bluuebunny/crossref_metadata_2025 huggingface dataset:
Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer
Authors: Brown Benjamin P. , Zhang Yun-Kai , Kim Soyeon , Finneran Patrick , Yan Yingjun , Du Zhenfang , Kim Jiyoon , Hartzler Abigail Leigh , LeNoue-Newton Michele L. , Smith Adam W. , Meiler Jens , Lovly Christine M.
Published: July 2022

Oncogenic mutations within the epidermal growth factor receptor (EGFR) are found in 15 to 30% of all non–small-cell lung carcinomas. The term exon 19 deletion (ex19del) is collectively used to refer to more than 20 distinct genomic alterations within exon 19 that comprise the most common EGFR mutation subtype in lung cancer. Despite this heterogeneity, clinical treatment decisions are made irrespective of which EGFR ex19del variant is present within the tumor, and there is a paucity of information regarding how individual ex19del variants influence protein structure and function. Herein, we identified allele-specific functional differences among ex19del variants attributable to recurring sequence and structure motifs. We built all-atom structural models of 60 ex19del variants identified in patients and combined molecular dynamics simulations with biochemical and biophysical experiments to analyze three ex19del mutations (E746_A750, E746_S752 > V, and L747_A750 > P). We demonstrate that sequence variation in ex19del alters oncogenic cell growth, dimerization propensity, enzyme kinetics, and tyrosine kinase inhibitor (TKI) sensitivity. We show that in contrast to E746_A750 and E746_S752 > V, the L747_A750 > P variant forms highly active ligand-independent dimers. Enzyme kinetic analysis and TKI inhibition experiments suggest that E746_S752 > V and L747_A750 > P display reduced TKI sensitivity due to decreased adenosine 5′-triphosphate
K
m
. Through these analyses, we propose an expanded framework for interpreting ex19del variants and considerations for therapeutic intervention.
Multiple dimeric structures and strand-swap dimerization of E-cadherin in solution visualized by high-speed atomic force microscopy
Authors: Nishiguchi Shigetaka , Furuta Tadaomi , Uchihashi Takayuki
Published: July 2022

Classical cadherins play key roles in cell–cell adhesion. The adhesion process is thought to comprise mainly two steps: X-dimer and strand-swap (SS-) dimer formation of the extracellular domains (ectodomains) of cadherins. The dimerization mechanism of this two-step process has been investigated for type I cadherins, including E-cadherin, of classical cadherins, whereas other binding states also have been proposed, raising the possibility of additional binding processes required for the cadherin dimerization. However, technical limitations in observing single-molecule structures and their dynamics have precluded the investigation of the dynamic binding process of cadherin. Here, we used high-speed atomic force microscopy (HS-AFM) to observe full-length ectodomains of E-cadherin in solution and identified multiple dimeric structures that had not been reported previously. HS-AFM revealed that almost half of the cadherin dimers showed S- (or reverse S-) shaped conformations, which had more dynamic properties than the SS- and X-like dimers. The combined HS-AFM, mutational, and molecular modeling analyses showed that the S-shaped dimer was formed by membrane-distal ectodomains, while the binding interface was different from that of SS- and X-dimers. Furthermore, the formation of the SS-dimer from the S-shaped and X-like dimers was directly visualized, suggesting the processes of SS-dimer formation from S-shaped and X-dimers during cadherin dimerization.
Assessing the Publication Output in the Field of Forensic Science and Legal Medicine using Web of Science Database from 2011 to 2020
Authors: Öner Bedirhan Sezer , Orbay Metin
Published: July 2022

The aim of this study was threefold. First, it analyzed the characteristics of the publication outputs for the Legal Medicine (LM) category using the Web of Science (WoS) database during 2011–2020. Second, it discussed the distribution of the papers for the 25 most productive countries/regions in terms of quality and quantity, such as the h-index and GDP per capita. Finally, it investigated the trend and temporal stability of the journal impact factor (JIF) and determined the percentage of the journal self-citations. The findings suggested that the number of papers, the average number of pages of the papers, the average number of cited references in the papers, the average number of authors per paper, the percentage of open access papers, as well as international and domestic collaboration tended to increase regularly. However, the productivity was limited when compared to the whole WoS database, since there was no significant change in the number of the journals. The countries/regions with the highest number of publications were not those that made the most impact in terms of the widespread impact of the publications. The level of international cooperation and the funding for the research had dramatic impact on the visibility of papers. The average JIF has increased significantly while the journal self-citation rates have decreased in a similar way. The journals have had very stable (have not fluctuated) impact factors over time. During the period studied, the journals with the higher impact factors (Q1, Q2) published many more papers than journals with the lower impact factors (Q3, Q4).
Few shot cross equipment fault diagnosis method based on parameter optimization and feature mertic
Authors: Tao Hongfeng , Cheng Long , Qiu Jier , Stojanovic Vladimir
Published: July 2022

With the rapid development of industrial informatization and deep learning technology, modern data-driven fault diagnosis (MIFD) methods based on deep learning have been receiving attention from the industry. However, most of these methods require sufficient training samples to achieve the desired diagnostic effect, and the scarcity of fault samples in the actual industrial environment leads to the limitation of the development of MIFD methods. In addition, data-driven fault diagnosis methods often need to face cross-load or even cross-domain problems across different devices due to changes in equipment operating conditions and production requirements. In this paper, we design a parameter optimization and feature metric-based fault diagnosis method with few samples, called model unknown matching network model, for the problem of sparse fault samples and cross-domain between data sets in real industrial environments. The method combines both a parametric optimization-based meta-learning network, which extracts optimization information to adapt between different domains, and a metric-based metric learning network, which extracts metric information for similarity discriminations. The experimental results show that the method outperforms the current baseline method for the five-shot fault diagnosis problem of bearings under limited data conditions and achieves an accuracy of up to 94.4

%

in cross-device diagnosis experiments from bearings to gas regulators, indicating the feasibility of the method. The features are visualized by T-SNE to show the validity of the model.
On the relativistic conveyor belt
Authors: Güémez J , González-Lavín J
Published: July 2022

A relativistic four-vector fundamental equation formalism is used to analyse processes that are carried out on a conveyor belt, in reference frames S (with the conveyor belt at rest, ground) and

S

¯

(moving conveyor belt frame); these processes involve thermal effects. Examples solved are: a block thrown with initial speed on an inclined plane conveyor belt, and a ring launched with initial linear velocity on a moving belt. For each process, a four-vector fundamental equation is obtained, first in frame S, and then it is transformed by the Lorentz transformation to the process’ four-vector fundamental equation in

S

¯

. It is shown that Newton’s second law and the first law of thermodynamics are no-independent equations. In this description, Newton’s second law in frame

S

¯

, in which forces are non simultaneously applied, includes terms related to linear momentum for heat (relativistic Doppler effect). The first law of thermodynamics in

S

¯

includes the motor’s performed work to keep the belt moving at a constant speed (conveyor belt effect). Classical descriptions of processes are obtained by taking the relativistic equations’ low-speed limit, keeping the conveyor belt effect.
Joule heating in the mid-latitude ionosphere by high power HF radio waves
Authors: Birba M , Prokopiou I , Veldes G P
Published: July 2022

We present an estimation of the heating rate due to Joule heating in the F region of the ionosphere as a result of its interaction with high-power HF O-mode radio waves transmitted by a ground-based antenna. We refer to experiments conducted at Platteville, Colorado in the 70’s, i.e., at a mid-latitude ionosphere, as the ionospheric conditions and experimental facility parameters are well known. Analytical expressions for the electric field of the HF wave, ionospheric electric conductivity and heating rate are inserted into the calculations. The subsequent spatial and temporal changes in electron and ion temperatures were estimated. The results show that the electron temperatures demonstrate an increase of 115% above their unperturbed values and the ion temperatures demonstrate a corresponding increase of 13%.
New constraints on axion-gauge field dynamics during inflation from Planck and BICEP/Keck data sets
Authors: Campeti Paolo , Özsoy Ogan , Obata Ippei , Shiraishi Maresuke
Published: July 2022

We present new constraints on spectator axion-U(1) gauge field interactions during
inflation using the latest Planck (PR4) and BICEP/Keck 2018 data releases. This model can source
tensor perturbations from amplified gauge field fluctuations, driven by an axion rolling for a few
e-folds during inflation. The gravitational waves sourced in this way have a strongly
scale-dependent (and chiral) spectrum, with potentially visible contributions to
large/intermediate scale B-modes of the CMB. We first derive theoretical bounds on the model
imposing validity of the perturbative regime and negligible backreaction of the gauge field on the
background dynamics. Then, we determine bounds from current CMB observations, adopting a
frequentist profile likelihood approach. We study the behaviour of constraints for typical choices
of the model's parameters, analyzing the impact of different dataset combinations. We find that
observational bounds are competitive with theoretical ones and together they exclude a significant
portion of the model's parameter space. We argue that the parameter space still remains large and
interesting for future CMB experiments targeting large/intermediate scales B-modes.
The SAGEX review on scattering amplitudes*
Authors: Travaglini Gabriele , Brandhuber Andreas , Dorey Patrick , McLoughlin Tristan , Abreu Samuel , Bern Zvi , Bjerrum-Bohr N Emil J , Blümlein Johannes , Britto Ruth , Carrasco John Joseph M , Chicherin Dmitry , Chiodaroli Marco , Damgaard Poul H , Del Duca Vittorio , Dixon Lance J , Dorigoni Daniele , Duhr Claude , Geyer Yvonne , Green Michael B , Herrmann Enrico , Heslop Paul , Johansson Henrik , Korchemsky Gregory P , Kosower David A , Mason Lionel , Monteiro Ricardo , O’Connell Donal , Papathanasiou Georgios , Planté Ludovic , Plefka Jan , Puhm Andrea , Raclariu Ana-Maria , Roiban Radu , Schneider Carsten , Trnka Jaroslav , Vanhove Pierre , Wen Congkao , White Chris D
Published: July 2022

This is an introduction to, and invitation to read, a series of review articles on scattering amplitudes in gauge theory, gravity, and superstring theory. Our aim is to provide an overview of the field, from basic aspects to a selection of current (2022) research and developments.
Replication of spatial patterns with reversible and additive cellular automata
Authors: García-Morales Vladimir
Published: July 2022

In this article, the replication of arbitrary patterns by reversible and additive cellular automata is reported. The orbit of an 1D cellular automaton operating on p symbols that is both additive and reversible is explicitly given in terms of coefficients that appear in the theory of Gegenbauer polynomials. It is shown that if p is an odd prime, the pattern formed after (p − 1)/2 time steps from any arbitrary initial condition (spatially confined to a region of side less than p) replicates after p + (p − 1)/2 time steps in a way that resembles budding in biological systems.
Machining studies on Monel K − 500 using TiAlN coated tungsten carbide inserts under Ag nanoparticles incorporated modified pongamia pinnata oil lubrication
Authors: Emmanual L , Loganathan M , Karthikeyan T
Published: July 2022

Research investigations conducted in the past has shown that conventional petroleum based lubricants can be replaced with vegetable lubricants. Vegetable oil lubricants do not pollute the environment, as they are biodegradable. In this investigation, pongamia pinnata oil was used as lubricant, to during turning experiments. The physico chemical properties of modified pongamia pinnata oil were evaluated. Ag Nanoparticles were incorporated into the modified pongamia pinnata oil and it was subjected to tribological investigations. In this investigation, the effect of Ag nanoparticles in improving the lubricating aspects of the modified pongamia pinnata oil was studied. The aim of this investigation is to identify the effect of the nanoparticle incorporated bio- lubricant coolant on Monel K 500. In this study, using TiAlN coated triangular tungsten carbide inserts, Monel K 500 was subjected to turning under three conditions such as dry, minimum quantity lubrication and Ag nanoparticles incorporated vegetable oil lubrication. It was observed that the properties of the bio lubricant affected the turning output responses to such as cutting force, machining temperature, tool wear and surface roughness of the workpiece (Monel K 500). Machined surface was evaluated using scanning electron microscope, electron back scatter diffraction analysis and x-ray diffraction analysis. Turning operation conducted with 2% Ag nanoparticles incorporated modified pongamia pinnata oil lubrication was better than turning conducted under dry and lubricated conditions. Industrial wastes and toxic effluents can be minimised by switching over to bio lubricants and coolants.
A fast algorithm for spatiotemporal signals recovery using arbitrary dictionaries with application to electrocardiographic imaging
Authors: Caracciolo S F , Caiafa C F , Martínez Pería F D , Arini P D
Published: July 2022

This paper presents a method to solve a linear regression problem subject to group lasso and ridge penalisation when the model has a Kronecker structure. This model was developed to solve the inverse problem of electrocardiography using sparse signal representation over a redundant dictionary or frame. The optimisation algorithm was performed using the block coordinate descent and proximal gradient descent methods. The explicit computation of the underlying Kronecker structure in the regression was avoided, reducing space and temporal complexity. We developed an algorithm that supports the use of arbitrary dictionaries to obtain solutions and allows a flexible group distribution.
Improving antibody thermostability based on statistical analysis of sequence and structural consensus data
Authors: Jia Lei , Jain Mani , Sun Yaxiong
Published: July 2022

Background

The use of Monoclonal Antibodies (MAbs) as therapeutics has been increasing over the past 30 years due to their high specificity and strong affinity toward the target. One of the major challenges toward their use as drugs is their low thermostability, which impacts both efficacy as well as manufacturing and delivery.

Methods

To aid the design of thermally more stable mutants, consensus sequence-based method has been widely used. These methods typically have a success rate of about 50% with maximum melting temperature increment ranging from 10 to 32°C. To improve the prediction performance, we have developed a new and fast MAbs specific method by adding a 3D structural layer to the consensus sequence method. This is done by analyzing the close-by residue pairs which are conserved in >800 MAbs’ 3D structures.

Results

Combining consensus sequence and structural residue pair covariance methods, we developed an in-house application for predicting human MAb thermostability to guide protein engineers to design stable molecules. Major advantage of this structural level assessment is in significantly reducing the false positives by almost half from the consensus sequence method alone. This application has shown success in designing MAb engineering panels in multiple biologics programs.

Conclusions

Our data science-based method shows impacts in Mab engineering.
Negative regulation of salicylic acid-induced stomatal closure by glutathione in Arabidopsis thaliana
Authors: Akter Fahmida , Munemasa Shintaro , Nakamura Toshiyuki , Nakamura Yoshimasa , Murata Yoshiyuki
Published: July 2022

Salicylic acid (SA) is a ubiquitous phenolic phytohormone that induces stomatal closure. Glutathione (GSH) negatively regulates stomatal closure induced by other plant hormones such as abscisic acid (ABA) and methyl jasmonate (MeJA). However, the involvement of GSH in SA-induced stomatal closure is still unknown. We investigated the regulation of SA signaling by GSH in guard cells using an Arabidopsis thaliana mutant, cad2-1, which is deficient in the first GSH biosynthesis enzyme, γ-glutamylcysteine synthetase. Application of SA decreased stomatal apertures with decreasing intracellular GSH level in guard cells. Decreasing GSH by the cad2-1 mutation and by a GSH-decreasing chemical, 1-chloro-2,4-dinitrobenzene, enhanced the SA-induced stomatal closure. Treatment with glutathione monoethyl ester restored the GSH level in the cad2-1 guard cells and complemented the stomatal phenotype of the mutant. These results indicate that GSH negatively modulates SA-induced stomatal closure in A. thaliana.
Malate induces stomatal closure via a receptor-like kinase GHR1- and reactive oxygen species-dependent pathway in Arabidopsis thaliana
Authors: Mimata Yoshiharu , Munemasa Shintaro , Akter Fahmida , Jahan Israt , Nakamura Toshiyuki , Nakamura Yoshimasa , Murata Yoshiyuki
Published: July 2022

A primary metabolite malate is secreted from guard cells in response to the phytohormone abscisic acid (ABA) and elevated CO2. The secreted malate subsequently facilitates stomatal closure in plants. Here, we investigated the molecular mechanism of malate-induced stomatal closure using inhibitors and ABA signaling component mutants of Arabidopsis thaliana. Malate-induced stomatal closure was impaired by a protein kinase inhibitor, K252a, and also by the disruption of a receptor-like kinase GHR1, which mediates activation of calcium ion (Ca2+) channel by reactive oxygen species (ROS) in guard cells. Malate induced ROS production in guard cells while the malate-induced stomatal closure was impaired by a peroxidase inhibitor, salicylhydroxamic acid, but not by the disruption of Nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases, RBOHD and RBOHF. The malate-induced stomatal closure was impaired by Ca2+ channel blockers, verapamil, and niflumic acid. These results demonstrate that the malate signaling is mediated by GHR1 and ROS in Arabidopsis guard cells.
Testis-specific serine protease PRSS54 regulates acrosomal granule localization and sperm head morphogenesis in mice
Authors: Shen Chunling , Xiong Wenfeng , Li Chaojie , Ge Haoyang , Shen Yan , Tang Lingyun , Zhang Hongxin , Lu Shunyuan , Fei Jian , Wang Zhugang
Published: July 2022

Serine proteases (PRSS) constitute nearly one-third of all proteases, and many of them have been identified to be testis-specific and play significant roles during sperm development and male reproduction. PRSS54 is one of the testis-specific PRSS in mouse and human but its physiological function remains largely unclear. In the present study, we demonstrate in detail that PRSS54 exists not only in testis but also in mature sperm, exhibiting a change in protein size from 50 kDa in testis to 42 kDa in sperm. Loss of PRSS54 in mice results in male subfertility, acrosome deformation, defective sperm–zona penetration, and phenotypes of male subfertility and acrosome deformation can be rescued by Prss54 transgene. Ultrastructure analyses by transmission electronic microscopy further reveal various morphological abnormalities of Prss54−/− spermatids during spermiogenesis, including unfused vacuoles in acrosome, detachment and eccentrical localization of the acrosomal granules, and asymmetrical elongation of the nucleus. Subcellular localization of PRSS54 display that it appears in the acrosomal granule at the early phase of acrosome biogenesis, then extends along the inner acrosomal membrane, and ultimately presents in the acrosome region of the mature sperm. PRSS54 interacts with acrosomal proteins ZPBP1, ZPBP2, ACRBP, and ZP3R, and loss of PRSS54 affects the distribution of these proteins in testis and sperm, although their protein levels are largely unaffected. Moreover, Prss54−/− sperm are more sensitive to acrosome reaction inducers.
RNA profiling of human dorsal root ganglia reveals sex differences in mechanisms promoting neuropathic pain
Authors: Ray Pradipta R , Shiers Stephanie , Caruso James P , Tavares-Ferreira Diana , Sankaranarayanan Ishwarya , Uhelski Megan L , Li Yan , North Robert Y , Tatsui Claudio , Dussor Gregory , Burton Michael D , Dougherty Patrick M , Price Theodore J
Published: July 2022

Neuropathic pain is a leading cause of high-impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the dorsal root ganglia is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human dorsal root ganglia from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain-associated dorsal root ganglia.

We sequenced 70 human dorsal root ganglia, and among these 50 met inclusion criteria for sufficient neuronal mRNA signal for downstream analysis.

Our expression analysis revealed profound sex differences in differentially expressed genes including increase of IL1B, TNF, CXCL14 and OSM in male and CCL1, CCL21, PENK and TLR3 in female dorsal root ganglia associated with neuropathic pain. Coexpression modules revealed enrichment in members of JUN-FOS signalling in males and centromere protein coding genes in females. Neuro-immune signalling pathways revealed distinct cytokine signalling pathways associated with neuropathic pain in males (OSM, LIF, SOCS1) and females (CCL1, CCL19, CCL21). We validated cellular expression profiles of a subset of these findings using RNAscope in situ hybridization.

Our findings give direct support for sex differences in underlying mechanisms of neuropathic pain in patient populations.
Long-term structural brain changes in adult rats after mild ischaemic stroke
Authors: Syeda Warda , Ermine Charlotte M , Khilf Mohamed Salah , Wright David , Brait Vanessa H , Nithianantharajah Jess , Kolbe Scott , Johnston Leigh A , Thompson Lachlan H , Brodtmann Amy
Published: July 2022

Preclinical studies of remote degeneration have largely focused on brain changes over the first few days or weeks after stroke. Accumulating evidence suggests that neurodegeneration occurs in other brain regions remote to the site of infarction for months and even years following ischaemic stroke. Brain atrophy appears to be driven by both axonal degeneration and widespread brain inflammation. The evolution and duration of these changes are increasingly being described in human studies, using advanced brain imaging techniques. Here, we sought to investigate long-term structural brain changes in a model of mild focal ischaemic stroke following injection of endothlin-1 in adult Long–Evans rats (n = 14) compared with sham animals (n = 10), over a clinically relevant time-frame of 48 weeks. Serial structural and diffusion-weighted MRI data were used to assess dynamic volume and white matter trajectories. We observed dynamic regional brain volume changes over the 48 weeks, reflecting both normal changes with age in sham animals and neurodegeneration in regions connected to the infarct following ischaemia. Ipsilesional cortical volume loss peaked at 24 weeks but was less prominent at 36 and 48 weeks. We found significantly reduced fractional anisotropy in both ipsi- and contralesional motor cortex and cingulum bundle regions of infarcted rats (P < 0.05) from 4 to 36 weeks, suggesting ongoing white matter degeneration in tracts connected to but distant from the stroke. We conclude that there is evidence of significant cortical atrophy and white matter degeneration up to 48 weeks following infarct, consistent with enduring, pervasive stroke-related degeneration.
Protection Against the Omicron Variant Offered by Previous Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Retrospective Cohort Study
Authors: Rothberg Michael B , Kim Priscilla , Shrestha Nabin K , Kojima Lisa , Tereshchenko Larisa G
Published: July 2022

Background

Previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides strong protection against future infection. There is limited evidence on whether such protection extends to the Omicron variant.

Methods

This retrospective cohort study included 635 341 patients tested for SARS-CoV-2 via polymerase chain reaction from 9 March 2020 to 1 March 2022. Patients were analyzed according to the wave in which they were initially infected. The primary outcome was reinfection during the Omicron period (20 December 2021–1 March 2022). We used a multivariable model to assess the effects of prior infection and vaccination on hospitalization.

Results

Among the patients tested during the Omicron wave, 30.6% tested positive. Protection of prior infection against reinfection with Omicron ranged from 18.0% (95% confidence interval [CI], 13.0–22.7) for patients infected in wave 1 to 69.2% (95% CI, 63.4–74.1) for those infected in the Delta wave. In adjusted models, previous infection reduced hospitalization by 28.5% (95% CI, 19.1–36.7), whereas full vaccination plus a booster reduced it by 59.2% (95% CI, 54.8–63.1).

Conclusions

Previous infection offered less protection against Omicron than was observed in past waves. Immunity against future waves will likely depend on the degree of similarity between variants.
Spatio-temporal Influences on Cereal Aphid (Hemiptera: Aphididae) Population Dynamics and the Incidence of Barley Yellow Dwarf Virus
Authors: Van den Eynde Renik , De Keukelaere Laura , Landschoot Sofie , Pycke Bart , Claeys Jonas , Smets Sander , Van Leeuwen Thomas , Haesaert Geert
Published: July 2022

Problems with aphids in small grain cereals, either direct by feeding, or indirect by transmission of Barley Yellow Dwarf Virus, are expected to increase due to climate change and a recent ban on neonicotinoid seed treatments by the European Union. Moreover, insecticide resistance against pyrethroid insecticides is reported at multiple locations throughout the world. Therefore, a better understanding of cereal aphid population dynamics and increased attention towards an integrated pest management is needed. In this study, cereal aphids were monitored on 193 maize and small grain cereal fields throughout Flanders, Belgium. The population dynamics and species distribution were observed throughout the year and the effects of spatio-temporal variables were explored. A significant negative effect was found of grassland in a 1,000 m radius and a positive effect of grain maize in a 3,000 m radius around a small grain cereals field on the maximum infestation rate with aphids in autumn within this field. In a 3,000 m and 5,000 m radius, a significant positive effect of grain maize and a significant negative effect of other small grain cereals was found on the maximum infestation rate during the whole growing season within this field. The mean daily average temperature from 118 to 19 d before sowing had a significant positive effect on the maximum infestation rate in autumn. Mean precipitation, wind speed, and humidity from 52 to 26, 46 to 23, and 107 to 13 d before sowing respectively, had a significant negative effect on the maximum infestation rate in autumn.
Phylogenetic prioritization of HIV-1 transmission clusters with viral lineage-level diversification rates
Authors: Miller Rachel L , McLaughlin Angela , Liang Richard H , Harding John , Wong Jason , Le Anh Q , Brumme Chanson J , Montaner Julio S G , Joy Jeffrey B
Published: July 2022

Background and objectives

Public health officials faced with a large number of transmission clusters require a rapid, scalable and unbiased way to prioritize distribution of limited resources to maximize benefits. We hypothesize that transmission cluster prioritization based on phylogenetically derived lineage-level diversification rates will perform as well as or better than commonly used growth-based prioritization measures, without need for historical data or subjective interpretation.

Methodology

9822 HIV pol sequences collected during routine drug resistance genotyping were used alongside simulated sequence data to infer sets of phylogenetic transmission clusters via patristic distance threshold. Prioritized clusters inferred from empirical data were compared to those prioritized by the current public health protocols. Prioritization of simulated clusters was evaluated based on correlation of a given prioritization measure with future cluster growth, as well as the number of direct downstream transmissions from cluster members.

Results

Empirical data suggest diversification rate-based measures perform comparably to growth-based measures in recreating public heath prioritization choices. However, unbiased simulated data reveals phylogenetic diversification rate-based measures perform better in predicting future cluster growth relative to growth-based measures, particularly long-term growth. Diversification rate-based measures also display advantages over growth-based measures in highlighting groups with greater future transmission events compared to random groups of the same size. Furthermore, diversification rate measures were notably more robust to effects of decreased sampling proportion.

Conclusions and implications

Our findings indicate diversification rate-based measures frequently outperform growth-based measures in predicting future cluster growth and offer several additional advantages beneficial to optimizing the public health prioritization process.
Examination of phase-variable haemoglobin–haptoglobin binding proteins in non-typeable Haemophilus influenzae reveals a diverse distribution of multiple variants
Authors: Phillips Zachary N , Jennison Amy V , Whitby Paul W , Stull Terrence L , Staples Megan , Atack John M
Published: July 2022

Non-typeable Haemophilus influenzae (NTHi) is a major human pathogen for which there is no globally licensed vaccine. NTHi has a strict growth requirement for iron and encodes several systems to scavenge elemental iron and heme from the host. An effective NTHi vaccine would target conserved, essential surface factors, such as those involved in iron acquisition. Haemoglobin–haptoglobin binding proteins (Hgps) are iron-uptake proteins localized on the outer-membrane of NTHi. If the Hgps are to be included as components of a rationally designed subunit vaccine against NTHi, it is important to understand their prevalence and diversity. Following analysis of all available Hgp sequences, we propose a standardized grouping method for Hgps, and demonstrate increased diversity of these proteins than previously determined. This analysis demonstrated that genes encoding variants HgpB and HgpC are present in all strains examined, and almost 40% of strains had a duplicate, nonidentical hgpB gene. Hgps are also phase-variably expressed; the encoding genes contain a CCAA(n) simple DNA sequence repeat tract, resulting in biphasic ON–OFF switching of expression. Examination of the ON–OFF state of hgpB and hgpC genes in a collection of invasive NTHi isolates demonstrated that 58% of isolates had at least one of hgpB or hgpC expressed (ON). Varying expression of a diverse repertoire of hgp genes would provide strains a method of evading an immune response while maintaining the ability to acquire iron via heme. Structural analysis of Hgps also revealed high sequence variability at the sites predicted to be surface exposed, demonstrating a further mechanism to evade the immune system—through varying the surface, immune-exposed regions of the membrane anchored protein. This information will direct and inform the choice of candidates to include in a vaccine against NTHi.
3-indoleacetonitrile attenuates biofilm formation and enhances sensitivity to imipenem in Acinetobacter baumannii
Authors: Kashyap Shruti , Sidhu Harsimran , Sharma Prince , Capalash Neena
Published: July 2022

Acinetobacter baumannii poses a global danger due to its ability to resist most of the currently available antimicrobial agents. Furthermore, the rise of carbapenem-resistant A. baumannii isolates has limited the treatment options available. In the present study, plant auxin 3-indoleacetonitrile (3IAN) was found to inhibit biofilm formation and motility of A. baumannii at sublethal concentration. Mechanistically, 3IAN inhibited the synthesis of the quorum sensing signal 3-OH-C12-HSL by downregulating the expression of the abaI autoinducer synthase gene. 3IAN was found to reduce the minimum inhibitory concentration of A. baumannii ATCC 17978 against imipenem, ofloxacin, ciprofloxacin, tobramycin, and levofloxacin, and significantly decreased persistence against imipenem. Inhibition of efflux pumps by downregulating genes expression may be responsible for enhanced sensitivity and low persistence. 3IAN reduced the resistance to imipenem in carbapenem-resistant A. baumannii isolates by downregulating the expression of OXA β-lactamases (blaoxa-51 and blaoxa-23), outer membrane protein carO, and transporter protein adeB. These findings demonstrate the therapeutic potential of 3IAN, which could be explored as an adjuvant with antibiotics for controlling A. baumannii infections.
The Phylogenetic Position of the Enigmatic, Polypodium hydriforme (Cnidaria, Polypodiozoa): Insights from Mitochondrial Genomes
Authors: Novosolov Maria , Yahalomi Dayana , Chang E Sally , Fiala Ivan , Cartwright Paulyn , Huchon Dorothée
Published: July 2022

Polypodium hydriforme is an enigmatic parasite that belongs to the phylum Cnidaria. Its taxonomic position has been debated: whereas it was previously suggested to be part of Medusozoa, recent phylogenomic analyses based on nuclear genes support the view that P. hydriforme and Myxozoa form a clade called Endocnidozoa. Medusozoans have linear mitochondrial (mt) chromosomes, whereas myxozoans, as most metazoan species, have circular chromosomes. In this work, we determined the structure of the mt genome of P. hydriforme, using Illumina and Oxford Nanopore Technologies reads, and showed that it is circular. This suggests that P. hydriforme is not nested within Medusozoa, as this would entail linearization followed by recirculation. Instead, our results support the view that P. hydriforme is a sister clade to Myxozoa, and mt linearization in the lineage leading to medusozoans occurred after the divergence of Myxozoa + P. hydriforme. Detailed analyses of the assembled P. hydriforme mt genome show that: (1) it is encoded on a single circular chromosome with an estimated size of ∼93,000 base pairs, making it one of the largest metazoan mt genomes; (2) around 78% of the genome encompasses a noncoding region composed of several repeat types; (3) similar to Myxozoa, no mt tRNAs were identified; (4) the codon TGA is a stop codon and does not encode for tryptophan as in other cnidarians; (5) similar to myxozoan mt genomes, it is extremely fast evolving.
The Parkinson’s disease variant rs356182 regulates neuronal differentiation independently from alpha-synuclein
Authors: Prahl Jordan D , Pierce Steven E , van der Schans Edwin J C , Coetzee Gerhard A , Tyson Trevor
Published: July 2022

One of the most significant risk variants for Parkinson’s disease (PD), rs356182, is located at the PD-associated locus near the alpha-synuclein (α-syn) encoding gene, SNCA. SNCA-proximal variants, including rs356182, are thought to function in PD risk through enhancers via allele-specific regulatory effects on SNCA expression. However, this interpretation discounts the complex activity of genetic enhancers and possible non-conical functions of α-syn. Here we investigated a novel risk mechanism for rs356182. We use CRISPR-Cas9 in LUHMES cells, a model for dopaminergic midbrain neurons, to generate precise hemizygous lesions at rs356182. The PD-protective (A/−), PD-risk (G/−) and wild-type (A/G) clones were neuronally differentiated and then compared transcriptionally and morphologically. Among the affected genes was SNCA, whose expression was promoted by the PD-protective allele (A) and repressed in its absence. In addition to SNCA, hundreds of genes were differentially expressed and associated with neurogenesis and axonogenesis—an effect not typically ascribed to α-syn. We also found that the transcription factor FOXO3 specifically binds to the rs356182 A-allele in differentiated LUHMES cells. Finally, we compared the results from the rs356182-edited cells to our previously published knockouts of SNCA and found only minimal overlap between the sets of significant differentially expressed genes. Together, the data implicate a risk mechanism for rs356182 in which the risk-allele (G) is associated with abnormal neuron development, independent of SNCA expression. We speculate that these pathological effects manifest as a diminished population of dopaminergic neurons during development leading to the predisposition for PD later in life.
Taking Dignity Seriously to Protect Manual Scavengers in India: Lessons from the UN Human Rights Committee
Authors: Gupta Aishani
Published: July 2022

This article analyses the Indian caste-based occupation of sanitation work undertaken without protective equipment—manual scavenging. The current legal framework on manual scavenging in India suggests that demolishing dry latrines will abolish manual scavenging. This approach overlooks the coercive nature of the caste system and is therefore an inadequate solution for abolishing manual scavenging. Hence, this article asks ‘how can the legal system provide better legal protections to manual scavengers when the caste system that underpins the practice is deeply entrenched in Indian society?’ The article examines one possible answer—taking dignity more seriously. It demonstrates that manual scavenging is a dignitarian problem by mapping the main dignitarian harms that arise from it, such as humiliation, loss of autonomy and tensions with group dignity. Ultimately, it proposes using dignity in line with the jurisprudence of the UN Human Rights Committee to provide more comprehensive legal protections for manual scavengers.
Testing Mechanisms of Vision: Sea Urchin Spine Density Does Not Correlate with Vision-Related Environmental Characteristics
Authors: Notar Julia C , Meja Bernice , Johnsen Sönke
Published: July 2022

Synopsis

Sea urchins do not have eyes, yet they are capable of resolving simple images. One suggestion as to the mechanism of this capability is that the spines shade off-axis light from reaching the photosensitive test (skeleton). Following this hypothesis, the density of spines across the body determines the resolution (or sharpness) of vision by restricting the incidence of light on the photosensitive skin of the animal, creating receptive areas of different minimum resolvable angles. Previous studies have shown that predicted resolutions in several species closely match behaviorally determined resolutions, ranging from 10° to 33°. Here, we present a comparative morphological survey of spine density with species representatives from 22 of the 24 families of regular sea urchins (Class Echinoidea) in order to better understand the relative influences of phylogenetic history and three visually relevant environmental variables on this trait. We estimated predicted resolutions by calculating spine densities from photographs of spineless sea urchin tests (skeletons). Analyses showed a strong phylogenetic signal in spine density differences between species. Phylogenetically-corrected Generalized Least Squares models incorporating all habitat parameters were the most supported, and no particular parameter was significantly correlated with spine density. Spine density is subject to multiple, overlapping selective pressures and therefore it is possible that either (1) spine density does not mediate spatial vision in echinoids, or (2) visual resolution via spine density is a downstream consequence of sea urchin morphology rather than a driving force of adaptation in these animals.
On K-Stability for Fano Threefolds of Rank 3 and Degree 28
Authors: Fujita Kento
Published: July 2022

We show that there exists a K-stable smooth Fano threefold of the Picard rank $3$, the anti-canonical degree $28,$ and the third Betti number $2$.
Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story
Authors: Bialasiewicz Seweryn , May Meryta , Tozer Sarah , Day Rebecca , Bernard Anne , Zaugg Julian , Gartrell Kyana , Alexandersen Soren , Chamings Anthony , Wang Claire Y T , Clark Julia , Grimwood Keith , Heney Claire , Schlapbach Luregn J , Ware Robert S , Speers David , Andrews Ross M , Lambert Stephen
Published: July 2022

Background

A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections.

Methods

HPeV3-positive samples collected from hospitalized infants aged 5–252 days in 2 Australian states (2013–2020) and from a community-based birth cohort (2010–2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples.

Results

Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3′ end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019–2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants.

Conclusions

HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence.
IR Theory and the Core–Periphery Structure of Global IR: Lessons from Citation Analysis
Authors: Risse Thomas , Wemheuer-Vogelaar Wiebke , Havemann Frank
Published: July 2022

This article contributes to two debates about international relations (IR) as a discipline: first, how global is IR, and how is it structured? Second, what is the state of theory in IR? We conducted (co-) citation analyses of both Web of Science (WoS) and—for the first time— non-WoS publications from Europe, North America, Latin America, Africa, and Asia. With regard to the first question, we find that global IR resembles a core–periphery structure as a “hub and spoke” system whereby transatlantic core nodes are interconnected to each other and to some periphery nodes, while the periphery nodes are connected to the core but not to each other. IR scholarship in the periphery quotes the transatlantic theory cluster but is not linked to each other, not even in the same region. Knowledge produced in the periphery has to go through the transatlantic core in order to be recognized globally. As to the transatlantic core, we identify two major (co-) citation clusters: one committed to IR theory-building across issue areas from a variety of perspectives and the other focused on security studies with a strong emphasis on quantitative methods. With regard to the second question, global IR hangs together through references to the IR theory cluster consisting of North American and European authors who appear to define what IR theory is. Scholars in the periphery refer to this transatlantic IR theory cluster when engaging in theory-building. IR theories have become rather diverse and pluralistic, even in the core. While scholars still refer to the big “isms,” they use them around the globe in a synthesizing manner.
Digital vaccine passports and digital health diplomacy: an online model WHO simulation
Authors: Godinho Myron Anthony , Liaw Siaw-Teng , Kanjo Chipo , Marin Heimar F , Martins Henrique , Quintana Yuri
Published: July 2022

In the wake of Coronavirus disease 2019 (COVID-19), several nations have sought to implement digital vaccine passports (DVPs) to enable the resumption of international travel. Comprising a minimum dataset for each unique individual, DVPs have the makings of a global electronic health record, broaching key issues involved in building a global digital health ecosystem. Debate simulations offer a safe, interactive space to foster participatory policy discussions for advancing digital health diplomacy. This study used an online simulation of a Model World Health Assembly to critically analyze the sociotechnical issues associated with the global implementation of DVPs, and to generate useful insights and questions about the role of diplomacy in global digital health. The debate arguments addressed and provided insights into the technological, scientific, ethical, legal, policy, and societal aspects of DVPs. Reflecting on the simulation, we discuss its opportunities and challenges for the digitalization, decolonization, decentralization, and democratization of participatory policymaking.