Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

<p>Abstract</p> <p>Introduction</p> <p>Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations.</p> <p>Case presentation</p> <p>We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.</p> <p>Conclusion</p> <p>It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.</p

Sound can improve visual search in developmental dyslexia

We examined whether developmental dyslexic adults suffer from sluggish attentional shifting (SAS; Hari and Renvall in Trends Cogn Sci 5:525–532, 2001) by measuring their shifting of attention in a visual search task with dynamic cluttered displays (Van der Burg et al. in J Exp Psychol Human 34:1053–1065, 2008). Dyslexics were generally slower than normal readers in searching a horizontal or vertical target among oblique distracters. However, the addition of a click sound presented in synchrony with a color change of the target drastically improved their performance up to the level of the normal readers. These results are in line with the idea that developmental dyslexics have specific problems in disengaging attention from the current fixation, and that the phasic alerting by a sound can compensate for this deficit

Targeting of GFP-Cre to the Mouse Cyp11a1 Locus Both Drives Cre Recombinase Expression in Steroidogenic Cells and Permits Generation of Cyp11a1 Knock Out Mice

To permit conditional gene targeting of floxed alleles in steroidogenic cell-types we have generated a transgenic mouse line that expresses Cre Recombinase under the regulation of the endogenous Cytochrome P450 side chain cleavage enzyme (Cyp11a1) promoter. Mice Carrying the Cyp11a1-GC (GFP-Cre) allele express Cre Recombinase in fetal adrenal and testis, and adrenal cortex, testicular Leydig cells (and a small proportion of Sertoli cells), theca cells of the ovary, and the hindbrain in postnatal life. Circulating testosterone concentration is unchanged in Cyp11(+/GC) males, suggesting steroidogenesis is unaffected by loss of one allele of Cyp11a1, mice are grossly normal, and Cre Recombinase functions to recombine floxed alleles of both a YFP reporter gene and the Androgen Receptor (AR) in steroidogenic cells of the testis, ovary, adrenal and hindbrain. Additionally, when bred to homozygosity (Cyp11a1(GC/GC)), knock-in of GFP-Cre to the endogenous Cyp11a1 locus results in a novel mouse model lacking endogenous Cyp11a1 (P450-SCC) function. This unique dual-purpose model has utility both for those wishing to conditionally target genes within steroidogenic cell types and for studies requiring mice lacking endogenous steroid hormone production

History, epidemiology and regional diversities of urolithiasis

Archeological findings give profound evidence that humans have suffered from kidney and bladder stones for centuries. Bladder stones were more prevalent during older ages, but kidney stones became more prevalent during the past 100 years, at least in the more developed countries. Also, treatment options and conservative measures, as well as ‘surgical’ interventions have also been known for a long time. Our current preventive measures are definitively comparable to those of our predecessors. Stone removal, first lithotomy for bladder stones, followed by transurethral methods, was definitively painful and had severe side effects. Then, as now, the incidence of urolithiasis in a given population was dependent on the geographic area, racial distribution, socio-economic status and dietary habits. Changes in the latter factors during the past decades have affected the incidence and also the site and chemical composition of calculi, with calcium oxalate stones being now the most prevalent. Major differences in frequency of other constituents, particularly uric acid and struvite, reflect eating habits and infection risk factors specific to certain populations. Extensive epidemiological observations have emphasized the importance of nutritional factors in the pathogenesis of urolithiasis, and specific dietary advice is, nowadays, often the most appropriate for prevention and treatment of urolithiasis

Sediment source fingerprinting: benchmarking recent outputs, remaining challenges and emerging themes

Abstract: Purpose: This review of sediment source fingerprinting assesses the current state-of-the-art, remaining challenges and emerging themes. It combines inputs from international scientists either with track records in the approach or with expertise relevant to progressing the science. Methods: Web of Science and Google Scholar were used to review published papers spanning the period 2013–2019, inclusive, to confirm publication trends in quantities of papers by study area country and the types of tracers used. The most recent (2018–2019, inclusive) papers were also benchmarked using a methodological decision-tree published in 2017. Scope: Areas requiring further research and international consensus on methodological detail are reviewed, and these comprise spatial variability in tracers and corresponding sampling implications for end-members, temporal variability in tracers and sampling implications for end-members and target sediment, tracer conservation and knowledge-based pre-selection, the physico-chemical basis for source discrimination and dissemination of fingerprinting results to stakeholders. Emerging themes are also discussed: novel tracers, concentration-dependence for biomarkers, combining sediment fingerprinting and age-dating, applications to sediment-bound pollutants, incorporation of supportive spatial information to augment discrimination and modelling, aeolian sediment source fingerprinting, integration with process-based models and development of open-access software tools for data processing. Conclusions: The popularity of sediment source fingerprinting continues on an upward trend globally, but with this growth comes issues surrounding lack of standardisation and procedural diversity. Nonetheless, the last 2 years have also evidenced growing uptake of critical requirements for robust applications and this review is intended to signpost investigators, both old and new, towards these benchmarks and remaining research challenges for, and emerging options for different applications of, the fingerprinting approach

The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage

Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks

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Not AvailableThe major wide-compatibility gene locus S5 in rice (Oryza sativa L.) located on chromosome 6 has been recently cloned and a 136-bp deletion in the candidate gene encoding aspartyl protease has been characterized to be specific for wide-compatible varieties, while many single nucleotide polymorphisms have been identified at S5 between indica and japonica rice types. In the present study, we designed a PCR-based multiplex functional marker system targeting the deletion and the SNPs for precise determination of the allelic status at S5. By deploying the marker system, the allelic status at the S5 locus in 584 rice genotypes has been assayed. A total of 116 genotypes, including 11 cultivars, two known wide-compatible varieties, 48 IRRI germplasm lines, 12 Indian aromatic rice genotypes, 37 restorer lines and six breeding lines, have been identified to possess the 136-bp deletion specific for the neutral allele at S5. The marker system was able to clearly distinguish indica and japonica alleles from the neutral allele and has been validated in a mapping population derived from the three-way cross IR36/Dular//Akihikari, which segregated for spikelet sterility/fertility. The functional marker system targeting S5 developed in the present study will be very useful in rapid identification of wide-compatible genotypes, in predicting the success of inter-subspecific crosses and in targeted introgression of the wide-compatible allele of S5 into elite indica and japonica rice varieties.Not Availabl