sperm of the common bedbug, Cimex lectularius, was consistent with the presence of flavins and NAD(P)H. The mean fluorescence lifetimes showed smaller variation in sperm extracted from the male (tau m, τ_m = 1.54–1.84 ns) than in that extracted from the female sperm storage organ (tau m, τ_m = 1.26–2.00 ns). The fluorescence lifetime histograms revealed four peaks. These peaks (0.18, 0.92, 2.50 and 3.80 ns) suggest the presence of NAD(P)H and flavins and show that sperm metabolism can be characterized using fluorescence lifetime imaging. The difference in fluorescence lifetime variation between the sexes is consistent with the notion that female animals alter the metabolism of sperm cells during storage. It is not consistent, however, with the idea that sperm metabolism represents a sexually selected character that provides females with information about the male genotype.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Flammenpyrolytische Silikatbeschichtung bei Normaldruck als Alternative zu Vakuumverfahren. Combustion CVD of silica as an alternative method to vakuum treatment

In advancement of Pyrosil®‐technology a new kind of precursor delivery was developed, build and tested on real substrates. A Lab‐demonstrator was build to demonstrate the resources of the technology.     

Kommunikationsoberfläche Membran‐ Vorbild für moderne Nanoanalytik

A central event in the life of a cellular system is the interaction between the exterior and the interior compartments. Biochemical signals arrive at the cellular surface, bind to their membrane bound receptor followed by a conformational change triggering the release of an internal chemical or electrical signal.This basic principle is followed by all our perceptive abilities like sense of smell or taste, but also by different signal transduction pathways involved in nerve conductivity, vision, sense of touch or hearing. To follow and mimic this principle of parallel registration is one of the aims of modern nanobiotechnology. If we are able to specifically biofunctionalize small arrays of a solid surface, which could be an electrode or a semiconductor, this approach will enable us to build up devices called “biochips” or “biosensors” that allow the determination of bioactive molecules with high specificity at lowest concentrations. Potential pharmacological active substrates might be screened as well as new receptors may be determined. Applications in genomics as well as proteomics are realistic. The major prerequisite for such a broad spectrum of applications is the fabrication of receptive surfaces. Biomolecules have to be surface‐adsorbed in a highly reproducible, oriented and well organised fashion, a task which in biology is taken by the cellular membranes as external or internal receptive surfaces. The physical principles like hydrogen bonds, electrostatic or hydrophobic interactions that lead to such an organized surface are well known. To synthesize molecular building blocks and to position them onto an otherwise unspecific surface is one of the challenges of nanobiotechnology combining biological knowledge and chemical skills with biophysical techniques that allow to handle or analyze even single molecules.     

Synchronous Full-Scan for Asynchronous Handshake Circuits

Handshake circuits form a special class of asynchronous circuits that has enabled the industrial exploitation of the asynchronous potential such as low power, low electromagnetic emission, and increased cryptographic security. In this paper we present a test solution for handshake circuits that brings synchronous test-quality to asynchronous circuits. We add a synchronous mode of operation to handshake circuits that allows full controllability and observability during test. This technique is demonstrated on some industrial examples and gives over 99% stuck-at fault coverage, using test-pattern generators developed for synchronous circuits. The paper describes how such a full-scan mode can be achieved, including an approach to minimize the number of dummy latches in case latches are used in the data path of the handshake circuit.     

Intramolecular crosslinking of poly(vinyl alcohol)

Poly(vinyl alcohol) is crosslinked in dilute solution (c=0.1 wt%) with glutaraldehyde. The reaction product is characterized by viscometry and gel permeation chromatography (g.p.c.). The intrinsic viscosity decreases with increasing degree of crosslinking and does not depend on temperature. G.p.c. reveals that the reaction product is not homogeneous, but consists of a mixture of particles with different sizes, possibly both intra- and intermolecularly crosslinked molecules. The intramolecularly crosslinked molecules are smaller in size than the initial polymer molecules and their size depends on the degree of crosslinking. They possess a narrow particle size distribution even if the initial polymer sample had a broad molecular weight distribution.