bluuebunny/crossref_metadata_2025 huggingface dataset:
Integral field unit for the existing imaging and spectroscopy instrument, FOCAS
Authors: Ozaki Shinobu , Fukushima Mitsuhiro , Iwashita Hikaru , Mitsui Kenji , Hattori Takashi , Lee Chien-Hsiu , Tanaka Yoko , Tsuzuki Toshihiro , Miyazaki Satoshi , Yamashita Takuya , Okada Norio , Obuchi Yoshiyuki
Published: September 2020

The Faint Object Camera and Spectrograph (FOCAS) is an optical imaging and spectroscopy instrument for the Subaru Telescope. It has been a workhorse instrument since the first-light phase of the telescope. We describe an integral field unit (IFU) that has recently been installed in FOCAS. The IFU utilizes an image slicer that divides a ${13{^{\prime \prime }_{.}}5}$ × ${10{^{\prime \prime }_{.}}0}$ field of view into 23 stripes, with a width of ${0{^{\prime \prime }_{.}}435}$. A sky spectrum separated from an object by approximately ${5{^{\prime }_{.}}2}$ can be obtained at the same time as an object spectrum. Test observations confirmed that the image quality of the IFU does not degrade the ${0{^{\prime \prime }_{.}}435}$ sampling, and that slice width and length are consistent with the design. Highly reflective multilayer dielectric coatings were coated on all the mirrors in the IFU, thereby offering a high mean IFU throughput of ∼85% over the field. However, the outer part of the field showed throughput degradation, which was mainly caused by vignetting as a result of misalignment. The flat-fielding accuracy was degraded by the vignetting, with the variation depending on the direction of the telescope.
Coeliac disease is a risk factor for the development of seronegative arthritis in patients with autoimmune thyroid disease
Authors: Lupoli Gelsy Arianna , Tasso Marco , Costa Luisa , Caso Francesco , Scarpa Raffaele , Del Puente Antonio , Peluso Rosario
Published: September 2020

Objective

Hashimoto’s thyroiditis is known to cluster with other systemic autoimmune disorders. Rheumatic manifestations, such as a seronegative non-erosive polyarthritis have been described. The aim of this study was to evaluate the characteristics and the prevalence of rheumatic features in thyroiditis patients, and to ascertain whether the association with systemic autoimmune disorders improved the arthritis manifestations.

Methods

In total, 180 thyroiditis patients were enrolled. Major clinical and demographic characteristics have been recorded. Patients underwent a rheumatological clinical assessment and extra-articular manifestations allowing for a differential diagnosis with systemic autoimmune diseases and spondyloarthropathy. Presence of systemic autoimmune diseases was recorded.

Results

A total of 8.33% of thyroiditis patients shown a peripheral inflammatory arthritis (P = 0.002). Female gender (P = 0.042) and thyroid peroxidase (TPOAbs) positivity (P = 0.001) were more frequent. In total, 37 patients had systemic autoimmune diseases (P = 0.0003). A significant high prevalence of coeliac disease and Addison disease was found (P = 0.034 and P = 0.049, respectively). In patients with coeliac disease, the articular manifestations were more frequent (21.21%) (P = 0.001) and the risk to develop joint involvement was 2.96.

Conclusion

Although we found an articular involvement in about one-third of thyroiditis patients, the prevalence of inflammatory arthropathy was only 8.33%. The prevalence of other coexisting autoimmune disorders was 34.26% with a significant prevalence of coeliac disease (7.41%). Thyroiditis patients with coeliac disease have an articular involvement more frequently than those without. In these patients, we have found a high risk of developing arthritis than patients with only thyroiditis, suggesting cumulative autoimmune effects in the developing articular involvement.
Ageing unequally in Europe
Authors: Olivera Javier
Published: September 2020

To shed light on the quality of the ageing experience in Europe and its heterogeneity, this study adapts and computes the Active Ageing Index—an index constructed at the country level to monitor ageing quality in Europe—at the individual level. This strategy allows the measuring of inequality in the experience of active ageing and is flexible enough to consider different value judgements in the overall assessment of the quality of life while ageing. The study examines the predictors of this inequality by using regressions with a Gini-recentred influence function. It finds that education plays a very significant role in reducing inequality, though its influence varies across countries. Furthermore, the study uncovers large variance in the quality of the ageing experience across Europe. For instance, more than 50% of the populations of Romania, Lithuania and Bulgaria show a level of active ageing quality lower than that of the bottom decile of the distribution in Sweden.
The Limits of Gaining Rights while Remaining Marginalized: The Deferred Action for Childhood Arrivals (DACA) Program and the Psychological Wellbeing of Latina/o Undocumented Youth
Authors: Patler Caitlin , Hamilton Erin R , Savinar Robin L
Published: September 2020

Policies that expand the rights of marginalized groups provide an additional level of structural integration, but these changes do not always come with broad social acceptance or recognition. What happens when a legally marginalized group attains increased rights but not full political or social inclusion? In particular, what are the mental health implications of these transitions for impacted groups? We bring together theories of liminal legality and stress process to offer a framework for understanding how expansions in the legal rights of a highly politicized and vulnerable social group can be initially beneficial, but can attenuate due to renewed or new stress events, chronic stressors, and anticipatory stressors. We use the case of Latina/o immigrant youth who transitioned from undocumented legal status to temporarily protected status under the Deferred Action for Childhood Arrivals (DACA) program. Analyses of representative California statewide survey data from 2007 to 2018, combined with surveys and in-depth interviews with DACA recipients, suggest that without full social and structural inclusion, legal transitions that expand rights will produce short-term psychological benefits that do not hold up over time.
Sleep deprivation and compensatory cognitive effort on a visual information processing task
Authors: Sullan Molly J , Drummond Sean P A , Granholm Eric
Published: September 2020

Study Objectives

Total sleep deprivation (TSD) is often associated with worse performance on tasks of attention and working memory, but some studies show no performance changes. One possibility is that greater compensatory cognitive effort is put forth to achieve similar results after TSD. We aimed to better understand the relationship between TSD, cognitive engagement, and performance outcomes following TSD.

Methods

Twenty healthy adults completed cognitive testing following a night of normal sleep and again after ~55 hours of TSD. Participants detected target letters in low (3-item) and high (10-item) load visual letter displays on the span of apprehension task with concurrent pupillometry, a measure of cognitive effort.

Results

We found significantly poorer detection accuracy and marginally longer response times following TSD across both arrays. In both arrays, significantly greater preparatory pupillary responses were found just prior to array onset. There was also a significant session by array interaction for pupillary responses, such that significantly greater dilation was found for the 3-letter array after TSD, while a nonsignificant decline in dilation was found following the 10-letter array after TSD.

Conclusions

These results suggest a complex relationship between attentional control and cognitive resource allocation following TSD. Sleep-deprived individuals may allocate more compensatory cognitive effort to easier tasks but choose to disengage from more challenging cognitive tasks that have little perceived reward or probability of success to preserve diminishing cognitive resources. More work is needed to better delineate the underlying neurological systems involved in these processing load-dependent attentional control mechanisms after TSD.
The effects of enzymatically treated soybean meal on growth performance and intestinal structure, barrier integrity, inflammation, oxidative status, and volatile fatty acid production of nursery pigs
Authors: Ruckman Leigh A , Petry Amy L , Gould Stacie A , Kerr Brian J , Patience John F
Published: September 2020

The objective of this experiment was to determine the impact of diets containing increasing amounts of enzymatically treated soybean meal (ESBM) but decreasing amounts of soybean meal (SBM) on growth performance, intestinal structure, and barrier integrity, inflammation, and oxidative status in weaned pigs. A total of 480 pigs [6.3 ± 1.2 kg body weight (BW)] were blocked by initial BW and pens (n = 12 per treatment) were randomly allotted to one of four dietary treatments. Diets were fed in three phases (days 0–14, 14–28, and 28–35) over a 35-d period. The four dietary treatments consisted of a negative control diet (NC): the NC with 7.0% ESBM (ESBM1), the NC with 14.0% ESBM (ESBM2), and the NC with 21.0% ESBM (ESBM3). Soybean meal was reduced proportionately in each treatment. In phase 2, ESBM inclusion was decreased by 50% (3.5%, 7.0%, and 10.5% ESBM, respectively); phase 3 was a common diet and contained no ESBM. Fecal score was visually ranked weekly using a four-point scale. Intestinal tissue, digesta, and blood samples were collected from 48 pigs (1 per pen) on day 10. Data were analyzed using PROC MIXED of SAS (9.4) with pen as the experimental unit; diet and block were considered fixed effects. Linear and quadratic contrasts were used to determine the effect of increasing ESBM. Overall, ESBM2 and ESBM3 decreased final BW, average daily gain, and average daily feed intake compared to NC and ESBM1 (diet, P < 0.05; linear, P < 0.05). Overall fecal score (diet, P < 0.05) and fecal dry matter (P < 0.05) were improved by feeding ESBM diets compared to NC. Volatile fatty acid (VFA) concentration of acetate, propionate, butyrate, and total VFA in ileal contents increased as ESBM inclusion increased (P < 0.05). Colonic VFA concentration was not impacted (P > 0.10). Total antioxidant capacity was increased by ESBM (P < 0.05). The concentration of mucosal interleukin-4 increased as the inclusion of ESBM increased (linear, P < 0.05). Messenger ribonucleic acid abundance of occludin and zonula-occludens-1 in ileal tissue was increased by ESBM1 or ESBM2 (P < 0.05). In conclusion, increasing the dietary levels of ESBM over 7% had a negative impact on nursery pig performance, but ESBM positively impacted fecal score. Feeding ESBM improved oxidative status and intestinal barrier integrity while increasing ileal VFA production but had minimal impact on intestinal inflammation or morphology. Further research is needed to determine the optimal inclusion level of ESBM.
Canopy position affects photosynthesis and anatomy in matureEucalyptustrees in elevated CO2
Authors: Crous K Y , Campany C , López R , Cano F J , Ellsworth D S
Published: September 2020

Leaves are exposed to different light conditions according to their canopy position, resulting in structural and anatomical differences with consequences for carbon uptake. While these structure–function relationships have been thoroughly explored in dense forest canopies, such gradients may be diminished in open canopies, and they are often ignored in ecosystem models. We tested within-canopy differences in photosynthetic properties and structural traits in leaves in a mature Eucalyptus tereticornis canopy exposed to long-term elevated CO2 for up to 3 years. We explored these traits in relation to anatomical variation and diffusive processes for CO2 (i.e., stomatal conductance, gs, and mesophyll conductance, gm) in both upper and lower portions of the canopy receiving ambient and elevated CO2. While shade resulted in 13% lower leaf mass per area ratio (MA) in lower versus upper canopy leaves, there was no relationship between leaf nitrogen concentration (Nmass) and canopy gap fraction. Both maximum carboxylation capacity (Vcmax) and maximum electron transport (Jmax) were ~18% lower in shaded leaves and were also reduced by ~22% with leaf aging. In mature leaves, we found no canopy differences for gm or gs, despite anatomical differences in MA, leaf thickness and mean mesophyll thickness between canopy positions. There was a positive relationship between net photosynthesis and gm or gs in mature leaves. Mesophyll conductance was negatively correlated with mean parenchyma length, suggesting that long palisade cells may contribute to a longer CO2 diffusional pathway and more resistance to CO2 transfer to chloroplasts. Few other relationships between gm and anatomical variables were found in mature leaves, which may be due to the open crown of Eucalyptus. Consideration of shade effects and leaf-age-dependent responses to photosynthetic capacity and mesophyll conductance are critical to improve canopy photosynthesis models and will improve the understanding of long-term responses to elevated CO2 in tree canopies.
Knowledge, attitudes and practices concerning visceral leishmaniasis among residents of a sporadic transmission area in southeast Brazil
Authors: Limongi Jean E , Costa Luiz C G P , Perissato Izabela L , Giorgiani Mariana , Rocha Máyra B , Faria Larissa F D , Valente Hiléia C O , Oliveira Stefan V
Published: September 2020

Background

In the last four decades, visceral leishmaniasis (VL) has undergone an urbanization process in Brazil. This research aimed to assess the knowledge, attitudes and practices concerning VL among residents of a sporadic transmission urban area in southeast Brazil.

Methods

A community-based, cross-sectional quantitative study was conducted. Scores for knowledge, attitudes and practices concerning VL were evaluated and the bivariate analysis was performed.

Results

The analysis indicated that 29.9% had good knowledge, 5.2% had appropriate attitudes and 62.1% had appropriate practices. Notwithstanding that, pivotal practices for controlling VL had unsatisfactory individual frequencies. Good knowledge on VL was related to women, a higher level of education, a higher income, the place of residence and having pets. Appropriate attitudes were related to the place of residence. The practices had no significant associations with the sociodemographic and epidemiological variables.

Conclusion

This study demonstrated that even in the area of disease transmission, knowledge on VL is very limited, including at the most basic level. In order to achieve effectiveness in actions against VL in Brazil, the participation of the affected communities is imperative, therefore popular health education interventions are necessary to improve the population's understanding of the disease and to avoid inappropriate attitudes and practices.
Validation and Precision of Mixed Reality Technology in Baha Attract Implant Surgery
Authors: Tian Xu , Gao Zhi-qiang , Zhang Zhu-hua , Chen Yu , Zhao Yang , Feng Guo-dong
Published: September 2020

Objective:

To test the feasibility of image-guided Baha Attract implant surgery with mixed reality (MR) in the form of the HoloLens to visualize critical structures and facilitate precise Baha implant placement.

Methods:

A cadaveric case study of bilateral Baha Attract implant approaches was conducted using Star Atlas MR three-dimensional (3D) medical interaction system guidance at the Otolaryngology Department of PUMCH, Beijing, China. The accuracy of visual surface registration was determined by the target registration error (TRE) between the predefined points on the preoperative 3D holographic Baha Attract implant model and the postoperatively reconstructed 3D model.

Results:

Bilateral Baha Attract implantation was completed successfully for all four cadaveric heads using the Star Atlas MR 3D medical interaction system with the HoloLens. The preoperative 3D digital model characteristics (including bone quality and thickness and avoidance of cranial vessels, air cells, and cranial sutures) corresponded well with the 3D model of the actual implantation reconstructed postoperatively. The median TRE of our system was 2.97 mm (ranging from 1.98 to 4.58 mm) in terms of distance and 2.76 degrees (ranging from 0.59 to 6.4 degrees) in terms of angle.

Conclusions:

Applying MR technology in the form of the HoloLens in Baha Attract implant surgery is feasible and could improve the accuracy of the surgery. The described MR system for Baha Attract implantation has the potential to improve the surgeon's confidence, as well as the surgical safety, efficiency, and precision.
Diurnal Variation in Medical Emergency Team Calls at a Tertiary Care Children’s Hospital
Authors: Conway Susan R. , Tegtmeyer Ken , Wheeler Derek S. , Loechtenfeldt Allison , Stalets Erika L. , Brady Patrick W.
Published: September 2020

Introduction:

Medical emergency teams (METs) bring critical care expertise to the bedsides of hospital ward patients who may be deteriorating. Diurnal variation in MET activation rates may identify inconsistencies in the detection of patients needing intervention. We aimed to determine whether such variation exists at our tertiary care children’s hospital.

Methods:

In this retrospective cohort study, we collected data including date and time of MET and disposition following MET for all inpatients at Cincinnati Children’s Hospital Medical Center with a MET call between January 2008 and May 2014. The analysis compared the MET rate between days and nights, weekdays and weekends, and before and after nursing shift change.

Results:

The number of METs per hour varied throughout the day. More METs were called during the day than at night (0.7 calls/shift ± 0.95 vs 0.6 ± 0.9, P < 0.001). There were also more METs per day on weekdays than weekends (1.4 ± 1 calls/d vs 1.2 ± 1, P < 0.001). Daytime METs were more likely to lead to transfer to the intensive care unit or operating room than those called at night (61.9% vs. 52.9%, P < 0.001). MET activation rates did not differ significantly in the 2 hours before nursing shift change compared to the 2 hours after.

Conclusions:

At our large tertiary care children’s hospital, there are both diurnal variations and variations across weekdays versus weekends in the MET activation rate. This difference may indicate variations in our ability to detect deteriorating patients on the wards and be further studied.
Comparing geographic information system–based estimates with trauma center registry data to assess the effects of additional trauma centers on system access
Authors: Winchell Robert J. , Broecker Justine , Kerwin Andrew J. , Eastridge Brian , Crandall Marie
Published: September 2020

BACKGROUND

Geographic information systems (GISs) are often used to analyze trauma systems. Geographic information system–based approaches can model access to a trauma center (TC), including estimates of transport time and population coverage, when accurate trauma registry and emergency medical systems (EMS) data are not available. We hypothesized that estimates of trauma system performance calculated using a standard GIS method with public data would be comparable with trauma registry data.

METHODS

A standardized GIS-based method was used to estimate metrics of TC access in a regional trauma system in which the number of TCs increased from one to three during a 3-year period. Registry data from the index TC in the system were evaluated for different periods during this evolution. The number of admissions to the TC in different periods was compared with changes predicted by the GIS-based model, and the distribution of observed ground-based transportation times was compared with the predicted distribution.

RESULTS

With the addition of two TCs to the system, the volume of patients transported by ground to the index TC decreased by 30%. However, the model predicted a 68% decrease in population having the shortest predicted transport time to the index TC. The model predicted the geographic trend seen in the registry data, but many patients were transported to the index TC even though it was not the closest center. Observed transport times were uniformly shorter than predicted times.

CONCLUSION

The GIS-based model qualitatively predicted changes in distribution of trauma patients, but registry data highlight that field triage decisions are more complex than model assumptions. Similarly, transport times were systematically overestimated. This suggests that model assumptions, such as vehicle speed, based on normal traffic may not fully reflect emergency medical systems (EMS) operations. There remains great need for metrics to guide policy based on widely available data.

LEVEL OF EVIDENCE

Epidemiological, level III.
Fluviibacter phosphoraccumulans gen. nov., sp. nov., a polyphosphate-accumulating bacterium of Fluviibacteraceae fam. nov., isolated from surface river water
Authors: Watanabe Keiji , Morohoshi Sho , Kunihiro Tadao , Ishii Yuichi , Takayasu Lena , Ogata Yusuke , Shindo Chie , Suda Wataru
Published: September 2020

Three aerobic, Gram-stain-negative, non-motile, rod-shaped bacteria, designated as strains SHINM1T, ICHIJ1 and ICHIAU1, were isolated from surface river water (Saitama Prefecture, Japan). Phylogenetic analyses based on 16S rRNA and 40 marker gene sequences revealed that the strains formed a distinct phylogenetic lineage within the order

Rhodocyclales

. The three strains shared 100 % 16S rRNA gene similarity. Growth occurred at 15–30 °C and pH 6.0–9.5, but not in the presence of ≥1.0 % (w/v) NaCl. The isolates stained positive for intracellular polyphosphate granules. The major cellular fatty acids were C16 : 0, summed feature 2 (C12 : 1 aldehyde and/or iso-C16 : 1 I and/or C14 : 0 3-OH), summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c) and summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c). The major polar lipids were phosphatidylethanolamine and an unidentified phospholipid. The predominant quinone system of strain SHINM1T was ubiquinone-8 and its DNA G+C content was 56.7 mol%. Genome sequencing of the three isolates revealed a genome size of 2.29–2.43 Mbp and average nucleotide identity by orthology values of ≥98.9 %. Based on the results of phenotypic and phylogenetic analyses, strains SHINM1T, ICHIJ1 and ICHIAU1 represent a novel species of a new genus, for which the name Fluviibacter phosphoraccumulans gen. nov., sp. nov. is proposed, within a new family, Fluviibacteraceae fam. nov. of the order

Rhodocyclales

. The type strain is SHINM1T (=JCM 32071T=NCIMB 15105T).
Paenibacillus apii sp. nov., a novel nifH gene-harbouring species isolated from the rhizospheres of vegetable plants grown in different regions of northern China
Authors: Tong Shuai , Wang Li-wei , Sun Yu-chen , Khan Mohammad Sayyar , Gao Jun-lian , Sun Jian-guang
Published: September 2020

Two nifH gene-harbouring bacterial strains were isolated from rhizospheres of different vegetable plants grown in different regions of northern PR China. The two strains possessed almost identical 16S rRNA gene sequences. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between the two strains were 99.21 and 93.6% respectively, suggesting they belong to one species. Based on 16S rRNA gene phylogeny, the two strains were clustered together with

Paenibacillus rhizophilus

7197T,

Paenibacillus sabinae

T27T and

Paenibacillus forsythiae

T98T, but on a separate branch. Novelty of the species was confirmed by ANI and dDDH comparisons between the type strain 7124T and its closest relatives, since the obtained values were considerably below the proposed thresholds for the species delineation. The genome size of strain 7124T was 5.40 Mb, comprising 5050 predicted genes with a DNA G+C content of 52.3 mol%. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and three unidentified lipids. The major cellular fatty acids were anteiso-C15  :  0 (52.9%) and C16  :  0 (23.4 %). Menaquinone-7 was reported as the major respiratory quinone. The diamino acid in the cell-wall peptidoglycan was found to be meso-diaminopimelic acid. Based on phylogenetic, genomic, chemotaxonomic and phenotypic data, the two isolates are considered to represent a novel species of the genus

Paenibacillus

, for which the name Paenibacillus apii sp. nov. is proposed, with 7124T (=DSM 103172T=CGMCC 1.15689T) as type strain.
Identification and functional analyses of a cell-death inhibitor encoded by guinea pig cytomegalovirus gp38.1 in cell culture and in animals
Authors: Noguchi Kazuma , Majima Ryuichi , Takahashi Keita , Iwase Yoshihiko , Yamada Souichi , Satoh Keisuke , Koshizuka Tetsuo , Inoue Naoki
Published: September 2020

Cytomegaloviruses (CMVs) employ an array of strategies designed to interfere with host defence responses against pathogens. Studies on such evasion mechanisms are important for understanding the pathogenesis of CMV diseases. Although guinea pig CMV (GPCMV) provides a useful animal model for congenital CMV infection, its evasion strategies are not fully elucidated. Here, we analysed a genome locus that may encode gene products for the GPCMV evasion mechanisms and found the following. (1) RACE analyses identified five transcripts in the GP38-gp38.4 locus, one of which was a spliced product encoding gp38.1. Similarities in the splicing pattern and gene position of gp38.1 to human CMV UL37 and its exon 1 encoding vMIA (viral mitochondria-localized inhibitor of apoptosis) suggest that the gp38.1 gene encodes an apoptosis inhibitor. (2) In a transient transfection assay, gp38.1 localized in the mitochondria and relocated BAX from the cytoplasm to the mitochondria, although its co-localization with BAK was not evident. Further, the expression of gp38.1 partially reduced staurosporine-induced apoptosis. (3) GPCMV defective in the gp38.1 ORF (Δ38.1) and the virus that rescues the defect (r38.1) were generated. Guinea pig fibroblast cells infected with Δ38.1 died earlier than r38.1-infected cells, which resulted in the lower yields of Δ38.1. (4) In animals, viral loads in the spleens of r38.1-infected guinea pigs were higher than those in the spleens of Δ38.1-infected animals. In conclusion, although GPCMV gp38.1 exerts a vMIA-like function, its inhibitory effect was not robust, suggesting the presence of additional inhibitory molecule(s), such as a BAK-specific inhibitor.
Antisense oligonucleotide therapy for SCN2A gain-of-function epilepsy
Authors: Li Melody , Jancovski Nikola , Jafar-Nejad Paymaan , Burbano Lisseth Estefania , Rollo Ben , Richards Kay , Drew Lisa , Sedo Alicia , Pachernegg Svenja , Soriano Armand , Jia Linghan , Blackburn Todd , Roberts Blaine , Nemiroff Alex , Dalby Kelley , Maljevic Snezana , Reid Christopher , Rigo Frank , Petrou Steven
Published: September 2020

The clinical spectrum associated with SCN2Ade novomutations (DNMs) continues to expand and includes autism spectrum disorder with or without seizures, in addition to early and late seizure onset developmental and epileptic encephalopathies (DEEs). Recent biophysical studies on SCN2A variants suggest that the majority of early seizure onset DEE DNMs cause gain of function. Gain of function in SCN2A, the principal sodium channel of excitatory pyramidal neurons, would result in heightened neuronal activity and is likely to underlie the pathology seen in early seizure onset DEE patients. Supratherapeutic dosing of the non-selective sodium channel blocker phenytoin, is effective in controlling seizures in these patients but does not impact neurodevelopment, raising the idea that more profound and specific reduction in SCN2A function could significantly improve clinical outcome. To test the potential therapeutic benefit of reducing SCN2A in early seizure onset DEE we centrally administered an antisense oligonucleotide (ASO) targeting mouse Scn2a (Scn2a ASO) to a mouse model of human SCN2A early seizure onset DEE. Mice were genetically engineered to harbour the human equivalent SCN2A p.R1882Q mutation (Q/+), one of the most recurrent mutations in early seizure onset DEE. Q/+ mice presented with spontaneous seizures at postnatal day (P) 1 and did not survive beyond P30. Intracerebroventricular Scn2a ASO administration into Q/+ mice between P1-2 (that reduced Scn2a mRNA levels by 50%) significantly extended lifespan and markedly reduced spontaneous seizures occurrence. Across a range of cognitive and motor behavioural tests, Scn2a ASO treated Q/+ mice were largely indistinguishable from wildtype (+/+) mice. Further improvements in survival and behaviour were seen by adjustment of dosing regimens during development. Scn2a ASO efficacy was also evident at the cellular level. Whole cell patch clamp recording showed that Scn2a ASO administration reversed changes in neuronal excitability in layer 2/3 pyramidal neurons of Q/+ mice to levels seen in +/+ mice. Safety was assessed in +/+ mice and showed a developmental stage dependent tolerability and a favourable therapeutic index. This study suggests that a human SCN2A gapmer ASO could profoundly and safely impact early seizure onset DEE patients and heralds a new era of precision therapy in neurodevelopmental disorders.
c-Myb expression is critical to maintain proliferation and glucose metabolism of large pre-B cells
Authors: Daamen Andrea R. , Crittenden Rowena B. , Bender Timothy P.
Published: September 2020

The c-Myb transcription factor is required for the differentiation of CD19+B-lineage cells and plays significant roles from the specification of the B cell lineage to the survival of pro-B cells. c-Myb coordinates the survival of pro-B cells with the expression of genes required for transition to the large pre-B cell stage of differentiation. However, it is not known if c-Myb is important for the proliferative expansion or subsequent differentiation into small pre-B cells. Here we demonstrate that c-Myb expression is important for large pre-B cell survival, proliferation, and differentiation into small pre-B cells. Utilizing genome-wide analysis, we found that c-Myb was important for maintaining glucose uptake and utilization and exogenous expression of Glut1 and Hk1 rescued large pre-B cell recovery and survival. Furthermore, we found that c-Myb is important for repression of Ikaros and Aiolos and our c-Myb-dependent gene signature was enriched in an Ikaros footprint of genes that drive cell cycle exit and the large to small pre-B cell transition. However, upon loss of c-Myb expression, inhibition of Ikaros activity was able to restore certain Ikaros-mediated gene expression changes but was insufficient to rescue recovery of large pre-B cell numbers. We found that c-Myb regulates glucose utilization and glucose-dependent survival through Hk1 in an Ikaros-independent manner. Thus, c-Myb regulation of glucose metabolism is critical to maintain large pre-B cell survival while repression of the Ikaros-mediated gene expression program is critical to prevent premature cell cycle exit and premature differentiation into small pre-B cells.
Nanoparticle-mediated microRNA-145 Delivery for Vascular Smooth Muscle Cell Phenotype Modulation and Atherosclerosis Treatment
Authors: Chin Deborah D. , Poon Christopher , Wang Jonathan , Joo Johan , Ong Victor , Jiang Zhangjingyi , Cheng Kayley , Plotkin Anastasia , Magee Gregory A. , Chung Eun Ji
Published: September 2020

Vascular smooth muscle cells (VSMCs) change from contractile to the synthetic phenotype during atherogenesis and 30-70% of cells that make up plaques have been elucidated to be of VSMC origin. MicroRNA-145 (miR-145) is responsible for regulating VSMC phenotypic switching, and low miR-145 levels in circulation have been linked with atherosclerosis. Hence, we developed nanoparticles for targeted delivery of miR-145 by synthesizing micelles co-assembled with miR-145 and the CCR2-binding peptides for plaque targeting. The miR cargo was protected in micelles from premature endosomal degradation and rescued contractile markers in synthetic VSMCs and SMCs isolated from patient arteriesin vitro. In ApoE-/- mid-stage atherosclerotic mice, miR-145 micelles halted plaque growth and maintained contractile phenotypes similar to baseline levels. In early-stage atherosclerosis, a single dose of miR-145 micelles prevented lesion growth by 49%. We present the potential of miR-145 micelles as a therapeutic that can be applied longitudinally and intervene throughout atherosclerosis pathogenesis.
R-spondins are BMP receptor antagonists in early embryonic development
Authors: Lee Hyeyoon , Seidl Carina , Sun Rui , Glinka Andrei , Niehrs Christof
Published: September 2020

BMP signalling plays key roles in development, stem cells, adult tissue homeostasis, and disease. How BMP receptors are extracellularly modulated and in which physiological context, is therefore of prime importance. R-spondins (RSPOs) are a small family of secreted proteins that co-activate WNT signalling and function as potent stem cell effectors and oncogenes. Evidence is mounting that RSPOs act WNT-independently but how and in which physiological processes remains enigmatic. Here we show that RSPO2 and RSPO3 also act as BMP antagonists. RSPO2 is a high affinity ligand for the type I BMP receptor BMPR1A/ALK3, and it engages ZNRF3 to trigger internalization and degradation of BMPR1A. In earlyXenopusembryos, Rspo2 is a negative feedback inhibitor in the BMP4 synexpression group and regulates dorsoventral axis formation. We conclude that R-Spondins are bifunctional ligands, which activate WNT- and inhibit BMP signalling via ZNRF3, with implications for development and cancer.
Carry on caring: infected females maintain their level of parental care despite suffering high mortality
Authors: Ratz Tom , Monteith Katy M. , Vale Pedro F. , Smiseth Per T.
Published: September 2020

Parental care is a key component of an organism’s reproductive strategy that is thought to trade-off with allocation towards immunity. Yet it is unclear how caring parents respond to pathogens: do infected parents reduce their amount of care as a sickness behaviour or simply from being ill, or do they prioritise their offspring by maintaining high levels of care? Here we explored the consequences of infection by the pathogenSerratia marcescenson mortality, time spent providing care, reproductive output, and expression of immune genes of female parents in the burying beetleNicrophorus vespilloides. We compared untreated control females with infected females that were inoculated with live bacteria, immune-challenged females that were inoculated with heat-killed bacteria, and injured females that were injected with buffer. We found that infected and immune-challenged females mounted an immune response and that infected females suffered increased mortality. Nevertheless, infected and immune-challenged females maintained their normal level of care and reproductive output. There was thus no evidence that infection led to either a decrease or an increase in parental care or reproductive output. Our results show that parental care, which is generally highly flexible, can remain remarkably robust and consistent despite the elevated mortality caused by infection by pathogens. Overall, these findings suggest that infected females maintain a high level of parental care; a strategy that may ensure that offspring receive the necessary amount of care but that might be detrimental to the parents’ own survival or that may even facilitate disease transmission to offspring.
Visual perceptual learning generalizes to untrained effectors
Authors: Awada Asmara , Bakhtiari Shahab , Pack Christopher C.
Published: September 2020

Visual perceptual learning (VPL) is an improvement in visual function following training. Although the practical utility of VPL was once thought to be limited by its specificity to the precise stimuli used during training, more recent work has shown that such specificity can be overcome with appropriate training protocols. In contrast, relatively little is known about the extent to which VPL exhibits motor specificity. Indeed, previous studies have shown that training paradigms that require one type of response (e.g., a button press) do not necessarily transfer to those that require a different response (e.g., a mouse movement). In this work, we have examined the effector specificity of VPL by training observers on tasks that maintain the same visual stimuli and task structure, but that require different effectors to indicate the response. We find that, in these conditions, VPL transfers fully between manual and oculomotor responses. These results are consistent with the idea that VPL entails the learning of a decision rule that can generalize across effectors.
Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development
Authors: Samocha Alexandr , Doh Hanna M. , Sitarama Vaishnavi , Nguyen Quy H. , Gbenedio Oghenekevwe , Rudolf Joshua D. , Eckalbar Walter L. , Barczak Andrea J. , Miao Yi , Garcia K. Christopher , Lawson Devon , Werb Zena , Kessenbrock Kai , Depeille Philippe , Roose Jeroen P.
Published: September 2020

During puberty, robust morphogenesis occurs in the mammary gland; stem- and progenitor-cells develop into mature basal- and luminal-cells to form the ductal tree. The receptor signals that govern this process in mammary epithelial cells (MECs) are incompletely understood. The EGFR has been implicated and here we focused on EGFR’s downstream pathway component Rasgrp1. We find that Rasgrp1 dampens EGF-triggered signals in MECs. Biochemically andin vitro,Rasgrp1perturbation results in increased EGFR-Ras-PI3K-AKT and mTORC1-S6 kinase signals, increased EGF-induced proliferation, and aberrant branching-capacity in 3D cultures. However,in vivo, Rasgrp1perturbation results in delayed ductal tree maturation with shortened branches and reduced cellularity.Rasgrp1-deficient MEC organoids revealed lower frequencies of basal cells, the compartment that incorporates stem cells. Molecularly, EGF effectively counteracts Wnt signal-driven stem cell gene signature in organoids. Collectively, these studies demonstrate the need for fine-tuning of EGFR signals to properly instruct mammary epithelium during puberty.
Recursive splicing is a rare event in the mouse brain
Authors: Moon Sohyun , Zhao Ying-Tao
Published: September 2020

Recursive splicing (RS) is a splicing mechanism to remove long introns from messenger RNA precursors of long genes. Compared to the hundreds of RS events identified in humans and drosophila, only ten RS events have been reported in mice. To further investigate RS in mice, we analyzed RS in the mouse brain, a tissue that is enriched in the expression of long genes. We found that nuclear total RNA sequencing is an efficient approach to investigate RS events. We analyzed 1.15 billion uniquely mapped reads from the nuclear total RNA sequencing data in the mouse cerebral cortex. Unexpectedly, we only identified 20 RS sites, suggesting that RS is a rare event in the mouse brain. We also identified that RS is constitutive between excitatory and inhibitory neurons and between sexes in the mouse cerebral cortex. In addition, we found that the primary sequence context is associated with RS splicing intermediates and distinguishes RS AGGT site from non-RS AGGT sites, indicating the importance of the primary sequence context in RS sites. Moreover, we discovered that cryptic exons may use an RS-like mechanism for splicing. Overall, our findings provide novel insights into RS in long genes.
TTAPE-Me dye is not selective to cardiolipin and responds to main anionic phospholipids unspecifically
Authors: Pyrshev Kyrylo , Yesylevskyy Semen , Bogdanov Mikhail
Published: September 2020

Identification, visualization and quantitation of cardiolipin (CL) in biological membranes is of great interest due to important structural and physiological roles of this lipid. Selective fluorescent detection of CL using non-covalently bound fluorophore TTAPE-Me (1,1,2,2-tetrakis[4-(2-trimethylammonioethoxy)-phenylethene) has been recently proposed. However, this dye was only tested on wild-type mitochondria or liposomes containing neglegible amounts of other anionic lipids, such as PG and PS. No clear preference of TTAPE-Me for binding to CL compared to PG and PS was found in our experiments. The shapes of the emission spectra for these anionic phospholipids were also found to be indistinguishable. Our experiments and complementary molecular dynamics simulations suggest that fluorescence intensity of TTAPE-Me is regulated by dynamic equilibrium between emitting dye, bound to anionic lipids by means of unspecific electrostatic attraction, and non-emitting dye aggregates in aqueous solution. Therefore, TTAPE-Me is not suitable for detection, visualization and localization of CL in the presence of PS and PG present in physiological amounts in the membranes of eukaryotic and prokaryotic cells, respectively.
Estimating the time since admixture from phased and unphased molecular data
Authors: Janzen Thijs , Pina Verónica Miró
Published: September 2020

After admixture, recombination breaks down genomic blocks of contiguous ancestry. The breakdown of these blocks forms a new ‘molecular clock’, that ticks at a much faster rate than the mutation clock, enabling accurate dating of admixture events in the recent past. However, existing theory on the break down of these blocks, or the accumulation of delineations between blocks, so called ‘junctions’, has mostly been limited to using regularly spaced markers on phased data. Here, we present an extension to the theory of junctions using the Ancestral Recombination Graph that describes the expected number of junctions for any distribution of markers along the genome. Furthermore, we provide a new framework to infer the time since admixture using unphased data. We demonstrate both the phased and unphased methods on simulated data and show that our new extensions performs better than previous methods, especially for smaller population sizes and for more ancient admixture times. Lastly, we demonstrate the applicability of our method on an empirical dataset of labcrosses of yeast (Saccharomyces cerevisae) and on two case studies of hybridization in swordtail fish andPopulustrees.
Crystal structure of bis{μ-2-[bis(2-hydroxyethyl)amino]ethanolato}bis(μ-3,5-dimethylpyrazolato)tricopper(II) dibromide sesquihydrate
Authors: Vynohradov Oleksandr S. , Pavlenko Vadim A. , Naumova Dina D. , Partsevska Sofiia V. , Shova Sergiu , Safarmamadov Safarmamad M.
Published: September 2020

In the title bicyclic trinuclear pyrazolate aminoalcohol complex, [Cu3(C5H7N2)2(C6H14NO3)2]Br2·1.5H2O, the central Cu atom lies on a center of symmetry and is involved in the formation of two five-membered rings. It has a coordination number of 4, is in a distorted tetrahedral environment and is connected by the bridging oxygen atoms of the deprotonated OH groups of different aminoalcohol groups, and by the N atoms of deprotonated dimethylpyrazole ligands. The peripheral Cu atom is in a trigonal–bipyramidal coordination environment formed by the nitrogen atom of the deprotonated bridging dimethylpyrazole unit, the bridging oxygen atom of the deprotonated OH group, two oxygen atoms of the protonated hydroxy groups and the nitrogen atom of triethanolamine. One of the C atoms and the Br− anion were found to be disordered over two positions with occupancy factors of 0.808 (9):0.192 (9) and 0.922 (3):0.078 (3), respectively.
Diaquabis(4-ferrocenyl-1,1,1-trifluoro-4-oxobutan-2-olato)cobalt(II)
Authors: Wang Shujing , Han Heguo , Han Yuyang
Published: September 2020

In the title compound, [CoFe2(C5H5)2(C9H5F3O2)2(H2O)2], the central Co atom has an octahedral coordination geometry defined by two chelating trifluoromethyl-β-diketone ferrocene ligands and two aqua ligands, with the latter in a cis disposition. The Cp rings in both ferrocene groupings are close to eclipsed. In the crystal, O—H...O hydrogen bonds link the molecules into [100] chains.
Antioxidant, hypoglycemic and anti-hypertensive properties of extracts derived from peel, fruit and kernel of Salak
Authors: Tan Seok Shin , Tan Seok Tyug , Tan Chin Xuan
Published: September 2020

Purpose

Salak (Salacca zalacca) is an underutilised fruit. The bioactivities of this fruit have rarely been studied scientifically. Thus, the present study aimed to determine the antioxidant activity of extracts derived from the peel, fruit and kernel of the Salak fruit, as well as the hypoglycemic and anti-hypertensive properties of Salak peel extracts.

Design/methodology/approach

The peel, fruit and kernel of the Salak were extracted using distilled water, methanol and ethanol. Antioxidant activities, angiotensin-converting enzyme (ACE) and alpha-amylase inhibition properties of the extracts were estimated via in vitro standard methods. Besides, the total phenolic content (TPC) and total flavonoid content (TFC) of the extracts were also determined in the present study. The antioxidant activities of different parts of Salak extracts were determined by ferric-reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) methods. Percent of radical scavenging properties were calculated via DPPH assay. The hypoglycemic and anti-hypertensive properties of Salak peel were evaluated using alpha-amylase inhibition and ACE assays, respectively.

Findings

Fruit extracts of Salak in methanol were found to exhibit the highest TPC (10.27 ± 0.12 mg GAE/g), TFC (11.04 ± 0.89 mg CE/g) and antioxidant properties amongst all samples whereby the TPC and TFC were strongly correlated with antioxidant activities. On the other hand, distilled water extracted Salak kernel showed to have the lowest TPC (0.53 ± 0.05 mg GAE/g), TFC (0.37 ± 0.01 mg CE/g) and antioxidant properties amongst all the Salak extracts. Peel extracts exhibit comparable antioxidant activities with fruit extracts in the current findings. In addition, peel extracts indicated some extend of ACE and alpha-amylase inhibition activities regardless of the solvents used. Methanol and ethanol peel extracts indicated no significant difference (p < 0.05) ACE (98%) and alpha-amylase (90%) inhibition activities. However, distilled water extracted Salak peel showed significantly lower ACE and alpha-amylase inhibition in comparison to methanol and ethanol peel extracts.

Originality/value

The present findings suggested that the fruit of Salak exhibits the highest antioxidant properties, followed by the peel and lastly, the kernel, which shows the lowest antioxidant properties amongst all the samples. The results also indicated that the peel extracts have ACE and alpha-amylase inhibition activities.
Potential consequences of COVID-19 for sustainable meat consumption: the role of food safety concerns and responsibility attributions
Authors: Yang Xisi
Published: September 2020

Purpose

While coping with severe damages of the ongoing coronavirus outbreak worldwide, this study enlightens the potential effects of the pandemic on young adults' willingness to avoid game meat consumption as well as to purchase animal welfare products.

Design/methodology/approach

In a structural equation model (N = 234), food safety concerns and perceived responsibility for a future change of individuals, marketers and the government as predictors are related to behavioral intentions. Further, two antecedents of food safety concern including risk perception and anxiety related to coronavirus disease 2019 (COVID-19) are tested.

Findings

Using a Chinese sample, results indicated that food safety concern – triggered by risk perception and anxiety – negatively affected willingness to buy animal welfare products. Perceived responsibility of marketers' change positively relates to people's willingness to avoid game meat and to buy animal welfare products, while the latter is also positively related to perceived governmental responsibility.

Practical implications

Consumers demand marketers to improve safety and hygiene standards as it is a necessary condition for adopting sustainable consumption behaviors. Animal welfare products have the potential to pronounce the demanded level of product safety, while the game meat market needs to be prepared for necessary adaptations for coping with the adverse effects of COVID-19.

Originality/value

This article adds knowledge to the behavioral consequences of a viral hazard in the context of sustainable food choices while relating those to attribution theories and food safety concerns.