The Increasing Use of Interesterified Lipids in the Food Supply and Their Effects on Health Parameters

A variety of modified fats that provide different functionalities are used in processed foods to optimize product characteristics and nutrient composition. Partial hydrogenation results in the formation of trans FAs (TFAs) and was one of the most widely used modification processes of fats and oils. However, the negative effects of commercially produced TFAs on serum lipoproteins and risk for cardiovascular disease resulted in the Institute of Medicine and the 2010 US Dietary Guidelines for Americans both recommending that TFA intake be as low as possible. After its tentative 2013 determination that use of partially hydrogenated oils is not generally regarded as safe, the FDA released its final determination of the same in 2015. Many food technologists have turned to interesterified fat as a replacement. Interesterification rearranges FAs within and between a triglyceride molecule by use of either a chemical catalyst or an enzyme. Although there is clear utility of interesterified fats for retaining functional properties of food, the nutrition and health implications of long-term interesterified fat consumption are less well understood. The Technical Committee on Dietary Lipids of the North American Branch of the International Life Sciences Institute sponsored a workshop to discuss the health effects of interesterified fats, identify research needs, and outline considerations for the design of future studies. The consensus was that although interesterified fat production is a feasible and economically viable solution for replacing dietary TFAs, outstanding questions must be answered regarding the effects of interesterification on modifying certain aspects of lipid and glucose metabolism, inflammatory responses, hemostatic parameters, and satiety

Rare variants in the sodium-dependent phosphate transporter gene SLC34A3 explain missing heritability of urinary stone disease

Urinary stone disease (USD) is a major health burden affecting over 10% of the United Kingdom population. While stone disease is associated with lifestyle, genetic factors also strongly contribute. Common genetic variants at multiple loci from genome-wide association studies account for 5% of the estimated 45% heritability of the disorder. Here, we investigated the extent to which rare genetic variation contributes to the unexplained heritability of USD. Among participants of the United Kingdom 100,000-genome project, 374 unrelated individuals were identified and assigned diagnostic codes indicative of USD. Whole genome gene-based rare variant testing and polygenic risk scoring against a control population of 24,930 ancestry-matched controls was performed. We observed (and replicated in an independent dataset) exome-wide significant enrichment of monoallelic rare, predicted damaging variants in the SLC34A3 gene for a sodium-dependent phosphate transporter that were present in 5% cases compared with 1.6% of controls. This gene was previously associated with autosomal recessive disease. The effect on USD risk of having a qualifying SLC34A3 variant was greater than that of a standard deviation increase in polygenic risk derived from GWAS. Addition of the rare qualifying variants in SLC34A3 to a linear model including polygenic score increased the liability-adjusted heritability from 5.1% to 14.2% in the discovery cohort. We conclude that rare variants in SLC34A3 represent an important genetic risk factor for USD, with effect size intermediate between the fully penetrant rare variants linked with Mendelian disorders and common variants associated with USD. Thus, our findings explain some of the heritability unexplained by prior common variant genome-wide association studies

A phase I randomized therapeutic MVA-B vaccination improves the magnitude and quality of the T cell immune responses in HIV-1-infected subjects on HAART

Trial Design Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART. Methods The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination. Results MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1- specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses

PETAL LOSS, a trihelix transcription factor gene, regulates perianth architecture in the Arabidopsis flower

Perianth development is specifically disrupted in mutants of the PETAL LOSS (PTL) gene, particularly petal initiation and orientation. We have cloned PTL and show that it encodes a plant-specific trihelix transcription factor, one of a family previously known only as regulators of light-controlled genes. PTL transcripts were detected in the early-developing flower, in four zones between the initiating sepals and in their developing margins. Strong misexpression of PTL in a range of tissues universally results in inhibition of growth, indicating that its normal role is to suppress growth between initiating sepals, ensuring that they remain separate. Consistent with this, sepals are sometimes fused in ptl single mutants, but much more frequently in double mutants with either of the organ boundary genes cup-shaped cotyledon1 or 2. Expression of PTL within the newly arising sepals is apparently prevented by the PINOID auxin-response gene. Surprisingly, PTL expression could not be detected in petals during the early stages of their development, so petal defects associated with PTL loss of function may be indirect, perhaps involving disruption to signalling processes caused by overgrowth in the region. PTL-driven reporter gene expression was also detected at later stages in the margins of expanding sepals, petals and stamens, and in the leaf margins; thus, PTL may redundantly dampen lateral outgrowth of these organs, helping define their final shape

Characteristics associated with significantly worse quality of life in mycosis fungoides/Sezary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study

Background Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. Aim To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. Methods Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. Results The study population consisted of 237 patients [60 center dot 3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (beta = 8 center dot 61; P = 0 center dot 003) and alopecia (beta = 9 center dot 71, P = 0 center dot 02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2 center dot 14, 95% confidence interval (CI) 1 center dot 19-3 center dot 89] and emotions (OR 1 center dot 88, 95% CI 1 center dot 09-3 center dot 27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. Conclusions HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients.Peer reviewe

Rare disease gene association discovery in the 100,000 Genomes Project

\ua9 The Author(s) 2025. Up to 80% of rare disease patients remain undiagnosed after genomic sequencing1, with many probably involving pathogenic variants in yet to be discovered disease–gene associations. To search for such associations, we developed a rare variant gene burden analytical framework for Mendelian diseases, and applied it to protein-coding variants from whole-genome sequencing of 34,851 cases and their family members recruited to the 100,000 Genomes Project2. A total of 141 new associations were identified, including five for which independent disease–gene evidence was recently published. Following in silico triaging and clinical expert review, 69 associations were prioritized, of which 30 could be linked to existing experimental evidence. The five associations with strongest overall genetic and experimental evidence were monogenic diabetes with the known β cell regulator3,4UNC13A, schizophrenia with GPR17, epilepsy with RBFOX3, Charcot–Marie–Tooth disease with ARPC3 and anterior segment ocular abnormalities with POMK. Further confirmation of these and other associations could lead to numerous diagnoses, highlighting the clinical impact of large-scale statistical approaches to rare disease–gene association discovery

Rare disease gene association discovery in the 100,000 Genomes Project

Up to 80% of rare disease patients remain undiagnosed after genomic sequencing1, with many probably involving pathogenic variants in yet to be discovered disease–gene associations. To search for such associations, we developed a rare variant gene burden analytical framework for Mendelian diseases, and applied it to protein-coding variants from whole-genome sequencing of 34,851 cases and their family members recruited to the 100,000 Genomes Project2. A total of 141 new associations were identified, including five for which independent disease–gene evidence was recently published. Following in silico triaging and clinical expert review, 69 associations were prioritized, of which 30 could be linked to existing experimental evidence. The five associations with strongest overall genetic and experimental evidence were monogenic diabetes with the known β cell regulator3,4 UNC13A, schizophrenia with GPR17, epilepsy with RBFOX3, Charcot–Marie–Tooth disease with ARPC3 and anterior segment ocular abnormalities with POMK. Further confirmation of these and other associations could lead to numerous diagnoses, highlighting the clinical impact of large-scale statistical approaches to rare disease–gene association discovery

The techno-ecological practice as the politics of ontological coalitions

The paper focuses on the art projects aimed at visualizing (grasping) the physical or biological phenomena through interfaces and / or installations designed specifically for such purpose. Such works often mirror the post-­digital condition of our time where the digital technologies constitute the common background for everyday activities, no longer having the allure of "new" and "exciting" (Berry, Dieter et al., 2015). In this process, both the networked technologies of wireless communication and the act of crossing the boundaries between the digital and the physical play the crucial role as the post-­digital networked imagery increasingly becomes directly connected to the physical environment. I would like to ponder on the questions of processuality and relationality involved in such instances where the complexity of the hybrid works of art clearly transgresses the paradigm of representationalism (Thrift, 2008;; Anderson and Harrison, 2010;; Kember and Zylinska, 2012). The particular attention is given to the fact that such artworks bond different ontological realms (discursive, physical, digital) and different agents (human and non-­human, carbon-­based and software-­based) forging “ontological coalitions” (Malafouris, 2013). Throughout the article the mutlirealist and relational perspective is offered, inspired by the propositions of Gilbert Simondon and Etienne Souriau. Based on the research project supported by National Science Centre Poland ("The aesthetics of post-­digital imagery: between new materialism and object-­oriented philosophy", 2016/21/B/HS2/00746)