bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of distinctive mismatch tolerance between Rad51 and Dmc1 in homologous recombination
Authors: Xu Jingfei , Zhao Lingyun , Peng Sijia , Chu Huiying , Liang Rui , Tian Meng , Connell Philip P , Li Guohui , Chen Chunlai , Wang Hong-Wei
Published: November 2021

Homologous recombination (HR) is a primary DNA double-strand breaks (DSBs) repair mechanism. The recombinases Rad51 and Dmc1 are highly conserved in the RecA family; Rad51 is mainly responsible for DNA repair in somatic cells during mitosis while Dmc1 only works during meiosis in germ cells. This spatiotemporal difference is probably due to their distinctive mismatch tolerance during HR: Rad51 does not permit HR in the presence of mismatches, whereas Dmc1 can tolerate certain mismatches. Here, the cryo-EM structures of Rad51–DNA and Dmc1–DNA complexes revealed that the major conformational differences between these two proteins are located in their Loop2 regions, which contain invading single-stranded DNA (ssDNA) binding residues and double-stranded DNA (dsDNA) complementary strand binding residues, stabilizing ssDNA and dsDNA in presynaptic and postsynaptic complexes, respectively. By combining molecular dynamic simulation and single-molecule FRET assays, we identified that V273 and D274 in the Loop2 region of human RAD51 (hRAD51), corresponding to P274 and G275 of human DMC1 (hDMC1), are the key residues regulating mismatch tolerance during strand exchange in HR. This HR accuracy control mechanism provides mechanistic insights into the specific roles of Rad51 and Dmc1 in DNA double-strand break repair and may shed light on the regulatory mechanism of genetic recombination in mitosis and meiosis.
Aggregation-induced barrier to oxygen—a new AIE mechanism for metal clusters with phosphorescence
Authors: Jin Yan , Peng Qiu-Chen , Li Si , Su Hui-Fang , Luo Peng , Yang Ming , Zhang Xin , Li Kai , Zang Shuang-Quan , Tang Ben Zhong , Mak Thomas C W
Published: November 2021

Metal clusters are useful phosphors, but highly luminescent examples are quite rare. Usually, the phosphorescence of metal clusters is hindered by ambient O2 molecules. Transforming this disadvantage into an advantage for meaningful applications of metal clusters presents a formidable challenge. In this work, we used ligand engineering to judiciously prepare colour-tuneable and brightly emitting Cu(I) clusters that are ultrasensitive to O2 upon dispersion in a fluid solution or in a solid matrix. When the O2 scavenger dimethyl sulfoxide (DMSO) was used as the solvent, joint photo- and oxygen-controlled multicolour switches were achieved for the first time for metal cluster-based photopatterning and photo-anticounterfeiting. More importantly, an aggregation-induced barrier to oxygen, a new aggregation-induced emission mechanism for metal clusters, was proposed, providing a new pathway to realizing the intense emission of metal clusters in the aggregated state. These results are expected to promote the application of metal clusters and enrich the luminescence theory of metal cluster aggregates.
After the New Queer Cinema
Authors: Rich B. Ruby
Published: November 2021

This chapter historicizes the work of the New Queer Cinema (NQC), a term coined by the author to describe a group of groundbreaking films that emerged in the late 1980s and early 1990s. It argues that the NQC sensibility fueled subsequent imaginative film and television, from makers as diverse as Ang Lee, Todd Haynes, Silas Howard, and Celine Sciamma. At the heart of the chapter is the conviction that contemporary politics demand a new framework for queer and trans media, namely the idea of intersectionality, demonstrated by makers and artists such as Janelle Monae, Allie Logout, Wu Tsang, The Nest Collective, and the trio of Mika Gustafson, Olivia Kastebring, and Christina Tsiobanelis. Intersectionality enables mutuality, recognition, and alliance in a time of deep division and terror; it asks queer media makers to take transgression beyond personal expressions and identity into collective acts of world making.
The cross-section measurement for the 3H(e, e′K+)nnΛ reaction
Authors: Suzuki K N , Gogami T , Pandey B , Itabashi K , Nagao S , Okuyama K , Nakamura S N , Tang L , Abrams D , Akiyama T , Androic D , Aniol K , Gayoso C Ayerbe , Bane J , Barcus S , Barrow J , Bellini V , Bhatt H , Bhetuwal D , Biswas D , Camsonne A , Castellanos J , Chen J-P , Chen J , Covrig S , Chrisman D , Cruz-Torres R , Das R , Fuchey E , Gnanvo K , Garibaldi F , Gautam T , Gomez J , Gueye P , Hague T J , Hansen O , Henry W , Hauenstein F , Higinbotham D W , Hyde C E , Kaneta M , Keppel C , Kutz T , Lashley-Colthirst N , Li S , Liu H , Mammei J , Markowitz P , McClellan R E , Meddi F , Meekins D , Michaels R , Mihovilovič M , Moyer A , Nguyen D , Nycz M , Owen V , Palatchi C , Park S , Petkovic T , Premathilake S , Reimer P E , Reinhold J , Riordan S , Rodriguez V , Samanta C , Santiesteban S N , Sawatzky B , Širca S , Slifer K , Su T , Tian Y , Toyama Y , Uehara K , Urciuoli G M , Votaw D , Williamson J , Wojtsekhowski B , Wood S A , Yale B , Ye Z , Zhang J , Zheng X
Published: November 2021

The small binding energy of the hypertriton leads to predictions of the non-existence of bound hypernuclei for isotriplet three-body systems such as nnΛ. However, invariant mass spectroscopy at GSI has reported events that may be interpreted as the bound nnΛ state. The nnΛ state was sought by missing-mass spectroscopy via the (e, e′K+) reaction at Jefferson Lab’s experimental Hall A. The present experiment has higher sensitivity to the nnΛ-state investigation in terms of better precision by a factor of about three. The analysis shown in this article focuses on the derivation of the reaction cross-section for the 3H(γ*, K+)X reaction. Events that were detected in an acceptance, where a Monte Carlo simulation could reproduce the data well ($|\delta p/p| \lt 4\%$), were analyzed to minimize the systematic uncertainty. No significant structures were observed with the acceptance cuts, and the upper limits of the production cross-section of the nnΛ state were obtained to be 21 and $31 \, \rm {nb} \, \rm {sr}^{-1}$ at the $90\%$ confidence level when theoretical predictions of (−BΛ, Γ) = (0.25, 0.8) MeV and (0.55, 4.7) MeV, respectively, were assumed. The cross-section result provides valuable information for examining the existence of nnΛ.
Legal professional privilege—what do we make of it in jurisdiction Malta? Part 1
Authors: Galea Patrick
Published: November 2021

Malta is a European Union and Commonwealth Member, and among the family of the “mixed” jurisdictions, being a Civil Law jurisdiction with extensive Common Law experience. This article will assess Legal Professional Privilege in the small island state. The historical, domestic and contemporary ECHR/EU sources, along with other areas such as the sometimes-blurred distinction or overlapping between professional secrecy, confidentiality and Privilege and the jurisprudential contribution of the Maltese Courts, are reviewed. The review addresses ethical standards including the recommendations of the Council of European Bars, joint and common-interest Privilege, whether Privilege on legal advice in a foreign jurisdiction can be upheld, the situation of internal counsel and the “Iniquity Exception.” The conclusion is that Malta does not distinguish between legal advice and litigation Privilege but acknowledges and applies one-unitary privilege to encompass both.
Endothelial SIRT1 as a Target for the Prevention of Arterial Aging: Promises and Challenges
Authors: Begum Musammat Kulsuma , Konja Daniels , Singh Sandeep , Chlopicki Stefan , Wang Yu
Published: November 2021

SIRT1, a member of the sirtuin family of longevity regulators, possesses potent activities preventing vascular aging. The expression and function of SIRT1 in endothelial cells are downregulated with age, in turn causing early vascular aging and predisposing various vascular abnormalities. Overexpression of SIRT1 in the vascular endothelium prevents aging-associated endothelial dysfunction and senescence, thus the development of hypertension and atherosclerosis. Numerous efforts have been directed to increase SIRT1 signaling as a potential strategy for different aging-associated diseases. However, the complex mechanisms underlying the regulation of SIRT1 have posed a significant challenge toward the design of specific and effective therapeutics. This review aimed to provide a summary on the regulation and function of SIRT1 in the vascular endothelium and to discuss the different approaches targeting this molecule for the prevention and treatment of age-related cardiovascular and cerebrovascular diseases.
Saturday Night Myelopathy
Authors: Martin Andrew J. , Garcia Maria C.
Published: November 2021

Introduction:

Myelopathy is a common condition with a variety of causes, often eluding diagnosis for some time. Prolonged flexion after surgical procedures has been described.

Case Report:

A 20-year-old female presented with acute paraparesis after polysubstance drug intoxication and a period of prolonged neck flexion while unconscious. Imaging demonstrated extensive cervicothoracic central cord signal change, in addition to posterior neck musculature hyperintensity. Additional workup directed to other causes was negative. The patient was diagnosed with flexion myelopathy and was treated with a course of steroids, with marked improvement.

Conclusions:

The clinician should consider the possibility of flexion-related myelopathy particularly in cases of drug intoxication or prolonged unconsciousness. Signal change within cervical musculature may provide additional clues and allow diagnosis in a timely manner.
Prevalence of the need for adaptive seating systems among children with cerebral palsy in Egypt
Authors: Abdallah Mohamed Adel , Abdelaziem Faten , Soliman Mostafa
Published: November 2021

Background:

An adaptive seating system is a basic rehabilitation need for children and youth with cerebral palsy (CP) as it supports the structure and function of the musculoskeletal system and can positively affect their activities and participation. Despite the importance of adaptive seating systems, there is limited access to such systems in low-income countries.

Objectives:

To determine the percentage of children and youth between 4 and 18 years of age with CP in Egypt whose activity level and sitting ability suggest the need for an adaptive seating system.

Study design:

Observational cross-sectional study.

Methods:

One hundred ninety-three participants were included after fulfilling the criteria of the Surveillance of Cerebral Palsy of Europe. Their level of activity was assessed by a physical therapist using the Gross Motor Function Classification System (GMFCS), and their sitting ability was evaluated using the Level of Sitting Scale (LSS). Participants were considered to require an adaptive seating system if they scored GMFCS level IV or V and LSS level 1–5 concurrently.

Results:

Approximately 44% of the study participants were classified as GMFCS level IV or V and LSS level 1-5, suggesting that they were in need of an adaptive seating system.

Conclusions:

There is a large percentage of children and youth with CP in Egypt who need an adaptive seating system to be integrated into their rehabilitation.
New perspectives on mobile genetic elements: a paradigm shift for managing the antibiotic resistance crisis
Authors: Ghaly Timothy M. , Gillings Michael R.
Published: November 2021

Mobile genetic elements (MGEs) are primary facilitators in the global spread of antibiotic resistance. Here, we present novel ecological and evolutionary perspectives to understand and manage these elements: as selfish entities that exhibit biological individuality, as pollutants that replicate and as invasive species that thrive under human impact. Importantly, each viewpoint suggests new means to control their activity and spread. When seen as biological individuals, MGEs can be regarded as therapeutic targets in their own right. We highlight promising conjugation-inhibiting compounds that could be administered alongside antibiotic treatment. Viewed as pollutants, sewage treatment methods could be modified to efficiently remove antimicrobials and the resistance genes that they select. Finally, by recognizing the invasive characteristics of MGEs, we might apply strategies developed for the management of invasive species. These include environmental restoration to reduce antimicrobial selection, early detection to help inform appropriate antibiotic usage, and biocontrol strategies that target MGEs, constituting precision antimicrobials. These actions, which embody the One Health approach, target different characteristics of MGEs that are pertinent at the cellular, community, landscape and global levels. The strategies could act on multiple fronts and, together, might provide a more fruitful means to combat the global resistance crisis.

This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.
Transposable elements promote the evolution of genome streamlining
Authors: van Dijk Bram , Bertels Frederic , Stolk Lianne , Takeuchi Nobuto , Rainey Paul B.
Published: November 2021

Eukaryotes and prokaryotes have distinct genome architectures, with marked differences in genome size, the ratio of coding/non-coding DNA, and the abundance of transposable elements (TEs). As TEs replicate independently of their hosts, the proliferation of TEs is thought to have driven genome expansion in eukaryotes. However, prokaryotes also have TEs in intergenic spaces, so why do prokaryotes have small, streamlined genomes? Using anin silicomodel describing the genomes of single-celled asexual organisms that coevolve with TEs, we show that TEs acquired from the environment by horizontal gene transfer can promote the evolution of genome streamlining. The process depends on local interactions and is underpinned by rock–paper–scissors dynamics in which populations of cells with streamlined genomes beat TEs, which beat non-streamlined genomes, which beat streamlined genomes, in continuous and repeating cycles. Streamlining is maladaptive to individual cells, but improves lineage viability by hindering the proliferation of TEs. Streamlining does not evolve in sexually reproducing populations because recombination partially frees TEs from the deleterious effects they cause.

This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.
Deeper than you think: partisan-dependent brain response
Authors: Katabi Noa , Simon Hadas , Yakim Sharon , Ravreby Inbal , Yeshurun Yaara
Published: November 2021

Recent political polarization has highlighted the extent to which individuals with opposing views experience ongoing events in markedly different ways. In this study, we explored the neural mechanisms underpinning this phenomenon. We conducted functional magnetic resonance image (fMRI) scanning right- and left-wing participants watching political videos just before the 2019 elections in Israel. Behavioral results demonstrated significant differences between left- and right-wing participants in their interpretation of the videos’ content. Neuroimaging results revealed partisanship-dependent differences in both high-order regions and early-motor and somato-sensory regions, although no such differences were found with regard to neutral content. Moreover, we found that most of the political content was more potent in synchronizing participants with right-wing views, and that this synchronization was observed already in early visual and auditory cortices. These results suggest that political polarization is not limited to higher-order processes as previously thought, but rather emerges already in motor and sensory regions.
Viral dynamics and immune responses to foot-and-mouth disease virus in African buffalo (Syncerus caffer)
Authors: Perez-Martin Eva , Beechler Brianna , Scott Katherine , de Klerk-Lorist Lin-Mari , Zhang Fuquan , Limon Georgina , Dugovich Brian , Gubbins Simon , Botha Arista , Juleff Nicholas , Hetem Robyn , van Schalkwyk Louis , Maree Francois F. , Jolles Anna , Charleston Bryan
Published: November 2021

Foot-and-mouth disease (FMD) is one of the most important livestock diseases restricting international trade. While it is clear that African buffalo (Syncerus caffer) act as the main wildlife reservoir, viral and immune response dynamics during FMD virus acute infection have not been described before in this species. We used experimental needle inoculation and contact infections with three Southern African Territories serotypes to assess clinical, virological and immunological dynamics for thirty days post infection. Clinical FMD in the needle inoculated buffaloes was mild and characterised by pyrexia. Despite the absence of generalised vesicles, all contact animals were readily infected with their respective serotypes within the first 2-9 days after being mixed with needle challenged buffaloes. Irrespective of the route of infection or serotype there were positive associations between the viral loads in blood and the induction of host innate pro-inflammatory cytokines and acute phase proteins. Viral loads in blood and tonsils were tightly correlated during the acute phase of the infection, however, viraemia significantly declined after a peak at 4 days post infection (dpi), which correlated with the presence of detectable neutralising antibodies. In contrast, infectious virus was isolated in the tonsils until the last sampling point (30 dpi) in most animals. The pattern of virus detection in serum and tonsil swabs was similar for all three serotypes in the direct challenged and contact challenged animals.

We have demonstrated for the first time, that African buffalo are indeed systemically affected by FMD virus and clinical FMD in buffalo is characterized by a transient pyrexia. Despite the lack of FMD lesions, infection of African buffalo was characterised by high viral loads in blood and oropharynx, rapid and strong host innate and adaptive immune responses and high transmissibility.
Synthesis of High-Resolution Research-Quality MRI Data from Clinical MRI Data in Patients with COVID-19
Authors: Cali Ryan J. , Freeman Holly J. , Billot Benjamin , Barra Megan E. , Fischer David , Sanders William R. , Huang Susie Y. , Conklin John , Fischl Bruce , Iglesias Juan Eugenio , Edlow Brian L.
Published: November 2021

Pathophysiological mechanisms of neurological disorders in patients with coronavirus disease 2019 (COVID-19) are poorly understood, partly because of a lack of high-resolution neuroimaging data. We applied SynthSR, a convolutional neural network that synthesizes high-resolution isotropic research-quality data from thick-slice clinical MRI data, to a cohort of 11 patients with severe COVID-19. SynthSR successfully synthesized T1-weighted MPRAGE data at 1 mm spatial resolution for all 11 patients, each of whom had at least one brain lesion. Correlations between volumetric measures derived from synthesized and acquired MPRAGE data were strong for the cortical grey matter, subcortical grey matter, brainstem, hippocampus, and hemispheric white matter (r=0.84 to 0.96, p≤0.001), but absent for the cerebellar white matter and corpus callosum (r=0.04 to 0.17, p>0.61). SynthSR creates an opportunity to quantitatively study clinical MRI scans and elucidate the pathophysiology of neurological disorders in patients with COVID-19, including those with focal lesions.
Postprandial dynamics of proglucagon cleavage products and their relation to metabolic health
Authors: Wagner Robert , Eckstein Sabine S. , Fritsche Louise , Prystupa Katsiaryna , Hörber Sebastian , Häring Hans-Ulrich , Birkenfeld Andreas L. , Peter Andreas , Fritsche Andreas , Heni Martin
Published: November 2021

While oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health. We used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from an extensively phenotyped study cohort.

Glucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36 % of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin kinetics were significantly different between suppressors and non-suppressors (p=0.004 and p=0.002, respectively) with higher concentrations of both hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01).

Glucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype that is known to be indicative for reduced cardiovascular risk, cancer incidence, and mortality.
A slow road from meat dominance to more sustainable diets: an analysis of purchase preferences
Authors: Erkkola Maijaliisa , Kinnunen Satu M , Vepsäläinen Henna R , Meinilä Jelena M , Uusitalo Liisa , Konttinen Hanna , Saarijärvi Hannu , Fogelholm Mikael , Nevalainen Jaakko
Published: November 2021

Background

Achieving a sustainable and healthy diet requires increased replacement of red meat with more sustainable foods. There is a call for novel methodologies to assess the potential of different interventions and policies in enhancing the transition from the current to more sustainable choices.

Objective

We aimed to characterize consumer clusters with similar preferences in protein sources, to compare the purchase prices of these foods, and to identify ongoing transitions from one protein source to another.

Design

Grocery purchase data with individual attributes on 29,437 consenting loyalty card holders were analyzed over 2.3 year period. We designed a sequence analysis to group participants to clusters with similar purchase preferences over the follow-up period and to estimate transition probabilities between preferences. We studied the determinants of prevalent purchase profiles by ordinal logistic models.

Results

We identified six participant profiles with similar preferences in four protein sources: red meat, poultry, fish, and plant-based foods. Red meat dominated the purchase preferences and showed the highest persistence over time. The majority (70%) of the participants demonstrated somewhat mixed purchase profiles. A step-by-step transition from red meat towards plant-based food preference seems most likely via poultry and fish. Overall, low income was not a barrier to a more sustainable purchase profile, while price may deter the purchase of fish. The most important resources in choosing more sustainable profiles were education and stage of family life.

Conclusions

Societal incentives for sustainable food choices seem most crucial at transition stages of life course and for the less educated. Here we also demonstrate that grocery purchase data offer a valuable tool for monitoring the progressive transition towards a healthy and sustainable food system.
Macrophage polarization in cesarean scar diverticulum
Authors: Huang Jinfa , Liu Xiaochun , Hou Yi , Liu Yixuan , Liao Kedan , Xie Ning , Deng Kaixian
Published: November 2021

Aims

To determine immunohistochemical features and correlations between M1/M2 polarization status with disease severity of post-cesarean scar diverticulum (CSD).

Methods

Histological and immunohistological staining were performed and inflammatory (CD16, CD163, and TNF-α), fibrosis (α-SMA), and angiogenic (CD31) markers were examined in uterine tissues collected from patients with uterine scar diverticula (CSD) (n=37) and cesarean section (CS) (n=3).

Results

CSD tissues have higher expression of α-SMA, TNF-α, CD16, and CD31 and lower expression of CD163 than CS tissue (P <0.05). Compared with adjacent tissues, thick-walled blood vessels, glands, and fibrotic sites have higher expression of α-SMA, TNF-α, and CD16. Statistical correlation was observed between the expression of CD16 and TNF-α (R = 0.693, P <0.001), α-SMA (R = 0.404, P <0.05), and CD31 (R = 0.253, P <0.05) in CSD tissues, especially with the ratio of CD16/CD163 (R = 0.590, P <0.01). A more significant difference was observed between the expression of CD16/CD163 and α-SMA (R = 0.556, P <0.001), TNF-α (R = 0.633, P <0.0001) and CD31 (R = 0.336, P <0.05) Statistical correlation.

Conclusion

In this study, TNF-α, α-SMA, CD16, and CD31 proteins were overexpressed in all CSD cases, and CD16/CD163 was positively correlated with tissue inflammation, fibrosis, and neovascularization. Abnormal mononuclear macrophage infiltration may be involved in the origin and progression of CSD.
The effects of walking in nature on negative and positive affect in adult psychiatric outpatients with major depressive disorder: A randomized-controlled study
Authors: Watkins-Martin Kia , Bolanis Despina , Richard-Devantoy Stéphane , Pennestri Marie-Hélène , Malboeuf-Hurtubise Catherine , Philippe Frederick , Guindon Julie , Gouin Jean-Philippe , Ouellet-Morin Isabelle , Geoffroy Marie-Claude
Published: November 2021

Background

While walking in nature has been shown to improve affect in adults from the community to a greater extent than walking in urban settings, it is unknown whether such findings can be generalized to individuals suffering from depression. Using a parallel group design, this randomized controlled trial examined the effects of a single walk in nature versus urban settings on negative and positive affect in adult psychiatric outpatients diagnosed with major depressive disorder (MDD).

Method

Participants recruited from a psychiatric outpatient clinic for adults with MDD were randomly assigned to a nature or urban walk condition. Thirty-seven adults (mean age=49 years) completed a single 60-minute walk. Negative and positive affect were assessed using The Positive and Negative Affect Schedule or PANAS at 6 time points: before the walk, halfway during the walk, immediately post-walk, at home before bedtime, 24 hours post-walk, and 48 hours post-walk.

Results

Controlling for baseline levels of affect before the walk, individuals who walked in nature experienced overall lower levels of negative affect, F(1, 35.039)=4.239, p=.047, compared to those who walked in urban settings. Positive affect did not differ across walk conditions.

Limitations

The generalizability of results are limited by the small sample size and the presence of more female than male participants.

Conclusions

Walking in nature might be a useful strategy to improve the affect of adults with MDD. Future research should investigate different ways to integrate the beneficial effects of nature exposure into existing treatment plans for psychiatric outpatients with MDD.
Spatial resolution of an integrated C4+CAM photosynthetic metabolism
Authors: Moreno-Villena Jose J , Zhou Haoran , Gilman Ian S , Tausta S. Lori , Cheung C. Y. Maurice , Edwards Erika J
Published: November 2021

C4 and CAM photosynthesis have repeatedly evolved in plants over the past 30 million years. Because both repurpose the same set of enzymes but differ in their spatial and temporal deployment, they have long been considered as distinct and incompatible adaptations. Remarkably, Portulaca contains multiple C4 species that perform CAM when droughted. Spatially explicit analyses of gene expression reveal that C4 and CAM systems are completely integrated in P. oleracea, with CAM and C4 carbon fixation occurring in the same cells and CAM-generated metabolites likely incorporated directly into the C4 cycle. Flux balance analysis corroborates the gene expression and predicts an integrated C4+CAM system under drought. This first spatially explicit description of a C4+CAM photosynthetic metabolism presents a new blueprint for crop improvement.
Cortical encoding during word reading in bilinguals: parallel interdigitated distributed networks support convergent linguistic functioning
Authors: Geng Shujie , Guo Wanwan , Xu Kunyu , Jia Tianye , Zhou Wei , Blakemore Colin , Tan Li-Hai , Cao Miao , Feng Jianfeng
Published: November 2021

Word reading includes a series of cognitive processes that convert low-level visual characteristics to neural representations. However, the consistency of the neural mechanisms for processing these cognitive components across different writing systems in bilinguals remains inconclusive. Here, we explored this question by employing representational similarity analysis with a semantic access task involving Chinese words, English words and Chinese pinyin. Distinct anatomical distribution patterns were detected for each type of brain representation across ideographic and alphabetic languages, resulting in 100% classification accuracy. Meanwhile, convergent cognitive components processing was found in the core language-related regions in left hemisphere, including the inferior frontal gyrus, temporal pole, superior and middle temporal gyrus, precentral gyrus and supplementary motor areas. Broadly, our findings indicated that the neural basis for word recognition of different writing systems in bilinguals was divergent in anatomical locations of neural representations for specialized processing but convergent in cognitive domains, which supported and enriched the assimilation-accommodation hypothesis.

Teaser

Cortical encoding linguistic processing across languages was support by parallel interdigitated distributed networks but convergent in cognitive domains.
A brainstem integrator for self-localization and positional homeostasis
Authors: Yang En , Zwart Maarten F. , Rubinov Mikail , James Benjamin , Wei Ziqiang , Narayan Sujatha , Vladimirov Nikita , Mensh Brett D. , Fitzgerald James E. , Ahrens Misha B.
Published: November 2021

To accurately track self-location, animals need to integrate their movements through space. In amniotes, representations of self-location have been found in regions such as the hippocampus. It is unknown whether more ancient brain regions contain such representations and by which pathways they may drive locomotion. Fish displaced by water currents must prevent uncontrolled drift to potentially dangerous areas. We found that larval zebrafish track such movements and can later swim back to their earlier location. Whole-brain functional imaging revealed the circuit enabling this process of positional homeostasis. Position-encoding brainstem neurons integrate optic flow, then bias future swimming to correct for past displacements by modulating inferior olive and cerebellar activity. Manipulation of position-encoding or olivary neurons abolished positional homeostasis or evoked behavior as if animals had experienced positional shifts. These results reveal a multiregional hindbrain circuit in vertebrates for optic flow integration, memory of self-location, and its neural pathway to behavior.
Effect of species, size, and chimerism on the susceptibility of Caribbean brain coral recruits to stony coral tissue loss disease (SCTLD)
Authors: Williamson Olivia M. , Dennison Caroline E. , O’Neil Keri L. , Baker Andrew C.
Published: November 2021

Stony coral tissue loss disease (SCTLD) has devastated coral populations along Florida’s Coral Reef and beyond. Although widespread infection and mortality of adult colonies have been documented, no studies have yet investigated the susceptibility of recruits to this disease. Here, we exposed eight-month-old Diploria labyrinthiformis recruits and four-month-old Colpophyllia natans recruits to two sequential doses of SCTLD in the laboratory to track infection and assess potential resilience. Both species began to develop lesions as early as 48 h after exposure began. During the first dose, 59.0% of C. natans recruits lost all tissue (died) within two to eight days of developing lesions, whereas D. labyrinthiformis recruits experienced significantly slower rates of tissue loss and minimal eventual mortality. In C. natans, larger recruits and those fused into groups of multiple genets (chimeras) exhibited the highest survivorship. In contrast, smaller and/or single (ungrouped) recruits had the lowest survivorship (9.9 - 26.5%). After 20 days, a second SCTLD dose was delivered to further test resistance in remaining recruits, and all recruits of both species succumbed within 6 days. Although no recruits showed absolute resistance to SCTLD following repeated exposures, our results provide evidence that interactions between species, size, and chimerism can impact relative resistance. This study represents the first report of SCTLD in Caribbean coral recruits and carries implications for natural species recovery and reef restoration efforts. Additional research on the susceptibility of coral juveniles to SCTLD is urgently needed, to include different species, locations, parents, and algal symbionts, with the goal of assessing relative susceptibility and identifying potential sources of resilience for this critical life history stage.
Meisosomes, folded membrane platforms, link the epidermis to the cuticle inC. elegans
Authors: Aggad Dina , Brouilly Nicolas , Omi Shizue , Essmann Clara L. , Dehapiot Benoit , Savage-Dunn Cathy , Richard Fabrice , Cazevieille Chantal , Politi Kristin A. , Hall David H. , Pujol Remy , Pujol Nathalie
Published: November 2021

Apical extracellular matrices (aECMs) form a physical barrier to the environment. InC. elegans, the epidermal aECM, the cuticle, is composed mainly of different types of collagen, associated in circumferential ridges separated by furrows. Here, we show that in mutants lacking furrows, the normal intimate connection between the epidermis and the cuticle is lost, specifically at the lateral epidermis, where, in contrast to the dorsal and ventral epidermis, there are no hemidesmosomes. At the ultrastructural level, there is a profound alteration of structures that we term “meisosomes”, in reference to eisosomes in yeast. We show that meisosomes are composed of stacked parallel folds of the epidermal plasma membrane, alternately filled with cuticle. We propose that just as hemidesmosomes connect the dorsal and ventral epidermis, above the muscles, to the cuticle, meisosomes connect the lateral epidermis to it. Moreover, furrow mutants present marked modifications of the biomechanical properties of their skin and exhibit a constitutive damage response in the epidermis. As meisosomes co-localise to macrodomains enriched in phosphatidylinositol (4,5) bisphosphate, they might act, like eisosomes, as signalling platforms, to relay tensile information from the aECM to the underlying epidermis, as part of an integrated stress response to damage.
PcoB is a defense outer membrane protein that facilitates cellular uptake of copper
Authors: Li Ping , Nayeri Niloofar , Gorecki Kamil , Becares Eva Ramos , Wang Kaituo , Mahato Dhani Ram , Andersson Magnus , Abeyrathna Sameera , Lindkvist-Petersson Karin , Meloni Gabriele , Missel Julie Winkel , Gourdon Pontus
Published: November 2021

Copper (Cu) is one of the most abundant trace metals in all organisms, involved in a plethora of cellular processes. Yet elevated concentrations of the element are harmful, and interestingly prokaryotes are more sensitive for environmental Cu stress than humans. Various transport systems are present to maintain intracellular Cu homeostasis, including the prokaryotic plasmid-encoded multiprotein pco operon, which is generally assigned as a defense mechanism against elevated Cu concentrations. Here we structurally and functionally characterize the outer membrane component of the Pco system, PcoB, recovering a 2.2 Å structure, revealing a classical β-barrel architecture. Unexpectedly, we identify a large opening on the extracellular side, linked to a considerably electronegative funnel that becomes narrower towards the periplasm, defining an ion conducting pathway as also supported by metal binding quantification via ICP-MS and MD simulations. However, the structure is partially obstructed towards the periplasmic side, and yet flux is permitted in the presence of a Cu gradient as shown by functional characterization in vitro. Complementary in vivo experiments demonstrated that isolated PcoB confers increased sensitivity towards Cu. Aggregated, our findings indicate that PcoB serves to permit Cu import. Thus, it is possible the Pco system physiologically accumulates Cu in the periplasm as a part of an unorthodox defense mechanism against metal stress. These results point to a previously unrecognized principle of maintaining Cu homeostasis and may as such also assist in the understanding and in efforts towards combatting bacterial infections of Pco-harboring pathogens.
An evolutionarily conserved cis-regulatory element of Nkx3.2 contributes to early jaw joint morphology in zebrafish
Authors: Leyhr Jake , Waldmann Laura , Filipek-Górniok Beata , Zhang Hanqing , Allalou Amin , Haitina Tatjana
Published: November 2021

The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element of Nkx3.2 that is deeply conserved in gnathostomes but undetectable in the jawless hagfish. This enhancer is active in the developing jaw joint region of the zebrafish Danio rerio, and was thus designated as jaw joint regulatory sequence 1 (JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 leads to a transient jaw joint deformation and partial fusion. Emergence of this Nkx3.2 enhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws.
easier: interpretable predictions of antitumor immune response from bulk RNA-seq data
Authors: Lapuente-Santana Óscar , Marini Federico , Ustjanzew Arsenij , Finotello Francesca , Eduati Federica
Published: November 2021

Immunotherapy with immune checkpoint blockers (ICB) is associated with striking clinical success, but only in a small fraction of patients. Thus, we need computational biomarker-based methods that can anticipate which patients will respond to treatment. Current established biomarkers are imperfect due to their incomplete view of the tumor and its microenvironment. We have recently presented a novel approach that integrates transcriptomics data with biological knowledge to study tumors at a more holistic level. Validated in four different solid cancers, our approach outperformed the state-of-the-art methods to predict response to ICB. Here, we introduce estimate systems immune response (easier), an R/Bioconductor package that applies our approach to quantify biomarkers and assess patients’ likelihood to respond to immunotherapy, providing just the patients’ baseline bulk-tumor RNA-sequencing (RNA-seq) data as input.
A spatial multi-omics atlas of the human lung reveals a novel immune cell survival niche
Authors: Madissoon Elo , Oliver Amanda J. , Kleshchevnikov Vitalii , Wilbrey-Clark Anna , Polanski Krzysztof , Orsi Ana Ribeiro , Mamanova Lira , Bolt Liam , Richoz Nathan , Elmentaite Rasa , Pett J. Patrick , Huang Ni , He Peng , Dabrowska Monika , Pritchard Sophie , Tuck Liz , Prigmore Elena , Knights Andrew , Oszlanczi Agnes , Hunter Adam , Vieira Sara F. , Patel Minal , Georgakopoulos Nikitas , Mahbubani Krishnaa , Saeb-Parsy Kourosh , Clatworthy Menna , Bayraktar Omer Ali , Stegle Oliver , Kumasaka Natsuhiko , Teichmann Sarah A. , Meyer Kerstin B.
Published: November 2021

Multiple distinct cell types of the human lung and airways have been defined by single cell RNA sequencing (scRNAseq). Here we present a multi-omics spatial lung atlas to define novel cell types which we map back into the macro- and micro-anatomical tissue context to define functional tissue microenvironments. Firstly, we have generated single cell and nuclei RNA sequencing, VDJ-sequencing and Visium Spatial Transcriptomics data sets from 5 different locations of the human lung and airways. Secondly, we define additional cell types/states, as well as spatially map novel and known human airway cell types, such as adult lung chondrocytes, submucosal gland (SMG) duct cells, distinct pericyte and smooth muscle subtypes, immune-recruiting fibroblasts, peribronchial and perichondrial fibroblasts, peripheral nerve associated fibroblasts and Schwann cells. Finally, we define a survival niche for IgA-secreting plasma cells at the SMG, comprising the newly defined epithelial SMG-Duct cells, and B and T lineage immune cells. Using our transcriptomic data for cell-cell interaction analysis, we propose a signalling circuit that establishes and supports this niche. Overall, we provide a transcriptional and spatial lung atlas with multiple novel cell types that allows for the study of specific tissue microenvironments such as the newly defined gland-associated lymphoid niche (GALN).
AlphaFill: enriching the AlphaFold models with ligands and co-factors
Authors: Hekkelman Maarten L. , de Vries Ida , Joosten Robbie P. , Perrakis Anastassis
Published: November 2021

Artificial intelligence (AI) methods for constructing structural models of proteins on the basis of their sequence are having a transformative effect in biomolecular sciences. The AlphaFold protein structure database makes available hundreds of thousands of protein structures. However, all these structures lack cofactors essential for their structural integrity and molecular function (e.g. hemoglobin lacks a bound heme), key ions essential for structural integrity (e.g. zinc-finger motifs) or catalysis (e.g. Ca2+or Zn2+in metalloproteases), and ligands that are important for biological function (e.g. kinase structures lack ADP or ATP). Here, we present AlphaFill, an algorithm based on sequence and structure similarity, to “transplant” such “missing” small molecules and ions from experimentally determined structures to predicted protein models. These publicly available structural annotations are mapped to predicted protein models, to help scientists interpret biological function and design experiments.
The role of four cholesterol-recognition motifs localized between amino acid residues 400-550 in regulating translocation and lytic activity of Adenylate Cyclase Toxin
Authors: Amuategi Jone , Alonso Rocío , Ostolaza Helena
Published: November 2021

Adenylate Cyclase Toxin (ACT or CyaA) is an important virulence factor secreted by Bordetella pertussis, the bacterium causative of whooping cough, playing an essential role in the establishment of infection in the respiratory tract. ACT is a pore-forming cytolysin belonging to the RTX (Repeats in ToXin) family of leukotoxins, capable of permeabilizing several cell types and pure lipid vesicles. Besides, the toxin delivers its N-terminal adenylate cyclase domain into the target cytosol, where catalyzes the conversion of ATP into cAMP, which affects cell signalling. In this study we have made two major observations. First, we show that ACT binds free cholesterol, and identify in its sequence 38 potential cholesterol-recognition motifs. Second, we reveal that four of those motifs are real, functional cholesterol-binding sites. Mutations of the central phenylalanine residues in said motifs have an important impact on the ACT lytic and translocation activities, suggesting their direct intervention in cholesterol recognition and toxin functionality. From our data a likely transmembrane topology can be inferred for the ACT helices constituting the translocation and the hydrophobic regions. From this topology a simple and plausible mechanism emerges by which ACT could translocate its AC domain into target cells, challenging previous views in the field. Blocking the ACT-cholesterol interactions might thus be an effective approach for inhibiting ACT toxicity on cells, and this could help in mitigating the severity of pertussis disease in humans.
Recurrent evolution of cross-resistance in response to selection for improved post-infection survival in Drosophila melanogaster
Authors: Singh Aparajita , Basu Aabeer , Shit Biswajit , Hegde Tejashwini , Bansal Nitin , Prasad Nagaraj Guru
Published: November 2021

The host susceptibility to one pathogen can decrease, increase, or remain unaffected by virtue of the host evolving resistance towards a second pathogen. Negative correlations between a host susceptibility to different pathogens is an often-cited explanation for maintenance of genetic variation in immune function determining traits in a host population. In this study, we investigated the change in susceptibility of Drosophila melanogaster flies to various novel bacterial pathogens after being experimentally selected for increased resistance to one particular bacterial pathogen. We independently selected flies to become more resistant towards Enterococcus faecalis and Pseudomonas entomophila, and baring a few exceptions the evolved populations exhibited cross-resistance against the range of pathogens tested in the study. Neither the identity of the native pathogen nor the host sex was major determining factors in predicting the pattern of cross-resistance exhibited by the selected populations. We therefore report that a generalized cross-resistance to novel pathogens can repeatedly evolve in response to selection for resistance against a single pathogen.
Effect of landscape structure on genetic structure of the Lesser horseshoe bat (Rhinolophus hipposideros) in Britanny colonies
Authors: Rodriguez Alexandra , Petit Eric
Published: November 2021

Some species are difficult to observe and others, need to be not disturbed because of their vulnerability. In response to the difficulty of studying the dispersal behaviors of these species, some areas of biology have been combined in order to access the information despite practical limitations. Here we present the combination of several methodologies from landscape ecology to non- invasive population genetics that allow us to obtain important information onRinolophus hipposideros, a vulnerable European bat. We genotyped 18 georeferrenced colonies in Brittany (France) from droppings collected in their refuges. We used 6 microsatellite markers in order to obtain the genetic distances between them. On the other hand we calculated Euclidian distances between the refuges occupied by these colonies and some ecological distances with the Pathmatrix module of ArcGis 3.2. We tested hypothesis about the difficulty of dispersal of the species in areas without forest cover or with a low density of hedges. Thanks to the Monmonier algorithm we could infer possible genetic barriers between the colonies and we could compare their location to the presence of landscape barriers (areas with little tree cover). We detected a pattern of isolation by distance that reveals limited dispersal capacities in the species but no pattern linked to ecological distances. We found that some of the neighboring colonies with greater genetic distances between them were located in areas with low density of hedges which could suggest an impact of this landscape element in their movements. Finer studies should allow us to conclude on the need or not of forest cover in the dispersal of this species.

Abstract Figure