Miracle-dz/UniFAR-FTUs huggingface dataset:
Unique cell biological profiles of retinal disease-causing missense mutations in the polarity protein Crumbs

ABSTRACT Mutations in human crumbs 1 (CRB1) are a major cause of retinal diseases that lead to blindness. CRB1 is a transmembrane protein found in the inner segment of photoreceptor cells (PRCs) and the apical membrane of Müller glia. The function of the extracellular region of CRB1 is poorly understood, although more than 80 disease-causing missense mutations have been mapped to it. We have recreated four of these mutations, affecting different extracellular domains, in Drosophila Crumbs (Crb). Crb regulates epithelial polarity and growth, and contributes to PRC differentiation and survival. The mutant Crb isoforms showed a remarkable diversity in protein abundance, subcellular distribution and ability to rescue the lack of endogenous Crb, elicit a gain-of-function phenotype or promote PRC degeneration. Interestingly, although expression of mutant isoforms led to a substantial rescue of the developmental defects seen in crb mutants, they accelerated PRC degeneration compared to that seen in retinas that lacked Crb, indicating that the function of Crb in cellular differentiation and cell survival depends on distinct molecular pathways. Several Crb mutant proteins accumulated abnormally in the rhabdomere and affected rhodopsin trafficking, suggesting that abnormal rhodopsin physiology contributes to Crb/CRB1-associated retinal degeneration. Highlighted Article: Analysis of Drosophila crb mutations demonstrates that the Crb extracellular region controls protein level and distribution, and suggests that human disease-causing CRB1 missense mutations affect rhodopsin trafficking.
Weight-gain patterns from prepregnancy until delivery among women in Central Java, Indonesia.

BACKGROUND Representative data on pregnancy weight-gain patterns from developing countries are scarce. The reasons include difficulties in obtaining population-based samples and in collecting data before and throughout pregnancy. OBJECTIVE The objective was to measure weight-gain patterns from prepregnancy until after delivery in a population-based sample of rural Indonesian women. DESIGN Two cross-sectional surveys of nutritional status among nonpregnant women of reproductive age were carried out through a surveillance system in Purworejo District, Central Java, Indonesia, in 1996 and 1997. Between 1996 and 1998, 846 newly pregnant women were enrolled in a cohort study in which weight was monitored monthly throughout pregnancy. Prepregnancy weights and other anthropometric measures were available for 251 of the women who had live births. RESULTS Before pregnancy, 16.7% of the women had chronic energy deficiency and 10.0% were obese. The mean total pregnancy weight gain for all the women was 8.3 +/- 3.6 kg, and 79% did not meet the international recommendation regarding weight gain for their prepregnant body mass index. The rate of weight gain was highest during the second trimester (0.34 kg/wk). In the first and third trimesters, it was 0.08 and 0.26 kg/wk, respectively. Total weight gain was associated with prepregnant body mass index, education, and socioeconomic status. CONCLUSIONS Many women in rural Central Java, Indonesia, enter pregnancy with suboptimal nutritional status. For most of these women, total weight gain during pregnancy is insufficient. It is likely that this contributes to adverse health outcomes for both the mothers and their newborns.
Polyphenoloxidase Silencing Affects Latex Coagulation in Taraxacum Species1[W]

Latex is the milky sap that is found in many different plants. It is produced by specialized cells known as laticifers and can comprise a mixture of proteins, carbohydrates, oils, secondary metabolites, and rubber that may help to prevent herbivory and protect wound sites against infection. The wound-induced browning of latex suggests that it contains one or more phenol-oxidizing enzymes. Here, we present a comprehensive analysis of the major latex proteins from two dandelion species, Taraxacum officinale and Taraxacum kok-saghyz, and enzymatic studies showing that polyphenoloxidase (PPO) is responsible for latex browning. Electrophoretic analysis and amino-terminal sequencing of the most abundant proteins in the aqueous latex fraction revealed the presence of three PPO-related proteins generated by the proteolytic cleavage of a single precursor (pre-PPO). The laticifer-specific pre-PPO protein contains a transit peptide that can target reporter proteins into chloroplasts when constitutively expressed in dandelion protoplasts, perhaps indicating the presence of structures similar to plastids in laticifers, which lack genuine chloroplasts. Silencing the PPO gene by constitutive RNA interference in transgenic plants reduced PPO activity compared with wild-type controls, allowing T. kok-saghyz RNA interference lines to expel four to five times more latex than controls. Latex fluidity analysis in silenced plants showed a strong correlation between residual PPO activity and the coagulation rate, indicating that laticifer-specific PPO plays a major role in latex coagulation and wound sealing in dandelions. In contrast, very little PPO activity is found in the latex of the rubber tree Hevea brasiliensis, suggesting functional divergence of latex proteins during plant evolution.
Intake of lignans is associated with serum enterolactone concentration in Finnish men and women.

The mammalian lignans (a form of phytoestrogens), metabolically derived by the intestinal microflora from dietary precursors, may have several health benefits. Information concerning their dietary sources and bioavailability is scarce. We assessed lignan intake via a 24-h dietary recall (n = 2852) and determined serum enterolactone (EL) concentration (n = 1784) in 25- to 64-y-old Finnish men and women participating in a national survey in 1997. Mean intake of lignans [sum of matairesinol (MAT) and secoisolariciresinol (SECO)] in men and women was 173 microg/d (19 microg/MJ) and 151 microg/d (23 microg/MJ), respectively. SECO made up over two thirds of the total lignan intake. The major sources of SECO were fruit, berries and cereals, whereas MAT derived almost exclusively from cereals. Lignan intake was positively associated with serum EL concentration (r = 0.19, P < 0.0001), i.e., the mean EL concentration in the highest quintile of lignan intake was 50% higher than that in the lowest quintile. We conclude that lignans are common components of the Finnish diet, although the mean daily intake is low (<0.2 mg). The main dietary sources of lignans, i.e., whole grain, vegetables and fruits, are foods commonly associated with lower risk of cardiovascular diseases and cancer. Serum EL concentration is a feasible biomarker of lignan intake.
Quantitative trait locus determining dietary macronutrient intakes is located on human chromosome 2p22.

BACKGROUND Obesity is generally accompanied by increased food intake. OBJECTIVE We sought to identify the genes influencing variation in dietary macronutrient intakes in Mexican Americans. DESIGN We conducted a genome-wide scan by using data derived from food-frequency questionnaires in 816 participants from the San Antonio Family Heart Study. Household effect was simultaneously estimated in a variance component model with the use of SOLAR. RESULTS All dietary intake measures (total calories, proteins, fat, saturated fat, monounsaturated fat, polyunsaturated fat, carbohydrates, and sucrose) were moderately heritable. Household effect was insignificant except on total calories and sucrose. Suggestive evidence of linkage with saturated fat intake was found on chromosome 2p22 near marker D2S1346 [logarithm of odds (LOD) = 2.62]. Intakes of total calories, fat, protein, and monounsaturated fat were also suggestively linked to the same marker. A significant linkage signal on chromosome 2p22 for leptin concentrations and fat mass was localized in this population, so we used leptin or fat mass as a covariate. Multipoint LOD scores for saturated fat dropped to 1.27 and 1.90, respectively, which suggested that this region on chromosome 2p contributes to both saturated fat intake and body adiposity. This chromosomal region contains the proopiomelanocortin gene (POMC). However, 2 polymorphisms in exon 3 of the POMC gene showed no association with saturated fat intake. CONCLUSIONS The results strengthen the hypothesis that chromosome 2p22 harbors genes that influence a variety of obesity-related phenotypes, including macronutrient intakes.
Infinitary Normalization

In infinitary orthogonal first-order term rewriting the properties confluence (CR), Uniqueness of Normal forms (UN), Parallel Moves Lemma (PML) have been generalized to their infinitary versions CR∞, UN∞, PML∞, and so on. Several relations between these properties have been established in the literature. Generalization of the termination properties, Strong Normalization (SN) and Weak Normalization (WN) to SN∞ and WN∞ is less straightforward. We present and explain the definitions of these infinitary normalization notions, and establish that as a global property of orthogonal TRSs they coincide, so at that level there is just one notion of infinitary normalization. Locally, at the level of individual terms, the notions are still different. In the setting of orthogonal term rewriting we also provide an elementary proof of UN∞, the infinitary Unique Normal form property.
Diet and intestinal enzyme adaptation: implications for gastrointestinal disorders.

Recent studies have demonstrated that the human intestinal enzymes of carbohydrate digestion and metabolism can be regulated by dietary sugars. These studies have utilized direct assay of intestinal mucosal enzyme activity. Mucosa has been obtained by the use of peroral jejunal biopsy techniques which provide 10-15 mg of mucosa in a safe, simple and reproducible manner. Dietary sucrose, as compared to dietary glucose, increases the activities of the jejunal disaccharidases, sucrase and maltase, but not lactase. Fructose reproduces the sucrose effect and appears to be the active principle in the sucrose molecule. Lactose deprivation or lactose feeding does not alter lactase activity. Fructose has been useful in treating one patient with sucrase-isomaltase deficiency. Jejunal glycolytic enzyme activities are also regulated by dietary sugars. Certain enzymes are highest with specific dietary carbohydrates, lower with other sugars and lowest on a carbohydrate-free diet. The regulation of human jejunal glycolytic enzyme activity takes place in hours, whereas the change in disaccharidase activity occurs in 2-5 days. The mechanism of this regulation is not known. Additional investigations have shown that jejunal glycolytic enzyme activities but not the disaccharidases are controlled by oral folic acid as well. This effect occurs within 1 day also. The mechanism is unknown. Large doses of folate have been of benefit in a few patients with certain glycolytic enzyme deficiency states. Preliminary studies have demonstrated that selected patients with chronic undiagnosed intestinal disorders fail to manifest an adaptive response of their jejunal glycolytic enzyme activities to dietary sugars. This condition has been termed a "maladaptation syndrome. ".
Chronicle of the Institute of Medicine physical activity recommendation: how a physical activity recommendation came to be among dietary recommendations.

Under a contract from the US Department of Health and Human Services, a multidisciplinary expert panel was appointed to review "the scientific literature regarding macronutrients and energy and develop estimates of daily intake that are compatible with good nutrition throughout the life span and that may decrease the risk of chronic disease. " Within the overall context of the charge, the panel sought to quantify rates and components of daily energy expenditure in healthy adults with body mass indexes (in kg/m(2)) of 18.5-25, in growing children (in the 5th-85th percentiles of weight-for-length), and in pregnant and lactating women. The recommendation for adults became the daily energy intake necessary to cover total daily energy expenditure (TEE). For special cases, dietary macronutrients and energy to support child growth and pregnancy and lactation by women were considered. TEE was based on the results of doubly labeled water studies, and the TEE results were presented in units of physical activity level (PAL = TEE/BEE) and DeltaPAL, where BEE is the basal rate of energy expenditure extrapolated to 24 h. Most adults (66%) maintaining a BMI in the healthful range had PAL values >1.6, or the equivalent of > or =60 min of physical activity of moderate intensity each day. Hence, on the basis of the doubly labeled water data and the results of epidemiologic studies, the physical activity recommendation for adults was judged to be 60 min/d. The recommendation for children was for a minimum of 60 min/d. In conclusion, dietary and physical activity recommendations for healthful living are inextricably intertwined. Adequate physical activity provides protection against chronic diseases and helps to balance energy expenditure and intake.
Higher Contrast Requirement for Letter Recognition and Macular RGC+ Layer Thinning in Glaucoma Patients and Older Adults

Purpose Growing evidence suggests the involvement of the macula even in early stages of glaucoma. However, little is known about the impact of glaucomatous macular damage on central pattern vision. Here we examine the contrast requirement for letter recognition and its relationship with retinal thickness in the macular region. Methods A total of 40 participants were recruited: 13 patients with glaucoma (mean age = 65.6 ± 6.6 years), 14 age-similar normally sighted adults (59.1 ± 9.1 years), and 13 young normally sighted adults (21.0 ± 2.0 years). For each participant, letter-recognition contrast thresholds were obtained using a letter recognition task in which participants identified English letters presented at varying retinal locations across the central 12° visual field, including the fovea. The macular retinal ganglion cell plus inner plexiform (RGC+) layer thickness was also evaluated using spectral-domain optical coherence tomography (SD-OCT). Results Compared to age-similar normal controls, glaucoma patients exhibited a significant increase in letter-recognition contrast thresholds (by 236%, P < 0.001) and a significant decrease in RGC+ layer thickness (by 17%, P < 0.001) even after controlling for age, pupil diameter, and visual acuity. Compared to normal young adults, older adults showed a significant increase in letter-recognition contrast thresholds and a significant decrease in RGC+ layer thickness. Across all subjects, the thickness of macular RGC+ layer was significantly correlated with letter-recognition contrast thresholds, even after correcting for pupil diameter and visual acuity (r = −0.65, P < 0.001). Conclusions Our results show that both glaucoma and normal aging likely bring about a thinning of the macular RGC+ layer; the macular RGC+ layer thickness appears to be associated with the contrast requirements for letter recognition in central vision.
Who's Better, Who's Best: Skill Determination in Video using Deep Ranking

This paper presents a method for assessing skill of performance from video, for a variety of tasks, ranging from drawing to surgery and rolling dough. We formulate the problem as pairwise and overall ranking of video collections, and propose a supervised deep ranking model to learn discriminative features between pairs of videos exhibiting different amounts of skill. We utilise a two-stream Temporal Segment Network to capture both the type and quality of motions and the evolving task state. Results demonstrate our method is applicable to a variety of tasks, with the percentage of correctly ordered pairs of videos ranging from 70% to 82% for four datasets. We demonstrate the robustness of our approach via sensitivity analysis of its parameters. We see this work as effort toward the automated and objective organisation of how-to videos and overall, generic skill determination in video.
BeMobil: Developing a user-friendly and motivating telerehabilitation system for motor relearning after stroke

Motor relearning after stroke is a lengthy process which should be continued after patients get discharged from the clinic. This project aims at developing a system for telerehabilitation which enables stroke patients to exercise at home autonomously or under supervision of a therapist. The system includes haptic therapy devices which are more promising and beneficial for stroke rehabilitation than non-haptic approaches. In this paper, we present the results of two initial studies investigating specific design solutions for the patient's user interface. In the first study, we developed four interactive prototypes illustrating different navigation concepts. A usability test was conducted to identify the best suitable concept. In the second study we followed a participatory design approach to create a set of design solutions for a motivating instant visual feedback for exercising with the haptic devices. The current project status and next steps are described.
Promotion of invasion by mutant RAS is dependent on activation of the WASF3 metastasis promoter gene

Metastasis represents an end stage in the evolution of cancer progression and has been related to specific genetic pathways. Overexpression of mutant RAS in particular appears to promote invasion and metastasis, although exactly how this occurs has not been well characterized. It was previously showed that activation of the WASF3 protein regulates actin cytoskeleton dynamics that promote invasion. In this report, how WASF3 overexpression interacts with mutant RAS to increase invasion and metastasis was investigated. The ability of RAS to promote invasion and metastasis was shown to be dependent on WASF3 activation in a PI3K and AKT dependent manner. Proteomics analysis demonstrates the presence of AKT in the WASF3 immunocomplex which is enhanced by overexpression of mutant RAS. During these processes activation of ERK1/2 is not affected by loss of WASF3 expression. Analysis of the relative involvement of p85 and p110 in the WASF3 complex demonstrates that mutant RAS promotes dissociation of p85 promoting activation of p110. These studies provide a deeper understanding of the critical role for WASF3 in facilitating increased invasion potential in cancer cells expressing mutant RAS and supports the idea that targeting WASF3 in metastatic cells overexpressing RAS may be used to suppress invasion and metastasis.
The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women: a randomized crossover study.

BACKGROUND Evidence suggests that soy isoflavones act as estrogen agonists and have beneficial skeletal effects, but the effects on calcium metabolism in humans are not known. OBJECTIVE This study tested whether soybean isoflavones, soy protein, or both alter calcium metabolism in postmenopausal women. DESIGN Calcium metabolism in 15 postmenopausal women was studied by using metabolic balance and kinetic modeling in a randomized, crossover design of three 1-mo controlled dietary interventions: soy protein isolate enriched with isoflavones (soy-plus diet), soy protein isolate devoid of isoflavones (soy-minus diet), and a casein-whey protein isolate (control diet). RESULTS There was no significant difference between the diets in net acid excretion (P = 0.12). Urinary calcium excretion was significantly (P < 0.01) less with consumption of either of the soy diets (soy-plus diet: 85 +/- 34 mg/d; soy-minus diet: 80 +/- 34 mg/d) than with consumption of the control diet (121 +/- 63 mg/d), but fractional calcium absorption was unaffected by treatment. Endogenous fecal calcium was significantly (P < 0.01) greater with consumption of the soy-minus diet than with consumption of the other diets. Total fecal calcium excretion, bone deposition and resorption, and calcium retention were not significantly affected by the dietary regimens. CONCLUSIONS The lower urinary calcium seen with the consumption of an isolated soy protein than with that of an isolated milk protein was not associated with improved calcium retention. This finding reinforces the importance of evaluating all aspects of calcium metabolism. Soy isoflavones did not significantly affect calcium metabolism.
Unsupervised Abbreviation Detection in Clinical Narratives

Clinical narratives in electronic health record systems are a rich resource of patient-based information. They constitute an ongoing challenge for natural language processing, due to their high compactness and abundance of short forms. German medical texts exhibit numerous ad-hoc abbreviations that terminate with a period character. The disambiguation of period characters is therefore an important task for sentence and abbreviation detection. This task is addressed by a combination of co-occurrence information of word types with trailing period characters, a large domain dictionary, and a simple rule engine, thus merging statistical and dictionary-based disambiguation strategies. An F-measure of 0.95 could be reached by using the unsupervised approach presented in this paper. The results are promising for a domain-independent abbreviation detection strategy, because our approach avoids retraining of models or use case specific feature engineering efforts required for supervised machine learning approaches.
B-6 vitamers and 4-pyridoxic acid in the plasma, erythrocytes, and urine of postmenopausal women.

BACKGROUND Although many studies have reported reduced vitamin B-6 status with aging, little information is available about the specific effects of menopause. OBJECTIVE We aimed to examine vitamin B-6 metabolism in premenopausal and early postmenopausal women. DESIGN We examined dietary intake and vitamin B-6 metabolites in the plasma, erythrocytes, and urine of 30 premenopausal women (x +/- SD age: 41.9 +/- 4.8 y) and 30 women (aged 54.0 +/- 3.8 y) who were 4.0 +/- 1.4 y past menopause. RESULTS Vitamin B-6 intake in the postmenopausal group (1.97 +/- 0.40 mg/d) was significantly greater than that in the premenopausal group (1.63 +/- 0.50 mg/d). Plasma pyridoxal phosphate (PLP) and pyridoxal concentrations and erythrocyte PLP, pyridoxal, and pyridoxamine phosphate concentrations were in the normal range in both groups and did not differ significantly between the 2 groups. Plasma and erythrocyte 4-pyridoxic acid (4-PA) concentrations were significantly higher in the postmenopausal group than in the premenopausal group, which may have been due at least partly to the slightly higher vitamin B-6 intake of the former group. Erythrocyte 4-PA was correlated (r = -0.37, P < 0.01) with serum estradiol in both groups. Urinary 4-PA did not differ significantly between the 2 groups. The serum phosphate concentration was higher in the postmenopausal group than in the premenopausal group, and it was correlated (r = 0.40, P < 0.01) with plasma PLP. Inhibition of alkaline phosphatase by the increased phosphate may help to increase plasma PLP. CONCLUSION Menopause may not necessarily be associated with a decrease in vitamin B-6 status.