bluuebunny/crossref_metadata_2025 huggingface dataset:
Unified classification of mouse retinal ganglion cells using function, morphology, and gene expression
Authors: Goetz Jillian , Jessen Zachary F. , Jacobi Anne , Mani Adam , Cooler Sam , Greer Devon , Kadri Sabah , Segal Jeremy , Shekhar Karthik , Sanes Joshua , Schwartz Gregory W.
Published: June 2021

Classification and characterization of neuronal types are critical for understanding their function and dysfunction. Neuronal classification schemes typically rely on measurements of electrophysiological, morphological, and molecular features, but aligning such datasets has been challenging. Here, we present a unified classification of mouse retinal ganglion cells (RGCs), the sole retinal output neurons. We used visually-evoked responses to classify 1859 mouse RGCs into 42 types. We also obtained morphological or transcriptomic data from subsets and used these measurements to align the functional classification to publicly available morphological and transcriptomic data sets. We created an online database that allows users to browse or download the data and to classify RGCs from their light responses using a machine learning algorithm. This work provides a resource for studies of RGCs, their upstream circuits in the retina, and their projections in the brain, and establishes a framework for future efforts in neuronal classification and open data distribution.
Development of the Wheat Practical Haplotype Graph Database as a Resource for Genotyping Data Storage and Genotype Imputation
Authors: Jordan Katherine W. , Bradbury Peter J. , Miller Zachary R. , Nyine Moses , He Fei , Fraser Max , Anderson Jim , Mason Esten , Katz Andrew , Pearce Stephen , Carter Arron H. , Prather Samuel , Pumphrey Michael , Chen Jianli , Cook Jason , Liu Shuyu , Rudd Jackie C. , Wang Zhen , Chu Chenggen , Ibrahim Amir M. H. , Turkus Jonathan , Olson Eric , Nagarajan Ragupathi , Carver Brett , Yan Liuling , Taagen Ellie , Sorrells Mark , Ward Brian , Ren Jie , Akhunova Alina , Bai Guihua , Bowden Robert , Fiedler Jason , Faris Justin , Dubcovsky Jorge , Guttieri Mary , Brown-Guedira Gina , Buckler Ed , Jannink Jean-Luc , Akhunov Eduard D.
Published: June 2021

To improve the efficiency of high-density genotype data storage and imputation in bread wheat (Triticum aestivum L.), we applied the Practical Haplotype Graph (PHG) tool. The wheat PHG database was built using whole-exome capture sequencing data from a diverse set of 65 wheat accessions. Population haplotypes were inferred for the reference genome intervals defined by the boundaries of the high-quality gene models. Missing genotypes in the inference panels, composed of wheat cultivars or recombinant inbred lines genotyped by exome capture, genotyping-by-sequencing (GBS), or whole-genome skim-seq sequencing approaches, were imputed using the wheat PHG database. Though imputation accuracy varied depending on the method of sequencing and coverage depth, we found 93% imputation accuracy with 0.01x sequence coverage, which was only slightly lower than the accuracy obtained using the 0.5x sequence coverage (96.9%). Compared to Beagle, on average, PHG imputation was ~4% (p-value = 0.00027) more accurate, and showed 27% higher accuracy at imputing a rare haplotype introgressed from a wild relative into wheat. The reduced accuracy of imputation with GBS data (90.4%) is likely associated with the small overlap between GBS markers and the exome capture dataset, which was used for constructing PHG. The highest imputation accuracy was obtained with exome capture for the wheat D genome, which also showed the highest levels of linkage disequlibrium and proportion of identity-by-descent regions among accessions in our reference panel. We demonstrate that genetic mapping based on genotypes imputed using PHG identifies SNPs with a broader range of effect sizes that together explain a higher proportion of genetic variance for heading date and meiotic crossover rate compared to previous studies.
A reference-quality, fully annotated genome from a Puerto Rican individual
Authors: Zimin Aleksey , Shumate Alaina , Shinder Ida , Heinz Jakob , Puiu Daniela , Pertea Mihaela , Salzberg Steven L.
Published: June 2021

Until 2019, the human genome was available in only one fully-annotated version, GRCh38, which was the result of 18 years of continuous improvement and revision. Despite dramatic improvements in sequencing technology, no other genome was available as an annotated reference until 2019, when the genome of an Ashkenazi individual, Ash1, was released. In this study, we describe the assembly and annotation of a second individual genome, from a Puerto Rican individual whose DNA was collected as part of the Human Pangenome project. The new genome, called PR1, is the first true reference genome created from an individual of African descent. Due to recent improvements in both sequencing and assembly technology, and particularly to the use of the recently completed CHM13 human genome as a guide to assembly, PR1 is more complete and more contiguous than either GRCh38 or Ash1. Annotation revealed 37,755 genes (of which 19,999 are protein-coding), including 12 additional gene copies that are present in PR1 and missing from CHM13. 57 genes have fewer copies in PR1 than in CHM13, 9 map only partially, and 3 genes (all non-coding) from CHM13 are entirely missing from PR1.
Using networks to analyze and visualize the distribution of overlapping reading frames in virus genomes
Authors: Muñoz-Baena Laura , Poon Art F. Y.
Published: June 2021

Gene overlap occurs when two or more genes are encoded by the same nucleotides. This phenomenon is found in all taxonomic domains, but is particularly common in viruses, where it may increase the information content of compact genomes or influence the creation of new genes. Here we report a global comparative study of overlapping reading frames (OvRFs) of 12,609 virus reference genomes in the NCBI database. We retrieved metadata associated with all annotated reading frames in each genome record to calculate the number, length, and frameshift of OvRFs. Our results show that while the number of OvRFs increases with genome length, they tend to be shorter in longer genomes. The majority of overlaps involve +2 frameshifts, predominantly found in ds-DNA viruses. However, the longest overlaps involve no shift in reading frame (+0), increasing the selective burden of the same nucleotide positions within codons, instead of exposing additional sites to purifying selection. Next, we develop a new graph-based representation of the distribution of OvRFs among the reading frames of genomes in a given virus family. In the absence of an unambiguous partition of reading frames by homology at this taxonomic level, we used an alignment-free k-mer based approach to cluster protein coding sequences by similarity. We connect these clusters with two types of directed edges to indicate (1) that constituent reading frames are adjacent in one or more genomes, and (2) that the reading frames overlap. These adjacency graphs not only provide a natural visualization scheme, but also a novel statistical framework for analyzing the effects of gene- and genome-level attributes on the frequencies of overlaps.
Towards rainy high Arctic winters: how ice-encasement impacts tundra plant phenology, productivity and reproduction
Authors: Le Moullec Mathilde , Hendel Anna-Lena , Petit Bon Matteo , Jónsdóttir Ingibjörg Svala , Varpe Øystein , van der Wal René , Beumer Larissa Teresa , Layton-Matthews Kate , Isaksen Ketil , Hansen Brage Bremset
Published: June 2021

The Arctic is warming rapidly, with winters warming up to seven times as fast as summers in some regions. Warm spells in winter lead to more frequent extreme rain-on-snow events that alter snowpack conditions and can encapsulate tundra vegetation in ‘basal ice’ (‘icing’) for several months. However, tundra climate change studies have mainly focused on summer warming. Here, we investigate icing effects on vascular plant phenology, productivity, and reproduction in a pioneer field experiment in high Arctic Svalbard, simulating rain-on-snow and resultant icing in five consecutive winters, assessing vascular plant responses throughout each subsequent growing season. We also tested whether icing responses were modified by experimentally increased summer temperatures. Icing alone delayed early phenology of the dominant shrub,Salix polaris, but with evidence for a ‘catch-up’ (through shortened developmental phases and increased community-level primary production) later in the growing season. This compensatory response occurred at the expense of delayed seed maturation and reduced community-level inflorescence production. Both the phenological delay and allocation trade-offs were associated with icing-induced lags in spring thawing and warming of the soil, crucial to regulating plant nutrient availability and acquisition. Experimental summer warming modified icing effects by advancing and accelerating plant phenology (leaf and seed development), thus increasing primary productivity already early in the growing season, and partially offsetting negative icing effects on reproduction. Thus, winter and summer warming must be considered simultaneously to predict tundra plant climate change responses. Our findings demonstrate that winter warm spells can shape high Arctic plant communities to a similar level as summer warming. However, the absence of accumulated effects over the years reveals an overall resistant community which contrasts with earlier studies documenting major die-off. As rain-on-snow events will be rule rather than exception in most Arctic regions, we call for similar experiments in coordinated circumpolar monitoring programmes across tundra plant communities.
Consciousness is supported by near-critical cortical electrodynamics
Authors: Toker Daniel , Pappas Ioannis , Lendner Janna D. , Frohlich Joel , Mateos Diego M. , Muthukumaraswamy Suresh , Carhart-Harris Robin , Paff Michelle , Vespa Paul M. , Monti Martin M. , Sommer Friedrich T. , Knight Robert T. , D’Esposito Mark
Published: June 2021

Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition, and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, for the first time, we empirically identify the specific critical point near which conscious cortical dynamics operate as the edge-of-chaos critical point, or the boundary between periodicity/stability and chaos/instability. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magne-toencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, GABAergic anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of cortical dynamics away from this critical point; conversely, we show that psychedelics may increase the information-richness of cortical activity by tuning cortical electrodynamics closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC), and show that assessing the proximity of cortical electrodynamics to the edge-of-chaos critical point may be clinically useful as a new biomarker of consciousness.

Significance Statement

What changes in the brain when we lose consciousness? One possibility is that the loss of consciousness corresponds to a transition of the brain’s electric activity away from edge-of-chaos criticality, or the knife’s edge in between stability and chaos. Recent mathematical developments have produced novel tools for testing this hypothesis, which we apply for the first time to cortical recordings from diverse brain states. We show that the electric activity of the cortex is indeed poised near the boundary between stability and chaos during conscious states and transitions away from this boundary during unconsciousness, and that this transition disrupts cortical information processing.
Solute carrier 5A5 regulates systemic glucose homeostasis by mediating glucose absorption in the Drosophila midgut
Authors: Li Yue , Wang Weidong , Lim Hui-Ying
Published: June 2021

The small intestine is the first organ that is exposed to and absorbs dietary glucose and thus represents the first of a continuum of events that modulates normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in curbing metabolic disorders. However, so far, the mechanisms known to regulate SGLT1, the primary intestinal glucose transporter, are mainly elucidated from in vitro studies. The Drosophila midgut, functional equivalence of the small intestine, could serve as an efficient in vivo model system for studying intestinal glucose transporter regulation; however, no glucose transporter has yet been identified in the midgut. Here, we report that the Drosophila Solute Carrier 5A5 (dSLC5A5) is homologous to SGLT1 and is highly expressed in the midgut. The knockdown of dSLC5A5 decreases systemic and circulating sugar levels and decreases glucose uptake into the enterocytes. In contrary, the overexpression of dSLC5A5 elevates systemic and circulating sugar levels and promotes glucose uptake into the enterocytes. We show that dSLC5A5 undergoes dynamin-dependent endocytosis in the enterocyte apical membrane, and that dSLC5A5 endocytosis is essential for the glucose uptake capability of dSLC5A5. Moreover, we provide evidence supporting that intracellular lysosomal degradation of endocytosed dSLC5A5 plays a significant role in the maintenance of dSLC5A5 level in the enterocyte apical membrane. We further show that short-term exposure to glucose upregulates SLC5A5 abundance in the enterocyte apical membrane. Finally, we show that the loss or gain of dSLC5A5 ameliorates or exacerbates the high sugar diet (HSD)-mediated glucose metabolic defects. Together, our studies uncovered the first Drosophila glucose transporter in the midgut and reveal new mechanisms that regulate glucose transporters in the enterocyte apical membranes.
Drug-dependent morphological transitions in spherical and worm-like polymeric micelles define stability and pharmacological performance of micellar drugs
Authors: Lim Chaemin , Ramsey Jacob D. , Hwang Duhyeong , Teixeira Susana C. M. , Poon Chi-Duen , Strauss Joshua D , Sokolsky-Papkov Marina , Kabanov Alexander V.
Published: June 2021

Significant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy has not been adequately addressed. We addressed this gap by assessing pharmacological efficacy of polymeric micelles with spherical and worm-like morphologies. We observed that poly(2-oxazoline)-based polymeric micelles can be elongated over time from a spherical structure to worm-like structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. We further evaluated the role of different morphologies of olaparib micelles on pharmacological performance against a triple-negative breast cancer tumor (TNBC) model. Spherical micelles accumulated rapidly in the tumor tissue while retaining large amounts of drug; worm-like micelles accumulated more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug–micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles.
Generalized additive models to analyze non-linear trends in biomedical longitudinal data using R: Beyond repeated measures ANOVA and Linear Mixed Models
Authors: Mundo Ariel I. , Muldoon Timothy J. , Tipton John R.
Published: June 2021

1

In biomedical research, the outcome of longitudinal studies has been traditionally analyzed using therepeated measures analysis of variance(rm-ANOVA) or more recently,linear mixed models(LMEMs). Although LMEMs are less restrictive than rm-ANOVA as they can work with unbalanced data and non-constant correlation between observations, both methodologies assume a linear trend in the measured response. It is common in biomedical research that the true trend response is nonlinear and in these cases the linearity assumption of rm-ANOVA and LMEMs can lead to biased estimates and unreliable inference.

In contrast, GAMs relax the linearity assumption of rm-ANOVA and LMEMs and allow the data to determine the fit of the model while also permitting incomplete observations and different correlation structures. Therefore, GAMs present an excellent choice to analyze longitudinal data with non-linear trends in the context of biomedical research. This paper summarizes the limitations of rm-ANOVA and LMEMs and uses simulated data to visually show how both methods produce biased estimates when used on data with non-linear trends. We present the basic theory of GAMs and using reported trends of oxygen saturation in tumors, we simulate example longitudinal data (2 treatment groups, 10 subjects per group, 5 repeated measures for each group) to demonstrate their implementation in R. We also show that GAMs are able to produce estimates with non-linear trends even when incomplete observations exist (with 40% of the simulated observations missing). To make this work reproducible, the code and data used in this paper are available at:https://github.com/aimundo/GAMs-biomedical-research.
PD-1 checkpoint blockade disrupts CD4 T cell regulated adaptive B cell tolerance to foreign antigens
Authors: Dufaud Chad R. , Shuparski Andrew G. , Higgins Brett W. , McHeyzer-Williams Louise J. , McHeyzer-Williams Michael G.
Published: June 2021

Adaptive B cell immunity to environmental antigens must be regulated by multiple CD4 T cell dependent tolerance mechanisms. Using integrated single cell strategies, we demonstrate that acute PD-1 blockade induces extensive and selective local anti-inflammatory IgG1 plasma cell (PC) differentiation. Expansion of pre-existing IgG1 germinal center (GC) B cell and enhanced GC programming without memory B cell involvement reveals an isotype-specific GC checkpoint that blocks steady-state IgG1 antibody maturation. While there was no adjuvant impact on immunization, acute PD-1 checkpoint blockade exaggerates anti-commensal IgG1 antibody production, alters microbiome composition and exerts its action in a CD4 T cell dependent manner. These findings reveal a PD-1 controlled adaptive B cell tolerance checkpoint that selectively constrains maturation of pre-existing anti-inflammatory antibodies to prevent over-reaction to steady-state foreign antigens.

In Brief

PD-1 controls an adaptive B cell tolerance checkpoint in steady-state germinal centers to inhibit the maturation and production of IgG1 antibody with pre-existing foreign specificities.

Highlights

– Acute PD-1 blockade induces extensive IgG1 PC differentiation at homeostasis

– PD-1 blockade releases an IgG1 GC B cell checkpoint that drives expansion and PC formation

– No adjuvant effect on foreign antigen but expansion of pre-existing IgG1 specificities to non-self

– PD-1 exerts CD4 T cell dependent tolerance in the GC to restrict IgG1 maturation to non-self

Graphical Abstract
A Novel Local Explainability Approach for Spectral Insight into Raw Eeg-Based Deep Learning Classifiers
Authors: Ellis Charles A. , Miller Robyn L. , Calhoun Vince D.
Published: June 2021

The frequency domain of electroencephalography (EEG) data has developed as a particularly important area of EEG analysis. EEG spectra have been analyzed with explainable machine learning and deep learning methods. However, as deep learning has developed, most studies use raw EEG data, which is not well-suited for traditional explainability methods. Several studies have introduced methods for spectral insight into classifiers trained on raw EEG data. These studies have provided global insight into the frequency bands that are generally important to a classifier but do not provide local insight into the frequency bands important for the classification of individual samples. This local explainability could be particularly helpful for EEG analysis domains like sleep stage classification that feature multiple evolving states. We present a novel local spectral explainability approach and use it to explain a convolutional neural network trained for automated sleep stage classification. We use our approach to show how the relative importance of different frequency bands varies over time and even within the same sleep stages. Furthermore, to better understand how our approach compares to existing methods, we compare a global estimate of spectral importance generated from our local results with an existing global spectral importance approach. We find that the δ band is most important for most sleep stages, though β is most important for the non-rapid eye movement 2 (NREM2) sleep stage. Additionally, θ is particularly important for identifying Awake and NREM1 samples. Our study represents the first approach developed for local spectral insight into deep learning classifiers trained on raw EEG time series.
Measuring the metabolic evolution of glioblastoma throughout tumor development, regression, and recurrence with hyperpolarized magnetic resonance
Authors: Salzillo Travis C. , Mawoneke Vimbai , Weygand Joseph , Shetty Akaanksh , Gumin Joy , Zacharias Niki M. , Gammon Seth T. , Piwnica-Worms David , Fuller Gregory N. , Logothetis Christopher J. , Lang Frederick F. , Bhattacharya Pratip K.
Published: June 2021

Rapid diagnosis and therapeutic monitoring of aggressive diseases such as glioblastoma can improve patient survival by providing physicians the time to optimally deliver treatment. This research tested whether metabolic imaging with hyperpolarized MRI could detect changes in tumor progression faster than conventional anatomic MRI in patient-derived glioblastoma murine models. To capture the dynamic nature of cancer metabolism, hyperpolarized MRI, NMR spectroscopy, and immunohistochemistry were performed at several time-points during tumor development, regression, and recurrence. Hyperpolarized MRI detected significant changes of metabolism throughout tumor progression whereas conventional MRI was less sensitive. This was accompanied by aberrations in amino acid and phospholipid lipid metabolism and MCT1 expression. Hyperpolarized MRI can help address clinical challenges such as identifying malignant disease prior to aggressive growth, differentiating pseudoprogression from true progression, and predicting relapse. The individual evolution of these metabolic assays as well as their correlations with one another provides context for further academic research.
Including imprecisely georeferenced specimens improves accuracy of species distribution models and estimates of niche breadth
Authors: Smith Adam B. , Murphy Stephen J. , Henderson David , Erickson Kelley D.
Published: June 2021

Aim

Museum and herbarium specimen records are frequently used to assess species’ conservation status and responses to climate change. Typically, occurrences with imprecise geolocality information are discarded because they cannot be matched confidently to environmental conditions, and are thus expected to increase uncertainty in downstream analyses. However, using only precisely georeferenced records risks undersampling of species’ environmental and geographic distributions. We present two related methods to allow the use of imprecisely georeferenced occurrences in biogeographic analysis.

Innovation

Our two procedures assign imprecise records to the 1) locations or 2) climates that are closest to the geographic or environmental centroid of the precise records of a species. For virtual species, including imprecise records alongside precise records improved the accuracy of ecological niche models projected to the present and the future, especially for species with~20 or fewer precise occurrences. Using only precise records underestimates loss in suitable habitat and overestimates the amount of suitable habitat in both the present and future. Including imprecise records also improves estimates of niche breadth and extent of occurrence. An analysis of 44 species of North AmericanAsclepias(Apocynaceae) yielded similar results.

Main conclusions

Existing studies examining the effects of spatial imprecision compare outcomes based on precise records to the same records with spatial error added to them. However, in real-world cases, analysts possess a mix of precise and imprecise records and must decide whether to retain or discard the latter. Discarding imprecise records can undersample species’ geographic and environmental distributions and lead to mis-estimation of responses to past and future climate change. Our method, for which we provide a software implementation in the enmSdmX package for R, is simple to employ and can help leverage the large number of specimen records that are typically deemed “unusable” because of spatial imprecision in their geolocation.
Spatial neglect in the digital age – Influence of presentation format on patients’ test behavior
Authors: Rosenzopf Hannah , Sperber Christoph , Wortha Franz , Wiesen Daniel , Muth Annika , Klein Elise , Möller Korbinian , Karnath Hans-Otto
Published: June 2021

Computerization of diagnostic neglect tests can deepen our knowledge of neglect specific abnormalities, by effortlessly providing additional behavioral markers that are hardly extractable from existing paper-and-pencil versions. However, so far it is not known whether the digitization and/or a change in size format impact neglect patients’ search behavior and test scores and thus require adjustments of cut-off criteria. We compared the Center of cancellation (CoC) measure of right hemisphere stroke patients with spatial neglect in two cancellation tasks across different modalities (paper-and-pencil vs. digital) and display sizes (small, medium, large). We found that the CoC measure did neither vary considerably between paper-and-pencil versus digital versions, nor between different digital size formats. The CoC derived from cancellation tasks thus seems robust to test digitization. A further aim of the present study was to evaluate three additional parameters of search behavior which became available through digitization. We observed slower search behavior, increased distance between two consecutively identified items, and signs of a more strategic search for neglect patients than control patients without neglect. Machine learning classifications indicated that – beyond the CoC measure – the latter three variables can help to differentiate stroke patients with spatial neglect from thosewithout.
PATAN-domain response regulators interact with the Type IV pilus motor to control phototactic orientation in the cyanobacterium Synechocystis sp. PCC 6803
Authors: Han Yu , Jakob Annik , Engel Sophia , Wilde Annegret , Schuergers Nils
Published: June 2021

Many prokaryotes show complex behaviors that require the intricate spatial and temporal organization of cellular protein machineries, leading to asymmetrical protein distribution and cell polarity. One such behavior is cyanobacterial phototaxis which relies on the dynamic localization of the Type IV pilus motor proteins in response to light. In the cyanobacterium Synechocystis, various signaling systems encompassing chemotaxis-related CheY- and PatA-like response regulators are critical players in switching between positive and negative phototaxis depending on the light intensity and wavelength. In this study, we show that PatA-type regulators evolved from chemosensory systems. Using fluorescence microscopy and yeast-two-hybrid analysis, we demonstrate that they localize to the inner membrane, where they interact with the N-terminal cytoplasmic domain of PilC and the pilus assembly ATPase PilB1. By separately expressing the subdomains of the response regulator PixE, we confirm that only the N-terminal PATAN domain interacts with PilB1, localizes to the membrane, and is sufficient to reverse phototactic orientation. These experiments established that the PATAN domain is the principal output domain of PatA-type regulators which we presume to modulate pilus extension by binding to the pilus motor components.
Bamboos flower after the return of almost the same sun-moon phasing as at seedling emergence
Authors: Clerget Benoit
Published: June 2021

All Asian woody bamboo species of economic importance are semelparous. They remain vegetative during time intervals that are specific to each species and range from three to 120 years, with notable concentrations around a series of values (3, 7-8, 14-17, 29-36, 42-48, 61-64, and 120 years). Then, they flower gregariously within a short period. Entire forests temporarily disappear during these periods, and the dates of these dramatic events have been recorded over the last 200 years.

While searching for a correlated environmental cue, I have found that the concentrations of flowering cycles were highly correlated with the series of successive returns of almost the same sun-moon phasing as at seedling emergence. On basis of knowledge on plant photoperiod sensitivity, I hypothesize that bamboo plants i) run a lunar cellular clock that is set at the full moon, ii) retain in their cellular memory the exact sun-moon phasing of the year of their emergence as seedlings, and iii) inhibit flowering until the occurrence of a unique, species-specific sun-moon phasing that is shifted by a precise amount from the sun-moon phasing at their emergence. Recent evidence of plant responses to lunar cycles supports this hypothesis, for which experimental evidence is now anticipated.

Highlight

The long-standing enigma of the triggering of the gregarious flowering of bamboos is possibly solved. Flowering would be inhibited until the occurrence of the species-specific sun-moon phasing.
A comprehensive in silico investigation into the nsSNPs of Drd2 gene predicts significant functional consequences in dopamine signaling and pharmacotherapy
Authors: Lira Samia Sultana , Ahammad Ishtiaque
Published: June 2021

DRD2 is a neuronal cell surface protein involved in brain development and function. Variations in the Drd2 gene have clinical significance since DRD2 is a pharmacotherapeutic target for treating psychiatric disorders like ADHD and schizophrenia. Despite numerous studies on the disease association of single nucleotide polymorphisms (SNPs) in the intronic regions, investigation into the coding regions is surprisingly limited. In this study, we aimed at identifying potential functionally and pharmaco-therapeutically deleterious non-synonymous SNPs of Drd2. A wide array of bioinformatics tools was used to evaluate the impact of nsSNPs on protein structure and functionality. Out of 260 nsSNPs retrieved from the dbSNP database, initially 9 were predicted as deleterious by 15 tools. Upon further assessment of their domain association, conservation profile, homology models and inter-atomic interaction, the mutant F389V was considered as the most impactful. In-depth analysis of F389V through Molecular Docking and Dynamics Simulation revealed a decline in affinity for its native agonist dopamine and an increase in affinity for the antipsychotic drug risperidone. Remarkable alterations in binding interactions and stability of the protein-ligand complex in simulated physiological conditions were also noted. These findings will improve our understanding of the consequence of nsSNPs in disease-susceptibility and therapeutic efficacy.
Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant
Authors: Moss Tonya , May Melanie , Flanagan-Steet Heather , Caylor Raymond , Jiang Yong-Hui , McDonald Marie , Friez Michael , McConkie-Rosell Allyn , Steet Richard
Published: June 2021

Variants in the X-linked gene AIFM1 (apoptosis-inducing factor mitochondria-associated 1) are associated with a highly variable clinical presentation that encompasses motor neuropathy, ataxia, encephalopathies, deafness, and cognitive impairment. AIFM1 encodes a mitochondrial flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide (NADH) oxidoreductase, with roles in the regulation of respiratory complex assembly and function, production of reactive oxygen species, and the coordination of a caspase-independent type of apoptosis known as parthanatos. In this report, we describe a missense AIFM1 variant (absent in reference population databases; c.506C > T, p.Pro169Leu) identified in the proband and sibling of a family with three affected males. The proband, his brother, and their maternal uncle all exhibited severe multisystem pathology, metabolic acidosis, and early demise. Metabolic testing on the proband revealed normal activity of the pyruvate dehydrogenase complex in skin fibroblasts. Absent or partial deficiency of cytochrome c oxidase was found in muscle fibers, however, supporting a Complex IV mitochondrial deficiency. Functional studies carried out on fibroblasts from the proband demonstrated reduced steady state levels of the AIFM1 protein, decreased Complex I subunit abundance, elevated sensitivity to the apoptosis inducer staurosporine, and increased nuclear condensation when grown in galactose-containing media. The reduced abundance of AIFM1 in the patient cells could not be stabilized with riboflavin or protease inhibitor treatment. Together, these findings suggest that the normal function of the AIFM1 gene product within mitochondria, and its response to apoptotic stimuli, are impaired by this variant, likely accounting for the severity of the phenotype seen in these patients. These findings also imply tissue-specific effects of this variant on different mitochondrial complexes. This study expands the genetic and phenotypic spectrum associated with AIFM1 variants, with the combination of exome sequencing and functional studies allowing a diagnosis to finally be confirmed for this family.
Synthesis and crystal structure of a one-dimensional chain-like strontium(II) coordination polymer built of N-methyldiethanolamine and isobutyrate ligands
Authors: Seiss Maximilian , Schmitz Sebastian , Börner Martin , Monakhov Kirill Yu.
Published: June 2021

The one-dimensional coordination polymer (I) [Sr(ib)2(H2mda)]
n
(Hib = isobutyric acid, C4H8O2, and H2mda = N-methyldiethanolamine, C5H13NO2), namely, catena-poly[[(N-methyldiethanolamine-κ3
O,N,O′)strontium(II)]-di-μ2-isobutyrato-κ3
O,O′:O;κ3
O:O,O′], was prepared by the one-pot aerobic reaction of [Zr6O4(OH)4(ib)12(H2O)]·3Hib with Sr(NO3)2 and H2mda in the presence of MnCl2 and Et3N in acetonitrile. The use of MnCl2 is key to the isolation of I as high-quality colorless crystals in good yield. The molecular solid-state structure of I was determined by single-crystal X-ray diffraction. Compound I crystallizes in the monoclinic space group P21/c and shows a one-dimensional polymeric chain structure. Each monomeric unit of this coordination polymer consists of a central SrII ion in the NO8 coordination environment of two deprotonated ib− ligands and one fully protonated H2mda ligand. The C and O atoms of the H2mda ligand were refined as disordered over two sets of sites with site occupancies of 0.619 (3) and 0.381 (3). Compound I shows thermal stability up to 130°C in air.
Dynamic accountability and the role of risk reporting during a global pandemic
Authors: Crovini Chiara , Schaper Stefan , Simoni Lorenzo
Published: June 2021

Purpose

This article lays out some conceptual considerations of how dynamic accountability and risk reporting practices could be tailored during and after a global pandemic.

Design/methodology/approach

This conceptual paper seeks to foster the debate on the crucial role of risk reporting considering the impact and uncertainty caused by the coronavirus disease 2019 (COVID-19) pandemic and stakeholder information needs in this context. The authors draw upon neo-Durkheimian institutional and legitimacy theories and elements of the accounting and risk management literature to discuss the challenges that the pandemic poses to risk recognition and assessment and the subsequent disclosure decision of risk information.

Findings

Risk reporting has its roots in risk recognition and assessment. To live up to their accountability in these times of uncertainty, organisations need to address their stakeholders' new and changing information needs. Ad hoc disclosures and linking risk management and reporting to their business models (BM) would improve the risk recognition and assessment practices and the meaningfulness of the disclosed information. Hence, we provide some examples and discuss potential avenues to address these challenges and adapt risk reporting accordingly.

Originality/value

This conceptual paper contributes to the risk reporting and accountability research fields. Previous studies on communication during a crisis have focused on sustainability reporting. Thus, this study contributes to that literature by considering the role of risk reporting in times of an unexpected large-scale global crisis, such as the COVID-19 pandemic, and by highlighting possibilities for moving risk reporting towards becoming more accountability based.
An evolutionary computational method to formulate the response of unbonded concrete overlays to temperature loading
Authors: Zhang Qianyun , Vandenbossche Julie M. , Alavi Amir H.
Published: June 2021

Purpose

Unbonded concrete overlays (UBOLs) are commonly used in pavement rehabilitation. The current models included in the Mechanistic-Empirical Pavement Design Guide cannot properly predict the structural response of UBOLs. In this paper, a multigene genetic programming (MGGP) approach is proposed to derive new prediction models for the UBOLs response to temperature loading.

Design/methodology/approach

MGGP is a promising variant of evolutionary computation capable of developing highly nonlinear explicit models for characterizing complex engineering problems. The proposed UBOL response models are formulated in terms of several influencing parameters including joint spacing, radius of relative stiffness, temperature gradient and adjusted load/pavement weight ratio. Furthermore, linear regression models are developed to benchmark the MGGP models.

Findings

The derived design equations accurately characterize the UBOLs response under temperature loading and remarkably outperform the regression models. The conducted parametric analysis implies the efficiency of the MGGP-based model in capturing the underlying physical behavior of the UBOLs response to temperature loading. Based on the results, the proposed models can be reliably deployed for design purposes.

Originality/value

A challenge in the design of UBOLs is that their interlayer effects have not been directly considered in previous design procedures. To achieve better performance predictions, it is necessary to capture the effect of the interlayer in the design process. This study addresses this important issue via developing new models that can efficiently account for the effects of interlayer on the stress and deflections. In addition, it provides an insight into the effect of several parameters influencing the deflections of the UBOLs. From a computing perspective, a powerful evolutionary computation technique is introduced that overcomes the shortcomings of existing machine learning methods.
Does venture capital help to promote open innovation practice? Evidence from China
Authors: Yi Rui , Wang Haojun , Lyu Bei , Xia Qinghua
Published: June 2021

Purpose

The study aims to empirically study the effect of venture capital on open innovation of China's enterprises.

Design/methodology/approach

This paper selects China's A-share listed companies on the small and medium-sized enterprises (SMEs) board and the Growth Enterprise Market from 2014 to 2018 as research samples to empirically study the effect of venture capital on open innovation of China's enterprises.

Findings

The authors find that venture capital can significantly promote open innovation of enterprises. This promoting effect is more significant when the venture capital institutions have profounder industry experience, higher shareholding ratio and are syndicated. Further research finds that venture capital mainly promotes open innovation through three mechanisms: increasing monetary funds, improving absorptive capacity and strengthening executive incentives, and the effect of venture capital on open innovation is significantly different under the conditions of different regions, industries and property rights.

Originality/value

This paper not only reveals the effect of venture capital on enterprises' open innovation and the specific mechanism, but also provides empirical evidence for emerging economies to build a national innovation ecosystem and make use of capital markets to accelerate innovation strategies.
“Sand” or “grease” effect? The impact of corruption on the investment volume of public−private partnerships
Authors: Fleta-Asín Jorge , Muñoz Fernando
Published: June 2021

Purpose

Some scholars argue that corruption hinders economies and investment because it generates extra costs, while others suggest that it can act as a stimulus. Their mixed empirical findings have prompted the analysis of whether investors' attitude towards corruption changes depending on its degree of prevalence.

Design/methodology/approach

The authors examined 4,518 public–private partnerships (PPPs) located in 46 developing countries for the period 1997–2017. The data were collected from the World Bank PPP database. The authors investigated the relationship between the amount of investment in PPP projects and the level of corruption using regression with multilevel mixed effects.

Findings

Corruption and the amount of investment in PPP projects are inversely related at the low and high end of the spectrum of corruption, but the relationship is positive towards the middle. Further analysis revealed that this was spurred by high investment PPP projects in less developed countries.

Originality/value

The findings allow the authors to reconcile the opposing positions in the literature through a “sand–grease–sand the wheels” effect between the volume of investment and corruption, which can be configured as a reverse S-shape consisting of three stages.
Does healthcare service quality affect outbound medical tourists’ satisfaction and loyalty? Experience from a developing country
Authors: Mahmud Md. Shahed , Lima Reshma Pervin , Rahman Md. Mahbubar , Rahman Shafiqur
Published: June 2021

Purpose

Poor quality of services in the health-care sector of the developing countries like Bangladesh forces affluent patients to seek advanced medical treatment from abroad. The purpose of this study is to explore the outbound medical tourists’ satisfaction and loyalty on the basis of the quality of the health-care service provided by foreign medical institutions.

Design/methodology/approach

The medical tourists from Bangladesh who have got medical services from Indian medical institutions were taken as a sample by applying a purposive sampling technique. For the measurement of outbound medical tourists’ satisfaction, the dimensions of the HEALTHQUAL model were adopted. A self-administrated questionnaire was the major tool for collecting data from the respondents. Using partial least square-structural equation model multivariate statistical technique and with the aid of SmartPLS software, primary data collected from 218 final respondents were analyzed.

Findings

The findings of this study reveal that four dimensions of the HEALTHQUAL model, namely, empathy, tangibility, efficiency, and safety have a significant positive impact on building medical tourists’ overall satisfaction, and then the overall satisfaction also has a positive level of significance on building loyalty towards foreign medical service providers.

Practical implications

The findings of this study can be a helpful instrument for the developing countries to rethink and reshuffle their own existing health-care system for providing quality medical services and at the same time, the medical tourists importing countries to sharpen their existing service quality as well as to attract more medical tourists in the future.

Originality/value

A handful of research has been carried out, especially focused on health-care service quality measurement and the relationship of health-care service quality with satisfaction and loyalty from the perspective of developing countries outbound medical tourists. Thus, this research work will give a flavor to think of health-care service quality in a different dimension.
Supply chain, geographical indicator and blockchain: provenance model for commodity
Authors: Sharma Mohita Gangwar
Published: June 2021

Purpose

Many commodity supply chains suffer from an unfair value distribution across the supply chain like “Coffee Paradox.” This study explores the coffee supply chain to determine how the country of origin–geographical indicator can be used as a method of fair distribution of value and provenance across the supply chain effectuated by the blockchain technology. By looking at an exemplar case study for India, this study provides insights into diverse research streams and practice.

Design/methodology/approach

Based on the case method, analyzing the implementation of blockchain in the coffee industry by a leading Indian software implementation of the logic, dynamics and forces for a provenance model has been devised. It further adopts a stakeholder cum institutional theory framework to understand the logical implementation of a blockchain project embedded in a territorial logic for a commodity supply chain.

Findings

This study specifically looks at coffee which is representative of a commodity supply chain. It also explores how the malaise of unfair value distribution gets addressed by bringing farmers and the consumers on a common platform facilitated by blockchain technology. This study contributes to the literature on blockchain, territory, commodity and supply chain. Using stakeholder cum institutional theory, this study helps to explore how the implementation is successful by different actors in the supply chain through collaboration.

Research limitations/implications

This study provides a new stream of multi-disciplinary study at the interface of supply chain, technology, international trade and geography.

Practical implications

Blockchains are embedded in the supply chain, and supply chains are embedded in territories. This linkage is paramount and the ability to make these blockchain projects successful requires the deep study of the interaction of territory, technology and actors from the provenance angle. De-commodification of coffee can be actualized through blockchain.

Social implications

The coffee paradox and skewed value distribution is also a social problem wherein the farmers do not get the right price of their produce and are exploited. This case also highlights how this social malaise can be addressed and rightful and equitable distribution of value happens across the value chain.

Originality/value

This linkage between territory, blockchain, commodity supply chain and institutions has not been discussed in the literature. Adopting the territorial design approach, this study is an attempt to stimulate inter-disciplinary conversations and thereby create a provenance framework for commodity and research questions for scholars from different disciplines and divergent disciplinary perspectives.