bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of a functionally selective ghrelin receptor (GHSR
1a
) ligand for modulating brain dopamine
Authors: Gross J. D. , Kim D. W. , Zhou Y. , Jansen D. , Slosky L. M. , Clark N. B. , Ray C. R. , Hu X. , Southall N. , Wang A. , Xu X. , Barnaeva E. , Wetsel W. C. , Ferrer M. , Marugan J. J. , Caron M. G. , Barak L. S. , Toth K.
Published: March 2022

Significance

The modulation of growth hormone secretagogue receptor-1a (GHSR
1a
) signaling is a promising strategy for treating brain conditions of metabolism, aging, and addiction. GHSR
1a
activation results in pleiotropic physiological outcomes through distinct and pharmacologically separable G protein– and β-arrestin (βarr)–dependent signaling pathways. Thus, pathway-selective modulation can enable improved pharmacotherapeutics that can promote therapeutic efficacy while mitigating side effects. Here, we describe the discovery of a brain-penetrant small molecule, N8279 (NCATS-SM8864), that biases GHSR
1a
conformations toward Gα
q
activation and reduces aberrant dopaminergic behavior in mice. N8279 represents a promising chemical scaffold to advance the development of better treatments for GHSR
1a
-related brain disorders involving the pathological dysregulation of dopamine.
Dosage compensation inBombyx moriis achieved by partial repression of both Z chromosomes in males
Authors: Rosin Leah F. , Chen Dahong , Chen Yang , Lei Elissa P.
Published: March 2022

Significance

Genes on sex chromosomes (i.e. human chX) are regulated differently in males and females to balance gene expression levels between sexes (XY vs. XX). This sex-specific regulation is called dosage compensation (DC). DC is achieved by altering the shape and compaction of sex chromosomes specifically in one sex. In this study, we use Oligopaints to examine DC in silkworms. This study visualizes this phenomenon in a species with ZW sex chromosomes, which evolved independently of XY. Our data support a long-standing model for how DC mechanisms evolved across species, and we show potential similarity between DC in silkworms and nematodes, suggesting that this type of DC may have emerged multiple independent times throughout evolution.
Interactions between twins and dislocations in ZK60 alloy under dynamic compression
Authors: Zhou Le , Li Yutian , He Zhenyu , Wang Zhi , Liu Shimeng , Wang Feng , Mao Pingli , Liu Zheng
Published: March 2022

The interactions between [Formula: see text] tension twins and dislocations of ZK60 alloy under dynamic compression were investigated by electron backscattering diffraction and transmission electron microscopy. The samples were divided into two groups, where group-1 experienced primary deformation with different strains (4, 6, 9, and 12%) and group-2 experienced secondary deformation based on the primary deformation (4% + 8%, 6% + 6%, 9% + 3%) to reach the final deformation of 12%. The results reveal that the [Formula: see text] tension twins are the dominant deformation mechanism during the early stages of deformation, and the volume fraction of [Formula: see text] tension twins and dislocation density increase with the increase in deformation. Moreover, the twin boundaries and dislocations generated during the primary deformation become the resistance to the dislocations motion during the secondary deformation.
Fyn and TOM1L1 are recruited to clathrin-coated pits and regulate Akt signaling
Authors: Cabral-Dias Rebecca , Lucarelli Stefanie , Zak Karolina , Rahmani Sadia , Judge Gurjeet , Abousawan John , DiGiovanni Laura F. , Vural Dafne , Anderson Karen E. , Sugiyama Michael G. , Genc Gizem , Hong Wanjin , Botelho Roberto J. , Fairn Gregory D. , Kim Peter K. , Antonescu Costin N.
Published: March 2022

The epidermal growth factor (EGF) receptor (EGFR) controls many aspects of cell physiology. EGF binding to EGFR elicits the membrane recruitment and activation of phosphatidylinositol-3-kinase, leading to Akt phosphorylation and activation. Concomitantly, EGFR is recruited to clathrin-coated pits (CCPs), eventually leading to receptor endocytosis. Previous work uncovered that clathrin, but not receptor endocytosis, is required for EGF-stimulated Akt activation, and that some EGFR signals are enriched in CCPs. Here, we examine how CCPs control EGFR signaling. The signaling adaptor TOM1L1 and the Src-family kinase Fyn are enriched within a subset of CCPs with unique lifetimes and protein composition. Perturbation of TOM1L1 or Fyn impairs EGF-stimulated phosphorylation of Akt2 but not Akt1. EGF stimulation also triggered the TOM1L1- and Fyn-dependent recruitment of the phosphoinositide 5-phosphatase SHIP2 to CCPs. Thus, the recruitment of TOM1L1 and Fyn to a subset of CCPs underlies a role for these structures in the support of EGFR signaling leading to Akt activation.
Cdc14 spatiotemporally dephosphorylates Atg13 to activate autophagy during meiotic divisions
Authors: Feng Wenzhi , Argüello-Miranda Orlando , Qian Suhong , Wang Fei
Published: March 2022

Autophagy is a conserved eukaryotic lysosomal degradation pathway that responds to environmental and cellular cues. Autophagy is essential for the meiotic exit and sporulation in budding yeast, but the underlying molecular mechanisms remain unknown. Here, we show that autophagy is maintained during meiosis and stimulated in anaphase I and II. Cells with higher levels of autophagy complete meiosis faster, and genetically enhanced autophagy increases meiotic kinetics and sporulation efficiency. Strikingly, our data reveal that the conserved phosphatase Cdc14 regulates meiosis-specific autophagy. Cdc14 is activated in anaphase I and II, accompanying its subcellular relocation from the nucleolus to the cytoplasm, where it dephosphorylates Atg13 to stimulate Atg1 kinase activity and thus autophagy. Together, our findings reveal a meiosis-tailored mechanism that spatiotemporally controls meiotic autophagy activity to ensure meiosis progression, exit, and sporulation.
The investigation of the luminescent structure of thallium-doped cesium iodide (CsI:Tl) basing on the first-principles coupled with spectral analysis
Authors: Gao T J , Wang H D , Lu Jing-Bin , Yue Song , Chao Sun , Duan De-fang
Published: March 2022

The luminescent structure of thallium-doped cesium iodide (CsI:Tl) and the behavior of electrons during luminescence are studied at great length based on the conventional first-principles calculation combined with ordinary spectroscopic analysis befittingly in this work. The hybrid functionals based on a screened Coulomb potential (HSE) is used to visualize the energy band structure of the experimental sample’s system, and the corresponding relationship between the transition behavior of CsI:Tl energy levels and the spectrum is studied more accurately. We show the complete energy conversion process clearly, which involves the crystal beginning to receive the energy of a photon until the moment of de-excitation. All the fluorescence process is completed by Tl+ ions that replace Cs+ ions. Our results verify and complement the previous theories and potentially provide important references for the adjustment and design of the detectors and imaging equipment in different fields.
Assessment of damage in composites using static component generation of ultrasonic guided waves
Authors: Jiang Chang , Zhang Changyu , Li Weibin , Deng Mingxi , Ng Ching-Tai
Published: March 2022

Static component (SC) generation of guided waves (GWs), which combines the high sensitivity of acoustic nonlinearity to micro-damage and low attenuative effect, has great potential for damage assessment in large composite structures. The present work explores the use of SC generation of GWs for assessing damages in carbon fiber reinforced polymer (CFRP) composite laminates. The features including mode, waveform, and cumulative effect of the generated SC in composites are numerically investigated by three-dimensional finite element modeling and simulation. A dynamic displacement measurement method based on piezoelectric transducers is accordingly proposed and experimentally verified. The cumulative SC pulse generated from primary GW tone-burst with a finite duration, is observed and verified numerically and experimentally. It is found that the magnitude of the generated SC pulse is linearly proportional to the quadratic material nonlinearity. Experimental results demonstrate that the generated SC pulse of GW under group velocity matching condition, is an effective means to assess the hygrothermal damage and low-velocity impact damage in CFRP composite plates. The performed experimental examination validates the feasibility of the proposed approach for damage assessment in CFRP composites.
Topological Lifshitz transitions, orbital currents, and interactions in low-dimensional Fermi gases in synthetic gauge fields
Authors: Huang Chen-How , Tezuka Masaki , Cazalilla Miguel A
Published: March 2022

Low-dimensional systems of interacting fermions in a synthetic gauge field have been experimentally realized using two-component ultra-cold Fermi gases in optical lattices. Using a two-leg ladder model that is relevant to these experiments, we have studied the signatures of topological Lifshitz transitions and the effects of the inter-species interaction U on the gauge-invariant orbital current in the regime of large intra-leg hopping Ω. Focusing on non-insulating regimes, we have carried out numerically exact density-matrix renormalization-group (DMRG) calculations to compute the orbital current at fixed particle number as a function of the interaction strength and the synthetic gauge flux per plaquette. Signatures of topological Lifshitz transitions where the number Fermi points changes are found to persist even in the presence of very strong repulsive interactions. This numerical observation suggests that the orbital current can be computed from an appropriately renormalized mean-field band structure, which is also described here. Quantitative agreement between the mean-field and the DMRG results in the intermediate interaction regime where U ≲ Ω is demonstrated. We also have observed that interactions can change the sign of the current susceptibility at zero field and induce Lifshitz transitions between two metallic phases, which is also captured by the mean-field theory. Correlation effects beyond mean-field theory in the oscillations of the local inter-leg current are also reported. We argue that the observed robustness against interactions makes the orbital current a good indicator of the topological Lifshitz transitions.
The band structure of the whole spectrum of an N-body cold system containing atoms with arbitrary integer spin and dominated by singlet pairing force
Authors: He Y Z , Liu Y M , Li Z B , Bao C G
Published: March 2022

The spectra of N-boson systems with arbitrary nonzero spin

f

have been studied. Firstly, only the singlet pairing interaction is considered, a set of exact eigenstates together with the eigenenergies are analytically obtained. The completeness of this set is proved. The analytical expression allows us to see clearly the spin textures of various states different in N and/or

f

, and to find out the similarity and relationship lying among them. Secondly, the effect of other interactions is evaluated via exact numerical calculations on the systems with a smaller N. Some features and notable phenomena that might emerge in high-

f

systems, say, the ground band might have extremely high level density, have been discussed.
Probable decay modes of even–even superheavy nuclei
Authors: Pathak Deepika , Singh Navdeep , Singh Pardeep , Kaur Paramjit , Kaur Harjeet , Jain Sudhir R
Published: March 2022

Cluster-decay half-lives (

T

1

/

2

c
,
th

(
s
)

) of even–even nuclei are calculated employing interaction potential involving Coulomb and proximity potentials and, the obtained results are compared with the experimental ones. In order to study cluster radioactivity in even–even superheavy nuclei (SHN), we evaluate the required disintegration energies (Q

c
-values) utilizing periodic-orbit theory within microscopic-macroscopic formalism and hence, predict the logarithmic values of

T

1

/

2

c
,
th

's for even–even 298−312Og and 296−310120 nuclei. Among various isotopes of daughter nuclei, products produced with minimum value of Gibbs free energy are chosen for our investigation. Also, an analysis of the branching ratios enables us to determine the dominant mode of decay among α − decay, spontaneous fission (SF) and cluster-decay in these SHN. The emissions of 90Kr from 298Og and 94Sr cluster from 296,298120 SHN are found to be the dominant mode of decay. Our results are in agreement with those obtained using UDL method except for few cases. We believe that this work can play a significant role in the experiments leading to identification of exotic nuclei.
Event Detection and Reconstruction Using Neural Networks in TES Devices: a Case Study for Athena/X-IFU
Authors: Vega-Ferrero J. , Ceballos M. T. , Cobo B. , Carrera F. J. , García P. , Puyol-Gruart J.
Published: March 2022

Transition Edge Sensors detector devices, like the core of the X-IFU instrument that will be on-board the Athena X-ray Observatory, produce current pulses as a response to the incident X-ray photons. The reconstruction of these pulses has been traditionally performed by means of a triggering algorithm based on the derivative signal overcoming a threshold (detection) followed by an optimal filtering (to retrieve the energy of each event). However, when the arrival of the photons is very close in time, the triggering algorithm is incapable of detecting all the individual pulses which are thus piled-up. In order to improve the efficiency of the detection and energy-retrieval process, we study here an alternative approach based on Machine Learning techniques to process the pulses. For this purpose, we construct and train a series of Neural Networks (NNs) not only for the detection but also for the recovering of the arrival time and the energy of simulated X-ray pulses. The data set used to train the NNs consists of simulations performed with the sixte/xifusim software package, the Athena/X-IFU official simulator. The performance of our NN classification clearly surpasses the detection performance of the classical triggering approach for the full range of photon energy combinations, showing excellent metrics and very competitive computing efficiency. However, the precision obtained for the recovery of the energy of the photons cannot currently compete with the standard optimal filtering algorithm, despite its much better computing efficiency.
Fasting and Postload Nonesterified Fatty Acids and Glucose Dysregulation in Older Adults
Authors: Shitole Sanyog G , Biggs Mary L , Ix Joachim H , Fretts Amanda M , Tracy Russell P , Siscovick David S , Djoussé Luc , Mukamal Kenneth J , Kizer Jorge R
Published: March 2022

To evaluate the association of nonesterified fatty acids (NEFA) with dysglycemia in older adults, NEFA levels were measured among participants in the Cardiovascular Health Study (United States; enrolled 1989–1993). Associations with insulin sensitivity and pancreatic β-cell function, and with incident type 2 diabetes mellitus (DM), were examined. The sample comprised 2,144 participants (aged 77.9 (standard deviation, 4.5) years). Participant data from the Cardiovascular Health Study visit in 1996–1997 was used with prospective follow-up through 2010. Fasting and postload NEFA showed significant associations with lower insulin sensitivity and pancreatic β-cell function, individually and on concurrent adjustment. Over median follow-up of 9.7 years, 236 cases of DM occurred. Postload NEFA were associated with risk of DM (per standard deviation, hazard ratio = 1.18, 95% confidence interval: 1.08, 1.29), but fasting NEFA were not (hazard ratio = 1.12, 95% confidence interval: 0.97, 1.29). The association for postload NEFA persisted after adjustment for putative intermediates, and after adjustment for fasting NEFA. Sex and body mass index modified these associations, which were stronger for fasting NEFA with DM in men but were accentuated for postload NEFA in women and among leaner individuals. Fasting and postload NEFA were related to lower insulin sensitivity and pancreatic β-cell function, but only postload NEFA were associated with increased DM. Additional study into NEFA metabolism could uncover novel potential targets for diabetes prevention in elders.
Supervised capacity preserving mapping: a clustering guided visualization method for scRNA-seq data
Authors: Zhai Zhiqian , Lei Yu L , Wang Rongrong , Xie Yuying
Published: March 2022

Motivation

The rapid development of scRNA-seq technologies enables us to explore the transcriptome at the cell level on a large scale. Recently, various computational methods have been developed to analyze the scRNAseq data, such as clustering and visualization. However, current visualization methods, including t-SNE and UMAP, are challenged by the limited accuracy of rendering the geometric relationship of populations with distinct functional states. Most visualization methods are unsupervised, leaving out information from the clustering results or given labels. This leads to the inaccurate depiction of the distances between the bona fide functional states. In particular, UMAP and t-SNE are not optimal to preserve the global geometric structure. They may result in a contradiction that clusters with near distance in the embedded dimensions are in fact further away in the original dimensions. Besides, UMAP and t-SNE cannot track the variance of clusters. Through the embedding of t-SNE and UMAP, the variance of a cluster is not only associated with the true variance but also is proportional to the sample size.

Results

We present supCPM, a robust supervised visualization method, which separates different clusters, preserves the global structure and tracks the cluster variance. Compared with six visualization methods using synthetic and real datasets, supCPM shows improved performance than other methods in preserving the global geometric structure and data variance. Overall, supCPM provides an enhanced visualization pipeline to assist the interpretation of functional transition and accurately depict population segregation.

Availability and implementation

The R package and source code are available at https://zenodo.org/record/5975977#.YgqR1PXMJjM.

Supplementary information

Supplementary data are available at Bioinformatics online.
BWA-MEME: BWA-MEM emulated with a machine learning approach
Authors: Jung Youngmok , Han Dongsu
Published: March 2022

Motivation

The growing use of next-generation sequencing and enlarged sequencing throughput require efficient short-read alignment, where seeding is one of the major performance bottlenecks. The key challenge in the seeding phase is searching for exact matches of substrings of short reads in the reference DNA sequence. Existing algorithms, however, present limitations in performance due to their frequent memory accesses.

Results

This article presents BWA-MEME, the first full-fledged short read alignment software that leverages learned indices for solving the exact match search problem for efficient seeding. BWA-MEME is a practical and efficient seeding algorithm based on a suffix array search algorithm that solves the challenges in utilizing learned indices for SMEM search which is extensively used in the seeding phase. Our evaluation shows that BWA-MEME achieves up to 3.45× speedup in seeding throughput over BWA-MEM2 by reducing the number of instructions by 4.60×, memory accesses by 8.77× and LLC misses by 2.21×, while ensuring the identical SAM output to BWA-MEM2.

Availability and implementation

The source code and test scripts are available for academic use at https://github.com/kaist-ina/BWA-MEME/.

Supplementary information

Supplementary data are available at Bioinformatics online.
An ensemble approach to predict binding hotspots in protein–RNA interactions based on SMOTE data balancing and Random Grouping feature selection strategies
Authors: Zhou Tong , Rong Jie , Liu Yang , Gong Weikang , Li Chunhua
Published: March 2022

Motivation

The identification of binding hotspots in protein–RNA interactions is crucial for understanding their potential recognition mechanisms and drug design. The experimental methods have many limitations, since they are usually time-consuming and labor-intensive. Thus, developing an effective and efficient theoretical method is urgently needed.

Results

Here, we present SREPRHot, a method to predict hotspots, defined as the residues whose mutation to alanine generate a binding free energy change ≥2.0 kcal/mol, while others use a cutoff of 1.0 kcal/mol to obtain balanced datasets. To deal with the dataset imbalance, Synthetic Minority Over-sampling Technique (SMOTE) is utilized to generate minority samples to achieve a dataset balance. Additionally, besides conventional features, we use two types of new features, residue interface propensity previously developed by us, and topological features obtained using node-weighted networks, and propose an effective Random Grouping feature selection strategy combined with a two-step method to determine an optimal feature set. Finally, a stacking ensemble classifier is adopted to build our model. The results show SREPRHot achieves a good performance with SEN, MCC and AUC of 0.900, 0.557 and 0.829 on the independent testing dataset. The comparison study indicates SREPRHot shows a promising performance.

Availability and implementation

The source code is available at https://github.com/ChunhuaLiLab/SREPRHot.

Supplementary information

Supplementary data are available at Bioinformatics online.
Age-Related Changes in the Nasopharyngeal Microbiome Are Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Symptoms Among Children, Adolescents, and Young Adults
Authors: Hurst Jillian H , McCumber Alexander W , Aquino Jhoanna N , Rodriguez Javier , Heston Sarah M , Lugo Debra J , Rotta Alexandre T , Turner Nicholas A , Pfeiffer Trevor S , Gurley Thaddeus C , Moody M Anthony , Denny Thomas N , Rawls John F , Clark James S , Woods Christopher W , Kelly Matthew S
Published: March 2022

Background

Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not well understood. The upper respiratory microbiome undergoes substantial shifts during childhood and is increasingly recognized to influence host defense against respiratory pathogens. Thus, we sought to identify upper respiratory microbiome features associated with SARS-CoV-2 infection susceptibility and illness severity.

Methods

We collected clinical data and nasopharyngeal swabs from 285 children, adolescents, and young adults (<21 years) with documented SARS-CoV-2 exposure. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and evaluated for age-adjusted associations between microbiome characteristics and SARS-CoV-2 infection status and respiratory symptoms.

Results

Nasopharyngeal microbiome composition varied with age (PERMANOVA, P < .001; R2 = 0.06) and between SARS-CoV-2–infected individuals with and without respiratory symptoms (PERMANOVA, P  = .002; R2 = 0.009). SARS-CoV-2–infected participants with Corynebacterium/Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles (OR: .38; 95% CI: .18–.81). Using generalized joint attributed modeling, we identified 9 bacterial taxa associated with SARS-CoV-2 infection and 6 taxa differentially abundant among SARS-CoV-2–infected participants with respiratory symptoms; the magnitude of these associations was strongly influenced by age.

Conclusions

We identified interactive relationships between age and specific nasopharyngeal microbiome features that are associated with SARS-CoV-2 infection susceptibility and symptoms in children, adolescents, and young adults. Our data suggest that the upper respiratory microbiome may be a mechanism by which age influences SARS-CoV-2 susceptibility and illness severity.
IL-23 Monoclonal Antibodies for IBD: So Many, So Different?
Authors: McDonald Benjamin D , Dyer Emma C , Rubin David T
Published: March 2022

Interleukin [IL]-23 is a member of the IL-12 family of cytokines and has been implicated in multiple inflammatory disorders including psoriasis, psoriatic arthritis, and the inflammatory bowel diseases [IBDs]. Blockade of both IL-12 and IL-23 using an antibody that targets a shared subunit is highly effective in treating psoriasis, and recent data suggest similar efficacy in IBD with minimal adverse events. In this review, we summarise published data on the efficacy of anti-IL-12/23 therapies in IBD as well as emerging data on more selective anti-IL-23 specific therapies. Last, we discuss novel therapeutics under development which target the IL-23 pathway in unique ways and suggest that a biomarker-driven approach will soon guide clinicians to prescribe anti-IL-23 therapies to the patients most likely to respond to them.
Cardiac sympathetic denervation in the prevention of genetically mediated life-threatening ventricular arrhythmias
Authors: Schwartz Peter J. , Ackerman Michael J.
Published: March 2022

Proper management of patients affected by genetic disorders causing life-threatening arrhythmias is important for several reasons, including even societal ones, given the predominantly young age of those affected. Incorrect management often has dire consequences, ranging from unnecessary psychologic damage for the patients whose life becomes too limited by the fear of sudden death to equally avoidable tragedies when the entire armamentarium of effective therapies is not fully utilized. In this review, we focus primarily on long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) and deal specifically with the clinical impact of the most commonly used cardiac sympathetic denervation (CSD), namely left cardiac sympathetic denervation (LCSD). The two of us have used LCSD in the management of our patients with either LQTS or CPVT for a very long time and have been involved in ∼500 such interventions. It is on the basis of this personal and direct experience that we wish to share our views with clinical cardiologists and electrophysiologists, adult and paediatric, and with genetic cardiologists. We will begin by reviewing the history and rationale underlying sympathetic denervation therapy and will continue with a disease-specific intensification of therapy, and then with a discussion on how the impressive efficacy of LCSD should translate into guideline-directed therapy in both current and future guidelines, in order to upgrade the quality of care in the era of precision medicine.
Electromechanical reciprocity and arrhythmogenesis in long-QT syndrome and beyond
Authors: Odening Katja E , van der Linde Henk J , Ackerman Michael J , Volders Paul G A , ter Bekke Rachel M A
Published: March 2022

An abundance of literature describes physiological and pathological determinants of cardiac performance, building on the principles of excitation–contraction coupling. However, the mutual influencing of excitation–contraction and mechano-electrical feedback in the beating heart, here designated ‘electromechanical reciprocity’, remains poorly recognized clinically, despite the awareness that external and cardiac-internal mechanical stimuli can trigger electrical responses and arrhythmia. This review focuses on electromechanical reciprocity in the long-QT syndrome (LQTS), historically considered a purely electrical disease, but now appreciated as paradigmatic for the understanding of mechano-electrical contributions to arrhythmogenesis in this and other cardiac conditions. Electromechanical dispersion in LQTS is characterized by heterogeneously prolonged ventricular repolarization, besides altered contraction duration and relaxation. Mechanical alterations may deviate from what would be expected from global and regional repolarization abnormalities. Pathological repolarization prolongation outlasts mechanical systole in patients with LQTS, yielding a negative electromechanical window (EMW), which is most pronounced in symptomatic patients. The electromechanical window is a superior and independent arrhythmia-risk predictor compared with the heart rate-corrected QT. A negative EMW implies that the ventricle is deformed—by volume loading during the rapid filling phase—when repolarization is still ongoing. This creates a ‘sensitized’ electromechanical substrate, in which inadvertent electrical or mechanical stimuli such as local after-depolarizations, after-contractions, or dyssynchrony can trigger abnormal impulses. Increased sympathetic-nerve activity and pause-dependent potentiation further exaggerate electromechanical heterogeneities, promoting arrhythmogenesis. Unraveling electromechanical reciprocity advances the understanding of arrhythmia formation in various conditions. Real-time image integration of cardiac electrophysiology and mechanics offers new opportunities to address challenges in arrhythmia management.
The HOG pathway and the regulation of osmoadaptive responses in yeast
Authors: de Nadal Eulàlia , Posas Francesc
Published: March 2022

Cells coordinate intracellular activities in response to changes in the extracellular environment to maximize their probability of survival and proliferation. Eukaryotic cells need to adapt to constant changes in the osmolarity of their environment. In yeast, the high-osmolarity glycerol (HOG) pathway is responsible for the response to high osmolarity. Activation of the Hog1 stress-activated protein kinase (SAPK) induces a complex program required for cellular adaptation that includes temporary arrest of cell cycle progression, adjustment of transcription and translation patterns, and the regulation of metabolism, including the synthesis and retention of the compatible osmolyte glycerol. Hog1 is a member of the family of p38 SAPKs, which are present across eukaryotes. Many of the properties of the HOG pathway and downstream-regulated proteins are conserved from yeast to mammals. This review addresses the global view of this signaling pathway in yeast, as well as the contribution of Dr Hohmann's group to its understanding.
The Constructionist Approach to Emotional Aging: Theoretical Insights and Predictions
Authors: Mikkelsen Mai Bjørnskov , O’Toole Mia Skytte
Published: March 2022

In this article, we introduce a constructionist approach to understanding emotional aging in adulthood. The purpose of the paper is to show how constructionism offers a promising avenue for gaining new insights into age-related changes in emotional experiences. We begin by introducing the constructionist theoretical framework and illustrating how constructionism may shape conceptualizations of emotional aging in adulthood. We compare the constructionist conceptualization of emotional aging with existing conceptualizations of emotional aging derived from prominent theories of emotional aging, focusing on how such conceptualizations highlight different aspects of emotional aging (e.g., different mechanisms) and overlook or downplay other aspects. We conclude by explicating what constructionism may offer research on emotional aging, including considerations of research agendas, study designs, and method of measurement.
A Panel Study of Attitudes toward Ethnic Minorities and the Role of Changes in Individuals’ Economic Situations
Authors: Hendriks Inge , Lubbers Marcel , Scheepers Peer
Published: March 2022

This study applies the dynamic perspective of realistic conflict theory to assess whether and the extent that individuals’ negative attitudes toward ethnic minorities changed and were linked to changes in individuals’ economic situations. Employing Dutch panel data, we found that negative attitudes toward ethnic minorities were remarkably stable. Differences in attitudes toward ethnic minorities were more pronounced between individuals than within individuals. The small changes that did occur over the 10-year study period were hardly explained by economic characteristics. Only increased individual dissatisfaction with the national financial situation was associated with more negative attitudes. These results cast doubt on whether attitudes toward ethnic minorities are susceptible to change and raise questions about realistic conflict theory’s relevance in explaining attitudinal change.
Transcriptome Analysis of Plasmodium falciparum Isolates From Benin Reveals Specific Gene Expression Associated With Cerebral Malaria
Authors: Guillochon E , Fraering J , Joste V , Kamaliddin C , Vianou B , Houzé L , Baudrin L G , Faucher J F , Aubouy A , Houzé S , Cot M , Argy N , Taboureau O , Bertin G I ,   NeuroCM group, Alao Jules , Affolabi Dissou , Biokou Bibiane , Degbelo Jean-Eudes , Deloron Philippe , Dramane Latifou , Jafari-Guemouri Sayeh , Labrunie Anaïs , Ladipo Yélé , Lathiere Thomas , Massougbodji Achille , Mowendabeka Audrey , Papin Jade , Pipy Bernard , Preux Pierre-Marie , Raymondeau Marie , Royo Jade , Sossou Darius , Techer Brigitte
Published: March 2022

Cerebral malaria (CM) is the severest form of Plasmodium falciparum infection. Children under 5 years old are those most vulnerable to CM, and they consequently have the highest risk of malaria-related death. Parasite-associated factors leading to CM are not yet fully elucidated. We therefore sought to characterize the gene expression profile associated with CM, using RNA sequencing data from 15 CM and 15 uncomplicated malaria isolates from Benin. Cerebral malaria parasites displayed reduced circulation times, possibly related to higher cytoadherence capacity. Consistent with the latter, we detected increased var genes abundance in CM isolates. Differential expression analyses showed that distinct transcriptome profiles are signatures of malaria severity. Genes involved in adhesion, excluding variant surface antigens, were dysregulated, supporting the idea of increased cytoadhesion capacity of CM parasites. Finally, we found dysregulated expression of genes in the entry into host pathway that may reflect greater erythrocyte invasion capacity of CM parasites.
Structural insight into replicative helicase loading in Escherichia coli
Authors: Horikoshi Naoki , Kurumizaka Hitoshi
Published: March 2022

DNA replication is an essential, precisely regulated process that occurs once in a cell cycle. In the Gram-negative bacterium Escherichia coli, the replicative helicase EcDnaB and the helicase loader EcDnaC play key roles in the initiation step at the replication origin, oriC. EcDnaB and EcDnaC form a heterododecamer, in which hexameric EcDnaB is bound to hexameric EcDnaC. Using genetic, biochemical and structural biology approaches, many groups have probed the mechanism of replicative helicase loading, using helicases and helicase loaders from various species. Recent X-ray crystallography and cryogenic electron microscopy (cryo-EM) structural studies of the EcDnaB–EcDnaC complex revealed that the interaction of DnaC with DnaB triggers distortion accumulation on the closed ring of hexameric DnaB, inducing DnaB subunits to adopt the open helical form for replication progression. The high-resolution crystal structure of the DnaB–DnaC complex solved by Nagata et al. contributed to a better understanding of the conformational rearrangement of the DnaB ring. In addition to the structural alterations in DnaB subunits by DnaC, the binding of single-stranded DNA (ssDNA) substrates alters the ATP- and ADP-bound forms of DnaB and DnaC. These studies have proposed mechanisms by which DnaC regulates helicase loading onto ssDNA.
Modeling Realized Covariance Matrices: A Class of Hadamard Exponential Models
Authors: Bauwens Luc , Otranto Edoardo
Published: March 2022

Time series of realized covariance matrices can be modeled in the conditional autoregressive Wishart model family via dynamic correlations or via dynamic covariances. Extended parameterizations of these models are proposed, which imply a specific and time-varying impact parameter of the lagged realized covariance (or correlation) on the next conditional covariance (or correlation) of each asset pair. The proposed extensions guarantee the positive definiteness of the conditional covariance or correlation matrix with simple parametric restrictions, while keeping the number of parameters fixed or linear with respect to the number of assets. Two empirical studies reveal that the extended models have superior forecasting performances than their simpler versions and benchmark models.
Discretionary Responses in Frontline Encounters: Balancing Standardization with the Ethics of Office
Authors: Pedersen Kirstine Zinck , Pors Anja Svejgaard
Published: March 2022

Policy reforms of public service encounters often seek to control, delegate, or eliminate discretion at the frontline. In this article, we show that rather than eclipsing discretion, the technologies meant to standardize and optimize decision making in public service delivery introduce rough categorizations and scripts for action that make new types of discretionary responses and workarounds necessary. Here, accounts of street-level discretion as grounded in self-serving coping strategies are inadequate to capture discretion-as-used in the frontline encounter. The article proposes a Weberian ethics of office approach to frontline discretion that contributes to current more appreciative perspectives on street-level discretion. Through a comparative ethnography of first encounters in three Danish public service bureaucracies, we develop a typology of office-based discretionary responses to standardization. We label the three types as adaptive handling, attentive compensation, and affective encouragement. Our study of doctors, midwives, and citizen-service bureaucrats suggests that discretionary possibilities differ in relation to organizational context and level of professional training. However, across cases the discretionary responses are indicative of the frontline practitioners’ casuistic practices of balancing professional virtues, client-orientation, and managerial demands in the quest to deliver fair and responsive services. Accordingly, securing the conditions for the exercise of discretion in frontline encounters is essential to the responsible provision of public services.
The effects ofEpichloëendophytes on the growth and competitiveness ofAchnatherum sibiricumare mediated by soil microbe diversity
Authors: Qu Yaobing , Qin Tianzi , Shi Xinjian , Chen Jing , Liu Hui , Zhao Nianxi , Gao Yubao , Ren Anzhi
Published: March 2022

Many grasses are infected by systemic fungal endophytes that occur in aboveground plant tissues. Both aboveground endophytic fungi and belowground soil microbes can influence plant growth, but studies on their simultaneous effects on plant growth and competitiveness are limited. This study aims to investigate whether the role of aboveground endophytic fungi in the growth and competitive ability of the host grasses was influenced by soil microbes. In this study, we used Epichloë endophyte-infected and endophyte-free Achnatherum sibiricum as plant materials. A wet sieving method was adopted to obtain microbial inocula with different diversities (com, combined microbe fraction, high diversity; sm, small microbe fraction, low diversity). A three-factor randomized block design was used. The first factor was the endophyte infection status of A. sibiricum. The second factor was the microbial composition of the soil inocula. The third factor was the planting type. Growth and competitive characters were measured after 16 weeks. The results showed that a soil microbe inoculation was detrimental to the growth of A. sibiricum. Epichloë endophytes significantly mitigated the inhibitory effect of soil microbes on A. sibiricum planted alone. When A. sibiricum was planted with Stipa grandis, there was a significant interaction between Epichloë endophytes and soil microbes on the interspecific competition of A. sibiricum. When inoculated with small microbial community fraction, Epichloë endophytes significantly improved the interspecific competitive ability of host plants. When inoculated with combined microbial community fraction, however, Epichloë endophytes had no significant effect on host competition. The results showed that the interaction between Epichloë endophytes and soil microbes contributed more to the interspecific competitive ability than either Epichloë endophytes or soil microbes alone.
Tension offloading improves cutaneous scar formation in Achilles tendon repair
Authors: Abbas Darren B , Lintel Hendrik , Griffin Michelle , Guardino Nicholas J , Guo Jason L , Spielman Amanda F , Cotterell Asha C , Parker Jennifer B L , Januszyk Michael , Wan Derrick C
Published: March 2022

Hypertrophic scar formation and non-healing wounds following Achilles tendon repair arise from poor vascularity to the incisional site or from excess mechanical stress/strain to the incision during the healing process. The embrace® scar therapy dressing is a tension offloading device for incisional scars. This study explored the effects of tension offloading during Achilles scar formation. A healthy 30-year-old male without any medical co-morbidities developed an acute rupture of his left Achilles tendon. The patient underwent open repair 1 week after injury. At post-operative day (POD) 14, the patient started daily tension offloading treatment on the inferior portion of the incision through POD 120. By POD 120, the untreated portion of the Achilles incision appeared hypertrophic and hyperpigmented, while the treated portion of the scar appeared flat with minimal pigmentation changes. The 12-week treatment of tension offloading on an Achilles tendon repair incision significantly improved cosmesis compared to untreated incision.
An unusual case of complete pathological response to Paget’s disease of the breast
Authors: Okonofua Daisy , Soh Chien Lin , Tafazal Habib
Published: March 2022

Mammary Paget’s disease is a rare form of breast cancer present in ~0.5–2.8% of breast cancers. The patients have a poorer prognosis, and usually, the appropriate therapy is based on the pathologic findings of the mass and axillary staging. This report adds the outcomes of Paget’s disease following neoadjuvant chemotherapy to the literature by description of a case of a 48-year-old patient with Paget’s disease who had a complete pathological response to Paget’s disease of the breast following neoadjuvant chemotherapy.
Immune responses against different variants of SARS-CoV-2 including Omicron following 6 months of administration of heterologous prime-boost COVID-19 vaccine
Authors: Sapkal Gajanan , Kant Rajni , Dwivedi Gaurav , Sahay Rima R , Yadav Pragya D , Deshpande Gururaj R , Singh Rajeev , Nyayanit Dimpal A , Patil Deepak Y , Shete-Aich Anita M , Zaman Kamran , Chaudhari Anil K , Gupta Nivedita , Panda Samiran , Abraham Priya , Bhargava Balram
Published: March 2022

Comparative analysis at 1- and 6-month post-vaccination showed modest reduction in S1-RBD IgG antibody and NAb titers against B.1, Alpha, Beta and Delta variants in heterologous and homologous vaccine recipients groups. However, significant reduction in NAb titers against Omicron in vaccinees’ sera post-6 months underlines need for cautious prospective follow-up.
Stellar multiplicity and stellar rotation: insights from APOGEE
Authors: Daher Christine Mazzola , Badenes Carles , Tayar Jamie , Pinsonneault Marc , Koposov Sergey E , Kratter Kaitlin , Moe Maxwell , Anguiano Borja , Godoy-Rivera Diego , Majewski Steven , Carlberg Joleen K , Walker Matthew G , Buttry Rachel , Dixon Don , Serna Javier , Stassun Keivan G , De Lee Nathan , Hernández Jesús , Nitschelm Christian , Stringfellow Guy S , Troup Nicholas W
Published: March 2022

We measure rotational broadening in spectra taken by the Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey to characterize the relationship between stellar multiplicity and rotation. We create a sample of 2786 giants and 24 496 dwarfs with stellar parameters and multiple radial velocities from the APOGEE pipeline, projected rotation speeds vsin i determined from our own pipeline, and distances, masses, and ages measured by Sanders & Das. We use the statistical distribution of the maximum shift in the radial velocities, ΔRVmax, as a proxy for the close binary fraction to explore the interplay between stellar evolution, rotation, and multiplicity. Assuming that the minimum orbital period allowed is the critical period for Roche Lobe overflow and rotational synchronization, we calculate theoretical upper limits on expected vsin i and ΔRVmax values. These expectations agree with the positive correlation between the maximum ΔRVmax and vsin i values observed in our sample as a function of log(g). We find that the fast rotators in our sample have a high occurrence of short-period [log(P/d) ≲ 4] companions. We also find that old, rapidly rotating main-sequence stars have larger completeness-corrected close binary fractions than their younger peers. Furthermore, rapidly rotating stars with large ΔRVmax consistently show differences of 1–10 Gyr between the predicted gyrochronological and measured isochronal ages. These results point towards a link between rapid rotation and close binarity through tidal interactions. We conclude that stellar rotation is strongly correlated with stellar multiplicity in the field, and caution should be taken in the application of gyrochronology relations to cool stars.
A two-zone model as origin of hard TeV spectrum in extreme BL lacs
Authors: Aguilar-Ruiz E , Fraija N , Galván-Gámez A , Benítez E
Published: March 2022

The emission of the so-called extreme BL Lacs poses challenges to the particle acceleration models. The hardness of their spectrum, ≲ 2, in the high-energy band demands unusual parameters using the standard one-zone synchrotron self-Compton (SSC) model with a deficient magnetized plasma. Some authors use either two-zone or hadronic/lepto-hadronic models to relax these atypical values. In this work, we present a lepto-hadronic two-zone model to explain the multi-wavelength observations of the six best-known extreme BL Lacs. The very-high-energy gamma-ray observations are described by the photo-hadronic processes in a blob close to the AGN core and by SSC and external inverse Compton-processes in an outer blob. The photo-hadronic interactions occur when accelerated protons in the inner blob interact with annihilation line photons from a sub-relativistic pair plasma. The X-ray observations are described by synchrotron radiation from the outer blob. The parameter values found from the description of the spectral energy distribution for each object with our phenomenological model are similar to each other, and lie in the typical range reported in BL Lacs.