bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetic and molecular basis for improving heat stress tolerance in wheat
Authors: Sun Lv , Wen Jingjing , Peng Huiru , Yao Yingyin , Hu Zhaorong , Ni Zhongfu , Sun Qixin , Xin Mingming
Published: December 2021

Wheat production requires at least ~ 2.4% increase per year rate by 2050 globally to meet food demands. However, heat stress results in serious yield loss of wheat worldwide. Correspondingly, wheat has evolved genetic basis and molecular mechanisms to protect themselves from heat-induced damage. Thus, it is very urgent to understand the underlying genetic basis and molecular mechanisms responsive to elevated temperatures to provide important strategies for heat-tolerant varieties breeding. In this review, we focused on the impact of heat stress on morphology variation at adult stage in wheat breeding programs. We also summarize the recent studies of genetic and molecular factors regulating heat tolerance, including identification of heat stress tolerance related QTLs/genes, and the regulation pathway in response to heat stress. In addition, we discuss the potential ways to improve heat tolerance by developing new technologies such as genome editing. This review of wheat responses to heat stress may shed light on the understanding heat-responsive mechanisms, although the regulatory network of heat tolerance is still ambiguous in wheat.
Global Heritage, Religion, and Secularism
Authors: Rico Trinidad
Published: December 2021

Religion and spirituality have been scarcely addressed in heritage preservation history, discourse, and practice. More recently, increased interest in the intersections between the study of religion and heritage preservation in both academic studies and institutional initiatives highlight obstacles that the field has yet to overcome theoretically and methodologically. This Element surveys the convergences of religious and heritage traditions. It argues that the critical heritage turn has not adequately considered the legacy of secularism that underpins the history and contemporary practices of heritage preservation. This omission is what has left the field of heritage studies ill-equipped to support the study and management of a heritage of religion broadly construed.
Anti-Corruption Protests and University Students: Evidence from Russian Cities
Authors: Nikolayenko Olena
Published: December 2021

There are conflicting theoretical expectations regarding students' protest behaviour in contemporary autocracies. On the one hand, in line with a resource model of political participation, university students are more likely to protest than their peers without higher education. On the other hand, university students in autocracies might refrain from high-risk activism in exchange for their own financial well-being and career advancement. To address this debate, the article leverages data on anti-corruption protests organized by the opposition politician Alexei Navalny in March 2017. Results show that anti-corruption protests were larger in Russian cities with a larger university student population. Next, employing individual-level data from the fifth wave of the European Values Survey, multinomial logistic regression analysis demonstrates that university students participated in demonstrations at a higher rate than non-students of the same age. More broadly, these findings yield insights into subnational variation in mass mobilization in a repressive political regime.
Own-Party Bias: How Voters Evaluate Electoral Outcomes
Authors: Baekgaard Martin
Published: December 2021

A voluminous literature documents that citizens' perceptions of democracy are shaped by electoral victories and defeats, but what reasoning do citizens use to evaluate parties as winners or losers? Drawing on research on partisan-motivated reasoning, I propose an own-party bias in winner–loser evaluations according to which voters evaluate the electoral fate of their party more favourably than that of other parties. Data gathered in the aftermath of the Danish parliamentary election in 2015 support this expectation. Citizens are more inclined to interpret the election outcome as successful for their preferred party, regardless of the actual election result. This is more pronounced the stronger their partisan attachment and among the less politically knowledgeable, who also assign less importance to objective indicators of electoral success. The findings have implications for our understanding of electoral winners and losers and of how electoral results shape party support and polarization.
The evaluation of a training course to enhance intellectual disability awareness amongst law enforcement officers: a pilot study
Authors: Gulati Gautam , Cusack Alan , Murphy Valerie , Kelly Brendan D. , Kilcommins Shane , Dunne Colum P.
Published: December 2021

Objectives:

Disability awareness training is mandated by the United Nations Convention on People with Disabilities (UNCRPD), but there is a paucity of evidence regarding the systematic evaluation of the effectiveness of such training. This study describes the evaluation of a pilot intellectual disability awareness programme for law enforcement officers (LEOs) in Ireland.

Methods:

Pre-and post-training Likert scales and a semi-structured survey were used to evaluate the effectiveness of an intellectual disabilities awareness programme delivered to LEOs. Quantitative differences in Likert scores and thematic analyses of practice-based responses were used in evaluation.

Results:

Twenty-two LEOs participated in the training and 11 completed the evaluation cycle. Statistically significant improvements were found in participants’ self-rated knowledge of intellectual disability, their understanding of the challenges faced by people with intellectual disabilities in law enforcement interactions, their communication skills and their knowledge of how to approach a person with a disability in crisis. Thematic analysis excavated potential practical application of learning around pre-arrest considerations, recognition of disability, communication skills and need for procedural safeguards.

Conclusions:

An approach grounded in the views of people with intellectual disabilities and with emphasis on recognition of disability, communication, accessibility of information and providing appropriate support in custody, appears to promote improvement in self-reported knowledge and prospective application in LEOs. The findings of this study are potentially applicable to countries that have ratified the UNCRPD.
What are the letters e and é in a language with vowel reduction? The case of Catalan
Authors: Marcet Ana , Fernández-López María , Baciero Ana , Sesé Albert , Perea Manuel
Published: December 2021

Although the Latin-based orthographies of most Western languages employ vowels with accent marks (e.g., é vs. e), extant models of letter and word recognition are agnostic as to whether these accented letters and their non-accented counterparts are represented by common or separate abstract units. Recent research in French with a masked priming alphabetic decision task was interpreted as favoring the idea that accented and non-accented vowels are represented by separate abstract orthographic units (orthographic account: é↛e and e↛é; Chetail & Boursain, 2019). However, a more parsimonious explanation is that salient (accented) vowels are less perceptually similar to non-salient (non-accented) vowels than vice versa (perceptual account: e→é, but é↛e; Perea et al., 2021a; Tversky, 1977). To adjudicate between the two accounts, we conducted a masked priming alphabetic decision experiment in Catalan, a language with a complex orthography-to-phonology mapping for non-accented vowels (e.g., e→/e/, /ə/, /ε/). Results showed faster responses in the identity than in the visually similar condition for accented targets (é–É < e–É), but not for non-accented targets (e–E = é–E). Neither of the above accounts can fully capture this pattern. We propose an explanation based on the rapid activation of both orthographic and phonological codes.
General Practitioners’ Roles in Disaster Health Management: Perspectives of Disaster Managers
Authors: Burns Penelope L. , FitzGerald Gerard J. , Hu Wendy C. , Aitken Peter , Douglas Kirsty A.
Published: December 2021

Introduction:

General Practitioners (GPs) are inevitably involved when disaster strikes their communities. Evidence of health care needs in disasters increasingly suggests benefits from greater involvement of GPs, and recent research has clarified key roles. Despite this, GPs continue to be disconnected from disaster health management (DHM) in most countries.

Study Objective:

The aim of this study was to explore the perspectives of disaster management professionals in two countries, across a range of all-hazard disasters, regarding the roles and contributions of GPs to DHM, and to identify barriers to, and benefits of, more active engagement of GPs in disaster health care systems.

Methods:

A qualitative research methodology using semi-structured interviews was conducted with a purposive sample of Disaster Managers (DMs) to explore their perspectives arising from experiences and observations of GPs during disasters from 2009 through 2016 in Australia or New Zealand. These involved all-hazard disasters including natural, man-made, and pandemic disasters. Responses were analyzed using thematic analysis.

Results:

These findings document support from DM participants for greater integration of GPs into DHM with New Zealand DMs reporting GPs as already a valuable integrated contributor. In contrast, Australian DMs reported barriers to inclusion that needed to be addressed before sustained integration could occur. The two most strongly expressed barriers were universally expressed by Australian DMs: (1) limited understanding of the work GPs undertake, restricting DMs’ ability to facilitate GP integration; and (2) DMs’ difficulty engaging with GPs as a single group. Other considerations included GPs’ limited DHM knowledge, limited preparedness, and their heightened vulnerability.

Strategies identified to facilitate greater integration of GPs into DHM where it is lacking, such as Australia, included enhanced communication, awareness, and understanding between GPs and DMs.

Conclusion:

Experience from New Zealand shows systematic, sustained integration of GPs into DHM systems is achievable and valuable. Findings suggest key factors are collaboration between DMs and GPs at local, state, and national levels of DHM in planning and preparedness for the next disaster. A resilient health care system that maximizes capacity of all available local health resources in disasters and sustains them into the recovery should include General Practice.
Dynamic ecophenotypy in the Silurian Monograptidae (Graptolithina)
Authors: WHITTINGHAM Misha , SPIRIDONOV Andrej , RADZEVIČIUS Sigitas
Published: December 2021

The monograptids from the Wenlock and Ludlow (mid- to late Silurian) of the palaeotropical Baltic Basin exhibit thickened ring structures (sicular annuli) over their initial phase of growth. Appearing before the lundgreni extinction event, they persisted throughout the remainder of the Silurian, fluctuating in number over that period. To better understand the mechanisms controlling their development and variation, counts of sicular annuli were taken from three well cores in Lithuania, compared between species in each sample and compared with contemporaneous gamma ray data, accompanied by the stable isotope (δ13C), and acritarch diversity data. Mean counts of annuli fluctuated greatly over the studied interval, but showed negligible variation between species, indicating that the trait is ecophenotypic. The fluctuation in annulus presence aligned with variations in fourth- and fifth-order cycles derived from the gamma ray trends, which represent significant sea level fluctuations, δ13C ratios, and primary productivity, suggesting that annuli were more plentiful in high-stand states which are associated with the wetter climate and more productive conditions, whereas dryer, less productive conditions were not conducive to annulus development. In light of this evidence, we hypothesise that the action of upwelling as a result of intensified storm events during wetter periods would have encouraged phytoplankton blooms, increasing construction of annuli. These results show the potential utility of sicular annuli in the study of Silurian climate change and give new insights into graptolite palaeoecology.
Nationwide trends in prevalence of underweight, overweight, and obesity among people with disabilities in South Korea from 2008 to 2017
Authors: Lee Dong-Hwa , Kim So Young , Park Jong Eun , Jeon Hyun Jeong , Park Jong-Hyock , Kawachi Ichiro
Published: December 2021

Objectives

This study investigated the 10-year trends of weight and prevalence of underweight, overweight and obesity according to disability grade and types compared with those without disabilities.

Methods

This serial cross-sectional analysis was conducted using national disability registration data with national general health checkup data from 2008 to 2017. Age-standardized prevalence of underweight and obesity were analyzed for each year, according to the presence, type, and severity of disabilities. Odds of underweight, overweight, obesity, and severe obesity were examined by multinomial logistic regression after adjusting for socio-demographic and clinical variables using data in 2017.

Results

Over 10 million subjects in each year were included in the analysis. In 2017, 14,246,785 people with age between 19 and 110 years were included and 53.1% was men. For 10 years, age-standardized prevalence of obesity and severe obesity showed significant increases regardless of sex and presence of disability. However, age-standardized underweight prevalence in people without disability tended to decrease whereas it was an increase in 2012 and the prevalence has remained steady since in people with disability. People with disabilities had higher odds of underweight compared to those without disability (OR 1.41, 95% CI 1.38–1.44 in male and OR 1.31, 95% CI 1.28–1.34 in female), especially in those with severe disabilities (OR 2.00, 95% CI 1.94–2.06 in male and OR 1.83, 95% CI 1.77–1.89 in female). Women with disabilities are more likely to be obese than those without disabilities regardless of disability severity (OR 1.40, 95% CI 1.38–1.41). Participants with mental disorder showed the highest prevalence of obesity, followed by epilepsy and developmental disability.

Conclusions

Having a disability was associated with higher odds/probability of both obesity and underweight. The intersection of female, severe disability, and mental/developmental disabilities was associated with probability of severe obesity. Simultaneous efforts are needed to develop health policy to reduce both the prevalence of obesity and underweight.
Thermo-optically induced transparency on a photonic chip
Authors: Clementi Marco , Iadanza Simone , Schulz Sebastian A. , Urbinati Giulia , Gerace Dario , O’Faloain Liam , Galli Matteo
Published: December 2021

Controlling the optical response of a medium through suitably tuned coherent electromagnetic fields is highly relevant in a number of potential applications, from all-optical modulators to optical storage devices. In particular, electromagnetically induced transparency (EIT) is an established phenomenon in which destructive quantum interference creates a transparency window over a narrow spectral range around an absorption line, which, in turn, allows to slow and ultimately stop light due to the anomalous refractive index dispersion. Here we report on the observation of a new form of both induced transparency and amplification of a weak probe beam in a strongly driven silicon photonic crystal resonator at room temperature. The effect is based on the oscillating temperature field induced in a nonlinear optical cavity, and it reproduces many of the key features of EIT while being independent of either atomic or mechanical resonances. Such thermo-optically induced transparency will allow a versatile implementation of EIT-analogs in an integrated photonic platform, at almost arbitrary wavelength of interest, room temperature and in a practical, low cost, and scalable system.
Tumor-associated macrophages promote PD-L1 expression in tumor cells by regulating PKM2 nuclear translocation in pancreatic ductal adenocarcinoma
Authors: Xia Qing , Jia Jing , Hu Chupeng , Lu Jinying , Li Jiajin , Xu Haiyan , Fang Jianchen , Feng Dongju , Wang Liwei , Chen Yun
Published: December 2021

In many types of cancer, tumor cells prefer to use glycolysis as a major energy acquisition method. Here, we found that the 18fluoro-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-based markers were positively associated with the expression of programmed cell death ligand 1 (PD-L1), pyruvate kinase M2 (PKM2), both of which indicate poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the regulatory mechanism of PD-L1 remains elusive. In this study, we confirmed that transforming growth factor-beta1 (TGF-β1) secreted by tumor-associated macrophages (TAMs) was a key factor contributing to the expression of PD-L1 in PDAC cells by inducing the nuclear translocation of PKM2. Using co-immunoprecipitation and chromatin immunoprecipitation assays, we demonstrated that the interaction between PKM2 and signal transducer and activator of transcription 1 (STAT1) was enhanced by TGF-β1 stimulation, which facilitated the transactivation of PD-L1 by the binding of PKM2 and STAT1 to its promoter. In vivo, PKM2 knockdown decreased PD-L1 expression in PDAC cells and inhibited tumor growth partly by promoting natural killer cell activation and function, and the combination of PD-1/PD-L1 blockade with PKM2 knockdown limited tumor growth. In conclusion, PKM2 significantly contributes to TAM-induced PD-L1 overexpression and immunosuppression, providing a novel target for immunotherapies for PDAC.
Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors
Authors: Carter Angela M. , Kumar Nilesh , Herring Brendon , Tan Chunfeng , Guenter Rachael , Telange Rahul , Howse Wayne , Viol Fabrice , McCaw Tyler R. , Bickerton Hayden H. , Gupta Priyanka , Gillardon Frank , Woltering Eugene A. , Dhall Deepti , Totenhagen John , Banerjee Ronadip R. , Kurian Elizabeth M. , Reddy Sushanth , Chen Herbert , Schrader Joerg , Bart Rose J. , Mukhtar M. Shahid , Bibb James A.
Published: December 2021

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bi-transgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in β-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. The utility of this model is enhanced by the ability to form tumor-derived allografts. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.
Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver
Authors: Zhong Liping , Huang Yong , He Jian , Yang Nuo , Xu Banghao , Ma Yun , Liu Junjie , Tang Chao , Luo Chengpiao , Wu Pan , Lai Zongqiang , Huo Yu , Lu Tao , Huang Dongni , Gong Wenlin , Gan Lu , Luo Yiqun , Zhang Zhikun , Liu Xiyu , Zhao Yongxiang
Published: December 2021

Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.
Millimeter-scale vertical partitioning of nitrogen cycling in hypersaline mats reveals prominence of genes encoding multi-heme and prismane proteins
Authors: Maza-Márquez P , Lee M D , Detweiler A M , Bebout B M
Published: December 2021

Microbial mats are modern analogues of the first ecosystems on the Earth. As extant representatives of microbial communities where free oxygen may have first been available on a changing planet, they offer an ecosystem within which to study the evolution of biogeochemical cycles requiring and inhibited by oxygen. Here, we report the distribution of genes involved in nitrogen metabolism across a vertical oxygen gradient at 1 mm resolution in a microbial mat using quantitative PCR (qPCR), retro-transcribed qPCR (RT-qPCR) and metagenome sequencing. Vertical patterns in the presence and expression of nitrogen cycling genes, corresponding to oxygen requiring and non-oxygen requiring nitrogen metabolism, could be seen across gradients of dissolved oxygen and ammonium. Metagenome analysis revealed that genes annotated as hydroxylamine dehydrogenase (proper enzyme designation EC 1.7.2.6, hao) and hydroxylamine reductase (hcp) were the most abundant nitrogen metabolism genes in the mat. The recovered hao genes encode hydroxylamine dehydrogenase EC 1.7.2.6 (HAO) proteins lacking the tyrosine residue present in aerobic ammonia oxidizing bacteria (AOB). Phylogenetic analysis confirmed that those proteins were more closely related to ɛHao protein present in Campylobacterota lineages (previously known as Epsilonproteobacteria) rather than oxidative HAO of AOB. The presence of hao sequences related with ɛHao protein, as well as numerous hcp genes encoding a prismane protein, suggest the presence of a nitrogen cycling pathway previously described in Nautilia profundicola as ancestral to the most commonly studied present day nitrogen cycling pathways.
The caspase-6–p62 axis modulates p62 droplets based autophagy in a dominant-negative manner
Authors: Valionyte Evelina , Yang Yi , Griffiths Sophie A. , Bone Amelia T. , Barrow Elizabeth R. , Sharma Vikram , Lu Boxun , Luo Shouqing
Published: December 2021

SQSTM1/p62, as a major autophagy receptor, forms droplets that are critical for cargo recognition, nucleation, and clearance. p62 droplets also function as liquid assembly platforms to allow the formation of autophagosomes at their surfaces. It is unknown how p62-droplet formation is regulated under physiological or pathological conditions. Here, we report that p62-droplet formation is selectively blocked by inflammatory toxicity, which induces cleavage of p62 by caspase-6 at a novel cleavage site D256, a conserved site across human, mouse, rat, and zebrafish. The N-terminal cleavage product is relatively stable, whereas the C-terminal product appears undetectable. Using a variety of cellular models, we show that the p62 N-terminal caspase-6 cleavage product (p62-N) plays a dominant-negative role to block p62-droplet formation. In vitro p62 phase separation assays confirm this observation. Dominant-negative regulation of p62-droplet formation by caspase-6 cleavage attenuates p62 droplets dependent autophagosome formation. Our study suggests a novel pathway to modulate autophagy through the caspase-6–p62 axis under certain stress stimuli.
Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ)
Authors: Degtjarik Oksana , Golovenko Dmitrij , Diskin-Posner Yael , Abrahmsén Lars , Rozenberg Haim , Shakked Zippora
Published: December 2021

In response to genotoxic stress, the tumor suppressor p53 acts as a transcription factor by regulating the expression of genes critical for cancer prevention. Mutations in the gene encoding p53 are associated with cancer development. PRIMA-1 and eprenetapopt (APR-246/PRIMA-1MET) are small molecules that are converted into the biologically active compound, methylene quinuclidinone (MQ), shown to reactivate mutant p53 by binding covalently to cysteine residues. Here, we investigate the structural basis of mutant p53 reactivation by MQ based on a series of high-resolution crystal structures of cancer-related and wild-type p53 core domains bound to MQ in their free state and in complexes with their DNA response elements. Our data demonstrate that MQ binds to several cysteine residues located at the surface of the core domain. The structures reveal a large diversity in MQ interaction modes that stabilize p53 and its complexes with DNA, leading to a common global effect that is pertinent to the restoration of non-functional p53 proteins.
Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma
Authors: Zoumpoulidou Georgia , Alvarez-Mendoza Carlos , Mancusi Caterina , Ahmed Ritika-Mahmuda , Denman Milly , Steele Christopher D. , Tarabichi Maxime , Roy Errin , Davies Lauren R. , Manji Jiten , Cristalli Camilla , Scotlandi Katia , Pillay Nischalan , Strauss Sandra J. , Mittnacht Sibylle
Published: December 2021

Loss-of-function mutations in the RB1 tumour suppressor are key drivers in cancer, including osteosarcoma. RB1 loss-of-function compromises genome-maintenance and hence could yield vulnerability to therapeutics targeting such processes. Here we demonstrate selective hypersensitivity to clinically-approved inhibitors of Poly-ADP-Polymerase1,2 inhibitors (PARPi) in RB1-defective cancer cells, including an extended panel of osteosarcoma-derived lines. PARPi treatment results in extensive cell death in RB1-defective backgrounds and prolongs survival of mice carrying human RB1-defective osteosarcoma grafts. PARPi sensitivity is not associated with canonical homologous recombination defect (HRd) signatures that predict PARPi sensitivity in cancers with BRCA1,2 loss, but is accompanied by rapid activation of DNA replication checkpoint signalling, and active DNA replication is a prerequisite for sensitivity. Importantly, sensitivity in backgrounds with natural or engineered RB1 loss surpasses that seen in BRCA-mutated backgrounds where PARPi have established clinical benefit. Our work provides evidence that PARPi sensitivity extends beyond cancers identifiable by HRd and advocates PARP1,2 inhibition as a personalised strategy for RB1-mutated osteosarcoma and other cancers.
DeepRank: a deep learning framework for data mining 3D protein-protein interfaces
Authors: Renaud Nicolas , Geng Cunliang , Georgievska Sonja , Ambrosetti Francesco , Ridder Lars , Marzella Dario F. , Réau Manon F. , Bonvin Alexandre M. J. J. , Xue Li C.
Published: December 2021

Three-dimensional (3D) structures of protein complexes provide fundamental information to decipher biological processes at the molecular scale. The vast amount of experimentally and computationally resolved protein-protein interfaces (PPIs) offers the possibility of training deep learning models to aid the predictions of their biological relevance. We present here DeepRank, a general, configurable deep learning framework for data mining PPIs using 3D convolutional neural networks (CNNs). DeepRank maps features of PPIs onto 3D grids and trains a user-specified CNN on these 3D grids. DeepRank allows for efficient training of 3D CNNs with data sets containing millions of PPIs and supports both classification and regression. We demonstrate the performance of DeepRank on two distinct challenges: The classification of biological versus crystallographic PPIs, and the ranking of docking models. For both problems DeepRank is competitive with, or outperforms, state-of-the-art methods, demonstrating the versatility of the framework for research in structural biology.
Bayesian optimization with adaptive surrogate models for automated experimental design
Authors: Lei Bowen , Kirk Tanner Quinn , Bhattacharya Anirban , Pati Debdeep , Qian Xiaoning , Arroyave Raymundo , Mallick Bani K.
Published: December 2021

Bayesian optimization (BO) is an indispensable tool to optimize objective functions that either do not have known functional forms or are expensive to evaluate. Currently, optimal experimental design is always conducted within the workflow of BO leading to more efficient exploration of the design space compared to traditional strategies. This can have a significant impact on modern scientific discovery, in particular autonomous materials discovery, which can be viewed as an optimization problem aimed at looking for the maximum (or minimum) point for the desired materials properties. The performance of BO-based experimental design depends not only on the adopted acquisition function but also on the surrogate models that help to approximate underlying objective functions. In this paper, we propose a fully autonomous experimental design framework that uses more adaptive and flexible Bayesian surrogate models in a BO procedure, namely Bayesian multivariate adaptive regression splines and Bayesian additive regression trees. They can overcome the weaknesses of widely used Gaussian process-based methods when faced with relatively high-dimensional design space or non-smooth patterns of objective functions. Both simulation studies and real-world materials science case studies demonstrate their enhanced search efficiency and robustness.
Mental imagery of object motion in weightlessness
Authors: Gravano Silvio , Lacquaniti Francesco , Zago Myrka
Published: December 2021

Mental imagery represents a potential countermeasure for sensorimotor and cognitive dysfunctions due to spaceflight. It might help train people to deal with conditions unique to spaceflight. Thus, dynamic interactions with the inertial motion of weightless objects are only experienced in weightlessness but can be simulated on Earth using mental imagery. Such training might overcome the problem of calibrating fine-grained hand forces and estimating the spatiotemporal parameters of the resulting object motion. Here, a group of astronauts grasped an imaginary ball, threw it against the ceiling or the front wall, and caught it after the bounce, during pre-flight, in-flight, and post-flight experiments. They varied the throwing speed across trials and imagined that the ball moved under Earth’s gravity or weightlessness. We found that the astronauts were able to reproduce qualitative differences between inertial and gravitational motion already on ground, and further adapted their behavior during spaceflight. Thus, they adjusted the throwing speed and the catching time, equivalent to the duration of virtual ball motion, as a function of the imaginary 0 g condition versus the imaginary 1 g condition. Arm kinematics of the frontal throws further revealed a differential processing of imagined gravity level in terms of the spatial features of the arm and virtual ball trajectories. We suggest that protocols of this kind may facilitate sensorimotor adaptation and help tuning vestibular plasticity in-flight, since mental imagery of gravitational motion is known to engage the vestibular cortex.
A third SARS-CoV-2 spike vaccination improves neutralization of variants-of-concern
Authors: Brinkkemper Mitch , Brouwer Philip J. M. , Maisonnasse Pauline , Grobben Marloes , Caniels Tom G. , Poniman Meliawati , Burger Judith A. , Bontjer Ilja , Oomen Melissa , Bouhuijs Joey H. , van der Linden Cynthia A. , Villaudy Julien , van der Velden Yme U. , Sliepen Kwinten , van Gils Marit J. , Le Grand Roger , Sanders Rogier W.
Published: December 2021

The emergence of SARS-CoV-2 variants that are more resistant to antibody-mediated neutralization pose a new hurdle in combating the COVID-19 pandemic. Although vaccines based on the original Wuhan sequence have been shown to be effective at preventing COVID-19, their efficacy is likely to be decreased against more neutralization-resistant variants-of-concern (VOC), in particular, the Beta variant originating in South Africa. We assessed, in mice, rabbits, and non-human primates, whether a third vaccination with experimental Wuhan-based Spike vaccines could alleviate this problem. Our data show that a third immunization improves neutralizing antibody titers against the variants-of-concern, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). After three vaccinations, the level of neutralization against Beta was similar to the level of neutralization against the original strain after two vaccinations, suggesting that simply providing a third immunization could nullify the reduced activity of current vaccines against VOC.
A salty deep ocean as a prerequisite for glacial termination
Authors: Knorr Gregor , Barker Stephen , Zhang Xu , Lohmann Gerrit , Gong Xun , Gierz Paul , Stepanek Christian , Stap Lennert B.
Published: December 2021

Deglacial transitions of the middle to late Pleistocene (terminations) are linked to gradual changes in insolation accompanied by abrupt shifts in ocean circulation. However, the reason these deglacial abrupt events are so special compared with their sub-glacial-maximum analogues, in particular with respect to the exaggerated warming observed across Antarctica, remains unclear. Here we show that an increase in the relative importance of salt versus temperature stratification in the glacial deep South Atlantic decreases the potential cooling effect of waters that may be upwelled in response to abrupt perturbations in ocean circulation, as compared with sub-glacial-maximum conditions. Using a comprehensive coupled atmosphere–ocean general circulation model, we then demonstrate that an increase in deep-ocean salinity stratification stabilizes relatively warm waters in the glacial deep ocean, which amplifies the high southern latitude surface ocean temperature response to an abrupt weakening of the Atlantic meridional overturning circulation during deglaciation. The mechanism can produce a doubling in the net rate of warming across Antarctica on a multicentennial timescale when starting from full glacial conditions (as compared with interglacial or subglacial conditions) and therefore helps to explain the large magnitude and rapidity of glacial terminations during the late Quaternary.
Micro-Meta App: an interactive tool for collecting microscopy metadata based on community specifications
Authors: Rigano Alessandro , Ehmsen Shannon , Öztürk Serkan Utku , Ryan Joel , Balashov Alexander , Hammer Mathias , Kirli Koray , Boehm Ulrike , Brown Claire M. , Bellve Karl , Chambers James J. , Cosolo Andrea , Coleman Robert A. , Faklaris Orestis , Fogarty Kevin E. , Guilbert Thomas , Hamacher Anna B. , Itano Michelle S. , Keeley Daniel P. , Kunis Susanne , Lacoste Judith , Laude Alex , Ma Willa Y. , Marcello Marco , Montero-Llopis Paula , Nelson Glyn , Nitschke Roland , Pimentel Jaime A. , Weidtkamp-Peters Stefanie , Park Peter J. , Alver Burak H. , Grunwald David , Strambio-De-Castillia Caterina
Published: December 2021

For quality, interpretation, reproducibility and sharing value, microscopy images should be accompanied by detailed descriptions of the conditions that were used to produce them. Micro-Meta App is an intuitive, highly interoperable, open-source software tool that was developed in the context of the 4D Nucleome (4DN) consortium and is designed to facilitate the extraction and collection of relevant microscopy metadata as specified by the recent 4DN-BINA-OME tiered-system of Microscopy Metadata specifications. In addition to substantially lowering the burden of quality assurance, the visual nature of Micro-Meta App makes it particularly suited for training purposes.
Soundscape and ambient noise levels of the Arctic waters around Greenland
Authors: Ladegaard Michael , Macaulay Jamie , Simon Malene , Laidre Kristin L. , Mitseva Aleksandrina , Videsen Simone , Pedersen Michael Bjerre , Tougaard Jakob , Madsen Peter Teglberg
Published: December 2021

A longer Arctic open water season is expected to increase underwater noise levels due to anthropogenic activities such as shipping, seismic surveys, sonar, and construction. Many Arctic marine mammal species depend on sound for communication, navigation, and foraging, therefore quantifying underwater noise levels is critical for documenting change and providing input to management and legislation. Here we present long-term underwater sound recordings from 26 deployments around Greenland from 2011 to 2020. Ambient noise was analysed in third octave and decade bands and further investigated using generic detectors searching for tonal and transient sounds. Ambient noise levels partly overlap with previous Arctic observations, however we report much lower noise levels than previously documented, specifically for Melville Bay and the Greenland Sea. Consistent seasonal noise patterns occur in Melville Bay, Baffin Bay and Greenland Sea, with noise levels peaking in late summer and autumn correlating with open water periods and seismic surveys. These three regions also had similar tonal detection patterns that peaked in May/June, likely due to bearded seal vocalisations. Biological activity was more readily identified using detectors rather than band levels. We encourage additional research to quantify proportional noise contributions from geophysical, biological, and anthropogenic sources in Arctic waters.
Cotton soot derived carbon nanoparticles for NiO supported processing temperature tuned ambient perovskite solar cells
Authors: Bhandari Shubhranshu , Roy Anurag , Ali Mir Sahidul , Mallick Tapas Kumar , Sundaram Senthilarasu
Published: December 2021

The emergence of perovskite solar cells (PSCs) in a "catfish effect" of other conventional photovoltaic technologies with the massive growth of high-power conversion efficiency (PCE) has given a new direction to the entire solar energy field. Replacing traditional metal-based electrodes with carbon-based materials is one of the front-runners among many other investigations in this field due to its cost-effective processability and high stability. Carbon-based perovskite solar cells (c-PSCs) have shown great potential for the development of large scale photovoltaics. First of its kind, here we introduce a facile and cost-effective large scale carbon nanoparticles (CNPs) synthesis from mustard oil assisted cotton combustion for utilization in the mesoporous carbon-based perovskite solar cell (PSC). Also, we instigate two different directions of utilizing the carbon nanoparticles for a composite high temperature processed electrode (HTCN) and a low temperature processed electrode (LTCN) with detailed performance comparison. NiO/CNP composite thin film was used in high temperature processed electrodes, and for low temperature processed electrodes, separate NiO and CNP layers were deposited. The HTCN devices with the cell structure FTO/c-TiO2/m-TiO2/m-ZrO2/high-temperature NiO-CNP composite paste/infiltrated MAPI (CH3NH3PbI3) achieved a maximum PCE of 13.2%. In addition, high temperature based carbon devices had remarkable stability of ~ 1000 h (ambient condition), retaining almost 90% of their initial efficiency. In contrast, LTCN devices with configuration FTO/c-TiO2/m-TiO2/m-ZrO2/NiO/MAPI/low-temperature CNP had a PCE limit of 14.2%, maintaining ~ 72% of the initial PCE after 1000 h. Nevertheless, we believe this promising approach and the comparative study between the two different techniques would be highly suitable and adequate for the upcoming cutting-edge experimentations of PSC.
A robust approach for industrial small-object detection using an improved faster regional convolutional neural network
Authors: Saeed Faisal , Ahmed Muhammad Jamal , Gul Malik Junaid , Hong Kim Jeong , Paul Anand , Kavitha Muthu Subash
Published: December 2021

With the increasing pace in the industrial sector, the need for a smart environment is also increasing and the production of industrial products in terms of quality always matters. There is a strong burden on the industrial environment to continue to reduce impulsive downtime, concert deprivation, and safety risks, which needs an efficient solution to detect and improve potential obligations as soon as possible. The systems working in industrial environments for generating industrial products are very fast and generate products rapidly, sometimes leading to faulty products. Therefore, this problem needs to be solved efficiently. Considering this problem in terms of faulty small-object detection, this study proposed an improved faster regional convolutional neural network-based model to detect the faults in the product images. We introduced a novel data-augmentation method along with a bi-cubic interpolation-based feature amplification method. A center loss is also introduced in the loss function to decrease the inter-class similarity issue. The experimental results show that the proposed improved model achieved better classification accuracy for detecting our small faulty objects. The proposed model performs better than the state-of-the-art methods.
Enlargement of female pupils when perceiving something cute
Authors: Kuraguchi Kana , Kanari Kei
Published: December 2021

It is reported that women’s pupils dilate when they see a baby; it is unclear if this pupillary response is caused by the perception of cuteness itself. Since many objects besides babies can be perceived as cute, we investigated whether the perception of cuteness, or the type of object observed, is related to pupil dilation. In the first experiment, female participants were requested to rate the subjective cuteness of greyscale pictures of objects such as animals and foods; their pupil sizes were measured. The results showed a significant positive correlation between perceived cuteness and participants’ pupil dilation. In the second experiment, participants rated the cuteness of images of female faces. Results revealed a significant negative correlation between perceived cuteness and pupil dilation. In our study, perceiving cuteness enlarged female observers’ pupils except when observing female faces. Positive reactions associated with cuteness may be premised on the existence of unconscious perceptual alterations and physical responses.
Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity
Authors: Dy Alane Blythe C. , Langlais Paul R. , Barker Natalie K. , Addison Kenneth J. , Tanyaratsrisakul Sasipa , Boitano Scott , Christenson Stephanie A. , Kraft Monica , Meyers Deborah , Bleecker Eugene R. , Li Xingnan , Ledford Julie G.
Published: December 2021

Surfactant protein A (SP-A) is well-known for its protective role in pulmonary immunity. Previous studies from our group have shown that SP-A mediates eosinophil activities, including degranulation and apoptosis. In order to identify potential binding partners on eosinophils for SP-A, eosinophil lysates were subjected to SP-A pull-down and tandem mass spectrometry (MS/MS) analysis. We identified one membrane-bound protein, myeloid-associated differentiation marker (MYADM), as a candidate SP-A binding partner. Blocking MYADM on mouse and human eosinophils ex vivo prevented SP-A from inducing apoptosis; blocking MYADM in vivo led to increased persistence of eosinophilia and airway hyper-responsiveness in an ovalbumin (OVA) allergy model and increased airways resistance and mucus production in a house dust mite (HDM) asthma model. Examination of a subset of participants in the Severe Asthma Research Program (SARP) cohort revealed a significant association between epithelial expression of MYADM in asthma patients and parameters of airway inflammation, including: peripheral blood eosinophilia, exhaled nitric oxide (FeNO) and the number of exacerbations in the past 12 months. Taken together, our studies provide the first evidence of MYADM as a novel SP-A-associated protein that is necessary for SP-A to induce eosinophil apoptosis and we bring to light the potential importance of this previously unrecognized transmembrane protein in patients with asthma.
The importance of selecting the correct site to apply spinal manipulation when treating spinal pain: Myth or reality? A systematic review
Authors: Nim Casper G. , Downie Aron , O’Neill Søren , Kawchuk Gregory N. , Perle Stephen M. , Leboeuf-Yde Charlotte
Published: December 2021

The concept that spinal manipulation therapy (SMT) outcomes are optimized when the treatment is aimed at a clinically relevant joint is commonly assumed and central to teaching and clinical use (candidate sites). This systematic review investigated whether clinical effects are superior when this is the case compared to SMT applied elsewhere (non-candidate sites). Eligible study designs were randomized controlled trials that investigated the effect of spinal manipulation applied to candidate versus non-candidate sites for spinal pain. We obtained data from four different databases. Risk of bias was assessed using an adjusted Cochrane risk of bias tool, adding four items for study quality. We extracted between-group differences for any reported outcome or, when not reported, calculated effect sizes from the within-group changes. We compared outcomes for SMT applied at a ‘relevant’ site to SMT applied elsewhere. We prioritized methodologically robust studies when interpreting results. Ten studies, all of acceptable quality, were included that reported 33 between-group differences—five compared treatments within the same spinal region and five at different spinal regions. None of the nine studies with low or moderate risk of bias reported statistically significant between-group differences for any outcome. The tenth study reported a small effect on pain (1.2/10, 95%CI − 1.9 to − 0.5) but had a high risk of bias. None of the nine articles of low or moderate risk of bias and acceptable quality reported that “clinically-relevant” SMT has a superior outcome on any outcome compared to “not clinically-relevant” SMT. This finding contrasts with ideas held in educational programs and clinical practice that emphasize the importance of joint-specific application of SMT.