bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid learning in a native predator shifts diet preferences towards invasive prey
Authors: Alexander M. E. , Skein L. , Robinson T. B.
Published: March 2022

Biological invasions often exert negative impacts on native communities and can disrupt a range of biotic interactions such as those between predators and prey. For example, when invasive species alter the foraging landscape, native predators can fail to recognize them as profitable prey because of unfamiliarity. This study therefore investigated whether a native predator (rock lobsterJasus lalandii) can develop a new preference for an invasive prey (musselSemimytilus patagonicus) following conditioning through a short-term exposure. Conditioned lobsters, exposed to onlyS. patagonicusfor a month, demonstrated a significant change in preference for the novel invasive prey, which was found to contrast with non-conditioned lobsters that continued to show predator preferences toward a native mussel (Choromytilus meridionalis). There is therefore potential for native predators such asJ. lalandiito adapt and switch towards feeding on an abundant invasive prey, even if they avoid it at first. This indicates that rapid learning can occur in a species exposed to novel food resources and demonstrates that native species can adapt to biological invasions.
Key thermally dimorphic fungal pathogens: shaping host immunity
Authors: Höft Maxine A. , Duvenage Lucian , Hoving J. Claire
Published: March 2022

Exposure to fungal pathogens from the environment is inevitable and with the number of at-risk populations increasing, the prevalence of invasive fungal infection is on the rise. An interesting group of fungal organisms known as thermally dimorphic fungi predominantly infects immunocompromised individuals. These potential pathogens are intriguing in that they survive in the environment in one form, mycelial phase, but when entering the host, they are triggered by the change in temperature to switch to a new pathogenic form. Considering the growing prevalence of infection and the need for improved diagnostic and treatment approaches, studies identifying key components of fungal recognition and the innate immune response to these pathogens will significantly contribute to our understanding of disease progression. This review focuses on key endemic dimorphic fungal pathogens that significantly contribute to disease, including
Histoplasma
,
Coccidioides
and
Talaromyces
species. We briefly describe their prevalence, route of infection and clinical presentation. Importantly, we have reviewed the major fungal cell wall components of these dimorphic fungi, the host pattern recognition receptors responsible for recognition and important innate immune responses supporting adaptive immunity and fungal clearance or the failure thereof.
Telomeric replication stress: the beginning and the end for alternative lengthening of telomeres cancers
Authors: Lu Robert , Pickett Hilda A.
Published: March 2022

Telomeres are nucleoprotein structures that cap the ends of linear chromosomes. Telomeric DNA comprises terminal tracts of G-rich tandem repeats, which are inherently difficult for the replication machinery to navigate. Structural aberrations that promote activation of the alternative lengthening of telomeres (ALT) pathway of telomere maintenance exacerbate replication stress at ALT telomeres, driving fork stalling and fork collapse. This form of telomeric DNA damage perpetuates recombination-mediated repair pathways and break-induced telomere synthesis. The relationship between replication stress and DNA repair is tightly coordinated for the purpose of regulating telomere length in ALT cells, but has been shown to be experimentally manipulatable. This raises the intriguing possibility that induction of replication stress can be used as a means to cause toxic levels of DNA damage at ALT telomeres, thereby selectively disrupting the viability of ALT cancers.
Error cancellation
Authors: Foerster Anna , Steinhauser Marco , Schwarz Katharina A. , Kunde Wilfried , Pfister Roland
Published: March 2022

The human cognitive system houses efficient mechanisms to monitor ongoing actions. Upon detecting an erroneous course of action, these mechanisms are commonly assumed to adjust cognitive processing to mitigate the error's consequences and to prevent future action slips. Here, we demonstrate that error detection has far earlier consequences by feeding back directly onto ongoing motor activity, thus cancelling erroneous movements immediately. We tested this prediction of immediate auto-correction by analysing how the force of correct and erroneous keypress actions evolves over time while controlling for cognitive and biomechanical constraints relating to response time and the peak force of a movement. We conclude that the force profiles are indicative of active cancellation by showing indications of shorter response durations for errors already within the first 100 ms, i.e. between the onset and the peak of the response, a timescale that has previously been related solely to error detection. This effect increased in a late phase of responding, i.e. after response force peaked until its offset, further corroborating that it indeed reflects cancellation efforts instead of consequences of planning or initiating the error.
Life in the freezer: protein metabolism in Antarctic fish
Authors: Fraser Keiron P. P. , Peck Lloyd S. , Clark Melody S. , Clarke Andrew , Hill Simeon L.
Published: March 2022

Whole-animal,
in vivo
protein metabolism rates have been reported in temperate and tropical, but not Antarctic fish. Growth in Antarctic species is generally slower than lower latitude species. Protein metabolism data for Antarctic invertebrates show low rates of protein synthesis and unusually high rates of protein degradation. Additionally, in Antarctic fish, increasing evidence suggests a lower frequency of successful folding of nascent proteins and reduced protein stability. This study reports the first whole-animal protein metabolism data for an Antarctic fish. Groups of Antarctic,
Harpagifer antarcticus
, and temperate,
Lipophrys pholis
, fish were acclimatized to a range of overlapping water temperatures and food consumption, whole-animal growth and protein metabolism measured. The rates of protein synthesis and growth in Antarctic, but not temperate fish, were relatively insensitive to temperature and were significantly lower in
H. antarcticus
at 3°C than in
L. pholis
. Protein degradation was independent of temperature in
H. antarcticus
and not significantly different to
L. pholis
at 3°C, while protein synthesis retention efficiency was significantly higher in
L. pholis
than
H. antarcticus
at 3°C. These results suggest Antarctic fish degrade a significantly larger proportion of synthesized protein than temperate fish, with fundamental energetic implications for growth at low temperatures.
[3+2]-Cycloaddition of azomethine ylides to 5-methylidene-3-aryl-2-сhalcogen-imidazolones: access to dispiro indolinone-pyrrolidine-imidazolones
Authors: Kukushkin Maxim E. , Kondratieva Alexandra A. , Karpov Nikita A. , Shybanov Dmitry E. , Tafeenko Viktor A. , Roznyatovsky Vitaly A. , Grishin Yuri K. , Moiseeva Anna A. , Zyk Nikolai V. , Beloglazkina Elena K.
Published: March 2022

A synthesis of dispiro derivatives from 5-methylidene-2-chalcogenimidazolones and azomethine ylides generated from isatins and N-substituted
α
-amino acids has been developed.
Missing He–McKellar–Wilkens geometric quantum phase
Authors: Bakke K.
Published: March 2022

We discuss the appearance of a missing geometric quantum phase from the interaction of the permanent electric dipole moment of a neutral particle with the magnetic field produced by a uniform distribution of the magnetic charges inside an infinitely long non-conductor cylinder with an inner radius

r

a

. This geometric quantum phase is associated with the missing magnetic charge per unit length in a region with a cylindrical shape of radius

r

a

and gives rise to an analogue of the He–McKellar–Wilkens geometric quantum phase. By searching for bound state solutions, we show that an Aharonov–Bohm-type effect arises from the influence of the missing geometric quantum phase on the eigenvalues of energy.
Collective states in a ring network of theta neurons
Authors: Omel'chenko Oleh , Laing Carlo R.
Published: March 2022

We consider a ring network of theta neurons with non-local homogeneous coupling. We analyse the corresponding continuum evolution equation, analytically describing all possible steady states and their stability. By considering a number of different parameter sets, we determine the typical bifurcation scenarios of the network, and put on a rigorous footing some previously observed numerical results.
Divergent paths in the evolutionary history of maternally transmitted clam symbionts
Authors: Perez Maëva , Breusing Corinna , Angers Bernard , Beinart Roxanne A. , Won Yong-Jin , Young C. Robert
Published: March 2022

Vertical transmission of bacterial endosymbionts is accompanied by virtually irreversible gene loss that results in a progressive reduction in genome size. While the evolutionary processes of genome reduction have been well described in some terrestrial symbioses, they are less understood in marine systems where vertical transmission is rarely observed. The association between deep-sea vesicomyid clams and chemosynthetic Gammaproteobacteria is one example of maternally inherited symbioses in the ocean. Here, we assessed the contributions of drift, recombination and selection to genome evolution in two extant vesicomyid symbiont clades by comparing 15 representative symbiont genomes (1.017–1.586 Mb) to those of closely related bacteria and the hosts' mitochondria. Our analyses suggest that drift is a significant force driving genome evolution in vesicomyid symbionts, though selection and interspecific recombination appear to be critical for maintaining symbiont functional integrity and creating divergent patterns of gene conservation. Notably, the two symbiont clades possess putative functional differences in sulfide physiology, anaerobic respiration and dependency on environmental vitamin B12, which probably reflect adaptations to different ecological habitats available to each symbiont group. Overall, these results contribute to our understanding of the eco-evolutionary processes shaping reductive genome evolution in vertically transmitted symbioses.
Feather growth and quality across passerines is explained by breeding rather than moulting latitude
Authors: Horák Kryštof , Bobek Lukáš , Adámková Marie , Kauzál Ondřej , Kauzálová Tereza , Manialeu Judith Pouadjeu , Nguelefack Télesphore Benoît , Nana Eric Djomo , Jønsson Knud Andreas , Munclinger Pavel , Hořák David , Sedláček Ondřej , Tomášek Oldřich , Albrecht Tomáš
Published: March 2022

Tropical bird species are characterized by a comparatively slow pace of life, being predictably different from their temperate zone counterparts in their investments in growth, survival and reproduction. In birds, the development of functional plumage is often considered energetically demanding investment, with consequences on individual fitness and survival. However, current knowledge of interspecific variation in feather growth patterns is mostly based on species of the northern temperate zone. We evaluated patterns in tail feather growth rates (FGR) and feather quality (stress-induced fault bar occurrence; FBO), using 1518 individuals of 167 species and 39 passerine families inhabiting Afrotropical and northern temperate zones. We detected a clear difference in feather traits between species breeding in the temperate and tropical zones, with the latter having significantly slower FGR and three times higher FBO. Moreover, trans-Saharan latitudinal migrants resembled temperate zone residents in that they exhibited a comparatively fast FGR and low FBO, despite sharing moulting environments with tropical species. Our results reveal convergent latitudinal shifts in feather growth investments (latitudinal syndrome) across unrelated passerine families and underscore the importance of breeding latitude in determining cross-species variation in key avian life-history traits.
Higher-order sequences of vocal mimicry performed by male Albert's lyrebirds are socially transmitted and enhance acoustic contrast
Authors: Backhouse Fiona , Dalziell Anastasia H. , Magrath Robert D. , Welbergen Justin A.
Published: March 2022

Most studies of acoustic communication focus on short units of vocalization such as songs, yet these units are often hierarchically organized into higher-order sequences and, outside human language, little is known about the drivers of sequence structure. Here, we investigate the organization, transmission and function of vocal sequences sung by male Albert's lyrebirds (Menura alberti), a species renowned for vocal imitations of other species. We quantified the organization of mimetic units into sequences, and examined the extent to which these sequences are repeated within and between individuals and shared among populations. We found that individual males organized their mimetic units into stereotyped sequences. Sequence structures were shared within and to a lesser extent among populations, implying that sequences were socially transmitted. Across the entire species range, mimetic units were sung with immediate variety and a high acoustic contrast between consecutive units, suggesting that sequence structure is a means to enhance receiver perceptions of repertoire complexity. Our results provide evidence that higher-order sequences of vocalizations can be socially transmitted, and that the order of vocal units can be functionally significant. We conclude that, to fully understand vocal behaviours, we must study both the individual vocal units and their higher-order temporal organization.
Long-range sequential dependencies precede complex syntactic production in language acquisition
Authors: Sainburg Tim , Mai Anna , Gentner Timothy Q.
Published: March 2022

To convey meaning, human language relies on hierarchically organized, long-range relationships spanning words, phrases, sentences and discourse. As the distances between elements (e.g. phonemes, characters, words) in human language sequences increase, the strength of the long-range relationships between those elements decays following a power law. This power-law relationship has been attributed variously to long-range sequential organization present in human language syntax, semantics and discourse structure. However, non-linguistic behaviours in numerous phylogenetically distant species, ranging from humpback whale song to fruit fly motility, also demonstrate similar long-range statistical dependencies. Therefore, we hypothesized that long-range statistical dependencies in human speech may occur independently of linguistic structure. To test this hypothesis, we measured long-range dependencies in several speech corpora from children (aged 6 months–12 years). We find that adult-like power-law statistical dependencies are present in human vocalizations at the earliest detectable ages, prior to the production of complex linguistic structure. These linguistic structures cannot, therefore, be the sole cause of long-range statistical dependencies in language.
Population viscosity promotes altruism under density-dependent dispersal
Authors: Kanwal Jasmeen , Gardner Andy
Published: March 2022

A basic mechanism of kin selection is population viscosity, whereby individuals do not move far from their place of birth and hence tend to be surrounded by relatives. In such circumstances, even indiscriminate altruism among neighbours will often involve interactions between kin, which has a promoting effect on the evolution of altruism. This has the potential to explain altruistic behaviour across the whole tree of life, including in taxa for which recognition of kin is implausible. However, population viscosity may also intensify resource competition among kin, which has an inhibitory effect on altruism. Indeed, in the simplest scenario, in which individuals disperse with a fixed probability, these two effects have been shown to exactly cancel such that there is no net impact of viscosity on altruism. Here, we show that if individuals are able to disperse conditionally upon local density, they are favoured to do so, with more altruistic neighbourhoods exhibiting a higher rate of dispersal and concomitant relaxation of kin competition. Comparing across different populations or species, this leads to a negative correlation between overall levels of dispersal and altruism. We demonstrate both analytically and using individual-based simulations that population viscosity promotes the evolution of altruism under density-dependent dispersal.
Does scent attractiveness reveal women's ovulatory timing? Evidence from signal detection analyses and endocrine predictors of odour attractiveness
Authors: Mei Mei , Grillot Rachel L. , Abbey Craig K. , Emery Thompson Melissa , Roney James R.
Published: March 2022

Odour cues associated with shifts in ovarian hormones indicate ovulatory timing in females of many nonhuman species. Although prior evidence supports women's body odours smelling more attractive on days when conception is possible, that research has left ambiguous how diagnostic of ovulatory timing odour cues are, as well as whether shifts in odour attractiveness are correlated with shifts in ovarian hormones. Here, 46 women each provided six overnight scent and corresponding day saliva samples spaced five days apart, and completed luteinizing hormone tests to determine ovulatory timing. Scent samples collected near ovulation were rated more attractive, on average, relative to samples from the same women collected on other days. Importantly, however, signal detection analyses showed that rater discrimination of fertile window timing from odour attractiveness ratings was very poor. Within-women shifts in salivary oestradiol and progesterone were not significantly associated with within-women shifts in odour attractiveness. Between-women, mean oestradiol was positively associated with mean odour attractiveness. Our findings suggest that raters cannot reliably detect women's ovulatory timing from their scent attractiveness. The between-women effect of oestradiol raises the possibility that women's scents provide information about overall cycle fecundity, though further research is necessary to rigorously investigate this possibility.
Development of a COVID-19 risk-assessment model for participants at an outdoor music festival: Evaluation of the validity and control measure effectiveness
Authors: Murakami Michio , Fujita Tsukasa , Li Pinqi , Imoto Seiya , Yasutaka Tetsuo
Published: March 2022

We developed an environmental exposure model to estimate the Coronavirus Disease 2019 (COVID-19) risk among participants at an outdoor music festival and validated the model using a real cluster outbreak case. Furthermore, we evaluated the extent to which the risk could be reduced by additional infection control measures such as negative proofs of antigen tests on the day of the event, wearing masks, disinfection of environmental surfaces, and vaccination. The total number of already- and newly-infected individuals who participated in the event according to the new model was 47.0 (95% uncertainty interval: 12.5–185.5), which is in good agreement with the reported value (45). Among the additional control measures, vaccination, mask-wearing, and disinfection of surfaces were determined to be effective. Based on the combination of all measures, a 94% risk reduction could be achieved. In addition to setting a benchmark for an acceptable number of newly-infected individuals at the time of an event, the application of this model will enable us to determine whether it is necessary to implement additional measures, limit the number of participants, or refrain from holding an event.
Alzheimer’s Disease Classification Using Cluster-based Labelling for Graph Neural Network on Heterogeneous Data
Authors: McCombe Niamh , Bamrah Jake , Sanchez-Bornot Jose M. , Finn David P. , McClean Paula L. , Wong-Lin KongFatt ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: March 2022

Biomarkers for Alzheimer’s disease (AD) diagnosis do not always correlate reliably with cognitive symptoms, making clinical diagnosis inconsistent. In this study, the performance of a graphical neural network (GNN) classifier based on data-driven diagnostic classes from unsupervised clustering on heterogeneous data, is compared to the performance of a classifier using clinician diagnosis as outcome. Unsupervised clustering on tau-PET and cognitive and functional assessment data was performed. Five clusters embedded in a nonlinear UMAP space were identified. The individual clusters revealed specific feature characteristics with respect to clinical diagnosis of AD, gender, family history, age, and underlying neurological risk factors. In particular, one cluster comprised mainly diagnosed AD cases. All cases within this cluster were re-labelled AD cases. The re-labelled cases are characterised by high cerebrospinal fluid amyloid beta (CSF Aβ) levels at a younger age, even though Aβ data was not used for clustering. A GNN model was trained using the relabelled data with a multiclass area-under-the-curve (AUC) of 95.2%, higher than the AUC of a GNN trained on clinician diagnosis (91.7%; p=0.02). Overall, our work suggests that more objective cluster-based diagnostic labels combined with GNN classification may have value in clinical risk stratification and diagnosis of AD.
Attempt to replicate voxel-based morphometry analysis in fibromyalgia: Detection of below threshold differences framed by contributions of variable clinical presentation to low reproducibility
Authors: Baker Anne K. , Nanda Meghna , Park Su Hyoun , Martucci Katherine T.
Published: March 2022

Background

Fibromyalgia is a prevalent chronic pain condition characterized by widespread pain and sensory hypersensitivity. While much remains unknown about fibromyalgia’s neurobiological underpinnings, central nervous system alterations appear to be heavily implicated in its pathophysiology. Previous research examining brain structural abnormalities associated with fibromyalgia has yielded inconsistent findings. Thus, we followed previous methods to examine brain gray matter differences in fibromyalgia. We hypothesized that, relative to healthy controls, participants with fibromyalgia would exhibit lower gray matter volume in regions consistently implicated in fibromyalgia: the anterior cingulate cortex and medial prefrontal cortex.

Methods

This study used magnetic resonance imaging to evaluate regional and whole brain differences in gray matter among females with and without fibromyalgia. Group differences were analyzed with two-sample t-tests, controlling for total intracranial volume.

Results

No significant differences in regional or whole brain gray matter volumes were detected between fibromyalgia and healthy controls.

Conclusions

Results add to an existing body of disparate findings regarding brain gray matter volume differences in fibromyalgia, and suggest structural differences previously detected in fibromyalgia should be examined for reproducibility. Absent significant differences may also suggest that functional, but not structural, brain adaptations are primarily associated with fibromyalgia.
Tract-based white matter hyperintensity patterns in patients with Systemic Lupus Erythematosus using an unsupervised machine learning approach
Authors: Rumetshofer Theodor , Inglese Francesca , de Bresser Jeroen , Mannfolk Peter , Strandberg Olof , Jönsen Andreas , Bengtsson Anders , Nilsson Markus , Knutsson Linda , Lätt Jimmy , Steup-Beekman Gerda M. , Huizinga Tom W.J. , van Buchem Mark A. , Ronen Itamar , Sundgren Pia C.
Published: March 2022

Currently, little is known about the spatial distribution of white matter hyperintensities (WMH) in the brain of patients with Systemic Lupus erythematosus (SLE). Previous lesion markers, such as number and volume, ignore the strategic location of WMH. The goal of this work was to develop a fully-automated method to identify predominant patterns of WMH across WM tracts based on cluster analysis. A total of 221 SLE patients with and without neuropsychiatric symptoms from two different sites were included in this study. WMH segmentations and lesion locations were acquired automatically. Cluster analysis was performed on the WMH distribution in 20 WM tracts. Our pipeline identified five distinct clusters with predominant involvement of the forceps major, forceps minor, as well as right and left anterior thalamic radiations and the right inferior fronto-occipital fasciculus. The patterns of the affected WM tracts were consistent over the SLE subtypes and sites. Our approach revealed distinct and robust tract-based WMH patterns within SLE patients. This method could provide a basis, to link the location of WMH with clinical symptoms. Furthermore, it could be used for other diseases characterized by presence of WMH to investigate both the clinical relevance of WMH and underlying pathomechanism in the brain.
NKG2A and HLA-E define a novel alternative immune checkpoint axis in bladder cancer
Authors: Salomé Bérengère , Sfakianos John P. , Daza Jorge , Charap Andrew , Hammer Christian , Banchereau Romain , Farkas Adam M. , Geanon Daniel , Kelly Geoffrey , de Real Ronaldo M. , Lee Brian , Beaumont Kristin G. , Shroff Sanjana , Wang Yuan Shuo A. , Wang Ying-chih , Thin Tin Htwe , Garcia-Barros Monica , Hegewisch-Solloa Everardo , Mace Emily M. , Wang Li , O’Donnell Timothy , Chowell Diego , Fernandez-Rodriguez Ruben , Skobe Mihaela , Taylor Nicole , Kim-Schulze Seunghee , Sebra Robert P. , Palmer Doug , Clancy-Thompson Eleanor , Hammond Scott , Kamphorst Alice O. , Malmberg Karl-Johan , Marcenaro Emanuela , Romero Pedro , Brody Rachel , Viard Mathias , Yuki Yuko , Martin Maureen , Carrington Mary , Mehrazin Reza , Wiklund Peter , Mellman Ira , Mariathasan Sanjeev , Zhu Jun , Galsky Matthew D. , Bhardwaj Nina , Horowitz Amir
Published: March 2022

PD-1/PD-L1-blockade immunotherapies have limited efficacy in the treatment of muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma. Here, we show thatKLRC1(NKG2A) expression associates with improved survival and responsiveness to PD-L1 blockade immunotherapy inCD8Ahighbladder tumors. The loss of antigen presentation is a common mechanism for tumor escape in bladder cancer. NKG2A+CD8 T cells are able to circumvent HLA-ABC loss through TCR-independent cytotoxicity, which is partly mediated by DNAM-1. In bladder tumors, NKG2A is acquired on a subset of PD-1+CD8 T cells, alongside stronger tissue-residency memory features, TCR-independent cytotoxicity and evidence of recent proliferation. HLA-E is low but variably expressed on bladder tumors. When expressed, NKG2A+CD8 T cell anti-tumor responses to HLA-ABC-deficient tumors are inhibited and partly restored upon NKG2A blockade. Overall, our study identifies an alternative path for CD8 T cell exhaustion, that is mediated by NKG2A upregulation and TCR-independent cytotoxicity.
Strategic stabilization of arousal boosts sustained attention
Authors: de Gee J.W. , Mridha Z. , Hudson M , Shi Y. , Ramsaywak H. , Smith S. , Karediya N. , Thompson M. , Jaspe K. , Jiang H. , Zhang W. , McGinley M. J.
Published: March 2022

Changes in autonomic arousal, such as mounting sleep pressure, and changes in motivation, such as fluctuating environmental reward statistics, both profoundly influence behavior. Our experience tells us that we have some capacity to control our arousal when doing so is important, such as staying awake while driving a motor vehicle. However, little is known about how decision computations are jointly influenced by arousal and motivation, including whether animals, such as rodents, can adapt their arousal state to their needs. Here, we developed and show results from an auditory feature-based sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply novel signal detection theoretic and accumulation-to-bound modeling approaches in a large behavioral cohort. We find that both pupil-linked arousal and task utility have major impacts on multiple aspects of performance. Although substantial arousal fluctuations persist across utility conditions, mice partially stabilize their arousal near an intermediate, and optimal, level when task utility is high. Behavioral analyses show that multiple elements of behavior improve during high task utility and that arousal influences some, but not all, of them. Specifically, arousal influences the likelihood and timescale of sensory evidence accumulation, but not the quantity of evidence accumulated per time step while attending. In sum, the results establish specific decision-computational signatures of arousal, motivation, and their interaction, in attention. So doing, we provide an experimental and analysis framework for studying arousal self-regulation in neurotypical brains and diseases such as attention-deficit/hyperactivity disorder.
A-type FHFs mediate resurgent currents through TTX-resistant voltage-gated sodium channels
Authors: Xiao Yucheng , Theile Jonathan W. , Zybura Agnes , Pan Yanling , Lin Zhixin , Cummins Theodore R.
Published: March 2022

Resurgent currents (INaR) produced by voltage-gated sodium channels are required for many neurons to maintain high-frequency firing, and contribute to neuronal hyperexcitability and disease pathophysiology. Here we show, for the first time, that INaR can be reconstituted in a heterologous system by co-expression of sodium channel α-subunits and A-type fibroblast growth factor homologous factors (FHFs). Specifically, A-type FHFs induces INaR from Nav1.8, Nav1.9 tetrodotoxin-resistant neuronal channels and, to a lesser extent, neuronal Nav1.7 and cardiac Nav1.5 channels. Moreover, we identified the N-terminus of FHF as the critical molecule responsible for A-type FHFs-mediated INaR. Among the FHFs, FHF4A is the most important isoform for mediating Nav1.8 and Nav1.9 INaR. In nociceptive sensory neurons, FHF4A knockdown significantly reduces INaR amplitude and the percentage of neurons that generate INaR, substantially suppressing excitability. Thus, our work reveals a novel molecular mechanism underlying TTX-resistant INaR generation and provides important potential targets for pain treatment.
Circulating mast cell progenitors migrate to atopic dermatitis-like skin then adapt locally
Authors: Keith Yuki Honda , Honda Tetsuya , Ono Sachiko , Lee Bernett , Hanakawa Sho , Ishida Yoshihiro , Nakamizo Satoshi , Kabashima Kenji
Published: March 2022

Background

Mast cells (MCs) are tissue-resident immune cells that are classified into two subsets in mice: connective tissue-type MCs (CTMCs) and mucosal type MCs (MMCs). Although both CTMCs and MMCs can be induced from bone marrow (BM)-derived hematopoietic stem cells (HSCs) in vitro, recent research on MC ontogeny has revealed that MMCs are maintained with a supply of BM-derived HSCs, while CTMCs are maintained locally by self-proliferation in steady state in vivo. However, how CTMCs, such as skin MCs, are maintained in an inflammatory state such as atopic dermatitis (AD) remains to be fully elucidated. Methods: MC903-induced AD model was used to identify BM-derived MCs in the skin. The infiltration and proliferation of MCs were evaluated by flow cytometry using CD45.1 BM-chimera mice and parabiosis. BM-derived MCs in AD-like skin were compared to resident MCs (rMCs) in gene expressions by RNA sequence analysis. The fate of BM-derived MCs in AD-like skin was investigated for expressions of CTMC markers and responses to compound 48/80. Results: In AD-like skin, significant increase of both rMCs and BM-derived MCs was observed. BM-derived MCs were derived from circulating MC progenitors (MCps) and were distinguished from rMCs by integrinβ7 expression, which was gradually downregulated in the skin. RNA sequence analysis showed that integrinβ7+ MCs in the skin shared characteristics of both MMC and CTMC. Integrinβ7+ MCs proliferated in situ and acquired the CTMC phenotypes in AD-like skin. Conclusions: Skin MCs are maintained in AD-like skin by both local proliferation of rMCs and infiltration/proliferation of BM-derived MCs, which differentiate toward CTMC in the skin.
Optimized Workflow for Enrichment and Identification of Biotinylated Peptides using Tamavidin 2-REV for BioID and Cell Surface Proteomics
Authors: Nishino Kohei , Yoshikawa Harunori , Motani Kou , Kosako Hidetaka
Published: March 2022

Chemical or enzymatic biotinylation of proteins is widely used in various studies, and proximity-dependent biotinylation coupled to mass spectrometry is a powerful approach for analyzing protein–protein interactions in living cells. We recently developed a simple method to enrich biotinylated peptides using Tamavidin 2-REV, an engineered avidin-like protein with reversible biotin-binding capability. However, the low abundance of protein biotinylation in cells required large amounts of cellular proteins to detect enough biotinylated peptides. Here we optimized the workflow for efficient enrichment and identification of biotinylated peptides. The most efficient recovery was achieved by heat inactivation of trypsin, prewashing Tamavidin 2-REV beads, clean-up of biotin solution, mock elution, and the optimal temperature and salt concentration for elution. Using the optimized workflow, over 2-fold more biotinylated peptides were identified with higher purity from RAW264.7 macrophages expressing TurboID-fused STING. In addition, sequential digestion with Glu-C and trypsin led to the identification of biotinylation sites that were not identified by trypsin digestion alone. Furthermore, the combination of this workflow with TMT labeling enabled large-scale quantification of cell surface proteome changes upon EGF stimulation. This workflow would be useful not only for BioID and cell surface proteomics but also for various other applications based on protein biotinylation.
A scoping systematic review of implementation frameworks to effectively transition interventions into clinical practice in oncology, nuclear medicine and radiology
Authors: Delanerolle Gayathri , Cavalini Heitor , Phiri Peter , Gelling Leslie
Published: March 2022

Background

Clinical research studies have made significant strides globally requiring clear processes to transition research interventions into clinical practice. Theoretically, implementation of novel interventions require clear methods as part of a fit-for-purpose (FFP) framework comprising of effective adaptation processes in conjunction with practice policies. Implementation science (IS) based operational research (OR) is vital in global health as it addresses the ‘know-how-do’ gap using a real-world setting to achieve best practices to sustain healthcare. Despite this, limited OR is available to evaluate and validate implementation frameworks for complex clinical specialties such as oncology, diagnostic radiology (DR), nuclear medicine (NM) and interventional radiology (IR). This is the first study to systematically review implementation frameworks including its’ validity and applicability in healthcare.

Method

We searched 17 databases including PubMed, Medline/OvidSP, Science Direct, PROSPERO, PRISMA, PubMed Health, Embase, EBSCOhost, SciELO, TRIP, ProQuest, Academic search complete, Ageline, Cochrane, Web-of-Science and BIOSIS using a comprehensive search strategy and MeSH indexing to review publications from January 1st 1980 to 31st March 2019 in English. We selected 20 publications as per the inclusion/exclusion criteria developed under a review protocol registered with PROSPERO (CRDG42019124020).

Findings

There were no publications indicating a validated framework or a specific system used to implement evidence based interventions (EBIs) within oncology, IR, NM and DR although there were generalized implementation processes, adaptation models and policies. Furthermore, validation studies were not conducted against these frameworks to review their applicability and viability in healthcare especially in the UK.

Interpretation

It is evident there is a research implementation gap in healthcare and further research is required to establish a fit for purpose framework to cover multiple ‘blind spots’ using a real-world (RW) setting. Current evidence also suggests, alignment of academic theories to healthcare including its applicability to various clinical specialties is needed.
Recovery of kicking kinematics and performance following intermittent high-intensity running bouts in young soccer players: can a local cooling intervention help?
Authors: Palucci Vieira Luiz H , Carling Christopher , Kalva-Filho Carlos A , Santinelli Felipe B , Velluto Lorenzo A G , da Silva João Pedro , Kellis Eleftherios , Barbieri Fabio A
Published: March 2022

Repeated high-intensity running (RHIR) exercise is known to affect central and peripheral functioning. Declines in RHIR performance are exacerbated by environmental heat stress. Accordingly, the use of post-exercise cooling strategies (COOL) is recommended as it may assist recovery. The present study aimed to investigate, in a hot environment (> 30ºC), the effects of local COOL following RHIR on indices of soccer kicking movement and performance in youth soccer. Fifteen academy under-17 players (16.27 ± 0.86 years-old; all post-PHV), acting as their own controls, participated. In #Experiment 1, players completed an all-out RHIR protocol (10 × 30 m bouts interspersed with 30 s intervals). In #Experiment 2, the same players performed the same running protocol under two conditions, 1) 5 minutes of COOL where ice packs were applied to the quadriceps and hamstrings regions and, 2) a control condition involving only passive resting. In both experiments, perceptual measures [ratings of perceived exertion (RPE), pain and recovery], thigh temperature and kick-derived video kinematics (hip, knee, ankle and foot) and performance (ball speed and placement) were collected at baseline and post exercise and intervention. In the first experiment, RHIR led to moderate-to-large increases (p< 0.03) in RPE (d= 4.08), ankle eversion/inversion angle (d= 0.78) and mean radial error (d= 1.50) and small-to-large decreases (p< 0.04) in recovery (d= -1.83) and average/peak ball speeds (d= -0.42–-0.36). In the second experiment RPE (p< 0.01; Kendall’sW= 0.30) and mean radial error (p= 0.057; η2= 0.234) increased only post-control. Significant small declines in ball speed were also observed only post-control (p< 0.05;d= 0.35). Post-intervention CMfootvelocity was moderately faster in COOL as compared to control (p= 0.04;d= 0.60). RHIR acutely impaired kicking movement, ball speed and placement in youth soccer players. However, a short period of local cryotherapy may be beneficial in counteracting declines in indices of kicking performance in hot environment.

Trial registration number

#RBR-8prx2m - ReBEC Brazilian Clinical Trials Registry
13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial
Authors: Elkazzaz Mahmoud , Abo-Amer Yousry Esam-Eldin , Ahmed Amr , Haydara Tamer
Published: March 2022

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people causing over 2.4 million deaths over the world, and it is still expanding. Given the urgency of the COVID-19 pandemic, the clinical investigation of approved drugs is a promising alternative to find a timely effective treatment. In this randomized trial, we investigated the activity of both oral and aerosolized 13 cis retinoic acid in the treatment of SARS-COV-2 added to standard of care treatment in patients with COVID-19 versus standard of care treatment alone. This was a randomized controlled trial conducted at Kafrelsheikh University’s Quarantine Hospitals, Egypt. After obtaining informed consent, forty patients with a confirmed diagnosis of COVID-19 were enrolled in the study. They were randomly assigned to one of two groups: Group I; 20 patients received aerosolized and oral 13 cis retinoic acid plus standard of care treatment (13 cis RA group) and Group II; 20 patients received only standard care treatment as a control group. The two groups were age and gender matched. There was no statistically significant difference between them in any of the baseline characteristics or laboratory parameters. The results showed that there was a high significant difference between the two groups regarding intensive care unit (ICU) admission, mortality and improvement (P<0.05). Only 10.52 % of patients in the 13 cis retinoic acid group needed ICU admission compared to 28.57 % in the control arm. There was no mortality in the 13 cis retinoic acid group, whereas about 14.35% were died in the group II. All patients who received 13 cis retinoic acid noticed a high improvement (P<0.001), and the mean value for clinical improvement was 16.3±4.5 days. There was no significant difference regarding the laboratory parameters before and after 14 days of treatment in the group of patients received the standard of care treatment (P=0.66). Univariate logistic regression analysis showed overall mortality was significantly related to the patient’s age, serum ferritin, C-reactive protein, oxygen saturation, the presence of diabetes mellitus, obesity, and abdominal pain. We conclude that 13 cis retinoic acid is a promising drug in the treatment of patients with COVID-19 infection, when added to the standard of care treatment.
SNARE assembly enlightened by cryo-EM structures of a synaptobrevin-Munc18-1-syntaxin-1 complex
Authors: Stepien Karolina P. , Xu Junjie , Zhang Xuewu , Bai Xiaochen , Rizo Josep
Published: March 2022

Munc18-1 forms a template to recruit and organize assembly of the SNARE complex that triggers neurotransmitter release, binding first to a closed conformation of syntaxin-1 where its N-terminal region interacts with the SNARE motif, and later binding to synaptobrevin. However, the mechanism of SNARE complex assembly remains unclear. Here we report two cryo-EM structures of Munc18-1 bound to cross-linked syntaxin-1 and synaptobrevin. The structures allow visualization of how syntaxin-1 opens and reveal how part of the syntaxin-1 N-terminal region can help nucleate interactions between the N-termini of the syntaxin-1 and synaptobrevin SNARE motifs while their C-termini bind to distal sites of Munc18-1. Mutagenesis, SNARE complex assembly assays and reconstitution experiments support a model whereby these interactions are critical to initiate SNARE complex assembly.

One Sentence Summary

Cryo-EM structures reveal key insights into the molecular mechanism of neuronal SNARE complex assembly templated by Munc18-1
Quantifying the immunological distinctiveness of emerging SARS-CoV-2 variants in the context of prior regional herd exposure
Authors: Niesen Michiel J.M. , Murugadoss Karthik , Lenehan Patrick J. , Marchler-Bauer Aron , Wang Jiyao , Connor Ryan , Brister J. Rodney , Venkatakrishnan AJ , Soundararajan Venky
Published: March 2022

The COVID-19 pandemic has seen the persistent emergence of immune-evasive SARS-CoV-2 variants under the selection pressure of natural and vaccination-acquired immunity. However, it is currently challenging to quantify how immunologically distinct a new variant is compared to all the prior variants to which a population has been exposed. Here we define ‘Distinctiveness’ of SARS-CoV-2 sequences based on a proteome-wide comparison with all prior sequences from the same geographical region. We observe a correlation between Distinctiveness relative to contemporary sequences and future change in prevalence of a newly circulating lineage (Pearson r = 0.75), suggesting that the Distinctiveness of emergent SARS-CoV-2 lineages is associated with their competitive fitness. We further show that the average Distinctiveness of sequences belonging to a lineage, relative to the Distinctiveness of other sequences that occur at the same place and time (n = 944 location/time data points), is predictive of future increases in prevalence (AUC = 0.88, 0.86-0.90 95% confidence interval). By assessing the Delta variant in India versus Brazil, we show that the same lineage can have different Distinctiveness-contributing positions in different geographical regions depending on the other variants that previously circulated in those regions. Finally, we find that positions that constitute epitopes contribute disproportionately (20-fold higher than the average position) to Distinctiveness. Overall, this study suggests that real-time assessment of new SARS-CoV-2 variants in the context of prior regional herd exposure via Distinctiveness can augment genomic surveillance efforts.
Bio-inspired neural networks implement different recurrent visual processing strategies than task-trained ones do
Authors: Lindsay Grace W. , Mrsic-Flogel Thomas D. , Sahani Maneesh
Published: March 2022

Behavioral studies suggest that recurrence in the visual system is important for processing degraded stimuli. There are two broad anatomical forms this recurrence can take, lateral or feedback, each with different assumed functions. Here we add four different kinds of recurrence—two of each anatomical form—to a feedforward convolutional neural network and find all forms capable of increasing the ability of the network to classify noisy digit images. Specifically, we take inspiration from findings in biology by adding predictive feedback and lateral surround suppression. To compare these forms of recurrence to anatomically-matched counterparts we also train feedback and lateral connections directly to classify degraded images. Counter-intuitively, we find that the anatomy of the recurrence is not related to its function: both forms of task-trained recurrence change neural activity and behavior similarly to each other and differently from their bio-inspired anatomical counterparts. By using several analysis tools frequently applied to neural data, we identified the distinct strategies used by the predictive versus task-trained networks. Specifically, predictive feedback de-noises the representation of noisy images at the first layer of the network and decreases its dimensionality, leading to an expected increase in classification performance. Surprisingly, in the task-trained networks, representations are not de-noised over time at the first layer (in fact, they become ‘noiser’ and dimensionality increases) yet these dynamics do lead to de-noising at later layers. The analyses used here can be applied to real neural recordings to identify the strategies at play in the brain. Our analysis of an fMRI dataset weakly supports the predictive feedback model but points to a need for higher-resolution cross-regional data to understand recurrent visual processing..