bluuebunny/crossref_metadata_2025 huggingface dataset:
Intact finger representation within primary sensorimotor cortex of Musician’s Dystonia
Authors: Sadnicka A , Wiestler T , Butler K , Altenmüller E , Edwards MJ , Ejaz N , Diedrichsen J
Published: December 2021

Musician’s dystonia presents with a persistent deterioration of motor control during musical performance. A predominant hypothesis has been that this is underpinned by maladaptive neural changes to the somatotopic organisation of finger representations within primary somatosensory cortex. Here, we tested this hypothesis by investigating the finger-specific activity patterns in the primary somatosensory and motor cortex using functional MRI in nine musicians with dystonia and nine healthy musicians. A purpose-built keyboard device allowed functional MRI characterisation of activity patterns elicited during passive extension and active finger presses of individual fingers. We analysed the data using both traditional spatial analysis and state-of-the art multivariate analyses. Our analysis reveals that digit representations in musicians were poorly captured by spatial measures. An optimised spatial metric found clear somatotopy but no difference in the spatial geometry between fingers. Representational similarity analysis was confirmed as a highly reliable technique and more consistent than all spatial metrics evaluated. Significantly, the dissimilarity architecture was equivalent for musicians with and without dystonia and no expansion or spatial shift of digit representation maps were found in the symptomatic group. Our results therefore suggest that the neural representation of generic finger maps in primary sensorimotor cortex is intact in Musician’s dystonia. These results are against the idea that task-specific dystonia is associated with a distorted hand somatotopy and suggests that task-specific dystonia is due to a higher order disruption of skill encoding. Such a formulation can better explain the task-specific deficit and offers mechanistic insight for therapeutic interventions.
Employment status and its associated factor for patients 12 months after intensive care: Secondary analysis of the SMAP-HoPe-study
Authors: Unoki Takeshi , Kitayama Mio , Sakuramoto Hideaki , Ouchi Akira , Kuribara Tomoki , Yamaguchi Takako , Uemura Sakura , Fukuda Yuko , Haruna Junpei , Tsujimoto Takahiro , Hino Mayumi , Shiba Yuko , Nagao Takumi , Shirasaka Masako , Satoi Yosuke , Toyoshima Miki , Masuda Yoshiki
Published: December 2021

Returning to work is a serious issue that affects patients who are being discharged from the intensive care unit (ICU). This study aimed to clarify the employment status and the perceived household financial status of ICU patients 12 months following discharge from the ICU. Additionally, a hypothesis of whether depressive symptoms were associated with subsequent unemployment status was tested. This study was a subgroup analysis using data from the published Survey of Multicenter Assessment with Postal questionnaire for Post-Intensive Care Syndrome (PICS) for Home Living Patients (the SMAP-HoPe study) in Japan. The patients included those who had a history of staying in the ICU for at least three nights and had been living at home for one year following discharge, between October 2019 and July 2020. We assessed employment status, subjective cognitive functions, household financial status, Hospital Anxiety and Depression Scale scores, and EuroQOL-5 dimensions of physical function at 12 months following intensive care. This study included 328 patients who were known to be employed prior to ICU admission. The median age was 64 (Interquartile Range [IQR] 52-72), and males were predominant (86%). Seventy-nine (24%) of those evaluated were unemployed. The number of patients who reported worsened financial status was significantly higher in the unemployed group. (p<.01) Multivariate analysis showed that higher age (Odds Ratio [OR]: 1.06, 95% Confidence Interval [CI]: 1.03-1.08]) and severity of depressive symptoms (OR: 1.13 [95% CI: 1.05-1.23]) were independent factors for employment status after 12 months from being discharged from the ICU. These factors were determined to be significant even after adjusting for sex, physical function, and cognitive function. We found that one-fourth of our patients who had been employed prior to ICU admission were subsequently unemployed 12 months following ICU discharge. Additionally, depressive symptoms were associated with unemployment status. The government and the local municipalities should provide medical and financial support to such patients. Additionally, community support for such patients is warranted.
The impact of the COVID-19 pandemic on hospital services for patients with cardiac diseases: a scoping review
Authors: de Lange Mats , Carvalho Ana Sofia , Fernandes Óscar Brito , Lingsma Hester , Klazinga Niek , Kringos Dionne
Published: December 2021

Background

The repercussions of the COVID-19 pandemic concern care in many clinical areas, including cardiology. We aim to assess the impact of the COVID-19 pandemic on hospital care for cardiac patients.

Methods

Scoping review. Performance indicators were extracted and collated to inform on changes in the use of health services and care provided during January - June 2020.

Results

Database searches yielded 6277 articles, of which 838 articles met the inclusion criteria during initial screening. After full-text screening, 94 articles were considered for data extraction. In total, 1637 indicators were retrieved, showing large variation in the indicators and their definitions. Most of the indicators that provided information on changes in number of admissions (n=118, 88%) signalled a decrease in admissions; 88% (n=15) of the indicators showed patients’ delayed presentation and 40% (n=54) showed patients in a worse clinical condition. A reduction in diagnostic and treatment procedures was signalled by 95% (n=18) and 81% (n=64) of the indicators reporting on cardiac procedures, respectively. Length of stay decreased in 58% (n=21) of the indicators and acute coronary syndromes treatment times increased in 61% (n=65) of the indicators. Outpatient activity decreased in 94% (n=17) of the indicators related with outpatient care, whereas telehealth utilization increased in 100% (n=6). Outcomes worsened in 40% (n=35) of the indicators, and mortality rates increased in 52% (n=31).

Conclusion

All phases of the hospital cardiac care pathway were affected. This information could support the planning of care during the ongoing pandemic and in future events.
Assessing Open Science practices in physical activity behaviour change intervention evaluations
Authors: Norris Emma , Sulevani Isra , Finnerty Ailbhe N. , Castro Oscar
Published: December 2021

Objectives

Concerns on the lack of reproducibility and transparency in science have led to a range of research practice reforms, broadly referred to as ‘Open Science’. The extent that physical activity interventions are embedding Open Science practices is currently unknown. In this study, we randomly sampled 100 reports of recent physical activity behaviour change interventions to estimate the prevalence of Open Science practices.

Methods

One hundred reports of randomised controlled trial physical activity behaviour change interventions published between 2018-2021 were identified. Open Science practices were coded in identified reports, including: study pre-registration, protocol sharing, data-, materials- and analysis scripts-sharing, replication of a previous study, open access publication, funding sources and conflict of interest statements. Coding was performed by two independent researchers, with inter-rater reliability calculated using Krippendorff’s alpha.

Results

78% of the 100 reports provided details of study pre-registration and 41% provided evidence of a published protocol. 4% provided accessible open data, 8% provided open materials and 1% provided open analysis scripts. 73% of reports were published as open access and no studies were described as replication attempts. 93% of reports declared their sources of funding and 88% provided conflicts of interest statements. A Krippendorff’s alpha of 0.73 was obtained across all coding.

Conclusion

Open data, materials, analysis and replication attempts are currently rare in physical activity behaviour change intervention reports, whereas funding source and conflict of interest declarations are common. Future physical activity research should increase the reproducibility of their methods and results by incorporating more Open Science practices.
The prostate tissue-based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy
Authors: Heaphy Christopher M. , Joshu Corinne E. , Barber John R. , Davis Christine , Lu Jiayun , Zarinshenas Reza , Giovannucci Edward , Mucci Lorelei A. , Stampfer Meir J. , Han Misop , De Marzo Angelo M. , Lotan Tamara L. , Platz Elizabeth A. , Meeker Alan K.
Published: December 2021

Purpose

Current biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision-making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer-associated stromal cells – the telomere biomarker – is strongly associated with progression to metastasis and prostate cancer death after prostatectomy independent of currently used pathologic indicators.

Experimental Design

We optimized our method allowing for semi-automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in tissue microarrays from five cohort studies of men surgically treated for clinically localized disease (N=2,255). We estimated the relative risk (RR) of progression to metastasis (N=311) and prostate cancer death (N=85) using models appropriate to each study’s design adjusting for age, prostatectomy stage, and tumor grade, which then we meta-analyzed using inverse variance weights.

Results

Compared with men who had less variable telomere length among prostate cancer cells and longer telomere length in prostate cancer-associated stromal cells, men with the combination of more variable and shorter telomere length, had 3.76-times the risk of prostate cancer death (95% CI 1.37-10.3; p=0.01) and had 2.23-times the risk of progression to metastasis (95% CI 0.99-5.02, P=0.05). The telomere biomarker was associated with prostate cancer death in men with intermediate risk disease (Grade Groups 2/3: RR=9.18, 95% CI 1.14- 74.0, p=0.037) and with PTEN intact tumors (RR=6.74, 95% CI 1.46-37.6, p=0.015).

Conclusions

The telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically-treated men.

Translational Relevance

Current prognostic biomarkers in localized prostate cancer are inadequate imperfect predictors; therefore, new biomarkers are needed to improve the prognostic classification and management of these patients. In a five-cohort study, we confirmed that the tissue-based telomere biomarker – the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer-associated stromal cells – was associated with progression to metastasis and prostate cancer death independent of currently used prognostic indicators after prostatectomy for clinically-localized disease. Importantly, the telomere biomarker was associated with poor outcome in men with intermediate risk disease, as well as in men with intact PTEN tumors. Thus, this tissue-based telomere biomarker has the translational potential to improve treatment and surveillance decision-making.
Black-box testing in motor sequence learning
Authors: Maceira-Elvira Pablo , Timmermann Jan E. , Popa Traian , Schmid Anne-Christine , Krakauer John W. , Morishita Takuya , Wessel Maximilian J. , Hummel Friedhelm C.
Published: December 2021

During learning of novel motor sequences, practice leads to the consolidation of hierarchical structures, namely motor chunks, facilitating the accurate execution of sequences at increasing speeds. Recent studies show that such hierarchical structures are largely represented upstream of the primary motor cortex in the motor network, suggesting their function to be more related to the encoding, storage, and retrieval of sequences rather than their sole execution. We isolated different components of motor skill acquisition related to the consolidation of spatiotemporal features and followed their evolution over training. We found that optimal motor skill acquisition relies on the storage of the spatial features of the sequence in memory, followed by the optimization of its execution and increased execution speeds (i.e., a shift in the speed-accuracy trade-off) early in training, supporting the model proposed by Hikosaka in 1999. Contrasting the dynamics of these components during ageing, we identified less-than-optimal mechanisms in older adults explaining the observed differences in performance. We applied noninvasive brain stimulation in an attempt to support the aging brain to compensate for these deficits. The present study found that anodal direct current stimulation applied over the motor cortex restored the mechanisms involved in the consolidation of spatial features, without directly affecting the speed of execution of the sequence. This led older adults to sharply improve their accuracy, resulting in an earlier yet gradual emergence of motor chunks. The results suggest the early storage of the sequence in memory, largely independent of motor practice, is crucial for an optimal motor acquisition and retrieval of this motor behavior. Nevertheless, the consolidation of optimal temporal patterns, detected as motor chunks at a behavioral level, is not a direct consequence of storing the sequence elements, but rather of motor practice.
MSD2, an apoplastic Mn-SOD, contributes to root skotomorphogenic growth by modulating ROS distribution in Arabidopsis
Authors: Chen Huize , Lee Jinsu , Lee Jung-Min , Han Minsoo , Emonet Aurélia , Lee Jiyoun , Jia Xingtian , Lee Yuree
Published: December 2021

Reactive oxygen species (ROS) play essential roles as a second messenger in various physiological processes in plants. Due to their oxidative nature, ROS can also be harmful. Thus, the generation and homeostasis of ROS are tightly controlled by multiple enzymes. Membrane-localized NADPH oxidases are well known to generate ROS during developmental and stress responses, but the metabolic pathways of the superoxide (O2·−) generated by them in the apoplast are poorly understood, and the identity of the apoplastic superoxide dismutase (SOD) is unknown in Arabidopsis. Here, we show that a putative manganese SOD, MSD2 is secreted and possesses a SOD activity that can be inhibited by nitration at tyrosine 68. The expression of MSD2 in roots is light condition-dependent, suggesting that MSD2 may act on ROS metabolism in roots during the light-to-dark transition. Root architecture is governed by ROS distribution that exhibits opposite gradient of H2O2 and O2·−, which is indeed altered in etiolated msd2 mutants and accompanied by changes in the onset of differentiation. These results provide a missing link in our understanding of ROS metabolism and suggest that MSD2 plays a role in root skotomorphogenesis by regulating ROS distribution, thereby playing a pivotal role in plant growth and development.
Maternal parity affects Day 8 embryo gene expression in old mares
Authors: Derisoud Emilie , Jouneau Luc , Gourtay Clothilde , Margat Anne , Archilla Catherine , Jaszczyszyn Yan , Legendre Rachel , Daniel Nathalie , Peynot Nathalie , Dahirel Michèle , Briot Laurie , De Geoffroy Frédéric , Duranthon Véronique , Chavatte-Palmer Pascale
Published: December 2021

As sport career is a priority in most of equine breeds, mares are frequently bred for the first time at an advanced age. Both age and first gestation were shown to have a deleterious effect on reproduction outcomes, respectively on fertility and offspring weight but the effect mare’s parity in older mares on embryo quality has never been considered. The aim of this project was to determine the effect of old mare’s nulliparity on gene expression in embryos. Day 8 post ovulation embryos were collected from old (10-16 years old) nulliparous (ON, N=5) or multiparous (OM, N=6) non-nursing Saddlebred mares, inseminated with the semen of one stallion. Pure (TE_part) or inner cell mass enriched (ICMandTE) trophoblast were obtained by embryo bisection and paired end, non-oriented RNA sequencing (Illumina, NextSeq500) was performed on each hemi-embryo. To discriminate gene expression in the ICM from that in the TE, deconvolution (DeMixT R package) was used on the ICMandTE dataset. Differential expression was analyzed (DESeq2) with embryo sex and diameter as cofactors using a false discovery rate <0.05 cutoff. Although the expression of only a few genes was altered by mare’s nulliparity (33 in ICM and 23 in TE), those genes were related to nutrient exchanges and responses to environment signaling, both in ICM and TE, suggesting that the developing environment from these mares are not optimal for embryo growth. In conclusion, being nulliparous and old does not seem to be the perfect match for embryonic development in mares.

Summary sentence

Mare’s parity in old mares impacts the expression of genes related to development and molecule exchanges in ICM and TE of blastocysts suggesting an adaptation to an altered environment.
A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies
Authors: Carpen Laura , Falvo Paolo , Orecchioni Stefania , Mitola Giulia , Hillje Roman , Mazzara Saveria , Mancuso Patrizia , Pileri Stefano , Raveane Alessandro , Bertolini Francesco
Published: December 2021

Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as anti-PD-1, have shown combinatorial clinical activity with chemotherapy in triple negative breast cancer (TNBC) delineating some therapeutic combinations as more effective than others. However, a clear overview of the main immune cell populations involved in these treatments has never been provided.

Here, an assessment of the immune landscape in the tumour microenvironment (TME) of two TNBC mouse models (4T1 and EMT6 cell lines) has been performed using single-cell RNA sequencing (scRNA-seq) technology. Specifically, immune cells were evaluated in untreated conditions and after being treated with chemotherapy or immunotherapy used as single agents or in combination. A decrease of regulatory T cells, compared to the untreated TME, was found in treatments within vivoefficacy as well as γδ T cells, which have a pro-tumoral activity in mice. Focusing on Cd8 T cells, across all the conditions, a general increase of exhausted-like Cd8 T cells was confirmed in pre-clinical treatments with low efficacy; on the other hand, an opposite trend was found for the proliferative Cd8 T cells. Regarding macrophages, M2-like cells were found enriched in treatments with low efficacy while opposite behaviour was associated with M1-like macrophages. For both cell lines, similar proportions of B cells were detected with an increase of proliferative B cells in treatments that involved cisplatin in combination with anti-PD-1. The fine-scale characterization of the immune TME in this work can lead to new insights on the diagnosis and treatment of TNBC for a possible application at the clinical level.
Metabolite Damage and Damage-Control in a Minimal Genome
Authors: Haas Drago , Thamm Antje M. , Sun Jiayi , Huang Lili , Sun Lijie , Beaudoin Guillaume A.W. , Wise Kim S. , Lerma-Ortiz Claudia , Bruner Steven D. , Breuer Marian , Luthey-Schulten Zaida , Lin Jiusheng , Wilson Mark A. , Brown Greg , Yakunin Alexander F. , Kurilyak Inna , Folz Jacob , Fiehn Oliver , Glass John I. , Hanson Andrew D. , Henry Christopher S. , de Crécy-Lagard Valérie
Published: December 2021

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes with known metabolite damage repair or preemption functions were identified and experimentally validated, including 5-formyltetrahydrofolate cyclo-ligase, CoA disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and spontaneous side reactions. This extension revealed that several key metabolite damage-control systems remain to be identified in JCVI-Syn3A, such as that for methylglyoxal.
AraC binds the p75NTRtransmembrane domain to induce neurodegeneration in mature neurons
Authors: Lopes-Rodrigues Vanessa , Boxy Pia , Sim Eunice , Park Dong Ik , Carbonell Josep , Andersson Annika , Fernández-Suárez Diana , Nykjær Anders , Kisiswa Lilian
Published: December 2021

Background

Cytosine arabinoside (AraC) is one of the main therapeutic treatments for several types of cancer including acute myeloid leukaemia. However, after high dose AraC chemotherapy regime, patients develop severe neurotoxicity and neurodegeneration in the central nervous system leading to cerebellar ataxia, dysarthria, nystagmus, somnolence and drowsiness. AraC induces apoptosis in dividing cells, however, the mechanism by which it leads to neurite degeneration and cell death in mature neurons remains unclear. We hypothesized that the upregulation of the death receptor p75NTRis responsible for AraC-mediated neurodegeneration and cell death in leukemia patients undergoing AraC treatment.

Methods

To determine the role of AraC-p75NTRsignalling in degeneration of mature cerebellar granule neurons, we used primary cultures from p75NTRknockout andp75NTRCys259mice. Evaluation of neurodegeneration, cell death and p75NTRsignalling was done by immunohistochemistry and immunoblotting. To assess the direct interaction between AraC and p75NTR, we performed isothermal dose response-cellular thermal shift and AraTM assays as well as Homo-FRET anisotropy imaging.

Results

We show that AraC induces neurite degeneration and programmed cell death of mature cerebellar granule neurons in a p75NTR-dependent manner. Mechanistically, AraC binds to Proline 252 and Cysteine 256 of the p75NTRtransmembrane domain and selectively uncouples p75NTRfrom the NFκB survival pathway. This in turn, exacerbates the activation of the cell death/JNK pathway by recruitment of TRAF6 to p75NTR.

Conclusion

Our findings identify p75NTRas a novel molecular target to develop treatments to counteract AraC-mediated neurodegeneration.
Dual role of strigolactone receptor signaling partner in inhibiting substrate hydrolysis
Authors: Sobecks Briana L. , Chen Jiming , Shukla Diwakar
Published: December 2021

Plant branch and root growth relies on metabolism of the strigolactone (SL) hormone. The interaction between the SL molecule, Oryza sativa DWARF14 (D14) SL receptor, and D3 F-box protein has been shown to play a critical role in SL perception. Previously, it was believed that D3 only interacts with the closed form of D14 to induce downstream signaling, but recent experiments indicate that D3, as well as its C-terminal helix (CTH), can interact with the open form as well to inhibit strigolactone signaling. Two hypotheses for the CTH induced inhibition are that either the CTH affects the conformational ensemble of D14 by stabilizing catalytically inactive states, or the CTH interacts with SLs in a way that prevents them from entering the binding pocket. In this study, we have performed molecular dynamics (MD) simulations to assess the validity of these hypotheses. We used an apo system with only D14 and the CTH to test the active site conformational stability and a holo system with D14, the CTH, and an SL molecule to test the interaction between the SL and CTH. Our simulations show that the CTH affects both active site conformation and the ability of SLs to move into the binding pocket. In the apo system, the CTH allosterically stabilized catalytic residues into their inactive conformation. In the holo system, significant interactions between SLs and the CTH hindered the ability of SLs to enter the D14 binding pocket. These two mechanisms account for the observed decrease in SL binding to D14 and subsequent ligand hydrolysis in the presence of the CTH.
Rapid, Reference-Free Human Genotype Imputation with Denoising Autoencoders
Authors: Dias Raquel , Evans Doug , Chen Shang-Fu , Chen Kai-Yu , Chan Leslie , Torkamani Ali
Published: December 2021

Genotype imputation is a foundational tool for population genetics. Standard statistical imputation approaches rely on the co-location of large whole-genome sequencing-based reference panels, powerful computing environments, and potentially sensitive genetic study data. This results in computational resource and privacy-risk barriers to access to cutting-edge imputation techniques. Moreover, the accuracy of current statistical approaches is known to degrade in regions of low and complex linkage disequilibrium.

Artificial neural network-based imputation approaches may overcome these limitations by encoding complex genotype relationships in easily portable inference models. Here we demonstrate an autoencoder-based approach for genotype imputation, using a large, commonly-used reference panel, and spanning the entirety of human chromosome 22. Our autoencoder-based genotype imputation strategy achieved superior imputation accuracy across the allele-frequency spectrum and across genomes of diverse ancestry, while delivering at least 4-fold faster inference run time relative to standard imputation tools.
Age-related changes in microRNAs expression in cruciate ligaments of wild-stock house mice
Authors: Kharaz Yalda A. , Goljanek-Whysall Katarzyna , Nye Gareth , Hurst Jane , McArdle Anne , Comerford Eithne J.
Published: December 2021

Aim

Cruciate ligaments (CLs) of the knee joint are commonly injured following trauma or ageing. MicroRNAs (miRs) are potential therapeutic targets in musculoskeletal disorders. This study aimed to 1) identify if wild-stock house (WSH) mice are an appropriate model to study age-related changes of the knee joint and 2) investigate expression of miRs in ageing murine CLs.

Methods

Knee joints were collected from 6 and 24 months old C57BL/6 and WSH mice (Mus musculus domesticus) for histological analysis. RNA extraction and qPCR gene expression were performed on CLs in 6, 12, 24, and 30 month WSH old mice. Expression of miR targets in CLs was determined, followed by analysis of predicted mRNA target genes and Ingenuity Pathway Analysis.

Results

Higher CL and knee OARSI histological scores were found in 24 month old WSH mice compared to 6 and 12 month old C57BL/6 and 6 month old WSH mice (p< 0.05). miR-29a and miR-34a were upregulated in 30 month-old WSH mice in comparison to 6, 12 and 24-month-old WSH mice (p<0.05). Ingenuity Pathway Analysis on miR-29a and 34a targets was associated with inflammation through interleukins, TGFβ and Notch genes and p53 signalling. Collagen type I alpha 1 chain (COL1A1) correlated negatively with both miR-29a (r= -0.35) and miR-34a (r= -0.33).

Conclusion

The findings of this study support WSH house mice as an accelerated ageing model of the murine knee joint. This study also indicated that miR-29a and 34a may be important regulators of COL1A1 gene expression in murine CLs.
Physics Augmented U-Net: A High-Frequency Aware Generative Prior for Microscopy
Authors: Pradeepkumar Jathurshan , Anandakumar Mithunjha , Kugathasan Vinith , Seeber Andrew , Wadduwage Dushan N.
Published: December 2021

A key challenge in optical microscopy is to image fast at high-resolution. To address this problem, we propose “Physics Augmented U-Net”, which combines deep learning and structured illumination microscopy (SIM). In SIM, the structured illumination aliases out-of-band high-frequencies to the passband of the microscope; thus SIM captures some high-frequencies even when the image is sampled at low-resolution. To utilize these features, we propose a three-element method: 1) a modified U-Net model, 2) a physics-based forward model of SIM 3) an inference algorithm combining the two models. The modified U-Net architecture is similar to the seminal work, but the bottleneck is modified by concatenating two latent vectors, one encoding low-frequencies (LFLV), and the other encoding high-frequencies (HFLV). LFLV is learned by U-Net contracting path, and HFLV is learned by a second encoding path. In the inference mode, the high-frequency encoder is removed; HFLV is then optimized to fit the measured microscopy images to the output of the forward model for the generated image by the U-Net. We validated our method on two different datasets under different experimental conditions. Since a latent vector is optimized instead of a 2D image, the inference mode is less computationally complex. The proposed model is also more stable compared to other generative prior-based methods. Finally, as the forward model is independent of the U-Net, Physics Augmented U-Net can enhance resolution on any variation of SIM without further retraining.
Community Composition of Bacteria Isolated from Swiss Banknotes Varies Depending on Collection Environment
Authors: Bischofberger Anna M. , Hall Alex R.
Published: December 2021

Humans interact constantly with surfaces and associated microbial communities in the environment. The factors shaping the composition of these communities are poorly understood: some proposed explanations emphasize the influence of local habitat conditions (niche-based explanations), while others point to geographic structure and the distance among sampled locations (dispersal-based explanations). However, the relative roles of these different drivers for microbial community assembly on human-associated surfaces are not clear. Here, we used a combination of sampling, sequencing (16S rRNA) and culturing to show that the composition of banknote-associated bacterial communities varies depending on the local collection environment. Using banknotes collected from various locations and types of shops across Switzerland, we found taxonomic diversity dominated by families such asPseudomonadaceaeandStaphylococcaceae, but with banknote samples from particular types of shops (especially butcher shops) having distinct community structure. By contrast, we found no evidence of geographic structure: similarity of community composition did not decrease with increasing distance among sampled locations. These results show that microbial communities associated with banknotes, one of the most commonly encountered and exchanged human-associated surfaces, can reflect the local environmental conditions (in this case, the type of shop), and the signal for this type of variation was stronger than that for geographic structure among the locations sampled here.
Overexpression of NDR1 Leads to Pathogen Resistance at Elevated Temperatures
Authors: Samaradivakara Saroopa P. , Chen Huan , Lu Yi-Ju , Li Pai , Kim Yongsig , Tsuda Kenichi , Mine Akira , Day Brad
Published: December 2021

Abiotic and biotic environments influence a myriad of plant-related processes, including growth, development, and the establishment and maintenance of interaction(s) with microbes. As a driver of this signaling between plants and microbes, the role of plant hormones in both surveillance and signaling has emerged as a point of intersection between plant-abiotic and -biotic responses. In the current study, we elucidate a role for NON-RACE-SPECIFIC DISEASE RESISTANCE1 (NDR1) by exploiting effector-triggered immunity (ETI) to define the regulation of plant host immunity in response to both pathogen infection and elevated temperature. We generated time-series RNA sequencing data of WT Col-0, a NDR1 overexpression line, as well as ndr1 and ics1-2 mutant plants under elevated temperature. Not surprisingly, the NDR1-overexpression line showed genotype-specific gene expression changes related to defense response and immune system function. Interestingly, overexpression of NDR1 revealed a role for NDR1 in immune system function; specifically, we describe a mechanism that intersects with Pseudomonas syringae, type-III effector translocation, R-protein signaling complex stabilization, and sustained levels of SA at elevated temperature during ETI. The results described herein support a role for NDR1 in maintaining cell signaling during simultaneous exposure to elevated temperature and avirulent pathogen stressors.

One-sentence summary

NDR1 is required for Pst-AvrRpt2 triggered ETI at elevated temperature.
CURT1A and CURT1C mediate distinct stages of plastid conversion inArabidopsis
Authors: Liang Zizhen , Yeung Wai Tsun , Ki Mai Keith Ka , Ma Juncai , Liu Zhongyuan , Chong Yau-Lun Felix , Kang Byung-Ho
Published: December 2021

The crystalline structure of prolamellar bodies (PLBs) and light-induced etioplasts-to-chloroplasts transformation have been investigated with electron microscopy methods. However, these studies suffer from chemical fixation artifacts and limited volumes of tomographic reconstruction. We have examinedArabidopsis thalianacotyledon samples preserved by high-pressure freezing with scanning transmission electron tomography to visualize larger volumes in etioplasts and their conversion into chloroplasts. PLB tubules were arranged in a zinc blende-type lattice like carbon atoms in diamonds. Within 2 hours after illumination, the lattice collapsed from the PLB exterior and the disorganized tubules merged to form fenestrated sheets that eventually matured into lamellar thylakoids. These planar thylakoids emerging from PLBs overlapped or folded into grana stacks in PLBs’ vicinity. Since the nascent lamellae had curved membrane at their tips, we examined the localization of CURT1 proteins.CURT1Atranscript was most abundant in de-etiolating cotyledon samples, and CURT1A concentrated at the peripheral PLB. Incurt1amutant etioplasts, thylakoid sheets were swollen and failed to develop stacks. Incurt1cmutant, however, PLBs had cracks in their lattices, indicating that CURT1C contributes to cubic crystal growth under darkness. Our data provide evidence that CURT1A and CURT1C play distinct roles in the etioplast and chloroplast biogenesis.
Demographic feedbacks can hamper the spatial spread of a gene drive
Authors: Girardin Léo , Débarre Florence
Published: December 2021

Abstract

This paper is concerned with a reaction–diffusion system modeling the fixation and the invasion in a population of a gene drive (an allele biasing inheritance, increasing its own transmission to offspring). In our model, the gene drive has a negative effect on the fitness of individuals carrying it, and is therefore susceptible of decreasing the total carrying capacity of the population locally in space. This tends to generate an opposing demographic advection that the gene drive has to overcome in order to invade. While previous reaction–diffusion models neglected this aspect, here we focus on it and try to predict the sign of the traveling wave speed. It turns out to be an analytical challenge, only partial results being within reach, and we complete our theoretical analysis by numerical simulations. Our results indicate that taking into account the interplay between population dynamics and population genetics might actually be crucial, as it can effectively reverse the direction of the invasion and lead to failure. Our findings can be extended to other bistable systems, such as the spread of cytoplasmic incompatibilities caused by Wolbachia.
iDEP-assisted isolation of insulin secretory vesicles
Authors: Barekatain Mahta , Liu Yameng , Wang Zhongying , Cherezov Vadim , Fraser Scott E. , White Kate L , Hayes Mark A.
Published: December 2021

Organelle heterogeneity and inter-organelle associations within a single cell contribute to the limited sensitivity of current organelle separation techniques, thus hindering organelle subpopulation characterization. Here we use direct current insulator-based dielectrophoresis (DC-iDEP) as an unbiased separation method and demonstrate its capability by identifying distinct distribution patterns of insulin vesicles from pancreatic β-cells. A multiple voltage DC-iDEP strategy with increased range and sensitivity has been applied, and a differentiation factor (ratio of electrokinetic to dielectrophoretic mobility) has been used to characterize features of insulin vesicle distribution patterns. We observed a significant difference in the distribution pattern of insulin vesicles isolated from glucose-stimulated cells relative to unstimulated cells, in accordance with functional maturation of vesicles upon glucose stimulation, and interpret this to be indicative of high-resolution separation of vesicle subpopulation. DC-iDEP provides a path for future characterization of subtle biochemical differences of organelle subpopulations within any biological system.
Distinct ribosome states trigger diverse mRNA quality control pathways
Authors: Veltri Anthony J. , D’Orazio Karole N. , Lessen Laura N. , Loll-Krippleber Raphael , Brown Grant W. , Green Rachel
Published: December 2021

Key protein adapters couple translation to mRNA decay on specific classes of problematic mRNAs in eukaryotes. Slow decoding on non-optimal codons leads to codon-optimality-mediated decay (COMD) and prolonged arrest at stall sites leads to no-go decay (NGD). The identities of the decay factors underlying these processes and the mechanisms by which they respond to translational distress remain open areas of investigation. We use carefully-designed reporter mRNAs to perform genetic screens and functional assays inS. cerevisiae. We characterize the roles of Hel2 and Syh1 in coordinating translational repression and mRNA decay on NGD reporter mRNAs, finding that Syh1 acts as the primary link to mRNA decay in NGD. Importantly, we observe that these NGD factors are not involved in the degradation of mRNAs enriched in non-optimal codons. Further, we establish that a key factor previously implicated in COMD, Not5, contributes modestly to the degradation of an NGD-targeted mRNA. Finally, we use ribosome profiling to reveal distinct ribosomal states associated with each reporter mRNA that readily rationalize the contributions of NGD and COMD factors to degradation of these reporters. Taken together, these results provide new mechanistic insight into the role of Syh1 in NGD and define the molecular triggers that determine how distinct pathways target mRNAs for degradation in yeast.
Allosteric Regulation of Human Plastins
Authors: Schwebach Christopher L. , Kudryashova Elena , Agrawal Richa , Zheng Weili , Egelman Edward H. , Kudryashov Dmitri S.
Published: December 2021

Plastins/fimbrins are conserved actin-bundling proteins contributing to motility, cytokinesis, and other cellular processes by organizing actin assemblies of strikingly different geometries as in aligned bundles and branched networks. We propose that this unique ability stems from an allosteric communication between plastins’ two actin-binding domains (ABD1/2) engaged in a tight spatial association. We found that although ABD1 binds actin first, ABD2 can bind to actin three orders of magnitude stronger if not inhibited by an equally strong allosteric engagement with ABD1. Binding of ABD1 to actin lessened the inhibition, enabling weak bundling within aligned bundles. A mutation mimicking physiologically relevant phosphorylation at the ABD1-ABD2 interface strongly reduced their association, dramatically potentiating actin cross-linking. Cryo-EM reconstruction revealed the ABD1-actin interface and enabled modeling of the plastin bridge to confirm domain separation in parallel bundles. The characteristic domain organization with a strong allosteric inhibition imposed by ABD1 on ABD2 allows plastins to tune cross-linking, contributing to the assembly and remodeling of actin assemblies with different morphological and functional properties defining the unique place of plastins in actin organization.
Ikaros family proteins regulate developmental windows in the mouse retina through convergent and divergent transcriptional programs
Authors: Javed Awais , Mattar Pierre , Cui Allie , Cayouette Michel
Published: December 2021

Temporal identity factors regulate the competence of neural progenitors to generate specific cell types in a time-dependent manner, but how they operate remains poorly defined. In the developing mouse retina, the Ikaros zinc finger transcription factor Ikzf1 regulates the production of early-born cell types, except cone photoreceptors. In this study we show that Ikzf4, another Ikaros family protein, cooperates with Ikzf1 to control cone photoreceptor production during early stages of retinal development, whereas at late stages, when Ikzf1 is no longer expressed in progenitors, Ikzf4 is instead required for Müller glia production. Using CUT&RUN sequencing, we find that both Ikzf1 and Ikzf4 generally bind to the same genes involved in cone development and other early-born fates, but at different cis-regulatory elements. In late-stage progenitors, Ikzf4 re-localizes to bind target genes involved in Müller glia development and regulate their expression. Specifically, we show that Ikzf4 maintains Hes1 expression in differentiating cells using two Ikzf GGAA binding sites at the Hes1 promoter, thereby favouring Müller glia fate commitment. These results uncover a combinatorial role for Ikaros family members in nervous system development and provide mechanistic insights on how they temporally regulate cell fate output.
The AdcACB/AdcAII system is Essential for Zinc Homeostasis and an Important Contributor of Enterococcus faecalis Virulence
Authors: Lam Ling Ning , Brunson Debra N. , Molina Jonathan J. , Flores-Mireles Ana L. , Lemos José A.
Published: December 2021

Bacterial pathogens require a variety of micronutrients for growth, including trace metals such as iron, manganese, and zinc (Zn). Despite their relative abundance in host environments, access to these metals is severely restricted during infection due to host-mediated defense mechanisms collectively known as nutritional immunity. Despite a growing appreciation of the importance of Zn in host-pathogen interactions, the mechanisms of Zn homeostasis and the significance of Zn to the pathophysiology of E. faecalis, a major pathogen of nosocomial and community-associated infections, have not been investigated. Here, we show that E. faecalis encoded an ABC-type transporter AdcACB and an orphan substrate-binding lipoprotein AdcAII that work cooperatively to maintain Zn homeostasis. Simultaneous inactivation of adcA and adcAII or the entire adcACB operon led to significant reduction in intracellular Zn under Zn-restricted conditions, heightened sensitivity to Zn-chelating agents including human calprotectin, aberrant cell morphology, and impaired fitness in serum ex vivo. Additionally, inactivation of adcACB and adcAII significantly reduced bacterial tolerance towards cell envelope-targeting antibiotics, which may be associated to altered fatty acid abundance and species. Lastly, we show that the AdcACB/AdcAII system contributes to E. faecalis virulence in an invertebrate (Galleria mellonella) infection model and in two catheter-associated mouse infection models that recapitulate many of the host conditions associated with enterococcal human infections. Collectively, this report reveals that high-affinity Zn import is essential for the pathogenesis of E. faecalis indicating that the surface-associated AdcA and AdcAII lipoproteins are potential therapeutic targets.
Reproductive developmental dynamics during the early and intermediate prepuberal periods in Nelore breed (Bos indicus) calves
Authors: Kawamoto Taynan Stonoga , Viana João Henrique Moreira , Franco Maurício Machaim , Faria Otávio Augusto Costa de , Fidelis Andrei Antonioni Guedes , Figueiredo Ricardo Alamino
Published: December 2021

The demand for calves as oocyte donors for in vitro embryo production is growing. However, Bos indicus have a late puberty, and some aspects of the reproductive physiology during the prepubertal period remain unclear. We characterized endocrine and morpho-functional reproductive features in Nelore calves (n=8) at 2-5 (early prepubertal period, EPP) and from 8-11 months old (mo., intermediate prepubertal period, IPP). The calves’ ovaries and uterus were B-mode transrectal ultrasonography examined, and blood samples were collected every second week. The antral follicles number and size, and ovarian and uterine horn diameters, were recorded, and plasma FSH and LH concentrations were measured (RIA). Non-pregnant, non-lactating cyclic Nelore cows (n=8) were used as controls for endocrine endpoints. Somatic development was monitored by monthly weighing, and 3D scanning of the rump area. The somatic and endocrine endpoints were compared within and between EPP and IPP, and between each period and control cows. Associations were determined by the Spearman correlation method, and the developmental rates were determined by non-linear regression. All morphological endpoints, except antral follicle count, increased (P < 0.001) from the EPP to the IPP. However, within each period differences occurred only at EPP. During the EPP LH and FSH plasma concentrations were similar (P > 0.05), whereas during the IPP LH was lower (P < 0.05) and FSH was higher (P < 0.001) than control cows. The EPP calves showed moderate to high positive correlations among ovarian, uterine, and somatic endpoints. Conversely, the IPP such correlations were mostly weak. In summary, distinct ovarian activity and development patterns of primary and secondary sexual characteristics occurred in Nelore calves at 2-5 mo compared to 8-11 mo.
The impact of family harmony on family SMEs' performance: the mediating role of information technologies
Authors: Dutot Vincent , Bergeron Francois , Calabrò Andrea
Published: December 2021

Purpose

With the increasing digitalization processes taking place in different industries, the success of family small and medium-sized enterprises (SMEs) appears to be more under threat than for any other types of organizations, especially when information technologies (ITs) are not adequately used and managed. To grow and increase the chances of survival, family SMEs need more than ever IT. Stemming from agency theory, the aim of this article is to understand whether family harmony impacts the performance of family SMEs and to what extent IT mediates this relationship.

Design/methodology/approach

The research follows a quantitative approach, based on a sample of 182 family SMEs. Structured equation modeling, through SmartPLS, was employed to validate the research model.

Findings

This study’s main findings suggest that family harmony positively impacts firm performance and that IT governance and strategy mediate positively this relationship.

Research limitations/implications

First, the relatively limited number of respondents limits the degree of representativeness of all family SMEs. Replicating the research with a larger number of respondents could strengthen the findings. Second, this study is limited to French firms and future research could extend the findings by looking at cross-country comparisons.

Practical implications

Family SMEs are encouraged to link their IT governance with their IT strategy in order to increase their organizational performance. A favorable family harmony will make it easier to choose and implement a richer IT strategy and put in place an adequate IT governance function.

Originality/value

This research offers an enriched knowledge of the roles of family harmony and technological innovation in family SMEs and IT contexts as significant predictors of organizational performance. It contributes to family firm theory through the identification of three determinants of family SMEs' performance.