bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland
Authors: Vennekens Annelies , Laporte Emma , Hermans Florian , Cox Benoit , Modave Elodie , Janiszewski Adrian , Nys Charlotte , Kobayashi Hiroto , Malengier-Devlies Bert , Chappell Joel , Matthys Patrick , Garcia Marie-Isabelle , Pasque Vincent , Lambrechts Diether , Vankelecom Hugo
Published: June 2021

Significance

The pituitary is our master endocrine gland. Local damage and aging present important threats. We started to decrypt the ill-defined regulation of the gland’s stem cells, typically dormant but acutely activated upon damage. Single-cell transcriptomics uncovered interleukin-6 as a pituitary stem cell activator upon local damage, corroborated in vivo and in vitro using stem cell–derived organoids. This competence extinguishes at aging, concurrent with a raised inflammatory state in the older gland (inflammaging). However, the aging pituitary’s stem cells retain intrinsic activatability, resurfacing once released from their impeding tissue milieu. Our insights may instigate tactics to refrain the pituitary from aging or rejuvenate the aging gland. The single-cell transcriptomic database provides a powerful resource to decipher pituitary damage and aging.
Localized chondro-ossification underlies joint dysfunction and motor deficits in the
Fkbp10
mouse model of osteogenesis imperfecta
Authors: Lim Joohyun , Lietman Caressa , Grol Matthew W. , Castellon Alexis , Dawson Brian , Adeyeye Mary , Rai Jyoti , Weis MaryAnn , Keene Douglas R. , Schweitzer Ronen , Park Dongsu , Eyre David R. , Krakow Deborah , Lee Brendan H.
Published: June 2021

Significance

Osteogenesis imperfecta (OI), also known as brittle bone disease, commonly features low bone mass and frequent fractures. We and others have previously identified mutations that cause joint deformities in OI patients. However, mechanisms responsible for joint pathologies in OI are poorly understood. Here, we have established a mouse model of OI joint dysfunction that is caused by mutations in
Fkbp10
. Our mouse model recapitulates key features of
FKBP10
OI patients, including reduced collagen cross-linking and joint deformities. In addition, we found that inflammation and altered matrix signaling is associated with joint abnormalities in
Fkbp10
mutant animals. Overall, our work provides a valuable model that can be used to identify novel therapies to treat joint dysfunction in OI and OI-related diseases.
Proteasomal conformation controls unfolding ability
Authors: Cresti Julianna R. , Manfredonia Abramo J. , Bragança Christopher E. , Boscia Joseph A. , Hurley Christina M. , Cundiff Mary D. , Kraut Daniel A.
Published: June 2021

Significance

In eukaryotic cells, the proteasome is responsible for most protein degradation. Because of this central role, the proteasome is of interest in diseases ranging from cancer to neurodegeneration. The proteasome undergoes ATP hydrolysis–driven conformational changes during its catalytic cycle that are important for its activity. In this work, we established a system to use Förster resonance energy transfer to characterize these conformational changes. We show that previous predictions of protein interactions that alter equilibria between resting and active forms of the proteasome are correct, and accessing those active conformations allows the proteasome to better unfold and degrade hard-to-degrade substrates. These results suggest that controlling the proteasome’s conformation might be a regulatory strategy to be exploited in drug design.
A mycorrhiza-associated receptor-like kinase with an ancient origin in the green lineage
Authors: Montero Héctor , Lee Tak , Pucker Boas , Ferreras-Garrucho Gabriel , Oldroyd Giles , Brockington Samuel F. , Miyao Akio , Paszkowski Uta
Published: June 2021

Receptor-like kinases (RLKs) are key cell signaling components. The rice ARBUSCULAR RECEPTOR-LIKE KINASE 1 (OsARK1) regulates the arbuscular mycorrhizal (AM) association postarbuscule development and belongs to an undefined subfamily of RLKs. Our phylogenetic analysis revealed that
ARK1
has an ancient paralogue in spermatophytes,
ARK2
. Single
ark2
and
ark1/ark2
double mutants in rice showed a nonredundant AM symbiotic function for
OsARK2
. Global transcriptomics identified a set of genes coregulated by the two RLKs, suggesting that
OsARK1
and
OsARK2
orchestrate symbiosis in a common pathway. ARK lineage proteins harbor a newly identified SPARK domain in their extracellular regions, which underwent parallel losses in ARK1 and ARK2 in monocots. This protein domain has ancient origins in streptophyte algae and defines additional overlooked groups of putative cell surface receptors.
Quantum non-Gaussianity criteria based on vacuum probabilities of original and attenuated state
Authors: Fiurášek Jaromír , Lachman Lukáš , Filip Radim
Published: June 2021

Quantum non-Gaussian states represent an important class of highly non-classical states whose preparation requires quantum operations or measurements beyond the class of Gaussian operations and statistical mixing. Here we derive criteria for certification of quantum non-Gaussianity based on probability of vacuum in the original quantum state and a state transmitted through a lossy channel with transmittance T. We prove that the criteria hold for arbitrary multimode states, which is important for their applicability in experiments with broadband sources and single-photon detectors. Interestingly, our approach allows to detect quantum non-Gaussianity using only one photodetector instead of complex multiplexed photon detection schemes, at the cost of increased experimental time. We also formulate a quantum non-Gaussianity criterion based on the vacuum probability and mean photon number of the state and we show that this criterion is closely related to the criteria based on pair of vacuum probabilities. We illustrate the performance of the obtained criteria on the example of realistic imperfect single-photon states modeled as a mixture of vacuum and single-photon states with background Poissonian noise.
The FAST Galactic Plane Pulsar Snapshot survey: I. Project design and pulsar discoveries
⋆
Authors: Han J. L. , Wang Chen , Wang P. F. , Wang Tao , Zhou D. J. , Sun Jing-Hai , Yan Yi , Su Wei-Qi , Jing Wei-Cong , Chen Xue , Gao X. Y. , Hou Li-Gang , Xu Jun , Lee K. J. , Wang Na , Jiang Peng , Xu Ren-Xin , Yan Jun , Gan Heng-Qian , Guan Xin , Huang Wen-Jun , Jiang Jin-Chen , Li Hui , Men Yun-Peng , Sun Chun , Wang Bo-Jun , Wang H. G. , Wang Shuang-Qiang , Xie Jin-Tao , Xu Heng , Yao Rui , You Xiao-Peng , Yu D. J. , Yuan Jian-Ping , Yuen Rai , Zhang Chun-Feng , Zhu Yan
Published: June 2021

Discovery of pulsars is one of the main goals for large radio telescopes. The Five-hundred-meter Aperture Spherical radio Telescope (FAST), that incorporates an L-band 19-beam receiver with a system temperature of about 20 K, is the most sensitive radio telescope utilized for discovering pulsars. We designed the snapshot observation mode for a FAST key science project, the Galactic Plane Pulsar Snapshot (GPPS) survey, in which every four nearby pointings can observe a cover of a sky patch of 0.1575 square degrees through beam-switching of the L-band 19-beam receiver. The integration time for each pointing is 300 seconds so that the GPPS observations for a cover can be made in 21 minutes. The goal of the GPPS survey is to discover pulsars within the Galactic latitude of ± 10° from the Galactic plane, and the highest priority is given to the inner Galaxy within ± 5°. Up to now, the GPPS survey has discovered 201 pulsars, including currently the faintest pulsars which cannot be detected by other telescopes, pulsars with extremely high dispersion measures (DMs) which challenge the currently widely used models for the Galactic electron density distribution, pulsars coincident with supernova remnants, 40 millisecond pulsars, 16 binary pulsars, some nulling and mode-changing pulsars and rotating radio transients (RRATs). The follow-up observations for confirmation of new pulsars have polarization-signals recorded for polarization profiles of the pulsars. Re-detection of previously known pulsars in the survey data also leads to significant improvements in parameters for 64 pulsars. The GPPS survey discoveries are published and will be updated at http://zmtt.bao.ac.cn/GPPS/.
Accretion properties of MAXI J1813-095 during its failed outburst in 2018
Authors: Jana Arghajit , Jaisawal Gaurava K. , Naik Sachindra , Kumari Neeraj , Chatterjee Debjit , Chatterjee Kaushik , Bhowmick Riya , Chakrabarti Sandip K. , Chang Hsiang-Kuang , Debnath Dipak
Published: June 2021

We present the results obtained from detailed timing and spectral studies of a black hole candidate MAXI J1813–095 using Swift, NICER, and NuSTAR observations during its 2018 outburst. The timing behavior of the source is mainly studied by examining NICER light curves in the 0.5–10 keV range. We did not find any signature of quasi-periodic oscillations in the power density spectra of the source. We carry out spectral analysis with a combined disk blackbody & power law model, and physical two-component advective flow (TCAF) model. From the combined disk blackbody & power-law model, we extracted thermal and non-thermal fluxes, photon index and inner disk temperature. We also find evidence for weak reflection in the spectra. We have tested the physical TCAF model on a broadband spectrum from NuSTAR and Swift/XRT. The parameters like mass accretion rates, the size of Compton clouds and the shock strength are extracted. Our result affirms that the source remained in the hard state during the entire outburst which indicates a ‘failed’ outburst. We estimate the mass of the black hole as 7.4 ± 1.5 M
⊙ from the spectral study with the TCAF model. We apply the LAOR model for the Fe Kα line emission. From this, the spin parameter of the black hole is ascertained as a* > 0.76$ The inclination angle of the system is estimated to be in the range of 28° – 45° from the reflection model. We find the source distance to be ∼ 6 kpc.
Wastewater treatment and Mycoremediation by P. ostreatus mycelium
Authors: Bhatnagar A , Tamboli E , Mishra A
Published: June 2021

Wastewater from industries contains a considerable amount of chemicals and is characterized by high biological oxygen demand (BOD), heavy metals, intense color and are thus toxic to the environment. White-rot fungi such as Oyster mushrooms are comprised of high biomass and various degradative enzymes that add to another dimension of use, such as mycoremediation. The mushroom was maintained in vitro in mycelial form. Remazol Brilliant Blue R (RBBR), Methyl Red (M.R.), and Malachite Green (M.G.) dyes, which are recalcitrant dyes that are often used for the preparation of many polymeric dyes, and textile dyeing, were used to test the decolorization potential of natural isolates of oyster mushroom. Mycelium was grown in the presence of RBBR, MR, and M.G. at a concentration of 100μM. It was found to decolorize more than 70%, 95%, and 80% of RBBR, MR, and M.G. dye, respectively, within 6 days. Mushroom mycelium was also tested for its lead tolerance and heavy metal biosorption potential. Lead tolerance was studied up to 500mg/L, which shows species′ latent growth with fungal morphology changes. Biosorption ability was observed by the use of Inductively Coupled Plasma spectrometry, which shows lowered concentrations of heavy metals (Pb, Cr, Ni) after 5 days of mycelial growth in the presence of these metals. The isolated strain was also found to have significant decolorizing and degrading potential for synthetic dyes and phenolic compounds in industrial effluents. This study focuses on edible oyster mushrooms′ ability to develop environmentally less aggressive processes in the treatment of industrial effluents.
Relationship between the water storage and cultivated area in the dry season in Lam Pao Operation and Maintenance Project
Authors: Luangcharoenlarp S , Changjan A
Published: June 2021

This research aims to study the relationship between water storage and cultivated area in the dry season. The study was in the Lam Pao operation and maintenance project, Kalasin province. The long term data records from 1987 to 2020, a total of 33 years, including the amount of water storage in the Lam Pao reservoir and the cultivated area in the dry season (December to May) were analyzed using the Multiple Regression Analysis. The results of the study showed that the maximum cultivated area was in 2020. The total area of 300,353 rai comprised of 295,304 rai of dry season rice, 97 rai of field crops, 100 rai of vegetables, 1,496 rai of fish pond and 3,356 rai of shrimp pond. The minimum cultivated area was in 1994. The total area of of 3,419 rai comprised of 209 rai of dry season rice, 2,552 rai of field crops, 488 rai of vegetables. 35 rai of fish ponds and 135 rai of shrimp ponds. It can be concluded that the amount of water storage at the beginning of the dry season is significantly correlated with cultivated area in the dry season.
Compliant Mechanism and Origami usage in Aerospace and Space Application
Authors: Mathew Bilji c , bharatpatil Vishal , Anilchamoli  , Raikwar Muskan , Negi Mahesh Singh , Singh Harparlad
Published: June 2021

It is 2021 of the 21st century, the world is already shifting dramatically towards complex machinery and procedures. A Compliant mechanism can help to make things simpler and elegant by decreasing the member elements in the machinery. We use flexure joints and simple members to perform operations. We focused on the aerospace uses of compliant mechanisms likebistable monolithic devices, deployable arrays by figuring out the origami oblivion applications, temporary or permanent structures, and mainly focused on Aerospace Applications. Well, looking for a more sustainable approach to the current space applications and planetary technologies that can behold the promises of primary mission goals. We mostly rely on rigid mechanisms for performing motions and transmission, here we showcase the actual science behind the flexible deformations lead to easier, cheap, and less complexity to the mechanism. The global sustainability part is considered in this paper while designing and material the components. The thickness of the material brings the mathematical models into the picture by which the origami is structure is formed and graphs analysisshows the compliant motions of the structure.
Evolution of Agritech Business 4.0 – Architecture and Future Research Directions
Authors: Eashwar S , Chawla Paras
Published: June 2021

Protection of farmer’s welfare, improving their standard of living and maintaining the connect between urban and rural population are important for sustainable development. Agriculture 4.0 based on Industry 4.0 evolved to produce crops in different manner by applying new technologies, adopt emerging technologies to bring efficiency in food web, incorporate cross industry technologies and applications. Agri Food 4.0 is a survey based on industrial farming using advancements in Blockchain, Artificial Intelligence, IOT, Big Data. The challenge is to make the technologies interoperable and also to integrate agriculture production with food distribution network. In this research work, we propose to present the architecture of Agritech Business 4.0, a transparent model to integrate agriculture production with food distribution network by adopting I4.0 technologies. It is necessary to have a common framework that uses Internet of Things, Smart DLT, Big Data Analytics etc. thereby the communication between the technologies can be harnessed for better agricultural production, food security, transparency and decentralization. We have also presented few open research problems and future research directions in this paper.
Breeding of Vicia faba L. in relation to drought resistance
Authors: Kurkina Yulia , Batlutskaya Irina , Klueva Violetta , Degtyareva Kristina , Mackanina Olesya
Published: June 2021

The collection of broad beans for a number of years in the soil and climatic conditions of the city of south of the central chernozem region of Russia on the territory of the National Research University “BelGU” have been studied. The Yu. N. Kurkina field method was used to determine the drought tolerance of bean plants. An analysis of the totality of ecological and morphological traits of forage bean varieties of different origins revealed varieties with pronounced xeromorphicity with low plant heights and narrow leaves. The varieties with high drought resistance have been identified. During the period when fruits are already forming in the lower nodes of plants, and pollination and fertilization are taking place in the flowers of the upper tiers, excess moisture negatively affects the emerging seed yield. A strong correlation was found between the productivity of the green mass and the amount of precipitation at the beginning of flowering. Seed productivity of beans is negatively reflected by high temperatures during the periods of germination and budding, and low temperatures during ripening of fruits and seeds. The productivity of green mass is more strongly influenced by temperature than precipitation
Environmental Impact Bonds: a common framework and looking ahead
Authors: Brand M W , Quesnel Seipp K , Saksa P , Ulibarri N , Bomblies A , Mandle L , Allaire M , Wing O , Tobin-de la Puente J , Parker E A , Nay J , Sanders B F , Rosowsky D , Lee J , Johnson K , Gudino-Elizondo N , Ajami N , Wobbrock N , Adriaens P , Grant S B , Wright S , Gartner T , Knight Z , Gibbons J P
Published: June 2021

A frequent barrier to addressing some of our world’s most pressing environmental challenges is a lack of funding. Currently, environmental project funding largely comes from philanthropic and public sources, but this does not meet current needs. Increased coordination and collaboration between multiple levels and sectors of government, in addition to private sector funding, can help address the environmental funding challenge. New financial tools and strategies can enable this transition and facilitate uptake of innovative solutions. One such mechanism, the Environmental Impact Bond (EIB), is an emerging financial tool with the potential to transform the environmental funding landscape. However, these financial instruments are not well understood or recognized beyond those actively involved in EIB projects or in the field of conservation finance. As EIBs gain momentum, there is a clear need for a common framework, including definitions and nomenclature, research needs, and outlook for the future. In this paper, we define EIB mechanics, elucidate the difference between EIBs and Green Bonds, and propose a common vocabulary for the field. Drawing on first-hand experience with the few EIBs which have been deployed, we review and assess lessons learned, trends, and paths for the future. Finally, we propose a set of future targets and discuss research goals for the field to unify around. Through this work, we identify a concrete set of research gaps and objectives, providing evidence for EIBs as one important tool in the environmental finance toolbox.
Indolent B-Lineage Precursor Populations Identified by Flow Cytometry and Immunohistochemistry in Benign Lymph Nodes
Authors: Stone Andrew B , Grzywacz Bartosz J , Courville Elizabeth L , Linden Michael A
Published: June 2021

Objectives

In this retrospective study, we report a series of benign lymph nodes showing small populations of normal B-cell precursors characterized by flow cytometry and immunohistochemistry.

Methods

Ten cases identified during clinical flow cytometry practice were retrospectively reanalyzed with particular attention to hematogone categorization and enumeration. Immunohistochemical staining was performed on five excisional lymph node biopsy specimens to characterize the morphologic correlate.

Results

Populations of hematogones ranging from 0.13% to 1.86% (median, 0.51%) of all viable leukocytes were demonstrated in 10 benign lymph node samples from eight different patients ranging in age from 17 to 45 years (median, 37.5). These hematogones showed a characteristic immunophenotype (CD19+/CD10+) and maturational pattern by flow cytometry, with progression from stage 1 (median, 0.03%) to stage 2 (median, 0.19%) to stage 3 (median, 0.26%) seen in all cases. Immunohistochemical staining on five excisional biopsy specimens demonstrated a distinct perisinusoidal distribution of CD10+/CD20+ cells with a subset of TdT+ cells, providing a morphologic correlate.

Conclusions

To our knowledge, this is the first study to characterize distinct hematogone populations within benign lymph nodes by both flow cytometry and immunohistochemistry. Recognizing these normal B-cell precursor populations is important to avoid their miscategorization as a CD10+ B-cell neoplasm.
Relationships between creatinine increase and mortality rates in patients given vancomycin in 76 hospitals: The increasing role of infectious disease pharmacists
Authors: Yu Kalvin C , Yamaga Cynthia , Vankeepuram Latha , Tabak Ying P
Published: June 2021

Purpose

Vancomycin is a commonly used antimicrobial with the potential for renal toxicity. We evaluated vancomycin duration, changes in renal function after vancomycin initiation (“post-vancomycin” renal function changes), and associated mortality risk among hospitalized patients.

Methods

We analyzed data from 76 hospitals and excluded patients with a baseline serum creatinine concentration (SCr) of >3.35 mg/dL. We estimated mortality risk relative to vancomycin duration and the magnitude of post-vancomycin SCr change, controlling for demographics, baseline SCr, underlying diseases, clinical acuity, and comorbidities.

Results

Among 128,993 adult inpatients treated with vancomycin, 49.0% did not experience SCr elevation. Among the remaining patients, 26.0%, 11.4%, 8.8% and 4.8% experienced increases in post-vancomycin SCr of 1% to 20%, 21% to 40%, 41% to 100%, and greater than 100%, respectively. Compared to mortality risk among patients with a vancomycin therapy duration between 4 and 5 days (the lowest-mortality group), longer vancomycin therapy duration was not independently associated with higher mortality risk after adjusting for confounders. In contrast, there was a graded relationship between post-vancomycin SCr elevation and mortality. Multivariable adjusted mortality odds ratios ranged from 1.60 to 13.66, corresponding to SCr increases of 10% and greater than 200%, respectively.

Conclusion

Half of patients given vancomycin did not experience SCr elevation and had the lowest mortality, suggesting that vancomycin can be used safely if renal function is stabilized. In the large study cohort, vancomycin duration itself was not an independent predictor of mortality. Post-vancomycin SCr elevation appeared to be a driver of in-hospital mortality. Even a 10% post-vancomycin SCr increase was associated with an increased mortality risk. This finding stresses the importance of closely monitoring renal function and may support the value of pharmacokinetic dosing.
Inquiry and confirmation
Authors: Falbo Arianna
Published: June 2021

A puzzle arises when combining two individually plausible, yet jointly incompatible, norms of inquiry. On the one hand, it seems that one should not inquire into a question while believing an answer to that question. But, on the other hand, it seems rational to inquire into a question while believing its answer, if one is seeking confirmation. Millson (2021), who has recently identified this puzzle, suggests a possible solution, though he notes that it comes with significant costs. I offer an alternative solution, which does not involve these costs. The best way to resolve the puzzle is to reject the prohibition on inquiring into a question while believing an answer to it. Resolving the puzzle in this way makes salient two fruitful areas in the epistemology of inquiry that merit further investigation. The first concerns the nature of the inquiring attitudes and the second concerns the aim(s) of inquiry.
Mutual mate preferences and assortative mating in relation to a carotenoid-based color trait in blue tits
Authors: Caro Samuel P , Pierre Léo , Bergès Matthieu , Bakker Raldi , Doutrelant Claire , Bonadonna Francesco
Published: June 2021

Choosing an appropriate sexual partner is a critical decision for many animal species. However, many mechanisms involved in mate choice are still poorly understood. Do both males and females choose their sexual partners, do both sexes use the same criteria for choosing, and do their own phenotype influence the choices they make, are questions that need further investigation. Over two successive experiments conducted in captivity with hand-reared blue tits (Cyanistes caeruleus), we manipulated the color of the chest plumage, a secondary sexual trait that reflects an individual’s condition, to create two different color morphs (one pale and one colored). We then tested whether both sexes express a preference, whether they are attracted to the same morphs, and if the subjects’ own chest color influences the preference they show. Our data reveal that both sexes are choosy, with females tending to be slightly choosier than males. We also show that both sexes preferentially select individuals with a pale chest plumage over colorful individuals, and this was again more pronounced in females. Finally, paler individuals tend to be selected by birds that are themselves pale, even if this phenotype matching was not very robust. Such a preference for paler individuals is intriguing because mates are predicted to associate with individuals displaying higher, not lower, value of quality signals. It could result from adaptive mechanisms related to avoidance of aggressiveness in a confined environment, avoidance of conflicting sexual signals within individuals, or from cultural mechanisms leading to a preference for individuals that match its own phenotype.
PAX2GRAPHML: a python library for large-scale regulation network analysis using BioPAX
Authors: Moreews François , Simon Hugo , Siegel Anne , Gondret Florence , Becker Emmanuelle
Published: June 2021

PAX2GRAPHML is an open-source Python library that allows to easily manipulate BioPAX source files as regulated reaction graphs described in.graphml format. The concept of regulated reactions, which allows connecting regulatory, signaling and metabolic levels, has been used. Biochemical reactions and regulatory interactions are homogeneously described by regulated reactions involving substrates, products, activators and inhibitors as elements. PAX2GRAPHML is highly flexible and allows generating graphs of regulated reactions from a single BioPAX source or by combining and filtering BioPAX sources. Supported by the graph exchange format .graphml, the large-scale graphs produced from one or more data sources can be further analyzed with PAX2GRAPHML or standard Python and R graph libraries.

Availability and implementation

https://pax2graphml.genouest.org.
Cheetah-MS: a web server to model protein complexes using tandem cross-linking mass spectrometry data
Authors: Khakzad Hamed , Happonen Lotta , Malmström Johan , Malmström Lars
Published: June 2021

Protein–protein interactions (PPIs) are central in many biological processes but difficult to characterize, especially in complex, unfractionated samples. Chemical cross-linking combined with mass spectrometry (MS) and computational modeling is gaining recognition as a viable tool in protein interaction studies. Here, we introduce Cheetah-MS, a web server for predicting the PPIs in a complex mixture of samples. It combines the capability and sensitivity of MS to analyze complex samples with the power and resolution of protein–protein docking. It produces the quaternary structure of the PPI of interest by analyzing tandem MS/MS data (also called MS2). Combining MS analysis and modeling increases the sensitivity and, importantly, facilitates the interpretation of the results.

Availability and implementation

Cheetah-MS is freely available as a web server at https://www.txms.org.
Humoral and Cellular Immune Responses Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Human Coronaviruses After Single BNT162b2 Vaccination
Authors: Stankov Metodi V , Cossmann Anne , Bonifacius Agnes , Dopfer-Jablonka Alexandra , Ramos Gema Morillas , Gödecke Nina , Scharff Anna Zychlinsky , Happle Christine , Boeck Anna-Lena , Tran Anh Thu , Pink Isabell , Hoeper Marius M , Blasczyk Rainer , Winkler Martin S , Nehlmeier Inga , Kempf Amy , Hofmann-Winkler Heike , Hoffmann Markus , Eiz-Vesper Britta , Pöhlmann Stefan , Behrens Georg M N
Published: June 2021

Background

Vaccine-induced neutralizing antibodies are key in combating the coronavirus disease 2019 (COVID-19) pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and prolonged or severe disease courses. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC)—B.1.1.7 (United Kingdom), B.1.351 (South Africa), and P.1 (Brazil)—may exacerbate this issue, as the latter two are able to evade control by antibodies.

Methods

We assessed humoral and T-cell responses against SARS-CoV-2 wild-type (WT), VOC, and endemic human coronaviruses (hCoVs) that were induced after single and double vaccination with BNT162b2.

Results

Despite readily detectable immunoglobulin G (IgG) against the receptor-binding domain of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 WT and VOC-specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T-cell frequencies reactive for WT and B.1.1.7 and B.1.351 variants.

Conclusions

These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.
The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing (June 2021)
Authors: Hanson Kimberly E , Altayar Osama , Caliendo Angela M , Arias Cesar A , Englund Janet A , Hayden Mary K , Lee Mark J , Loeb Mark , Patel Robin , El Alayli Abdallah , Sultan Shahnaz , Falck-Ytter Yngve , Lavergne Valery , Mansour Razan , Morgan Rebecca L , Murad M Hassan , Patel Payal , Bhimraj Adarsh , Mustafa Reem A
Published: June 2021

Immunoassays designed to detect SARS-CoV-2 protein antigens are now commercially available. The most widely used tests are rapid lateral flow assays that generate results in ~15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 antigen (Ag) assays have also been developed. The overall accuracy of SARS-CoV-2 Ag tests, however, is not well defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best-practice guidance related to SARS-CoV-2 Ag testing. This guideline is the third in a series of rapid, frequently updated COVID-19 diagnostic guidelines developed by IDSA. IDSA’s goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators, and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and nonmedical settings. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 5 diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals as well as assess single versus repeat testing strategies. Data on the clinical performance of US Food and Drug Administration SARS-CoV-2 Ag tests with Emergency Use Authorization are mostly limited to single, one-time testing versus standard nucleic acid amplification testing (NAAT) as the reference standard. Rapid Ag tests have high specificity and low to modest sensitivity compared with reference NAAT methods. Antigen test sensitivity is heavily dependent on viral load, with differences observed between symptomatic compared with asymptomatic individuals and the time of testing post-onset of symptoms. Based on these observations, rapid reverse transcriptase–polymerase chain reaction (RT-PCR) or laboratory-based NAAT remain the diagnostic methods of choice for diagnosing SARS-CoV-2 infection. However, when molecular testing is not readily available or is logistically infeasible, Ag testing can help identify some individuals with SARS-CoV-2 infection. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.
How Many Pop-Stacks Does It Take To Sort A Permutation?
Authors: Albert Michael , Vatter Vincent
Published: June 2021

Pop-stacks are variants of stacks that were introduced by Avis and Newborn in 1981. Coincidentally, a 1982 result of Unger implies that every permutation of length $n$ can be sorted by $n-1$ passes through a deterministic pop-stack. We give a new proof of this result inspired by Knuth’s zero-one principle.
Race and genetics versus ‘race’ in genetics
Authors: Duello Theresa M , Rivedal Shawna , Wickland Colton , Weller Annika
Published: June 2021

Lay Summary

A review of the medical literature since the completion of the Human Genome Project in 2003 revealed that race, a social construct created to justify slavery, continues to be used as a genetic category, due to a lack of understanding of the continuous nature of human genetic variation.
A risk scoring system for seafood supply chain breaches and examination of freshwater fish imported to Australia
Authors: Williams Michelle , Hernandez-Jover Marta , Williams Thomas , Shamsi Shokoofeh
Published: June 2021

Legislative changes have altered the way imported edible seafood is inspected in Australia. Greater onus of responsibility has been placed on exporting countries to provide documentary evidence of adherence to internally recognized food safety standards. According to global trade agreements, any additional safety tests applied to freshwater fish imported into Australia must be justified. Therefore, the aim of this study was to develop a risk scoring method to provide justification for identifying countries as ‘Freshwater fish high risk’ and to examine the seafood they export to Australia for seafood supply chain breaches. Scoring was conducted using six predictor variables, identified in the literature as important contributors to seafood supply chain breaches, to achieve the outcome variable, Country considered ‘Freshwater fish high risk’. Sixty-seven fish fillets (9.55 kg) of the same species were examined from the third highest scoring country (Country 20) and 562 (5.6 kg) whole fish from the sixth highest scoring country (Country 22). Country 20 had supply chain breaches of 28 macroscopic yellow cysts in one fillet. Two hundred and thirteen parasites and other supply chain breaches were identified in fish from Country 22, including retained liver (91 per cent), visible mud (11 per cent), a variety of debris (16 per cent) and, depending on the commodity code, these fish were imported to Australia under full intestine (90 per cent), retained gills (89 per cent), and partial intestine (9 per cent). Three serious physical hazards were recovered from the edible portion of three ‘consumer-ready’ fish and snails of Genus Lymnaea and Indoplanorbis were recovered from gill mud also from ‘consumer-ready’ fish. The study showed variable results from the scoring system and vast differences in seafood supply chain breaches between the third and sixth highest scoring countries.
Comparing the clinical application values of the Degree of Ulcerative Colitis Burden of Luminal Inflammation (DUBLIN) score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) in patients with ulcerative colitis
Authors: Zhang Xiao-Fei , Li Peng , Ding Xue-Li , Chen Hao , Wang Shao-Jun , Jin Sheng-Bo , Guo Jing , Tian Zi-Bin
Published: June 2021

Background

The significance of endoscopic evaluation in the diagnosis and management of ulcerative colitis (UC) has been widely recognized. Over the years, scholars have established several endoscopic scores. Herein, we assessed the clinical application value of the Mayo Endoscopic Subscore (Mayo ES), the Degree of Ulcerative Colitis Burden of Luminal Inflammation (DUBLIN) score, and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score in UC patients, by comparing their correlation with disease activity and their predictive potential for treatment response and clinical outcomes.

Methods

UC patients hospitalized from September 2015 to September 2019 were retrospectively analysed. We employed Spearman's rank correlation coefficient to assess the linear association of the assessed endoscopic scores with the clinical parameters. The receiver-operating characteristic curve was applied to evaluate the predictive capabilities of the endoscopic scores for treatment escalation and 1-year readmission.

Results

A total of 178 patients were enrolled; most of them (82%) suffered moderate or severe colitis. Among them, 48 (27%) patients received treatment escalation and 59 (33%) were readmitted within 1 year. The DUBLIN and UCEIS scores demonstrated higher correlations with clinical parameters than the Mayo ES. The DUBLIN scores significantly differed between patients with mild, moderate, and severe colitis (all P < 0.001). The UCEIS scores demonstrated the best predictabilities for treatment escalation and 1-year readmission with an area under the curve of 0.88 and 0.75, respectively. Compared to the UCEIS and DUBLIN scores, the predictive capabilities of the Mayo ES for treatment escalation (both P < 0.001) and 1-year readmission (P < 0.001 and P = 0.002, respectively) were lower. The UCEIS scores exhibited a significant difference between the steroid-responsive group and the steroid-dependent or steroid-refractory group (both P < 0.001), while no significant differences in the Mayo ES and DUBLIN scores were found among the three groups (both P > 0.05).

Conclusion

This study demonstrates that both the DUBLIN and UCEIS scores outperform the Mayo ES in assessing disease severity and predicting treatment response and clinical outcomes in UC patients.
Conservation of a DNA Replication Motif among Phylogenetically Distant Budding Yeast Species
Authors: Maria Haniam , Kapoor Shivali , Liu Tao , Rusche Laura N
Published: June 2021

Eukaryotic DNA replication begins at genomic loci termed origins, which are bound by the origin recognition complex (ORC). Although ORC is conserved across species, the sequence composition of origins is more varied. In the budding yeast Saccharomyces cerevisiae, the ORC-binding motif consists of an A/T-rich 17 bp “extended ACS” sequence adjacent to a B1 element composed of two 3-bp motifs. Similar sequences occur at origins in closely related species, but it is not clear when this type of replication origin arose and whether it predated a whole-genome duplication that occurred around 100 Ma in the budding yeast lineage. To address these questions, we identified the ORC-binding sequences in the nonduplicated species Torulaspora delbrueckii. We used chromatin immunoprecipitation followed by sequencing and identified 190 ORC-binding sites distributed across the eight T. delbrueckii chromosomes. Using these sites, we identified an ORC-binding motif that is nearly identical to the known motif in S. cerevisiae. We also found that the T. delbrueckii ORC-binding sites function as origins in T. delbrueckii when cloned onto a plasmid and that the motif is required for plasmid replication. Finally, we compared an S. cerevisiae origin with two T. delbrueckii ORC-binding sites and found that they conferred similar stabilities to a plasmid. These results reveal that the ORC-binding motif arose prior to the whole-genome duplication and has been maintained for over 100 Myr.
Revisiting the notion of deleterious sweeps
Authors: Johri Parul , Charlesworth Brian , Howell Emma K , Lynch Michael , Jensen Jeffrey D
Published: June 2021

It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites—both in the presence and absence of interference amongst deleterious mutations—and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.
Associations of Word Memory, Verbal Fluency, Processing Speed, and Crystallized Cognitive Ability With One-Legged Balance Performance in Mid- and Later Life
Authors: Blodgett Joanna M , Cooper Rachel , Davis Daniel H J , Kuh Diana , Hardy Rebecca
Published: June 2021

Background

Cognitive integration of sensory input and motor output plays an important role in balance. Despite this, it is not clear if specific cognitive processes are associated with balance and how these associations change with age. We examined longitudinal associations of word memory, verbal fluency, search speed, and reading ability with repeated measures of one-legged balance performance.

Method

Up to 2 934 participants in the MRC National Survey of Health and Development, a British birth cohort study, were included. At age 53, word memory, verbal fluency, search speed, and reading ability were assessed. One-legged balance times (eyes closed) were measured at ages 53, 60–64, and 69 years. Associations between each cognitive measure and balance time were assessed using random-effects models. Adjustments were made for sex, death, attrition, height, body mass index, health conditions, health behaviors, education, and occupational class.

Results

In sex-adjusted models, 1 SD higher scores in word memory, search speed, and verbal fluency were associated with 14.1% (95% CI: 11.3, 16.8), 7.2% (4.4, 9.9), and 10.3% (7.5, 13.0) better balance times at age 53, respectively. Higher reading scores were associated with better balance, although this association plateaued. Associations were partially attenuated in mutually adjusted models and effect sizes were smaller at ages 60–64 and 69. In fully adjusted models, associations were largely explained by education, although remained for word memory and search speed.

Conclusions

Higher cognitive performance across all measures was independently associated with better balance performance in midlife. Identification of individual cognitive mechanisms involved in balance could lead to opportunities for targeted interventions in midlife.
Vigorous Physical Activity and Cognitive Trajectory Later in Life: Prospective Association and Interaction by Apolipoprotein E e4 in the Nurses’ Health Study
Authors: Fassier Philippine , Kang Jae Hee , Lee I-Min , Grodstein Francine , Vercambre Marie-Noël
Published: June 2021

Background

The apolipoprotein E (APOE) e4 allele is a well-established genetic risk factor of brain aging. Vigorous physical activity may be particularly important in APOE-e4 carriers, but data have been inconsistent, likely due to differences in the timing of the physical activity assessment, definition of cognitive decline, and/or sample size.

Methods

We prospectively evaluated the association between vigorous physical activity and cognition assessed at least 9 years later, according to APOE-e4 carrier status. Biennially from 1986, Nurses’ Health Study participants reported their leisure-time physical activities. Starting in 1995–2001 and through 2008, participants (aged 70+ years) underwent up to 4 repeated cognitive telephone assessments (6 tasks averaged together using z-scores).

Results

Among 7252 women, latent process mixed models identified 3 major patterns of cognitive change over 6 years: high-stable, medium-stable, and decline. Taking the high-stable cognitive trajectory as the outcome reference in multinomial logistic regressions, highest tertile of vigorous physical activity (≥5.9 metabolic-equivalent [MET]-hours/wk) compared to lowest tertile (≤0.9 MET-hours/wk) was significantly associated with subsequent lower likelihood of the medium-stable trajectory in the global score (odds ratio [OR] [95% CI] = 0.72 [0.63, 0.82]), verbal memory (OR [95% CI] = 0.78 [0.68–0.89]), and telephone interview of cognitive status score (OR [95% CI] = 0.81 [0.70–0.94]). Vigorous physical activity was also associated with lower likelihood of decline in category fluency (OR [95% CI] = 0.72 [0.56, 0.92]). We observed some evidence (p-interaction = .07 for the global score) that the association was stronger among APOE-e4 carriers than noncarriers (OR [95% CI] = 0.60 [0.39, 0.92] vs 0.82 [0.59, 1.16]).

Conclusion

Midlife vigorous physical activity was associated with better cognitive trajectories in women in their seventies, with suggestions of stronger associations among APOE-e4 carriers.
Perceived Discrimination, Nativity, and Cognitive Performance in a Multiethnic Study of Older Adults: Findings From the Kaiser Healthy Aging and Diverse Life Experiences Study
Authors: Meza Erika , Peterson Rachel , Gilsanz Paola , George Kristen M , Miles Sunita J , Eng Chloe W , Mungas Dan M , Mayeda Elizabeth Rose , Glymour M Maria , Whitmer Rachel A
Published: June 2021

Background

Despite growing research on the association between discrimination and disparities in cognitive aging, an evidence gap remains on how the association varies by racial/ethnic group. This study evaluates the associations of experiences of discrimination with cognitive function and whether these associations varied by race/ethnicity and nativity.

Method

Using the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort (N = 1 712) with approximately equal groups of Black, White, Latino, and Asian community-dwelling older adults aged 65 years and older, we evaluated the associations between self-reported experiences of everyday and major lifetime discrimination with overall cognitive performance and domain-specific cognition (verbal episodic memory, semantic memory, and executive functioning) across race/ethnicity and nativity. Linear regression models examined the cross-sectional association between self-reported experiences of everyday and major lifetime discrimination with z-standardized coefficients for cognition. We tested for effect modification by race and nativity. All models controlled for age, sex, and education.

Results

Among KHANDLE participants (mean age: 76 years; SD: 6.8), everyday discrimination was not associated with cognitive scores. Major lifetime discrimination was associated with better average cognitive scores among Black participants but not among other racial/ethnic groups. Major lifetime discrimination was associated with better average cognitive scores among U.S.-born but not among non-U.S.-born individuals.

Conclusion

Our findings do not imply that discrimination improves cognition, but rather suggest that future research should include more detailed measures on discrimination and unfair treatment that could help disentangle the extent to which relationships are causal or reflect some other underlying factor.