HM+ and HM+?He (M = Group 2 metal): chemical or physical interactions?

We investigate the HM+–He complexes (M = Group 2 metal) using quantum chemistry. Equilibrium geometries are linear for M = Be and Mg, and bent for M = Ca–Ra; the explanation for this lies in the differing nature of the highest occupied molecular orbitals in the two sets of complexes. The difference primarily occurs as a result of the formation of the H–M+ bond, and so the HM+ diatomics are also studied as part of the present work. The position of the He atom in the complexes is largely determined by the form of the electron density. HM+. . . He binding energies are obtained and are surprisingly high for a helium complex. The HBe+. . . He value is almost 3000 cm−1, which is high enough to suspect contributions from chemical bonding. This is explored by examining the natural orbital density and by population analyses

Evaluation of Magnetic Micro- and Nanoparticle Toxicity to Ocular Tissues

Purpose: Magnetic nanoparticles (MNPs) may be used for focal delivery of plasmids, drugs, cells, and other applications. Here we ask whether such particles are toxic to ocular structures. Methods: To evaluate the ocular toxicity of MNPs, we asked if either 50 nm or 4 mm magnetic particles affect intraocular pressure, corneal endothelial cell count, retinal morphology including both cell counts and glial activation, or photoreceptor function at different time points after injection. Sprague-Dawley rats (n = 44) were injected in the left eye with either 50 nm (3 ml, 1.65 mg) or 4 mm(3ml, 1.69 mg) magnetic particles, and an equal volume of PBS into the right eye. Electroretinograms (ERG) were used to determine if MNPs induce functional changes to the photoreceptor layers. Enucleated eyes were sectioned for histology and immunofluorescence. Results: Compared to control-injected eyes, MNPs did not alter IOP measurements. ERG amplitudes for a-waves were in the 100–250 mV range and b-waves were in the 500–600 mV range, with no significant differences between injected and noninjected eyes. Histological sectioning and immunofluorescence staining showed little difference in MNP-injected animals compared to control eyes. In contrast, at 1 week, corneal endothelial cell numbers were significantly lower in the 4 mm magnetic particle-injected eyes compared to either 50 nm MNP- or PBS-injected eyes. Furthermore, iron deposition was detected after 4 mm magnetic particle but not 50 nm MNP injection

Can environmental or occupational hazards alter the sex ratio at birth? A systematic review

More than 100 studies have examined whether environmental or occupational exposures of parents affect the sex ratio of their offspring at birth. For this review, we searched Medline and Web of Science using the terms ‘sex ratio at birth’ and ‘sex ratio and exposure’ for all dates, and reviewed bibliographies of relevant studies to find additional articles. This review focuses on exposures that have been the subject of at least four studies including polychlorinated biphenyls (PCBs), dioxins, pesticides, lead and other metals, radiation, boron, and g-forces. For paternal exposures, only dioxins and PCBs were consistently associated with sex ratios higher or lower than the expected 1.06. Dioxins were associated with a decreased proportion of male births, whereas PCBs were associated with an increased proportion of male births. There was limited evidence for a decrease in the proportion of male births after paternal exposure to DBCP, lead, methylmercury, non-ionizing radiation, ionizing radiation treatment for childhood cancer, boron, or g-forces. Few studies have found higher or lower sex ratios associated with maternal exposures. Studies in humans and animals have found a reduction in the number of male births associated with lower male fertility, but the mechanism by which environmental hazards might change the sex ratio has not yet been established

Produktion och karaktärisering av alternativa scaffold proteins för medicinska applikationer

Antibodies, as forerunners in the field of biological drugs, are originally an organism’s answer to the invasion of different pathogens. Today, antibodies are a common treatment for many chronic diseases such as the immune-mediated inflammatory diseases rheumatoid arthritis or psoriasis. It is suspected that the cytokines interleukin 17a (IL17a) and interleukin 17c (IL17c) are involved in those diseases and are commonly treated with antibodies that inhibit the cytokines. Even though antibodies have been a huge success as biological drugs they also have downsides when it comes to their production, size and stability. In quest of finding alternatives to antibodies in diagnostics and therapy, a novel class of biologics has been developed. So-called alternative scaffold proteins are small polypeptide chains that can be engineered to show affinity towards different biomarkers. ABD-Derived Affinity ProTeins or ADAPTs are one example of these alternative scaffolds that can be modified to bind a biomarker as target and keep their affinity to Human Serum Albumin (HSA) at the same time, making them bispecific. In this project, twenty-four previously selected ADAPT binder candidates that have shown good prospects towards IL17a and IL17c in previous experiments were cloned, produced, purified and characterized to determine if they show potential as tools in diagnostics or therapy of autoimmune diseases. The proteins were produced in E. coli, purified by affinity chromatography and characterized using Surface Plasmon Resonance (SPR), Circular Dichroism (CD) and Size Exclusion Chromatography (SEC). All candidates were successfully cloned into E. coli and out of these, 10 could be produced and 5 showed affinity towards their target using SPR. Examination by SEC and CD showed that the protein variants did not seem to be structurally stable and hints of impurities in the samples could be detected. This and a low yield could be further confirmed via SDS-PAGE. In conclusion, binders were produced that could theoretically be promising candidates as tools in diagnostics or therapy of chronic diseases were IL17a and/or IL17c are important. Nevertheless, in order to support these claims further investigations and developments are necessary.Antikroppar, som föregångare inom området biologiska läkemedel, är ursprungligen en organisms svar på invasionen av olika patogen. Idag är antikroppar en vanlig behandling för många kroniska sjukdomar, såsom de immunmedierade inflammatoriska sjukdomarna reumatoid artrit eller psoriasis. Cytokinerna interleukin 17a (IL17a) och interleukin 17c (IL17c) tros vara involverade i dessa sjukdomar och behandlas vanligtvis med antikroppar som hämmar cytokinerna. Trots att antikroppar har varit en stor framgång som biologiska läkemedel har de också nackdelar när det gäller deras produktion, storlek och stabilitet. För att hitta alternativ till antikroppar inom diagnostik och terapi har en ny klass av biologiska läkemedel utvecklats. Så kallade alternative scaffold proteins är små polypeptidkedjor som kan manipuleras för att visa affinitet gentemot olika biomarkörer. ABD-Derived Affinity ProTeins eller ADAPTs är ett exempel på dessa alternative scaffolds som kan modifieras för att binda en biomarkör som mål utan att påverka affiniteten till Humant Serum Albumin (HSA), vilket gör dem bispecifika. I detta projekt klonades, producerades, renades och karakteriserades tjugofyra tidigare utvalda ADAPT-bindarkandidater som har visat goda förutsättningar gentemot IL17a och IL17c i tidigare experiment. Proteinerna producerades i E. coli, renades genom affinitetskromatografi och karakteriserades med användning av Surface Plasmon Resonance (SPR), Circular Dichroism (CD) och Size Exclusion Chromatography (SEC). Alla kandidater klonades framgångsrikt i E. coli och av dessa kunde 10 produceras. Fem bindare visade affinitet till deras mål med SPR. Undersökning med SEC och CD visade dock att proteinvarianterna inte var strukturellt stabila och antydan till föroreningar kunde detekteras i proverna. Detta och ett lågt utbyte kunde ytterligare bekräftas via SDS-PAGE. Sammanfattningsvis kunde bindare producerades och dessa kan teoretiskt vara lovande kandidater till diagnostik eller terapi av kroniska sjukdomar där IL17a och/eller IL17c är viktiga. För att stödja dessa påståenden krävs dock ytterligare experiment och utveckling av bindarna