Letter from Lucy Webster, R. Squire, W.F. Webster, and Alice M. Squire to John Muir, 1864 Jan 25

[2] Dear friend Muir I am now seated to write you a few lines to let you know that I am well and hope these few lines will find you the same There have been a great many men enlisting and there is a great many more to go to war. I wish this war would soon end but I fear it will be a long time before [illegible] rebellion is Crushed. Mr Muir I thank you a thousand times for [thoes?] images alltho they never entered our house. W. F. Webster[3] Dear Mr Muir I will write a few lines to you now the rest got through. I thank you very much for those presents. Those imagyes got broke the boys was playing ball and [they?] threw it through the window and hit them and broke them all to pieces but we got the bell Eddys Gilberts folks have moved down to Green County so he does not come to school this winter. A lady from Bellvile teaches our school. We have [99?] scholars. Weston and Charley came here to school this winter their Father has enlisted. I got that picture from Mrs. Heebys but it does not look much as it did for it was clean then but it is dirty now and looks real bad. They are having a singing school down to Storytown this winter Alice M SquireMr John Muir, 00347 [4]I shall have to explain the reason for delaying to send this letter or you will think we were very negligent, I have a Niece attending school at the University, and she said she would see the janitor and get him to bring those things you left, to her room, And she took your letter, lest she might forget, And if we could not remember your address, and did not get your letter again, until yesterday. Mr Squire has gone back to his Reg\u27t. and we feel very sad about it. I went up Saturday, expecting to see him but they had sent him away two days before, His Regiment are at Natehes. R Squire[1] January 11th 1864Dear friend Muir We received your kind letter and was very glad to hear from you and to know that you was enjoying yourself among your friends. we are all well at present we are going to school but do not have a very good one this winter we have a female teacher. Gilbert McKeeby is teaching up to the white school house this winter [Nett?] goes up there to school, Mr [illegible] people are as well as usual Willie as mischievous as ever. Sophia Mc Keeby is teaching down to Story town. Mr Smoles people I believe are all well Henerette and Jacob come here to school they had the great affliction to loose a son who came home sick from the army, Mrs Harper has returned from the east they are all well. I think of no more to write at present. write soon good by. [Long?] Webster64

A comparison of didodecyldimethylammonium bromide adsorbed at mica/water and silica/water interfaces using neutron reflection.

The layer structure of the dichain alkyl ammonium surfactant, didodecyldimethylammonium bromide (DDAB), adsorbed from water on to silica and mica surfaces has been determined using neutron reflection. Although sometimes considered interchangeable surfaces for study, we present evidence of significant differences in the adsorbed layer structure below the critical micelle concentration. A complete DDAB bilayer was assembled at the water/mica interface at concentrations below the critical micelle concentration (CMC). In contrast it is not until the CMC was reached that the complete bilayer structure formed on the oxidised silicon crystal. Removal of the complete bilayer on both surfaces was attempted by both washing and ion exchange yet the adsorbed structure proved tenacious.BPThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jcis.2016.06.01

Development of a targeted forensic test for the identification of Eurasian beaver DNA

Eurasian beaver (Castor fiber) has recently been reintroduced in Scotland after more than 400 years of extinction and in 2019 received legal protection; deliberate killing or disturbing beavers without a license is therefore now an offense. We present a validated polymerase chain reaction (PCR)-based Eurasian beaver identification test for use in forensic casework where persecution of Eurasian beaver is suspected. Primers were designed to target a 271 base pair region of the mitochondrial cytochrome b (Cytb) gene in Eurasian beavers, and positive amplicons were confirmed by sequence analysis. Validation was carried out across two laboratories in Scotland, and included studies on sensitivity, specificity, reproducibility, and robustness. The developed test reliably detects Eurasian beaver DNA to the lower limit of 0.1 pg DNA input and differentiates Castor fiber from other species, including congeners. In conclusion, the developed test was successfully optimized and validated to identify Eurasian beaver DNA and will be a valuable tool in wildlife forensic laboratories in cases of suspected persecution of Eurasian beavers

Ceramide synthase TLCD3B is a novel gene associated with human recessive retinal dystrophy

PURPOSE: Previous studies suggest that ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. However, no pathogenic variant in ceramide synthases has been identified in human patients and knockout of various ceramide synthases in mice has not led to photoreceptor degeneration. METHODS: Exome sequencing was used to identify candidate disease genes in patients with vision loss as confirmed by standard evaluation methods, including electroretinography (ERG) and optical coherence tomography. The vision loss phenotype in mice was evaluated by ERG and histological analyses. RESULTS: Here we have identified four patients with cone-rod dystrophy or maculopathy from three families carrying pathogenic variants in TLCD3B. Consistent with the phenotype observed in patients, the Tlcd3bKO/KO mice exhibited a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina. CONCLUSION: Our results provide a link between loss-of-function variants in a ceramide synthase gene and human retinal dystrophy. Establishment of the Tlcd3b knockout murine model, an in vivo photoreceptor cell degeneration model due to loss of a ceramide synthase, will provide a unique opportunity in probing the role of ceramide in survival and function of photoreceptor cells

The development of color categories in two languages: a longitudinal study

This study unites investigations into the linguistic relativity of color categories with research on children's category acquisition. Naming, comprehension, and memory for colors were tracked in 2 populations over a 3-year period. Children from a seminomadic equatorial African culture, whose language contains 5 color terms, were compared with a group of English children. Despite differences in visual environment, language, and education, they showed similar patterns of term acquisition. Both groups acquired color vocabulary slowly and with great individual variation. Those knowing no color terms made recognition errors based on perceptual distance, and the influence of naming on memory increased with age. An initial perceptually driven color continuum appears to be progressively organized into sets appropriate to each culture and language

SSBP1-Disease Update: Expanding the Genetic and Clinical Spectrum, Reporting Variable Penetrance and Confirming Recessive Inheritance.

Funder: Wellcome TrustPURPOSE: To report novel genotypes and expand the phenotype spectrum of SSBP1-disease and explore potential disease mechanism. METHODS: Five families with previously unsolved optic atrophy and retinal dystrophy underwent whole genome sequencing as part of the National Institute for Health Research BioResource Rare-Diseases and the UK's 100,000 Genomes Project. In silico analysis and protein modelling was performed on the identified variants. Deep phenotyping including retinal imaging and International Society for Clinical Electrophysiology of Vision standard visual electrophysiology was performed. RESULTS: Seven individuals from five unrelated families with bilateral optic atrophy and/or retinal dystrophy with extraocular signs and symptoms in some are described. In total, 6 SSBP1 variants were identified including the previously unreported variants: c.151A>G, p.(Lys51Glu), c.335G>A p.(Gly112Glu), and c.380G>A, p.(Arg127Gln). One individual was found to carry biallelic variants (c.380G>A p.(Arg127Gln); c.394A>G p.(Ile132Val)) associated with likely autosomal recessive SSBP1-disease. In silico analysis predicted all variants to be pathogenic and Three-dimensional protein modelling suggested possible disease mechanisms via decreased single-stranded DNA binding affinity or impaired higher structure formation. CONCLUSIONS: SSBP1 is essential for mitochondrial DNA replication and maintenance, with defects leading to a spectrum of disease that includes optic atrophy and/or retinal dystrophy, occurring with or without extraocular features. This study provides evidence of intrafamilial variability and confirms the existence of an autosomal recessive inheritance in SSBP1-disease consequent upon a previously unreported genotype

Assessment of the incorporation of CNV surveillance into gene panel next-generation sequencing testing for inherited retinal diseases.

BACKGROUND: Diagnostic use of gene panel next-generation sequencing (NGS) techniques is commonplace for individuals with inherited retinal dystrophies (IRDs), a highly genetically heterogeneous group of disorders. However, these techniques have often failed to capture the complete spectrum of genomic variation causing IRD, including CNVs. This study assessed the applicability of introducing CNV surveillance into first-tier diagnostic gene panel NGS services for IRD. METHODS: Three read-depth algorithms were applied to gene panel NGS data sets for 550 referred individuals, and informatics strategies used for quality assurance and CNV filtering. CNV events were confirmed and reported to referring clinicians through an accredited diagnostic laboratory. RESULTS: We confirmed the presence of 33 deletions and 11 duplications, determining these findings to contribute to the confirmed or provisional molecular diagnosis of IRD for 25 individuals. We show that at least 7% of individuals referred for diagnostic testing for IRD have a CNV within genes relevant to their clinical diagnosis, and determined a positive predictive value of 79% for the employed CNV filtering techniques. CONCLUSION: Incorporation of CNV analysis increases diagnostic yield of gene panel NGS diagnostic tests for IRD, increases clarity in diagnostic reporting and expands the spectrum of known disease-causing mutations

Color categories: Evidence for the cultural relativity hypothesis

The question of whether language affects our categorization of perceptual continua is of particular interest for the domain of color where constraints on categorization have been proposed both within the visual system and in the visual environment. Recent research (Roberson, Davies, & Davidoff, 2000; Roberson et al., in press) found substantial evidence of cognitive color differences between different language communities, but concerns remained as to how representative might be a tiny, extremely remote community. The present study replicates and extends previous findings using additional paradigms among a larger community in a different visual environment. Adult semi-nomadic tribesmen in Southern Africa carried out similarity judgments, short-term memory and long-term learning tasks. They showed different cognitive organization of color to both English and another language with the five color terms. Moreover, Categorical Perception effects were found to differ even between languages with broadly similar color categories. The results provide further evidence of the tight relationship between language and cognition

Scaling up health policies and services in low- and middle-income settings

"Scaling up" effective health services is high on the policy agendas of many countries and international agencies. The current concern has been driven by growing recognition both of the challenges of achieving the health-related Millennium Development Goals (MDGs) in many countries, and of the need to ensure that the increased resources for health channelled through disease-specific health initiatives are able generate health gain at scale. Effective and cost-effective interventions exist to address many of the major causes of disease burden in the developing world, but coverage of many of these services remains low. There is a substantial gap between what could be achieved and what is actually being achieved in terms of health improvement in low- and middle-income countries

Whole genome sequencing reveals novel mutations causing autosomal dominant inherited macular degeneration

BACKGROUND: Age-related macular degeneration (AMD) is a common sight threatening condition. However, there are a number of monogenic macular dystrophies that are clinically similar to AMD, which can potentially provide pathogenetic insights. METHODS: Three siblings from a non-consanguineous Greek-Cypriot family reported central visual disturbance and nyctalopia. The patients had full ophthalmic examinations and color fundus photography, spectral-domain ocular coherence tomography and scanning laser ophthalmoscopy. Targeted polymerase chain reaction (PCR) was performed as a first step to attempt to identify suspected mutations in C1QTNF5 and TIMP3 followed by whole genome sequencing. RESULTS: The three patients were noted to have symptoms of nyctalopia, early paracentral visual field loss and, in older patients, central vision loss. Imaging identified pseudodrusen, retinal atrophy and RPE-Bruch’s membrane separation. Whole genome sequencing of the proband revealed two novel heterozygous variants in C1QTNF5, c.556C>T, and c.569C>G. The mutation segregated with disease in this family, occurred in cis, and resulted in missense amino acid changes P186S and S190W in C1QTNF5. In silico modeling of the variants revealed that the S190W mutations was likely to have the greatest pathologic effect and that the combination of the mutations was likely to have an additive effect. CONCLUSIONS: The novel mutations in C1QTNF5 identified here expand the genotypic spectrum of mutations causing late-onset retinal dystrophy