Infection tracking in travellers using a mobile app (ITIT): the pilot study

BACKGROUND: Current surveillance of travellers' health captures only a small proportion of illness events. We aimed to evaluate the usability and feasibility of using an app to enable travellers to self-report illness. METHOD: This pilot study assesses a novel mobile application called Infection Tracking in Travellers (ITIT) that records travel-related symptoms with associated geolocation and weather data. Participants were recruited in three Swiss travel clinics between December 2021 and March 2022. A feedback survey was used to examine app ease of use, and data from the app was used to examine travel and illness patterns as a proof-of-concept for the larger ITIT study. RESULTS: Participants were recruited from Zurich, Basel, and Geneva, with 37 individuals completing a total of 394 questionnaires in 116 locations in Asia, Africa, the Americas, and Europe. Illness symptoms were reported by 41% of participants, 67% of which were respiratory. The post travel questionnaire showed that all participants found the app easy to use and 63% said they would recommend it to others. Several users provided suggestions for improved usability. CONCLUSION: The app fulfilled its function as a research tool linking infection symptoms with geolocation and climate data

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia

Mutations in SCN2A cause epilepsy syndromes of variable severity including neonatal-infantile seizures. In one case, we previously described additional childhood-onset episodic ataxia. Here, we corroborate and detail the latter phenotype in three further cases. We describe the clinical characteristics, identify the causative SCN2A mutations and determine their functional consequences using whole-cell patch-clamping in mammalian cells. In total, four probands presented with neonatal-onset seizures remitting after five to 13 months. In early childhood, they started to experience repeated episodes of ataxia, accompanied in part by headache or back pain lasting minutes to several hours. In two of the new cases, we detected the novel mutation p.Arg1882Gly. While this mutation occurred de novo in both patients, one of them carries an additional known variant on the same SCN2A allele, inherited from the unaffected father (p.Gly1522Ala). Whereas p.Arg1882Gly alone shifted the activation curve by -4 mV, the combination of both variants did not affect activation, but caused a depolarizing shift of voltage-dependent inactivation, and a significant increase in Na+ current density and protein production. p.Gly1522Ala alone did not change channel gating. The third new proband carries the same de novo SCN2A gain-of-function mutation as our first published case (p.Ala263Val). Our findings broaden the clinical spectrum observed with SCN2A gain-of-function mutations, showing that fairly different biophysical mechanisms can cause a convergent clinical phenotype of neonatal seizures and later onset episodic ataxia.Peer reviewe

Spectrum of Phenotypic, Genetic, and Functional Characteristics in Patients With Epilepsy With KCNC2 Pathogenic Variants

Background and ObjectivesKCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyze the clinical phenotype, genetic background, and biophysical function of disease-associated Kv3.2 variants.MethodsIndividuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic, and functional analysis. Cases were referred through clinical and research collaborations. Selected de novo variants were examined electrophysiologically in Xenopus laevis oocytes.ResultsWe identified novel KCNC2 variants in 18 patients with various forms of epilepsy, including genetic generalized epilepsy (GGE), developmental and epileptic encephalopathy (DEE) including early-onset absence epilepsy, focal epilepsy, and myoclonic-atonic epilepsy. Of the 18 variants, 10 were de novo and 8 were classified as modifying variants. Eight drug-responsive patients became seizure-free using valproic acid as monotherapy or in combination, including severe DEE cases. Functional analysis of 4 variants demonstrated gain of function in 3 severely affected DEE cases and loss of function in 1 case with a milder phenotype (GGE) as the underlying pathomechanisms.DiscussionThese findings implicate KCNC2 as a novel causative gene for epilepsy and emphasize the critical role of KV3.2 in the regulation of brain excitability

MscS-like mechanosensitive channels in plants and microbes

The challenge of osmotic stress is something all living organisms must face as a result of environmental dynamics. Over the past three decades, innovative research and cooperation across disciplines have irrefutably established that cells utilize mechanically gated ion channels to release osmolytes and prevent cell lysis during hypoosmotic stress. Early electrophysiological analysis of the inner membrane of Escherichia coli identified the presence of three distinct mechanosensitive activities. The subsequent discoveries of the genes responsible for two of these activities, the mechanosensitive channels of large (MscL) and small (MscS) conductance, led to the identification of two diverse families of mechanosensitive channels. The latter of these two families, the MscS family, consists of members from bacteria, archaea, fungi, and plants. Genetic and electrophysiological analysis of these family members has provided insight into how organisms use mechanosensitive channels for osmotic regulation in response to changing environmental and developmental circumstances. Furthermore, determining the crystal structure of E. coli MscS and several homologues in several conformational states has contributed to our understanding of the gating mechanisms of these channels. Here we summarize our current knowledge of MscS homologues from all three domains of life and address their structure, proposed physiological functions, electrophysiological behaviors, and topological diversity

Husbandry Of Monodelphis Domestica In The Study Of Mammalian Embryogenesis

Monodelphis domestica, commonly called the laboratory opossum, is a useful laboratory animal for studying marsupial embryogenesis and mammalian development. Females breed year-round and the animals can be sustainably bred indoors. The authors draw on their own laboratory\u27s experience to supplement previously published research on laboratory opossums. They describe a breeding protocol that reliably produces timed-pregnant M. domestica. Additionally, the authors discuss general laboratory opossum husbandry techniques and describe how to collect, handle and culture embryos

Identifying feature-specific genes that in a donor plant provide a predetermined feature, useful for example for preparing transgenic plants colonizable by mycorrhiza, comprises screening fusions of donor and acceptor genetic materials

Abstract: NOVELTY - Identifying feature-specific genes (A) that in a donor plant (D), provide a predetermined feature comprises: (a) preparing genetic donor material from (D); (b) preparing genetic receptor material from receptor plant (R) lacking the feature; (c) heterologous fusion of the two to form hybrid material (H); (d) culturing H and identifying model plants with the feature; and (e) genetic analysis to identify those genes that are part of (D), as (A). USE - The method is useful for identifying feature-specific genes (A) that in a donor plant (D), provide a predetermined feature (claimed). The method is used to identify feature-specific genes and to generate transgenic or chimeric plants with preselected features for use in forestry, agriculture, environmental protection, pharmaceuticals and production of active compounds. A particular feature is susceptibility to colonization by mycorrhizal fungi, which provide nutrients, trace elements and water, and increase resistance to e.g. heavy metals, but other features are e.g. ability to produce alginate; resistance to stressful conditions; or rapid growth, e.g. where genes from low-value trees are transferred to more valuable timber trees. ADVANTAGE - The method is applicable to a large number of different features. DETAILED DESCRIPTION - Identifying feature-specific genes (A) that, in a donor plant (D), cause appearance of a predetermined feature comprises: (a) preparing genetic donor material from (D); (b) preparing genetic receptor material from a receptor plant (R) that lacks the feature; (c) heterologous fusion of the two materials to form hybrid material (H); (d) culturing H and identifying at least one model plant with the feature; and (e) genetic analysis of this plant to identify those genes that are part of (D), as (A). INDEPENDENT CLAIMS are also included for the following: (1) Genetic manipulation of plants in which a feature-specific gene, or gene cluster, is identified by the new method then transferred; (2) Hybrid plants produced by method (1); (3) Transgenic plants containing at least one (A) that has been identified by the new method; and (4) Apparatus for identifying (A), especially by the new method. Technology Focus/Extension Abstract: TECHNOLOGY FOCUS - BIOTECHNOLOGY - Preferred Process: Step (d) includes selection under conditions where hybrid material containing (A) has better survival than other hybrid material, especially culture in a physical or chemical medium against which only donor material is resistant. The donor material is genetically modified by incorporation of a known resistance gene into at least one chromosome (or segment) of (D). Selection may use promoter-reporter genes and the donor material has been subjected to chromosomal segregation, optionally also to chromosomal labeling by binding specific markers to chromosomes or their segments. Once an (A) has been detected, its location on particular chromosomes or segments of (D) is determined.Preferred Apparatus: This includes devices for preparing donor and receptor materials, fusion, and culture (including a selection step), and genetic analysis