bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurosyphilis Mimicking Behavioral Variant of Frontotemporal Dementia in a 59-Year-Old Man
Authors: Caroppo Paola , Villa Cristina , Del Sole Angelo , Bernardi Gaetano , Carradori Silvia , Tiraboschi Pietro , Giaccone Giorgio , Prioni Sara
Published: May 2022

We present the case of a man exhibiting a clinical phenotype of behavioral variant of frontotemporal dementia (bvFTD). The man had developed psychiatric disturbances with verbal aggressiveness over a few months, followed by cognitive and frontal behavioral disorders, fulfilling the clinical criteria for bvFTD. Atrophy and hypometabolism in frontotemporal regions were consistent with the diagnosis. However, serum-screening exams for syphilis infection were positive, and CSF analysis, despite a negative Venereal Disease Research Laboratory Test, suggested the diagnosis of neurosyphilis. After specific antibiotic therapy, the man’s behavioral abnormalities and cognitive deficits notably improved, confirming neurosyphilis as the cause of the clinical phenotype. The cognitive deficits completely recovered 1 year post therapy and remained stable for 2 years. After ∼2½ years from the first treatment, the man’s behavioral disorders mildly worsened, at which time we re-evaluated him. His cognition was stable, and a positive Venereal Disease Research Laboratory Test confirmed the diagnosis of neurosyphilis. With this case, we demonstrated that in some instances, neurosyphilis can mimic frontotemporal dementia. As a cause of treatable dementia, it should be considered in the differential diagnosis of bvFTD, particularly when psychiatric symptoms and a rapid cognitive decline are noted, even in the presence of brain atrophy and/or hypometabolism.
Ralstonia mannitolilytica: an emerging multidrug-resistant opportunistic pathogen in a tertiary care hospital setting
Authors: Siddiqui Tasneem , Patel Sangram Singh , Sinha Richa , Ghoshal Ujjala , Sahu Chinmoy
Published: May 2022

Introduction.

Ralstonia mannitolilytica

is a rare opportunistic pathogen capable of causing a serious infection in immunocompromised patients. Our objective was to describe all cases of

R. mannitolilytica

bloodstream infection identified within 2 years at our tertiary care centre, focusing on clinical characteristics, risk factors, antibiotic sensitivity patterns, management and outcomes.

Case Series. We compiled a descriptive case series including 14 non-duplicate

R. mannitolilytica

isolates obtained from bloodstream infection samples from the microbiology laboratory of a tertiary care centre from June 2019 to June 2021. All isolates were initially identified based on their morphological properties and biochemical reactions, and then underwent matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) examination for confirmation of identity. Antibiotic susceptibility testing was performed using the Kirby–Bauer disc diffusion method and Vitek 2. All 14 patients presented with symptoms of fever and/or chills, and a positive blood culture for

R. mannitolilytica

. After 48 h of incubation, no

Ralstonia

growth was reported from any of the current environmental or pharmaceutical water samples. Chemotherapy (9/14), mechanical ventilation (4/14), steroid use (2/14) and diabetes mellitus (1/14) were associated risk factors in our patients. The antibiotic sensitivity panel showed maximum resistance to aminoglycosides (64.3%) and no resistance to cefoperazone/sulbactum. Patients received treatment with cefoperazone/sulbactum and meropenem or ceftazidime. Thirteen patients recovered with antibiotic therapy and one patient succumbed to his illness.

Conclusion.

R. mannitolilytica

can cause bloodstream infections in immunocompromised patients. It is likely to be missed or underreported due to lack of clinical awareness. MALDI-TOF MS is helpful in rapid identification.

R. mannitolilytica

is resistant to many routinely used antibiotics, including carbapenems.
Sphingomonas psychrotolerans sp. nov., isolated from root surface of Leontopodium leontopodioides in the Tianshan Mountains, Xinjiang, China
Authors: Luo Yang , Zhou Meng , Wang Fang , Sheng Hongmei
Published: May 2022

A novel rod-shaped, Gram-stain-negative, aerobic bacterial strain, designated Cra20T, was isolated from the root surface of Leontopodium leontopodioides collected in the Tianshan Mountains, Xinjiang, PR China. Phylogenetic analysis based on 16S rRNA gene sequences, indicated that strain Cra20T was affiliated with the genus

Sphingomonas

, and was most closely related to

Sphingomonas gei

ZFGT-11T (99.0 %),

Sphingomonas naasensis

KIS18-15T (97.8%) and

Sphingomonas kyeonggiensis

THG-DT81T (97.2 %). The average nucleotide identity values between strain Cra20T,

S. gei

ZFGT-11T,

S. naasensis

KIS18-15T and

S. kyeonggiensis

THG-DT81T were 86.2, 84.2 and 78.2 %, respectively. The genomic DNA G+C content of strain Cra20T was 65.6 mol% (whole genome sequence), and Q-10 was the predominant ubiquinone. The major cellular fatty acids of strain Cra20T were summed feature 8 (comprising C18 : 1 
ω6c and/or C18 : 1 
ω7c, 67.3 %) and C14 : 0 2-OH (6.4 %). On the basis of genotypic, phenotypic and biochemical data, strain Cra20T is considered to represent a novel species of the genus

Sphingomonas

, for which the name Sphingomonas psychrotolerans sp. nov. is proposed. The type strain is Cra20T (=CGMCC 1.15510T=NBRC 112697T).
KIF1A is kinetically tuned to be a super-engaging motor under hindering loads
Authors: Pyrpassopoulos Serapion , Gicking Allison M. , Zaniewski Taylor M. , Hancock William O. , Ostap E. Michael
Published: May 2022

KIF1A is a highly processive vesicle transport motor in the kinesin-3 family. Mutations in KIF1A lead to neurodegenerative diseases including hereditary spastic paraplegia. We applied optical tweezers to study the ability of KIF1A to generate and sustain force against hindering loads. We used both the three-bead assay, where force is oriented parallel to the microtubule, and the traditional single-bead assay, where force is directed along the radius of the bead, resulting in a vertical force component. The average force and attachment duration of KIF1A in the three-bead assay were substantially greater than those observed in the single-bead assay. Thus, vertical forces accelerate termination of force ramps of KIF1A. Average KIF1A termination forces were slightly lower than the kinesin-1 KIF5B, and the median attachment duration of KIF1A was >10-fold shorter than KIF5B under hindering loads. KIF1A rapidly reengages with microtubules after detachment, as observed previously. Strikingly, quantification enabled by the three-bead assay shows that reengagement largely occurs within 2 ms of detachment, indicating that KIF1A has a nearly tenfold faster reengagement rate than KIF5B. We found that rapid microtubule reengagement is not due to KIF1A’s positively charged loop-12; however, removal of charge from this loop diminished the unloaded run length at near physiological ionic strength. Both loop-12 and the microtubule nucleotide state have modulatory effects on reengagement under load, suggesting a role for the microtubule lattice in KIF1A reengagement. Our results reveal adaptations of KIF1A that lead to a novel model of super-engaging transport under load.
The U.S. faculty job market survives the SARS-CoV-2 global pandemic
Authors: Kozik Ariangela J , Hagan Ada , Jadavji Nafisa M , Smith Christopher T , Haage Amanda
Published: May 2022

Purpose

This paper aims to identify the extent to which the COVID-19 pandemic disrupted the academic job market and the ways in which faculty job applicants altered their applications in response to a changing academia.

Design/methodology/approach

The data presented here is the portion relevant to COVID-19 collected in a survey of faculty job applicants at the end of the 2019-2020 job cycle in North America (spring 2020). An additional “mid-pandemic” survey was used in fall 2020 for applicants participating in the following job search cycle to inquire about how they were adapting their application materials. A portion of data from the 2020-2022 job cycle surveys was used to represent the “late-pandemic”. Job posting data from the Higher Education Recruitment Consortium (HERC) is also used to study job availability.

Findings

Examination of faculty job postings from 2018 through 2022 found that while they decreased in 2020, the market recovered in 2021 and beyond. While the market recovered, approximately 10% of the faculty job offers reported by 2019–20 survey respondents were rescinded. Respondents also reported altering their application documents in response to the pandemic as well as delaying or even abandoning their faculty job search.

Originality

This paper provides a longitudinal perspective with quantitative data on how the academic job market changed through the major events of the COVID-19 pandemic in North America, a subject of intense discussion and stress, particularly amongst early career researchers.
Development of the Intestinal Microbiome in Cystic Fibrosis in Early Life
Authors: Price Courtney E. , Hampton Thomas H. , Valls Rebecca A. , Barrack Kaitlyn E. , O’Toole George A. , Madan Juliette C. , Coker Modupe O.
Published: May 2022

Cystic Fibrosis is a heritable disease that causes altered physiology at mucosal sites; these changes result in chronic infection in the lung, significant gastrointestinal complications as well as dysbiosis of the gut microbiome, although the latter has been less well explored. Here, we describe the longitudinal development of the gut microbiome in a cohort of children with cystic fibrosis (cwCF) from birth through early childhood (0-4 years of age) using 16S rRNA gene amplicon sequencing of stool samples as a surrogate for the gut microbiota. Similar to healthy populations, alpha diversity of the gut microbiome increases significantly with age, but diversity plateaus ∼2 years of age for this CF cohort. Several taxa that have been associated with dysbiosis in CF change with age towards a more healthy-like composition; notable exceptions include Akkermansia, which decreases with age, and Blautia, which increases with age. We also examined the relative abundance and prevalence of nine taxa associated with CF lung disease, several of which persist across early life, highlighting the possibility of the lung being seeded directly from the gut early in life. Finally, we applied the Crohn’s dysbiosis index to each sample, and found that high Crohn’s-associated dysbiosis early in life (<2 years) was associated with significantly lower Bacteroides in samples collected from 2-4 years of age. Together, these data indicate a persisting dysbiosis in the gut microbiota as well as markers associated with inflammatory bowel disease early in life for cwCF.

IMPORTANCE

Cystic Fibrosis is a heritable disease that disrupts ion transport at mucosal surfaces, causing a buildup of mucus and dysregulation of microbial communities in both the lungs and the intestines. Persons with CF are known to have dysbiotic gut microbial communities, but the development of these communities over time beginning at birth have not been thoroughly studied. Here, we describe the development of the gut microbiome of cwCF throughout the first four years of life, during the critical window of both gut microbiome and immune development. Our findings indicate a persisting dysbiosis, the possibility of the gut microbiota as a reservoir of airway pathogens and a surprisingly early indication of a microbiota associated with inflammatory bowel disease.
Is point wise analysis of the Humphrey visual field feasible as a primary outcome in idiopathic intracranial hypertension?
Authors: Mollan Susan P , Bodoza Samuel , Ní Mhéalóid Áine , Mitchell James L , Miller Neil R. , Montesano Giovanni , Crabb David P , Wall Michael , Brock Kristian , Sinclair Alexandra J
Published: May 2022

Purpose

Using the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) data, this study aimed to determine if point analysis of the Humphrey visual field (HVF) could be more informative than the perimetric mean deviation (PMD) as an IIH trial outcome measure.

Methods

IIH:WT was a randomized controlled trial that recruited 66 people with active IIH (mean ± standard deviation age 32 ± 7.8 years). Event-based analysis using a pointwise analysis of the numerical sensitivity data was performed. The number of participants that would be eligible for analysis was calculated when the data were enriched to reflect a medically treated cohort defined as a PMD between -2dB to -7dB.

Results

The HVF 24-2 mean ± standard deviation PMD in the worse eye was ™3.5 ± 1.1dB, (range,™2.0 to ™6.4dB), and point sensitivity showed a preference for peripheral and blind spot locations. Those points between 0 and -10dB demonstrated negligible ability to improve compared with those between -10dB and -25dB. In evaluating feasibility for a medical intervention trial, 346 points were available for analysis between -10dB and -25dB bilaterally compared with 4123 in baseline sensitivities of 0 to -10dB.

Conclusions

Mildly affected baseline sensitivities were unlikely to show considerable change over 24 months. There were fewer points available for analysis and greater variability if moderately affected baseline points were chosen. If point analysis was used as an outcome measure in a medical intervention trial, the majority of points would not demonstrate clinically meaningful change, thus offering little advantage over PMD.
Perception of self- and externally-generated visual stimuli: Evidence from EEG and behaviour
Authors: Ody Edward , Straube Benjamin , He Yifei , Kircher Tilo
Published: May 2022

Efference copy-based forward model mechanisms may help us to distinguish between self- and externally-generated sensory consequences. Previous studies have shown that neural activity and perception associated with self-initiated sensory consequences are reduced (sensory suppression). For example, event-related potentials (ERPs) elicited by tones that follow a button press are reduced in amplitude relative to ERPs elicited by passively attended tones. However, previous EEG studies investigating visual stimuli in this context are rare, provide inconclusive results, and lack adequate control conditions with passive movements. Furthermore, although self-initiation is known to modulate behavioural responses, it is not known whether differences in the amplitude of ERPs also reflect differences in perception of sensory outcomes. In this study, we presented to participants visual stimuli consisting of grey discs following either active button presses, or passive button presses, in which an electromagnet moved the participant’s finger. Two discs presented visually 500-1250 ms apart followed each button press, and participants judged which of the two was more intense. Early components of the primary visual response (N1 and P2) over the occipital electrodes were suppressed in the active condition. Interestingly, suppression in the intensity judgement task was only correlated with suppression of the visual P2 component. These data support the notion of efference copy-based forward model predictions in the visual sensory modality, but especially later processes (P2) seem to be perceptually relevant. Taken together, the results challenge the assumption that N1 differences reflect perceptual suppression and emphasise the relevance of the P2 ERP component.
Internally-controlled and dynamic optical measures of functional tumor biology
Authors: Chung Taemoon , Garcia Libia , Swamynathan Manojit M. , Froeling Fieke E.M. , Trotman Lloyd C. , Tuveson David A. , Lyons Scott K.
Published: May 2022

Imaging defined aspects of functional tumor biology with bioluminescent reporter transgenes is a popular approach amongst the research community in drug development, as it is sensitive, relatively high-throughput and low cost. However, the lack of internal controls subject functional bioluminescence to a number of unpredictable variables that reduce this powerful tool to semi-quantitative interpretation of large-scale effects. Here we report the generation of sensitive and quantitative live reporters for two key measures of functional cancer biology and pharmacologic stress: the cell cycle and oxidative stress. We developed a two-colored readout, where two independent enzymes convert a common imaging substrate into spectrally distinguishable light. The signal intensity of one color is dependent upon biological state, whereas the other color is constitutively expressed. The ratio of emitted colored light corrects the functional signal for independent procedural variables, substantially improving the robustness and interpretation of relatively low-fold changes in functional signal intensity after drug treatment.

The application of these readouts in vitro is highly advantageous, as peak cell response to therapy can now be readily visualized for single or combination treatments and not simply assessed at an arbitrary and destructive timepoint. Spectral imaging in vivo can be challenging, but we also present evidence to show that the reporters can work in this context as well. Collectively, the development and validation of these internally controlled reporters allow researchers to robustly and dynamically visualize tumor cell biology in response to treatment. Given the prevalence of bioluminescence imaging, this presents significant and much needed opportunities for preclinical therapeutic development.
Modified methods for bovine sperm RNA isolation for consistent quality and RNA yield
Authors: Dewry Raju Kumar , Mohanty Tushar Kumar , Nath Sapna , Bhakat Mukesh , Yadav Hanuman Prasad , Baithalu Rubina Kumari
Published: May 2022

Sperm mRNA transcriptional profiling can be used to evaluate the fertility of breeding bulls. This study aimed to compare the modified RNA isolation methods for higher RNA yield and quality from freshly ejaculated sperm of cattle and buffalo bull for further transcriptome analysis. Ten fresh ejaculates from each Sahiwal (n = 10 bulls x 10 ejaculates) and Murrah bulls (n = 10 bulls x 10 ejaculates) were used for RNA isolation. Swim-up technique was used for live sperm separation and recovery. From the recovered live sperm, total sperm RNA was isolated by conventional methods (TRIzol, Double TRIzol), membrane-based methods combined with TRIzol (RNeasy + TRIzol) with the addition of β-mercaptoethanol (BME) and Kit (RNeasy mini) methods in fresh semen. Among different isolation methods; the membrane-based modified methods combined with TRIzol (RNeasy + TRIzol) with the addition of β-mercaptoethanol (BME) resulted significantly (P < 0.05) higher total RNA quantity (300-340 ng/μL) and better purity in different concentrations of spermatozoa viz., 30-40 million, 70-80 million and 300-400 million sperm. The study concluded that the inclusion of BME to the combined membrane-based methods with somatic cell lysis buffer solution was best for constant increased yield and purity of RNA isolation from Sahiwal cattle and Murrah buffalo bull sperm. This method will help with the interpretation of data from animal models and the consistency of clinical assessments of male factor fertility employing RNA molecular biomarkers.
Ubx5-Cdc48 assists the protease Wss1 at DNA-protein crosslink sites in yeast
Authors: Noireterre Audrey , Bagdiul Ivona , Serbyn Nataliia , Stutz Françoise
Published: May 2022

DNA-protein crosslinks (DPCs) pose a serious threat to genome stability. The yeast proteases Wss1, 26S proteasome and Ddi1 are safeguards of genome integrity by acting on a plethora of DNA-bound proteins in different cellular contexts. The AAA ATPase Cdc48/p97 is known to assist Wss1/SPRTN in clearing DNA-bound complexes, however its contribution to DPC proteolysis remains unclear. Here, we show that the Cdc48 adaptor Ubx5 is detrimental in yeast mutants defective in DPC processing. Using an inducible site-specific crosslink, we show that Ubx5 accumulates at persistent DPC lesions in the absence of Wss1, which prevents their efficient removal from the DNA. Abolishing Cdc48 binding or complete loss of Ubx5 suppresses the sensitivity of wss1Δ cells to DPC inducing agents by favoring alternate repair pathways. We provide evidence for cooperation of Ubx5-Cdc48 and Wss1 in the genotoxin-induced degradation of RNAPII, a described candidate substrate of Wss1. We propose that Ubx5-Cdc48 assists Wss1 for proteolysis of a subset of DNA-bound proteins. Together, our findings reveal a central role for Ubx5 in DPC clearance and repair.
Generating Interacting Protein Sequences using Domain-to-Domain Translation
Authors: Meynard-Piganeau Barthelemy , Fabbri Caterina , Weigt Martin , Pagnani Andrea , Feinauer Christoph
Published: May 2022

Motivation

Being able to artificially design novel proteins of desired function is pivotal in many biological and biomedical applications. Generative statistical modeling has recently emerged as a new paradigm for designing amino acid sequences, including in particular models and embedding methods borrowed from Natural Language Processing (NLP). However, most approaches target single proteins or protein domains, and do not take into account any functional specificity or interaction with the context. To extend beyond current computational strategies, we develop a method for generating protein domain sequences intended to interact with another protein domain. Using data from natural multi-domain proteins, we cast the problem as a translation problem from a given interactor domain to the new domain to be generated, i.e. we generate artificial partner sequences conditional on an input sequence.

Results

Evaluating our model’s quality using diverse metrics, in part related to distinct biological questions, we show that our method outperforms state-of-the-art shallow auto-regressive strategies. We also explore the possibility of fine-tuning pre-trained large language models for the same task and of using Alphafold 2 for assessing the quality of sampled sequences.
TRACKING HEMATOPOIETIC STEM CELL EVOLUTION IN A WISKOTT-ALDRICH CLINICAL TRIAL
Authors: Pellin Danilo , Biasco Luca , Scala Serena , Serio Clelia Di , Wit Ernst C.
Published: May 2022

Hematopoietic Stem Cells (HSC) are the cells that give rise to all other blood cells and, as such, they are crucial in the healthy development of individuals. Wiskott-Aldrich Syndrome (WAS) is a severe disorder affecting the regulation of hematopoietic cells and is caused by mutations in the WASP gene. We consider data from a revolutionary gene therapy clinical trial, where HSC harvested from 3 WAS patients’ bone marrow have been edited and corrected using viral vectors. Upon re-infusion into the patient, the HSC multiply and differentiate into other cell types. The aim is to unravel the cell multiplication and cell differentiation process, which has until now remained elusive.

This paper models the replenishment of blood lineages resulting from corrected HSC via a multivariate, density-dependent Markov process and develops an inferential procedure to estimate the dynamic parameters given a set of temporally sparsely observed trajectories. Starting from the master equation, we derive a system of non-linear differential equations for the evolution of the first- and second-order moments over time. We use these moment equations in a generalized method-of-moments framework to perform inference. The performance of our proposal has been evaluated by considering different sampling scenarios and measurement errors of various strengths using a simulation study. We also compared it to another state-of-the-art approach and found that our method is statistically more efficient.

By applying our method to the Wiskott-Aldrich Syndrome gene therapy data we found strong evidence for a myeloid-based developmental pathway of hematopoietic cells where fates of lymphoid and myeloid cells remain coupled even after the loss of erythroid potential.

All code used in this manuscript can be found in the online Supplement, and the latest version of the code is available at github. com/dp3ll1n/SLCDP_v1.0.
A high-throughput approach to predict A-to-I effects on RNA structure indicates a change of double-stranded content in non-coding RNAs
Authors: Ponti Riccardo Delli , Broglia Laura , Vandelli Andrea , Armaos Alexandros , Burgas Marc Torrent , Sanchez de Groot Natalia , Tartaglia Gian Gaetano
Published: May 2022

RNA molecules undergo a number of chemical modifications whose effects can alter their structure and molecular interactions. Previous studies have shown that RNA editing can impact the formation of ribonucleoprotein complexes and influence the assembly of membrane-less organelles such as stress-granules. For instance, N6-methyladenosine (m6A) enhances SG formation and N1-methyladenosine (m1A) prevents their transition to solid-like aggregates. Yet, very little is known about adenosine to inosine (A-to-I) modification that is very abundant in human cells and not only impacts mRNAs but also non-coding RNAs. Here, we built the CROSSalive predictor of A-to-I effects on RNA structure based on high-throughput in-cell experiments. Our method shows an accuracy of 90% in predicting the single and double-stranded content of transcripts and identifies a general enrichment of double-stranded regions caused by A-to-I in long intergenic non-coding RNAs (lincRNAs). For the individual cases of NEAT1, NORAD and XIST, we investigated the relationship between A-to-I editing and interactions with RNA-binding proteins using available CLIP data. We found that A-to-I editing is linked to alteration of interaction sites with proteins involved in phase-separation, which suggests that RNP assembly can be influenced by A-to-I. CROSSalive is available athttp://service.tartaglialab.com/new_submission/crossalive.
Multicellular Aligned Bands Disrupt Global Collective Cell Behavior
Authors: Jebeli Mahvash , Lopez Samantha K. , Goldblatt Zachary E. , McCollum Dannel , Mana-Capelli Sebastian , Wen Qi , Billiar Kristen
Published: May 2022

Mechanical stress patterns emerging from collective cell behavior have been shown to play critical roles in morphogenesis, tissue repair, and cancer metastasis. In our previous work utilizing microcontact printing to geometrically constrain valvular interstitial cell monolayers into specific shapes, we demonstrated that the general patterns of observed cell alignment, size, and apoptosis correlate with predicted mechanical stress fields if nonuniform cell properties are used in the computational models. However, these radially symmetric models did not predict the substantial heterogeneity in cell behavior observed in individual circular aggregates. The goal of this study is to determine how the heterogeneities in cell behavior emerge over time and diverge from the predicted collective cell behavior. Cell-cell interactions in circular multicellular aggregates of valvular interstitial cells were studied with time-lapse imaging ranging from hours to days, and migration, proliferation, and traction stresses were measured. Our results indicate that individual elongated cells create strong local alignment within pre-confluent cell populations on the microcontact printed protein islands. These cells influence the alignment of additional cells to create dense, locally aligned bands of cells which disrupt the global behavior. Cells are highly elongated at the endpoints of the bands yet have decreased spread area in the middle and reduced mobility. Although traction stresses at the endpoints of bands are enhanced, even to the point of detaching aggregates from the culture surface, the cells in dense bands exhibit reduced proliferation, less nuclear YAP, and increased apoptotic rates indicating a low stress environment. These findings suggest that strong local cell-cell interactions between primary fibroblastic cells can disrupt the global collective cellular behavior leading to substantial heterogeneity of cell behaviors in constrained monolayers. This local emergent behavior within aggregated fibroblasts may play an important role in development and disease of connective tissues.
Neural mechanisms for the localization of externally generated tactile motion
Authors: Chinta Suma , Pluta Scott R.
Published: May 2022

During tactile localization, animals must differentiate stimuli caused by their own volitional movement from externally generated object motion. To determine a neural basis for this ability, we examined the mouse superior colliculus (SC), which contains multiple egocentric maps of sensorimotor space. By placing mice in a whisker-guided virtual reality, we discovered a rapidly adapting neural response that strongly preferred external over self-generated changes in tactile space. This transient response only emerged when external motion gained contact with a whisker, arguing that stimulus adaptation was whisker-specific. The accumulation of sensory evidence through active sensing and repetitions in external motion controlled the size of the transient response. Population-level firing rates among transiently responsive neurons accurately encoded the direction of external motion. These data reveal that stimulus-specific adaptation together with accumulating sensorimotor predictions in SC neurons enhance the localization of unexpected motion in the environment.
T cell Egress via Lymphatic Vessels Limits the Intratumoral T cell Repertoire in Melanoma
Authors: Steele Maria M. , Dryg Ian D. , Murugan Dhaarini , Femel Julia , Bois Haley du , Hill Cameron , Leachman Sancy A. , Chang Young H. , Coussens Lisa M. , Lund Amanda W.
Published: May 2022

Antigen-specific CD8+T cell accumulation in tumors is a prerequisite for effective immunotherapy, and yet, the mechanisms of lymphocyte transit remain poorly defined. We find that tumor-associated lymphatic vessels control T cell exit from tumors via the chemokine CXCL12, and intratumoral antigen encounter tunes CXCR4 expression on effector CD8+T cells. Only high affinity antigen downregulates CXCR4 and upregulates the CXCL12 decoy receptor, ACKR3, thereby reducing CXCL12 sensitivity and promoting T cell retention. A diverse repertoire of functional tumor-specific CD8+T cells exit the tumor, thereby limiting tumor control. CXCR4 inhibition and loss of lymphatic-specific CXCL12 boosts T cell retention and enhances response to therapeutic immune checkpoint blockade. Strategies that limit T cell egress, therefore, provide a new tool to boost immunotherapy response.

One-Sentence Summary

Lymphatic vessel-mediated, antigen-dependent CD8+T cell egress limits T cell accumulation in melanomas and impairs anti-tumor immunity.
Wide genome transcription and metabolome profiles reprogrammed by sucrose under xenobiotic constraints
Authors: Berthomé Richard , Dumas Anne-Sophie , Jarde Emilie , Ryzhenko Nataliia , Barbas Evangelos , El Amrani Abdelhak
Published: May 2022

Plants have developed strategies to adapt quickly to environmental changes. However, the regulation of these adaptive responses and coordination of signals network remains poorly understood for many environmental constraints. Indeed, signalling molecules play a central role in environmental stimuli and may coordinate plants development under environmental cues. Sucrose is the major transport carbohydrate in higher plants, in addition to its metabolic role; recent investigations suggested that sucrose impact the plasticity of plant development by controlling gene expression. Sucrose was also suggested as a ROS scavenger and as a signalling molecule. In this paper we showed that sucrose mitigated phenanthrene induced stress. Since, exogenous sucrose allowed growth and chlorophyll accumulation in the presence of high phenanthrene concentrations, whereas Arabidopsis development was blocked and seedlings were unable to accumulate chlorophyll in the presence of phenanthrene solely. To decipher the earlier molecular changes involved in sucrose tolerance to phenanthrene, wide transcriptional genes analysis and targeted metabolic profiling were carried out. We showed that sucrose driving plant response was associated with a deep reconfiguration of both genes expression and metabolites accumulation during the first hours of treatment, suggesting that sucrose, allowed plants to sustain the primary metabolism and to overcome the phenanthrene induced injuries.
The histone variant H2A.W cooperates with chromatin modifications and linker histone H1 to maintain transcriptional silencing of transposons in Arabidopsis
Authors: Bourguet Pierre , Yelagandula Ramesh , To Taiko Kim , Osakabe Akihisa , Alishe Archana , Lu Rita Jui-Hsien , Kakutani Tetsuji , Chen Pao-Yang , Berger Frédéric
Published: May 2022

Transposable elements (TEs) are marked by a complex array of chromatin modifications, but a central unifying mechanism for how they are silenced remains elusive. Histone H3 Lysine 9 methylation (H3K9me) is an important component of heterochromatin in most eukaryotes, including plants. In flowering plants, the specialized histone variant H2A.W occupies nucleosomes found at TE sequences. This variant is deposited by the chromatin remodeler DDM1 and confers specific biophysical properties to the nucleosomes.

Here we use genetic and genomic strategies to evaluate the role of H2A.W in transposon silencing in Arabidopsis. Compared with mutants lacking either H2A.W or H3K9me, the combined loss of both H2A.W and H3K9me causes a dramatic increase in both the number of expressed TEs and their expression levels. Synergistic effects are also observed when H2A.W is lost in combination with histone H1 or CH methylation. Collectively, these TEs are also upregulated in mutants lacking DDM1, which are impaired in H2A.W deposition and lose heterochromatic marks.

We conclude that H2A.W acts in combination with different elements of heterochromatin to maintain silencing across a large spectrum of TEs present primarily in pericentric heterochromatin in Arabidopsis. In mammals, the DDM1 ortholog LSH deposits macroH2A to heterochromatin and silences TEs. We thus propose that specialized H2A variants localized to heterochromatin interact with a complex array of histone modifications to silence TEs in eukaryotes.
Leveraging a natural murine meiotic drive to suppress invasive populations
Authors: Gierus Luke , Birand Aysegul , Bunting Mark D. , Godahewa Gelshan I. , Piltz Sandra G. , Oh Kevin P. , Piaggio Antoinette J. , Threadgill David W. , Godwin John , Edwards Owain , Cassey Phillip , Ross Joshua V. , Prowse Thomas A. A. , Thomas Paul Q.
Published: May 2022

Invasive rodents, including house mice, are a major cause of environmental damage and biodiversity loss, particularly in island ecosystems. Eradication can be achieved through the distribution of rodenticide, but this approach is expensive to apply at scale, can have negative impacts (e.g. on non-target species, or through contamination), has animal ethics concerns, and has restrictions on where it can be used. Gene drives, which exhibit biased inheritance, have been proposed as a next generation strategy to control invasive alien pests and disease vectors. However, synthetic gene drives including CRISPR homing drives have proven to be technically challenging to develop in mice. Thethaplotype is a naturally-occurring segregation distortion locus with highly biased transmission from heterozygous males. Here we propose a novel gene drive strategy for population suppression,tCRISPR, that leveragesthaplotype bias and an embedded SpCas9/gRNA transgene to spread inactivating mutations in a haplosufficient female fertility gene. Using spatially explicit individual-basedin silicomodelling, we show that polyandry, sperm competition, dispersal, and transmission bias are critical factors fortCRISPR-mediated population suppression. Modelling of realistic parameter values indicates thattCRISPRcan eradicate an island population of 200,000 mice while the unmodifiedthaplotype fails under the same conditions. We also demonstrate feasibility of this approach by engineeringtCRISPRmice in a safe split drive format.tCRISPRmice exhibit high transmission of the modifiedthaplotype, and efficient generation and transmission of inactivating mutations in a recessive female fertility gene, crucially, at levels for which the modelling predicts that population eradication can occur. This is the first example of a feasible gene drive system for invasive alien rodent population control.
Visuomotor learning promotes visually evoked activity in the medial prefrontal cortex
Authors: Peters Andrew J. , Marica Andrada-Maria , Fabre Julie M.J. , Harris Kenneth D. , Carandini Matteo
Published: May 2022

The medial prefrontal cortex (mPFC) is necessary for executing many learned associations between stimuli and movement. It is unclear, however, whether activity in the mPFC reflects sensory or motor aspects of sensorimotor associations and whether it evolves gradually during learning. To address these questions, we recorded cortical activity with widefield calcium imaging while mice learned a visuomotor task. The task involved associating a visual stimulus with a forelimb movement. After learning, the mPFC showed stimulus-evoked activity both during task performance and during passive viewing, when the stimulus evoked no action. This stimulus-evoked activity closely tracked behavioral performance across training, exhibiting jumps between training days. Electrophysiological recordings localized this activity to the secondary motor and anterior cingulate cortex. We conclude that learning a visuomotor task promotes a route for visual information to reach the prefrontal cortex, which develops responses to the relevant visual stimuli even outside the context of the task.
Revitalising project management office operations in an engineering-service contractor organisation: a key performance indicator based performance management approach
Authors: Mahabir Randell Jared , Pun Kit Fai
Published: May 2022

Purpose

Existing studies on project performance improvement mainly investigate project management (PM) execution processes. Limited publications investigate the project management office's (PMO) proficiency in facilitating proper PM practice. This paper identifies the key performance indicators (KPI) of PMO operations and develops a KPI-based performance management system (KPMS) for revitalising PMO performance for an engineering-service contractor (ESC).

Design/methodology/approach

A four-phase study was initiated at an ESC in Trinidad and Tobago (T&T). Phase-1 established historical project performance and PMO challenges via documentary analysis. Empirical data from the PMO staff and management was acquired at Phase-2 to determine PMO process value-drivers and strategic roles. Phase-3 comprised the development of a modified PMO process and the KPMS, whereas Phase-4 evaluated the efficacy of the PMO process and the KPMS framework in a trial period.

Findings

The ESC's existing PMO process lacked significant value-drivers of its PM practice. The company also overlooked strategic PMO roles. Trial implementation of the modified PMO process achieved improved project performance, which stakeholders attributed to the value-driven processes and guidance provided by the KPMS. The KPMS, when used in tandem with Earned Value Management (EVM) index score review revealed core performance aspects that could facilitate continuous improvement of the PMO process at the ESC.

Practical implications

Findings provide an adequate basis for policy creation regarding PMO performance evaluation and guidance for companies contemplating a similar endeavour. A viable model for PMO performance management and improvement is proffered. The findings and the model would provide a platform for subsequent research in the areas of PMO development and business process improvement.

Originality/value

This is the first study conducted to obtain management and practitioners' inputs on developing a PMO performance management framework in a project-based contractor organisation in T&T. Various PMO challenges and implications of improvements specific to engineering-service contractors and similar organisations were determined.
Impact of environmental scanning on organizational resilience and competitive advantage: a study of Egyptian SMEs
Authors: YahiaMarzouk Yasmine , Jin Jiafei
Published: May 2022

Purpose

This paper aims to examine the impact of environmental scanning (ES) on competitive advantage (CA) through the mediation of organizational resilience dimensions within manufacturing small and medium-sized enterprises (SMEs) in Egypt.

Design/methodology/approach

This study adopts a cross-sectional design to collect data. This study used a self-administered questionnaire to collect data from a sample of 249 Egyptian SMEs. This study employed the Smart partial least square structural equation modeling technique to test the hypotheses.

Findings

ES positively affects CA both directly and indirectly through the mediation of organizational resilience dimensions, namely, robustness and agility. However, ES does not affect integrity; therefore, integrity does not mediate the ES–CA relationship. These results indicate that organizational resilience partially mediates the relationship between ES and CA.

Research limitations/implications

The sample size was small, covering only Egyptian manufacturing SMEs. The results may be different in the service sector and other countries. The study was cross-sectional which could not trace the long-term effects of ES and organizational resilience on CA. Therefore, a longitudinal study should be conducted, based on resource availability.

Practical implications

Managers in Egyptian SMEs should scan their environments to build organizational resilience and, in turn, enhance their CA.

Originality/value

To the best of the authors’ knowledge, this research is among the first endeavors to investigate the role of ES in building CA through organizational resilience in the context of Egyptian SMEs.
Institutional determinants of IJV partner choice in Europe: a host-country, a home-country or a third-country partner?
Authors: Konara Palitha , Yang Yi
Published: May 2022

Purpose

This study aims to examine the international joint venture (IJV) partnership strategy in Europe from an institutional perspective. A firm operating in a foreign country via an IJV can partner with a local firm from the host country, a firm from the same home country or a firm from a third country. This study takes the first step in examining the determinants of these partner choices.

Design/methodology/approach

This study tests hypotheses based on a data set of 637 IJVs in Europe.

Findings

Foreign firms are less likely to operate in a partnership with a firm from the home country or from a third country (compared to operate in a partnership with a local firm) when the host country institutions are weaker or institutional distance is larger. Also, foreign firms’ disinclination to operate in a partnership with a firm from the home/third country when the host country institutions are weaker or institutional distance is larger will diminish with greater host-country experience.

Practical implications

This study provides important insights for firms for evaluating partner choice and potential collaborations in the European region with heterogenous institutions.

Originality/value

The partner choice among the above three forms has been neglected in the literature. This study first conceptualized that the institutional profile of the host country and institutional distance between the host country and the home country can determine the partner choice.
Cause analysis of construction collapse accidents using association rule mining
Authors: Shao Lijia , Guo Shengyu , Dong Yimeng , Niu Hongying , Zhang Pan
Published: May 2022

Purpose

The construction collapse is one of the most serious accidents since it has several attributes (e.g. accident type and consequence) and its occurrence involves various kinds of causal factors (e.g. human factors). The impact of causal factors on construction collapse accidents and the interrelationships among causal factors remain poorly explored. Thus, the purpose of this paper is to use association rule mining (ARM) for cause analysis of construction collapse accidents.

Design/methodology/approach

An accident analytic framework is developed to determine the accident attributes and causal factors, and then ARM is introduced as the method for data mining. The data are from 620 historical accident records on government websites of China from 2010 to 2020. Through the generated association rules, the impact of causal factors and the interrelationships among causal factors are explored.

Findings

Collapse accident is easily caused by human factors, material and machine condition and management factors. Furthermore, the results show a close interrelationship between many causal factors and construction scheme and organization. The earthwork collapse is greatly related to environmental condition and the scaffolding collapse is greatly related to material and machine condition.

Practical implications

This study found relevant knowledge about the key causes for different types of construction collapses. Besides, several suggestions are further provided for construction units to prevent construction collapse accidents.

Originality/value

This study uses data mining methods to extract knowledge about the causes of collapse accidents. The impact of causal factors on various types of construction collapse accidents and the interrelationships among causal factors are explained from historical accident data.
From teamwork to psychological well-being and job performance: the role of CSR in the workplace
Authors: Kim Ho-Seok , Kim Minseong , Koo Dongwoo
Published: May 2022

Purpose

Although the positive impact of corporate social responsibility (CSR) initiatives on personal and organizational outcomes has been studied in the fields of human resource management and the hospitality industry, scholars in these fields still consider CSR as a promising area with potential. Drawing upon the dual concern and the attribution theories, this study aims to identify three stages of formations from teamwork with colleagues and personal benefits to organizational benefits from social responsibilities of hospitality companies via an integrated research model.

Design/methodology/approach

With the data collected from 324 frontline employees in hospitality enterprises in South Korea, this study empirically investigated the interrelationship to predict frontline employees’ job performance.

Findings

The empirical results from structural equation modeling indicated that perceived management support for CSR and perceived colleague support for CSR had significant influence on empathetic concern for colleague and anticipated positive affect, separately. Also, empathetic concern significantly affected psychological well-being and job satisfaction, while an anticipated positive affect significantly influenced job satisfaction. Finally, psychological well-being and job satisfaction had a significant impact on job performance.

Practical implications

This study provides several managerial implications for maximizing the effectiveness of hospitality companies’ CSR practices, enhancing frontline employees’ psychological well-being, job satisfaction and job performance.

Originality/value

Based on the empirical findings, this study provided meaningful theoretical and managerial implications to maximize the effectiveness of CSR initiatives and maximize frontline employees’ job performance in the hospitality industry.