bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of TAMP family on the tight junction strand network and barrier function in epithelial cells
Authors: Saito Akira C. , Endo Chisato , Fukazawa Yugo , Higashi Tomohito , Chiba Hideki
Published: September 2022

Occludin, tricellulin, and marvelD3 belong to the tight junction (TJ)‐associated MARVEL protein family. Occludin and tricellulin jointly contribute to TJ strand branching point formation and epithelial barrier maintenance. However, whether marvelD3 has the same function remains unclear. Furthermore, the roles of the carboxy‐terminal cytoplasmic tail, which is conserved in occludin and tricellulin, on the regulation of TJ strand morphology have not yet been explored in epithelial cells. We established tricellulin/occludin/marveld3 triple‐gene knockout (tKO) MDCK II cells and evaluated the roles of marvelD3 in the TJ strand structure and barrier function using MDCK II cells and a mathematical model. The complexity of TJ strand networks and paracellular barrier did not change in tKO cells compared to that in tricellulin/occludin double‐gene knockout (dKO) cells. Exogenous marvelD3 expression in dKO cells did not increase the complexity of TJ strand networks and epithelial barrier tightness. The expression of the carboxy‐terminal truncation mutant of tricellulin restored the barrier function in the dKO cells, whereas occludin lacking the carboxy‐terminal cytoplasmic tail was not expressed on the plasma membrane. These data suggest that marvelD3 does not affect the morphology of TJ strands and barrier function in MDCK II cells and that the carboxy‐terminal cytoplasmic tail of tricellulin is dispensable for barrier improvement.
Neuronal imbalance of excitation and inhibition in schizophrenia: a scoping review of gamma‐band ASSR findings
Authors: Onitsuka Toshiaki , Tsuchimoto Rikako , Oribe Naoya , Spencer Kevin M. , Hirano Yoji
Published: September 2022

Recent empirical findings suggest that altered neural synchronization, which is hypothesized to be associated with an imbalance of excitatory (E) and inhibitory (I) neuronal activities, may underlie a core pathophysiological mechanism in patients with schizophrenia. The auditory steady‐state response (ASSR) examined by electroencephalography (EEG) and magnetoencephalography (MEG) has been proposed as a potential biomarker for evaluating altered neural synchronization in schizophrenia. For this review, we performed a comprehensive literature search for papers published between 1999 and 2021 examining ASSRs in patients with schizophrenia. Almost all EEG‐ASSR studies reported gamma‐band ASSR reductions, especially to 40‐Hz stimuli both in power and/or phase synchronization in chronic and first‐episode schizophrenia. In addition, similar to EEG‐ASSR findings, MEG‐ASSR deficits to 80‐Hz stimuli (high gamma) have been reported in patients with schizophrenia. Moreover, the 40‐Hz ASSR is likely to be a predictor of the onset of schizophrenia. Notably, increased spontaneous (or ongoing) broadband (30–100 Hz) gamma power has been reported during ASSR tasks, which resembles the increased spontaneous gamma activity reported in animal models of E/I imbalance. Further research on ASSRs and evoked and spontaneous gamma oscillations is expected to elucidate the pathophysiology of schizophrenia with translational implications.
Quality of life assessment in childhood vitiligo in a tertiary care center in India
Authors: Dev Anubha , Narayan Vignesh , Vinay Keshavamurthy , Bishnoi Anuradha , Parsad Davinder , Kumaran Muthu Sendhil
Published: September 2022

The impact of vitiligo on quality of life (QOL) of children is not well studied. In this cross‐sectional study, QOL in the form of Children's Dermatology Life Quality Index (CDLQI) was assessed in 114 children with vitiligo over a year. The mean CDLQI was 2.72 ± 3.35. There was a significant correlation of body surface area involved with the DLQI and the impairment was higher in older children. The psychosocial burden of vitiligo in children cannot be ignored and must be tackled early on in order to prevent an ever lasting impact on young minds.
Linseed oil in boar's diet improved in vivo fertility and antioxidant status
Authors: Singh Mahak , Mollier Rongsennangba Talimoa , Patton Renphamo Nzanthung , Pongener Nungshitula , Bordoloi Lahar Jayoti , Kumar Rakesh , Katiyar Rahul , Khan Meraj Haider , Rajkhowa Dipjayoti , Mishra Vinay Kumar
Published: September 2022

The reactive oxygen species (ROS) which are produced during storage of boar semen are causing oxidative stress and leads to poor fertility. Also, tropical and sub‐tropical weather condition adversely impacts the physicomorphological quality and fertility of boar sperm. The aim of this study was to examine the effects of feeding linseed oil to boar on its seminal attributes, sperm kinetics, biomarkers of antioxidant, fatty acid profile of seminal plasma (SP) and sperm and in vivo fertility. Six Hampshire crossbreed boars were fed with 90 ml linseed oil (LIN) whereas six Hampshire crossbreed boars were fed 90 ml canola oil (CON) for 16 weeks. Sperm quality was evaluated (60 ejaculates for each group; a total of 120 ejaculates) for motility, livability, abnormal morphology, acrosomal membrane integrity, hypo‐osmotic swelling test (HOST) and sperm kinetic parameters by computer assisted semen analysis (CASA) at 0 h and at 72 h of storage at 17°C. Biomarkers of antioxidant (glutathione peroxidase; GPx, catalase; CAT, total antioxidant capacity; TAC) and malondialdehyde (MDA) were measured in SP and serum. Gas chromatography–mass spectrometry (GC–MS) was used for the estimation of fatty acid composition of SP and sperm. Boars fed with linseed oil had higher semen volume (p < .01) and more total sperm numbers (p < .01). Feeding linseed oil to boar enhanced seminal attributes (p < .05) at 0 h as well as at 72 h of storage. Linseed oil feeding (p < .01) improved biomarkers of antioxidants and significantly (p < .01) lowered the lipid peroxidation in serum and SP. Linseed oil feeding (p < .05) increased the proportion of alpha linolenic (ALA), arachidonic and docosahexaenoic (DHA) fatty acids in SP. The ratio of n‐6 to n‐3 fatty acids in sperm increased significantly (p < .01) in treatment group. Farrowing rate was significantly (p < .05) higher in treatment group. In conclusion, feeding linseed oil to boar improved the in vivo fertility, enhanced antioxidant capacity and increased the DHA content of SP and sperm.
The attitudes of religious group leaders towards xenotransplantation: A focus group study
Authors: Hurst Daniel J , Padilla Luz A. , Cooper David KC , Walters Wendy , Paris Wayne
Published: September 2022

Clinical trials of xenotransplantation (XTx) may start in coming years. Religious views have been mentioned as possible barriers to XTx acceptance. While there have been reports on perspectives of theologians in regard to XTx, no report has studied the perspectives of community religious leaders. A focus group was conducted with a sample of members of the following faith groups: Islam, Catholicism, and Protestantism. Qualitative content analysis was performed to identify interpretive themes. Four themes emerged. Participants were receptive to the idea of XTx and expressed no religious barriers to accepting a pig xenograft as a lifesaving therapy but did express certain concerns. Religious leaders accept the idea of XTx and do not see it as contradictory to their beliefs. However, some concerns were raised. Future studies addressing these concerns and exploring the potential role of religious leaders in educating the community on XTx are needed.
FLUID FLOW INDUCED BY AN ELASTIC PLATE IN HEAVING MOTION
Authors: Hlaing Win Khin May , Kato Kentaro , Sung Hyung Jin , Obi Shinnosuke
Published: September 2022

We perform three-dimensional simulations of an elastic plate heaving in a sinusoidal motion with different frequencies to explore the effects of the forcing heaving frequency on the hydrodynamic force generation and flow structures. It is aimed to simulate the motion of a rectangular elastic plate, representing a simplified flexible wing or fin, placed in an open water tank as in a corresponding experimental study. The top edge of the plate oscillates sinusoidally in water at rest. Simulations are conducted for the fluid structure interaction of an elastic plate with a special version of the open-source library C++ OpenFOAM, foam-extend-3.2. The plate oscillates at different heaving frequencies in a range of 3.5 Hz and 4.5 Hz. Experiments are carried out to validate our simulations. The results are in a good agreement with the experiment in terms of the representation of the resonant frequency and the induced hydrodynamic forces. It is found that the hydrodynamic force and propulsive efficiency are mainly affected by the elastic deformation and forcing heaving frequencies. The generated thrust is observed to be significantly enhanced at the resonant frequency, while the propulsive efficiency is increased at the heaving frequency which is greater than the resonant frequency. The results of our simulations point to the importance of resonant flapping frequency for considering the optimal heaving frequency to achieve the best performance and to get the improved thrust force, which are crucial for the locomotion of birds, insects, fishes, flapping-based micro air and underwater vehicles.
MECHANISM OF BOULDER TRANSPORT DURING EXTREME WAVE EVENTS ALONG THE EASTERN FLANK OF THE ARABIAN SEA
Authors: Khan Afzal , Singh Avichal , S Gadhavi Mahendrasinh , N Malik Javed
Published: September 2022

The study presents hydrodynamic mechanism of boulder transportation along the rocky coastal margins with a case study from the eastern flank of the Arabian Sea. Limestone blocks ranging in size from small (1.3, 0.95, 0.35) m to large (2.9, 1.68, 0.5)m scattered over a rocky platform were considered for the approximation of wave energy. The boulders with prominent imbrications indicative of flow direction were used to assess the minimum flow velocity to initiate boulder transport during extreme wave events. The irregular /polyhedral boulders, previously a part of sub-aerially exposed jointed limestone strata, were detached and transported from the rocky coastal platform under the impact of high energy waves. We calculated velocity and height for dynamic waves required to transport boulders onshore using boulder dimensions i.e., length (a-axis), width (b-axis), and height (c-axis). By applying hydrodynamic equations, it is deduced that the average wave velocity required to transport boulders of such dimensions onshore must be ≥7.28m/s and the corresponding average wave heights must be ≥5.51m and ≥1.38m in case of the storm and tsunami events respectively. Based on largest clast recorded, ≈7m high storm waves and ≈2m high tsunami waves are capable of transporting ≈2.5m3 tabular boulders along rocky coastal margins. Since this region has documented records of very-severe cyclonic storms affecting the coastal landscape in addition to the widespread impact of 1945 tsunami, we suggest that boulders deposition on the eastern flank had received inputs from storm as well as tsunami events for the last few decades.
An Exploratory Survey on the Adoption of Blockchain Technology in Streamlining Malaysia Real Estate During Covid-19 Pandemic
Authors: Jasimin Tuti Haryati , Nordin Muhammad Faris
Published: September 2022

The global pandemic outbreak of Covid-19 and the restrictions on movement have created an unprecedented crisis for the real estate industry with mounting pressure including on property management. The higher-than-normal occupancy and load especially on strata residential buildings during the movement control order (MCO) leads to a more crucial task for property managers to ensure that every part of the building was in good working order. A high transmissible virus poses various challenges in property managers’ jobs including maintenance, inspections, viewing, and marketing the property. Accordingly, the pandemic has created a greater sense of urgency than before for real estate companies to increase technology usage by having an automated real estate record involving the buying or selling process. This study aims to explore the potential opportunities of blockchain adoption in the real estate management process. The objectives of this study are: i) to investigate the challenges of real estate managers in managing the real estate during the pandemic; ii) to study the benefits of blockchain technology adoption in the real estate management process, and (iii) to examine the opportunities of blockchain to enhance in streamlining the real estate management process. This research engages with the qualitative nature of the research strategy due to the explorative character by conducting the unstructured interview with the real estate players involved in managing the properties. All the collected materials have been transcribed and categorized to ensure that they could be analysed through NVivo, a qualitative data analysis programme. The expected outcome of this study will provide scientific evidence on the readiness of the Malaysian real estate industry to embrace technology by digitalizing the property management which is in line with the vision of the government to ensure Malaysia makes the Digital Leap into the Fourth Industrial Revolution (IR 4.0)
COVID 19: Are Our Green Areas Enough for People’s Well-being
Authors: Wan Ismail Wan Azlina , Fitry Rosley Muhamad Solehin , Wan Ibrahim Wan Yusryzal , Abdul Rahman Syumi Rafida
Published: September 2022

Malaysians’ overall well-being, particularly in urban areas, has been seriously affected physically and emotionally due to the series of imposed lockdowns in the country. The number of mental health problems such as depression, anxiety, and loneliness has increased tremendously during the lockdown period. Various studies suggest that these mental health issues could be coped with if people are allowed to access urban greeneries and public green spaces during the pandemic. However, the degree to how adequate existing green areas are to fulfil an urban community’s needs with strict social distancing compliance is still vaguely interpreted in the literature. It is still arguable that the current 10 per cent green area requirement is still relevant to the current context of the COVID-19 pandemic. This study aims to determine the sufficient amount of green areas for people’s well-being during the pandemic, based on the local population, accessibility to green areas, and compliance with the new norm of social distancing by a minimum of one meter. Therefore, an urban neighbourhood in Iskandar Puteri, Johor, Malaysia was selected and simulated using GIS spatial analysis based on the highlighted parameters. As a result, the study found that the current size of existing green areas in the neighbourhood is insufficient in terms of compliance with the parameters, especially Malaysia’s social distancing requirements. This study could provide a platform for future planning to include pandemic risk reduction into urban planning policies, especially in the context of Malaysia, to cater to future uncertainties
Landscape Design Toward Covid-19 in the Old Town Semarang, Indonesia
Authors: Kurniati Rina , Kurniawati Wakhidah , Kusumo Dewi Diah Intan , Syahri Endah Kartika
Published: September 2022

A significant increase in Covid-19 cases worldwide disrupted many sectors. The virus transmission through the air requires that people limit outdoor activities and apply social distancing. However, outdoor activities cannot be avoided because it is how people meet their daily needs. The urban landscape design arrangement is crucial, especially in public spaces. Old Town Semarang is a location with the potential for high outdoor activities, especially tourism. CCTV data shows that tourists could reach up to 500 people per day, and the average visitor does a comply with health protocols. This is worsened by the unadopted landscape conditions in this area to the current pandemic conditions. Therefore, a landscape design approach is needed to adapt to visitors' needs and minimize virus transmission. This research examined the effect of landscape design on Covid-19 in the Old Town area. Data were collected on the existing landscape conditions, cultural heritage, and the distribution of positive Covid-19 cases and analyzed using spatial analysis, design simulation, and quantitative descriptive. The results were presented as simulation or landscape design recommendations according to cultural heritage elements and health protocols. The recommendations are a division of activity zones with a visitor quota system, and optimization of health facilities, signage for physical distance, as well as a clean and healthy lifestyle for visitors.
Adaptation of the Pedestrian Walkways Design along the Trans Semarang Bus Corridor to COVID-19
Authors: Kusumo Dewi Diah Intan , Rakhmatulloh Anita Ratnasari , Syahri Endah Kartika
Published: September 2022

COVID-19 cases continue to increase in Indonesia, with an estimated value of 719,000 and an 8.37% mortality rate, due to the severity and potency of the deadly disease. One of the provinces that mostly contributes to the high mortality rate is Central Java, especially in populous areas like Semarang City. The spread of the virus occurs through direct contact between humans, forcing physical and social distances to become more important, especially in public spaces. Based on these conditions, city planning experts reportedly suggests a public space re-design process, adaptable to the current pandemic conditions, in order to provide a comfortable, safer, and sustainable urban life. Therefore, this study aims to analyze the integration of the mass transportation system (the Bus Trans Semarang) with the readjustment and redesign potentials of pedestrian walkways, in response to the COVID-19 pandemic. For the past two years, the development of pedestrian walkways has become an integral part of the Semarang City Government, in order to realize a sustainable transportation system. Furthermore, the pandemic has presently made pedestrian walkways less functional, due to public concerns on its spread in external areas. The retrieval spatial-based data of this study focused on the bus stops for the Trans Semarang Bus Corridor, which were potential points for the emergence of walking activities. The method used in the measurement of pedestrian activity included behavioral mapping and urban design analysis. This was to identify the pedestrian design indicators that were adaptive to the pandemic conditions. The simulation methods also assisted the data visualization process, by using spatial applications such as ArcGIS and Sketchup. After this, the calculation of the capacity was carried out, to determine the maximum limit of the available spaces. The results were in the form of indicators, such as additional width, lane division, as well as provision of health and hygiene facilities. These were the main recommendations applied on the pedestrian walkways' environmental characteristics, at various points in Semarang City.
Evaluation the Impact of Spatial Configuration on Socio-Economic Parameters in Emerging Shopping Centers. Case study of Ritaj Mall in Constantine, Algeria
Authors: Zinai Manel , Chaouche Salah
Published: September 2022

This article questions the impact of the spatial configuration on user behavior and economic performance in the multi-level shopping center of Ritaj Mall in Constantine, Algeria. For ten years, large private real estate operators invest in different kinds of commercial building. The arrival of this new shopping complex in Algerian cities sis an opportunity to examine the question of architectural quality, especially that numerous papers and the theses have criticized the architectural production in Algerian, mainly in the residential and public sectors. Through the spatial analysis of the circulation spaces, the movement distribution and the architectural design parameters, the objective of this text is to better understand the correlation between “conceived” spaces and “lived” spaces. Their correlation constitutes a determining index of spatial qualities. For this purpose, an analysis is adopted according to a method of space syntax and completed by empirical surveys, and statistical correlation. Essentially, this paper shows that the axiality and interconnectedness of spaces largely determine the spatial quality of a commercial building. In addition, the central space (atrium) plays a determining role in the distribution of user flows over all vertical and horizontal spaces and extensions. It also shows the importance of spatial accessibility parameters in the distribution of economic and social activities
A Biomimetic Approach to Water Harvesting Strategies: An Architectural Point of View
Authors: Aslan Duygunur , Selçuk Semra Arslan , Mutlu Avinç Güneş
Published: September 2022

In the current century, due to global warming, pollution, climate change and the exponential growth of the world population, water resources are consumed at alarming rates. For this reason, sustainable methods of water harvesting have become an important research topic of today. In built environments, which are known to account for a significant share of total water consumption, places the development of alternative solutions for the acquisition and effective use of water to the forefront of the agenda. On the other hand, “nature” offers clues about how plant and animal species manage to use limited water resources with sustainable methods while also providing innovative solutions for “water harvesting”. In this context, this research seeks to answer “Can water harvesting strategies of living organisms that manage to obtain water via sustainable methods be transferred to building design through biomimicry?” In this direction, considering the potentials of biomimicry in architecture, plants and animals that are successful in water harvesting have been researched. In addition, biomimetic designs inspired by these living organisms have been analyzed. As a result of this analysis, it has been concluded that, with the use of biomimetic design techniques effective water harvesting methods can be developed for buildings
Formation and computational implications of assemblies in neural circuits
Authors: Miehl Christoph , Onasch Sebastian , Festa Dylan , Gjorgjieva Julijana
Published: September 2022

In the brain, patterns of neural activity represent sensory information and store it in non‐random synaptic connectivity. A prominent theoretical hypothesis states that assemblies, groups of neurons that are strongly connected to each other, are the key computational units underlying perception and memory formation. Compatible with these hypothesised assemblies, experiments have revealed groups of neurons that display synchronous activity, either spontaneously or upon stimulus presentation, and exhibit behavioural relevance. While it remains unclear how assemblies form in the brain, theoretical work has vastly contributed to the understanding of various interacting mechanisms in this process. Here, we review the recent theoretical literature on assembly formation by categorising the involved mechanisms into four components: synaptic plasticity, symmetry breaking, competition and stability. We highlight different approaches and assumptions behind assembly formation and discuss recent ideas of assemblies as the key computational unit in the brain.

image
A Fault Diagnosis Method for Lithium Batteries Based on Optimal Variational Modal Decomposition and Dimensionless Feature Parameters
Authors: Chang Chun , Tao Chen , Wang Shaojin , Zhang Ruhang , Tian Aina , Jiang Jiuchun
Published: September 2022

Due to the frequent occurrence of electric vehicles safety accidents caused by battery system failures, in order to ensure the normal operation of the vehicle, it is crucial to do a fault diagnosis of the electric vehicle lithium battery. This paper presents a fault diagnosis method for lithium batteries based on optimal variational modal decomposition and dimensionless feature parameters for identifying faulty batteries. The method first preprocesses the voltage signal of a lithium battery by optimal variable mode decomposition to obtain the high- and low-frequency components of the signal and reconstructs the high- and low-frequency components. Then, the dimensionless feature parameters are extracted according to the reconstructed signal, and feature reduction of the dimensionless feature parameters is carried out by a locally linear embedding algorithm. Finally, a local outlier factor algorithm is used to detect faulty batteries. After verified by the operation data before the real electric vehicle's thermal runaway failure, this method can detect the faulty battery timely and accurately.
Testing perceptual flexibility in speech through the categorization of whistled Spanish consonants by French speakers
Authors: Tran Ngoc Anaïs , Meunier Fanny , Meyer Julien
Published: September 2022

Whistled speech is a form of modified speech where, in non-tonal languages, vowels and consonants are augmented and transposed to whistled frequencies, simplifying their timbre. According to previous studies, these transformations maintain some level of vowel recognition for naive listeners. Here, in a behavioral experiment, naive listeners' capacities for the categorization of four whistled consonants (/p/, /k/, /t/, and /s/) were analyzed. Results show patterns of correct responses and confusions that provide new insights into whistled speech perception, highlighting the importance of frequency modulation cues, transposed from phoneme formants, as well as the perceptual flexibility in processing these cues.
Difference between frequency and suppression tuning curves in a two-dimensional cochlear model
Authors: Murakami Yasuki , Fuji Takumi
Published: September 2022

Suppression tuning curves (STCs) can be used to evaluate the cochlear frequency selectivity. However, the tip of the STC is located at a higher frequency than that of the frequency tuning curve (FTC) measured in the same preparation. Therefore, this study compares STCs from one-dimensional (1D) and two-dimensional (2D) cochlear models, which ignore and include short waves, respectively. The simulated STC tip is at a higher frequency than that of FTC in the 2D model, unlike the 1D model. The result suggests that short waves in the 2D model are responsible for the upward frequency of STC relative to FTC.
Continuous Thermoregulatory Responses to a Mass-Participation 89-km Ultramarathon Road Race
Authors: Byrne Christopher , Cosnefroy Aurelien , Eston Roger , Lee Jason K.W. , Noakes Tim
Published: September 2022

Purpose: To continuously measure body core temperature (Tc) throughout a mass-participation ultramarathon in subelite recreational runners to quantify Tc magnitude and the influence of aerobic fitness and body fat. Methods: Twenty-three participants (19 men and 4 women; age 45 [9] y; body mass 72.0 [9.3] kg; body fat 26% [6%]; peak oxygen uptake 50 [6] mL·kg−1·min−1) had gastrointestinal temperature measured during an 89-km ultramarathon. Prerace-to-postrace changes in body mass, plasma sodium, and fluid and food recall quantified body water balance. Results: In maximal environmental conditions of 26.3 °C and 53% humidity, 21 of the 23 participants finished in 10:28 (01:10) h:min while replacing 49% (27%) of sweat losses, maintaining plasma sodium (140 [3] mmol·L−1), and dehydrating by 4.1% (1.3%). Mean maximum Tc was 39.0 (0.5) (range 38.2–40.1 °C) with 90% of race duration ≤39.0 °C. Mean maximum ΔTc was 1.9 (0.9) (0.9–2.7 °C) with 95% of race duration ≤2.0 °C. Over 0 to 45 km, associations between ΔTc and peak oxygen uptake (positive) and body fat (negative) were observed. Over 58 to 89 km, associations between Tc and peak oxygen uptake (negative) and body fat (positive) were observed. Conclusions: Modest Tc responses were observed in recreational ultramarathon runners. Runners with higher levels of aerobic fitness and lower levels of body fat demonstrated the greatest changes in Tc during the first half of the race. Conversely, runners with lower levels of aerobic fitness and higher levels of body fat demonstrated the greatest absolute Tc in the final third of the race.
A neurogenetic mechanism of experience-dependent suppression of aggression
Authors: Ishii Kenichi , Cortese Matteo , Leng Xubo , Shokhirev Maxim N. , Asahina Kenta
Published: September 2022

Aggression is an ethologically important social behavior, but excessive aggression can be detrimental to fitness. Social experiences among conspecific individuals reduce aggression in many species, the mechanism of which is largely unknown. We found that loss-of-function mutation of
nervy
(
nvy
), a
Drosophila
homolog of vertebrate myeloid translocation genes (MTGs), increased aggressiveness only in socially experienced flies and that this could be reversed by neuronal expression of human MTGs. A subpopulation of octopaminergic/tyraminergic neurons labeled by
nvy
was specifically required for such social experience–dependent suppression of aggression, in both males and females. Cell type–specific transcriptomic analysis of these neurons revealed aggression-controlling genes that are likely downstream of
nvy
. Our results illustrate both genetic and neuronal mechanisms by which the nervous system suppresses aggression in a social experience–dependent manner, a poorly understood process that is considered important for maintaining the fitness of animals.
Pronounced sequence specificity of the TET enzyme catalytic domain guides its cellular function
Authors: Ravichandran Mirunalini , Rafalski Dominik , Davies Claudia I. , Ortega-Recalde Oscar , Nan Xinsheng , Glanfield Cassandra R. , Kotter Annika , Misztal Katarzyna , Wang Andrew H. , Wojciechowski Marek , Rażew Michał , Mayyas Issam M. , Kardailsky Olga , Schwartz Uwe , Zembrzycki Krzysztof , Morison Ian M. , Helm Mark , Weichenhan Dieter , Jurkowska Renata Z. , Krueger Felix , Plass Christoph , Zacharias Martin , Bochtler Matthias , Hore Timothy A. , Jurkowski Tomasz P.
Published: September 2022

TET (ten-eleven translocation) enzymes catalyze the oxidation of 5-methylcytosine bases in DNA, thus driving active and passive DNA demethylation. Here, we report that the catalytic domain of mammalian TET enzymes favor CGs embedded within basic helix-loop-helix and basic leucine zipper domain transcription factor–binding sites, with up to 250-fold preference in vitro. Crystal structures and molecular dynamics calculations show that sequence preference is caused by intrasubstrate interactions and CG flanking sequence indirectly affecting enzyme conformation. TET sequence preferences are physiologically relevant as they explain the rates of DNA demethylation in TET-rescue experiments in culture and in vivo within the zygote and germ line. Most and least favorable TET motifs represent DNA sites that are bound by methylation-sensitive immediate-early transcription factors and octamer-binding transcription factor 4 (OCT4), respectively, illuminating TET function in transcriptional responses and pluripotency support.
Distinctive exercise-induced inflammatory response and exerkine induction in skeletal muscle of people with type 2 diabetes
Authors: Pillon Nicolas J. , Smith Jonathon A. B. , Alm Petter S. , Chibalin Alexander V. , Alhusen Julia , Arner Erik , Carninci Piero , Fritz Tomas , Otten Julia , Olsson Tommy , van Doorslaer de ten Ryen Sophie , Deldicque Louise , Caidahl Kenneth , Wallberg-Henriksson Harriet , Krook Anna , Zierath Juleen R.
Published: September 2022

Mechanistic insights into the molecular events by which exercise enhances the skeletal muscle phenotype are lacking, particularly in the context of type 2 diabetes. Here, we unravel a fundamental role for exercise-responsive cytokines (
exerkines
) on skeletal muscle development and growth in individuals with normal glucose tolerance or type 2 diabetes. Acute exercise triggered an inflammatory response in skeletal muscle, concomitant with an infiltration of immune cells. These exercise effects were potentiated in type 2 diabetes. In response to contraction or hypoxia, cytokines were mainly produced by endothelial cells and macrophages. The chemokine CXCL12 was induced by hypoxia in endothelial cells, as well as by conditioned medium from contracted myotubes in macrophages. We found that CXCL12 was associated with skeletal muscle remodeling after exercise and differentiation of cultured muscle. Collectively, acute aerobic exercise mounts a noncanonical inflammatory response, with an atypical production of exerkines, which is potentiated in type 2 diabetes.
Two cooperative binding sites sensitize PI(4,5)P
2
recognition by the tubby domain
Authors: Thallmair Veronika , Schultz Lea , Zhao Wencai , Marrink Siewert J. , Oliver Dominik , Thallmair Sebastian
Published: September 2022

Phosphoinositides (PIs) are lipid signaling molecules that operate by recruiting proteins to cellular membranes via PI recognition domains. The dominant PI of the plasma membrane is phosphatidylinositol 4,5-bisphosphate [PI(4,5)P
2
]. One of only two PI(4,5)P
2
recognition domains characterized in detail is the tubby domain. It is essential for targeting proteins into cilia involving reversible membrane association. However, the PI(4,5)P
2
binding properties of tubby domains have remained enigmatic. Here, we used coarse-grained molecular dynamics simulations to explore PI(4,5)P
2
binding by the prototypic tubby domain. The comparatively low PI(4,5)P
2
affinity of the previously described canonical binding site is underpinned in a cooperative manner by a previously unknown, adjacent second binding site. Mutations in the previously unknown site impaired PI(4,5)P
2
-dependent plasma membrane localization in living cells and PI(4,5)P
2
interaction in silico, emphasizing its importance for PI(4,5)P
2
affinity. The two-ligand binding mode may serve to sharpen the membrane association-dissociation cycle of tubby-like proteins that underlies delivery of ciliary cargo.
Ramped measurement technique for robust high-fidelity spin qubit readout
Authors: Keith Daniel , Chung Yousun , Kranz Ludwik , Thorgrimsson Brandur , Gorman Samuel K. , Simmons Michelle Y.
Published: September 2022

State preparation and measurement of single-electron spin qubits typically rely on spin-to-charge conversion where a spin-dependent charge transition of the electron is detected by a coupled charge sensor. For high-fidelity, fast readout, this process requires that the qubit energy is much larger than the temperature of the system limiting the temperature range for measurements. Here, we demonstrate an initialization and measurement technique that involves voltage ramps rather than static voltages allowing us to achieve state-to-charge readout fidelities above 99% for qubit energies almost half that required by traditional methods. This previously unidentified measurement technique is highly relevant for achieving high-fidelity electron spin readout at higher temperature operation and offers a number of pragmatic benefits compared to traditional energy-selective readout such as real-time dynamic feedback and minimal alignment procedures.
Homoatomic cations: From [P
5
]
+
to [P
9
]
+
Authors: Frötschel-Rittmeyer Julia , Holthausen Michael , Friedmann Christian , Röhner David , Krossing Ingo , Weigand Jan J.
Published: September 2022

Recent synthetic approaches to a series of [P
9
]
X
salts (
X
= [F{Al(OR
F
)
3
}
2
], [Al(OR
F
)
4
], and (R
F
= C(CF
3
)
3
); Ga
2
Cl
7
) overcome limitations in classical synthesis methods that proved unsuitable for phosphorus cations. These salts contain the homopolyatomic cation [P
9
]
+
via (I) oxidation of P
4
with NO[F{Al(OR
F
)
3
}
2
], (II) the arene-stabilized Co(I) sandwich complex [Co(arene)
2
][Al(OR
F
)
4
] [arene =
ortho
-difluorobenzene (
o
-DFB) and fluorobenzene (FB)], or (III) the reduction of [P
5
Cl
2
][Ga
2
Cl
7
] with Ga[Ga
2
Cl
7
] as Ga(I) source in the presence of P
4
. Quantum chemical CCSD(T) calculations suggest that [P
9
]
+
formation from [Co(arene)
2
]
+
occurs via the nido-type cluster [(
o
-DFB)CoP
4
]
+
, which resembles the isoelectronic, elusive [P
5
]
+
. Apparently, the nido-cation [P
5
]
+
forms intermediately in all reactions, particularly during the Ga(I)-induced reduction of [P
5
Cl
2
]
+
and the subsequent pick up of P
4
to yield the final salt [P
9
][Ga
2
Cl
7
]. The solid-state structure of [P
9
][Ga
2
Cl
7
] reveals the anticipated
D
2d
-symmetric Zintl-type cage for the [P
9
]
+
cation. Our approaches show great potential to bring other [P

n

]
+
cations from the gas to the condensed phase.
Variant Polycomb complexes in
Drosophila
consistent with ancient functional diversity
Authors: Kang Hyuckjoon , Cabrera Janel R. , Zee Barry M. , Kang Heather A. , Jobe Jenny Marie , Hegarty Maeve B. , Barry Aurelie E. , Glotov Alexander , Schwartz Yuri B. , Kuroda Mitzi I.
Published: September 2022

Polycomb group (PcG) mutants were first identified in
Drosophila
on the basis of their failure to maintain proper
Hox
gene repression during development. The proteins encoded by the corresponding fly genes mainly assemble into one of two discrete Polycomb repressive complexes: PRC1 or PRC2. However, biochemical analyses in mammals have revealed alternative forms of PRC2 and multiple distinct types of noncanonical or variant PRC1. Through a series of proteomic analyses, we identify analogous PRC2 and variant PRC1 complexes in
Drosophila
, as well as a broader repertoire of interactions implicated in early development. Our data provide strong support for the ancient diversity of PcG complexes and a framework for future analysis in a longstanding and versatile genetic system.
A tetravalent TREM2 agonistic antibody reduced amyloid pathology in a mouse model of Alzheimer’s disease
Authors: Zhao Peng , Xu Yuanzhong , Jiang LuLin , Fan Xuejun , Li Leike , Li Xin , Arase Hisashi , Zhao Yingjun , Cao Wei , Zheng Hui , Xu Huaxi , Tong Qingchun , Zhang Ningyan , An Zhiqiang
Published: September 2022

Triggering receptor expressed on myeloid cells 2 (TREM2) plays crucial roles in Alzheimer’s disease (AD) by regulating microglia migration toward, and phagocytosis of oligomeric amyloid-β (oAβ) and amyloid plaques. Studies in rodent models of AD have shown that mice with increased TREM2 expression have reduced amyloid pathology. Here, we identified a TREM2 agonist monoclonal Ab (Ab18) by panning a phage-displayed single-chain variable fragment Ab library. By engineering the bivalent immunoglobulin G1 (IgG1) to tetra-variable domain immunoglobulin (TVD-Ig), we further increased the TREM2 activation by 100-fold. Stronger TREM2 activation led to enhanced microglia phagocytosis of the oAβ-lipid complex, migration toward oAβ, and improved microglia survival in vitro. Mechanistic studies showed increased TREM2 clustering on microglia by the tetravalent Ab18 TVD-Ig without altering microglial TREM2 amount. An engineered bispecific Ab targeting TREM2 and transferrin receptor (TfR; Ab18 TVD-Ig/αTfR) improved Ab brain entry by more than 10-fold with a broad brain parenchyma distribution. Weekly treatment of 5XFAD mice (a model of AD) with Ab18 TVD-Ig/αTfR showed a considerable reduction of amyloid burden with increased microglia migration to and phagocytosis of amyloid plaques, improved synaptic and neuronal marker intensity, improved cognitive functions, reduced endogenous tau hyperphosphorylation, and decreased phosphorylated neurofilament H immunostaining. This study demonstrated the feasibility of engineering multivalent TREM2 agonistic Ab coupled with TfR-mediated brain delivery to enhance microglia functions and reduce amyloid pathology in vitro and in vivo. This Ab engineering approach enables the development of effective TREM2-targeting therapies for AD.
Reassessment of Historical Clinical Trials Supports the Effectiveness of Phage Therapy
Authors: Marongiu Luigi , Burkard Markus , Lauer Ulrich M. , Hoelzle Ludwig E. , Venturelli Sascha
Published: September 2022

Phage therapy has become a hot topic in medical research due to the increasing prevalence of antibiotic-resistant bacteria strains. In the treatment of bacterial infections, bacteriophages have several advantages over antibiotics, including strain specificity, lack of serious side effects, and low development costs.
Residues L55 and W69 of Tva Mediate Entry of Subgroup A Avian Leukosis Virus
Authors: Chen Yuntong , Wang Suyan , Li Xinyi , Yu Mengmeng , Liu Peng , Meng Lingzhai , Guo Ru , Feng Xiaoyan , Liu Aijing , Qi Xiaole , Li Kai , Gao Li , Pan Qing , Zhang Yanping , Liu Changjun , Cui Hongyu , Wang Xiaomei , Gao Yulong
Published: September 2022

Retroviruses bind to cellular receptors through their envelope proteins, which is a crucial step in infection. While most retroviruses require two receptors for entry, ALV-A requires only one.
Pattern Recognition Receptors of Nucleic Acids Can Cause Sublethal Activation of the Mitochondrial Apoptosis Pathway during Viral Infection
Authors: Gradzka-Boberda Sylwia , Gentle Ian E. , Häcker Georg
Published: September 2022

A contribution of the mitochondrial apoptosis apparatus, in the absence of cell death, to the reaction of nonprofessional immune cells to viruses is suggested to play a role as a broad alert system of an infected cell: the apoptosis system can be activated by many upstream signals and could therefore act as a central coordinator of viral recognition. The proapoptotic activity of PRRs has been documented in multiple situations, but this activity seems too low to be meaningful, and a physiological significance of such activity is not immediately obvious.
Import and Export of Mannosylerythritol Lipids by Ustilago maydis
Authors: Becker Fabienne , Linne Uwe , Xie Xiulan , Hemer Anna-Lena , Bölker Michael , Freitag Johannes , Sandrock Björn
Published: September 2022

Fungi produce and secrete various secondary metabolites that can act as weapons against competitors, help in accessing nutrients, or assist in development and communication. One group of secondary metabolites are surface-active glycolipids, which have significant biotechnological potential as biodegradable detergents.
Treatment of Sindbis Virus-Infected Neurons with Antibody to E2 Alters Synthesis of Complete and nsP1-Expressing Defective Viral RNAs
Authors: Yeh Jane X. , Fan Yunfan , Bartlett Maggie L. , Zhang Xiaoyan , Sadowski Norah , Hauer Debra A. , Timp Winston , Griffin Diane E.
Published: September 2022

Alphaviruses are important causes of viral encephalomyelitis without approved treatments or vaccines. Antibody to the Sindbis virus (SINV) E2 glycoprotein is required for immune-mediated noncytolytic virus clearance from neurons.
Complete Genome Sequence of Glutamicibacter mysorens NBNZ-009, Isolated from Jin Lake Sediment
Authors: Wang Yueying , Su Xin , Liu Jie , Fang Wei , Zhu Lei
Published: September 2022

Members of the genus
Glutamicibacter
have been reported from soil samples or some industrial pollution environments. Here, we present the genome of strain
Glutamicibacter mysorens
NBNZ-009, which was isolated from sediment from Jin Lake (Wuhan, China). The genome consists of a 3.68-Mbp circular chromosome and possesses 3,372 coding sequences.
MetaPhage: an Automated Pipeline for Analyzing, Annotating, and Classifying Bacteriophages in Metagenomics Sequencing Data
Authors: Pandolfo Mattia , Telatin Andrea , Lazzari Gioele , Adriaenssens Evelien M. , Vitulo Nicola
Published: September 2022

Bacteriophages (viruses that infect bacteria) are the most abundant biological entities on earth and are increasingly studied as members of the resident microbiota community in many environments, from oceans to soils and the human gut. Their identification is of great importance to better understand complex bacterial dynamics and microbial ecosystem function.
Emodin Combined with Multiple-Low-Frequency, Low-Intensity Ultrasound To Relieve Osteomyelitis through Sonoantimicrobial Chemotherapy
Authors: Lu Feng , Wu Xinhui , Hu Huiqun , He Zixuan , Sun Jiacheng , Zhang Jiapeng , Song Xiaoting , Jin Xiangang , Chen Guofu
Published: September 2022

Antibiotic therapy is the first choice for clinical treatment of osteomyelitis, but the formation of bacterial biofilms and the emergence of many drug-resistant strains also create an urgent need to find an alternative treatment to effectively eliminate the infection. Recently, LFLIU has come to be considered a safe and promising method of debridement and antibacterial therapy.
Similarities of P1-Like Phage Plasmids and Their Role in the Dissemination of
bla
CTX-M-55
Authors: Wang Mianzhi , Jiang Li , Wei Jingyi , Zhu Heng , Zhang Junxuan , Liu Ziyi , Zhang Wenhui , He Xiaolu , Liu Yuan , Li Ruichao , Xiao Xia , Sun Yongxue , Zeng Zhenling , Wang Zhiqiang
Published: September 2022

As a PP, P1 DNA exists as a low-copy-number plasmid and replicates autonomously with a lysogenization style. This unique mode of P1-like elements probably indicates a stable contribution to antibiotic resistance.
Murine Hepatitis Virus, a Biosafety Level 2 Model for SARS-CoV-2, Can Remain Viable on Meat and Meat Packaging Materials for at Least 48 Hours
Authors: Featherstone Austin B. , Brown Amanda Claire , Chitlapilly Dass Sapna
Published: September 2022

The meat industry has been faced with astronomical challenges with the rampant spread of COVID-19 among meat processing plant workers. This has resulted in meat processing and packaging plant closures, creating bottlenecks everywhere in the chain, from farms to consumers, subsequently leading to much smaller production outputs and higher prices for all parties involved.
Understanding patient partnership in health systems: lessons from the Canadian patient partner survey
Authors: Abelson Julia , Canfield Carolyn , Leslie Myles , Levasseur Mary Anne , Rowland Paula , Tripp Laura , Vanstone Meredith , Panday Janelle , Cameron David , Forest Pierre-Gerlier , Sussman Daniel , Wilson Geoff
Published: September 2022

Objectives

To examine the sociodemographic characteristics, activities, motivations, experiences, skills and challenges of patient partners working across multiple health system settings in Canada.

Design

Online cross-sectional survey of self-identified patient partners.

Setting

Patient partners in multiple jurisdictions and health system organisations.

Participants

603 patient partners who had drawn on their experiences with the health system as a patient, family member or informal caregiver to try to improve it in some way, through their involvement in the activities of a group, organisation or government.

Results

Survey respondents predominantly identified as female (76.6%), white (84%) and university educated (70.2%) but were a heterogeneous group in the scope (activities and organisations), intensity (number of hours) and longevity (number of years) of their role. Primary motivations for becoming a patient partner were the desire to improve the health system based on either a negative (36.2%) or positive (23.3%) experience. Respondents reported feeling enthusiastic (83.6%), valued (76.9%) and needed (63.3%) always or most of the time; just under half felt they had always or often been adequately compensated in their role. Knowledge of the health system and the organisation they partner with are key skills needed. Two-thirds faced barriers in their role with over half identifying power imbalances. Less than half were able to see how their input was reflected in decisions or changes always or most of the time, and 40.3% had thought about quitting.

Conclusions

This survey is the first of its kind to examine at a population level, the characteristics, experiences and dynamics of a large sample of self-identified patient partners. Patient partners in this sample are a sociodemographically homogenous group, yet heterogeneous in the scope, intensity and longevity of roles. Our findings provide key insights at a critical time, to inform the future of patient partnership in health systems.