Comparative HPLC-MSn analysis of canine and human meibomian lipidomes: many similarities, a few differences

The aim of this study was to evaluate the lipidome of meibomian gland secretions in canines (cMGS) – a common pet and laboratory animal – and to compare it with that of human MGS (hMGS), to determine whether canines could be used as a valid experimental animal model in studies of the biochemistry and physiology of the human ocular surface in general, and of the Meibomian glands in particular. The MGS of both species were evaluated using HPLC in combination with atmospheric pressure chemical ionization ion trap mass spectrometry. The main lipid classes found in cMGS were very long chain cholesteryl esters, wax esters, (O-acyl)-omega-hydroxy fatty acids (OAHFA), and cholesteryl esters of OAHFA. The lipidomes of cMGS and hMGS were found to be qualitatively similar, which implies similar biosynthetic and biodegradation pathways in canines and humans. However, some quantitative differences between the two were observed

Ferroelectricity induced by interatomic magnetic exchange interaction

Multiferroics, where two or more ferroic order parameters coexist, is one of the hottest fields in condensed matter physics and materials science[1-9]. However, the coexistence of magnetism and conventional ferroelectricity is physically unfavoured[10]. Recently several remedies have been proposed, e.g., improper ferroelectricity induced by specific magnetic[6] or charge orders[2]. Guiding by these theories, currently most research is focused on frustrated magnets, which usually have complicated magnetic structure and low magnetic ordering temperature, consequently far from the practical application. Simple collinear magnets, which can have high magnetic transition temperature, have never been considered seriously as the candidates for multiferroics. Here, we argue that actually simple interatomic magnetic exchange interaction already contains a driving force for ferroelectricity, thus providing a new microscopic mechanism for the coexistence and strong coupling between ferroelectricity and magnetism. We demonstrate this mechanism by showing that even the simplest antiferromagnetic (AFM) insulator MnO, can display a magnetically induced ferroelectricity under a biaxial strain

Coexistence of the topological state and a two-dimensional electron gas on the surface of Bi2Se3

Topological insulators are a recently discovered class of materials with fascinating properties: While the inside of the solid is insulating, fundamental symmetry considerations require the surfaces to be metallic. The metallic surface states show an unconventional spin texture, electron dynamics and stability. Recently, surfaces with only a single Dirac cone dispersion have received particular attention. These are predicted to play host to a number of novel physical phenomena such as Majorana fermions, magnetic monopoles and unconventional superconductivity. Such effects will mostly occur when the topological surface state lies in close proximity to a magnetic or electric field, a (superconducting) metal, or if the material is in a confined geometry. Here we show that a band bending near to the surface of the topological insulator Bi$_2$Se$_3$ gives rise to the formation of a two-dimensional electron gas (2DEG). The 2DEG, renowned from semiconductor surfaces and interfaces where it forms the basis of the integer and fractional quantum Hall effects, two-dimensional superconductivity, and a plethora of practical applications, coexists with the topological surface state in Bi$_2$Se$_3$. This leads to the unique situation where a topological and a non-topological, easily tunable and potentially superconducting, metallic state are confined to the same region of space.Comment: 12 pages, 3 figure

Implementation of medicines pricing policies in sub-Saharan Africa: protocol for a systematic review

Introduction Ensuring universal availability and accessibility of medicines and supplies is critical for national health systems to equitably address population health needs. In sub-Saharan Africa (SSA), this is a recognised priority with multiple medicines pricing policies enacted. However, medicine prices have remained high, continue to rise and constrain their accessibility. In this systematic review, we aim to identify and analyse experiences of implementation of medicines pricing policies in SSA. Our ambition is for this evidence to contribute to improved implementation of medicines pricing policies in SSA. Methods and analysis We will search: Medline, Web of Science, Scopus, Global Health, Embase, Cairn.Info International Edition, Erudit and African Index Medicus, the grey literature and reference from related publications. The searches will be limited to literature published from the year 2000 onwards that is, since the start of the Millennium Development Goals. Published peer-reviewed studies of implementation of medicines pricing policies in SSA will be eligible for inclusion. Broader policy analyses and documented experiences of implementation of other health policies will be excluded. The team will collaboratively screen titles and abstracts, then two reviewers will independently screen full texts, extract data and assess quality of the included studies. Disagreements will be resolved by discussion or a third reviewer. Data will be extracted on approaches used for policy implementation, actors involved, evidence used in decision making and key contextual influences on policy implementation. A narrative approach will be used to synthesise the data. Reporting will be informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guideline. Ethics and dissemination No ethics approvals are required for systematic reviews. Results will be disseminated through academic publications, policy briefs and presentations to national policymakers in Ghana and mode widely across countries in SSA. PROSPERO registration number CRD42020178166

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Visualizing sound emission of elephant vocalizations: evidence for two rumble production types

Recent comparative data reveal that formant frequencies are cues to body size in animals, due to a close relationship between formant frequency spacing, vocal tract length and overall body size. Accordingly, intriguing morphological adaptations to elongate the vocal tract in order to lower formants occur in several species, with the size exaggeration hypothesis being proposed to justify most of these observations. While the elephant trunk is strongly implicated to account for the low formants of elephant rumbles, it is unknown whether elephants emit these vocalizations exclusively through the trunk, or whether the mouth is also involved in rumble production. In this study we used a sound visualization method (an acoustic camera) to record rumbles of five captive African elephants during spatial separation and subsequent bonding situations. Our results showed that the female elephants in our analysis produced two distinct types of rumble vocalizations based on vocal path differences: a nasally- and an orally-emitted rumble. Interestingly, nasal rumbles predominated during contact calling, whereas oral rumbles were mainly produced in bonding situations. In addition, nasal and oral rumbles varied considerably in their acoustic structure. In particular, the values of the first two formants reflected the estimated lengths of the vocal paths, corresponding to a vocal tract length of around 2 meters for nasal, and around 0.7 meters for oral rumbles. These results suggest that African elephants may be switching vocal paths to actively vary vocal tract length (with considerable variation in formants) according to context, and call for further research investigating the function of formant modulation in elephant vocalizations. Furthermore, by confirming the use of the elephant trunk in long distance rumble production, our findings provide an explanation for the extremely low formants in these calls, and may also indicate that formant lowering functions to increase call propagation distances in this species'