bluuebunny/crossref_metadata_2025 huggingface dataset:
Agrobacterium-Mediated Transient Transformation ofMarchantiaLiverworts
Authors: Iwakawa Hidekazu , Melkonian Katharina , Schlüter Titus , Jeon Hyung-Woo , Nishihama Ryuichi , Motose Hiroyasu , Nakagami Hirofumi
Published: August 2021

Agrobacterium-mediated transient gene expression is a rapid and useful approach for characterizing functions of gene products in planta. However, the practicability of the method in the model liverwort Marchantia polymorpha has not yet been thoroughly described. Here we report a simple and robust method for Agrobacterium-mediated transient transformation of Marchantia thalli and its applicability. When thalli of M. polymorpha were co-cultured with Agrobacterium tumefaciens carrying β-glucuronidase (GUS) genes, GUS staining was observed primarily in assimilatory filaments and rhizoids. GUS activity was detected 2 days after infection and saturated 3 days after infection. We were able to transiently co-express fluorescently tagged proteins with proper localizations. Furthermore, we demonstrate that our method can be used as a novel pathosystem to study liverwort–bacteria interactions. We also provide evidence that air chambers support bacterial colonization.
Genicular Nerve Anatomy and Its Implication for New Procedural Approaches for Knee Joint Denervation: A Cadaveric Study
Authors: Kim Jung H , Shustorovich Alexander , Arel Aaron T , Downie Sherry A , Cohen Steven P , Kim Soo Yeon
Published: August 2021

Objective

To verify the articular branch contributions in the human knee, delineate their anatomical variance, and outline the limitations of currently applied procedure protocols for denervation of the knee joint.

Design

A detailed anatomical dissection.

Setting

Cadavers in residence at the Albert Einstein College of Medicine.

Subjects

In total, 24 lower extremity specimens from 14 embalmed cadavers.

Methods

Human cadaveric dissections were performed on 24 lower extremities from 14 embalmed cadavers.

Results

This cadaveric study has demonstrated that the anterior knee receives sensory innervations from SMGN, SLGN, LRN, NVI, NVL, RFN, and IMGN. The courses of SMGN, SLGN, RFN, and IMGN are similar to recent anatomical studies. However, discrepancies exist in their relative anatomy to bony and radiographic landmarks.

Conclusions

Genicular denervation using classical anatomical landmarks may not be sufficient to treat the anterior knee joint pain. Our findings illustrate more accurate anatomic landmarks for the three-target paradigm and support additional targets for more complete genicular denervation. This cadaveric study provides robust anatomical findings that can provide a foundation for new anatomical landmarks and targets to improve genicular denervation outcomes.
Diagnosis of Achilles Insertional Tendinopathies by Algometry
Authors: Barbachan Mansur Nacime Salomão , Pereira Vinícius Felipe , Cunha Henrique Cesar Monteiro , Nunes Carlos Gilberto , Ferreira Danilo Santos , Sato Vitor Neves , Yamada André Fukunishi , Matsunaga Fabio Teruo , Belloti João Carlos , Tamaoki Marcel Jun Sugawara
Published: August 2021

Introduction

Diagnosis of Achilles insertional tendinopathies (AIT) is based on pain by tendon palpation. However, there is no consensus or standard with regard to the amount of force to be used during the evaluation. Algometry is a method of measuring the pressure applied in a specific region and can be a method for determining diagnosis values.

Goal

To determine a cutoff value for pain threshold (PT) in the assessment of AIT.

Design

This is a prospective case–control study of diagnostic accuracy, to develop a diagnostic criterion.

Methods

Forty asymptomatic individuals and forty patients with AIT, matched by age and sex, were evaluated and submitted to algometry for PT and for visual analog scale (VAS) levels with 3 kgf at the insertion of the calcaneal tendon by two different evaluators. Inter-observer reproducibility was assessed through the interclass correlation coefficient (ICC). Sensitivity and specificity calculations of PT and of VAS were calculated and plotted on a receiver operating characteristic curve.

Results

The lowest ICC found was 0.788. With regard to the diagnosis through PT , the 4.08-kgf value showed the best relation between sensitivity and specificity (92.5% and 92.5%, respectively). Algometry values lower than 4.08 were considered positive for disease. For the diagnosis of AIT through VAS with 3 kgf, the value of 2.98 was estabilished (sensitivity of 92.5% and specificity of 97.5%).

Conclusion

Algometry was shown to be a simple and reliable method for diagnosing AIT. Values of PT less than 4.08 kgf were found to be predictors of the disease.
Association between political group participation and depressive symptoms among older adults: an 11-year longitudinal study in Taiwan
Authors: Lin Yu-Chun , Yan Huang-Ting
Published: August 2021

Background

Given the speculation that political participation is causing an epidemic of depression, this study examined how participation in political and non-political groups influenced depressive symptoms among older adults in Taiwan.

Methods

The 11-year follow-up data from the Taiwan Longitudinal Study on Ageing, covering 5334 persons aged 50 years and older, were analysed using random-effects panel logit models.

Results

Engagement in social groups reduced the likelihood of depression (adjusted odds ratio [AOR]: 0.71, 95% confidence interval [CI]: 0.64–0.80). However, there was a greater likelihood of depressive symptoms among older adults who were engaged in political groups when compared with those who were engaged in non-political groups (AOR: 1.87, 95% CI: 1.31–2.65). For older adults who remained politically engaged, participation in a greater number of non-political group types was associated with a lower likelihood of depression (e.g. at 1: AOR: 0.53, 95% CI: 0.30–0.91; at 2+: AOR: 0.35, 95% CI: 0.18–0.67); this numbers-based effect was not prevalent among those who were solely engaged in non-political groups.

Conclusions

Political group attendance can result in negative mental health outcomes among older adults. Our findings suggest that reducing the prevalence of depression through social participation is conditional to the engagement type.
PRACTICAL CHALLENGES WITH IMAGING COVID-19 IN BRAZIL: MITIGATION IN AND BEYOND THE PANDEMIC
Authors: Bernardo Mônica O , Homayounieh Fatemeh , Ebrahimian Shadi , de Melo Tapajós Juliana Santana , de Moura Carvalho Luiz Cláudio , Varella Ricardo , Khoury Helen Jamil , Kalra Mannudeep K
Published: August 2021

Computed tomography (CT) provides useful information in patients with known or suspected COVID-19 infection. However, there are substantial variations and challenges in scanner technologies and scan practices that have negative effect on the image quality and can increase radiation dose associated with CT. Objective: In this article, we present major issues and challenges with use of CT at five Brazilian CT facilities for imaging patients with known or suspected COVID-19 infection and offer specific mitigating strategies. Methods: Observational, retrospective and prospective study of five CT facilities from different states and regions of Brazil, with approval of research and ethics committees. Results: The most important issues include frequent use of CT, lack of up-to-date and efficient scanner technologies, over-scanning and patient off-centring. Mitigating strategies can include updating scanner technology and improving scan practices.
Genetic selection indices for growth traits in Blanco-Orejinegro cattle
Authors: Ramírez Toro Edison J , Mourão Gerson Barreto , Martínez Sarmiento Rodrigo A , Cerón-Muñoz Mario F
Published: August 2021

Selection indices are used in genetic improvement programs, with the purpose of selectins simultaneous for several economically important traits. The objective of this study was to construct equations for selection indices in the Blanco-Orejinegro (BON) breed and to determine the index that would generate the greatest genetic progress. The information used included birth weight (BW), body weights adjusted to 120, 240, 480, and 720 days old (W120, W240, W240, 480 and W720, respectively), age at first calving (AFC) and interval between first and second calving (IBC) estimated breeding values. Two Smith and Hazel indices were calculated using variances (I1) and literature (I2), with a part two indices designed using information from experts and breeders (I3 and I4). All the indices favored the reduction of weight at birth. The I1 focused mainly on W120 and I2, I3 and I4 focused on 720. In general, the estimated indices obtained similar reliability and expected genetic differences I1 generated a decrease in direct BW. I2 generated the largest increases in BW and AFC. I3 and I4 generated positive changes in growth and reproductive traits, with I3 generating the greatest genetic gains in the population, especially for W240.
Many ways to land upright: novel righting strategies allow spotted lanternfly nymphs to land on diverse substrates
Authors: Kane Suzanne Amador , Bien Theodore , Contreras-Orendain Luis , Ochs Michael F. , Tonia Hsieh S.
Published: August 2021

Unlike large animals, insects and other very small animals are so unsusceptible to impact-related injuries that they can use falling for dispersal and predator evasion. Reorienting to land upright can mitigate lost access to resources and predation risk. Such behaviours are critical for the spotted lanternfly (SLF) (
Lycorma delicatula
), an invasive, destructive insect pest spreading rapidly in the USA. High-speed video of SLF nymphs released under different conditions showed that these insects self-right using both active midair righting motions previously reported for other insects and novel post-impact mechanisms that take advantage of their ability to experience near-total energy loss on impact. Unlike during terrestrial self-righting, in which an animal initially at rest on its back uses appendage motions to flip over, SLF nymphs impacted the surface at varying angles and then self-righted during the rebound using coordinated body rotations, foot–substrate adhesion and active leg motions. These previously unreported strategies were found to promote disproportionately upright, secure landings on both hard, flat surfaces and tilted, compliant host plant leaves. Our results highlight the importance of examining biomechanical phenomena in ecologically relevant contexts, and show that, for small animals, the post-impact bounce period can be critical for achieving an upright landing.
On in-plane drill rotations for Cosserat surfaces
Authors: Mohammadi Saem Maryam , Lewintan Peter , Neff Patrizio
Published: August 2021

We show under some natural smoothness assumptions that pure in-plane drill rotations as deformation mappings of a

C
2

-smooth regular shell surface to another one parametrized over the same domain are impossible provided that the rotations are fixed at a portion of the boundary. Put otherwise, if the tangent vectors of the new surface are obtained locally by only rotating the given tangent vectors, and if these rotations have a rotation axis which coincides everywhere with the normal of the initial surface, then the two surfaces are equal provided they coincide at a portion of the boundary. In the language of differential geometry of surfaces, we show that any isometry which leaves normals invariant and which coincides with the given surface at a portion of the boundary is the identity mapping.
Mega riverbed-patterns: linear and weakly nonlinear perspectives
Authors: Ali Sk Zeeshan , Dey Subhasish , Mahato Rajesh K.
Published: August 2021

In this paper, we explore the mega riverbed-patterns, whose longitudinal and vertical length dimensions scale with a few channel widths and the flow depth, respectively. We perform the stability analyses from both linear and weakly nonlinear perspectives by considering a steady-uniform flow in an erodible straight channel comprising a uniform sediment size. The mathematical framework stands on the dynamic coupling between the depth-averaged flow model and the particle transport model including both bedload and suspended load via the Exner equation, which drives the pattern formation. From the linear perspective, we employ the standard linearization technique by superimposing the periodic perturbations on the undisturbed system to find the dispersion relationship. From the weakly nonlinear perspective, we apply the centre–manifold-projection technique, where the fast dynamics of stable modes is projected on the slow dynamics of weakly unstable modes to obtain the Stuart–Landau equation for the amplitude dynamics. We examine the marginal stability, growth rate and amplitude of patterns for a given quintet formed by the channel aspect ratio, wavenumber of patterns, shear Reynolds number, Shields number and relative roughness number. This study highlights the sensitivity of pattern formation to the key parameters and shows how the classical results can be reconstructed on the parameter space.
Microbiome in human cancers
Authors: Menati Rashno Mohammad , Mehraban Hamed , Naji Behnaz , Radmehr Mohadeseh
Published: August 2021

A microbiome is defined as the aggregate of all microbiota that reside in human digestive system and other tissues. This microbiota includes viruses, bacteria, fungi that live in various human organs and tissues like stomach, guts, oesophagus, mouth cavity, urinary tract, vagina, lungs, and skin. Almost 20 % of malignant cancers worldwide are related to microbial infections including bacteria, parasites, and viruses. The human body is constantly being attacked by microbes during its lifetime and microbial pathogens that have tumorigenic effects in 15–20 % of reported cancer cases. Recent scientific advances and the discovery of the effect of microbes on cancer as a pathogen or as a drug have significantly contributed to our understanding of the complex relationship between microbiome and cancer. The aim of this study is to overview some microbiomes that reside in the human body and their roles in cancer.
Serpentinimonas gen. nov., Serpentinimonas raichei sp. nov., Serpentinimonas barnesii sp. nov. and Serpentinimonas maccroryi sp. nov., hyperalkaliphilic and facultative autotrophic bacteria isolated from terrestrial serpentinizing springs
Authors: Bird Lina J. , Kuenen J. Gijs , Osburn Magdalena R. , Tomioka Naotaka , Ishii Shun’ichi , Barr Casey , Nealson Kenneth H. , Suzuki Shino
Published: August 2021

Three highly alkaliphilic bacterial strains designated as A1T, H1T and B1T were isolated from two highly alkaline springs at The Cedars, a terrestrial serpentinizing site. Cells from all strains were motile, Gram-negative and rod-shaped. Strains A1T, H1T and B1T were mesophilic (optimum, 30 °C), highly alkaliphilic (optimum, pH 11) and facultatively autotrophic. Major cellular fatty acids were saturated and monounsaturated hexadecenoic and octadecanoic acids. The genome size of strains A1T, H1T and B1T was 2 574 013, 2 475 906 and 2 623 236 bp, and the G+C content was 66.0, 66.2 and 66.1 mol%, respectively. Analysis of the 16S rRNA genes showed the highest similarity to the genera

Malikia

(95.1–96.4 %),

Macromonas

(93.0–93.6 %) and

Hydrogenophaga

(93.0–96.6 %) in the family

Comamonadaceae

. Phylogenetic analysis based on 16S rRNA gene and phylogenomic analysis based on core gene sequences revealed that the isolated strains diverged from the related species, forming a distinct branch. Average amino acid identity values of strains A1T, H1T and B1T against the genomes of related members in this family were below 67 %, which is below the suggested threshold for genera boundaries. Average nucleotide identity by blast values and digital DNA–DNA hybridization among the three strains were below 92.0 and 46.6 % respectively, which are below the suggested thresholds for species boundaries. Based on phylogenetic, genomic and phenotypic characterization, we propose Serpentinimonas gen. nov., Serpentinimonas raichei sp. nov. (type strain A1T=NBRC 111848T=DSM 103917T), Serpentinimonas barnesii sp. nov. (type strain H1T= NBRC 111849T=DSM 103920T) and Serpentinimonas maccroryi sp. nov. (type strain B1T=NBRC 111850T=DSM 103919T) belonging to the family

Comamonadaceae

. We have designated Serpentinimonas raichei the type species for the genus because it is the dominant species in The Cedars springs.
MiSDEED: a synthetic multi-omics engine for microbiome power analysis and study design
Authors: Chlenski Philippe , Hsu Melody , Pe’er Itsik
Published: August 2021

MiSDEED is a command-line tool for generating synthetic longitudinal multi-omics data from simulated microbial environments. It generates relative-abundance timecourses under perturbations for an arbitrary number of samples and patients. All simulation parameters are exposed to the user to facilitate rapid power analysis and aid in study design. Users who want additional flexibility may also use MiSDEED as a Python package.

Availability and implementation

MiSDEED is written in Python and is freely available at https://github.com/pchlenski/misdeed.

Contact

pac@cs.columbia.edu
A computational approach for generating smooth estimates of motor unit discharge rates and visualizing population discharge characteristics
Authors: Beauchamp James. A. , Khurram Obaid U , Dewald Julius P.A. , Heckman Charles J. , Pearcey Gregory E P
Published: August 2021

Objective

Successive improvements in high density surface electromyography and decomposition techniques have facilitated an increasing yield in decomposed motor unit (MU) spike times. Though these advancements enhance the generalizability of findings and promote the application of MU discharge characteristics to inform the neural control of motor output, limitations remain. Specifically, 1) common approaches for generating smooth estimates of MU discharge rates introduce artifacts in quantification, which may bias findings, and 2) discharge characteristics of large MU populations are often difficult to visualize.

Approach

In the present study, we propose support vector regression (SVR) as an improved approach for generating continuous estimates of discharge rate and compare the fit characteristics of SVR to traditionally used methods, including Hanning window filtering and polynomial regression. Furthermore, we introduce ensembles as a method to visualize the discharge characteristics of large MU populations. We define ensembles as the average discharge profile of a subpopulation of MUs, composed of a time normalized ensemble average of all units within this subpopulation. Analysis was conducted with MUs decomposed from the tibialis anterior (N = 2128), medial gastrocnemius (N = 2673), and soleus (N = 1190) during isometric plantarflexion and dorsiflexion contractions.

Main Result

Compared to traditional approaches, we found SVR to alleviate commonly observed inaccuracies and produce significantly less absolute fit error in the initial phase of MU discharge and throughout the entire duration of discharge. Additionally, we found the visualization of MU populations as ensembles to intuitively represent population discharge characteristics with appropriate accuracy for visualization.

Significance

The results and methods outlined here provide an improved method for generating smooth estimates of MU discharge rate with SVR and present a unique approach to visualizing MU populations with ensembles. In combination, the use of SVR and generation of ensembles represent an efficient method for rendering population discharge characteristics.
Role of Efferocytosis in Oral Lichen Planus
Authors: Rooban Thavarajah , Ranganathan Kannan
Published: August 2021

Background

Oral lichen planus (OLP) is a chronic, immune mediated interface mucositis of oral mucosa. Though the apoptosis of keratinocytes is a feature of OLP, not much is known about the clearance of cell debris (efferocytosis) resulting from apoptosis. We postulate that there is a defective or delayed efferocytosis in OLP, which may have a role in modulating the immune response in OLP.

Methods

Published mRNA expression of tissue of 14 patients with OLP and 14 cases of normal tissues were subjected to differential analysis (DE) and a list of DE genes identified. From this list, the genes that involved in efferocytosis were collated, compared and their interactions are typed.

Result

In all, two studies fulfilled the inclusion and exclusion criteria. On combining the data, 1486 genes were significantly different between OLP and normal tissues. 28 of these 1486 genes are were associated with efferocytosis of which the suppression of LRP1, LDLR, ANAX2, C2, PBX1, PDCD4, S1PR5, CX3CL1, STAT6 and Wnt3A is indicative of defective or delayed efferocytosis in OLP. The role of pathways and associations were analyzed and is presented here.

Discussion and Conclusion

The study revealed that certain key genes mRNAs that are associated with efferocytosis are altered in OLP. They could delay or lead to defective efferocytosis. Studying such genes in detail could provide deeper understanding of the pathogenesis of the disease and the discovery of therapeutic targets.
Information theory-based approach towards studying anti-coincidence detection via graded amplitude dendritic action potentials
Authors: Sinha Vidhi
Published: August 2021

In contrast to typical all or none action potential, recent discovery of graded amplitude action potentials in cortical neurons enabled the dendrites to perform XOR computation, previously thought to be performed only at network level. Thus, these special neurons can perform anti-coincidence detection at the dendritic level, but a lot is unanswered about this phenomenon. Can such experimentally observed dendritic action potential generating system transmit information about stimuli having varying degrees of temporal overlap? Can the system add to the repertoire of computations performed at dendritic level by enhancing the information transmission about varying amplitude stimuli? In this information theory-based study done in single compartment and two-compartment dendritic models, it is shown that such a system can indeed transmit information about the temporal overlap of stimuli as well as amplitudes of stimuli even at high input noise levels. First, the calculation of mutual information between single stimulus and response i.e. I(S;R) with varying noise showed that the information about temporally overlapping nature of stimuli is precisely transmitted by such a system. Secondly, the time evolution of mutual information was simulated through data from the system and it positively reinforced the above-mentioned result. Next, varying amplitude input stimuli was provided to the system and calculation of mutual information between two stimuli and one response i.e. I(S1,S2;R) with varying noise levels revealed that such a system optimally transmits the information about stimuli even at high noise levels. Finally, calculation of this information measurement with respect to time in an experiment with constant overlap but varying input amplitude again positively reinforced the result.

Key Points

Information theory-based measurements were employed to assess the role of graded amplitude dendritic action potentials.

Action potentials (APs) with maximal amplitudes for threshold level stimuli and lower amplitudes for stronger stimuli were modelled with high voltage Ca2+ (HVA like) channels, Ca2+ dependent (BK-like) channel, leak channel and calcium pump in a single compartment model and two compartment dendritic model.

Analysis done here, on comparison with control compartment generating constant amplitude AP via standard Hodgkin-Huxley sodium potassium channel revealed that such a compartment shows optimal information transmission about both varying amplitudes input current stimuli as well as varying time overlap stimuli.
A Comparative Study on the knowledge and attitude of COVID-19 among Urban and Rural populations of Bangladesh
Authors: Hossain Ripon Md. Kamal , Khan Noor Muhammad , Khan A E M Adnan , Ahmed Rana , Afrin Safia , Sayed Md. Abu , Rahman Moghal Md. Mizanur
Published: August 2021

Aim

This study is aimed to identify the awareness and behavioral perspective on COVID-19 between urban and rural people of Bangladesh during the period of outbreak.

Methods

A community-based cross-sectional study was conducted in 30 districts of Bangladesh, where 322 participants from urban and 312 from rural area. Participants were selected through convenience sampling.

Results

Rural people are found to be much more inter connected to receive information from neighbor. Regarding the incubation periods and the general symptoms, knowledge differs significantly from urban to rural. Even their precautionary and transmission knowledge is found to associate in most of the cases. During this outbreak, urban people significantly increase their religious habits and also believe that there will some major change of life after outbreak.

Discussion

The study reflected that health education program needed to aware about COVID-19 in both urban and rural in Bangladesh that helps in formulating and executing communication and outbreak management.
Replacement of the Alpha variant of SARS-CoV-2 by the Delta variant in Lebanon between April and June 2021
Authors: Merhi Georgi , Trotter Alexander J. , de Oliveira Martins Leonardo , Koweyes Jad , Le-Viet Thanh , Naja Hala Abou , Buaini Mona Al , Prosolek Sophie J. , Alikhan Nabil-Fareed , Lott Martin , Tohmeh Tatiana , Badran Bassam , Jupp Orla J. , Gardner Sarah , Felgate Matthew W. , Makin Kate A. , Wilkinson Janine M. , Stanley Rachael , Sesay Abdul K. , Webber Mark A. , Davidson Rose K. , Ghosn Nada , Pallen Mark , Hasan Hamad , Page Andrew J. , Tokajian Sima
Published: August 2021

Background

The COVID-19 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Eastern Mediterranean Region. Lebanon experienced its largest wave of COVID-19 infections from January to April 2021. Limited genomic surveillance was undertaken, with just twenty six SARS-CoV-2 genomes available for this period, nine of which were from travellers from Lebanon detected by other countries. Additional genome sequencing is thus needed to allow surveillance of variants in circulation.

Methods

Nine hundred and five SARS-CoV-2 genomes were sequenced using the ARTIC protocol. The genomes were derived from SARS-CoV-2-positive samples, selected retrospectively from the sentinel COVID-19 surveillance network, to capture diversity of location, sampling time, gender, nationality and age.

Results

Although sixteen PANGO lineages were circulating in Lebanon in January 2021, by February there were just four, with the Alpha variant accounting for 97% of samples. In the following two months, all samples contained the Alpha variant. However, this had changed dramatically by June and July, when all samples belonged to the Delta variant.

Discussion

This study provides a ten-fold increase in the number of SARS-CoV-2 genomes available from Lebanon. The Alpha variant, first detected in the UK, rapidly swept through Lebanon, causing the country’s largest wave to date, which peaked in January 2021. The Alpha variant was introduced to Lebanon multiple times despite travel restrictions, but the source of these introductions remains uncertain. The Delta variant was detected in Gambia in travellers from Lebanon in mid-May, suggesting community transmission in Lebanon several weeks before this variant was detected in the country. Prospective sequencing in June/July 2021 showed that the Delta variant had completely replaced the Alpha variant in under six weeks.
Modeling and Multiobjective Optimization of Indoor Airborne Disease Transmission Risk and Associated Energy Consumption for Building HVAC Systems
Authors: Risbeck Michael J. , Bazant Martin Z. , Jiang Zhanhong , Lee Young M. , Drees Kirk H. , Douglas Jonathan D.
Published: August 2021

The COVID-19 pandemic has renewed interest in assessing how the operation of HVAC systems influences the risk of airborne disease transmission in buildings. Various processes, such as ventilation and filtration, have been shown to reduce the probability of disease spread by removing or deactivating exhaled aerosols that potentially contain infectious material. However, such qualitative recommendations fail to specify how much of these or other disinfection techniques are needed to achieve acceptable risk levels in a particular space. An additional complication is that application of these techniques inevitably increases energy costs, the magnitude of which can vary significantly based on local weather. Moreover, the operational flexibility available to the HVAC system may be inherently limited by equipment capacities and occupant comfort requirements. Given this knowledge gap, we propose a set of dynamical models that can be used to estimate airborne transmission risk and energy consumption for building HVAC systems based on controller setpoints and a forecast of weather conditions. By combining physics-based material balances with phenomenological models of the HVAC control system, it is possible to predict time-varying airflows and other HVAC variables, which are then used to calculate key metrics. Through a variety of examples involving real and simulated commercial buildings, we show that our models can be used for monitoring purposes by applying them directly to transient building data as operated, or they may be embedded within a multi-objective optimization framework to evaluate the tradeoff between infection risk and energy consumption. By combining these applications, building managers can determine which spaces are in need of infection risk reduction and how to provide that reduction at the lowest energy cost. The key finding is that both the baseline infection risk and the most energy-efficient disinfection strategy can vary significantly from space to space and depend sensitively on the weather, thus underscoring the importance of the quantitative predictions provided by the models.
Cleavage of histone H2A during embryonic stem cell differentiation destabilizes nucleosomes to counteract gene activation
Authors: Coradin Mariel , Cesare Joseph , Lan Yemin , Zhu Zhexin , Lund Peder J. , Sidoli Simone , Perez Yekaterina , Lu Congcong , Porter Elizabeth G. , Robert Charles W. M. , Garcia Benjamin A.
Published: August 2021

Histone proteolysis is a poorly understood phenomenon in which the N-terminal tails of histones are irreversibly cleaved by intracellular proteases. During development, histone post-translational modifications are known to orchestrate gene expression patterns that ultimately drive cell fate decisions. Therefore, deciphering the mechanisms of histone proteolysis is necessary to enhance the understanding of cellular differentiation. Here we show that H2A is cleaved by the lysosomal protease Cathepsin L during ESCs differentiation. Using quantitative mass spectrometry (MS), we identified L23 to be the primary cleavage site that gives rise to the clipped form of H2A (cH2A), which reaches a maximum level of ~1% of total H2A after four days of differentiation. Using ChIP-seq, we found that preventing proteolysis leads to an increase in acetylated H2A at promoter regions in differentiated ES cells. We also identified novel readers of different acetylated forms of H2A in pluripotent ES cells, such as members of the PBAF remodeling complex. Finally, we showed that H2A proteolysis abolishes this recognition. Altogether, our data suggests that proteolysis serves as an efficient mechanism to silence pluripotency genes and destabilize the nucleosome core particle.
Cryo-EM reveals disrupted human p97 allosteric activation by disease mutations and inhibitor binding
Authors: Caffrey Brian , Zhu Xing , Berezuk Alison , Tuttle Katharine , Chittori Sagar , Subramaniam Sriram
Published: August 2021

The human AAA ATPase p97, a potential cancer target, plays a vital role in clearing misfolded proteins. p97 dysfunction is also known to play a crucial role in several neurodegenerative disorders. Here, we present cryo-EM structural analyses of four disease mutants p97R155H, p97R191Q, p97A232E, p97D592N, as well as p97E470D, implicated in resistance to the drug CB-5083. These structures demonstrate that the mutations affect nucleotide-driven p97 allosteric activation by predominantly interfering with either the coupling between the D1 and N-terminal domains (p97R155H and p97R191Q), the inter-protomer interactions (p97A232E), or the coupling between D1 and D2 nucleotide domains (p97D592N, p97E470D). We also show that binding of the competitive inhibitor CB-5083 to the D2 domain prevents conformational changes similar to that seen for mutations that affect coupling between D1 and D2 domains. Our studies enable tracing of the path of allosteric activation across p97 and establish a common mechanistic link between active site inhibition and defects in allosteric activation by disease-causing mutations.
Age and sex dependent variability of type 2 dopamine receptors in the human brain: A large-scale PET cohort
Authors: Malén Tuulia , Karjalainen Tomi , Isojärvi Janne , Vehtari Aki , Bürkner Paul-Christian , Putkinen Vesa , Kaasinen Valtteri , Hietala Jarmo , Nuutila Pirjo , Rinne Juha , Nummenmaa Lauri
Published: August 2021

BACKGROUND

The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved.

METHODS

In this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018.

RESULTS

Striatal D2R availability decreased through age for both sexes and was higher in females versus males throughout age. BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135).

CONCLUSIONS

D2R density is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.
Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF
Authors: Aljahani Abrar , Hua Peng , Karpinska Magdalena A. , Quililan Kimberly , Davies James O.J. , Oudelaar A. Marieke
Published: August 2021

Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.
Dysregulation of Hepatitis B Virus Nucleocapsid Assembly with RNA-directed Small Ligands
Authors: Patel Nikesh , Abulwerdi Fardokht , Fatehi Farzad , Manfield Iain , Grice Stuart Le , Schneekloth John S. , Twarock Reidun , Stockley Peter G.
Published: August 2021

RNA sequences/motifs dispersed across the pre-genomic copy of the Hepatitis B Virus genome regulate formation of nucleocapsidsin vitroin an epsilon/polymerase independent fashion. These multiple RNA Packaging Signals (PSs) form stem-loops presenting in each loop a core protein recognition motif, -RGAG-. Small, drug-like molecules binding these motifs were identified by screening an immobilized library with a fluorescently-labelled RNA oligonucleotide encompassing the most conserved of these sites. This identified 66 “hits”, with affinities ranging from low nanomolar to high micromolar in SPR assays. High affinity ligand binding is dependent on the presence of the -RGAG-motif, which also appears to be the common element in cross-binding to other PS sites. Some of these compounds are potent inhibitors ofin vitrocore protein assembly around the HBV pre-genome. Mathematical modelling confirms the potential of these novel anti-viral drug targets for disrupting replication of this major human pathogen. Preliminary structure-activity relationships of the highest affinity compound reveal critical functional groups for PS-binding. PS-regulated assembly is easily adapted to high-throughput screening allowing future development of pharmacologically active compounds.
Upregulation of C4 characteristics does not consistently improve photosynthetic performance in intraspecific hybrids of a grass
Authors: Bianconi Matheus E. , Sotelo Graciela , Curran Emma V. , Milenkovic Vanja , Samaritani Emanuela , Dunning Luke T. , Bertolino Lígia T. , Osborne Colin P. , Christin Pascal-Antoine
Published: August 2021

C4 photosynthesis is thought to have evolved via intermediate stages, with changes towards the C4 phenotype gradually enhancing photosynthetic performance. This hypothesis is widely supported by modelling studies, but experimental tests are missing. Mixing of C4 components to generate artificial intermediates can be achieved via crossing, and the grass Alloteropsis semialata represents an outstanding system since it includes C4 and non-C4 populations. Here, we analyse F1 hybrids between C3 and C4, and C3+C4 and C4 genotypes to determine whether the acquisition of C4 characteristics increases photosynthetic performance. The hybrids have leaf anatomical characters and C4 gene expression profiles that are largely intermediate between those of their parents. Carbon isotope ratios are similarly intermediate, which suggests that a partial C4 cycle coexists with C3 carbon fixation in the hybrids. This partial C4 phenotype is associated with C4-like photosynthetic efficiency in C3+C4 x C4, but not in C3 x C4 hybrids, which are overall less efficient than both parents. Our results support the hypothesis that the photosynthetic gains from the upregulation of C4 characteristics depend on coordinated changes in anatomy and biochemistry. The order of acquisition of C4 components is thus constrained, with C3+C4 species providing an essential step for C4 evolution.
Nucleated Fish Erythrocyte Extracellular Traps (FEETs) release is an evolutionary conserved immune defence process
Authors: Rinaldi Giulia , de Haro Neila Álvarez , Desbois Andrew P. , Robb Calum T. , Rossi Adriano G.
Published: August 2021

Fish erythrocytes remain nucleated for their life-span, unlike mammalian erythrocytes which undergo enucleation. Asides transportation of oxygen, fish erythrocytes are capable of several immune defence processes. Nucleated fish erythrocytes represent prime candidates for carrying out ETotic responses. ETosis is an evolutionary conserved innate immune defence process found in both vertebrates and invertebrates, which involves the extrusion of DNA studded with antimicrobial proteins into the extracellular space serving to trap and kill microorganisms. In this report, we demonstrate that fish erythrocytes isolated from Danio rerio (zebrafish) produce ETotic-like responses when exposed to chemical and physiological stimuli. Furthermore, we found Salmo salar (Atlantic salmon) erythrocytes produce similar ETotic responses. We have termed these ET-like formations Fish Erythrocyte Extracellular Traps (FEETs). Interestingly, we discovered that mammalian inducers of NETosis, such as the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate and the calcium ionophore ionomycin, induced FEETs. Moreover, we found that FEETs are dependent upon activation of PKC and generation of mitochondrial reactive oxygen species. Thus, this brief report represents the first demonstration that fish erythrocytes can exhibit ETotic-like responses, unveiling a previously unknown function of nucleated erythrocytes, which sheds new light on the innate immune arsenal of erythrocytes.
Genetic risk estimates for offspring of patients with Stargardt disease
Authors: Cornelis Stéphanie S. , Runhart Esmee H. , Bauwens Miriam , Corradi Zelia , de Baere Elfride , Roosing Susanne , Haer-Wigman Lonneke , Dhaenens Claire-Marie , Vulto-van Silfhout Anneke T. , Cremers Frans P.M.
Published: August 2021

BACKGROUND

Genetic counseling in autosomal recessive Stargardt disease (STGD1) is complicated because of unknown frequencies of pathogenicABCA4alleles across populations, variable and unknown severity ofABCA4alleles, and incomplete penetrance.

METHODS

In this cross-sectional study, publishedABCA4variants were categorized by severity based on previous functional and clinical studies and current statistical comparisons of their frequencies in patients versus the general population, their observed versus expected homozygous occurrence in patients, and their occurrence in combination with established mild alleles in patients. The sum allele frequencies of these severity categories were used to estimate inheritance risks for offspring of STGD1 patients and carriers of pathogenicABCA4variants.

RESULTS

The risk for offspring of a STGD1 patient with the ‘severe|severe’ genotype or a ‘severe|mild with complete penetrance’ genotype to develop STGD1 at some moment in life was estimated at 2.8-3.1% (1 in 35-32 individuals) and 1.6-1.8% (1 in 62-57 individuals), respectively. The risk to develop STGD1 in childhood was estimated to be 2 to 4-fold lower: 0.7-0.8% (1 in 148-124) and 0.3-0.4% (1 in 295-248), respectively. For offspring of an unaffectedABCA4variant carrier from a STGD1 family who carries one severe or one mildABCA4variant with complete penetrance, the risk to develop STGD1 throughout life is 1.4-1.6% (1 in 71-64) and 0.19-0.21% (1 in 516-487), respectively.

CONCLUSION

We propose a genotype-based personalized counseling approach to appreciate the large differences in inheritance risk between individuals. We advocate considering the lower risk of early-onset STGD1 compared with the total STGD1 risk.
Microphaser - a small-scale phasing approach for improved personalized neopeptidome creation
Authors: Forster Jan , Lähnemann David , Paschen Annette , Schramm Alexander , Schuler Martin , Köster Johannes
Published: August 2021

Motivation

Haplotype phasing approaches have been shown to improve accuracy of the search space of neoantigen prediction by determining if adjacent variants are located on the same chromosomal copy. However, the aneuploid nature of cancer cells as well as the admixture of different clones in tumor bulk sequencing data are challenging the current diploid based phasing algorithms. We present microphaser, a small-scale phasing approach to improve haplotyping variants in cancer samples. Microphaser aims to create a more accurate neopeptidome for downstream neoantigen prediction.

Results

Microphaser achieves large concordance with state-of-the-art phasing-aware neoantigen prediction pipeline neoepiscope, with differences in edge cases and an improved filtering step.

Availability

Microphaser is written in the Rust programming language. It is made available via Github (https://github.com/koesterlab/microphaser)and Bioconda. The corresponding prediction pipeline (https://github.com/snakemake-workflows/dna-seq-neoantigen-prediction) has been written within the Snakemake workflow management system and can be deployed as part of the snakemake-workflows project.
Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants
Authors: McCallum Matthew , Walls Alexandra C. , Sprouse Kaitlin R. , Bowen John E. , Rosen Laura , Dang Ha V. , deMarco Anna , Franko Nicholas , Tilles Sasha W , Logue Jennifer , Miranda Marcos C. , Ahlrichs Margaret , Carter Lauren , Snell Gyorgy , Pizzuto Matteo Samuele , Chu Helen Y. , Van Voorhis Wesley C. , Corti Davide , Veesler David
Published: August 2021

Worldwide SARS-CoV-2 transmission leads to the recurrent emergence of variants, such as the recently described B.1.617.1 (kappa), B.1.617.2 (delta) and B.1.617.2+ (delta+). The B.1.617.2 (delta) variant of concern is causing a new wave of infections in many countries, mostly affecting unvaccinated individuals, and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing the impact of individual mutations on immune evasion. Mutations in the B.1.617.1 (kappa) and B.1.617.2 (delta) spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including an unexpected remodeling of the B.1.617.2 (delta) N-terminal domain. The binding affinity of the B.1.617.1 (kappa) and B.1.617.2 (delta) receptor-binding domain for ACE2 is comparable to the ancestral virus whereas B.1.617.2+ (delta+) exhibits markedly reduced affinity. We describe a previously uncharacterized class of N-terminal domain-directed human neutralizing monoclonal antibodies cross-reacting with several variants of concern, revealing a possible target for vaccine development.
Fostering ethical consumption in food sector: Insights from the Italian Solidarity Purchasing Groups
Authors: Sciarelli Mauro , Tani Mario , Prisco Anna , Caputo Francesco
Published: August 2021

Purpose

The paper aims at investigating antecedents and predictors of consumers' buying and consumption processes within the Italian Solidarity Purchasing Groups (SPGs) to enrich current debate about drivers and levers on which act for fostering ethical consumption in food sector.

Design/methodology/approach

Building upon the theory of planned behavior (TPB) a theoretical model is proposed for depicting possible antecedents and predictors of consumers' buying and consumption processes in food sector. The validity of the model has been tested via partial least squares structural equation modeling (PLS-SEM) using SmartPLS for analyzing primary data collected through a structured questionnaire from 354 consumers engaged in SPGs.

Findings

Within the domain of food buying and consumptions through SPGS, results show that consumers' behavior intention (BI) is influenced by consumers' attitude (ATT) and perceived behavioral control (PBC). Moreover, the research also demonstrates that consumers' ATT is influenced by consumers' ethical self-identity (ETH), consumers' willingness to support local economy (SLE), and food safety concern (FSC).

Originality/value

The study contributes to the ongoing debate on sustainable consumerism focusing the attention on SPGs as emerging social organizations inspired by ethical food consumption. Both theoretical development and empirical evidences enrich current knowledge about drivers and levers on which act for fostering ethical consumption in food sector.