A cost minimisation analysis of a telepaediatric otolaryngology service

Background: Paediatric ENT services in regional areas can be provided through telemedicine (tele-ENT) using videoconferencing or with a conventional outpatient department ENT service (OPD-ENT) in which patients travel to see the specialist. The objective of this study was to identify the least-cost approach to providing ENT services for paediatric outpatients

The Different Function of Single Phosphorylation Sites of Drosophila melanogaster Lamin Dm and Lamin C

Lamins' functions are regulated by phosphorylation at specific sites but our understanding of the role of such modifications is practically limited to the function of cdc 2 (cdk1) kinase sites in depolymerization of the nuclear lamina during mitosis. In our study we used Drosophila lamin Dm (B-type) to examine the function of particular phosphorylation sites using pseudophosphorylated mutants mimicking single phosphorylation at experimentally confirmed in vivo phosphosites (S25E, S45E, T435E, S595E). We also analyzed lamin C (A-type) and its mutant S37E representing the N-terminal cdc2 (mitotic) site as well as lamin Dm R64H mutant as a control, non-polymerizing lamin. In the polymerization assay we could observe different effects of N-terminal cdc2 site pseudophosphorylation on A- and B-type lamins: lamin Dm S45E mutant was insoluble, in contrast to lamin C S37E. Lamin Dm T435E (C-terminal cdc2 site) and R64H were soluble in vitro. We also confirmed that none of the single phosphorylation site modifications affected the chromatin binding of lamin Dm, in contrast to the lamin C N-terminal cdc2 site. In vivo, all lamin Dm mutants were incorporated efficiently into the nuclear lamina in transfected Drosophila S2 and HeLa cells, although significant amounts of S45E and T435E were also located in cytoplasm. When farnesylation incompetent mutants were expressed in HeLa cells, lamin Dm T435E was cytoplasmic and showed higher mobility in FRAP assay

Discordant Gene Expression Signatures and Related Phenotypic Differences in Lamin A- and A/C-Related Hutchinson-Gilford Progeria Syndrome (HGPS)

Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N), we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic) and lamin A and C-related (hereditary) HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657) in sporadic and hereditary HGPS, with 83.3% (75/90) concordant and 16.7% (15/90) discordant transcriptional changes. Among the concordant ones we observed down-regulation of TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat and dermal appendages, and loss of expression in dermal fibroblasts and periadnexial cells from a LMNAK542N/K542N patient further confirming its pivotal role in skin development. Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS. Finally, this study correlates reduced TWIST2 and OPG expression with increased osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis in hereditary HGPS

Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species–season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds

Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells

Background: Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown. Results: Here we identify Heterochromatin Protein 1β (HP1β) as an essential protein for proper differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs. In pluripotent and differentiated cells HP1β is differentially localized and differentially associated with chromatin. Deletion of HP1β, but not HP1aα, in ESCs provokes a loss of the morphological and proliferative characteristics of embryonic pluripotent cells, reduces expression of pluripotency factors and causes aberrant differentiation. However, in differentiated cells, loss of HP1β has the opposite effect, perturbing maintenance of the differentiation state and facilitating reprogramming to an induced pluripotent state. Microscopy, biochemical fractionation and chromatin immunoprecipitation reveal a diffuse nucleoplasmic distribution, weak association with chromatin and high expression levels for HP1β in ESCs. The minor fraction of HP1β that is chromatin-bound in ESCs is enriched within exons, unlike the situation in differentiated cells, where it binds heterochromatic satellite repeats and chromocenters. Conclusions: We demonstrate an unexpected duality in the role of HP1β: it is essential in ESCs for maintaining pluripotency, while it is required for proper differentiation in differentiated cells. Thus, HP1β function both depends on, and regulates, the pluripotent state

Characterization of lamin Mutation Phenotypes in Drosophila and Comparison to Human Laminopathies

Lamins are intermediate filament proteins that make up the nuclear lamina, a matrix underlying the nuclear membrane in all metazoan cells that is important for nuclear form and function. Vertebrate A-type lamins are expressed in differentiating cells, while B-type lamins are expressed ubiquitously. Drosophila has two lamin genes that are expressed in A- and B-type patterns, and it is assumed that similarly expressed lamins perform similar functions. However, Drosophila and vertebrate lamins are not orthologous, and their expression patterns evolved independently. It is therefore of interest to examine the effects of mutations in lamin genes. Mutations in the mammalian lamin A/C gene cause a range of diseases, collectively called laminopathies, that include muscular dystrophies and premature aging disorders. We compared the sequences of lamin genes from different species, and we have characterized larval and adult phenotypes in Drosophila bearing mutations in the lam gene that is expressed in the B-type pattern. Larvae move less and show subtle muscle defects, and surviving lam adults are flightless and walk like aged wild-type flies, suggesting that lam phenotypes might result from neuromuscular defects, premature aging, or both. The resemblance of Drosophila lam phenotypes to human laminopathies suggests that some lamin functions may be performed by differently expressed genes in flies and mammals. Such still-unknown functions thus would not be dependent on lamin gene expression pattern, suggesting the presence of other lamin functions that are expression dependent. Our results illustrate a complex interplay between lamin gene expression and function through evolution

The Nobel Prize in physics 2012 for ground-breaking experimental methods that enable measuring and manipulation of individual quantum systems

W 2012 roku Nagrodę Nobla w dziedzinie fizyki otrzymali Serge Haroche i David J. Wineland „za przełomowe eksperymentalne metody, które umożliwiają pomiar i manipulację pojedynczych układów kwantowych”. Ich odkrycia pozwalają na wielokrotne obserwacje stanów kwantowych obiektów, takich jak fotony i jony, bez dekoherencji, czyli wymuszonego sprowadzenia tych cząsteczek na stałe do jednego z możliwych stanów. Przeprowadzone eksperymenty polegają na uwięzieniu cząsteczek w odpowiednich pułapkach jonowych schłodzonych do temperatur bliskich zeru absolutnemu, umieszczonych w próżni, a następnie wykorzystaniu różnic w sposobie oddziaływania cząsteczek na otoczenie w mierzonych stanach kwantowych. Te odkrycia wpłynęły na badania związane m.in. z komputerami kwantowymi i dokładnością pomiaru czasu.The Nobel Prize in Physics 2012 was awarded to Serge Haroche and David J. Wineland „for ground-breaking experimental methods that enable measuring and manipulation of individual quantum systems”. Their discoveries enable observing quantum states of objects, such as photons and ions, without decoherence, that is without forcefully making the particle choose one of the states. The experiments are based on trapping the particles in appropriate ion traps, cooled to temperatures close to the absolute zero, placed in vacuum, and then using the differences in interaction of the particles in different quantum states with the environment. These discoveries enabled advancements in studies of quantum computers and precise time measurements

Impact of parameters of corneal pulse signal on accuracy of detection of a dicrotic pulse

Występowanie dykrotycznego kształtu sygnału pulsu rogówki oka jest powiązane z procesem starzenia się i występowaniem jaskry. Dotychczas procedura wykrywania dykrotyzmu wymagała równoległego synchronicznego pomiaru pulsu rogówki oka, sygnału EKG i sygnału pulsu krwi, jednak nowe badania mogą pozwolić na detekcję dykrotyzmu tylko za pomocą pomiaru sygnału pulsu rogówki. Dokładność wykrywania dykrotyzmu zależy od parametrów sygnału wejściowego: długości i częstotliwości próbkowania. Z powodu odruchu mrugania u niektórych pacjentów trudno jest uzyskać odpowiednio długi sygnał nieobejmujący odruchu mrugania. Przeprowadzono eksperymenty numeryczne w celu określenia minimalnych wymagań rejestracji sygnału wejściowego w celu uzyskania odpowiedniej jakości klasyfikacji. Rezultaty wskazują na możliwość uzyskania dostatecznej jakości klasyfikacji sygnałów krótszych od 10 sekund pod warunkiem zapewnienia odpowiedniej częstotliwości próbkowania.The presence of the ocular dicrotic pulse is associated with aging and the glaucoma incidence. Previous procedures for detecting ocular dicrotism required synchronous measurement of ECG and blood pulse signals. However, recent studies have offered an opportunity to detect ocular dicrotism from the corneal pulse signal alone. The accuracy of the detection procedure mainly depends on the input signal length and its sampling frequency. The acquisition of the corneal pulse signal is performed in suppress blinking conditions. Hence, it is often difficult to acquire a sufficiently long signal for the analysis. Numerical experiments were conducted to determine the minimum requirements of the input signal in order to obtain adequate classification rate. The results indicate the possibility of obtaining sufficient classification rates for signals shorter than 10 seconds provided an adequate sampling is maintained