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ABSTRACT: The effects of grass silage and red clover silage on milk fatty acid (FA) composition are extensively studied, but little is known of their effects on minor lipid constituents of milk fat globule membrane. We investigated the effects of forage:concentrate (FC) ratio in grass silage-based diets and forage type (grass silage vs. red clover silage) on selected molecular species of milk phospholipids (PL) and the FA composition of PL. Ten multiparous Nordic Red cows were offered following dietary treatments: grass silage-based diets containing 70:30 (HG) or 30:70 (LG) FC ratio or a red clover silage-based diet (RC) comprising 50:50 FC ratio on a dry matter basis. The most abundant molecular species within the phosphatidylcholines was 16:0–18:1 phosphatidylcholine that was increased by 18% in HG compared with LG milk. Dietary treatments did not affect the relative proportion of 18:1–18:1+18:0–18:2 phosphatidylethanolamine that was the most prevalent species (ca. 44%–45%) in that class. We identified the d18:1–22:0 sphingomyelin as the most abundant sphingomyelin species that tended to increase in HG milk compared with LG. The FC ratio did not affect the relative proportions of saturated FA nor monounsaturated FA in PL, but the proportion of cis-9 18:1 was elevated in HG versus LG milk, whereas the proportion of 18:2n-6 was 50% higher in LG versus HG milk. The RC diet increased monounsaturated FA and 18:3n-3 levels in PL compared with grass silage-based diets and decreased the relative proportion of saturated FA. However, the RC diet did not affect the relative proportion of polyunsaturated FA in PL, although red clover silage typically increases the proportion of polyunsaturated FA in milk fat. This study provides valuable knowledge of the minor lipid components in milk on species level in relation to common feeding strategies in high-forage systems.

Genome sequencing was performed on matched normal and tumor tissue from a 6.5-yr-old boy with a diagnosis of recurrent medulloblastoma. A pathogenic heterozygous c.432+1G>A canonical splice donor site variant in GNAS was detected on analysis of blood DNA. Analysis of tumor DNA showed the same splice variant along with copy-neutral loss of heterozygosity on Chromosome 20 encompassing GNAS, consistent with predicted biallelic loss of GNAS in the tumor specimen. This case strengthens the evidence implicating GNAS as a tumor-suppressor gene in medulloblastoma and highlights a scenario in which therapeutics targeting the cAMP pathway may be of great utility.

Abstract Purpose To determine the prevalence and associated factors of self-reported medication information needs among medication users in a general population aged 40 years and above – The Tromsø Study. Methods Cross-sectional study of medication users (n = 10,231) among participants in the Tromsø Study, a descriptive analysis of questionnaire data and multivariable logistic regression (n = 9,194). Results Sixteen percent of medication users expressed a need for more information about own medications. Overall, medication users agreed to a higher degree to have received information from the GP compared to the pharmacy. Concerned medication users and those disagreeing to have received information about side effects had the highest odds for needing more information (OR 5.07, 95% CI 4.43–5.81) and (OR 2.21, 95% CI 1.83–2.68), respectively. Medication users who used heart medications (e.g., nitroglycerin, antiarrhythmics, anticoagulants) (OR 1.71, 95% CI 1.46–2.01), medication for hypothyroidism (OR 1.36, 95% CI 1.13–1.64) or had moderately health anxiety had expressed need for medication information. Whereas medication users with lower education, those that never used internet to search for health advice, and medication users who disagreed to have received information about reason-for-use were associated with lower odds (OR 0.75, 95% CI 0.62–0.91), (OR 0.85, 95% CI 0.74–0.98) and (OR 0.68, 95% CI 0.53–0.88), respectively. Conclusion This study demonstrated that there is need for more information about own medications in a general population aged 40 years and above and shed light on several characteristics of medication users with expressed information need which is important when tailoring the right information to the right person.

Artikkelen utforsker hvordan yrkesfaglige programfaglærere forholder seg til språkrela­terte dilemmaer de opplever i undervisning av ordinære yrkesfagklasser, særlig knytta til elevers flerspråklighet. Jeg undersøker hvilke språk yrkesfaglærere oppgir å gi rom for i opplæringen, og hva lærernes språkrelaterte avgjørelser forteller om deres opplevde rom for aktørskap (Priestley et al., 2015; her jf. læreres profesjonelle handlingsrom). Med utgangspunkt i et språketnografisk datamateriale samla inn i 2020–2021 analyserer jeg utvalgte utdrag fra intervjuer med yrkesfaglærere ved hjelp av Jaffes (2009) (meta)sociolinguistic stance (her: holdningsposisjoner). Yrkesfaglærerne sikrer på ulike måter en norskspråklig ramme i klasserommet – et uttrykk for og bidrag til reproduksjon av en enspråklighetsideologi (Iversen, 2021b; Ortega, 2019; Woolard, 2020). Videre gir yrkesfaglærerne i større grad rom for engelsk enn andre språk, og artikkelen argumen­terer for at dette er et uttrykk for en idé om elitær flerspråklighet (Barakos & Selleck, 2019; Nørreby, 2020). Artikkelen viser hvordan yrkesfaglærernes språkideologiske holdningsposisjoner gir innsikt i deres opplevde profesjonelle handlingsrom. Hand­lingsrommet formes ikke bare av institusjonelle, praktiske, sosiale og materielle rammevilkår, men også av lærernes habitus og fremtidsvisualiseringer. For eksempel spiller faktorer knytta til elevers fremtidige yrkesliv og sosiale forhold i klassen inn i lærernes språkrelaterte avgjørelser. Jeg argumenterer for at også språkideologiske forhold – i utdanningskonteksten og i arbeidslivet – bidrar til å forme lærernes rom for aktørskap. Det er liten tvil om at lærerne har et profesjonelt handlingsrom de kan utnytte, og utnytter. Samtidig er ikke lærernes språkrelaterte avgjørelser bare lærernes egne, men også produkter av den institusjonelle strukturen de jobber innenfor.

Background The knowledge on bovine vaccines against respiratory viruses on bronchoalveolar fluid cells is scarce. Objective To compare the effects of a commercial intranasal (IN) and intramuscular (IM) vaccine against bovine respiratory disease (BRD) complex viruses on bronchoalveolar fluid cells of healthy heifers. Methods 21 healthy heifers were assigned to three treatment groups: control (CO, N = 7), intranasally vaccinated (IN) (n = 7), and intramuscularly vaccinated (IM) (n = 7). The IN group received 1 mL of the commercial vaccine in each nostril once containing attenuated BoHV-1, bPIV-3, and BRSV. The IM group was vaccinated with two doses of 2 mL with an interval of 21 days of the commercial vaccine containing attenuated BoHV-1, bPIV-3, and BRSV plus inactivated BVDV. At day 0 (D0), before the first vaccine dose, and at D3, D7, and D21, after the last vaccine dose, airway bronchoscopy was performed to observe local irritation and collect bronchoalveolar lavage fluid (BALF). The bronchoalveolar count, cytological evaluation, bronchoalveolar cell oxidative metabolism, and total bronchoalveolar IgA and IgG were measured. Results The IN vaccine increased neutrophil cellularity at D7 and D21 and total IgA at D3 in BALF. Total IgA in BALF also increased at D3 and oxidative metabolism of bronchoalveolar cells at D21 lowered compared to the CO group. Following IM vaccination there was no alteration of immunoglobulins or cell oxidative metabolism in BALF. Both vaccines reduced the number of alveolar macrophages. Conclusion Both vaccines induced bronchoalveolar inflammation during the establishment of the vaccine immunity, which was more expressive in the IN protocol.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons. Mutations in the SPTLC1 subunit of serine palmitoyltransferase (SPT), which catalyzes the first step in the de novo synthesis of sphingolipids (SLs), cause childhood-onset ALS. SPTLC1-ALS variants map to a transmembrane domain that interacts with ORMDL proteins, negative regulators of SPT activity. We show that ORMDL binding to the holoenzyme complex is impaired in cells expressing pathogenic SPTLC1-ALS alleles, resulting in increased SL synthesis and a distinct lipid signature. C-terminal SPTLC1 variants cause peripheral hereditary sensory and autonomic neuropathy type 1 (HSAN1) due to the synthesis of 1-deoxysphingolipids (1-deoxySLs) that form when SPT metabolizes L-alanine instead of L-serine. Limiting L-serine availability in SPTLC1-ALS–expressing cells increased 1-deoxySL and shifted the SL profile from an ALS to an HSAN1-like signature. This effect was corroborated in an SPTLC1-ALS pedigree in which the index patient uniquely presented with an HSAN1 phenotype, increased 1-deoxySL levels, and an L-serine deficiency. These data demonstrate how pathogenic variants in different domains of SPTLC1 give rise to distinct clinical presentations that are nonetheless modifiable by substrate availability.

Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2-Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MICOS). In MICOS-deficient cells, limiting PS transfer by Ups2-Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MICOS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function.

A lo largo de lo que va de siglo se viene observando en Gipuzkoa un posible aumento de la población nidificante de milano real Milvus milvus. Si bien parcialmente esta realidad se ha asociado a un incremento en el esfuerzo de muestreo, el proceso de colonización y aumento poblacional de la especie en la provincia parece evidente. Así, de la ausencia de aves reproductoras dada según el censo de 2004 se pasó a algo más de 20 parejas durante el periodo 2014-2015. En un contexto de declive en muchas zonas de España, la realidad de la especie en Gipuzkoa supone, hasta cierto punto, un caso anómalo. En este contexto, durante los últimos años se ha invertido un esfuerzo notable en el seguimiento de la especie. Este artículo resume los resultados del seguimiento de milano real en Gipuzkoa, actualizado para la temporada de cría de 2020. Se detectaron 32 territorios (parejas). La distribución de estos nidos en la provincia no es uniforme, ya que se detecta una concentración más alta de ellos en el sector más sudoriental del territorio. Se registró un éxito de cría alto (85,2%), así como una productividad de 2,0 pollos/pareja (rango: 1-3; 1,4 pollos/pareja se sumamos, también, las parejas que no llegaron a reproducirse), lo que confirma que Gipuzkoa es una zona buena para la reproducción de la especie. Esto puede jugar un papel clave no sólo en un posible proceso de consolidación de la población en la región, sino de colonización y reforzamiento poblacional en regiones limítrofes. Siendo Gipuzkoa una provincia muy forestal, el milano real tiende a ocupar zonas con mayor superficie relativa de hábitats abiertos, lo cual pone de relieve el valor de la campiña en la conservación de la especie. En este contexto, es importante impulsar el desarrollo de estudios orientados a determinar el uso del territorio así como las características que definen qué tipo de campiña es óptima para el milano real. ABSTRACT: Since the beginning of this century, the province of Gipuzkoa has witnessed a remarkable increase in its red kite Milvus milvus breeding population. Although this may in part be attributable to an increase in sampling efforts, the population of this species is clearly in expansion. This species was reported to be absent as a breeding bird in 2004, but during the period 2014-2015 more than 20 adult breeding birds were counted. In view of the fact that this species is in decline in many parts of Spain, the situation in Gipuzkoa is, to some extent, an anomaly. This study has been carried out with the goal of updating the size of the breeding population of the red kite in Gipuzkoa in 2020. Overall, 32 territories were detected. Their geographical distribution was not uniform, as many of them tended to be concentrated within the southeastern part of Gipuzkoa. The breeding parameters were high (success, 85.2%; productivity, 2.0 chicks/pair, range 1-3, 1.4 chicks/pair if we also consider those territories where breeding failed). This relatively high breeding output may play a role not only for the colonisation process already existing within the region, but also to reinforce other populations which breed close by. Gipuzkoa is a region with a very dense woodland cover, but the red kite tends to occupy open habitats, with a proportionally lower amount of wooded habitats. This highlights the great value of traditional farmland habitats for the conservation of the red kite in Gipuzkoa. Thus, it is important to promote studies aimed at determining the use of the territory as well as defining the optimal habitat for the species.

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base.

Abstract Background Although mosaic variation has been known to cause disease for decades, high-throughput sequencing technologies with the analytical sensitivity to consistently detect variants at reduced allelic fractions have only recently emerged as routine clinical diagnostic tests. To date, few systematic analyses of mosaic variants detected by diagnostic exome sequencing for diverse clinical indications have been performed. Methods To investigate the frequency, type, allelic fraction, and phenotypic consequences of clinically relevant somatic mosaic single nucleotide variants (SNVs) and characteristics of the corresponding genes, we retrospectively queried reported mosaic variants from a cohort of ~ 12,000 samples submitted for clinical exome sequencing (ES) at Baylor Genetics. Results We found 120 mosaic variants involving 107 genes, including 80 mosaic SNVs in proband samples and 40 in parental/grandparental samples. Average mosaic alternate allele fraction (AAF) detected in autosomes and in X-linked disease genes in females was 18.2% compared with 34.8% in X-linked disease genes in males. Of these mosaic variants, 74 variants (61.7%) were classified as pathogenic or likely pathogenic and 46 (38.3%) as variants of uncertain significance. Mosaic variants occurred in disease genes associated with autosomal dominant (AD) or AD/autosomal recessive (AR) (67/120, 55.8%), X-linked (33/120, 27.5%), AD/somatic (10/120, 8.3%), and AR (8/120, 6.7%) inheritance. Of note, 1.7% (2/120) of variants were found in genes in which only somatic events have been described. Nine genes had recurrent mosaic events in unrelated individuals which accounted for 18.3% (22/120) of all detected mosaic variants in this study. The proband group was enriched for mosaicism affecting Ras signaling pathway genes. Conclusions In sum, an estimated 1.5% of all molecular diagnoses made in this cohort could be attributed to a mosaic variant detected in the proband, while parental mosaicism was identified in 0.3% of families analyzed. As ES design favors breadth over depth of coverage, this estimate of the prevalence of mosaic variants likely represents an underestimate of the total number of clinically relevant mosaic variants in our cohort.