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A new generation of logarithmic reading charts has sparked interest in standardized reading performance analyses. Such reading charts have been developed according to the standards of the International Council of Ophthalmology. The print size progression in these calibrated charts is in accordance with the mathematical background of EN ISO 8596. These reading charts are: the Bailey–Lovie Word Reading Chart, the Colenbrander English Continuous Text Near Vision Cards, the Oculus Reading Probe II, the MNREAD Charts, the SKread Charts, and the RADNER Reading Charts. The test items used for these reading charts differ among the charts and are standardized to various extents. The Bailey–Lovie Charts, MNREAD Charts, SKread Charts, and RADNER Charts are also meant to measure reading speed and allow determination of further reading parameters such as reading acuity, reading speed based on reading acuity, critical print size, reading score, and logMAR/logRAD ratio. Such calibrated reading charts have already provided valuable insights into the reading performance of patients in many research studies. They are available in many languages and thus facilitate international communication about near visual performance. In the present review article, the backgrounds of these modern reading charts are presented, and their different levels of test-item standardization are discussed. Clinical research studies are mentioned, and a discussion about the immoderately high number of reading acuity notations is included. Using the logReading Acuity Determination ([logRAD] = reading acuity equivalent of logMAR) measure for research purposes would give reading acuity its own identity as a standardized reading parameter in ophthalmology.

Autosomal recessive congenital ichthyosis (ARCI) is a rare genetic disorder of the skin characterized by abnormal desquamation over the whole body. In this study we report four patients from three consanguineous Tunisian families with skin, eye, heart, and skeletal anomalies, who harbor a homozygous contiguous gene deletion syndrome on chromosome 15q26.3. Genome-wide SNP-genotyping revealed a homozygous region in all affected individuals, including the same microdeletion that partially affects two coding genes (ADAMTS17, CERS3) and abolishes a sequence for a long non-coding RNA (FLJ42289). Whereas mutations in ADAMTS17 have recently been identified in autosomal recessive Weill-Marchesani-like syndrome in humans and dogs presenting with ophthalmologic, cardiac, and skeletal abnormalities, no disease associations have been described for CERS3 (ceramide synthase 3) and FLJ42289 so far. However, analysis of additional patients with non-syndromic ARCI revealed a splice site mutation in CERS3 indicating that a defect in ceramide synthesis is causative for the present skin phenotype of our patients. Functional analysis of patient skin and in vitro differentiated keratinocytes demonstrated that mutations in CERS3 lead to a disturbed sphingolipid profile with reduced levels of epidermis-specific very long-chain ceramides that interferes with epidermal differentiation. Taken together, these data present a novel pathway involved in ARCI development and, moreover, provide the first evidence that CERS3 plays an essential role in human sphingolipid metabolism for the maintenance of epidermal lipid homeostasis.

The α/β-Hydrolase domain-containing protein 5 (ABHD5; also known as comparative gene identification-58, or CGI-58) is the causative gene of the Chanarin-Dorfman syndrome (CDS), a disorder mainly characterized by systemic triacylglycerol accumulation and a severe defect in skin barrier function. The clinical phenotype of CDS patients and the characterization of global and tissue-specific ABHD5-deficient mouse strains have demonstrated that ABHD5 is a crucial regulator of lipid and energy homeostasis in various tissues. Although ABHD5 lacks intrinsic hydrolase activity, it functions as a co-activating enzyme of the patatin-like phospholipase domain-containing (PNPLA) protein family that is involved in triacylglycerol and glycerophospholipid, as well as sphingolipid and retinyl ester metabolism. Moreover, ABHD5 interacts with perilipins (PLINs) and fatty acid-binding proteins (FABPs), which are important regulators of lipid homeostasis in adipose and non-adipose tissues. This review focuses on the multifaceted role of ABHD5 in modulating the function of key enzymes in lipid metabolism.

Recent advances in structural biology have provided insights into TRPC3, a TRP family member involved in various (patho)physiological processes. However, the lack of structural information on the channel’s open pore hampers understanding of its function and therapeutic potential. Cryogenic electron microscopy holds promise for elucidating TRPC3’s open-pore conformation, but challenges remain in isolating it without compromising function. Our study evaluated novel extraction agents in comparison to conventional detergents for isolating functional TRPC3 complexes from HEK293, Komagataella phaffii , and Expi293F cells, identifying Expi293F as optimal for TRPC3 expression. Among the extraction agents screened, dodecyl diglucoside (DDDG) and n -dodecyl-β-D-maltoside (DDM) were the most effective for extracting TRPC3. We successfully purified TRPC3 under native conditions, preserving its tetrameric structure and activity, as confirmed by electron microscopy, mass spectrometry and patch-clamp analysis. This study highlights the importance of extraction agents in advancing TRPC3 research and therapeutic development.

Purpose To develop 28 short sentence optotypes for the English version of the Radner Reading Charts that are as comparable as possible in number and length of words, as well as in difficulty and syntactical construction. Methods Thirty-four English sentences were constructed following the method used for other Radner Reading Charts to obtain “sentence optotypes” with comparable structure and the same lexical and grammatical difficulty. Best comparable sentences were statistically selected and standardized in 50 volunteers. Reading speed and the number of errors were determined. Validity was analyzed with a 124-word long 4th-grade paragraph of the Florida Comprehensive Assessment Test®. Computerized measurements of reading parameters were performed with the RADNER Reading Device (RAD-RD©; in conjunction with a PC and microphone). Results The mean reading speed obtained with the 28 selected short sentences was 201.53 ± 35.88 words per minute (wpm), as compared to 215.01 ± 30.37 wpm for the long paragraph. The mean reading times were 4.30 ± 0.79 s and 35.26 ± 4.85 s, respectively. The mean number of reading errors was 0.11 ± 0.34. The correlation between the short sentences and the long paragraph was high ( r  = 0.76; p  < 0.05; n  = 50). Reliability analyses yielded an overall Cronbach’s alpha coefficient of 0.9743. Conclusion The present study indicates that the 28 selected English sentence optotypes are comparable in terms of both lexical difficulty as well as in reading length, and it demonstrates the validity and reliability of such sentences as test items for determining reading parameters such as reading acuity and speed.

Catherine André, Judith Fischer and colleagues report that mutations in PNPLA1 cause congenital ichthyosis in humans and golden retriever dogs. Their findings suggest a role for PNPLA1 in the formation of the epidermal lipid barrier. Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.

Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy.Pajed et al. investigate the role of adipocyte hormone-sensitive lipase (HSL) in whole body energy homeostasis. They show that adipocyte-specific HSL Knockout (AHKO) mice fed high fat diet develop fatty liver. Interestingly, this phenotype reverses in aged AHKO mice, possibly due to blunted lipolytic activity in adipose tissue with pronounced lipodystrophy.

People with mutations in ATGL , a gene involved in lipid catabolism, suffer from neutral lipid storage disease and often from cardiomyopathy. Rudolf Zechner and his colleagues now show in mice that Atgl activity in cardiac muscle produces key lipid ligands for PPAR-α, a transcription factor that regulates proper lipid metabolism and fuel burning in this tissue. These results may explain the mechanisms responsible for the cardiomyopathy and offer a potential target for treatment. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that regulate genes involved in energy metabolism and inflammation. For biological activity, PPARs require cognate lipid ligands, heterodimerization with retinoic X receptors, and coactivation by PPAR-γ coactivator-1α or PPAR-γ coactivator-1β (PGC-1α or PGC-1β, encoded by Ppargc1a and Ppargc1b , respectively). Here we show that lipolysis of cellular triglycerides by adipose triglyceride lipase (patatin-like phospholipase domain containing protein 2, encoded by Pnpla2 ; hereafter referred to as Atgl) generates essential mediator(s) involved in the generation of lipid ligands for PPAR activation. Atgl deficiency in mice decreases mRNA levels of PPAR-α and PPAR-δ target genes. In the heart, this leads to decreased PGC-1α and PGC-1β expression and severely disrupted mitochondrial substrate oxidation and respiration; this is followed by excessive lipid accumulation, cardiac insufficiency and lethal cardiomyopathy. Reconstituting normal PPAR target gene expression by pharmacological treatment of Atgl-deficient mice with PPAR-α agonists completely reverses the mitochondrial defects, restores normal heart function and prevents premature death. These findings reveal a potential treatment for the excessive cardiac lipid accumulation and often-lethal cardiomyopathy in people with neutral lipid storage disease, a disease marked by reduced or absent ATGL activity.

The purpose of this study was to analyze statistically the test-retest and inter-chart reliability of three standardized Radner Reading Charts with respect to reading acuity, maximum reading speed, critical print size and LogRAD/LogMAR ratio and to quantitatively identify the sources of variability. At two testing sessions (3 to 4 weeks apart), 36 volunteers read monocularly all three Radner Reading Charts in randomized order (orthogonal Latin square design). The subjects were grouped according to their distance LogMAR visual acuity (group 1, 0.1 or better; group 2, 0.12-0.4; group 3, 0.42-0.8). Based on these 216 reading tests, crude correlations were calculated between the two testing sessions and between the three charts, and \"variance component analyses\" were performed for all variables. For all visual acuity groups and variables, the test-retest and the inter-chart reliability was high. The variance component analyses showed that the differences between individuals predominantly influenced the variance, whereas the effect of the test replication was low. The three charts caused minimal variability, indicating equality for clinical examinations. The standardized Radner Reading Charts provide clinically reliable and reproducible results for individuals with normal eyesight and for patients with visual impairment. These findings indicate that reading test systems, which consider the current international standards for visual acuity measurements (EN ISO 8596, NAS-NRC) and the psychophysical requirements for controlling optical item interactions, can provide reliable measures for clinical and scientific analyses of reading performance.