bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With Severity of COVID-19 Disease in a Multicenter Cohort of People With HIV in the United States, March–December 2020
Authors: Shapiro Adrienne E. , Bender Ignacio Rachel A. , Whitney Bridget M. , Delaney Joseph A. , Nance Robin M. , Bamford Laura , Wooten Darcy , Keruly Jeanne C. , Burkholder Greer , Napravnik Sonia , Mayer Kenneth H. , Webel Allison R. , Kim H. Nina , Van Rompaey Stephen E. , Christopoulos Katerina , Jacobson Jeffrey , Karris Maile , Smith Davey , Johnson Mallory O. , Willig Amanda , Eron Joseph J. , Hunt Peter , Moore Richard D. , Saag Michael S. , Mathews W. Christopher , Crane Heidi M. , Cachay Edward R. , Kitahata Mari M. ,   for the CFAR Network of Integrated Clinical Systems
Published: April 2022

Background:

Understanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies.

Setting:

Centers for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care.

Methods:

We identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020–December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores.

Results:

Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count <350 cells/mm3 [aRR 2.68; 95% confidence interval (CI): 1.93 to 3.71; P < 0.001] or lowest recorded CD4 count <200 cells/mm3 (aRR 1.67; 95% CI: 1.18 to 2.36; P < 0.005) had greater risks of hospitalization. HIV viral load and antiretroviral therapy status were not associated with hospitalization, although most of the PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared with other racial/ethnic groups (aRR 1.51; 95% CI: 1.04 to 2.19; P = 0.03). Chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher hospitalization risk. PWH who were older, not on antiretroviral therapy, and with current CD4 count <350 cells/mm3, diabetes, and chronic kidney disease were overrepresented among PWH who required intubation or died.

Conclusions:

PWH with CD4 count <350 cells/mm3, and a history of CD4 count <200 cells/mm3, have a clear excess risk of severe COVID-19, accounting for comorbidities associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination and early treatment and monitored closely for worsening illness.
DraculR: A web based application for in silico haemolysis detection in high throughput small RNA sequencing data
Authors: Smith Melanie D. , Leemaqz Shalem Y. , Jankovic-Karasoulos Tanja , McCullough Dylan , McAninch Dale , Breen James , Roberts Claire T. , Pillman Katherine A.
Published: April 2022

Motivation

The search for novel microRNA (miRNA) biomarkers in plasma is hampered by haemolysis, the lysis and subsequent release of red blood cell (RBC) contents, including miRNAs, into surrounding fluid. The biomarker potential of miRNAs comes in part from their multi-compartment origin, and the long-lived nature of miRNA transcripts in plasma, giving researchers a functional window for tissues that are otherwise difficult or disadvantageous to sample. The inclusion of RBC derived miRNA transcripts in downstream analysis introduces a source of error that is difficult to identify post hoc and may lead to spurious results. Where access to a physical specimen is not possible, our tool will provide an in silico approach to haemolysis prediction.

Results

We present DraculR, an interactive Shiny/R application that enables a user to upload microRNA expression data from short read sequencing of human plasma as a raw read counts table and interactively calculate a metric that indicates the degree of haemolysis contamination.

Availability and implementation

DraculR and its tutorial are freely available from (https://mxhp75.shinyapps.io/shinyVamp/). Code is available from (https://github.com/mxhp75/shinyVamp.git).
Evolutionary gain and loss of a plant pattern-recognition receptor for HAMP recognition
Authors: Snoeck Simon , Abramson Bradley W. , Garcia Anthony G. K. , Egan Ashley N. , Michael Todd P. , Steinbrenner Adam D.
Published: April 2022

Pattern recognition receptors (PRR) recognize distinct pathogen and herbivore-associated molecular patterns (PAMPs and HAMPs) and mediate activation of immune responses, but the evolution of new PRR sensing functions is not well understood. We employed comparative genomics and functional analysis to define evolutionary events leading to the sensing of the peptide HAMP inceptin (In11) by the PRR Inceptin Receptor (INR). Existing and de novo genome assemblies revealed that the presence of a functional INR gene corresponded with In11 response across 55 million years (my) of legume evolution, and that In11 recognition is unique to the clade of Phaseoloid legumes. The INR loci of certain Phaseoloid and non-Phaseoloid species also contain diverse INR-like homologues, suggesting that the evolution of INR receptor function ∼28 mya occurred after an ancestral gene insertion ∼32 mya. Functional analysis of chimeric and ancestrally reconstructed receptors revealed that specific AA differences in the C1 leucine-rich repeat (LRR) domain and C2 intervening motif likely mediated gain of In11 recognition. In summary, we present a conceptual model for the evolution of a defined PRR function based on patterns of INR variation in legumes.
Response to immune checkpoint blockade improved in pre-clinical model of breast cancer after bariatric surgery
Authors: Sipe Laura M. , Chaib Mehdi , Korba Emily B. , Jo Heejoon , Lovely Mary-Camille , Counts Brittany R. , Tanveer Ubaid , Clements Jared C. , John Neena A. , Daria Deidre , Marion Tony N. , Sekhri Radhika , Pingili Ajeeth K. , Teng Bin , Carson James A. , Hayes D. Neil , Davis Matthew J. , Pierre Joseph F. , Makowski Liza
Published: April 2022

Bariatric surgery is becoming more prevalent as a sustainable weight loss approach, with vertical sleeve gastrectomy (VSG) being the first line of surgical intervention. We and others have shown that obesity exacerbates tumor growth while diet-induced weight loss impairs obesity-driven progression. It remains unknown how bariatric surgery-induced weight loss impacts cancer progression or alters responses to therapy. Using a pre-clinical model of diet induced obesity followed by VSG or diet-induced weight loss, breast cancer progression and immune checkpoint blockade therapy was investigated. Weight loss by bariatric surgery or weight matched dietary intervention before tumor engraftment protected against obesity-exacerbated tumor progression. However, VSG was not as effective as dietary intervention in reducing tumor burden despite achieving a similar extent of weight and adiposity loss. Circulating leptin did not associate with changes in tumor burden. Uniquely, tumors in mice that received VSG displayed elevated inflammation and immune checkpoint ligand, PD-L1. Further, mice that received VSG had reduced tumor infiltrating T lymphocytes and cytolysis suggesting an ineffective anti-tumor microenvironment. VSG-associated elevation of PD-L1 prompted us to next investigate the efficacy of immune checkpoint blockade in lean, obese, and formerly obese mice that lost weight by VSG or weight matched controls. While obese mice were resistant to immune checkpoint blockade, anti-PD-L1 potently impaired tumor progression after VSG through improved anti-tumor immunity. Thus, in formerly obese mice, surgical weight loss followed by immunotherapy reduced breast cancer burden.
Evolutionary relationships and range evolution of greenhood orchids (subtribe Pterostylidinae): insights from plastid phylogenomics
Authors: Nargar Katharina , O’Hara Kate , Mertin Allison , Bent Stephen , Nauheimer Lars , Simpson Lalita , Zimmer Heidi , Molloy Bryan P.J. , Clements Mark A.
Published: April 2022

Australia harbours a rich and highly endemic orchid flora with over 90% of native species found nowhere else. However, little is known about the assembly and evolution of Australia’s orchid flora. Here, we used a phylogenomic approach to infer evolutionary relationships, divergence times, and range evolution in Pterostylidinae (Orchidoideae), the second largest subtribe in the Australian orchid flora, comprising the generaPterostylisandAchlydosa. Phylogenetic analysis of 75 plastid genes provided well-resolved and supported phylogenies. Intrageneric relationships inPterostyliswere clarified and monophyly of eight of ten sections supported.Achlydosawas found to not form part of Pterostylidinae and instead merits recognition at subtribal level, as Achlydosinae.

Pterostylidinae were inferred to have originated in temperate eastern Australia in the early Oligocene, coinciding with the complete separation of Australia from Antarctica and the onset of the Antarctic Circumpolar Current, which led to profound changes in the world’s climate. Divergence of all major lineages occurred during the Miocene, accompanied by increased aridification and seasonality of the Australian continent, resulting in strong vegetational changes from rainforest to more open sclerophyllous vegetation. The majority of extant species were inferred to have originated in the Quaternary, from the Pleistocene onwards. The rapid climatic oscillations during the Pleistocene may have acted as important driver of speciation in Pterostylidinae. The subtribe underwent lineage diversification mainly within its ancestral range, in temperate eastern Australia. Long-distance dispersals to southwest Australia commenced from the late Miocene onwards, after the establishment of the Nullarbor Plain, which constitutes a strong edaphic barrier to mesic plants. Range expansions from the mesic into the arid zone of eastern Australia (Eremaean region) commenced from the early Pleistocene onwards. Extant distributions of Pterostylidinae in other Australasian regions, such as New Zealand and New Caledonia, are of more recent origin, resulting from long-distance dispersals from the Pliocene onwards. Temperate eastern Australia was identified as key source area for dispersals to other Australasian regions.
Grace-AKO: A Novel and Stable Knockoff Filter for Variable Selection Incorporating Gene Network Structures
Authors: Tian Peixin , Hu Yiqian , Liu Zhonghua , Zhang Yan Dora
Published: April 2022

Motivation

Variable selection is a common statistical approach to identifying genes associated with clinical outcomes of scientific interest. There are thousands of genes in genomic studies, while only a limited number of individual samples are available. Therefore, it is important to develop a method to identify genes associated with outcomes of interest that can control finite-sample false discovery rate (FDR) in high-dimensional data settings.

Results

This article proposes a novel method named Grace-AKO for graph-constrained estimation (Grace), which incorporates aggregation of multiple knockoffs (AKO) with the network-constrained penalty. Grace-AKO can control FDR in finite-sample settings and improve model stability simultaneously. Simulation studies show that Grace-AKO has better performance in finite-sample FDR control than the original Grace model. We apply Grace-AKO to the prostate cancer data in The Cancer Genome Atlas (TCGA) program by incorporating prostate-specific antigen (PSA) pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) as the prior information. Grace-AKO finally identifies 47 candidate genes associated with PSA level, and more than 75% of the detected genes can be validated.

Availability and implementation

We developed an R package for Grace-AKO available at:https://github.com/mxxptian/GraceAKO

Contact

doraz@hku.hkorzl2509@cumc.columbia.edu
Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces
Authors: Peris David , Ubbelohde Emily J. , Kuang Meihua Christina , Kominek Jacek , Langdon Quinn K. , Adams Marie , Koshalek Justin A. , Hulfachor Amanda Beth , Opulente Dana A. , Hall David J. , Hyma Katie , Fay Justin C. , Leducq Jean-Baptiste , Charron Guillaume , Landry Christian R. , Libkind Diego , Gonçalves Carla , Gonçalves Paula , Sampaio José Paulo , Wang Qi-Ming , Bai Feng-Yan , Wrobel Russel L. , Hittinger Chris Todd
Published: April 2022

Species is the fundamental unit to quantify biodiversity. In recent years, the model yeast Saccharomyces cerevisiae has seen an increased number of studies related to its geographical distribution, population structure, and phenotypic diversity. However, seven additional species from the same genus have been less thoroughly studied, which has limited our understanding of the macroevolutionary leading to the diversification of this genus over the last 20 million years. Here, we report the geographies, hosts, substrates, and phylogenetic relationships for approximately 1,800 Saccharomyces strains, covering the complete genus with unprecedented breadth and depth. We generated and analyzed complete genome sequences of 163 strains and phenotyped 128 phylogenetically diverse strains. This dataset provides insights about genetic and phenotypic diversity within and between species and populations, quantifies reticulation and incomplete lineage sorting, and demonstrates how gene flow and selection have affected traits, such as galactose metabolism. These findings elevate the genus Saccharomyces as a model to understand biodiversity and evolution in microbial eukaryotes.
Responses of cortical neurons to intracortical microstimulation in awake primates
Authors: Yun Richy , Mishler Jonathan H. , Perlmutter Steve I. , Rao Rajesh P. N. , Fetz Eberhard E.
Published: April 2022

Intracortical microstimulation (ICMS) is commonly used in many experimental and clinical paradigms; however, its effects on the activation of neurons are still not completely understood. To document the responses of cortical neurons in non-human primates to stimulation, we recorded single unit activity while delivering single-pulse stimulation via Utah arrays implanted in primary motor cortex of three macaque monkeys. Stimuli between 5-50 μA delivered to single channels reliably evoked spikes in neurons recorded throughout the array with delays of up to 12 milliseconds. ICMS pulses also induced a period of inhibition lasting up to 150 ms that typically followed the initial excitatory response. Higher current amplitudes led to a greater probability of evoking a spike and extended the duration of inhibition. The likelihood of evoking a spike in a neuron was dependent on the spontaneous firing rate as well as the delay between its most recent spike time and stimulus onset. Tonic repetitive stimulation between 2 and 20 Hz often modulated both the probability of evoking spikes and the duration of inhibition, although high frequency stimulation in particular was more likely to change both responses. On a trial-by-trial basis, whether a stimulus evoked a spike did not affect the subsequent inhibitory response; however, their changes over time were frequently positively or negatively correlated. Our results document the complex dynamics of cortical neural responses to electrical stimulation that need to be considered when utilizing ICMS for scientific and clinical applications.

Significance statement

Intracortical microstimulation (ICMS) is commonly used to probe the cortex, and previous studies have characterized the responses of single neurons to ICMS. However, these studies typically explored the averaged effects of ICMS throughout each experimental session, rather than by a trial-by-trial basis for each stimulation pulse. By shifting the approach, we explored the dependence of neural responses to ICMS on the spontaneous neural activity as well as the dynamics of responses over time due to repetitive stimulation. Our results highlight how the responses of neurons to ICMS are likely the result of interactions between local excitatory and inhibitory cortical circuits. These results will help inform the design of ICMS for both basic research and clinically relevant stimulation protocols.
Milkweed plants bought at nurseries may expose monarch caterpillars to harmful pesticide residues
Authors: Halsch Christopher A. , Hoyle Sarah M. , Code Aimee , Fordyce James A. , Forister Matthew L.
Published: April 2022

The decline of monarch butterflies in both the eastern and western United States has garnered widespread public interest. Planting milkweeds, their larval host plants, has been promoted as one action individuals can take, but little is known with respect to potential pesticide contamination of store-bought milkweeds. In this study, we collected leaf samples from 235 milkweed plants purchased at 33 retail nurseries across the US to screen for pesticides. Across all samples, we detected 61 different pesticides with an average of 12.2 (±5.0) compounds per plant. While only 9 of these compounds have been experimentally tested on monarch caterpillars, 38% of samples contained a pesticide above a concentration shown to have a sub-lethal effect for monarchs. We detected only a modest predictive ability of retailer size and milkweed species; and plants with labels advertising their value for wildlife did not have fewer pesticides at concentrations known to have a negative effect on monarchs. These results demonstrate the extensiveness of pesticide exposure within nursery milkweeds and the potential impacts on monarchs and other insects exposed to store-bought plants.

Highlights

Milkweeds were collected from stores in the United States and screened for pesticides.

We detected multiple pesticides in every milkweed plant sampled.

Over one third of samples contained a pesticide at a known harmful concentration for monarchs.

Plants labeled as wildlife-friendly did not have fewer potentially harmful compounds.
Insights into the domestication of avocado and potential genetic contributors to heterodichogamy
Authors: Solares Edwin , Morales-Cruz Abraham , Balderas Rosa Figueroa , Focht Eric , Ashworth Vanessa E. T. M. , Wyant Skylar , Minio Andrea , Cantu Dario , Arpaia Mary Lu , Gaut Brandon S.
Published: April 2022

The domestication history of avocado (Persea americana) remains unclear, in part due to a lack of suitable genomic tools.

We created a reference genome from the Gwen varietal, which is closely related to the economically dominant Hass varietal. We also compiled a database of 34 resequenced accessions that represented the three botanical races of P. americana.

Our genome assembly had an N50 of 3.37 megabases, a BUSCO score of 91% and was scaffolded with a genetic map, producing 12 pseudo-chromosomes with 49,450 genes. We used the Gwen genome as a reference to investigate the population genomics of avocado. Our analyses were consistent with three separate domestication events; we estimated that the Mexican race diverged from the Lowland (formerly known as ‘West Indian’) and Guatemalan races >1 million years ago. We also identified putative targets of selective sweeps in domestication events; within the Guatemalan race, putative candidate genes were enriched for fruit development and ripening. We also investigated divergence between heterodichogamous flowering types.

With the help of a new reference genome, we inferred the domestication history of avocado and identified genes that may contribute to heterodichogamy, including genes with functions in pollination and floral development.
An in situ cut-and-paste genome editing platform mediated by CRISPR/Cas9 or Cas12a
Authors: Jiang Ping , Kemper Kevin M. , Chang Kai-Ti , Qian Cheng , Li Yulong , Guan Liying , van Hasselt Peter , Caradonna Salvatore J. , Strich Randy
Published: April 2022

Recombinant DNA technology mediated by restriction enzymes and ligases allows in vitro manipulation of a DNA segment isolated from the genome. Short overhangs generated by restriction enzymes facilitate efficient pasting together a DNA sequence and a vector. We adopted this recombinant DNA strategy to develop an in vivo recombinant-genome genome editing approach. Using the programmable endonuclease Cas9 or Cas12a as a restriction enzyme, we devised an in situcut-and-paste (iCAP) genome editing method that was tested in both mouse germline and human cell line platforms. Mouse gene loci Slc35f2 and Slc35f6 were each edited with in-frame insertion of a large APEX2-Cre cassette and concurrent FRT3 insertion at a second location providing proof of principle for the iCAP method. Further, a de nova single nucleotide mutation associated with MED13L syndrome was efficiently corrected in patient cells. Altogether, the iCAP method provides a single genome editing platform with flexibility and multiutility enabling versatile and precise sequence alterations, such as insertion, substitution, and deletion, at single or multiple locations within a genomic segment in mammalian genomes.
Factors Affecting Protein Recovery During Hsp40 Affinity Profiling
Authors: Montoya Maureen R. , Quanrud Guy M. , Mei Liangyong , Moñtano José L. , Hong Caleb , Genereux Joseph C.
Published: April 2022

Hsp40s, also termed J-domain proteins, play a central role in cellular protein homeostasis by promiscuously surveying the proteome for misfolded proteins. We have exploited this property to develop Hsp40 affinity profiling as a method for identifying proteins that misfold in response to cellular stresses. In this assay, we use the Hsp40FlagDNAJB8H31Qas our recognition element for misfolded proteins. This protein is exogenously introduced into cells, promoting interactions without regard for native protein clients. Herein, we evaluate potential approaches to improve the performance of this assay. We find that although intracellular crosslinking increases recovery of protein interactors, this is not enough to overcome the relative drop in DNAJB8 recovery. While the J-domain promotes Hsp70 association, it does not affect the yield of protein association with DNJAB8 underbasalconditions. By contrast, crosslinking and J-domain ablation both substantially increase relative protein interactor recovery with the structurally distinct Class B Hps40 DNAJB1 but are completely compensated by poorer yield of DNAJB1 itself. Cellular thermal stress promotes increased affinity between DNAJB8H31Qand interacting proteins, as expected for interactions driven by recognition of misfolded proteins. DNAJB8WTdoes not demonstrate such a property, suggesting that under stress misfolded proteins are handed off to Hsp70. Hence, we find that DNAJB8H31Qis still our most effective recognition element for the recovery of destabilized client proteins following cellular stress.

Raw data is accessible through the PRIDE Archive at PXD030633.
Phasor-Based Multi-Harmonic Unmixing for In-Vivo Hyperspectral Imaging
Authors: Vallmitjana Alexander , Lepanto Paola , Irigoin Florencia , Malacrida Leonel
Published: April 2022

Hyperspectral imaging (HSI) is a paramount technique in biomedical science, however, unmixing and quantification of each spectral component is a challenging task. Traditional unmixing relies on algorithms that need spectroscopic parameters from the fluorescent species in the sample. The phasor-based multi-harmonic unmixing method requires only the empirical measurement of the pure species to compute the pixel-wise photon fraction of every spectral component. Using simulations, we demonstrate the feasibility of the approach for up to 5 components and explore the use of adding a 6th unknown component representing autofluorescence. The simulations show that the method can be successfully used in typical confocal imaging experiments (with pixel photon counts between 101and 103). As a proof of concept, we tested the method in living cells, using 5 common commercial dyes for organelle labeling and we easily and accurately separate them. Finally, we challenged the method by introducing a solvatochromic probe, 6-Dodecanoyl-N,N-dimethyl-2-naphthylamine (LAURDAN), intended to measure membrane dynamics on specific subcellular membrane-bound organelles by taking advantage of the linear combination between the organelle probes and LAURDAN. We succeeded in monitoring the membrane order in the Golgi apparatus, Mitochondria, and plasma membrane in the same in-vivo cell and quantitatively comparing them. The phasor-based multi-harmonic unmixing method can help expand the outreach of HSI and democratize its use by the community for it does not require specialized knowledge.
Vaccination decreases the risk of influenza A virus reassortment with a concomitant increase in subgenomic genetic variation in pigs
Authors: Li Chong , Culhane Marie R. , Schroeder Declan C. , Cheeran Maxim C-J. , Pantoja Lucina Galina , Jansen Micah L. , Torremorell Montserrat
Published: April 2022

Although vaccination is broadly used in North American swine breeding herds, managing swine influenza is challenging primarily due to the continuous evolution of influenza A virus (IAV) and the ability of the virus to transmit among vaccinated pigs. Studies that have simultaneously assessed the impact of vaccination on the emergence of IAV reassortment and genetic variation in pigs are limited. Here we directly sequenced 28 bronchoalveolar lavage fluid (BALF) samples collected from vaccinated and unvaccinated pigs co-infected with H1N1 and H3N2 IAV strains, and characterized 202 individual viral plaques recovered from 13 BALF samples. We identified 54 reassortant viruses that were grouped in 16 distinct and 18 mixed genotypes. Notably, we found that prime-boost vaccinated pigs had less reassortant viruses than non-vaccinated pigs, likely due to a reduction in the number of days pigs were co-infected with both challenge viruses. However, direct sequencing from BALF samples revealed limited impact of vaccination on viral variant frequency, evolutionary rates, and nucleotide diversity in any IAV coding regions. Overall, our results highlight the value of IAV vaccination not only at limiting virus replication in pigs but also at protecting public health by restricting the generation of novel reassortants with zoonotic and/or pandemic potential.
Pulmonary dust foci as rat pneumoconiosis lesion induced by titanium dioxide nanoparticles in 13-week inhalation study
Authors: Yamano Shotaro , Goto Yuko , Takeda Tomoki , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Kasai Tatsuya , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Umeda Yumi
Published: April 2022

Background

Most toxicological studies on titanium dioxide (TiO2) particles to date have concentrated on carcinogenicity and acute toxicity, with few studies focusing of pneumoconiosis, which is a variety of airspace and interstitial lung diseases caused by particle-laden macrophages. The present study examined rat pulmonary lesions associated with pneumoconiosis after inhalation exposure to TiO2 nanoparticles (NPs).

Methods

Male and female F344 rats were exposed to 6.3, 12.5, 25, or 50 mg/m3 anatase type TiO2 NPs for 6 hours/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. After the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses.

Results

Numerous milky white spots were present in the lungs after exposure 25 and 50 mg/m3 TiO2 NPs. Histopathological analysis revealed that the spots were alveolar lesions, characterized predominantly by the agglomeration of particle-laden macrophages and the presence of reactive alveolar epithelial type 2 cell (AEC2) hyperplasia. We defined this characteristic lesion as pulmonary dust foci (PDF). The PDF is an inflammatory niche, with decreased vascular endothelial cells in the interstitium, and proliferating AEC2 transformed into alveolar epithelial progenitor cells. The AEC2 in the PDF had acquired DNA damage. Based on PDF induction, the lowest observed adverse effect concentration for pulmonary disorders in male and female rats in this study was 12.5 mg/m3 and 6.3 mg/m3, respectively. The no observed adverse effect concentration for male rats was 6.3 mg/m3. There was a sex difference in lung lesion development, with females showing more pronounced lesion parameters than males.

Conclusions

Inhalation exposure to TiO2 NPs caused PDF, an air-space lesion which is an alveolar inflammatory niche containing particle-laden macrophages and proliferating AEC2. This PDF histopathologically resembles some pneumoconiosis lesions (pulmonary siderosis and hard metal pneumoconiosis) in workers and lung disease in smokers, suggesting that it is an early pneumoconiosis lesion caused by exposure to TiO2 NPs in rats and a common alveolar reaction in mammals.
High temperature molecular motions within a model protomembrane architecture
Authors: Misuraca Loreto , Matsuo Tatsuhito , Cisse Aline , LoRicco Josephine , Caliò Antonio , Zanotti Jean-Marc , Demé Bruno , Oger Philippe , Peters Judith
Published: April 2022

Modern phospholipid membranes are known to be in a functional, physiological state, corresponding to the liquid crystalline phase, only under very precise external conditions. The phase is characterised by specific lipid motions, which seem mandatory to permit sufficient flexibility and stability for the membrane. It can be assumed that similar principles hold for proto-membranes at the origin of life although they were likely composed of simpler, single chain fatty acids and alcohols. In the present study we investigated molecular motions of four types of model membranes to shed light on the variations of dynamics and structure as a function of temperature as protocells might have existed close to hot vents. We find a clear hierarchy among the flexibilities of the samples, where some structural parameters seem to depend on the lipids used while others do not.
AMPK-p38 axis converts human pluripotent stem cells to naïve state
Authors: Yang Zhennan , Liu Yajing , Xu Huaigeng , Yamane Junko , Hotta Akitsu , Fujibuchi Wataru , Yamashita Jun K
Published: April 2022

Pluripotent stem cells (PSCs) have been reported to exhibit two stages of pluripotency, ‘primed’ and ‘naïve’ states. Typical human PSCs (hPSCs) are in the primed state. Though several methods for conversion from primed to naïve state have been reported, the mechanism of the process is not fully understood. Here, we report that 5’ adenosine monophosphate-activated protein kinase (AMPK) and its downstream p38 is a signaling axis that can induce the naïve conversion of hPSCs with single pathway activation. The simple addition of an AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), or overexpression of a constitutive active form of p38 (CA-p38) alone in primed hPSCs induced naïve hPSCs that satisfied naïve state criteria: differentiation ability to three germ layers and naïve state-specific transcriptional expression, epigenomic resetting, and mitochondrial activity. RNA-seq analysis demonstrated that our AICAR- or CA-p38-induced naïve hPSCs show closely similar gene expression patterns to naïve state human embryonic stem cells (HNES1) derived from human inner cell mass (ICM). This novel and simple naïve conversion method provides new avenues for understanding and elucidating the fundamental mechanism of naïve conversion.
Chaperone Requirements for De Novo Folding of Saccharomyces cerevisiae Septins
Authors: Hassell Daniel , Denney Ashley , Singer Emily , Benson Aleyna , Roth Andrew , Ceglowski Julia , Steingesser Marc , McMurray Michael
Published: April 2022

Polymers of septin protein complexes play cytoskeletal roles in eukaryotic cells. The specific subunit composition within complexes controls functions and higher-order structural properties. All septins have globular GTPase domains. The other eukaryotic cytoskeletal NTPases strictly require assistance from molecular chaperones of the cytosol, particularly the cage-like chaperonins, to fold into oligomerization-competent conformations. We previously identified cytosolic chaperones that bind septins and influence the oligomerization ability of septins carrying mutations linked to human disease, but it was unknown to what extent wild-type septins require chaperone assistance for their native folding. Here we use a combination of in vivo and in vitro approaches to demonstrate chaperone requirements for de novo folding and complex assembly by budding yeast septins. Individually purified septins adopted non-native conformations and formed non-native homodimers. In chaperonin- or Hsp70-deficient cells, septins folded slower and were unable to assemble post-translationally into native complexes. One septin, Cdc12, was so dependent on co-translational chaperonin assistance that translation failed without it. Our findings point to distinct translation elongation rates for different septins as a possible mechanism to direct a stepwise, co-translational assembly pathway in which general cytosolic chaperones act as key intermediaries.
The molecular organization of flat and curved caveolae indicates bendable structural units at the plasma membrane
Authors: Matthaeus Claudia , Sochacki Kem A. , Dickey Andrea , Puchkov Dmytro , Haucke Volker , Lehmann Martin , Taraska Justin W.
Published: April 2022

Caveolae are small coated inner plasma membrane invaginations found in many cell types. Their diverse functions span from endocytosis to signaling, regulating key cellular processes including lipid uptake, pathogen entry, and membrane tension. Caveolae undergo shape changes from flat to curved. It is unclear which proteins regulate this process. To address this gap, we studied the shapes of caveolae with platinum replica electron microscopy in six common cell types. Next, we developed a correlative multi-color stimulated emission depletion (STED) fluorescence and platinum replica EM imaging (CLEM) method to image caveolae-associated proteins at caveolae of different shapes at the nanoscale. Caveolins and cavins were found at all caveolae, independent of their curvature. EHD2, a classic caveolar neck protein, was strongly detected at both curved and flat caveolae. Both pacsin2 and the regulator EHBP1 were found only at a subset of caveolae. Pacsin2 was localized primarily to areas surrounding flat caveolae, whereas EHBP1 was mostly detected at spheres. Contrary to classic models, dynamin was absent from caveolae and localized only to clathrin-coated structures. Cells lacking dynamin showed no substantial changes to caveolae, suggesting that dynamin is not directly involved in caveolae curvature. Together, we provide a mechanistic map for the molecular control of caveolae shape by eight of the major caveolae-associated coat and regulatory proteins. We propose a model where caveolins, cavins, and EHD2 assemble as a cohesive structural unit regulated by more intermittent associations with pacsin2 and EHBP1. These complexes can flatten and curve, capturing membrane to enable lipid traffic and changes to the surface area of the cell.
RNAinsecta: A tool for prediction of pre-microRNA in insects using machine learning algorithms
Authors: Nath Adhiraj , Bora Utpal
Published: April 2022

Pre-MicroRNAs are the hairpin loops which produces microRNAs that negatively regulate gene expression in several organisms. In insects, microRNAs participate in several biological processes including metamorphosis, reproduction, immune response, etc. Numerous tools have been designed in recent years to predict pre-microRNA using binary machine learning classifiers where predictive models are trained with true and pseudo pre-microRNA hairpin loops. Currently however, there are no existing tool that is exclusively designed for insect pre-microRNA detection. In this experiment we trained machine learning classifiers such as Random Forest, Support Vector Machine, Logistic Regression and k-Nearest Neighbours to predict pre-microRNA hairpin loops in insects while using Synthetic Minority Over-sampling Technique and Near-Miss to handle the class imbalance. The trained model on Support Vector Machine achieved accuracy of 92.19% while the Random Forest attained an accuracy of 80.28% on our validation dataset. These models are hosted online as web application called RNAinsecta. Further, searching target for the predicted pre-microRNA in insect model organism Drosophila melanogaster has been provided in RNAinsecta using miRanda at the backend where experimentally validated genes regulated by microRNA are collected from miRTarBase as target sites. RNAinsecta is freely available at https://rnainsecta.in
Brain-wide projections and differential encoding of prefrontal neuronal classes underlying learned and innate threat avoidance
Authors: Gongwer Michael W. , Klune Cassandra B. , Couto João , Jin Benita , Enos Alexander S. , Chen Rita , Friedmann Drew , DeNardo Laura A.
Published: April 2022

To understand how the brain produces behavior, we must elucidate the relationships between neuronal connectivity and function. The medial prefrontal cortex (mPFC) is critical for complex functions including decision-making and mood. mPFC projection neurons collateralize extensively, but the relationships between mPFC neuronal activity and brain-wide connectivity are poorly understood. We performed whole-brain connectivity mapping and fiber photometry to better understand the mPFC circuits that control threat avoidance. Using tissue clearing and light sheet fluorescence microscopy we mapped the brain-wide axon collaterals of populations of mPFC neurons that project to nucleus accumbens (NAc), ventral tegmental area (VTA), or contralateral mPFC (cmPFC) in mice. We present DeepTraCE, for quantifying bulk-labeled axonal projections in images of cleared tissue, and DeepCOUNT, for quantifying cell bodies. Anatomical maps produced with DeepTraCE aligned with known axonal projection patterns and revealed class-specific topographic projections within regions. During threat avoidance, cmPFC and NAc-projectors encoded conditioned stimuli, but only when action was required to avoid threats. mPFC-VTA neurons encoded learned but not innate avoidance behaviors. Together our results present new and optimized approaches for quantitative whole-brain analysis and indicate that anatomically-defined classes of mPFC neurons have specialized roles in threat avoidance.
MAIT cells activate dendritic cells to promote T follicular helper cell differentiation and humoral immunity
Authors: Pankhurst Theresa E. , Buick Kaitlin H. , Lange Joshua L. , Marshall Andrew J. , Button Kaileen R. , Palmer Olga R. , Farrand Kathryn J. , Stewart Isabelle F. N. , Bird Thomas , Mason Ngarangi C. , Compton Benjamin J. , Comoletti Davide , Salio Mariolina , Cerundolo Vincenzo , Painter Gavin F. , Hermans Ian F. , Connor Lisa M.
Published: April 2022

Protective immune responses against respiratory pathogens, including influenza virus are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has largely been hampered by the lack of a suitable mucosal adjuvant. In this study we explore a novel class of adjuvant that harness mucosal-associated invariant T (MAIT) cells. We show evidence that intranasal immunisation of MAIT cell agonists co-administered with protein, including haemagglutinin from influenza A virus induced potent humoral immunity and immunoglobulin (Ig)A production, which protected mice against infection. MAIT cell adjuvant activity was mediated by CD40L-dependent activation of dendritic cells and subsequent priming of CD4+ T follicular helper cells. In summary, we show that MAIT cells are promising vaccine targets that can be utilised as cellular adjuvants in mucosal vaccines.
High-resolution electron time-of-flight spectrometers for angle-resolved measurements at the SQS Instrument at the European XFEL
Authors: De Fanis Alberto , Ilchen Markus , Achner Alexander , Baumann Thomas M. , Boll Rebecca , Buck Jens , Danilevsky Cyril , Esenov Sergey , Erk Benjamin , Grychtol Patrik , Hartmann Gregor , Liu Jia , Mazza Tommaso , Montaño Jacobo , Music Valerija , Ovcharenko Yevheniy , Rennhack Nils , Rivas Daniel , Rolles Daniel , Schmidt Philipp , Sotoudi Namin Hamed , Scholz Frank , Viefhaus Jens , Walter Peter , Ziółkowski Pawel , Zhang Haiou , Meyer Michael
Published: April 2022

A set of electron time-of-flight spectrometers for high-resolution angle-resolved spectroscopy was developed for the Small Quantum Systems (SQS) instrument at the SASE3 soft X-ray branch of the European XFEL. The resolving power of this spectrometer design is demonstrated to exceed 10 000 (E/ΔE), using the well known Ne 1s
−13p resonant Auger spectrum measured at a photon energy of 867.11 eV at a third-generation synchrotron radiation source. At the European XFEL, a width of ∼0.5 eV full width at half-maximum for a kinetic energy of 800 eV was demonstrated. It is expected that this linewidth can be reached over a broad range of kinetic energies. An array of these spectrometers, with different angular orientations, is tailored for the Atomic-like Quantum Systems endstation for high-resolution angle-resolved spectroscopy of gaseous samples.
Effect of synthesis time on plasmonic properties of Ag dendritic nanoforests
Authors: Huang Hung Ji , Chang Han-Wei , Lee Chia-Yen , Shiao Ming-Hua , Chiu Yen-Ling , Lee Pee-Yew , Lin Yung-Sheng
Published: April 2022

The effects of synthesis time on the plasmonic properties of Ag dendritic nanoforests on Si substrate (Ag-DNF/Si) samples synthesized through the fluoride-assisted galvanic replacement reaction were investigated. The Ag-DNF/Si samples were characterized using scanning electron microscopy, energy-dispersive X-ray spectroscopy, reflection spectroscopy, X-ray diffraction and surface-enhanced Raman spectroscopy (SERS). The prolonged reaction time led to the growth of an Ag-DNF layer and etched Si hole array. SEM images and variations in the fractal dimension index indicated that complex-structure, feather-like leaves became coral-like branches between 30 and 60 min of synthesis. The morphological variation during the growth of the Ag DNFs resulted in different optical responses to light illumination, especially those of light harvest and energy transformation. The sample achieved the most desirable light-to-heat conversion efficiency and SERS response with a 30 min growth time. A longer synthesis time or thicker Ag-DNF layer on the Si substrate did not have superior plasmonic properties.
Innovator or collaborator? A cognitive network perspective to vision formation
Authors: Zasa Federico P. , Verganti Roberto , Bellis Paola
Published: April 2022

Purpose

Having a shared vision is crucial for innovation. The purpose of this paper is to investigate the effect of individual propensity to collaborate and innovate on the development of a shared vision.

Design/methodology/approach

The authors build a network in which each node represents the vision of one individual and link the network structure to individual propensity of collaboration and innovativeness. During organizational workshops in four multinational organizations, the authors collected individual visions in the form of images as well as text describing the approach to innovation from 85 employees.

Findings

The study maps individual visions for innovation as a cognitive network. The authors find that individual propensity to innovate or collaborate is related to different network centrality. Innovators, individuals who see innovation as an opportunity to change and grow, are located at the center of the cognitive network. Collaborators, who see innovation as an opportunity to collaborate, have a higher closeness centrality inside a cluster.

Research limitations/implications

This paper analyses visions as a network linking recent research in psychology with the managerial longing for a more thorough investigation of group cognition. The study contributes to literature on shared vision creation, suggesting the role which innovators and collaborators can occupy in the process.

Originality/value

This paper proposes how an approach based on a cognitive network can inform innovation management. The findings suggest that visions of innovators summarize the visions of a group, helping the development of an overall shared vision. Collaborators on the other hand are representative of specific clusters and can help developing radical visions.
Innovation in the supply chain and big data: a critical review of the literature
Authors: Centobelli Piera , Cerchione Roberto , Cricelli Livio , Strazzullo Serena
Published: April 2022

Purpose

This paper aims to propose a framework investigating the diffusion and adoption process of big data (BD) in the supply chain (SC) as a tool to manage process innovation at technological, operational and strategical levels.

Design/methodology/approach

A comprehensive systematic literature methodology is used to develop the theoretical conceptual framework, which comprehensively describes and captures the innovative stages of BD technology adoption process in SC with a multilevel perspective.

Findings

Results show that BD has modified the supply network concept, starting from the dyadic relationships, triads up to the creation of a streamlined and integrated network. These changes are reflected in a novel integrated vision including both benefits and barriers.

Research limitations/implications

The proposed framework supports companies in redesigning the processes affected by the adoption of BD, helping them in identifying the critical elements, barriers, benefits and expected performance. One limitation is the focus of the study on the analysis of the processes of adoption of BD technology in the SC considering a particular structure of SC characterized by only two levels of supply and by a reduced number of members.

Originality/value

Although the role of BD in supply chain operations management (SCOM) is well acknowledged in the literature, its adoption and diffusion process from an interorganizational perspective is still missing. Specifically, the adoption stages of BD in SC have been defined at a strategic level, and successively the SC operations and technological perspective have been integrated to depict the operationalization of BD implementation and diffusion.
On the likelihood and type of merger and acquisition in the US listed companies: the role of females on the board
Authors: Ahmed Yousry , Song Yu , Elsayed Mohamed
Published: April 2022

Purpose

This paper aims to examine whether and how females on the board of directors affect US-listed companies’ merger and acquisition (M&A) decisions. Specifically, the paper concerns the impact of females in the boardroom on the likelihood and type of M&A deals (i.e. foreign vs domestic acquisitions and listed vs unlisted acquisitions).

Design/methodology/approach

Archival data of M&A deals using a sample of 17,899 firm-year observations of the US public companies from 2012 to 2018 are collected and examined using probit and logit models.

Findings

This paper offers three main results supporting the propositions of the behavioral consistency theory. First, female directors are negatively associated with the likelihood of making the acquisition. Second, female directors are positively associated with acquiring domestic rather than foreign targets. Third, female directors are positively associated with acquiring listed rather than unlisted targets.

Research limitations/implications

The findings provide additional evidence-based insights into the debate about diversity on boards with the aim of informing policy and offering practical recommendations for the effective implementation of gender diversity on the boards of companies.

Originality/value

Overall, consistent with the premise of behavioral theory, the results expand the literature on gender diversity by augmenting the argument that females’ behavior in corporate policies is viewed as opposition to change and a tendency toward risk aversion and thus, influences companies’ strategic investment decisions, such as M&A.