bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood-based transcriptomic signature panel identification for cancer diagnosis: Benchmarking of feature extraction methods
Authors: Vijayan Abhishek , Fatima Shadma , Sowmya Arcot , Vafaee Fatemeh
Published: March 2022

Liquid biopsy has shown promise for cancer diagnosis due to its minimally invasive nature and the potential for novel biomarker discovery. However, the low concentration of relevant blood-based biosources and the heterogeneity of samples (i.e. the variability of relative abundance of molecules identified), pose major challenges to biomarker discovery. Moreover, the number of molecular measurements or features (e.g., transcript read counts) per sample could be in the order of several thousand, whereas the number of samples is often substantially lower, leading to the curse of dimensionality. These challenges, among others, elucidate the importance of a robust biomarker panel identification or feature extraction step wherein relevant molecular measurements are identified prior to classification for cancer detection. In this work, we performed a benchmarking study on eleven feature extraction methods using transcriptomic profiles derived from different blood-based biosources. The methods were assessed both in terms of their predictive performance and the robustness of the biomarker panels in diagnosing cancer or stratifying cancer subtypes. While performing the comparison, the feature extraction methods are categorised into feature subset selection methods and transformation methods. A transformation feature extraction method, namely PLS-DA, was found to perform consistently superior in terms of classification performance, while a feature subset selection method, namely Ranger, selected feature sets that were the most robust to sub-sampling in terms of consistently selecting the same features. As part of the benchmarking study, a generic pipeline has been created and made available as an R package to ensure reproducibility of the results and allow for easy extension of this study to other datasets.
Parchment Glutamine Index (PQI): A novel method to estimate glutamine deamidation levels in parchment collagen obtained from low-quality MALDI-TOF data
Authors: Nair Bharath , Palomo Ismael Rodríguez , Markussen Bo , Wiuf Carsten , Fiddyment Sarah , Collins Matthew James
Published: March 2022

Parchment was used as a writing material in the Middle Ages and was made using animal skins by liming them with Ca(OH)2. During liming, collagen peptides containing Glutamine (Q) undergo deamidation resulting in a mass shift of 0.984 Da. Assessing the extent of deamidation can inform us about parchment production patterns and quality. In this study, we propose a simple three-step workflow, developed as an R package called 'MALDIpqi()', to estimate deamidation in parchment derived collagen using low-resolution MALDI-TOF spectra. After pre-processing raw spectra, we used weighted least-squares linear regression to estimate Q deamidation levels from the convoluted isotopic envelope for seven collagen-peptide markers. Finally, we employed a linear mixed effect model to predict the overall deamidation level of a parchment sample termed the Parchment Glutamine Index (PQI). To test the robustness of the workflow, we applied MALDIpqi() to previously published ZooMS data generated from almost an entire library of the Cistercian monastery at Orval Abbey, Belgium. In addition to reliably predicting PQI, we observed interesting patterns pertaining to parchment production. MALDIpqi() holds excellent potential for biocodicological and other archaeological studies involving collagen, such as bone, but we also foresee its application in the food and biomedical industry.
Hippocampal theta and episodic memory
Authors: Rudoler Joseph H. , Herweg Nora A. , Kahana Michael J.
Published: March 2022

Computational models of rodent physiology implicate hippocampal theta as a key modulator of learning and memory (Buzsaki & Moser, 2013; J. E. Lisman & Jensen, 2013), yet human hippocampal recordings have shown divergent theta correlates of memory formation. Herweg et al. (2020) suggest that decreases in memory-related broadband power mask narrowband theta increases. Their survey also notes that theta’s role in memory appears strongest in contrasts that isolate retrieval processes and when aggregating signals across large brain regions. We evaluate these hypotheses by analyzing human hippocampal recordings captured as 162 neurosurgical patients (N= 86 female) performed a free recall task. Using the irregular-resampling auto-spectral analysis to separate broad and narrow-band components of the field potential we show: 1) Broadband and narrowband components of theta exhibit opposite effects, with broadband signals decreasing and narrow-band theta increasing during successful encoding; 2) Whereas low-frequency theta oscillations increase prior to successful recall, higher-frequency theta and alpha oscillations decrease, masking theta’s positive effect when aggregating across the full band; 3) Theta’s effects on memory encoding and retrieval do not differ between reference schemes that accentuate local signals (bipolar) and those that aggregate across large reference (whole brain average). In line with computational models that ascribe a fundamental role for hippocampal theta in memory, our large-scale study of human hippocampal recordings shows that 3-4 Hz theta oscillations reliably increase during successful memory encoding and prior to spontaneous recall of previously studied items.

Significance statement

Analyzing recordings from 162 patients we resolve a long-standing question regarding the role of hippocampal theta oscillations in the formation and retrieval of episodic memories. We show that broadband spectral changes confound estimates of narrowband theta activity, thereby accounting for inconsistent results in the literature. After accounting for broadband effects, we find that increased theta activity marks successful encoding and retrieval of episodic memories, supporting rodent models that ascribe a key role for hippocampal theta in memory function.
HIV-1 infection induces functional reprogramming of female plasmacytoid dendritic cells associated with enhanced TLR7 expression
Authors: Abbas Flora , Youness Ali , Azar Pascal , Cenac Claire , Delobel Pierre , Guéry Jean-Charles
Published: March 2022

Plasmacytoid dendritic cells (pDCs) express TLR7, a ssRNA-sensor encoded on the X chromosome, which escapes X chromosome inactivation (XCI) in females. pDCs are specialized in the production of type 1 interferons (IFN-I) through TLR7 activation which mediates both immune cell activation and also reactivation of latent HIV-1. The effect of HIV-1 infection in women under antiretroviral therapy (ART) on pDC functional responses remains poorly understood. Here, we show that pDCs from HIV/ART women exhibit exacerbated production of IFN-α and TNF-α as compared to uninfected controls (UC) upon TLR7-activation. Because TLR7 can escape XCI in female pDCs, we measured the contribution of TLR7 allelic expression using SNP haplotypic markers to rigorously tag the allele of origin of TLR7 gene at single cell resolution. Herein, we provide evidence that the functional reprogramming of pDCs in HIV/ART women is associated with enhanced transcriptional activity of the TLR7 locus from both X chromosomes, rather than differences in the frequency of TLR7 bi-allelic cells. These data reinforce the interest in targeting the HIV-1 reservoir using TLR7 agonists in women.
The French Early Breast Cancer Cohort (FRESH): a resource for breast cancer research and evaluations of oncology practices based on the French National Healthcare System Database (SNDS)
Authors: Dumas Elise , Laot Lucie , Coussy Florence , Rejo Beatriz Grandal , Daoud Eric , Laas Enora , Kassara Amyn , Majdling Alena , Kabirian Rayan , Jochum Floriane , Gougis Paul , Michel Sophie , Houzard Sophie , Le Bihan-Benjamin Christine , Bousquet Philippe-Jean , Hotton Judicaël , Azencott Chloé-Agathe , Reyal Fabien , Hamy Anne-Sophie
Published: March 2022

Background

Breast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death in women. The French National Cancer Institute has created a national cancer cohort to promote cancer research and improve our understanding of cancer using the National Health Data System (SNDS). This cohort amalgamates all cancer sites, with no detailed separate data for early BC.

Objectives

We describe the French Early Breast Cancer Cohort (FRESH).

Methods

All French women aged 18 years or over, with early-stage BC newly diagnosed between January 1, 2011 and December 31, 2017, treated by surgery and registered in the general health insurance coverage plan were included in the cohort. Patients with suspected locoregional or distant metastases at diagnosis were excluded. BC treatments (surgery, chemotherapy, targeted therapy, radiotherapy, endocrine therapy), and diagnostic procedures (biopsy, cytology, imaging) were extracted from hospital discharge reports, outpatient care notes or pharmacy drug delivery data. BC subtype was inferred from the treatments received.

Results

We included 235,368 patients with early BC in the cohort (median age: 60 years). BC subtype distribution was as follows: luminal (80.2%), triple-negative (TNBC, 9.5%); HER2+ (10.3%), or unidentifiable (n=44,388, 18.9% of the cohort). Most patients underwent radiotherapy (n=200,685, 85.3%) and endocrine therapy (n=165,655, 70.4%), and 38.3% (n=90,252) received chemotherapy. Treatments and care pathways are described.

Conclusion

The FRESH Cohort is an unprecedented population-based resource facilitating future large-scale real-life studies aiming to improve care pathways and quality of care for BC patients.
People underestimate the change of airborne Corona virus exposure when changing distance to an infected person: On interpersonal distance, exposure time, face masks and perceived virus exposure
Authors: Svenson Ola
Published: March 2022

Participants judged airborne Corona virus exposure following a change of inter-personal distance and time of a conversation with an infected person with and without a face mask. About 75% of the participants underestimated how much virus exposure changes when the distance to an infected person changed. The smallest average face to face distance from an infected person without a mask that a participant judged as sufficiently safe was about 12 feet (3.67 m). Correlations showed that the more a person underestimated the effects of change of distance on exposure the shorter was that person’s own safety distance. On average the effects of different lengths of a conversation on exposure were correct, but those who judged the effects of time as smaller tended to select longer safety distances. Worry of own COVID-19 infection correlated with protective behaviors: keeping longer safety distances, avoiding public gatherings, postponement of meetings with friends. The results showed that the protective effects of both distancing and wearing a face mask were under-estimated by a majority of the participants. Implications of these results were discussed last.
Super-spreaders of novel coronaviruses that cause SARS, MERS and COVID-19 : A systematic review
Authors: Brainard Julii , Jones Natalia R. , Harrison Florence , Hammer Charlotte C. , Lake Iain R.
Published: March 2022

OBJECTIVE

Most index cases with novel coronavirus infections transmit disease to just 1 or 2 other individuals, but some individuals ‘super-spread’ – they are infection sources for many secondary cases. Understanding common factors that super-spreaders may share could inform outbreak models.

METHODS

We conducted a comprehensive search in MEDLINE, Scopus and preprint servers to identify studies about persons who were each documented as transmitting SARS, MERS or COVID-19 to at least nine other persons. We extracted data from and applied quality assessment to eligible published scientific articles about super-spreaders to describe them demographically: by age, sex, location, occupation, activities, symptom severity, any underlying conditions and disease outcome. We included scientific reports published by mid June 2021.

RESULTS

The completeness of data reporting was often limited, which meant we could not identify traits such as patient age, sex, occupation, etc. Where demographic information was available, for these coronavirus diseases, the most typical super-spreader was a male age 40+. Most SARS or MERS super-spreaders were very symptomatic and died in hospital settings. In contrast, COVID-19 super-spreaders often had a very mild disease course and most COVID-19 super-spreading happened in community settings.

CONCLUSION

Although SARS and MERS super-spreaders were often symptomatic, middle- or older-age adults who had a high mortality rate, COVID-19 super-spreaders often had a mild disease course and were documented to be any adult age (from 18 to 91 years old). More outbreak reports should be published with anonymised but useful demographic information to improve understanding of super-spreading, super-spreaders, and the settings that super-spreading happens in.
Prospectively validated augmented intelligence for disease-agnostic predictions of clinical success for novel therapeutics
Authors: Lovetrue Bragi , Lovetrue Idonae
Published: March 2022

Standalone artificial intelligence has not alleviated the long-term bottleneck of linearly extracting new knowledge from exponentially growing biological data, which has severely limited clinical success rates for drug discovery. We developed a ‘virtual patient’ augmented intelligence model that functionally reconstructed human physiology and human pathogenesis for high-fidelity simulations of drug-body interactions. We examined the clinical utility of ‘virtual patient’ in prospective predictions of clinical efficacy and safety of novel therapeutics regardless of prior clinical data availability, through a 24- month, public, prospective, large-scale, unbiased, and real-world validation study. ‘Virtual patient’ achieved 90.1% sensitivity and 82.0% precision with a 99% confidence across all major therapeutic areas, representing its capability of discovering 90.1% of all possible drug-indication pairs that could bring clinical benefits to patients, and its potential of increasing tenfold the baseline clinical success rate from 7.9% to 82.0%. ‘Virtual patient’ represents a methodological shift of drug discovery especially for age-related diseases by doing away with animal experiments whose data are hard to reproduce, virtualizing human trials whose outcomes are doomed to failure, initiating human trials whose participants are likely to benefit, and reducing R&D cycles and costs while increasing clinical efficacy and safety.

One-Sentence Summary

A prospectively validated ‘virtual patient’ achieved a 10.4-fold improvement in the clinical success rate for new drugs across all major diseases with 99% confidence.
Dissecting neural computations of the human auditory pathway using deep neural networks for speech
Authors: Li Yuanning , Anumanchipalli Gopala K. , Mohamed Abdelrahman , Lu Junfeng , Wu Jinsong , Chang Edward F.
Published: March 2022

The human auditory system extracts rich linguistic abstractions from the speech signal. Traditional approaches to understand this complex process have used classical linear feature encoding models, with limited success. Artificial neural networks have recently achieved remarkable speech recognition performance and offer potential alternative computational models of speech processing. We used the speech representations learned by state-of-the-art deep neural network (DNN) models to investigate neural coding across the ascending auditory pathway from the peripheral auditory nerve to auditory speech cortex. We found that representations in hierarchical layers of the DNN correlated well to neural activity throughout the ascending auditory system. Unsupervised speech models achieve the optimal neural correlations among all models evaluated. Deeper DNN layers with context-dependent computations were essential for populations of high order auditory cortex encoding, and the computations were aligned to phonemic and syllabic context structures in speech. Accordingly, DNN models trained on a specific language (English or Mandarin) predicted cortical responses in native speakers of each language. These results reveal convergence between representations learned in DNN models and the biological auditory pathway and provide new approaches to modeling neural coding in the auditory cortex.
Discovery of a novel jingmenvirus in Australian sugarcane Soldier fly (Inopus flavus) larvae
Authors: Colmant Agathe M.G. , Furlong Michael , Etebari Kayvan
Published: March 2022

In Australia, soldier flies are major pests of sugarcane, and they can cause significant yield losses in some areas, possibly due to virus transmission to the plants. We sequenced fly larvae salivary glands and identified a novel jingmenvirus, putatively named Inopus flavus jingmenvirus 1 (IFJV1). Phylogenetic trees confirmed that IFJV1 groups with insect-associated jingmenviruses, newly identified flavivirus-like viruses with a segmented genome. After the design and validation of molecular detection systems for IFJV1, larval homogenates were passaged on insect and vertebrate cells but IFJV1 could only be detected in the first two passages in insect cells and not at all in vertebrate cells. Despite this lack of consistent replication in laboratory models, this virus does replicate in its host Inopus flavus, as sequenced small RNA from larvae match the IFJV1 sequences, are predominantly 21 nucleotides-long and map to the whole sequences on both strands, which is typical of an actively replicating virus. This discovery confirms the worldwide presence of jingmenviruses, which until now had only been detected on four continents. However, the study of IFJV1 tropism and of the possible pathogenicity to its host or the sugarcane it parasitizes requires the development of a stable replication model.
Transcriptome profiling of barley and tomato shoot and root meristems unravels physiological variations underlying photoperiodic sensitivity
Authors: Schneider Michael , Vedder Lucia , Oyiga Benedict Chijioke , Mathew Boby , Schoof Heiko , Léon Jens , Naz Ali Ahmad
Published: March 2022

The average sowing date of crops in temperate climate zones has been shifted forwards by several days, resulting in a changed photoperiod regime at the emergence stage. In the present study, we performed a global transcriptome profiling of plant development genes in the seedling stage of root and shoot apical meristems of a photoperiod-sensitive species (barley) and a photoperiod insensitive species (tomato) in short-day conditions (8h). Variant expression indicated differences in physiological development under this short day-length regime between species and tissues. The barley tissue transcriptome revealed reduced differentiation compared to tomato. In addition, decreased photosynthetic activity was observed in barley, indicating a slower physiological development of shoot meristems than in tomatoes. The photomorphogenesis controlling cryptochrome gene cry1, with an effect on physiological differentiation, showed an underexpression in barley compared to tomato shoot meristems. This might lead to a cascade of suspended sink-source activities, which ultimately delay organ development and differentiation in barley shoot meristems under short photoperiods.
TNIP1 inhibits Mitophagy via interaction with FIP200 and TAX1BP1
Authors: Le Guerroué François , Werner Achim , Wang Chunxin , Youle Richard
Published: March 2022

Mitophagy is a form of selective autophagy that disposes of superfluous and potentially damage-inducing organelles in a tightly controlled manner. While the machinery involved in mitophagy induction is well known, the regulation of the components is less clear. For example, it is still unknown how the ULK1 complex is dissociated prior to closing of the autophagosome. Here, using Chemically Inducible Dimerization (CID) and mitophagy assays with the fluorescent probe mtKeima, we reveal that the ubiquitin binding domain-containing protein TNIP1 is able to induce mitophagy when ectopically targeted to mitochondria. Conversely, we demonstrate that TNIP1 knock down accelerates mitophagy rates, and that ectopic TNIP1 negatively regulates the rate of mitophagy. These functions of TNIP1 depend on a previously unrecognized, evolutionarily conserved LIR motif as well as its AHD3 domain, which are required for binding to the ULK1 complex member FIP200 and the autophagy receptor TAX1BP1, respectively. Taken together, our findings identify a novel negative regulator of mitophagy that acts at the early steps of autophagosome biogenesis and provide a molecular rationale for how the ULK1 complex might be dissociated from the closing autophagosome.
Expression and Purification of BsaXI Restriction Endonuclease and Engineering New Specificity from BsaXI Specificity (S) Subunit
Authors: Gidwani Sonal , Heiter Daniel , Xu Shuang-yong
Published: March 2022

BsaXI is a Type IIB restriction endonuclease (REase) that cleaves both sides of its recognition sequence 5’ ↓N9 AC N5 CTCC N10↓ 3’ (complement strand 5’ ↓N7 GGAG N5 GT N12↓ 3’), creating 3-base 3’ overhangs. Here we report the cloning and expression of bsaXIS and bsaXIRM genes in E. coli. BsaXI activity was successfully reconstituted by mixing the BsaXI RM fusion subunit with the BsaXI S subunit and the enzyme complex further purified by chromatography over 6 columns. As expected, the S subunit consisted of two subdomains encoding TRD1-CR1 (TRD, target recognition domain, CR, conserved region) for 5’ AC 3’, and TRD2-CR2 presumably specifying 5’ CTCC 3’. TRD1-CR1 (TRD2-CR2 deletion) or duplication of TRD1 (TRD1-CR1-TRD1-CR2) both generated a new specificity 5’ AC N5 GT 3’ when the S variants were complexed with the RM subunits. Circular permutation of TRD1 and TRD2, i.e. relocation of TRD2-CR2 to the N-terminus and TRD1-CR1 to the C-terminus generated the same specificity with the RM subunits, although some wobble cleavage was detected. The TRD2 domain in the BsaXI S subunit can be substituted by a close homolog (∼59% sequence identity) and generated the same specificity. However, TRD2-CR2 domain alone failed to express in E. coli, but CR1-TRD2-CR2 protein could be expressed and purified which showed partial nicking activity with the RM subunits. This work demonstrated that like Type I restriction systems, the S subunit of a Type IIB system could also be manipulated to create new specificities. Genome mining of BsaXI TRD2 homologs in GenBank found more than 36 orphan TRD2 homologs, implying that quite a few orphan TRD2s are present in microbial genomes that may be potentially paired with other TRDs to create new restriction specificities.
Individual neurophysiological signatures of spontaneous rhythm processing
Authors: Criscuolo A. , Schwartze M. , Henry M.J. , Obermeier C. , Kotz S.A.
Published: March 2022

When sensory input conveys rhythmic regularity, we can form predictions about the timing of upcoming events. Although rhythm processing capacities differ considerably between individuals, these differences are often obscured by participant- and trial-level data averaging procedures in M/EEG research. Here, we systematically assessed the neurophysiological variability displayed by individuals listening to isochronous equitone sequences interspersed with unexpected deviant tones. We first focused on rhythm tracking and tested the anticipatory phase alignment of delta-band activity to expected tone onsets. These analyses confirmed that individuals encode temporal regularities and form temporal predictions, but highlight clear inter- and intra-participant variability. This observation may indicate individual and flexible tracking mechanisms, which show consistency at the single-trial level, but variability over trials. We then modelled single-trial time-locked neural responses in the beta-band to investigate individual tendencies to spontaneously employ binary grouping (“tic-toc effect”). This approach identified binary (strong-weak), ternary (strong-weak-weak), and mixed accentuation patterns, confirming the superimposition of a basic beat pattern. Furthermore, we characterized individual grouping preferences and tendencies to use binary, ternary, or combined patterns over trials. Importantly, the processing of standard and deviant tones was modulated by the employed pattern. The current approach supports individualized neurophysiological profiling as a sensitive strategy to identify dynamically evolving neural signatures of rhythm and beat processing. We further suggest that close examination of neurophysiological variability is critical to improve our understanding of the individual and flexible mechanisms underlying the capacities to rapidly evaluate and adapt to environmental rhythms.

Significance statement

For decades, music, speech and rhythm research investigated how humans process, predict, and adapt to environmental rhythms. By adopting a single-trial and -participant approach, we avert the common pooling of EEG data in favor of individual time-varying neural signatures of rhythm tracking and beat processing. The results highlight large inter- and intra-individual differences in rhythm tracking, arguing against the typically documented phase-specificity for entrainment. On top of that, we characterize individual variability in beat processing, by showing that binary, ternary and other accentuation patterns are used over time, and ultimately affect the processing of (un-)expected auditory events. The approach aids individual neural profiling and may therefore allow identifying altered neural activity and its consequences in natural listening contexts.
Altered integration of excitatory inputs onto the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X Syndrome
Authors: Mitchell Diana E. , Miranda-Rottmann Soledad , Blanchard Maxime , Araya Roberto
Published: March 2022

To uncover how synaptic integration of feedforward sensory inputs is affected in autism spectrum disorders (ASD), we used two-photon uncaging of caged glutamate to activate two clustered spines in the basal dendrites of layer 5 (L5) pyramidal neurons from a mouse model of Fragile X syndrome (FXS), the most common genetic cause of ASD. While subthreshold excitatory inputs integrate linearly in wild-type animals, surprisingly those with FXS summate sublinearly, contradicting what would be expected of a hyperexcitable cortex typically associated with ASD. Knockdown of the regulatory β4 subunit of BK channels, rescues the synaptic integration, a result that was corroborated with numerical simulations. Taken together, these findings suggest that there is a differential impairment in the integration of feedforward sensory and feedback predictive inputs in L5 pyramidal neurons in FXS and potentially other forms of ASD. These results challenge the traditional view that FXS and other ASD are characterized by sensory hypersensitivity, but instead by hyposensitivity of sensory inputs and hypersensitivity of predictive inputs onto cortical neurons.
Single-cell Total RNA Miniaturized sequencing (STORM-seq) reveals differentiation trajectories of primary human fallopian tube epithelium
Authors: Johnson Benjamin K. , Rhodes Mary , Wegener Marc , Himadewi Pamela , Foy Kelly , Schipper Joshua L. , Siwicki Rebecca A. , Rossell Larissa L. , Siegwald Emily J. , Chesla Dave W. , Teixeira Jose M. , Sheridan Rachael T. C. , Adams Marie , Triche Timothy J. , Shen Hui
Published: March 2022

We present Single-cell TOtal RNA Miniaturized sequencing (STORM-seq), a full-length single-cell ribo-reduced RNA sequencing protocol, optimized to profile thousands of cells per run. Using off-the-shelf reagents and random hexamer priming, STORM-seq recovers comprehensive RNA profiles from single cells with library complexity approaching that of bulk RNA-seq. Importantly, STORM-seq does not require specialized equipment and can be performed using standard lab equipment. STORM-seq identifies thousands of additional coding and non-coding transcripts not detected by existing methods, and recovers clinically relevant structural variants at the single-cell level. We apply STORM-seq to primary human fallopian tube epithelium (FTE), a complex solid tissue key to both human reproductive biology and ovarian carcinogenesis. In differentiation trajectory analyses, the improved resolution from STORM-seq reveals intermediate/transitional cell states, and a putative progenitor cell population. The results support a trajectory from a bipotent progenitor population to ciliated and secretory cell types in normal FTE. These findings are consistent across human subjects, sequencing depths, and platforms. Long intergenic non-coding RNAs (lincRNAs) appear as key driver genes in both ciliated and secretory lineage trajectories, underscoring the importance of both coding and non-coding RNA in this tissue. By capturing essentially complete individual cellular transcriptomes, STORM-seq sheds new light on the transcriptional programs that establish cellular state and fate in complex tissues.
Mitochondrial Redox Adaptations Enable Aspartate Synthesis in SDH-deficient Cells
Authors: Hart Madeleine L. , Quon Evan , Vigil Anna-Lena B. G. , Engstrom Ian A. , Newsom Oliver J. , Davidsen Kristian , Hoellerbauer Pia , Carlisle Samantha M. , Sullivan Lucas B.
Published: March 2022

The oxidative tricarboxylic acid (TCA) cycle is a central mitochondrial pathway integrating catabolic conversions of NAD+ to NADH and anabolic production of aspartate, a key amino acid for cell proliferation. Several TCA cycle components are implicated in tumorigenesis, including loss of function mutations in subunits of succinate dehydrogenase (SDH), also known as complex II of the electron transport chain (ETC). Mechanistic understanding of how proliferating cells tolerate the metabolic defects of SDH loss is still lacking. Here, we identify that SDH supports cell proliferation through aspartate synthesis but, unlike other ETC impairments, is not restored by electron acceptor supplementation. Interestingly, we find aspartate production and cell proliferation are restored to SDH impaired cells by concomitant inhibition of ETC complex I (CI). We determine that the benefits of CI inhibition in this context are dependent on decreasing mitochondrial NAD+/NADH, which drives SDH-independent aspartate production. We also find that genetic loss or restoration of SDH selects for cells with concordant CI activity, establishing distinct modalities of mitochondrial metabolism for maintaining aspartate synthesis. Collectively, these data identify a metabolically beneficial mechanism for CI loss in proliferating cells and reveal that compartmentalized redox changes can impact cellular fitness.
Structural basis of Omicron immune evasion: A comparative computational study of Spike protein-Antibody interaction
Authors: Contractor Darshan , Globisch Christoph , Swaroop Shiv , Jain Alok
Published: March 2022

The COVID-19 pandemic has caused more than 424 million infections and 5.9 million deaths so far. The vaccines used against SARS-COV-2 by now have been able to develop some neutralising antibodies in the vaccinated human population and slow down the infection rate. The effectiveness of the vaccines has been challenged by the emergence of the new strains with numerous mutations in the spike (S) protein of SARS-CoV-2. Since S protein is the major immunogenic protein of the virus and also contains Receptor Binding Domain (RBD) that interacts with the human Angiotensin-Converting Enzyme 2 (ACE2) receptors, any mutations in this region should affect the neutralisation potential of the antibodies leading to the immune evasion. Several variants of concern (VOC) of the virus have emerged so far. Among them, the most critical are Delta (B.1.617.2), and recently reported Omicron (B. 1.1.529) which have acquired a lot of mutations in the spike protein. We have mapped those mutations on the modelled RBD and evaluated the binding affinities of various human antibodies with it. Docking and molecular dynamics simulation studies have been used to explore the effect of the mutations on the structure of the RBD and the RBD-antibody interaction. The analysis shows that the mutations mostly at the interface of a nearby region lower the binding affinity of the antibody by ten to forty per cent, with a downfall in the number of interactions formed as a whole and therefore, it implies the generation of immune escape variants. Notable mutations and their effect was characterised by performing various analyses that explain the structural basis of antibody efficacy in Delta and a compromised neutralisation effect for the Omicron variant. Our results pave the way for robust vaccine design that can be effective for many variants.

Graphical Abstract

Synopsis

The research study utilises comparative docking and MD simulations analyses to illustrate how mutations in delta and omicron variants affect the binding of antibodies to the spike receptor binding domain (RBD) of SARS CoV-2.
Crystal structure of cis-7,8-dihydroxy-5,10,15,20-tetraphenylchlorin and its zinc(II)–ethylenediamine complex
Authors: Chaudhri Nivedita , Brückner Christian , Zeller Matthias
Published: March 2022

The title chlorin, 2PhH2
, hydrogen-bonded to dimethylaminopyridine (DMAP), C44H32N4O2·C7H10N2, and its corresponding zinc(II) complex, 2PhZn, axially coordinated to ethylenediamine (EDA), [Zn(C44H30N4O2)]·C2H8N2, were isolated and crystallized by adventitious reduction of the corresponding osmate esters by DMAP and EDA, respectively. Known since 1996 and, inter alia, used for the preparation of a wide range of (planar and non-planar) chlorin analogues (so-called pyrrole-modified porphyrins), their conformational analyses in the solid state are important benchmarks. Both macrocycles are only modestly distorted from planarity and both are slightly more non-planar than the corresponding dimethoxy-derivative, but less planar than a free-base meso-pentafluorophenyl-based osmate ester. NSD analyses provide quantitative and qualitative analyses of the distortion modes. One origin of the non-planarity is presumably the avoidance of the eclipsed configuration of the two vic–cis diols on the pyrroline moiety; the resulting deformation of the pyrroline translates in some cases into the macrocycle. The structure of 2PhH2
features voids making up ca 26% of the unit-cell volume filled with highly disordered solvate molecules (chloroform and hexanes). 2PhZn crystallized with a 13.6 (4)% occupied solvate methanol molecule.
Application of machine learning in predicting pitting corrosion – electrochemical data around the open circuit potential
Authors: Boucherit Mohamed Nadir , Amzert Sid Ahmed , Arbaoui Fahd
Published: March 2022

Purpose

The purpose of this study is to confirm the idea that observing the electrochemical data of a steel polarized around its open circuit potential can provide insight into its performance against pitting corrosion. To confirm this idea a two-step work was carried out. The authors collected electrochemical data through experiments and exploited them through machine learning by building neural networks capable of predicting the behaviour of the steel against the pitting corrosion.

Design/methodology/approach

The electrochemical experiments consist in plotting voltammograms of the steel in chemical solutions of various degrees of corrosiveness. For each experiment, the authors observe how the open-circuit potential evolves over a period of 1 min, and following this, the authors observe the current evolution when they impose a potential scan that starts from the open-circuit potential. For each of these situations, the pitting potential Epit is noted. The authors then build different artificial neural networks, which after learning, can, by receiving electrochemical data, calculate a pitting potential Epit′. The performance of the neural networks is evaluated by the correlation of Epit and Epit′.

Findings

Through this work, different types of networks were compared. The results show that recurrent or convolutional networks can better capture the temporal nature of the input data.

Originality/value

The results of this work support the idea that the measurable electrochemical data around the free potential of a material can be correlated with its behaviour at more anodic potentials, particularly the initiation of pits.
Horizontal collaboration in the last mile distribution: gauging managerial response to disruption and abnormal demand
Authors: Argyropoulou Maria , Zissis Dimitris , Korfiatis Nikolaos , Zampou Eleni
Published: March 2022

Purpose

Last mile distribution is a crucial element of any supply chain network, and its complexity has challenged established practices and frameworks in the management literature. This is particularly evident when demand surges, as with recent lockdowns due to the COVID-19 pandemic and subsequent demand for home delivery services. Given the importance of this critical component, this study recommends horizontal collaboration as a possible solution for retailers seeking to improve the quality of their services.

Design/methodology/approach

This study investigates whether horizontal collaboration should be considered as an option for faster and greener distribution of groceries ordered online. Using the United Kingdom and Greek grocery markets that differ in terms of online grocery penetration, distribution network structure and delivery times, the study discusses how the effectiveness of pooling resources can create positive spillover effects for consumers, businesses and society.

Findings

Despite their differences, both markets indicate the need for horizontal collaboration in the highly topical issue of last mile delivery.

Originality/value

Taking a theoretical and practical view in cases of disruption and constant pressure in last mile distribution, horizontal collaboration supports retailers to coordinate routes, increase fleet and vehicle utilisation, reduce traffic and carbon emissions while improving customer satisfaction.
The impact of supply chain specific investments on firms’ market performance: the mediating role of innovation
Authors: Huo Baofeng , Guo Mengqiu , Tian Min
Published: March 2022

Purpose

Manufacturers’ specific investments (SIs) in a specific partner that are of lower value when used in an alternative relationship, such as training employees and tailoring systems to achieve better cooperation, can help improve market performance. However, previous studies lack a simultaneous focus on a manufacturer’s SIs in its upstream and downstream partners. The purpose of this study is to address the effects of manufacturers’ SIs in their suppliers and customers on the two types of innovation and market performance individually and jointly and the mediating effects of radical and incremental innovation on relationships between SIs and market performance.

Design/methodology/approach

This study tests proposed relationships based on data collected from 206 manufacturers in China using regression methods.

Findings

Results show that SIs in customers directly and indirectly affect market performance through radical and incremental innovation. However, SIs in suppliers cannot directly improve market performance but indirectly enhance market performance through radical innovation. Furthermore, results also show the interaction of SIs in suppliers and customers is positively related to market performance and radical innovation.

Originality/value

This study contributes to the literature on SIs by identifying supply chain SIs (SCSIs) through simultaneously focusing on SIs in suppliers and customers and exploring the direct and indirect effects of SCSIs on market performance. This study also contributes to the innovation literature by empirically verifying incremental and radical innovation as effective intermediaries that help convert SIs into the actual performance improvement.
Get to know me, homey: exploring critical, relational and racial literacy possibilities in co-excavative letter writing
Authors: Bell Jordan , Zaino Karen
Published: March 2022

Purpose

There is currently a dearth of research on the implications of the epistolary as a site for knowledge production. This paper aims to demystify the process of academic theorizing through the co-authors’ co-excavative epistolary method.

Design/methodology/approach

Through co-excavative epistolary practices, the co-authors’ relationship was deepened, the collective sense was made of Covid-19, and racial literacy-centered academic theorizing commenced. In the co-authors making meaning of their letter-writing data, they provide examples of and analyze their co-excavative letter-writing process.

Findings

The co-excavative epistolary method deepened the co-authors’ relationship to one another and improved their ability to produce useful and complicated knowledge.

Research limitations/implications

The co-excavative epistolary exchanges mark a new site for academic theorizing and incite creative approaches to academic co-writing, as well as more transparency about the academic writing process in general.

Social implications

Co-excavative methods disrupt traditional academic sites of knowledge production and engender space for relational intimacy.

Originality/value

The work introduces both a new method, co-excavative epistolary writing and a new rational framework, the critical dignity relational framework.
Luxury fashion consumption: a review, synthesis and research agenda
Authors: Aleem Aihoor , Loureiro Sandra Maria Correia , Bilro Ricardo Godinho
Published: March 2022

Purpose

This paper aims to review the topic of “luxury fashion consumption”, a field of recent interest for academics and practitioners. However, a literature review that can map the existing knowledge and aggregate it into relevant topics and offers a research agenda for future research is still lacking.

Methodology

This paper uses a systematic review and a text mining approach to analyse 73 articles on luxury fashion consumption aiming to clarify, rationalise and critically interpret the literature on luxury fashion consumption; identify the core topic, create an integrative framework of core constructs; and offer research gaps and suggest a research agenda for future studies.

Findings

From this analysis, eight major research topics are found and analysed (brand desire, authenticity, luxury markets, value perceptions, luxury retail experience, luxury brands communication, responsible consumption and sustainability and status signalling). Based on these topics and following the TCM framework, this review offers directions for future research.

Value

This research offers a text-mining review of luxury fashion consumption to help scholars and managers further develop this field, as there is no comprehensive review on the topic exploring the themes, theories, constructs and methods used in prior studies.
Structural behavior of small-scale reinforced concrete secant pile wall
Authors: El-Nimr Maher Taha , Basha Ali Mohamed , Abo-Raya Mohamed Mohamed , Zakaria Mohamed Hamed
Published: March 2022

Purpose

To predict the real behavior of the full-scale model using a scale model, optimized simulation should be achieved. In reinforced concrete (RC) models, scaling can be substantially more critical than in single-material models because of multiple reasons such as insufficient bonding strength between small-diameter steel bars and concrete, and excessive aggregate size. Overall, there is a shortfall of laboratory and field-testing studies on the behavior of secant pile walls under lateral and axial loads. Accordingly, the purpose of this study is to investigate the validity and the performance of the 1/10th scaled RC secant pile wall under the influence of different types of loading.

Design/methodology/approach

The structural performance of the examined models was evaluated using two types of tests: bending and axial compression. A self-compacting concrete mix was suggested, which provided the best concrete mix workability and appropriate compressive strength.

Findings

Under axial and bending loads, the failure modes were typical. Where the plain and reinforced concrete piles worked in tandem to support the load throughout the loading process, even when they failed. The experimental results were relatively consistent with some empirical equations for calculating the modulus of elasticity and critical buckling load. This confirmed the validity of the proposed model.

Originality/value

According to the analysis and verification of experimental tests, the proposed 1/10th scaled RC secant pile model can be used for future laboratory purposes, especially in the field of geotechnical engineering.
Measuring the Trustworthiness of Health Care Organizations and Systems
Authors: ANDERSON ANDREW , GRIFFITH DEREK M.
Published: March 2022

Policy Points

Current efforts to measure and improve trust in health care focus on changing patients’ attitudes rather than measuring and improving the trustworthiness of health care organizations and systems.

We present a conceptual model to understand and explain the constructs of trust and trustworthiness in the context of health care through the application of existing theories of human behavior.

Developing and publicly reporting measures that can enable patients, particularly from historically marginalized groups, to better assess the trustworthiness of providers is necessary to promote health care equity.
Cross‐species conservation of a transposase‐linked element enables genetic sexing of commercial populations of Russian sturgeon (Acipenser gueldenstaedtii)
Authors: Curzon Arie Y. , Shirak Andrey , Meerson Ari , Degani Gad , Hurvitz Avshalom , Ben‐Naim Naama , Domovitz Roee , Ron Micha , Seroussi Eyal
Published: March 2022

All‐female culture of sturgeon is essential for efficient caviar production. However, Russian sturgeon (Acipenser gueldenstaedtii) does not exhibit external sexual dimorphism, and therefore, commercial farms apply gonadal endoscopy or ultrasound at the earliest age of 4–5 years to separate the sexes, with ~90% accuracy. Recently, a dominant genomic marker (AllWSEX2) has been found with association to femaleness in sturgeons. We developed a duplex PCR (dAllWSEX2) with the adjacent bmp7 gene as an internal control, to validate an effective PCR. Robust amplification of control fragments was observed for all samples of our commercial A. gueldenstaedtii stock (n = 337). The dAllWSEX2 assay was significantly associated with sex (n = 43, p < 1.6 × 10−8), yet four (18%) of the endoscopy‐determined females were genetic males. To examine whether some females display a male genetic profile, we tested 96 egg‐producing females, which were all verified as genetic females, indicating that the observed mismatches may be attributed to wrong sexing by endoscopy. Application of dAllWSEX2 on 100 7‐month‐old fish showed no sex‐dependent differences in body weight, indicating that weighing is not an applicable tool for sorting females at a young age. Sanger sequencing of the bmp7 fragment revealed octaploidy and sex‐independent variation, suggesting that the critical sex‐determining region harboring AllWSEX2 is small. In keeping with a model of a single‐ploidy encoding female determination, AllWSEX2 showed no variation despite being a transposase‐linked repetitive element. Cross‐species conservation of AllWSEX2, and absence of annotated sex‐determination genes in this region suggests that, in sturgeons, the sex‐determining mechanism is different from mechanisms identified in other fish.