ABSTRACT
Congenital disorders of glycosylation (CDG) are a group of mostly autosomal recessive disorders primarily characterized by neurological abnormalities. Recently, we described a single CDG ...patient with a de novo mutation in the X‐linked gene, Signal Sequence Receptor 4 (SSR4). We performed whole‐exome sequencing to identify causal variants in several affected individuals who had either an undifferentiated neurological disorder or unsolved CDG of unknown etiology based on abnormal transferrin glycosylation. We now report eight affected males with either de novo (4) or inherited (4) loss of function mutations in SSR4. Western blot analysis revealed that the mutations caused a complete loss of SSR4 protein. In nearly all cases, the abnormal glycosylation of serum transferrin was only slightly above the accepted normal cutoff range.
Congenital Disorders of Glycosylation (CDG) lead to incomplete protein glycosylation. One disorder, SSR4‐CDG, was previously defined in a single patient. Here we present molecular analysis and clinical phenotypes of eight males with inherited and de novo mutations in X‐linked SSR4. Standard CDG biochemical analysis might easily miss them.
To assess whether persistent micronutrient deficiencies in Mongolian children identified in our earlier biochemical study are associated with inadequacies in quantity and/or quality in their ...complementary diets.
A cross-sectional study of breast-fed children aged 6-23 months, randomly selected from four districts in Ulaanbaatar and four provincial capitals.
Weight and length were measured, and sociodemographic status, feeding practices and nutrient adequacy of complementary foods for children aged 6-8 months (n 26), 9-11 months (n 29) and 12-23 months (n 73) were assessed via questionnaire and in-home interactive 24 h recalls.
No geographic differences existed so data were combined. Adherence to WHO infant and young child feeding practices was poor: few children were exclusively breast-fed up to 6 months of age or received the recommended number of feedings containing the recommended number of food groups. Nevertheless, energy intakes from complementary diets, primarily from cereals and non-nutritious snacks, were above WHO-estimated needs; <1 % of energy was from meat and eggs or fruits and vegetables. Median intakes and densities of most nutrients (except protein, thiamin and riboflavin) failed to meet WHO recommendations for at least two age groups, assuming average breast milk intake; greatest density deficits were for Fe > vitamin C > vitamin A > Zn > Ca.
Complementary feeding in Mongolia is compromised by deficits in several micronutrients but not energy, in part because of frequent consumption of non-nutritious snacks. The latter may interfere with breast-feeding and should be avoided. Instead, wheat-based complementary foods should be enriched with affordable cellular animal foods and fruits rich in vitamin C to combat existing micronutrient deficits.
Summary
Cattle vaccination against bovine tuberculosis (bTB) has been proposed as a supplementary method to help control the incidences of this disease. Bacillus Calmette–Guérin (BCG) is currently ...the only viable candidate vaccine for immunization of cattle against bTB, caused by Mycobacterium bovis (M. bovis). In an attempt to characterize the differences in the immune response following M. bovis infection between BCG‐vaccinated and non‐vaccinated animals, a combination of gross pathology, histopathology and immunohistochemical (IHC) analyses was used. BCG vaccination was found to significantly reduce the number of gross and microscopic lesions present within the lungs and lymph nodes. Additionally, the microscopically visible bacterial load of stages III and IV granulomas was reduced. IHC using cell surface markers revealed the number of CD68+ (macrophages), CD3+ (T lymphocytes) and WC1+ cells (γδ T cells) to be significantly reduced in lymph node granulomas of BCG‐vaccinated animals, when compared to non‐vaccinated animals. B lymphocytes (CD79a+) were significantly increased in BCG‐vaccinated cattle for granulomas at stages II, III and IV. IHC staining for iNOS showed a higher expression in granulomas from BCG‐vaccinated animals compared to non‐vaccinated animals for all stages, being statistically significant in stages I and IV. TGFβ expression decreased alongside the granuloma development in non‐vaccinated animals, whereas BCG‐vaccinated animals showed a slight increase alongside lesion progression. IHC analysis of the cytokines IFN‐γ and TNF‐α demonstrated significantly increased expression within the lymph node granulomas of BCG‐vaccinated cattle. This is suggestive of a protective role for IFN‐γ and TNF‐α in response to M. bovis infection. Findings shown in this study suggest that the use of BCG vaccine can reduce the number and severity of lesions, induce a different phenotypic response and increase the local expression of key cytokines related to protection.
The Korean Hanwoo cattle have been intensively selected for production traits, especially high intramuscular fat content. It is believed that ancient crossings between different breeds contributed to ...forming the Hanwoo, but little is known about the genomic differences and similarities between other cattle breeds and the Hanwoo. In this work, cattle breeds were grouped by origin into four types and used for comparisons: the Europeans (represented by six breeds), zebu (Nelore), African taurine (N'Dama) and Hanwoo. All animals had genotypes for around 680 000 SNPs after quality control of genotypes. Average heterozygosity was lower in Nelore and N'Dama (0.22 and 0.21 respectively) than in Europeans (0.26–0.31, with Shorthorn as outlier at 0.24) and Hanwoo (0.29). Pairwise FST analyses demonstrated that Hanwoo are more related to European cattle than to Nelore, with N'Dama in an intermediate position. This finding was corroborated by principal components and unsupervised hierarchical clustering. Using genome‐wide smoothed FST, 55 genomic regions potentially under positive selection in Hanwoo were identified. Among these, 29 were regions also detected in previous studies. Twenty‐four regions were exclusive to Hanwoo, and a number of other regions were shared with one or two of the other groups. These regions overlap a number of genes that are related to immune, reproduction and fatty acid metabolism pathways. Further analyses are needed to better characterize the ancestry of the Hanwoo cattle and to define the genes responsible to the identified selection peaks.
This study assessed whether pacing strategies are adopted during supramaximal exercise bouts lasting longer than 30 s.
Eight healthy males performed six Wingate anaerobic tests (WAnT). Subjects were ...informed that they were performing four 30-s WAnT, a 33-s, and a 36-s WAnT. However, they actually completed two trials of 30, 33, and 36 s each. Temporal feedback in the deception trials was manipulated so that subjects were unaware of the time discrepancy. Power output was determined from the angular displacement of the flywheel. The peak power (PPI), mean power (MPI), and fatigue (FI) indices were calculated for each trial.
Power output was similar for all trials up to 30 s. However, at 36 s, the power output was significantly lower in the 36-s deception trial compared with the 36-s informed trial (392 +/- 32 W vs 470 +/- 88 W) (P < 0.001). The MPI was significantly lower in the 36-s trials (714 +/- 76 W and 713 +/- 78 W) compared with the 30-s trials (745 +/- 65 W and 764 +/- 82 W) although they were not different at 30 s (764 +/- 83 W and 755 +/- 79 W). The significant reduction in FI was greatest in the 36-s deception trial.
The significant reduction in power output in the last 6 s of the 36-s deception trial, but not in the 36-s informed trial, indicates the presence of a preprogrammed 30-s "end point" based on the anticipated exercise duration from previous experience. The similarity in pacing strategy suggests that the pacing strategy is centrally regulated.
Abstract
SHADOWS 1, 2 is an intended future beam dump experiment in the CERN North Area, aiming to search for feebly interacting particles (FIPs) 3 created in 400 GeV/c proton interactions. Due to ...its proposed off-axis location alongside the K12 beamline 4, the SHADOWS detector can be placed potentially very close to the beam dump, enabling it to search for FIPs in unexplored parts of the parameter space. In order to guarantee good quality of a potential signal, it is crucial to reduce any backgrounds of Standard Model particles as much as possible. The dominant background downstream the beam dump is caused by muons 1. This introduces the need of a dedicated muon sweeping system consisting of magnetised iron blocks (MIBs) to actively mitigate this background component. We present the conceptional design studies in the framework of the Conventional Beams Working Group of the Physics Beyond Colliders Initiative at CERN 5, 6.
The ability to manipulate nano-particles at the nano-scale is critical for the development of active quantum systems. This paper presents a technique to manipulate diamond nano-crystals at the ...nano-scale using a scanning electron microscope, nano-manipulator and custom tapered optical fibre probes. The manipulation of a approximately 300 nm diamond crystal, containing a single nitrogen-vacancy centre, onto the endface of an optical fibre is demonstrated. The emission properties of the single photon source post manipulation are in excellent agreement with those observed on the original substrate.
Production of polyketides is accomplished through complex enzymes known as polyketide synthases (PKS); these enzymes have highly conserved domains that might be useful in screens for PKSs in diverse ...groups of organisms. A degenerate PCR-based approach was used to amplify PKS fragments of the ketosynthase domain from genomic DNA of a group of insect- and nematode-associated fungi. Of 157 isolates (representing 73 genera and 144 species) screened, 92 isolates generated PCR products of predicted size (approximately 300 bp). The ability to detect PKS domains was a function of the number of different primer pairs employed in the screen. Cloning and sequencing revealed that 66 isolates had at least one unique PKS sequence; ten members of this set contained multiple PKS fragments, for a total of 76 unique PKS fragments. Since PKS genes appear to be widespread among fungi, a PCR-based screening system appears to be an efficient, directed means to identify organisms having the potential to produce polyketides.
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