bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-orientation Quantitative Susceptibility Mapping identifies the Ventral Intermediate Nucleus of the Thalamus
Authors: Yu Fang Frank , Lee Dongyoung , Achilleos Michael , Feltrin Fabricio , Shah Bhavya R.
Published: July 2021

Introduction

The ventral intermediate nucleus (VIM) represents the primary target in the treatment of tremor. Accurate localization is extremely important given its proximity to other thalamic nuclei. We utilized single orientation quantitative susceptibility mapping (QSM) at 3T to directly visualize the VIM.

Methods

Four adult volunteers, one adult cadaver, and an essential tremor patient were scanned on a 3T MRI using a multi-echo gradient echo sequence. QSM images were generated using the improved sparse linear equation and least-squares (iLSQR) algorithm. Two adult subjects underwent multiple head orientation imaging for multi-orientation QSM reconstruction. The VIM was prospectively identified with direct visualization as well as indirect landmark-based localization.

Results

The bilateral VIM was consistently identified as a hypointense structure within the lateral thalamus, appearing similar on multi-orientation and single-orientation QSM, corresponding to the myelinated dentatorubrothalamic tract (DRTT). The indirect method resulted in a comparatively inferomedial localization, at times missing the VIM and DRTT.

Conclusion

Single-orientation QSM offers a clinically feasible, non-invasive imaging-based approach to directly localize the VIM.
A multimodal AI system for out-of-distribution generalization of seizure detection
Authors: Yang Yikai , Truong Nhan Duy , Eshraghian Jason K. , Maher Christina , Nikpour Armin , Kavehei Omid
Published: July 2021

Epilepsy is one of the most common severe neurological disorders worldwide. The International League Against Epilepsy (ILAE) define epilepsy as a brain disorder that generates (1) two unprovoked seizures more than 24 hrs apart, or (2) one unprovoked seizure with at least 60% risk of recurrence over the next ten years. Complete remission has been defined as ten years seizure free with the last five years medication free. This requires a cost-effective ambulatory ultra-long term out-patient monitoring solution. The common practice of self-reporting is inaccurate. Applying artificial intelligence (AI) to scalp electroencephalogram (EEG) interpretation is becoming increasingly common, but other data modalities such as electrocardiograms (ECGs) are simpler to collect and often recorded simultaneously with EEG. Both recordings contain biomarkers in the detection of seizures.

Here, we propose a state-of-the-art performing AI system that combines EEG and ECG for seizure detection, tested on clinical data with early evidence demonstrating generalization across hospitals. The model was trained and validated on the publicly available Temple University Hospital (TUH) dataset. To evaluate performance in a clinical setting, we conducted nonpatient-specific inference-only tests on three out-of-distribution datasets, including EPILEPSIAE (30 patients) and the Royal Prince Alfred Hospital (RPAH) in Sydney, Australia (31 patients shortlisted by neurologists and 30 randomly selected). Across all datasets, our multimodal approach improves the area under the receiver operating characteristic curve (AUC-ROC) by an average margin of 6.71% and 14.42% for prior state-of-the-art approaches using EEG and ECG alone, respectively. Our model’s state-of-the-art performance and robustness to out-ofdistribution datasets can improve the accuracy and efficiency of epilepsy diagnoses.
ERp44 is Required for Endocardial Cushion Development by Regulating VEGFA Secretion in Myocardium
Authors: Bi Youkun , Yang Zhiguang , Jin Meng , Zhai Kui , Wang Jun , Mao Yang , Liu Yang , Ding Mingqin , Wang Huiwen , Wang Fengchao , Ji Guangju
Published: July 2021

Rationale: Endocardial cushions are precursors of the valvoseptal complex that separates the four heart chambers and control blood flow through the heart. Abnormalities in endocardial cushion development lead to atrioventricular septal defects (AVSDs), which affect 1 in 2,100 live births. Several genes have been implicated in the development of endocardial cushions. Specifically, endoplasmic reticulum-resident protein 44 (ERp44) has been found to play a role in the early secretory pathway, but its function in heart development has not been well studied. Objective: The goal of this study was to investigate the role of ERp44 in heart development in mice. Approach and Results: Using conventional and tissue-specific knockout mouse models, we demonstrated that ERp44 plays a specific role in heart development. ERp44 knockout (KO) mice were smaller in size, and most mice died during early postnatal life. KO hearts exhibited the typical phenotypes of congenital heart diseases, such as abnormal heart shapes as well as severe septal and valvular defects. Similar phenotypes were found in cTnt-cre+/−; Erp44fl/fl mice, which indicated that myocardial ERp44 principally controls endocardial cushion formation. Further studies demonstrated that the deletion of ERp44 significantly decreased the proliferation of cushion cells and impaired the endocardial-mesenchymal transition (EndMT), which was followed by endocardial cushion dysplasia. Finally, we found that ERp44 directly bound to VEGFA and controlled its release. Conclusions: ERp44 contributes to the development of the endocardial cushion by affecting the EndMT of cushion cells by regulating VEGFA release in myocardial cells.
Identification of novel translated small ORFs in Escherichia coli using complementary ribosome profiling approaches
Authors: Stringer Anne , Smith Carol , Mangano Kyle , Wade Joseph T.
Published: July 2021

Small proteins of <51 amino acids are abundant across all domains of life but are often overlooked because their small size makes them difficult to predict computationally, and they are refractory to standard proteomic approaches. Ribosome profiling has been used to infer the existence of small proteins by detecting the translation of the corresponding open reading frames (ORFs). Detection of translated short ORFs by ribosome profiling can be improved by treating cells with drugs that stall ribosomes at specific codons. Here, we combine the analysis of ribosome profiling data for Escherichia coli cells treated with antibiotics that stall ribosomes at either start or stop codons. Thus, we identify ribosome-occupied start and stop codons for ~400 novel putative ORFs with high sensitivity. The newly discovered ORFs are mostly short, with 365 encoding proteins of <51 amino acids. We validate translation of several selected short ORFs, and show that many likely encode unstable proteins. Moreover, we present evidence that most of the newly identified short ORFs are not under purifying selection, suggesting they do not impact cell fitness, although a small subset have the hallmarks of functional ORFs.

IMPORTANCE

Small proteins of <51 amino acids are abundant across all domains of life but are often overlooked because their small size makes them difficult to predict computationally, and they are refractory to standard proteomic approaches. Recent studies have discovered small proteins by mapping the location of translating ribosomes on RNA using a technique known as ribosome profiling. Discovery of translated sORFs using ribosome profiling can be improved by treating cells with drugs that trap initiating ribosomes. Here, we show that combining these data with equivalent data for cells treated with a drug that stalls terminating ribosomes facilitates the discovery of small proteins. We use this approach to discover 365 putative genes that encode small proteins in Escherichia coli.
Identification of effector metabolites using exometabolite profiling of diverse microalgae
Authors: Brisson Vanessa , Mayali Xavier , Bowen Benjamin , Golini Amber , Thelen Michael , Stuart Rhona K. , Northen Trent R.
Published: July 2021

Dissolved exometabolites mediate algal interactions in aquatic ecosystems, but microalgal exometabolomes remain understudied. We conducted an untargeted metabolomic analysis of non-polar exometabolites exuded from four phylogenetically and ecologically diverse eukaryotic microalgal strains grown in the laboratory: freshwater Chlamydomonas reinhardtii, brackish Desmodesmus sp., marine Phaeodactylum tricornutum, and marine Microchloropsis salina, to identify released metabolites based on relative enrichment in the exometabolomes compared to cell pellet metabolomes. Exudates from the different taxa were distinct, but we did not observe clear phylogenetic patterns. We used feature based molecular networking to explore the identities of these metabolites, revealing several distinct di- and tripeptides secreted by each of the algae, lumichrome, a compound that is known to be involved in plant growth and bacterial quorum sensing, and novel prostaglandin-like compounds. We further investigated the impacts of exogenous additions of eight compounds selected based on exometabolome enrichment on algal growth. Of the these, five (lumichrome, 5’-S-methyl-5’-thioadenosine, 17-phenyl trinor prostaglandin A2, dodecanedioic acid, and aleuritic acid) impacted growth in at least one of the algal cultures. Two of these (dodecanedioic acid and aleuritic acid) produced contrasting results, increasing growth in some algae and decreasing growth in others. Together, our results reveal new groups of microalgal exometabolites, some of which could alter algal growth when provided exogenously, suggesting potential roles in allelopathy and algal interactions.

IMPORTANCE

Microalgae are responsible for nearly half of primary production on earth and play an important role in global biogeochemical cycling as well as in a range of industrial applications. Algal exometabolites are important mediators of algal-algal and algal-bacterial interactions that ultimately affect algal growth and physiology. In this study we characterize exometabolomes across marine and freshwater algae to gain insights into the diverse metabolites they release into their environments (“exudates”). We observe that while phylogeny can play a role in exometabolome content, environmental conditions or habitat origin (freshwater vs marine) are also important. We also find that several of these compounds can influence algal growth (as measured by chlorophyll production) when provided exogenously, highlighting the importance of characterization of these novel compounds and their role in microalgal ecophysiology.
Evolutionary divergence of the Wsp signal transduction system in β- and γ-proteobacteria
Authors: Kessler Collin , Mhatre Eisha , Cooper Vaughn , Kim Wook
Published: July 2021

Bacteria rapidly adapt to their environment by integrating external stimuli through diverse signal transduction systems. Pseudomonas aeruginosa, for example, senses surface-contact through the Wsp signal transduction system to trigger the production of cyclic di-GMP. Diverse mutations in wsp genes that manifest enhanced biofilm formation are frequently reported in clinical isolates of P. aeruginosa, and in biofilm studies of Pseudomonas spp. and Burkholderia cenocepacia. In contrast to the convergent phenotypes associated with comparable wsp mutations, we demonstrate that the Wsp system in B. cenocepacia does not impact intracellular cyclic di-GMP levels unlike that in Pseudomonas spp. Our current mechanistic understanding of the Wsp system is entirely based on the study of four Pseudomonas spp. and its phylogenetic distribution remains unknown. Here, we present the first broad phylogenetic analysis to date to show that the Wsp system originated in the β-proteobacteria then horizontally transferred to Pseudomonas spp., the sole member of the γ-proteobacteria. Alignment of 794 independent Wsp systems with reported mutations from the literature identified key amino acid residues that fall within and outside annotated functional domains. Specific residues that are highly conserved but uniquely modified in B. cenocepacia likely define mechanistic differences among Wsp systems. We also find the greatest sequence variation in the extracellular sensory domain of WspA, indicating potential adaptations to diverse external stimuli beyond surface-contact sensing. This study emphasizes the need to better understand the breadth of functional diversity of the Wsp system as a major regulator of bacterial adaptation beyond B. cenocepacia and select Pseudomonas spp.

Importance

The Wsp signal transduction system serves as an important model system for studying how bacteria adapt to living in densely structured communities known as biofilms. Biofilms frequently cause chronic infections and environmental fouling, and they are very difficult to eradicate. In Pseudomonas aeruginosa, the Wsp system senses contact with a surface, which in turn activates specific genes that promote biofilm formation. We demonstrate that the Wsp system in Burkholderia cenocepacia regulates biofilm formation uniquely from that in Pseudomonas species. Furthermore, a broad phylogenetic analysis reveals the presence of the Wsp system in diverse bacterial species, and sequence analyses of 794 independent systems suggest that the core signaling components function similarly but with key differences that may alter what or how they sense. This study shows that Wsp systems are highly conserved and more broadly distributed than previously thought, and their unique differences likely reflect adaptations to distinct environments.
Deep learning and cross-species analysis identify the influences of sex and cannabinoid signaling on cerebellar vermis morphology
Authors: Black Kylie , Pandey Om , McPherson Brent , Hainline John , Baygani Shawyon , Webb Brynna , Mier Tristen , Essex Amanda , Mackie Ken , Pestilli Franco , Kalinovsky Anna
Published: July 2021

The cerebellum is the only folded cortical structure present in both rodents and humans, allowing mechanistic studies of gyrification across species. In mice, the extent of anterior vermis folding and the shapes of white matter exhibit sex-dependent differences. We trained a deep convolutional neural network to predict biological sex from midline cerebellar MRI images, showing that human cerebellar midvermis contains sex-dependent anatomical features. Our comparative cross-species analysis shows that in both species, sex and anterior vermis folding patterns are not enough to predict an individual’s behavior because the variability in performance between individuals is far greater than the differences between conditions. Finally, utilizing constitutive cannabinoid receptor 1 (CB1) knockout (KO) mice, we identify developmental cannabinoid signaling as a novel molecular mechanism limiting secondary fissure formation.

Teaser

Males and females display differences in the architecture of cerebellar folding shaped by cannabinoid signaling during development.
Parallel processing in speech perception with local and global representations of linguistic context
Authors: Brodbeck Christian , Bhattasali Shohini , Cruz Heredia Aura A. L. , Resnik Philip , Simon Jonathan Z. , Lau Ellen
Published: July 2021

Speech processing is highly incremental. It is widely accepted that human listeners continuously use the linguistic context to anticipate upcoming concepts, words, and phonemes. However, previous evidence supports two seemingly contradictory models of how a predictive context is integrated with the bottom-up sensory input: Classic psycholinguistic paradigms suggest a two-stage process, in which acoustic input initially leads to local, context-independent representations, which are then quickly integrated with contextual constraints. This contrasts with the view that the brain constructs a single coherent, unified interpretation of the input, which fully integrates available information across representational hierarchies, and thus uses contextual constraints to modulate even the earliest sensory representations. To distinguish these hypotheses, we tested magnetoencephalography responses to continuous narrative speech for signatures of local and unified predictive models. Results provide evidence that listeners employ both types of models in parallel. Two local context models uniquely predict some part of early neural responses, one based on sublexical phoneme sequences, and one based on the phonemes in the current word alone; at the same time, even early responses to phonemes also reflect a unified model that incorporates sentence level constraints to predict upcoming phonemes. Neural source localization places the anatomical origins of the different predictive models in non-identical parts of the superior temporal lobes bilaterally, with the right hemisphere showing a relative preference for more local models. These results suggest that speech processing recruits both local and unified predictive models in parallel, reconciling previous disparate findings. Parallel models might make the perceptual system more robust, facilitate processing of unexpected inputs, and serve a function in language acquisition.

Impact statement

Speech processing engages multiple predictive models, using sublexical, word- and sentence contexts in parallel to anticipate upcoming phonemes.
Genomic evolution of the globally disseminated multidrug-resistantKlebsiella pneumoniaeclonal group 147
Authors: Rodrigues Carla , Desai Siddhi , Passet Virginie , Gajjar Devarshi , Brisse Sylvain
Published: July 2021

Background

The rapid emergence of multidrug-resistantKlebsiella pneumoniae(Kp) is largely driven by the spread of specific clonal groups (CG). Of these, CG147 includes 7-gene MLST sequence types ST147, ST273 and ST392. CG147 has caused nosocomial outbreaks across the world, but its global population dynamics remain unknown. Here, we report a pandrug-resistant ST147 clinical isolate from India (strain DJ) and define the evolution and global emergence of CG147.

Methods

Antimicrobial susceptibility testing (EUCAST guidelines) and genome sequencing (Illumina and Oxford Nanopore technologies, Unicycler assembly) were performed on strain DJ. Additionally, we collated 217 publicly available CG147 genomes (NCBI, May 2019). CG147 evolution was inferred within a temporal phylogenetic framework (BEAST) based on a recombination-free sequence alignment (Roary/Gubbins). Comparative genomic analyses focused on resistance and virulence genes and other genetic elements (BIGSdb, Kleborate, PlasmidFinder, PHASTER, ICEFinder and CRISPRCasFinder).

Results

Strain DJ had a pandrug resistance phenotype. Its genome comprised 7 plasmids and 1 linear phage-plasmid. Four carbapenemase genes were detected:blaNDM-5and 2 copies ofblaOXA-181in the chromosome, and a second copy ofblaNDM-5on an 84 kb IncFII plasmid. CG147 genomes carried a mean of 13 acquired resistance genes or mutations; 63% carried a carbapenemase gene and 83% harboredblaCTX-M. All CG147 genomes presented GyrA and ParC mutations and a common subtype IV-E CRISPR-Cas system. ST392 and ST273 emerged in 2005 and 1995, respectively. ST147, the most represented phylogenetic branch, was itself divided into two main clades with distinct capsular loci: KL64 (74%, DJ included, emerged in 1994 and disseminated worldwide, with carbapenemases varying among world regions) and KL10 (20%, 2002, predominantly found in Asian countries, associated with carbapenemases NDM and OXA-48-like). Further, subclades within ST147-KL64 differed in the yersiniabactin locus, OmpK35/K36 mutations, plasmid replicons and prophages. The absence of IncF plasmids in some subclades was associated with a possible activity of a CRISPR-Cas system.

Conclusions

K. pneumoniaeclonal group CG147 comprises pandrug- or extensively-resistant isolates and carries multiple and diverse resistance genes and mobile genetic elements, including chromosomalblaNDM-5. Its emergence is driven by the spread of several phylogenetic clades marked by their own genomic features and specific temporo-spatial dynamics. These findings highlight the need for precision surveillance strategies to limit the spread of particularly concerning CG147 subsets.
The MAP3Ks DLK and LZK direct diverse responses to axon damage in zebrafish peripheral neurons
Authors: Adula Kadidia Pemba , Shorey Mathew , Chauhan Vasudha , Nassman Khaled , Chen Shu-Fan , Rolls Melissa M , Sagasti Alvaro
Published: July 2021

The MAP3Ks Dual Leucine Kinase (DLK) and Leucine Zipper Kinase (LZK) are essential mediators of axon damage responses, but their responses are varied, complex, and incompletely understood. To characterize their functions in axon injury, we generated zebrafish mutants of each gene, labeled motor neurons (MN) and touch-sensing neurons in live zebrafish, precisely cut their axons with a laser, and assessed the ability of mutant axons to regenerate. DLK and LZK were required redundantly and cell autonomously for axon regeneration in MNs, but not in larval Rohon-Beard (RB) or adult dorsal root ganglion (DRG) sensory neurons. Surprisingly, indlk lzkdouble mutants, the spared branches of wounded RB axons grew excessively, suggesting that these kinases inhibit regenerative sprouting in damaged axons. Uninjured trigeminal sensory axons also grew excessively in mutants when neighboring neurons were ablated, indicating that these MAP3Ks are general inhibitors of sensory axon growth. These results demonstrate that zebrafish DLK and LZK promote diverse injury responses, depending on the neuronal cell identity and type of axonal injury.

Significance statement

The MAP3Ks DLK and LZK are damage sensors that promote diverse outcomes to neuronal injury, including axon regeneration. Understanding their context-specific functions is a prerequisite to considering these kinases as therapeutic targets. To investigate DLK and LZK cell-type specific functions, we created zebrafish mutants in each gene. Using mosaic cell labeling and precise laser injury we found that both proteins were required for axon regeneration in motor neurons, but, unexpectedly, were not required for axon regeneration in Rohon-Beard or dorsal root ganglion (DRG) sensory neurons, and negatively regulated sprouting in the spared axons of touch-sensing neurons. These findings emphasize that animals have evolved distinct mechanisms to regulate injury site regeneration and collateral sprouting, and identify differential roles for DLK and LZK in these processes.
PARP Inhibition Impedes the Maturation of Nascent DNA Strands During DNA Replication
Authors: Vaitsiankova Alina , Burdova Kamila , Hanzlikova Hana , Caldecott Keith W
Published: July 2021

PARP1 is implicated in the detection and repair of unligated Okazaki fragment intermediates, highlighting these structures as a potential source of genome breakage induced by PARP inhibition. In agreement with this, we show here that PARP1 activity is greatly elevated in chicken and human S phase cells in which FEN1 nuclease is genetically deleted, and that PARP activity is highest tens of kilobases behind DNA replication forks. Importantly, PARP inhibitor reduces the integrity of nascent DNA strands in both wild type chicken and human cells during DNA replication, and does so in FEN1−/− cells to an even greater extent that can be detected as post-replicative single-strand gaps within individual DNA fibres. Collectively, these data show that PARP inhibitors impede the maturation of Okazaki fragments in nascent DNA, implicating these canonical DNA replication intermediates in the cytotoxicity of these compounds.
Controlling Staphylococcus aureus by 2-[(Methylamino)methyl]phenol (2-MAMP) in a co-culture moderates the biofilm and virulence of Pseudomonas aeruginosa
Authors: Thamil Selvan Gopalakrishnan , Thirunavukkarasu Brindha , Pravallika Nerellapalli Nandini , Vasudevan Sahana , Palaniappan Balamurugan , Solomon Adline Princy
Published: July 2021

Staphylococcus aureus and Pseudomonas aeruginosa are the most encountered organisms in a polymicrobial chronic wound infection. Production of multiple virulence factors by this duo delays wound healing process. Notably, P. aeruginosa displays enhanced virulence in the presence of S. aureus by a peptidoglycan sensing mechanism. Thus, novel therapies are imperative to address polymicrobial infections effectively. Previously, it has been suggested that targeting S. aureus might be a possible approach to reduce the severity of P. aeruginosa in a polymicrobial infection. In this aspect, we have used 2-[(Methylamino)methyl]phenol (2-MAMP), our previously reported QS inhibitor to target S. aureus and phenotypically determine the virulence factors of P. aeruginosa under this condition. Analysis of major virulence factors of Pseudomonas viz. biofilm, pyocyanin and pyoveridine showed a significant reduction. The competitive index (CI) and relative increase ratio (RIR) were determined to understand the organisms’ interaction in co-culture. Results indicated competitiveness among the strains and on increasing ratios of S. aureus cells, co-existence was noticed. Further, as a sensible approach antibiotic – antivirulence drug combinations were tested on co-culture. Significant improvement in the growth inhibition was observed. Our preliminary results presented here would enable further research to address polymicrobial infection in a novel way.
Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals
Authors: Seo Ji-Won , Fu Kaiyu , Correa Santiago , Eisenstein Michael , Appel Eric A. , Tom Soh H.
Published: July 2021

The efficacy and safety of a chemotherapy regimen fundamentally depends on its pharmacokinetics. This is currently measured based on blood samples, but the abnormal vasculature and physiological heterogeneity of the tumor microenvironment can produce radically different drug pharmacokinetics relative to the systemic circulation. We have developed an implantable microelectrode array sensor that can collect such tissue-based pharmacokinetic data by simultaneously measuring intratumoral pharmacokinetics from multiple sites. We employ gold nanoporous microelectrodes that maintain robust sensor performance even after repeated tissue implantation and extended exposure to the tumor microenvironment. We demonstrate continuous in vivo monitoring of concentrations of the chemotherapy drug doxorubicin at multiple tumor sites in a rodent model, and demonstrate clear differences in pharmacokinetics relative to the circulation that could meaningfully affect drug efficacy and safety. This platform could prove valuable for preclinical in vivo characterization of cancer therapeutics, and may offer a foundation for future clinical applications.
Sliding of HIV-1 reverse transcriptase over DNA creates a transient P pocket – Targeting P-pocket by fragment screening
Authors: Singh Abhimanyu K. , Martinez Sergio E. , Gu Weijie , Nguyen Hoai , Schols Dominique , Herdewijn Piet , De Jonghe Steven , Das Kalyan
Published: July 2021

HIV-1 reverse transcriptase (RT) slides over an RNA/DNA or dsDNA substrate while copying the viral RNA to a proviral DNA. We report a crystal structure of RT/dsDNA complex in which RT overstepped the primer 3’-end of a dsDNA substrate and created a transient P-pocket at the priming site. We performed a high-throughput screening of 300 drug-like fragments by X-ray crystallography and identified binding of two to P-pocket, which is composed of structural elements from polymerase active site, primer grip, and template-primer that are resilient to drugresistance mutations. Analogs of a fragment were synthesized of which two showed noticeable RT inhibition. An engineered RT/DNA aptamer complex trapped the transient P-pocket in solution. Structures of the RT/DNA complex were determined with a fragment and a synthesized analog bound at P-pocket by single-particle cryo-EM. Identification of P-pocket and the devised structurebased platform provide an opportunity for designing new types of polymerase inhibitors.
Implicitly Learned Higher Order Associations Differentiates Recent and Remote Retrieval of Temporal Order Memory
Authors: Shridhar Shruti , Singh Vikram Pal , Bhatt Richa , Kundu Sankhanava , Balaji J.
Published: July 2021

Memory of an ordered sequence of distinct events requires encoding the temporal order as well as the intervals that separates these events. In this study, using order place association task where the animal learns to associate the location of the food pellet to the order of entry into the event arena, we probe the nature of temporal order memory in mice. In our task, individual trials, become distinct events, as the animal is trained to form unique association between entry order and a correct location. The inter-trial intervals (> 30 mins) are chosen deliberately to minimise the working memory contributions. We develop this paradigm initially using 4 order place associates and later extend it to 5 paired associates. Our results show that animals not only acquire these explicit (entry order to place) associations but also higher order associations that can only be inferred implicitly from the temporal order of these events. As an indicator of such higher order learning during the probe trail the mice exhibit predominantly prospective errors that declines proportionally with temporal distance. On the other hand, prior to acquiring the sequence the retrospective errors are dominant. Additionally, we also tested the nature of such acquisitions when temporal order CS is presented along with flavour as a compound stimulus comprising of order and flavour both simultaneously being paired with location. Results from these experiments indicate that the animal learns both order-place and flavour-place associations. Comparing with pure order place training, we find that the additional flavour in compound training did not interfere with the ability of the animals to acquire the order place associations. When tested remotely, pure order place associations could be retrieved only after a reminder training. Further higher order associations representing the temporal relationship between the events is markedly absent in the remote time.
Single cell tools for WormBase
Authors: Veiga Beltrame Eduardo da , Arnaboldi Valerio , Sternberg Paul W.
Published: July 2021

We present two web apps for interactively performing common tasks with single cell RNA sequencing data: scdefg for interactive differential expression and wormcells-viz for visualization of gene expression. We made these tools available with public C. elegans datasets curated by WormBase at single-cell.wormbase.org. They can also be readily deployed for use with any other datasets using the source code available at github.com/WormBase/scdefg and at github.com/WormBase/wormcells-viz.
Uniformity on generalized topological spaces
Authors: Dey Dipankar , Mandal Dhananjay , Mukherjee Manabendra Nath
Published: July 2021

Purpose

The present article deals with the initiation and study of a uniformity like notion, captioned μ-uniformity, in the context of a generalized topological space.

Design/methodology/approach

The existence of uniformity for a completely regular topological space is well-known, and the interrelation of this structure with a proximity is also well-studied. Using this idea, a structure on generalized topological space has been developed, to establish the same type of compatibility in the corresponding frameworks.

Findings

It is proved, among other things, that a μ-uniformity on a non-empty set X always induces a generalized topology on X, which is μ-completely regular too. In the last theorem of the paper, the authors develop a relation between μ-proximity and μ-uniformity by showing that every μ-uniformity generates a μ-proximity, both giving the same generalized topology on the underlying set.

Originality/value

It is an original work influenced by the previous works that have been done on generalized topological spaces. A kind of generalization has been done in this article, that has produced an intermediate structure to the already known generalized topological spaces.
Exploring the long-run relationship between financial inclusion and agricultural growth: evidence from Pakistan
Authors: Farooq Usman , Gang Fu , Guan Zhenzhong , Rauf Abdul , Chandio Abbas Ali , Ahsan Faiza
Published: July 2021

Purpose

This study aims to investigate the long-run relationship between financial inclusion and agricultural growth in Pakistan for the period of 1960–2018.

Design/methodology/approach

The autoregressive distributed lag (ARDL) approach, the Johansen co-integration test and the dynamic ordinary least squared (DOLS) method are used for the evaluation.

Findings

The results show that in both short- and long run, domestic credit has a significantly negative impact on the agricultural growth, while broad money and cropped area positively affected the agricultural growth in Pakistan in both cases.

Practical implications

The government and policymakers need to develop strategies that bring together agriculturalists on a single platform so that the government can clearly distinguish the interests of these farmers and can obtain precise information for allocating agricultural expenditure and easing access to credit for small-scale agriculturalists.

Originality/value

This is the first study to evaluate the impact of financial inclusion on the agricultural growth in Pakistan by using different econometric techniques, including the ARDL-bound approach, Johansen co-integration test and DOLS method.
Indian supply chain ecosystem readiness assessment for Industry 4.0
Authors: Tripathi Shubham , Gupta Manish
Published: July 2021

Purpose

The article analyses the current readiness of India to transform its supply chain ecosystem to smarter systems with Fourth Industrial Revolution.

Design/methodology/approach

The analysis is carried out in two stages. First, the readiness of India is assessed globally, and then the rate of transformation over the years and supporting policies are analyzed to understand the transformation potential. This analysis is done across nine identified macro factors namely government support, regulations, business environment, human resource, infrastructure, innovation capability, technological advancements, cybersecurity and digital awareness. The study combines empirical data from 2010 onwards with the strategic literature published by government bodies and institutions for analysis.

Findings

Results show that India's readiness is just above the global average with a score of 0.44 on a scale of 0–1 (most ready). Government and start-up culture are found to be leading transformation factors, while digital infrastructure, regulations and cybersecurity are most lacking areas.

Originality/value

This study is first of its kind to the best of our knowledge. The academic literature has not reported studies assessing Industry 4.0 readiness of supply chain ecosystem using macro factors for nations.
A review of empirical research on corporate social responsibility in emerging economies
Authors: Dartey-Baah Kwasi , Amoako George Kofi
Published: July 2021

Purpose

The purpose of this paper is to provide a systematic review of empirical research studies on corporate social responsibility (CSR) in emerging economies.

Design/methodology/approach

This paper employed a systematic literature review using research papers published on CSR in emerging economies from 2010 to 2019.

Findings

The findings of this paper show that the principal themes of published research articles on CSR in emerging economies are (1) effects of CSR, (2) drivers of CSR and (3) challenges of CSR. Additionally, publications on CSR in emerging economies have been dominated by studies that used quantitative approach and cross-sectional design. A significant number of studies also employed secondary data sources with most of these studies not being sensitive to sectoral influences

Research limitations/implications

The research is non-empirical.

Practical implications

CSR is an area that can mitigate some of the developmental challenges of emerging economies and also stimulate the economic growth of firms. Thus, governments and organisations must partner to provide suitable conditions that would influence organisations to incorporate CSR in their business plans.

Originality/value

This review is the first of its kind that identifies the principal thematic domains of research on CSR in emerging economies. This review also provides proof of the areas of research that need attention and also provides recommendation on future areas of study on CSR in emerging economies.
Weathering the storm: talent management in internationally oriented Greek small and medium-sized enterprises
Authors: Kravariti Foteini , Oruh Emeka Smart , Dibia Chianu , Tasoulis Konstantinos , Scullion Hugh , Mamman Aminu
Published: July 2021

Purpose

Based on a study of internationally oriented Greek small and medium-sized enterprises (SMEs), and using the lens of institutional theory, this paper extends the understanding of the extent to which Greece's institutional context influences talent management (TM). In so doing, the authors focussed on the key TM practices employed by SMEs to enhance and sustain TM: talent acquisition, development and retention. The authors also explore how these practices are shaped by the Greek institutional context.

Design/methodology/approach

Employing a multiple case-study approach, the authors conducted 18 interviews in six distinctive SMEs operating in north, central and southern Greece. The data were thematically analysed to identify patterns across all SMEs.

Findings

This study found that unlike multinational corporations, internationally oriented Greek SMEs adopt a more inclusive approach to TM practices as well as that the country's institutional context presented important yet not deterministic hurdles. The authors also found that SMEs adopt an opportunistic approach to talent acquisition by utilising appropriate available sources to reach out for available talent. The authors provided evidence that SMEs adopt a hybrid approach to talent development in addressing talent scarcity. Finally, this study reported that talent retention is significantly appreciated by SMEs, who offer a range of intrinsic and extrinsic incentives to retain their talented workforce.

Practical implications

This study provides stakeholders with insights into how effective TM practices can be considered a lifeline to organisational sustainability – particularly for SMEs in the contemporary challenging and fiercely competitive business environment. It also highlights the potential of inclusive TM practices to be part of an effective workforce management strategy: Relative to the prevailing institutional dynamic, stakeholders (policymakers and human resource practitioners) must engage in the multiple areas of individual talent acquisition, development and retention.

Originality/value

In a context of reforms, this study reports on TM practice in internationally oriented Greek SMEs. The authors also add to the literature on TM in SMEs by providing evidence on the conceptualisation and management of global talent in this context.
Limited sink but large storage: Biomass dynamics in naturally developing beech (Fagus sylvatica) and oak (Quercus robur,Quercus petraea) forests of north‐western Germany
Authors: Meyer Peter , Nagel Rouven , Feldmann Eike
Published: July 2021

Currently, the dynamics underlying the storage and acquisition of biomass, and thus carbon, in naturally developing forests are under debate. A better understanding of the biomass dynamics of forests is needed to clarify the role played by naturally developing forests in the mitigation of climate change.

Long‐term monitoring data from unmanaged strict forest reserves (SFRs) in north‐western Germany were used to analyse the biomass dynamics of pure beech, mixed beech and mixed oak forests. A complete balance of above‐ground woody biomass (biomass) and growth, density‐dependent and ‐independent mortality, as well as deadwood decay was derived. Density‐independent mortality served as a proxy for disturbance severity.

After a time since abandonment (TSA) of 50 years, the average biomass ranged between 334 t/ha in mixed oak and 478 t/ha in pure beech stands. The net change in biomass was positive in all forest types. Density‐independent mortality and decay rates were much lower than the growth rates. Pure beech forests reached higher levels of biomass, a higher net change in biomass, and more growth than either of the mixed forest types. Biomass increased linearly with TSA in pure beech stands but followed an asymptotic course in the mixed forests. In the latter, the net change in biomass and growth were consistent with a unimodal development pattern. The development of biomass could not be explained by the ageing of the tree communities.

Synthesis. We hypothesized that the observed biomass dynamics are a result of the interaction between resource supply within a limited growing space and the resource‐use efficiency of the tree stand in conjunction with disturbances. The still‐linear increase in the biomass of pure beech forests was assumed to reflect the high resource‐use efficiency of beech, especially its use of light. The above‐ground capacity of naturally developing broadleaved forests to store and acquire carbon is substantial. Accordingly, allowing broadleaved forests to develop naturally can contribute substantially to carbon storage and sequestration. However, our study also suggests that the above‐ground carbon sink decreases after several decades.
Mire plant diversity change over the last 10,000 years: Importance of isostatic land uplift, climate and local conditions
Authors: Blaus Ansis , Reitalu Triin , Poska Anneli , Vassiljev Jüri , Veski Siim
Published: July 2021

Mires or peatlands host unique biodiversity and provide many valuable ecosystem services. Mires often undergo different development phases during their evolution. Two mire phases that have clearly divergent hydrological regimes and characteristic biotas are minerotrophic fen and ombrotrophic bog. Open mires can be overgrown by trees and develop into peatland forests. Mire development trajectories are expected to be associated with three major factors—post‐glacial isostatic uplift, autogenic succession and climate‐induced changes. Understanding long‐term mire development is important for the conservation planning of these threatened habitats.

We use data from modern pollen samples to characterize differences between the pollen signal and to identify indicator pollen taxa for three mire development phases—open fens, forested fens and bogs. The modern reference samples are then used to support the interpretation of the sediment records in terms of mire development phases and related biodiversity changes in six mires within a 20 × 30 km area in western Saaremaa, Estonia. Palynological richness and phylogenetic diversity (PD) as well as Ellenberg indicator values are compared throughout the 10,000‐year history of the Saaremaa mires.

Pollen of herbaceous taxa discriminates between open fens, forested fens and bogs, and indicator pollen taxa can be associated with each mire phase. In general, the fen phases of the mires show higher richness and PD than the bog phases but there is considerable variation between the sites. The mire diversity peaks are often associated with transitional periods when high local community heterogeneity allows the coexistence of high numbers of taxa from different phylogenetic lineages.

Synthesis. When the initiation of mires in isostatic land uplift areas is closely related to water‐level changes and the position of the sites in relation to the sea, the development of mires and their biodiversity in the late Holocene is associated with local conditions but mediated by climate. The ongoing rapid climate change is likely to accelerate changes in existing mires, and while the transitional periods are characterized by high diversity, these periods are temporary, and the overall diversity of mires can be expected to decrease.
Revisiting multi‐stage models for upstream technology adoption: Evidence from rapid generation advance in rice breeding
Authors: Lenaerts Bert , de Mey Yann , Demont Matty
Published: July 2021

Adoption of new plant varieties has played a significant role in eradicating global hunger. Previous research has mainly focused on farmer adoption and impact of new crop varieties, although upstream adoption of technologies in plant breeding can generate substantial multiplier effects on downstream impacts. This study moves upstream in the innovation system to generate policy advice on adoption and transfer of accelerated rice breeding technologies. More specifically, we assess the determinants of global adoption of rapid generation advance (RGA) through a sample of 158 rice breeders operating in various research institutes worldwide. Moving upstream in the innovation system has important theoretical and empirical implications due to the smaller number of decision‐making units in the adoption process and the increasing role of institutional and managerial factors that may overrule individual adoption motivations. We revisit multi‐stage models and devise the most robust estimation method that can be used in this situation. To generate insights on the impact of individual versus institutional adopter characteristics on upstream technology adoption, we juxtapose the response curves of the determinants of RGA adoption in rice breeding among alternative adoption stages, levels of conditionality and model specifications. Our findings confirm the importance of institutional and managerial factors and suggest that adoption and transfer of breeding technologies require breeding institutes to provide an enabling environment in which breeders are encouraged to take risks and are given sufficient freedom to experiment with and implement new technologies.
The Pediatric Emergency Research Network (PERN): A decade of global research cooperation in paediatric emergency care
Authors: Klassen Terry P , Dalziel Stuart R , Babl Franz E , Benito Javier , Bressan Silvia , Chamberlain James , Chang Todd P , Freedman Stephen B , Kohn Loncarica Guillermo , Lyttle Mark D , Mintegi Santiago , Mistry Rakesh D , Nigrovic Lise E , Oostenbrink Rianne , Plint Amy C , Rino Pedro , Roland Damian , Van de Mosselaer Greg , Kuppermann Nathan
Published: July 2021

Objectives

The Pediatric Emergency Research Network (PERN) was launched in 2009 with the intent for existing national and regional research networks in paediatric emergency care to organise globally for the conduct of collaborative research across networks.

Methods

PERN has grown from five to eight member networks over the past decade. With an executive committee comprising representatives from all member networks, PERN plays a supportive and collaborative rather than governing role. The full impact of PERN's facilitation of international collaborative research, although somewhat difficult to quantify empirically, can be measured indirectly by the observed growth of the field, the nature of the increasingly challenging research questions now being addressed and the collective capacity to generate and implement new knowledge in treating acutely ill and injured children.

Results

Beginning as a pandemic response studying H1N1 influenza risk factors in children, PERN research has progressed to multiple observational studies and ongoing global randomised controlled trials (RCTs). As a recent example, PERN has developed sufficient network infrastructure to enable the rapid initiation of a prospective observational study in response to the current COVID‐19 pandemic.

Conclusions

Following its success with developing global research, the PERN goal now is to promote the implementation of scientific advances into everyday clinical practice by: (i) expanding the capacity for global RCTs; (ii) deepening the focus on implementation science; (iii) increasing attention to healthcare disparities; and (iv) expanding PERN's reach into resource‐restricted regions. Through these actions, PERN aims to meet the needs of acutely ill and injured children throughout the world.