bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale movement of eIF3 domains during translation initiation modulate start codon selection
Authors: Llácer Jose L , Hussain Tanweer , Dong Jinsheng , Villamayor Laura , Gordiyenko Yuliya , Hinnebusch Alan G
Published: September 2021

The eukaryotic initiation factor 3 (eIF3) complex is involved in every step of translation initiation, but there is limited understanding of its molecular functions. Here, we present a single particle electron cryomicroscopy (cryo-EM) reconstruction of yeast 48S ribosomal preinitiation complex (PIC) in an open conformation conducive to scanning, with core subunit eIF3b bound on the 40S interface near the decoding center in contact with the ternary complex eIF2·GTP·initiator tRNA. eIF3b is relocated together with eIF3i from their solvent interface locations observed in other PIC structures, with eIF3i lacking 40S contacts. Re-processing of micrographs of our previous 48S PIC in a closed state also suggests relocation of the entire eIF3b-3i-3g-3a-Cter module during the course of initiation. Genetic analysis indicates that high fidelity initiation depends on eIF3b interactions at the 40S subunit interface that promote the closed PIC conformation, or facilitate the relocation of eIF3b/eIF3i to the solvent interface, on start codon selection.
Vaptans or voluntary increased hydration to protect the kidney: how do they compare?
Authors: Bankir Lise , Guerrot Dominique , Bichet Daniel G
Published: September 2021

The adverse effects of vasopressin (AVP) in diverse forms of chronic kidney disease have been well described. They depend on the antidiuretic action of AVP mediated by V2 receptors (V2R). Tolvaptan, a selective V2R antagonist, is now largely used for the treatment of patients with autosomal dominant polycystic kidney disease. Another way to reduce the adverse effects of AVP is to reduce endogenous AVP secretion by a voluntary increase in fluid intake. These two approaches differ in several ways, including the level of thirst and AVP. With voluntary increased drinking, plasma osmolality will decline and so will AVP secretion. Thus, not only will V2R-mediated effects be reduced, but also those mediated by V1a and V1b receptors (V1aR and V1bR). In contrast, selective V2R antagonism will induce a loss of fluid that will stimulate AVP secretion and thus increase AVP's influence on V1a and V1b receptors. V1aR is expressed in the luminal side of the collecting duct (CD) and in inner medullary interstitial cells, and their activation induces the production of prostaglandins, mostly prostaglandin E2 (PGE2). Intrarenal PGE2 has been shown to reduce sodium and water reabsorption in the CD and increase blood flow in the renal medulla, both effects contributing to increase sodium and water excretion and reduce urine-concentrating activity. Conversely, non-steroidal anti-inflammatory drugs have been shown to induce significant water and sodium retention and potentiate the antidiuretic effects of AVP. Thus, during V2R antagonism, V1aR-mediated actions may be responsible for part of the diuresis observed with this drug. These V1aR-dependent effects do not take place with a voluntary increase in fluid intake. In summary, while both strategies may have beneficial effects, the information reviewed here leads us to assume that pharmacological V2R antagonism, with resulting stimulation of V1aR and increased PGE2 production, may provide greater benefit than voluntary high water intake. The influence of tolvaptan on the PGE2 excretion rate and the possibility to use somewhat lower tolvaptan doses than presently prescribed remain to be evaluated.
Improving Neurosurgery Resident Microdissection Through Placental Simulation
Authors: Alcalá Nicolas E , Pajer Hengameh B , Piazza Martin , Goodnight William , Yap Edward , Sasaki-Adams Deanna , Hobbs Gene W , Quinsey Carolyn S
Published: September 2021

Prior work has shown that the human placenta is an available and realistic model for microdissection simulation. We sought to find a measurable improvement in the technical skills of neurosurgical residents with deliberate practice of microdissection tasks using a placental model. Postgraduate year (PGY) 1 to 3 neurosurgery residents were consented. A 1-min video of each participant's baseline skills skeletonizing placental vessels was recorded. Participants underwent 10 practice sessions with intermittent informal feedback for 30-60 min over 18 mo. Another 1-min video was recorded following the 10th dissection. The videos were blinded and assessed by 3 board eligible or certified microsurgical neurosurgeons using a modified Objective Structured Assessment of Aneurysm Clipping Skills. Performance was compared via t-testing among four domains: instrument handling, time flow and forward planning, quality of dissection, and respect for tissue. Microdissection,  instrument handling, and quality of dissection were significantly improved after deliberate practice with the placental simulator (P < .05). Improvement was seen in time flow and forward planning and respect for tissue; however, this failed to be significant. Subjectively, residents expressed enjoyment performing the exercise. They also expressed a desire for demonstrations or videos to watch before practice sessions. The placental simulation model provides microsurgical skill development with minimal deliberate practice sessions. Practice exercises are favorably regarded and interest in continuing them is strong by residents. Residents expressed a desire to make the dissection more deliberate with demonstration, breakdown of steps, and mimicry, which could improve the effectiveness and enjoyment of the skills session.
Tobacco-Related Disparities Viewed Through the Lens of Intersectionality
Authors: Sheffer Christine E , Williams Jill M , Erwin Deborah O , Smith Phillip H , Carl Ellen , Ostroff Jamie S
Published: September 2021

Despite remarkable progress, tobacco control efforts are not equitably distributed, and tobacco-related disparities continue to contribute to significant health disparities. Our premise in this commentary is that Intersectionality can serve as a productive analytical framework for examining tobacco-related disparities across and within multiple marginalized populations. Intersectionality is a theoretical framework for understanding the multiple interlocking societal systems that bestow privilege and oppression and is increasingly being to the study of health inequities. We present a model and describe how tobacco-related disparities can be understood via critical elements of Intersectionality. We conclude that the application of Intersectionality to understanding tobacco-related disparities has potential to stimulate meaningful discussion and lead to new and innovative multilevel and cross-cutting interventions to eliminate tobacco-related disparities and foster culturally safe environment in which all people can thrive.

Implications

This commentary describes how Intersectionality can serve as a productive analytic framework for examining the development and maintenance of tobacco-related disparities across and within many marginalized groups.
We Should Not Use Randomization Procedures to Allocate Scarce Life-Saving Resources
Authors: Fumagalli Roberto
Published: September 2021

In the recent literature across philosophy, medicine and public health policy, many influential arguments have been put forward to support the use of randomization procedures (RAND) to allocate scarce life-saving resources (SLSR). In this paper, I provide a systematic categorization and a critical evaluation of these arguments. I shall argue that those arguments justify using RAND to allocate SLSR in fewer cases than their proponents maintain and that the relevant decision-makers should typically allocate SLSR directly to the individuals with the strongest claims to these resources rather than use RAND to allocate such resources.
Benchmarking in Academic Physical Therapy: A Multicenter Trial Using the PT-GQ Survey
Authors: Shields Richard K ,   The Benchmarking Research Advances Value in Education (BRAVE) Group, Ambler Steven B , Audette Jennifer , Austin Gary P , Berg-Poppe Patti , Bowden Mark G , Buford John A , Chevan Julia , Christensen Nicole , Krasinski Debra Clayton , Costello Ellen , Decker Ann Marie , Dupre Anne-Marie , Ellis Terry D , Frank Lynn , Fulk George D , Gagnon Kendra , Galen Sujay Saphire , Healey William E , Irrgang James J , Kirk-Sanchez Neva , Mahoney Edward C , Maňago Marc M , Michael McKeough D , Merians Alma S , Miller Amy H , Nesbit Kathryn C , North Sara E , Pabian Patrick S , Peck Kirk , Silkwood-Sherer Debbie , Talley Susan Ann , van Duijn Arie J , Scott Ward R , Dudley-Javoroski Shauna
Published: September 2021

Objective

Academic physical therapy has no universal metrics by which educational programs can measure outcomes, limiting their ability to benchmark to their own historical performance, to peer institutions, or to other health care professions. The PT-Graduation Questionnaire (GQ) survey, adapted from the Association of American Medical Colleges’ GQ, addresses this gap by offering both inter-professional insight and fine-scale assessment of physical therapist education. This study reports the first wave of findings from an ongoing multi-site trial of the PT-GQ among diverse academic physical therapy programs, including (1) benchmarks for academic physical therapy, and (2) a comparison of the physical therapist student experience to medical education benchmarks.

Methods

Thirty-four doctor of physical therapy (DPT) programs (13.2% nationwide sample) administered the online survey to DPT graduates during the 2019 to 2020 academic year. PT-GQ and Association of American Medical Colleges data were contrasted via Welch’s unequal-variance t test and Hedges g (effect size).

Results

A total of 1025 respondents participated in the study (response rate: 63.9%). The average survey duration was 31.8 minutes. Overall educational satisfaction was comparable with medicine, and respondents identified areas of curricular strength (eg, anatomy) and weakness (eg, pharmacology). DPT respondents provided higher ratings of faculty professionalism than medicine, lower rates of student mistreatment, and a lesser impact of within-program diversity on their training. One-third of respondents were less than “satisfied” with student mental health services. DPT respondents reported significantly higher exhaustion but lower disengagement than medical students, along with lower tolerance for ambiguity. Of DPT respondents who reported educational debt, one-third reported debt exceeding $150,000, the threshold above which the DPT degree loses economic power.

Conclusions

These academic benchmarks, using the PT-GQ, provided insight into physical therapist education and identified differences between physical therapist and medical student perceptions.

Impact

This ongoing trial will establish a comprehensive set of benchmarks to better understand academic physical therapy outcomes.
Significance of single β-mannanase supplementation on performance and energy utilization in broiler chickens, laying hens, turkeys, sows, and nursery-finish pigs: a meta-analysis and systematic review
Authors: Kiarie Elijah G , Steelman Samantha , Martinez, Marco , Livingston Kimberly
Published: September 2021

This review will give a brief description of β-mannans, abundance in feedstuffs, utility of supplemental feed β-mannanase, and subsequent animal responses. Soybean products and co-products of processing palm, coconut, and guar seeds are the major sources of β-mannans in poultry and livestock feed. β-Mannans are linear polymers of mannose residues linked by β-1,4 glycosidic bonds and their ingestion elicit undesirable and metabolically costly responses. Web of Science was searched to retrieve published studies for meta-analyses of the impact of supplemental β-mannanase on performance and digestibility in pigs and poultry. The mean difference (MD) between β-mannanase and control on average daily gain (g/d) was +0.23 (P = 0.013; 95% CI of 0.05; 0.41), +10.8 g/d (P = 0.0005; 95% CI of 6.6; 15.0 g/d), and +20.68 (P < 0.000; 95% CI of 17.15; 24.20 g/d) for broiler chickens, nursery pigs, and grow-finish pigs, respectively. The MD on β-mannanase improvement on feed conversion (FCR) was −0.02 (P < 0.0001) with 95% CI (−0.03; −0.02) suggesting a 2-to-3-point FCR improvement in broiler chickens. β-Mannanase improvement on gain to feed (G:F) was +13.8 g/kg (P = 0.027; 2.1; 25.4 g/kg) and +8.77 g/kg (6.32; 11.23 g/kg) in nursery and grow-finish pigs, respectively. β-Mannanase improved apparent metabolizable energy by 47 kcal/kg (P = 0.0004) with 95% CI (28.8; 65.7 kcal/kg) in broiler chickens. The improvement of gross energy digestibility in pigs was 1.08% unit with 95% CI (0.90; 1.26) translating to the release of between 30.6 and 42.8 kcal/kg of digestible energy. Although data were limited, β-mannanase improved egg production in laying hens linked to improved energy metabolism in laying hens linked to improved energy metabolism but had no impact on egg quality. Turkeys may be more adversely affected by β-mannans because of the high protein/amino acids requirements necessitating higher dietary inclusion of soybean meal. However, growth performance and feed efficiency responses of turkeys fed diets supplemented with β-mannanase were variable. In summary, β-mannanase supplementation improved performance linked to energy and nutrient utilization. However, the magnitude of response was variable within and between species indicating further application refinement is warranted to achieve consistent efficacy, and improved understanding of the functional contribution of β-mannans hydrolysis products.
Essential Versus Nonessential
Authors: Shive Nadia , Doorenbos Ardith Z. , Schmiege Sarah J. , Coats Heather
Published: September 2021

The COVID-19 pandemic has created disruptions and ethical tensions in palliative care research; however, ethical principles must continue to be applied for evaluating the safety of conducting research with seriously ill patient participants and nurse participants in an acute care setting. This randomized controlled trial is conducted in the acute care hospital and tests the effects of a narrative intervention versus usual care on the primary outcome of patients' perception of quality of communication with their nurses and the secondary outcome of biopsychosocial well-being. In accordance with local and institutional COVID-19 guidance, research activities were temporarily suspended in March 2020, and when allowed to resume, some aspects of the protocol were adapted to maximize safety for all stakeholders: patients/families, nurses, and the research team. This article (a) considers case perspectives of all stakeholders involved in a randomized controlled trial conducted in the acute care hospital setting during the COVID-19 pandemic, (b) describes the ethical dilemma and ethical principles in the context of the case, (c) discusses lessons learned while resuming clinical research activities, and (d) provides an ethical framework for the decision-making processes around vulnerability and safety in conducting research during a pandemic with persons living with serious illness.
A biophysical approach to assess weather impacts on honey bee colony winter mortality
Authors: Becsi Benedikt , Formayer Herbert , Brodschneider Robert
Published: September 2021

The western honey bee (
Apis mellifera
) is one of the most important insects kept by humans, but high colony losses are reported around the world. While the effects of general climatic conditions on colony winter mortality were already demonstrated, no study has investigated specific weather conditions linked to biophysical processes governing colony vitality. Here, we quantify the comparative relevance of four such processes that co-determine the colonies' fitness for wintering during the annual hive management cycle, using a 10-year dataset of winter colony mortality in Austria that includes 266 378 bee colonies. We formulate four process-based hypotheses for wintering success and operationalize them with weather indicators. The empirical data is used to fit simple and multiple linear regression models on different geographical scales. The results show that approximately 20% of winter mortality variability can be explained by the analysed weather conditions, and that it is most sensitive to the duration of extreme cold spells in mid and late winter. Our approach shows the potential of developing weather indicators based on biophysical processes and discusses the way forward for applying them in climate change studies.
Quota-based debiasing can decrease representation of the most under-represented groups
Authors: Smirnov I. , Lemmerich F. , Strohmaier M.
Published: September 2021

Many important decisions in societies such as school admissions, hiring or elections are based on the selection of top-ranking individuals from a larger pool of candidates. This process is often subject to biases, which typically manifest as an under-representation of certain groups among the selected or accepted individuals. The most common approach to this issue is debiasing, for example, via the introduction of quotas that ensure a proportional representation of groups with respect to a certain, often binary attribute. This, however, has the potential to induce changes in representation with respect to other attributes. For the case of two correlated binary attributes, we show that quota-based debiasing based on a single attribute can worsen the representation of the most under-represented intersectional groups and decrease the overall fairness of selection. Our results demonstrate the importance of including
all
relevant attributes in debiasing procedures and that more efforts need to be put into eliminating the root causes of inequalities as purely numerical solutions such as quota-based debiasing might lead to unintended consequences.
Ecological impacts of water-based recreational activities on freshwater ecosystems: a global meta-analysis
Authors: Schafft Malwina , Wegner Benjamin , Meyer Nora , Wolter Christian , Arlinghaus Robert
Published: September 2021

Human presence at water bodies can have a range of ecological impacts, creating trade-offs between recreation as an ecosystem service and conservation. Conservation policies could be improved by relying on robust knowledge about the relative ecological impacts of water-based recreation. We present the first global synthesis on recreation ecology in aquatic ecosystems, differentiating the ecological impacts of shore use, (shoreline) angling, swimming and boating. Impacts were assessed at three levels of biological organization (individuals, populations and communities) for several taxa. We screened over 13 000 articles and identified 94 suitable studies that met the inclusion criteria, providing 701 effect sizes. Impacts of boating and shore use resulted in consistently negative, significant ecological impacts across all levels of biological organization. The results were less consistent for angling and swimming. The strongest negative effects were observed in invertebrates and plants. Recreational impacts on birds were most pronounced at the individual level, but not significant at the community level. Due to publication bias and knowledge gaps, generalizations of the ecological impacts of aquatic recreation are challenging. Impacts depend less on the form of recreation. Thus, selectively constraining specific types of recreation may have little conservation value, as long as other forms of water-based recreation continue.
Genome-wide analysis provides a deeper understanding of the population structure of the Salmonella enterica serotype Paratyphi B complex in Bangladesh
Authors: Rahman Sadia Isfat Ara , Taylor-Brown Alyce , Khanam Farhana , Khan Ashraful Islam , Horesh Gal , Dyson Zoe A. , Begum Yasmin Ara , Chowdhury Emran Kabir , Qadri Firdausi , Dougan Gordon , Thomson Nicholas R.
Published: September 2021

The

Salmonella enterica

serotype Paratyphi B complex causes a wide range of diseases, from gastroenteritis to paratyphoid fever, depending on the biotypes Java and sensu stricto. The burden of Paratyphi B biotypes in Bangladesh is still unknown, as these are indistinguishable by

Salmonella

serotyping. Here, we conducted the first whole-genome sequencing (WGS) study on 79

Salmonella

isolates serotyped as Paratyphi B that were collected from 10 nationwide enteric disease surveillance sites in Bangladesh. Placing these in a global genetic context revealed that these are biotype Java, and the addition of these genomes expanded the previously described PG4 clade containing Bangladeshi and UK isolates. Importantly, antimicrobial resistance (AMR) genes were scarce amongst Bangladeshi S. Java isolates, somewhat surprisingly given the widespread availability of antibiotics without prescription. This genomic information provides important insights into the significance of S. Paratyphi B biotypes in enteric disease and their implications for public health.
Streptococcus pneumoniae serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from Streptococcus mitis
Authors: Kalizang'oma Akuzike , Chaguza Chrispin , Gori Andrea , Davison Charlotte , Beleza Sandra , Antonio Martin , Beall Bernard , Goldblatt David , Kwambana-Adams Brenda , Bentley Stephen D. , Heyderman Robert S.
Published: September 2021

Streptococcus pneumoniae

is an important global pathogen that causes bacterial pneumonia, sepsis and meningitis. Beta-lactam antibiotics are the first-line treatment for pneumococcal disease, however, their effectiveness is hampered by beta-lactam resistance facilitated by horizontal genetic transfer (HGT) with closely related species. Although interspecies HGT is known to occur among the species of the genus

Streptococcus

, the rates and effects of HGT between

Streptococcus pneumoniae

and its close relatives involving the penicillin binding protein (pbp) genes remain poorly understood. Here we applied the fastGEAR tool to investigate interspecies HGT in pbp genes using a global collection of whole-genome sequences of

Streptococcus mitis

,

Streptococcus oralis

and

S. pneumoniae

. With these data, we established that pneumococcal serotypes 6A, 13, 14, 16F, 19A, 19F, 23F and 35B were the highest-ranking serotypes with acquired pbp fragments.

S. mitis

was a more frequent pneumococcal donor of pbp fragments and a source of higher pbp nucleotide diversity when compared with

S. oralis

. Pneumococci that acquired pbp fragments were associated with a higher minimum inhibitory concentration (MIC) for penicillin compared with pneumococci without acquired fragments. Together these data indicate that

S. mitis

contributes to reduced β-lactam susceptibility among commonly carried pneumococcal serotypes that are associated with long carriage duration and high recombination frequencies. As pneumococcal vaccine programmes mature, placing increasing pressure on the pneumococcal population structure, it will be important to monitor the influence of antimicrobial resistance HGT from commensal streptococci such as

S. mitis

.
PERIPHERAL ARTERIOVENOUS MALFORMATIONS AND THEIR RESPONSE TO TREATMENT MODALITIES: A SINGLE SURGEON’S EXPERIENCE AT TERTIARY CARE HOSPITALS
Authors: Usman Rashid , Hussain Duaa Ajaz , Malik Muhammad Jamil , Anwar Muhammad Waseem , Ali Kishwar
Published: September 2021

Background

Peripheral arteriovenous malformations (AVMs) are congenital defects resulting in abnormal connections between veins and arteries. We investigated a group of patients with peripheral AVMs to determine whether there were any gender differences in disease presentation and the response of AVMs to various modalities of treatment.

Methodology

The patients in this cross-sectional study were divided into two groups based on gender and their demographic data, clinical presentation at the time of diagnosis and response to treatment was assessed. Both surgical and nonsurgical treatment options were used. Nonsurgical options employed in the study included immunotherapy, embolotherapy and ultrasound-guided foam sclerotherapy (UGFS)

Results

Out of 43 patients, 74.4% were females with a male to female ratio of 1:3. The mean age at presentation in males was 27 years and 17 years in females. 60% of the male patients presented with high-flow AVMs while 81% of the female patients presented with low-flow lesions instead. Half of the AVMs in males were on the trunk whereas, in females, 93.9% were on the extremities. UGFS alone was used in 95.3% of patients while 32.5% of patients underwent UGFS followed by surgical excision. One patient was treated with sirolimus. In 4.6% of cases, embolization followed by surgical excision was performed. Recurrence was recorded in 20.9% of cases.

Conclusions

The clinical presentation of AVMs is notably different among the two genders. Sclerotherapy and embolotherapy proved to be effective treatment options. Larger studies, however, are needed to substantiate these claims.
mRNA-1273 vaccine (Moderna): a better option than BNT162b2 (Pfizer) in kidney transplant recipients and dialysis patients?
Authors: Wijtvliet Veerle P. W. M. , Ariën Kevin K. , Abrams Steven , Couttenye Marie M. , Mestrez Fabienne , Mariën Joachim , De Winter Benedicte Y. , Van Damme Pierre , Pipeleers Lissa , Wissing Karl Martin , Abramowicz Daniel , Ledeganck Kristien J.
Published: September 2021

In this study of the humoral immune response after the SARS-CoV-2 mRNA vaccination, low seroconversion rates were noted in both kidney transplant recipients and dialysis patients after first dose administration. While in DP the seroconversion rate levelled up to 92.8% after a second dose of SARS-CoV-2 mRNA vaccination, KTR stayed behind with a seroconversion rate of 62.4%. Futhermore, vaccination with the mRNA-1273 vaccine (Moderna) resulted in both higher seroconversion rates and mean log-transformed antibody titer concentrations compared to BNT162b2 (Pfizer).
Efficacy of SARS-CoV-2 wastewater surveillance for detection of COVID-19 at a residential private college
Authors: Landstrom Michelle , Braun Evan , Larson Ellen , Miller Merrill , Holm Geoffrey H.
Published: September 2021

Many colleges and universities utilized wastewater surveillance testing for SARS-CoV-2 RNA as a tool to help monitor and mitigate the COVID-19 pandemic on campuses across the United States during the 2020-2021 academic year. We sought to assess the efficacy of one such program by analyzing wastewater RNA load data in relation to SARS-CoV-2 cases identified through individual surveillance testing. Almost 80% of the cases on campus were associated with positive wastewater tests, resulting in an overall positive predictive value of ∼79% (Chi square 48.1, Df = 1, p < 0.001). However, half of the positive wastewater samples occurred in the two weeks following the return of a student to the residence hall following isolation, and therefore were not useful in predicting new infections. When these samples were excluded, the positive predictive value of a positive wastewater sample was ∼54%. Overall, we conclude that the continued shedding of viral RNA by patients past the time of potential transmission confounds the identification of new cases using wastewater surveillance, and decreases its effectiveness in managing SARS-CoV-2 infections on a residential college campus.
Prediction of BAP1 mutations in uveal melanoma patients from histology images using weakly supervised deep learning-based whole slide image analysis
Authors: Mehdiratta Garv
Published: September 2021

While cases of uveal melanoma are relatively rare overall, it remains the most common intraocular cancer in adults and has a 10-year fatality rate of approximately 50% in metastatic patients with no effective treatment options. Mutations in BAP1, a tumor suppressor gene, have been previously found to be associated with the onset of metastasis in uveal melanoma patients. In this study, I utilize a weakly supervised deep learning-based pipeline in order to analyze whole slide images (WSIs) of uveal melanoma patients in conjunction with slide-level labels regarding the presence of BAP1 mutations. I demonstrate that there is a strong relationship between BAP1 mutations and physical tumor development in uveal melanoma and that my model is able to predict such relationships with an optimized mean test AUC of 0.86. My findings demonstrate that deep learning models are able to accurately predict patient-specific genotypic characteristics in uveal melanoma. Once integrated into and adapted to existing non-invasive ocular scanner technologies, my model would assist healthcare professionals in understanding the specific genetic profiles of their patients and provide more personalized treatment options in a safe, efficient manner, thus resulting in improved treatment outcomes.
Rapid semi-quantitative point of care diagnostic test for post vaccination antibody monitoring
Authors: Moeller Maria E. , Engsig Frederik N. , Bade Melanie , Fock Jeppe , Pah Pearlyn , Soerensen Anna Louise , Bang Didi , Donolato Marco , Benfield Thomas
Published: September 2021

Introduction

Point-of-care (POC)quantification of the antibody responses against the SARS-CoV-2 Spike protein can enable decentralized monitoring of immune responses after infection or vaccination. We evaluated a novel POC microfluidic cartridge-based device (ViroTrack Sero COVID-19 Total Ab) for quantitative detection of total antibodies against SARS-CoV-2 Spike trimeric spike protein and compared to standard laboratory chemiluminescence (CLIA) based tests.

Methods

Capillary- and venous blood samples were collected from 101 individuals employed at Copenhagen University Hospital, Denmark. Antibody responses were measured on capillary-, venous whole blood, plasma and diluted plasma samples directly on the POC instrument. POC results were available within seven minutes on the microfluidic cartridge reader. Plasma samples were analysed on the DiaSorin LIAISON® XL CLIA Analyzer using LIAISON® SARS-CoV-2 IgM, LIAISON® SARS-CoV-2 S1/S2 IgG and LIAISON® SARS-CoV-2 TrimericS IgG assays. The data from the CLIA platform was used as a reference.

Results

The Spearman rank’s correlation coefficient between ViroTrack Sero COVID-19 Total Ab and LIAISON® SARS-CoV-2 S1/S2 IgG and LIAISON® SARS-CoV-2 TrimericS IgG assays is found to be 0.86 and 0.90 respectively. ViroTrack Sero COVID-19 Total Ab furthermore showed high correlation (>0.86) among the different sample matrixes. The agreement for determination of samples >200 BAU/mL on POC and CLIA methods is estimated to be around 90%.

Conclusion

ViroTrack Sero Covid Total Ab is a very rapid and simple-to-use POC test with high sensitivity and high correlation of the numerical results expressed in BAU/mL when compared to a commercial CLIA assay.
Educational Attainment Polygenic Scores, Socioeconomic Factors, and Cortical Structure in Children and Adolescents
Authors: Merz Emily C. , Strack Jordan , Hurtado Hailee , Vainik Uku , Thomas Michael , Evans Alan , Khundrakpam Budhachandra
Published: September 2021

Background

Genome-wide polygenic scores for educational attainment (PGS-EA) and socioeconomic factors, which are correlated with each other, have been consistently associated with academic achievement and general cognitive ability in children and adolescents. Yet, the independent associations of PGS-EA and socioeconomic factors with specific underlying factors at the neural and neurocognitive levels are not well understood. The goal of this study was to examine the unique contributions of PGS-EA and parental education to cortical thickness (CT), cortical surface area (SA), and neurocognitive skills in children and adolescents.

Methods

Participants were typically developing children and adolescents (3-21 years of age; 53% male;N= 391). High-resolution, T1-weighted magnetic resonance imaging data were acquired. PGS-EA were computed based on the most recent genome-wide association study of educational attainment. Sustained attention, inhibitory control, working memory, vocabulary, and episodic memory were measured.

Results

PGS-EA and parental education were independently and significantly associated with SA, vocabulary, and attention outcomes but were not associated with CT. Vertex-wise analyses indicated that higher PGS-EA was significantly associated with greater SA in the left medial orbitofrontal gyrus and inferior frontal gyrus after accounting for parental education. Higher parental education was significantly associated with greater SA in the left parahippocampal gyrus after accounting for PGS-EA.

Conclusions

These findings suggest that education-linked genetics may influence SA, particularly in certain frontal regions, leading to variability in academic achievement. Results suggested genetic confounding in associations between parental education and SA in children and adolescents, with these associations remaining significant after controlling for PGS-EA.
Production of photocurrent and hydrogen gas from intact plant leaves
Authors: Shlosberg Yaniv , Meirovich Matan , Yehezkeli Omer , Schuster Gadi , Adir Noam
Published: September 2021

Here, we show that it is possible to harvest photocurrent directly from unprocessed plant tissues from terrestrial or aquatic environments in bio-photoelectrochemical cells (BPECs) and use the current to produce molecular H2. The source of electrons is shown to originate from the Photosystem II water-oxidation reaction and utilizes exported mediating molecules, especially NADPH. The photocurrent production is dependent on the concentration of the photosynthetic complexes, as an increase in total chlorophyll and oxygen evolution rates lead to increased photocurrent rates. The permeability of the outer leaf surface is another important factor in photocurrent harvesting. Different tissues produce photocurrent densities in the range of ∼ 1 – 10 mA / cm2 which is significantly higher than microorganism-based BPECs. The relatively high photocurrent and the simplicity of the plants BPEC may pave the way toward the development of future applicative photosynthetic based energy technologies.
Genomic Surveillance in Japan of AY.29—A New Sub-lineage of SARS-CoV-2 Delta Variant with C5239T and T5514C Mutations
Authors: Abe Takashi , Arita Masanori
Published: September 2021

In the present study, we report a new sub-lineage of the SARS-CoV-2 Delta variant called AY.29, which has C5239T and T5514C mutations. We investigated the monthly trend of AY.29 in Japan within 37,737 Delta variants downloaded on October 2, 2021. Among the total Japanese Delta variants, the AY.29 sub-lineage accounted for 95.1%. In terms of monthly trends, the sequences became predominant in June, and accounted for 95.4%, 97.6% and 90.5% of the reported sequences in July, August and September, respectively. Furthermore, the number of Delta variants imported from abroad during the Tokyo 2020 Olympics and Paralympics (held in August 2021) was extremely low during the fifth wave in Japan. Therefore, the epidemic of the new Delta variant is attributable to a newly occurring mutation in Japan.
The GET pathway serves to activate Atg32-mediated mitophagy by ER targeting of the Ppg1-Far complex
Authors: Onishi Mashun , Okamoto Koji
Published: September 2021

Mitophagy removes defective or superfluous mitochondria via selective autophagy. In yeast, the pro-mitophagic protein Atg32 localizes to the mitochondrial surface and interacts with the scaffold protein Atg11 to promote degradation of mitochondria. Although Atg32-Atg11 interactions are thought to be stabilized by Atg32 phosphorylation, how this posttranslational modification is regulated remains obscure. Here we show that cells lacking the guided entry of tail-anchored proteins (GET) pathway exhibit reduced Atg32 phosphorylation and Atg32-Atg11 interactions, which can be rescued by additional loss of the ER-resident Ppg1-Far complex, a multi-subunit phosphatase negatively acting in mitophagy. In GET-deficient cells, Ppg1-Far is predominantly localized to mitochondria. An artificial ER anchoring of Ppg1-Far in GET-deficient cells significantly ameliorates defects in Atg32-Atg11 interactions and mitophagy. Moreover, disruption of GET and Msp1, an AAA-ATPase that extracts non-mitochondrial proteins localized to the mitochondrial surface, elicits synthetic defects in mitophagy. Collectively, we propose that the GET pathway mediates ER targeting of Ppg1-Far, thereby preventing dysregulated suppression of mitophagy activation.
Non-target impacts of fungicide disturbance on phyllosphere yeasts in different crop species and management systems
Authors: Noel Zachary A. , Longley Reid , Niccolò Benucci Gian Maria , Trail Frances , Chilvers Martin I. , Bonito Gregory
Published: September 2021

Fungicides reduce fungal pathogen populations and are essential to food security. Fungicide disturbance of plant microbiomes has received limited attention. Understanding the impacts of fungicides on crop microbiomes in different cropping systems is vital to minimizing unintended consequences while maintaining their use for plant protection.

We used amplicon sequencing of fungi and prokaryotes in maize and soybean microbiomes before and after foliar fungicide application in leaves and roots from plots under long-term no-till and conventional tillage managements. We examine fungicide disturbance and microbiome resilience across these treatments.

Foliar fungicides directly affected phyllosphere fungal communities, but not root fungal communities or prokaryote communities. Impacts on fungal phyllosphere composition and resiliency were management-dependent and lasted more than thirty days. Fungicides lowered pathogen abundance in maize and soybean and decreased the abundance of Tremellomycetes yeasts, especially the Bulleribacidiaceae, including core microbiome members.

Fungicide application reduced network complexity in the soybean phyllosphere. Bulleribacidiaceae often co-occurred with Sphingomonas and Hymenobacter in control plots, but co-occurrences were altered in fungicide plots. Results indicate that foliar fungicides lower pathogen and non-target fungal abundance and may impact prokaryotes indirectly. No-till management was more resilient following fungicide disturbance and recovery.
Prior Covid-19 and high RBD-IgG levels correlate with protection against VOC-δ SARS-CoV-2 infection in vaccinated nursing home residents
Authors: Blain Hubert , Tuaillon Edouard , Pisoni Amandine , Soriteau Laure , Million Elodie , Léglise Marie-Suzanne , Bussereau Isabelle , Miot Stéphanie , Rolland Yves , Picot Marie-Christine , Bousquet Jean
Published: September 2021

Background

Nursing Home (NH) residents are at high risk of serious illness and death from coronavirus disease 2019 (Covid-19), especially with the SARS-CoV-2 variants of concerns (VOC). It is unknown as to whether a history of Covid-19 prior to the vaccine and post-vaccine RBD-IgG levels are predictors of BNT162b2 vaccine effectiveness against VOC–δ in nursing home residents.

Methods

We analyzed the data from two NHs that faced a VOC-δ outbreak in July-August 2021. These NHs had suffered prior Covid-19 outbreaks in 2020 and 2021. In many of the residents, RBD-IgG levels were measured 6 weeks after the second vaccine dose, i.e. 3 to 5 months before the VOC-δ outbreak onset, and again during the outbreak (SARS-CoV-2 IgG II Quant assay, Abbott Diagnostics). We compared residents with vs without prior Covid-19 for (i) VOC-δ incidence, (ii) the correlation between post-vaccine RBD-IgG levels and VOC-δ incidence, and (iii) the time-related change in RBD-IgG levels.

Results

Among the 140 analyzed residents (58 to 101 years; 94 females, 46 men, mean age: 84.6 yr ± 9.5 yr), one resident among the 44 with prior Covid-19 before vaccination developed a VOC-δ infection during the outbreak (1.3%) vs 55 of the 96 without Covid-19 prior to vaccination (57.3 %)(p<0.0001). The median value for RBD-IgG 6 weeks after the vaccine and during the outbreak was higher in residents with prior Covid-19 (31,553 AU/mL and 22,880 AU/mL) than in those without (1,050 AU/mL and 260 AU/mL)(p<0.0001). In residents without Covid-19 prior to vaccination, post-vaccination RDB-IgG levels did not predict protection against VOC-δ infection.

Conclusions

In contrary to residents with prior SARS-CoV-2 infection, those without a history of Covid-19 before two BNT162b2 doses are not protected against VOC-δ infection and their RBD-Ig-G levels are low 3 to 5 months after vaccination. This suggests that a booster vaccine dose should be considered in this group of residents for a better protection against VOC-δ infection.
Virological and Serological Characterization of SARS-CoV-2 Infections Diagnosed After mRNA BNT162b2 Vaccination
Authors: Colavita Francesca , Meschi Silvia , Maria Gruber Cesare Ernesto , Rueca Martina , Vairo Francesco , Matusali Giulia , Lapa Daniele , Giombini Emanuela , Carli Gabriella De , Spaziante Martina , Messina Francesco , Bonfiglio Giulia , Carletti Fabrizio , Lalle Eleonora , Fabeni Lavinia , Berno Giulia , Puro Vincenzo , Caro Antonino Di , Bartolini Barbara , Ippolito Giuseppe , Capobianchi Maria Rosaria , Castilletti Concetta
Published: September 2021

Coronavirus disease 2019 (COVID-19) vaccines are proving to be very effective in preventing severe illness; however, although rare, post-vaccine infections have been reported. The present study describes 94 infections (47.9% symptomatic, 52.1% asymptomatic), occurred in Lazio Region (Central Italy) in the first trimester 2021, after first or second dose of mRNA BNT162b2 vaccine. Median viral load at diagnosis was independent from number and time of vaccine dose administration, despite the higher proportion of samples with low viral load observed in fully vaccinated individuals. More importantly, infectious virus was cultured from NPS collected from both asymptomatic and symptomatic vaccinated individuals, suggesting that, at least in principle, they can transmit the infection to susceptible people. The majority of the post-vaccine infections here reported, showed pauci/asymptomatic clinical course, confirming the impact of vaccination on COVID-19 disease. Most cases (78%) showed infection in presence of neutralizing antibodies at the time of infection diagnosis, presumably attributable to vaccination, due to the concomitant absence of anti-N IgG in most cases. The proportion of post-vaccine infections attributed either to Alpha and Gamma VOCs was similar to the proportion observed in the contemporary unvaccinated population in Lazio region. In addition, mutational analysis did not suggest enrichment of a defined set of Spike protein substitutions depending on the vaccination status. Characterization of host and virus factors associated with vaccine breakthrough, coupled with intensive and continuous monitoring of involved viral strains, is crucial to adopt informed vaccination strategies.
Locally adapted oak populations along an elevation gradient display different molecular strategies to regulate bud phenology
Authors: Provost Gregoire Le , Lalanne Céline , Lesur Isabelle , Louvet Jean-Marc , Delzon Sylvain , Kremer Antoine , Labadie Karine , Aury Jean-Marc , Silva Corinne Da , Plomion Christophe
Published: September 2021

Research conducted

With the ongoing global warming, there are serious concerns about the persistence of locally adapted populations. Indeed, with the raising of temperature, the phenological cycle of tree species may be strongly affected since higher winter temperatures may have a negative impact on endodormancy release if chilling requirements are not fulfilled during winter and late frost in spring may expose trees if buds flush too early. Thus, Environmental gradients (showing continuous variations of environmental conditions) constitute a design of choice to analyze the effect of winter dormancy in locally adapted population.

Methods

In the present study, we used an elevation gradient in the Pyrenees to explore the gene expression network involved in dormancy regulation in natural populations of sessile oak locally adapted to temperature. Terminal buds were harvested during dormancy induction and release at different elevations. Then, gene expression was quantified using RNAseq and we used a likelihood ratio test to identify genes displaying significant dormancy, elevation or dormancy-by-elevation interaction effects.

Key results

Our results highlight molecular processes in locally adapted populations along this elevation cline, and made it possible to identify key dormancy-by-elevation responsive genes revealing that locally adapted populations have evolved distinct molecular strategies to adapt their bud phenology in response to environmental variation (i.e. temperature).
A novel mechanism for the loss of mRNA activity in lipid nanoparticle delivery systems
Authors: Packer Meredith , Gyawali Dipendra , Yerabolu Ravikiran , Schariter Joseph , White Phil
Published: September 2021

Lipid nanoparticle (LNP)-formulated mRNA vaccines were rapidly developed and deployed in response to the SARS-CoV-2 pandemic. Due to the labile nature of mRNA, identifying impurities that could affect product stability and efficacy is crucial to the long-term use of nucleic-acid based medicines. Herein reversed phase ion pair high performance liquid chromatography (RP-IP HPLC) was used to identify a class of impurity formed through lipid:mRNA reactions; such reactions are typically undetectable by traditional mRNA purity analytical techniques. The identified modifications render the mRNA untranslatable, leading to loss of protein expression. Specifically, an electrophilic impurity derived from the ionizable cationic lipid component is shown to be responsible. Mechanisms implicated in the formation of reactive species include oxidation and subsequent hydrolysis of the tertiary amine. It thus remains critical to ensure robust analytical methods and stringent manufacturing control to ensure mRNA stability and high activity in LNP delivery systems.
Structure of the Shaker Kv channel and mechanism of slow C-type inactivation
Authors: Tan Xiao-Feng , Bae Chanhyung , Stix Robyn , Fernández-Mariño Ana I. , Huffer Kate , Chang Tsg-Hui , Jiang Jiansen , Faraldo-Gómez José D. , Swartz Kenton J.
Published: September 2021

Voltage-activated potassium (Kv) channels open upon membrane depolarization and proceed to spontaneously inactivate. Inactivation controls neuronal firing rates and serves as a form of short-term memory, and is implicated in various human neurological disorders. Here, we use high-resolution cryo-electron microscopy and computer simulations to determine one of the molecular mechanisms underlying this physiologically crucial process. Structures of the activated Shaker Kv channel and of its W434F mutant in lipid bilayers demonstrate that C-type inactivation entails the dilation of the ion selectivity filter, and the repositioning of neighboring residues known to be functionally critical. Microsecond-scale molecular dynamics trajectories confirm these changes inhibit rapid ion permeation through the channel. This long-sought breakthrough establishes how eukaryotic K+ channels self-regulate their functional state through the plasticity of their selectivity filters.

One-Sentence Summary

Structures of the Shaker Kv channel reveal the mechanism of slow C-type inactivation involves dilation of the selectivity filter.