bluuebunny/crossref_metadata_2025 huggingface dataset:
Sinusoidal and rectangular Bragg grating filters: Design, fabrication, and comparative analysis
Authors: Saghaei Hamed , Elyasi Payam , Shastri Bhavin J.
Published: August 2022

In this paper, we compare the characteristics of several waveguide Bragg gratings (WBGs) with sinusoidal and rectangular corrugated sidewalls in high confinement integrated optics. Our measurements confirm the performance of both the rectangular and sinusoidal grating as band-rejection filters for TE-polarized signals in the telecom C-band. These measurements demonstrate record high extinction ratios of 35 and 28.91 dB for sinusoidal and rectangular WBGs with a rejection bandwidth as narrow as 4.42 and 6.165 nm. The simulation results and measurements show that the filter bandwidth and coupling coefficient can be changed by altering the corrugation width (ΔW), allowing us to control the filter’s quality factor precisely. The bandwidth of rectangular WBGs drops for ΔW>80 nm, constraining the design of devices requiring broadband WBGs. In contrast, the bandwidth of sinusoidal WBG continues to increase for ΔW>80 nm, providing a wider bandwidth for designers. These findings demonstrate the potential for effective integration of new photonic functionalities into low-footprint electro-optical waveguide tools for sensing, communicating, and computing applications.
Ag nanowires assisted CH3NH3PbBr3–ZnO heterostructure with fast negative photoconductive response
Authors: Lv Yujie , Chen Feng , Zhang Zhenhua , Chen Jinping , Tang Xiao , Shi Zengliang , Cui Qiannan , Xu Chunxiang
Published: August 2022

Due to its attractive interaction with light, negative photoconductivity (NPC) has received widespread attention and has been used in optoelectronic logic devices with excellent performance. However, long negative response time triggered by photogenerated carriers trapping mechanism became a bottleneck in further application. Therefore, an enhanced strategy that can speed up negative response is urgently needed. Herein, we prepared a zinc oxide microwire (ZnO MW)–silver nanowires (Ag NWs)–methylammonium lead halide perovskite (CH3NH3PbBr3) heterostructure with enhanced negative response than the previous NPC device. The Ag NWs with high mobility at the interface of ZnO and CH3NH3PbBr3 accelerate the photoresponse time from 50 to 5.4 s and improve the dark current recovery time by two orders of magnitude. This work provides a strategy to improve the negative response speed with simple operation, which represents a step toward applications in the field of fast NPC optoelectronics.
Correlation between the formation of new competing group and spatial scale for biodiversity in the evolutionary dynamics of cyclic competition
Authors: Park Junpyo
Published: August 2022

Securing space for species breeding is important in the evolution and maintenance of life in ecological sciences, and an increase in the number of competing species may cause frequent competition and conflict among the population in securing such spaces in a given area. In particular, for cyclically competing species, which can be described by the metaphor of rock–paper–scissors game, most of the previous works in microscopic frameworks have been studied with the initially given three species without any formation of additional competing species, and the phase transition of biodiversity via mobility from coexistence to extinction has never been changed by a change of spatial scale. In this regard, we investigate the relationship between spatial scales and species coexistence in the spatial cyclic game by considering the emergence of a new competing group by mutation. For different spatial scales, our computations reveal that coexistence can be more sensitive to spatial scales and may require larger spaces for frequencies of interactions. By exploiting the calculation of the coexistence probability from Monte-Carlo simulations, we obtain that certain interaction ranges for coexistence can be affected by both spatial scales and mobility, and spatial patterns for coexistence can appear in different ways. Since the issue of spatial scale is important for species survival as competing populations increase, we expect our results to have broad applications in the fields of social and ecological sciences.
Anomalous Ettingshausen effect in iron–carbon alloys
Authors: Nagasawa Ren , Oyanagi Koichi , Hirai Takamasa , Modak Rajkumar , Kobayashi Satoru , Uchida Ken-ichi
Published: August 2022

We have investigated the anomalous Ettingshausen effect (AEE) in iron–carbon alloys, i.e., cast irons and steel, using the lock-in thermography. All the alloys exhibit the clear AEE-induced temperature modulation, and their anomalous Ettingshausen coefficient is an order of magnitude greater than that of the pure iron at room temperature. The dimensionless figure of merit for AEE in the ductile cast iron is 55 times greater than that in the pure iron owing to the significant increase in the anomalous Ettingshausen coefficient. Our result reveals a potential of iron–carbon alloys as transverse thermoelectric materials, although the composition and microstructures optimizations are necessary.
Spatial patterns in the cover and composition of macroalgal assemblages on fringing and nearshore coral reefs
Authors: Webber K. , Srinivasan M. , Coppock A. G. , Jones G. P.
Published: August 2022

Context Although increases in macroalgal cover on coral reefs are often reported alongside declines in coral, the composition of algal assemblages and their spatial dynamics are not commonly investigated. Aims To quantify changes in macroalgal assemblage composition over two spatial environmental gradients, depth and distance from shore, within a nearshore reef system in Kimbe Bay, Papua New Guinea, where coral cover has declined. Methods Benthic cover was quantified at three depths (reef flat, 10 and 15 m) on the windward reef slopes of six reefs located three distances from shore (fringing reefs, and platform reefs 100–200 m and 0.7−1 km offshore). Key results Macroalgal cover was highest on the reef flat, and assemblage composition varied among depths and distances from shore. Macroalgal cover was not correlated with coral cover except where macroalgal cover was greater than 20%, where a negative correlation occurred. There was no correlation between macroalgal cover and turf algal cover. All three benthic groups were negatively correlated with the combined total cover of sand and gravel. Conclusions These results indicated a fine-scale spatial structure of macroalgal assemblages on coral reefs over a narrow depth range and short distance from shore and highlighted the importance of a solid substratum. Implications It is likely that the ecological interactions between corals and macroalgae vary considerably over narrow spatial gradients.
Vaccine provider views on the impact of COVID-19 on immunisation in general practice: a qualitative study
Authors: Morgan Tobias , Mahimbo Abela , Harris Mark , Heywood Anita
Published: August 2022

Background General practitioners and general practice nurses are the most trusted and experienced sources of vaccine information for Australians and are the principal providers of routine immunisation in New South Wales, Australia. This study explored perceived barriers and challenges to the rollout of the COVID-19 immunisation program and continued provision of routine immunisation through general practice. Methods Structured in-depth interviews were conducted between 29 April and 8 July 2021 with general practitionerss and general practice nurses working in accredited general practices in the Greater Sydney area. Interviews were transcribed verbatim and analysed thematically. Results Fifteen participants (12 general practitioners and three general practice nurses) were interviewed. Participants considered the COVID-19 vaccine rollout to significantly burden general practice at the cost of delivery of routine preventative care. Patient fear and anxiety and vaccine hesitancy were perceived as major challenges to the provision of all immunisations, exacerbated by media coverage of shifting recommendations related to COVID-19 vaccine adverse events. Inadequate communication from government bodies contributed to a perceived erosion of patient trust in general practice. Participants considered routine immunisation to be minimally disrupted owing to robust practice-based recall and reminder systems and legislated immunisation requirements for children. Conclusion The role of general practitioners and general practice nurses in the COVID-19 vaccine rollout was seen to be one of great burden and complexity. As the primary providers of immunisation in New South Wales, continued communication with and support for general practice, both financially and informationally, is pivotal to the sustained successful provision of routine and COVID-19 immunisation.
Who’s afraid of the big, bad predator? Contrasting effects of apex predator presence on the behaviour of a mesopredator
Authors: Welch Rebecca J. , Comley Jessica , Kok Armand D. , Taylor Jon M. , Parker Dan M.
Published: August 2022

Context Mesopredators experience top down pressure from apex predators, which may lead to behavioural changes such as spatial avoidance to reduce both interference and exploitative competition. However, apex predators may also facilitate mesopredators through the provision of carrion, so mesopredators should respond flexibly to the presence of apex predators. Aims We aimed to investigate the drivers of black-backed jackal (Canis mesomelas) space use and detection in areas with and without lions (Panthera leo). We predicted that jackal detection and space use will be greater if apex predators facilitate rather than suppress them. Additionally, we predicted that in the absence of lions, the relative abundance of small ungulate species may become important drivers of space use and detection, because jackals can switch from scavenging to hunting. Comparatively, in the presence of lions, larger ungulate species will become important drivers of space use and detection as these species become accessible to jackals through scavenging. Methods We used camera-trapping surveys, a single-species, single-season occupancy modelling approach, and the assessment of activity patterns to explore how apex predators influence the presence and probability of use of different sites in the Eastern Cape province of South Africa. Key results Apex predators both positively and negatively affected the detection of jackals, indicating that these mesopredators show behavioural flexibility at the individual site level. There was high overlap between jackal activity patterns in the presence and absence of lions; however, at one site with lions, jackal activity did not peak at night as observed at other sites. Conclusions Our results indicate that jackals demonstrate behavioural flexibility in the presence and absence of apex predators. Importantly, our results show that apex predators can both facilitate and suppress mesopredators, and that their behavioural responses are dependent on site-specific factors. Implications Our findings highlight that sympatric predator behaviours should be based on site-specific behaviours instead of the general patterns observed in more temperate systems.
Engineered IL13 variants direct specificity of IL13Rα2-targeted CAR T cell therapy
Authors: Stern Lawrence A. , Gholamin Sharareh , Moraga Ignacio , Yang Xin , Saravanakumar Supraja , Cohen Joseph R. , Starr Renate , Aguilar Brenda , Salvary Vanessa , Hibbard Jonathan C. , Kalbasi Anusha , Shepphird Jennifer K. , O’Hearn James , Garcia K. Christopher , Brown Christine E.
Published: August 2022

IL13Rα2 is an attractive target due to its overexpression in a variety of cancers and rare expression in healthy tissue, motivating expansion of interleukin 13 (IL13)–based chimeric antigen receptor (CAR) T cell therapy from glioblastoma into systemic malignancies. IL13Rα1, the other binding partner of IL13, is ubiquitously expressed in healthy tissue, raising concerns about the therapeutic window of systemic administration. IL13 mutants with diminished binding affinity to IL13Rα1 were previously generated by structure-guided protein engineering. In this study, two such variants, termed C4 and D7, are characterized for their ability to mediate IL13Rα2-specific response as binding domains for CAR T cells. Despite IL13Rα1 and IL13Rα2 sharing similar binding interfaces on IL13, mutations to IL13 that decrease binding affinity for IL13Rα1 did not drastically change binding affinity for IL13Rα2. Micromolar affinity to IL13Rα1 was sufficient to pacify IL13-mutein CAR T cells in the presence of IL13Rα1-overexpressing cells in vitro. Interestingly, effector activity of D7 CAR T cells, but not C4 CAR T cells, was demonstrated when cocultured with IL13Rα1/IL4Rα-coexpressing cancer cells. While low-affinity interactions with IL13Rα1 did not result in observable toxicities in mice, in vivo biodistribution studies demonstrated that C4 and D7 CAR T cells were better able to traffic away from IL13Rα1+ lung tissue than were wild-type (WT) CAR T cells. These results demonstrate the utility of structure-guided engineering of ligand-based binding domains with appropriate selectivity while validating IL13-mutein CARs with improved selectivity for application to systemic IL13Rα2-expressing malignancies.
Lactobacillus crispatus
Limits Bladder Uropathogenic
E. coli
Infection by Triggering a Host Type I Interferon Response
Authors: Song Chang Hyun , Kim Young Ho , Naskar Manisha , Hayes Byron W. , Abraham Mathew A. , Noh Joo Hwan , Suk Gyeongseo , Kim Min Jung , Cho Kyu Sang , Shin Minhye , Lee Eun-Jin , Abraham Soman N. , Choi Hae Woong
Published: August 2022

Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to antibiotic treatment. The recent discovery of endogenous
Lactobacillus
spp. in the bladders of healthy humans raised the question of whether these endogenous bacteria directly or indirectly impact intracellular bacterial burden in the bladder. Here, we report that in contrast to healthy women, female patients experiencing recurrent UTIs have a bladder population of
Lactobacilli
that is markedly reduced. Exposing infected human BECs to
L. crispatus
in vitro markedly reduced the intracellular uropathogenic
Escherichia coli
(UPEC) load. The adherence of
Lactobacilli
to BECs was found to result in increased type I interferon (IFN) production, which in turn enhanced the expression of cathepsin D within lysosomes harboring UPECs. This lysosomal cathepsin D–mediated UPEC killing was diminished in germ-free mice and type I IFN receptor–deficient mice. Secreted metabolites of
L. crispatus
seemed to be responsible for the increased expression of type I IFN in human BECs. Intravesicular administration of
Lactobacilli
into UPEC-infected murine bladders markedly reduced their intracellular bacterial load suggesting that components of the endogenous microflora can have therapeutic effects against UTIs.
Sharp thresholds limit the benefit of defector avoidance in cooperation on networks
Authors: Fahimipour Ashkaan K. , Zeng Fanqi , Homer Martin , Traulsen Arne , Levin Simon A. , Gross Thilo
Published: August 2022

Consider a cooperation game on a spatial network of habitat patches, where players can relocate between patches if they judge the local conditions to be unfavorable. In time, the relocation events may lead to a homogeneous state where all patches harbor the same relative densities of cooperators and defectors, or they may lead to self-organized patterns, where some patches become safe havens that maintain an elevated cooperator density. Here we analyze the transition between these states mathematically. We show that safe havens form once a certain threshold in connectivity is crossed. This threshold can be analytically linked to the structure of the patch network and specifically to certain network motifs. Surprisingly, a forgiving defector avoidance strategy may be most favorable for cooperators. Our results demonstrate that the analysis of cooperation games in ecological metacommunity models is mathematically tractable and has the potential to link topics such as macroecological patterns, behavioral evolution, and network topology.
Climate drives coupled regime shifts across subtropical estuarine ecosystems
Authors: Hesterberg Stephen G. , Jackson Kendal , Bell Susan S.
Published: August 2022

Ecological regime shifts are expected to increase this century as climate change propagates cascading effects across ecosystems with coupled elements. Here, we demonstrate that the climate-driven salt marsh–to–mangrove transition does not occur in isolation but is linked to lesser-known oyster reef–to–mangrove regime shifts through the provision of mangrove propagules. Using aerial imagery spanning 82 y, we found that 83% of oyster reefs without any initial mangrove cover fully converted to mangrove islands and that mean (± SD) time to conversion was 29.1 ± 9.6 y. In situ assessments of mangrove islands suggest substantial changes in ecosystem structure during conversion, while radiocarbon dates of underlying reef formation indicate that such transitions are abrupt relative to centuries-old reefs. Rapid transition occurred following release from freezes below the red mangrove (
Rhizophora mangle
) physiological tolerance limit (−7.3 °C) and after adjacent marsh-to-mangrove conversion. Additional nonclimate-mediated drivers of ecosystem change were also identified, including oyster reef exposure to wind-driven waves. Coupling of regime shifts arises from the growing supply of mangrove propagules from preceding and adjacent marsh-to-mangrove conversion. Climate projections near the mangrove range limit on the Gulf coast of Florida suggest that regime shifts will begin to transform subtropical estuaries by 2070 if propagule supply keeps pace with predicted warming. Although it will become increasingly difficult to maintain extant oyster habitat with tropicalization, restoring oyster reefs in high-exposure settings or active removal of mangrove seedlings could slow the coupled impacts of climate change shown here.
Lizards from warm and declining populations are born with extremely short telomeres
Authors: Dupoué Andréaz , Blaimont Pauline , Angelier Frédéric , Ribout Cécile , Rozen-Rechels David , Richard Murielle , Miles Donald , de Villemereuil Pierre , Rutschmann Alexis , Badiane Arnaud , Aubret Fabien , Lourdais Olivier , Meylan Sandrine , Cote Julien , Clobert Jean , Le Galliard Jean-François
Published: August 2022

Aging is the price to pay for acquiring and processing energy through cellular activity and life history productivity. Climate warming can exacerbate the inherent pace of aging, as illustrated by a faster erosion of protective telomere DNA sequences. This biomarker integrates individual pace of life and parental effects through the germline, but whether intra- and intergenerational telomere dynamics underlies population trends remains an open question. Here, we investigated the covariation between life history, telomere length (TL), and extinction risk among three age classes in a cold-adapted ectotherm (
Zootoca vivipara
) facing warming-induced extirpations in its distribution limits. TL followed the same threshold relationships with population extinction risk at birth, maturity, and adulthood, suggesting intergenerational accumulation of accelerated aging rate in declining populations. In dwindling populations, most neonates inherited already short telomeres, suggesting they were born physiologically old and unlikely to reach recruitment. At adulthood, TL further explained females’ reproductive performance, switching from an index of individual quality in stable populations to a biomarker of reproductive costs in those close to extirpation. We compiled these results to propose the aging loop hypothesis and conceptualize how climate-driven telomere shortening in ectotherms may accumulate across generations and generate tipping points before local extirpation.
Biosynthesis of tetrahydropapaverine and semisynthesis of papaverine in yeast
Authors: Jamil Osman K. , Cravens Aaron , Payne James T. , Kim Colin Y. , Smolke Christina D.
Published: August 2022

Tetrahydropapaverine (THP) and papaverine are plant natural products with clinically significant roles. THP is a precursor in the production of the drugs atracurium and cisatracurium, and papaverine is used as an antispasmodic during vascular surgery. In recent years, metabolic engineering advances have enabled the production of natural products through heterologous expression of pathway enzymes in yeast. Heterologous biosynthesis of THP and papaverine could play a role in ensuring a stable supply of these clinically significant products. Biosynthesis of THP and papaverine has not been achieved to date, in part because multiple pathway enzymes have not been elucidated. Here, we describe the development of an engineered yeast strain for de novo biosynthesis of THP. The production of THP is achieved through heterologous expression of two enzyme variants with activity on nonnative substrates. Through protein engineering, we developed a variant of
N
-methylcoclaurine hydroxylase with activity on coclaurine, enabling de novo norreticuline biosynthesis. Similarly, we developed a variant of scoulerine 9-
O
-methyltransferase capable of
O
-methylating 1-benzylisoquinoline alkaloids at the 3′ position, enabling de novo THP biosynthesis. Flux through the heterologous pathway was improved by knocking out yeast multidrug resistance transporters and optimization of media conditions. Overall, strain engineering increased the concentration of biosynthesized THP 600-fold to 121 µg/L. Finally, we demonstrate a strategy for papaverine semisynthesis using hydrogen peroxide as an oxidizing agent. Through optimizing pH, temperature, reaction time, and oxidizing agent concentration, we demonstrated the ability to produce semisynthesized papaverine through oxidation of biosynthesized THP.
Assignment of structural transitions during mechanical unwrapping of nucleosomes and their disassembly products
Authors: Díaz-Celis César , Cañari-Chumpitaz Cristhian , Sosa Robert P. , Castillo Juan P. , Zhang Meng , Cheng Enze , Chen Andy Q. , Vien Michael , Kim JeongHoon , Onoa Bibiana , Bustamante Carlos
Published: August 2022

Nucleosome DNA unwrapping and its disassembly into hexasomes and tetrasomes is necessary for genomic access and plays an important role in transcription regulation. Previous single-molecule mechanical nucleosome unwrapping revealed a low- and a high-force transitions, and force-FRET pulling experiments showed that DNA unwrapping is asymmetric, occurring always first from one side before the other. However, the assignment of DNA segments involved in these transitions remains controversial. Here, using high-resolution optical tweezers with simultaneous single-molecule FRET detection, we show that the low-force transition corresponds to the undoing of the outer wrap of one side of the nucleosome (∼27 bp), a process that can occur either cooperatively or noncooperatively, whereas the high-force transition corresponds to the simultaneous unwrapping of ∼76 bp from both sides. This process may give rise stochastically to the disassembly of nucleosomes into hexasomes and tetrasomes whose unwrapping/rewrapping trajectories we establish. In contrast, nucleosome rewrapping does not exhibit asymmetry. To rationalize all previous nucleosome unwrapping experiments, it is necessary to invoke that mechanical unwrapping involves two nucleosome reorientations: one that contributes to the change in extension at the low-force transition and another that coincides but does not contribute to the high-force transition.
The Na
+
/H
+
antiporter SALT OVERLY SENSITIVE 1 regulates salt compensation of circadian rhythms by stabilizing GIGANTEA in
Arabidopsis
Authors: Cha Joon-Yung , Kim Jeongsik , Jeong Song Yi , Shin Gyeong-Im , Ji Myung Geun , Hwang Ji-Won , Khaleda Laila , Liao Xueji , Ahn Gyeongik , Park Hee-Jin , Kim Dong Young , Pardo Jose M. , Lee Sang Yeol , Yun Dae-Jin , Somers David E. , Kim Woe-Yeon
Published: August 2022

The circadian clock is a timekeeping, homeostatic system that temporally coordinates all major cellular processes. The function of the circadian clock is compensated in the face of variable environmental conditions ranging from normal to stress-inducing conditions. Salinity is a critical environmental factor affecting plant growth, and plants have evolved the SALT OVERLY SENSITIVE (SOS) pathway to acquire halotolerance. However, the regulatory systems for clock compensation under salinity are unclear. Here, we show that the plasma membrane Na
+
/H
+
antiporter SOS1 specifically functions as a salt-specific circadian clock regulator via GIGANTEA (GI) in
Arabidopsis thaliana
. SOS1 directly interacts with GI in a salt-dependent manner and stabilizes this protein to sustain a proper clock period under salinity conditions. SOS1 function in circadian clock regulation requires the salt-mediated secondary messengers cytosolic free calcium and reactive oxygen species, pointing to a distinct regulatory role for SOS1 in addition to its function as a transporter to maintain Na
+
homeostasis. Our results demonstrate that SOS1 maintains homeostasis of the salt response under high or daily fluctuating salt levels. These findings highlight the genetic capacity of the circadian clock to maintain timekeeping activity over a broad range of salinity levels.
Homogeneous ice nucleation in an ab initio machine-learning model of water
Authors: Piaggi Pablo M. , Weis Jack , Panagiotopoulos Athanassios Z. , Debenedetti Pablo G. , Car Roberto
Published: August 2022

Molecular simulations have provided valuable insight into the microscopic mechanisms underlying homogeneous ice nucleation. While empirical models have been used extensively to study this phenomenon, simulations based on first-principles calculations have so far proven prohibitively expensive. Here, we circumvent this difficulty by using an efficient machine-learning model trained on density-functional theory energies and forces. We compute nucleation rates at atmospheric pressure, over a broad range of supercoolings, using the seeding technique and systems of up to hundreds of thousands of atoms simulated with ab initio accuracy. The key quantity provided by the seeding technique is the size of the critical cluster (i.e., a size such that the cluster has equal probabilities of growing or melting at the given supersaturation), which is used together with the equations of classical nucleation theory to compute nucleation rates. We find that nucleation rates for our model at moderate supercoolings are in good agreement with experimental measurements within the error of our calculation. We also study the impact of properties such as the thermodynamic driving force, interfacial free energy, and stacking disorder on the calculated rates.
PTX3 structure determination using a hybrid cryoelectron microscopy and AlphaFold approach offers insights into ligand binding and complement activation
Authors: Noone Dylan P. , Dijkstra Douwe J. , van der Klugt Teun T. , van Veelen Peter A. , de Ru Arnoud H. , Hensbergen Paul J. , Trouw Leendert A. , Sharp Thomas H.
Published: August 2022

Pattern recognition molecules (PRMs) form an important part of innate immunity, where they facilitate the response to infections and damage by triggering processes such as inflammation. The pentraxin family of soluble PRMs comprises long and short pentraxins, with the former containing unique N-terminal regions unrelated to other proteins or each other. No complete high-resolution structural information exists about long pentraxins, unlike the short pentraxins, where there is an abundance of both X-ray and cryoelectron microscopy (cryo-EM)-derived structures. This study presents a high-resolution structure of the prototypical long pentraxin, PTX3. Cryo-EM yielded a 2.5-Å map of the C-terminal pentraxin domains that revealed a radically different quaternary structure compared to other pentraxins, comprising a glycosylated D4 symmetrical octameric complex stabilized by an extensive disulfide network. The cryo-EM map indicated α-helices that extended N terminal of the pentraxin domains that were not fully resolved. AlphaFold was used to predict the remaining N-terminal structure of the octameric PTX3 complex, revealing two long tetrameric coiled coils with two hinge regions, which was validated using classification of cryo-EM two-dimensional averages. The resulting hybrid cryo-EM/AlphaFold structure allowed mapping of ligand binding sites, such as C1q and fibroblast growth factor-2, as well as rationalization of previous biochemical data. Given the relevance of PTX3 in conditions ranging from COVID-19 prognosis, cancer progression, and female infertility, this structure could be used to inform the understanding and rational design of therapies for these disorders and processes.
Early B cell factor 4 modulates FAS-mediated apoptosis and promotes cytotoxic function in human immune cells
Authors: Kubo Satoshi , Kataria Rhea , Yao Yikun , Gabrielski Justin Q. , Zheng Lixin , Markowitz Tovah E. , Chan Waipan , Song Jian , Boddapati Arun K. , Saeki Keita , Häupl Björn , Park Ann Y. , Cheng Yan H. , Cui Jing , Oellerich Thomas , Lenardo Michael J.
Published: August 2022

Apoptosis is a genetically regulated program of cell death that plays a key role in immune disease processes. We identified EBF4, a little-studied member of the early B cell factor (EBF) family of transcription factors, in a whole-genome CRISPR screen for regulators of Fas/APO-1/CD95-mediated T cell death. Loss of EBF4 increases the half-life of the c-FLIP protein, and its presence in the Fas signaling complex impairs caspase-8 cleavage and apoptosis. Transcriptome analysis revealed that EBF4 regulates molecules such as TBX21, EOMES, granzyme, and perforin that are important for human natural killer (NK) and CD8+T cell functions. Proximity-dependent biotin identification (Bio-ID) mass spectrometry analyses showed EBF4 binding to STAT3, STAT5, and MAP kinase 3 and a strong pathway relationship to interleukin-2 regulated genes, which are known to govern cytotoxicity pathways. Chromatin immunoprecipitation and DNA sequencing analysis defined a canonical EBF4 binding motif, 5′-CCCNNGG/AG-3′, closely related to the EBF1 binding site; using a luciferase-based reporter, we found a dose-dependent transcriptional response of this motif to EBF4. We also conducted assay for transposase-accessible chromatin sequencing in EBF4-overexpressing cells and found increased chromatin accessibility upstream of granzyme and perforin and in topologically associated domains in human lymphocytes. Finally, we discovered that the EBF4 has basal expression in human but not mouse NK cells and CD8+T cells and vanishes following activating stimulation. Together, our data reveal key features of a previously unknown transcriptional regulator of human cytotoxic immune function.
Annotating dialogue acts in speech data
Authors: Verdonik Darinka
Published: August 2022

The aims of this paper are to detect the most problematic issues related to dialogue act annotation in speech
corpora and to define basic categories of dialogue acts. I critically examine and test generic schemes that represent different
lines of dialogue act annotation: AMI, DART, ISO 24617–2 and SWBD-DAMSL. It is found that the most problematic issues regarding
dialogue act annotation are related to the distinction between the semantic and pragmatic meanings of utterances, the annotation
of metadiscourse, and the adequacy and informativeness of the tagset. The identified basic dialogue act categories are information
providing, information seeking, actions, social acts and metadiscourse. The findings help improve dialogue act annotation.
Othering within the gay dating community?
Authors: Labor Jonalou S. , Samonte Christian Jaycee , Bana Norberto D.
Published: August 2022

Gay men and the bakla in the Philippines have long battled invisibility that any chance to
perform their gendered identities is a welcome gamble and opportunity to self-represent and be visible. This study looked into the
nature of self-representation among gay and bakla in dating applications and how these representations become
source of tensions in the LGBTQ+ community. In this study, ten gay men and ten bakla were interviewed to
construct their self-representations and unearth the reasons why such presentations are enacted in the dating apps. Findings
showed that gay men displayed heteronormative gay masculinity. Further, most of the bakla self-censored their
profiles to get matches and dates. There were some bakla, however, who refused invisibility and used the apps as
space for showing their authentic gender identity. Results of this study also identified the role of technology in enabling
masculine idealizations that emphasize hegemonic masculinity while reinforcing bakla invisibility.
A language socialisation perspective on Swedish immersion in Finland
Authors: Björklund Siv , Mård-Miettinen Karita , Pakarinen Sanna
Published: August 2022

This retrospective review applies a language socialisation perspective in examining the findings of a four-year research project on Swedish immersion in Finland. Findings from nine sub-studies within the project are reported with a point-of-view from three key actors’ (teachers, students, and parents) language socialisation processes. Results show that a special feature of immersion teacher socialisation is its continuous attention toward the additive multilingual nature of immersion education, which requires sustained attention to multilingual language use and development. Students in Swedish immersion are socialised into the use of multiple languages in school and act as socialisation agents also outside school. They bring the immersion language to their homes and influence the family language use. Immersion may thus have a considerable influence on how majority language speakers self-identify as language users. Altogether, the sub-studies demonstrate that the benefits of immersion education extend well beyond learning success of students.
(Mis)translating Sensitive Content
Authors: Naranjo Beatriz
Published: August 2022

This article offers an exploratory approach to the role of anger in translation performance. We performed a study in which translation students translated a negative review containing opinions that they may potentially find offensive. Based on previous findings pointing to punishment and restoration of justice as the most common behaviors of anger, we predicted that angry translators would manipulate the text in an attempt to punish the author and/or mitigate the offensive content. We operationalized such manipulation by identifying attenuating and emphasizing strategies in target texts. While no significant differences were revealed between baseline and post-read anger levels, sentiment analysis tools revealed angry moods when applied to participants’ written opinions. Significant differences were also found for the strategies applied with more occurrences for attenuation than emphasis. However, these findings are acknowledged as preliminary; larger samples, control groups and more reliable indicators of anger would be necessary to corroborate these results.
Effect of post-heat treatment on microstructure and properties of EH47 steel CGHAZ
Authors: Yang Xiaocong , Di Xinjie , Ba Lingzhi , Zhang Jiarong , Li Chengning
Published: August 2022

To clarify the effect of post-heat treatment on the microstructure and mechanical properties of the coarse-grained heat-affected zone (CGHAZ) for EH47 steel, simulated CGHAZ specimens were subjected to post-heat treatment at 250°C for 1.0 h. The results showed that the microstructure of CGHAZ was composed of granular bainite (GB) and lath bainite (LB), and a large number of iron-carbon particles (∼81 nm) were precipitated after post-heat treatment. The relationship between dislocations, low-angle grain boundaries and iron-carbon particles was revealed by KAM values. The iron-carbon particles hindered the movement of sub-grain boundaries and dislocations, thereby increased the yield strength (∼120 MPa). The precipitation of iron-carbon particles caused the cracking of bainite ferrite and reducing the fracture toughness of CGHAZ.
Demands of professional female cycling races: Influence race level and race duration (single or multi‐day events)
Authors: van Erp Teun , Lamberts Robert P.
Published: August 2022

This study is governed by two aims: firstly, expanding the meagre knowledge store regarding the demands set by professional female road cycling and, secondly, ascertaining whether these demands vary in relation to different race‐levels and race duration (single‐ or multi‐day events). A total of 1349 female professional road races was analysed and demands (intensity, load and performance) were determined. Races were classified based on race level (i.e. Women's World Tour [WWT], level.1 and level.2 according to the International Cycling Federation) and race duration (single‐ or multi‐day events). Differences were assessed with a multilevel random intercept model whilst the strength of said differences were indicated by Cohen's d (0–0.19 trivial; 0.20–0.59 small; 0.60–1.1.9 moderate; 1.20–1.99 large; ≥2.00 very large). In general, no moderate differences for load and intensity were noted for the different race levels. This result contrasts with data obtained from male road cycling. Moderate higher 3 and 5 min maximal mean power (MMP) values were noted in the WWT compared to Level.2 races. More substantial differences were found to exist between single‐ and multi‐day races with single‐day races presenting small to large higher load and intensity values. In addition, single‐day races presented higher MMPs overall durations (5 s–60 min) although these differences can be rated trivial to small. This study contributes to the limited knowledge store describing demands in professional female cycling. The reported data provide valuable insights which may aid practitioners and/or coaches in preparing female professional cyclists for races.
Impacts of regional land-use patterns on ecosystem services in the typical agro-pastoral ecotone of northern China
Authors: Chen Huimin , Zhao Yu , Fu Xiao , Tang Mingfang , Guo Mingjie , Zhang Shiqi , Zhu Yu , Qu Laiye , Wu Gang
Published: August 2022

A comprehensive understanding of the spatial-temporal evolution and driving forces on ecosystem services (ES) is essential for the agro-pastoral ecotone’s ecological security in northern China. However, the land-use pattern (LULC) agglomeration with spatial differentiation in the pastoral and agricultural areas has been rarely concerned. Taking distinct LULC (1980–2018) in Chifeng as an example, we compared four crucial categories of ESs with InVEST. Using SEM, we further contrasted the effects of several variables on regional ES variations in pastoral-dominated (North) and agriculture-dominated (South) regions, respectively. Results revealed the conversion between forest and grassland oriented the LULC transformation in the North. In contrast, human-activitiy-oriented land tended to occupy environmentally sensitive places in the South. Similar ES variations were supplied with the North outperforming the South when soil conservation was omitted. As for the impacts of regional ES variations, the natural and LULC policies both showed positive effects, whereas the anthropogenic factors showed positive in the North, which was negative in the South. Therefore, the ecologically-maintained-dominant and ecologically-restored-dominant strategies should be separately adopted in the North and South. Our study provided appropriate regional ecological management suggestions for balancing the LULC-driven conflicts between ecological protection and regional development.
Profiling of epigenetic marker regions in murine ILCs under homeostatic and inflammatory conditions
Authors: Beckstette Michael , Lu Chia-Wen , Herppich Susanne , Diem Elia C. , Ntalli Anna , Ochel Aaron , Kruse Friederike , Pietzsch Beate , Neumann Katrin , Huehn Jochen , Floess Stefan , Lochner Matthias
Published: August 2022

Epigenetic modifications such as DNA methylation play an essential role in imprinting specific transcriptional patterns in cells. We performed genome-wide DNA methylation profiling of murine lymph node–derived ILCs, which led to the identification of differentially methylated regions (DMRs) and the definition of epigenetic marker regions in ILCs. Marker regions were located in genes with a described function for ILCs, such as Tbx21, Gata3, or Il23r, but also in genes that have not been related to ILC biology. Methylation levels of the marker regions and expression of the associated genes were strongly correlated, indicating their functional relevance. Comparison with T helper cell methylomes revealed clear lineage differences, despite partial similarities in the methylation of specific ILC marker regions. IL-33–mediated challenge affected methylation of ILC2 epigenetic marker regions in the liver, while remaining relatively stable in the lung. In our study, we identified a set of epigenetic markers that can serve as a tool to study phenotypic and functional properties of ILCs.
Single-cell analyses reveal early thymic progenitors and pre-B cells in zebrafish
Authors: Rubin Sara A. , Baron Chloé S. , Pessoa Rodrigues Cecilia , Duran Madeleine , Corbin Alexandra F. , Yang Song P. , Trapnell Cole , Zon Leonard I.
Published: August 2022

The zebrafish has proven to be a valuable model organism for studying hematopoiesis, but relatively little is known about zebrafish immune cell development and functional diversity. Elucidating key aspects of zebrafish lymphocyte development and exploring the breadth of effector functions would provide valuable insight into the evolution of adaptive immunity. We performed single-cell RNA sequencing on ∼70,000 cells from the zebrafish marrow and thymus to establish a gene expression map of zebrafish immune cell development. We uncovered rich cellular diversity in the juvenile and adult zebrafish thymus, elucidated B- and T-cell developmental trajectories, and transcriptionally characterized subsets of hematopoietic stem and progenitor cells and early thymic progenitors. Our analysis permitted the identification of two dendritic-like cell populations and provided evidence in support of the existence of a pre-B cell state. Our results provide critical insights into the landscape of zebrafish immunology and offer a foundation for cellular and genetic studies.
Postdevelopmental knockout of Orai1 improves muscle pathology in a mouse model of Duchenne muscular dystrophy
Authors: García-Castañeda Maricela , Michelucci Antonio , Zhao Nan , Malik Sundeep , Dirksen Robert T.
Published: August 2022

Duchenne muscular dystrophy (DMD), an X-linked disorder caused by loss-of-function mutations in the dystrophin gene, is characterized by progressive muscle degeneration and weakness. Enhanced store-operated Ca2+ entry (SOCE), a Ca2+ influx mechanism coordinated by STIM1 sensors of luminal Ca2+ within the sarcoplasmic reticulum (SR) and Ca2+-permeable Orai1 channels in the sarcolemma, is proposed to contribute to Ca2+-mediated muscle damage in DMD. To directly determine the impact of Orai1-dependent SOCE on the dystrophic phenotype, we crossed mdx mice with tamoxifen-inducible, muscle-specific Orai1 knockout mice (mdx-Orai1 KO mice). Both constitutive and SOCE were significantly increased in flexor digitorum brevis fibers from mdx mice, while SOCE was absent in fibers from both Orai1 KO and mdx-Orai1 KO mice. Compared with WT mice, fibers from mdx mice exhibited (1) increased resting myoplasmic Ca2+ levels, (2) reduced total releasable Ca2+ store content, and (3) a prolonged rate of electrically evoked Ca2+ transient decay. These effects were partially normalized in fibers from mdx-Orai1 KO mice. Intact extensor digitorum longus muscles from mdx mice exhibited a significant reduction of maximal specific force, which was rescued in muscles from mdx-Orai1 KO mice. Finally, during exposure to consecutive eccentric contractions, muscles from mdx mice displayed a more pronounced decline in specific force compared with that of WT mice, which was also significantly attenuated by Orai1 ablation. Together, these results indicate that enhanced Orai1-dependent SOCE exacerbates the dystrophic phenotype and that Orai1 deficiency improves muscle pathology by both normalizing Ca2+ homeostasis and promoting sarcolemmal integrity/stability.
Expression of ENaC subunits in epithelia
Authors: Frindt Gustavo , Meyerson Joel R. , Satty Alexandra , Scandura Joseph M. , Palmer Lawrence G.
Published: August 2022

The epithelial Na+ channel (ENaC) is a heterotrimeric protein whose assembly, trafficking, and function are highly regulated. To better understand the biogenesis and activation of the channel, we quantified the expression of individual subunits of ENaC in rat kidneys and colon using calibrated Western blots. The estimated abundance for the three subunits differed by an order of magnitude with the order γENaC ∼ βENaC ≫ αENaC in both organs. Transcript abundance in the kidney, measured with digital-drop PCR and RNAseq, was similar for the three subunits. In both organs, the calculated protein expression of all subunits was much larger than that required to account for maximal Na+ currents measured in these cells, implying a large excess of subunit protein. Whole-kidney biotinylation indicated that at least 5% of β and γ subunits in the kidney and 3% in the colon were expressed on the surface under conditions of salt restriction, which maximizes ENaC-dependent Na+ transport. This indicates a 10- to 100-fold excess of βENaC and γENaC subunits at the surface relative to the requirement for channel activity. We conclude that these epithelia make much more ENaC protein than is required for the physiological function of the channel. This could facilitate rapid regulation of the channels at the cell surface by insuring a large population of inactive, recruitable subunits.
The effect of gas-density gradient on high-harmonic generation from neon-filled cells using annular and Gaussian laser beams
Authors: Ansari A , Kumar M , Singhal H , Chakera J A
Published: August 2022

An experimental study was performed to explore the effect of gas-density gradient in laser propagation direction on high-harmonic generation from neon-filled cells using a 50 fs annular and Gaussian Ti:sapphire laser beam. It was observed that, despite 20% lower power, the photon flux of the high-harmonics generated using an annular beam under optimum parameter conditions (∼2.5 × 1010 photons/sec for the 37th order in a 5 mm long cell) is on par with the maximum photon flux generated using a full Gaussian beam (∼2 × 1010 photons/sec for the 37th order in a 15 mm long cell). To elucidate the underlying mechanism for the experimental observation, a numerical simulation of the propagation of both the annular and Gaussian laser beams inside the cell was performed. The simulation was extended to estimate the high-harmonic intensity, after incorporating the effect of laser defocusing, the electron trajectory resolved phase-matching, and gas-density gradient. The dominant role of short electron trajectories was observed in the case of the annular beam, whereas, in the case of the Gaussian beam, a contribution of both short and long trajectories was found. Our analysis shows that, in neon-filled cells, the gas-density gradient present at the laser exit end of the cell plays a dominant role in achieving a high photon flux using an annular laser beam. Further, the annular beam not only provides a higher flux but also has lower divergence and higher coherence. This study will be useful in attosecond pulse metrology as well as in imaging applications viz coherent diffractive imaging.