The beta‐actin gene (ACTB) encodes a ubiquitous cytoskeletal protein, essential for embryonic development in humans. De novo heterozygous missense variants in the ACTB are implicated in causing ...Baraitser–Winter cerebrofrontofacial syndrome (BWCFFS; MIM#243310). ACTB pathogenic variants are rarely associated with intestinal malformations. We report on a rare case of monozygotic twins presenting with proximal small bowel atresia and hydrops in one, and apple‐peel bowel atresia and laryngeal dysgenesis in the other. The twin with hydrops could not be resuscitated. Intensive and surgical care was provided to the surviving twin. Rapid trio genome sequencing identified a de novo missense variant in ACTB (NM_00101.3:c.1043C>T; p.(Ser348Leu)) that guided the care plan. The identical variant subsequently was identified in the demised twin. To characterize the functional effect, the variant was recreated as a pseudoheterozygote in a haploid wild‐type S. cerevisiae strain. There was an obvious growth defect of the yACT1S348L/WT pseudoheterozygote compared to a yACT1WT/WT strain when grown at 22°C but not when grown at 30°C, consistent with the yACT1 S348L variant having a functional defect that is dominant over the wild‐type allele. The functional results provide supporting evidence that the Ser348Leu variant is likely to be a pathogenic variant, including being associated with intestinal malformations in BWCFFS, and can demonstrate variable expressivity within monozygotic twins.
Rainwater as a resource has been underrated due to scientific misunderstandings about its quality, the lack of hydrologic design tools for small catchments, such as roofs, the preference for large ...infrastructures, and the small number of successful cases reported. This book summarizes 17 years of scientific research, operational monitoring, and practical demonstration projects made at Seoul National University Rainwater Research Center. A new paradigm of rainwater is proposed, which is to collect rainwater and use it, instead of draining it. Based on conventional hydrology and methodology, a hydrologic modelling method for micro-catchment is suggested. By incorporating several controllable measures into the design, the system can solve several water-related problems such as flooding, water conservation, emergency water storage, and groundwater recharge. Now is the time to adapt. Many good examples are reported from around the world, including South Korea. Fifty-nine South Korean cities have announced regulations and commitment to become ‘Rain Cities’ by offering financial incentives to rainwater management systems or subsidizing them. This book is written to give hope to those who seek to transform their community from a ‘Drain City’ to a ‘Rain City’. It has been prepared to clear the ambiguity about rainwater management and transform the experts as well as the citizens to become active proponents of rainwater. This book can be a guide to transform the world into Rain Cities, and become a viable solution toward Sustainable Development Goal Number 6.
Anthocyanins are a major group of red to blue spectrum plant pigments with many consumer health benefits. Anthocyanins are derived from the flavonoid pathway and diversified by glycosylation and ...methylation, involving the concerted action of specific enzymes. Blueberry and bilberry (
spp.) are regarded as 'superfruits' owing to their high content of flavonoids, especially anthocyanins. While ripening-related anthocyanin production in bilberry (
) and blueberry (
) is regulated by the transcriptional activator MYBA1, the role of specific structural genes in determining the concentration and composition of anthocyanins has not been functionally elucidated. We isolated three candidate genes,
(
),
(
) and
(
), from
, which were predominantly expressed in pigmented fruit skin tissue and showed high homology between bilberry and blueberry.
-mediated transient expression of
showed that overexpression of
in combination with
significantly increased anthocyanin concentration (3-fold). Overexpression of
showed no effect above that induced by
, while
modulated anthocyanin composition to produce delphinidin-3-galactosylrhamnoside, not naturally produced in tobacco. In strawberry (
), combined transient overexpression of
with a
´
from kiwifruit (
) modulated the anthocyanin profile to include galactosides and arabinosides of delphinidin and cyanidin, major anthocyanins in blueberry and bilberry. These findings provide insight into the role of the final steps of biosynthesis in modulating anthocyanin production in
and may contribute to the targeted breeding of new cultivars with improved nutritional properties.
Fruit quality is dependent on various factors including flavour, texture and colour. These factors are determined by the ripening process, either climacteric or non-climacteric. In grape berry, which ...is non-climacteric, the process is signalled by a complex set of hormone changes. Abscisic acid (ABA) is one of the key hormones involved in ripening, while sugar availability also plays a significant role in certain ripening aspects such as anthocyanin production. To understand the relative influence of hormone and sugar signalling
can prove problematic due to the physiological and environmental (abiotic and biotic) factors at play in vineyards. Here we report on the use of
detached berry culture to investigate the comparative significance of ABA and sugar in the regulation of Pinot noir berry anthocyanin production under controlled conditions. Using a factorial experimental design, pre-véraison berries were cultured on media with various concentrations of sucrose and ABA. After 15 days of
culture, the berries were analysed for changes in metabolites, hormones and gene expression. Results illustrated a stimulatory effect of sucrose and ABA on enhancing berry colour and a corresponding increase in anthocyanins. Increased ABA concentration was able to boost anthocyanin production in berries when sucrose supply was low. The sucrose and ABA effects on berry anthocyanins were primarily manifested through the up-regulation of transcription factors and other genes in the phenylpropanoid pathway, while in other parts of the pathway a down-regulation of key proanthocyanindin transcription factors and genes corresponded to sharp reduction in berry proanthocyanidins, irrespective of sucrose supply. Similarly, increased ABA was correlated with a significant reduction in berry malic acid and associated regulatory genes. These findings suggest a predominance of berry ABA over berry sugar in coordinating the physiological and genetic regulation of anthocyanins and proanthocyanins in Pinot noir grape berries.
Committee 2 of the International Commission on Radiological Protection (ICRP) has constructed mesh-type adult reference computational phantoms by converting the voxel-type ICRP Publication 110 adult ...reference computational phantoms to a high-quality mesh format, and adding those tissues that were below the image resolution of the voxel phantoms and therefore not included in the Publication 110 phantoms. The new mesh phantoms include all the necessary source and target tissues for effective dose calculations, including the 8–40-µm-thick target layers of the alimentary and respiratory tract organs, thereby obviating the need for supplemental organ-specific stylised models (e.g. respiratory airways, alimentary tract organ walls and stem cell layers, lens of the eye, and skin basal layer). To see the impact of the new mesh-type reference phantoms, dose coefficients for some selected external and internal exposures were calculated and compared with the current reference values in ICRP Publications 116 and 133, which were calculated by employing the Publication 110 phantoms and the supplemental stylised models. The new mesh phantoms were also used to calculate dose coefficients for industrial radiography sources near the body, which can be used to estimate the organ doses of the worker who is accidentally exposed by an industrial radiography source; in these calculations, the mesh phantoms were deformed to reflect the size of the worker, and also to evaluate the effect of posture on dose coefficients.
Objective The fate of the abdominal aorta and its branches after thoracic endovascular aortic repair for aortic dissection (TEVAR-AD) has not been studied. The objective of this study was to describe ...the midterm changes in abdominal aortic branch perfusion after TEVAR-AD. Methods A retrospective analysis of TEVAR-AD at a single institution from December 1, 2008, to March 31, 2015, was performed. Computed tomography angiography (CTA) images were reviewed to characterize the perfusion pattern changes of the celiac, superior mesenteric, inferior mesenteric, bilateral renal, and common iliac arteries. Risk factors associated with branch interventions were identified. Results During the study period, 68 patients underwent TEVAR-AD, 46 of whom had pre-TEVAR and post-TEVAR CTA images available for review. For post-TEVAR CTA, the most recent scans were selected for analysis. The mean period between CTA studies was 371 days. Indications for TEVAR-AD were persistent pain (41%), malperfusion (15%), rupture (6%), and aneurysmal degeneration (33%). Twenty-five patients (54%) were treated during the acute phase (<14 days). All patients had dissections extending to the paravisceral aorta. Of the 304 abdominal aortic branches analyzed, 8 required intervention (2.6%). Branch events requiring intervention included malperfusion (two) and aneurysms involving the branches (three). No intervention was performed for one asymptomatic inferior mesenteric artery occlusion. Of the remaining 295 branches, changes in perfusion patterns were observed in 16 (5.4%). Twelve branches (75%) demonstrated an increased true lumen contribution to perfusion. Four branches (25%) had increased false lumen contribution, without clinical evidence of malperfusion. Patients requiring branch interventions were more likely to have severe chronic kidney disease ( P = .012) and more extensive aortic zone coverage during TEVAR ( P = .003). On multivariable Cox proportional hazards analysis, coverage of four or more zones during TEVAR-AD was associated with branch intervention (odds ratio, 6.44; 95% confidence interval, 1.01-40.8). The estimated intervention-free patency of the abdominal aortic branches was 89% at 5 years. Conclusions Perfusion patterns of abdominal aortic branches remain largely stable after TEVAR-AD. The need for branch intervention is rare and associated with extensive aortic coverage.
Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 ...seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3-11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.
Objectives
We conducted a longitudinal cohort analysis to evaluate the association of pre‐treatment body mass index (BMI) with CD4 recovery, virological failure (VF) and cardiovascular risk disease ...(CVD) markers among people living with HIV (PLHIV).
Methods
Participants who were enrolled between January 2003 and March 2019 in a regional Asia HIV cohort with weight and height measurements prior to antiretroviral therapy (ART) initiation were included. Factors associated with mean CD4 increase were analysed using repeated‐measures linear regression. Time to first VF after 6 months on ART and time to first development of CVD risk markers were analysed using Cox regression models. Sensitivity analyses were done adjusting for Asian BMI thresholds.
Results
Of 4993 PLHIV (66% male), 62% had pre‐treatment BMI in the normal range (18.5–25.0 kg/m2), while 26%, 10% and 2% were underweight (< 18.5 kg/m2), overweight (25–30 kg/m2) and obese (> 30 kg/m2), respectively. Both higher baseline and time‐updated BMI were associated with larger CD4 gains compared with normal BMI. After adjusting for Asian BMI thresholds, higher baseline BMIs of 23–27.5 and > 27.5 kg/m2 were associated with larger CD4 increases of 15.6 cells/µL 95% confidence interval (CI): 2.9–28.3 and 28.8 cells/µL (95% CI: 6.6–50.9), respectively, compared with normal BMI (18.5–23 kg/m2). PLHIV with BMIs of 25–30 and > 30 kg/m2 were 1.27 times (95% CI: 1.10–1.47) and 1.61 times (95% CI: 1.13–2.24) more likely to develop CVD risk factors. No relationship between pre‐treatment BMI and VF was observed.
Conclusions
High pre‐treatment BMI was associated with better immune reconstitution and CVD risk factor development in an Asian PLHIV cohort.
The International Commission on Radiological Protection (ICRP) reference male and female adult phantoms, described in Publication 110, are voxel phantoms based on whole-body computed tomography scans ...of a male and a female patient, respectively. The voxel in-plane resolution and the slice thickness, of the order of a few millimetres, are insufficient for proper segmentation of smaller tissues such as the lens of the eye, the skin, and the walls of some organs. The calculated doses for these tissues therefore present some limitations, particularly for weakly penetrating radiation. Similarly, the Publication 110 phantoms cannot represent 8–40-µm-thick target regions in respiratory or alimentary tract organs. Separate stylised models have been used to represent these tissues for calculation of the ICRP reference dose coefficients (DCs). ICRP Committee 2 recently initiated a research project, the ultimate goal of which is to convert the Publication 110 phantoms to a high-quality polygon-mesh (PM) format, including all source and target regions, even those of the 8–40-µm-thick alimentary and respiratory tract organs. It is expected that the converted phantoms would lead to the same or very similar DCs as the Publication 110 reference phantoms for penetrating radiation and, at the same time, provide more accurate DCs for weakly penetrating radiation and small tissues. Additionally, the reference phantoms in the PM format would be easily deformable and, as such, could serve as a starting point to create phantoms of various postures for use, for example, in accidental dose calculations. This paper will discuss the current progress of the phantom conversion project and its significance for ICRP DC calculations.
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