Phylogenetic analysis of ferlin genes reveals ancient eukaryotic origins

<p>Abstract</p> <p>Background</p> <p>The ferlin gene family possesses a rare and identifying feature consisting of multiple tandem C2 domains and a C-terminal transmembrane domain. Much currently remains unknown about the fundamental function of this gene family, however, mutations in its two most well-characterised members, dysferlin and otoferlin, have been implicated in human disease. The availability of genome sequences from a wide range of species makes it possible to explore the evolution of the ferlin family, providing contextual insight into characteristic features that define the ferlin gene family in its present form in humans.</p> <p>Results</p> <p>Ferlin genes were detected from all species of representative phyla, with two ferlin subgroups partitioned within the ferlin phylogenetic tree based on the presence or absence of a DysF domain. Invertebrates generally possessed two ferlin genes (one with DysF and one without), with six ferlin genes in most vertebrates (three DysF, three non-DysF). Expansion of the ferlin gene family is evident between the divergence of lamprey (jawless vertebrates) and shark (cartilaginous fish). Common to almost all ferlins is an N-terminal C2-FerI-C2 sandwich, a FerB motif, and two C-terminal C2 domains (C2E and C2F) adjacent to the transmembrane domain. Preservation of these structural elements throughout eukaryotic evolution suggests a fundamental role of these motifs for ferlin function. In contrast, DysF, C2DE, and FerA are optional, giving rise to subtle differences in domain topologies of ferlin genes. Despite conservation of multiple C2 domains in all ferlins, the C-terminal C2 domains (C2E and C2F) displayed higher sequence conservation and greater conservation of putative calcium binding residues across paralogs and orthologs. Interestingly, the two most studied non-mammalian ferlins (Fer-1 and Misfire) in model organisms <it>C. elegans </it>and <it>D. melanogaster</it>, present as outgroups in the phylogenetic analysis, with results suggesting reproduction-related divergence and specialization of species-specific functions within their genus.</p> <p>Conclusions</p> <p>Our phylogenetic studies provide evolutionary insight into the ferlin gene family. We highlight the existence of ferlin-like proteins throughout eukaryotic evolution, from unicellular phytoplankton and apicomplexan parasites, through to humans. We characterise the preservation of ferlin structural motifs, not only of C2 domains, but also the more poorly characterised ferlin-specific motifs representing the DysF, FerA and FerB domains. Our data suggest an ancient role of ferlin proteins, with lessons from vertebrate biology and human disease suggesting a role relating to vesicle fusion and plasma membrane specialization.</p

Comparison of three molecular methods for the detection and speciation of Plasmodium vivax and Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Accurate diagnosis of <it>Plasmodium </it>spp. is essential for the rational treatment of malaria. Despite its many disadvantages, microscopic examination of blood smears remains the current "gold standard" for malaria detection and speciation. PCR assays offer an alternative to microscopy which has been shown to have superior sensitivity and specificity. Unfortunately few comparative studies have been done on the various molecular based speciation methods.</p> <p>Methods</p> <p>The sensitivity, specificity and cost effectiveness of three molecular techniques were compared for the detection and speciation of <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>from dried blood spots collected from 136 patients in western Thailand. The results from the three molecular speciation techniques (nested PCR, multiplex PCR, and real-time PCR) were used to develop a molecular consensus (two or more identical PCR results) as an alternative gold standard.</p> <p>Results</p> <p>According to the molecular consensus, 9.6% (13/136) of microscopic diagnoses yielded false negative results. Multiplex PCR failed to detect <it>P. vivax </it>in three mixed isolates, and the nested PCR gave a false positive <it>P. falciparum </it>result in one case. Although the real-time PCR melting curve analysis was the most expensive method, it was 100% sensitive and specific and least time consuming of the three molecular techniques investigated.</p> <p>Conclusion</p> <p>Although microscopy remains the most appropriate method for clinical diagnosis in a field setting, its use as a gold standard may result in apparent false positive results by superior techniques. Future studies should consider using more than one established molecular methods as a new gold standard to assess novel malaria diagnostic kits and PCR assays.</p

Plasmodium vivax trophozoites insensitive to chloroquine

© 2008 Sharrock et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Electrochromic Properties of Sol-Gel Prepared Hybrid Transition Metal Oxides A Short Review

This short review paper revisits the progress achieved in the last 10-15 years in the field of hybrid electrochromic materials, synthesized through sol-gel methods.During the recent decade, new avenues have been opened, exploring new concepts and particularly interesting applications of electrochromism. In this paper, we will discusssome of the new research directions in the field of electrochromism, together with novel applications of many electrochromic hybrid oxides. The most important incentive for enhanced properties of traditional materials has been the advent of nanotechnology. The discoveries in the field of synthesis of nanomaterials enabled to expand the materials and connect the morphological features of nanoparticles to the electrochromic properties at the macro level. This was possible because of the emergence of the new and more elaborate characterization methods, enabling to unveil hitherto unknown structural and morphological properties of electrochromic materials.It is important to mention the development of novel hybrid materials with significantly improved EC properties, where tungsten oxide is associated with carbonaceous materials such as MWCNT or graphene. These hybrid materials with enhanced EC properties, compared to the inorganic hybrids, will be remarkable in the future,for a series of novel applications.Retracing briefly the history of EC hybrid materials and summarizing the principal achievements will be useful not only for researchers in the field but for a wider readership as well

Przydatność kliniczna siatek centylowych urodzeniowej masy ciała w opiece nad noworodkiem

In view of the last few decades of progress within neonatology , the clinicians’ attentionis now focused on children with low bir th rate (&lt; 2,500 g) and with extremely low bir thrate (&lt; 1,000 g) in par ticular. Most of these patients are born prematurely . Assessmentof their physical maturity should be per formed within the first hours of their life. Whencross-referenced with anthropological measurements it guides fu rther management, aswell as mortality and morbidity prognostication. Various scales/scores are used to verifythe gestational age determined by the obstetricians. The current standard is the NewBallard Score (Dubowitz/Ballard). Centile charts allow for objective determination of theintrauterine growth as well as birth weight and measurements. Clinical utility of the chartsdepends on: population representativity, consideration for special cases (e.g. prematurity,number of foetuses in multiple pregnancy), if they are up to date and include seculartrends. Current neonatological standard in polish clinical practise are the Fenton’s growthcharts. However, they are based on a different population and there are no separate chartsfor multiple pregnancies available. Therefore, Polish growth charts are needed. These chartswould be representative for the neonatal population of this part of Europe and would takeinto account the social developments of the last few decades. Ideally, they should take thegestational age, gender and a number of foetuses into account. They would require a largeprospective study to validate them.W obliczu postępu, jaki dokonał się w neonatologii w ostatnich dekadach, uwaga lekarzy skupia się na populacji dzieci z małą [ < 2500g], a w szczególności skrajnie małą [500-999g] urodzeniową masą ciała. Większość z tych pacjentów stanowią noworodki urodzone przedwcześnie. Ocena ich dojrzałości powinna być dokonywana w pierwszych godzinach życia zewnątrzmacicznego. Odniesienie jej do wyników pomiarów antropometrycznych, dostarcza podstawowych informacji mających wpływ na postępowanie z noworodkiem i rokowanie względem chorobowości oraz śmiertelności. Pourodzeniowej weryfikacji wieku płodowego, oszacowanego przez położników, służą różne skale oceny. Obecnie podstawową jest New Ballard Score. W określeniu prawidłowości wewnątrzmacicznego wzrastania, a precyzyjniej - w obiektywizacji obserwacji z okresu ciąży i z pierwszego badania fizykalnego, pomocne są odpowiednio dobrane siatki centylowe wymiarów i urodzeniowej masy ciała. Przydatność kliniczna krzywych wzrastania zależy od ich: reprezentatywności dla danej populacji, uwzględnienia szczególnych uwarunkowań (np. wcześniactwa, ilości płodów w danej ciąży), oraz aktualności – z uwzględnieniem trendów, w tym sekularnych. W Polsce, w standardach w neonatologii, zalecane do stosowania w praktyce klinicznej są siatki centylowe Fentona. Przy ich tworzeniu nie wykorzystywano danych z populacji dzieci z tego regionu. Nie mają one także oddzielnych krzywych dla noworodków z ciąż wielopłodowych. Istnieje zatem potrzeba stworzenia polskich siatek centylowych, reprezentatywnych dla noworodków z tej części Europy i uwzględniających zmiany zachodzące w naszym społeczeństwie w ostatnich dekadach. Optymalnie, powinny być sporządzone z uwzględnieniem wieku postkoncepcyjnego, płci oraz z rozgraniczeniem ilości płodów w danej ciąży. Wskazane byłoby także przeprowadzenie prospektywnego badania, służącego ich walidacji

Implementation of Glucose-6-Phosphate Dehydrogenase (G6PD) testing for Plasmodium vivax case management, a mixed method study from Cambodia

Plasmodium vivax remains a challenge for malaria elimination since it forms dormant liver stages (hypnozoites) that can reactivate after initial infection. 8-aminoquinolone drugs kill hypnozoites but can cause severe hemolysis in individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. The STANDARD G6PD test (Biosensor) is a novel point-of-care diagnostic capable of identifying G6PD deficiency prior to treatment. In 2021, Cambodia implemented the Biosensor to facilitate radical cure treatment for vivax malaria. To assess the Biosensor’s implementation after its national rollout, a mixed-methods study was conducted in eight districts across three provinces in Cambodia. Interviews, focus group discussions, and observations explored stakeholders’ experiences with G6PD testing and factors influencing its implementation. Quantitative data illustrative of test implementation were gathered from routine surveillance forms and key proportions derived. Qualitative data were analyzed thematically. The main challenge to implementing G6PD testing was that only 49.2% (437/888) of eligible patients reached health centers for G6PD testing following malaria diagnosis by community health workers. Factors influencing this included road conditions and long distances to the health center, compounded by the cost of seeking further care and patients’ perceptions of vivax malaria and its treatment. 93.9% (790/841) of eligible vivax malaria patients who successfully completed referral (429/434) and directly presented to the health center (360/407) were G6PD tested. Key enabling factors included the test’s acceptability among health workers and their understanding of the rationale for testing. Only 36.5% (443/1213) of eligible vivax episodes appropriately received primaquine. 70.5% (165/234) of female patients and all children under 20 kilograms never received primaquine. Our findings suggest that access to radical cure requires robust infrastructure and income security, which would likely improve referral rates to health centers enabling access. Bringing treatment closer to patients, through community health workers and nuanced community engagement, would improve access to curative treatment of vivax malaria

Detection of Salivary Tryptase Levels in Children following Oral Food Challenges

BACKGROUND: Oral food challenge (OFC) is commonly used to diagnose food allergy. This test is time and resource intensive, and conclusions are not always unequivocal as this relies on the interpretation of symptoms. Therefore, an objective marker would improve the accuracy of the diagnostic workup of food allergy. OBJECTIVES: The aim of this study was to investigate whether tryptase can be detected in saliva of children following OFC. METHOD: Children from 3 to 18 years of age were eligible for inclusion if an OFC for peanut or tree nut had been recommended. Saliva samples were collected prior to the first dose and 5, 10, and 15 min following the last administered dose during OFC. Assay precision, spike-and-recovery, and assessment of lower limit of detection of the tryptase immunoassay were examined before analysis of tryptase in saliva was performed. RESULTS: A total of 30 children were included (median age 8 years, 63.3% male, 53.3% positive OFC outcome). Tryptase was detected in saliva samples. The mean of the change in baseline tryptase value to each saliva collecting time point was significantly different in patients with a positive OFC outcome compared to a negative outcome (p < 0.01). CONCLUSIONS: This study showed that tryptase can be detected in saliva of children following OFC. Increased levels of tryptase compared to baseline were found if the OFC outcome was positive, suggesting that measuring tryptase in saliva may be useful in the diagnosis of food allergy. Further research is needed to evaluate the potential association between tryptase levels and symptoms

Evolution of collective and noncollective structures in Xe-123

An experiment involving a heavy-ion-induced fusion-evaporation reaction was carried out where high-spin states of 123Xe were populated in the 80Se (48Ca,5n) 123Xe reaction at 207 MeV beam energy. Gamma-ray coincidence events were recorded with the Gammasphere Ge detector array. The previously known level scheme was confirmed and enhanced with the addition of five new band structures and several interband transitions. Cranked Nilsson-Strutinsky (CNS) calculations were performed and compared with the experimental results in order to assign configurations to the bands.Additional co-authors: T Lauritsen, S Zhu, A Korichi, P Fallon, B M Nyakó, and J Timá