bluuebunny/crossref_metadata_2025 huggingface dataset:
disperseNN2: a neural network for estimating dispersal distance from georeferenced polymorphism data
Authors: Smith Chris C. R. , Kern Andrew D.
Published: July 2023

Spatial genetic variation is shaped in part by an organism’s dispersal ability. We present a deep learning tool,disperseNN2, for estimating the mean per-generation dispersal distance from georeferenced polymorphism data. Our neural network performs feature extraction on pairs of genotypes, and uses the geographic information that comes with each sample. These attributes leddisperseNN2to outperform a state-of-the-art deep learning method that does not use explicit spatial information: the mean relative absolute error was reduced by 33% and 48% using sample sizes of 10 and 100 individuals, respectively.disperseNN2is particularly useful for non-model organisms or systems with sparse genomic resources, as it uses unphased, single nucleotide polymorphisms as its input. The software is open source and available fromhttps://github.com/kr-colab/disperseNN2, with documentation located athttps://dispersenn2.readthedocs.io/en/latest/.
A transcriptome-wide meta-analysis reveals lack of cancer-cell intrinsic determinants of response to immune checkpoint blockade
Authors: Guo Yu Amanda , Kulshrestha Tanmay , Chang Mei Mei , Kassam Irfahan , Revkov Egor , Rizzetto Simone , Tan Aaron C. , Tan Daniel S.W. , Tan Iain Beehuat , Skanderup Anders Jacobsen
Published: July 2023

Immune-checkpoint therapy (ICB) has conferred significant and durable clinical benefit to some cancer patients. However, most patients do not respond to ICB, and reliable biomarkers of ICB response are needed to improve patient stratification. Here, we performed a transcriptome-wide meta-analysis across 1,486 tumors from ICB-treated patients and tumors with expected ICB outcomes based on microsatellite status. Using a robust transcriptome deconvolution approach, we inferred cancer and stroma-specific gene expression differences and identified cell-type specific features of ICB response across cancer types. Consistent with current knowledge, stromal expression ofCXCL9,CXCL13, andIFNGwere the top determinants of favorable ICB response. In addition, we identified a group of potential immune-suppressive genes, includingFCER1A, associated with poor response to ICB. Strikingly, PD-L1 expression in stromal cells, but not cancer cells, is correlated with ICB response across cancer types. Furthermore, the unbiased transcriptome-wide analysis failed to identify cancer-cell intrinsic features of ICB response conserved across tumor types. Overall, our results challenge the prevailing dogma that cancer cells present tissue-agnostic molecular markers that modulate immune activity and ICB treatment response. These results have implications for the development of improved ICB treatments and diagnostics.
Modelling The Brain’s Response To Natural Scenes In The Bottleneck Space
Authors: Ndubuaku Henry
Published: July 2023

Abstract

Computational models that mirror the brain’s behaviour can help us understand human intelligence and SOTA techniques for modelling the brain’s response to visual stimuli use deep neural networks. However, the best-performing vision models are compute-intensive and functional brain activities are represented by high-dimensional matrices which exacerbate this inefficiency. To this end, we propose a novel approach which showed significant performance improvements by 1) Projecting both the visual stimuli features and brain responses to low-dimensional vectors and using a non-linear neural network to learn the mapping in the latent space. 2) Simultaneously modelling all vertices in the visual cortices of both the left and right hemispheres using an objective we call “Racing Loss”. 3) Incorporating tiny leaks of the ground truth during training of this network. 4) First pre-training this network on all subjects then fine-tuning on each. We show that our method additionally achieved 12% higher Noise-Normalized Mean Correlation Scores compared to fully fine-tuning large vision models to the high-dimensional brain responses.
Missing microbial eukaryotes and misleading meta-omic conclusions
Authors: Krinos Arianna I. , Brisbin Margaret Mars , Hu Sarah K. , Cohen Natalie R. , Rynearson Tatiana A. , Follows Michael J. , Schulz Frederik , Alexander Harriet
Published: July 2023

Meta-omics has become commonplace in the study of microbial eukaryotes. The explosion of available data has inspired large-scale analyses, including species or taxonomic group distribution mapping, gene catalog construction, and inference on the functional roles and activities of microbial eukaryotesin situ. However, genome and transcriptome databases are prone to misannotation biases, and meta-omic inventories may have no recoverable taxonomic annotation for more than half of assembled contigs or predicted proteins. Direct mapping solely to organisms of interest might introduce a problematic misattribution bias, while full databases can annotate any cataloged organism but may be imbalanced between taxa. Here, we explore the potential pitfalls of common approaches to taxonomic annotation of protistan meta-omic datasets. We argue that ongoing curation of genetic resources is critical in accurately annotating protistsin situin meta-omic datasets. Moreover, we propose that precise taxonomic annotation of meta-omic data is a clustering problem rather than a feasible alignment problem. We show that taxonomic membership of sequence clusters demonstrates more accurate estimated community composition than returning exact sequence labels, and overlap between clusters can address database shortcomings. Clustering approaches can be applied to diverse environments while continuing to exploit the wealth of annotation data collated in databases, and database selection and evaluation is a critical part of correctly annotating protistan taxonomy in environmental datasets. We re-analyze three environmental datasets at three levels of taxonomic hierarchy in order to illustrate the critical importance of both database completeness and curation in enabling accurate environmental interpretation.
Global meta-analysis reveals overall benefits of silvopastoral systems for biodiversity
Authors: Perez-Alvarez Ricardo , Chará Julián , Snyder Lauren D. , Bonatti Michelle , Sieber Stefan , Martin Emily A.
Published: July 2023

Domestic livestock grazing accounts for roughly one quarter of the world’s terrestrial surface and is a leading driver of biodiversity loss. Yet, it also provides a critical livelihood for nearly one billion smallholder farmers, creating a paradox that highlights the need for conservation strategies to balance human and ecological needs. Silvopastoral systems (SPS) integrate trees with livestock pastures, offering a promising solution to boost livestock productivity while safeguarding natural areas and biodiversity. However, evidence for the biodiversity benefits provided by SPS is limited to studies focusing on specific geographic regions or taxa. Through a global meta-analysis of 45 studies spanning 15 countries, four biogeographic regions, and seven taxa, we provide the first quantitative synthesis evaluating how SPS affect biodiversity and community stability relative to treeless pastures and natural forests. Overall, we show that SPS harbor higher levels of biodiversity (i.e., richness, abundance, and diversity) and stability than treeless pastures, and perform comparably to nearby forests. However, variations exist across regions and taxa, with the strongest positive responses in tropical dry regions and for low-mobility taxa like invertebrates and plants. Mammals, birds, and soil microorganisms, on the other hand, showed no significant biodiversity differences between treeless pastures and SPS. Thus, integrating SPS and protected areas as complementary components of a multifunctional landscape will be key to halting multi-taxa biodiversity loss and building sustainable livestock systems. Our findings support the conservation potential of SPS, while underscoring the need for strategic implementation to maximize benefits for biodiversity conservation.
Genetic consequences of improved river connectivity in brown trout (Salmo trutta, L.)
Authors: Moccetti Paolo , Dodd Jamie R. , Joyce Domino A. , Nunn Andy D. , Gillespie Ben , Bolland Jonathan D.
Published: July 2023

Fragmentation of watercourses poses a significant threat to biodiversity, particularly for migratory fish species. Mitigation measures such as fishways, have been increasingly implemented to restore river connectivity and support fish migration. The effects of such restoration efforts are typically tested using telemetry and fisheries methods, which do not fully capture the broader population movements that may have important consequences for population viability. We performed a before-and-after control-impact (BACI) study using genetic tools (SNPs) to investigate the effect of a newly implemented fishway, aiming to enhance upstream spawning migration of brown trout (Salmo trutta, Linnaeus) in a reservoir with two headwater tributaries fragmented by man-made weirs. Another reservoir with two barrier-free tributaries was also analysed as a control. Our results showed that the isolated brown trout population was spawning in the reservoir before the installation of the fishway, and we found genetic structuring and differentiation between fragmented headwater tributaries before the fishway construction, but not in the control reservoir. Unexpectedly, after the fishway construction we observed signals consistent with increased genetic differentiation between populations of newly recruited juvenile fish in the reservoir tributary and fish in the reservoir. We propose this was caused by newly enabled philopatric behaviour of brown trout to their natal spawning tributary. In contrast, we did not find any genetic changes in the tributary without a fishway or in the barrier-free reservoir system. Given the scarcity of similar studies, we advocate for an increased use of genetic analyses in BACI studies to monitor and evaluate the effect of efforts to restore habitat connectivity and inform future management strategies.
The Endosomal pH Regulator NHE6 is Required for Insulin-Stimulated Glucose Uptake in Adipocytes
Authors: Mekile Allatah X. , Makena Monish Ram , Gupta Ruby , White Cory J. , Bowman Ray Wesley , Patnayak Rachana L. , Lorenzo Damaris N. , Rao Rajini
Published: July 2023

Objective

Trafficking ofGLUcoseTransporter isoform4(GLUT4) from the adipocyte vesicular pool to the cell surface is tightly regulated by insulin to maintain glucose homeostasis in response to changing demands in energy consumption. Previously, endosomal Na+/H+exchanger 6 (NHE6, gene nameSLC9A6) was identified in adipocyte plasma membranes and shown to associate with GLUT4-positive vesicles. However, the functional contribution of NHE6 to GLUT4 trafficking and glucose uptake remained uncharacterized.

Methods

NHE6 was knocked down in 3T3L1 cells either before or after differentiation into adipocytes using lentiviral delivery of shRNA. Uptake of [3H] 2-deoxyglucose into adipocytes was quantified in response to insulin. We used epitope tagged constructs to distinguish between localization of vesicular and surface levels of NHE6 and GLUT4 proteins. Protein and transcript levels of components of the glucose signaling pathway were monitored by qPCR and Western analysis, respectively, in response to NHE6 knockdown and/or treatment with chemical modulators of endosomal pH.

Results

We show that insulin-stimulated glucose uptake in adipocytes is severely impaired upon NHE6 depletion. Correspondingly, insulin-stimulated surface expression of GLUT4 at the adipocyte plasma membrane was diminished in NHE6 knockdown cells due to a post-transcriptional decrease in basal GLUT4. Metformin response of GLUT4 was also muted in the absence of NHE6. Further, we demonstrate diminished activation of the GLUT4 translocation pathway in the absence of NHE6 via reduced expression of the insulin receptor and reduced phosphorylation of the downstream effector kinase Akt. Components of GLUT4 storage vesicles, including GLUT4, LRP1 and sortilin were downregulated in NHE6-knockdown adipocytes under basal conditions. Proteostatic control of key components of the insulin signaling pathway (insulin receptor, GLUT4) could be restored by chemical bypass of NHE6 using the V-ATPase inhibitor bafilomycin or the Na+/H+exchanger mimetic monensin.

Conclusions

Thus, NHE6 is critical for proper expression and trafficking of GLUT4. Basal expression of both insulin receptor and GLUT4 in NHE6 knockdown cells could be restored by bafilomycin-inhibition of the H+-ATPase or the H+ionophore monensin pointing to pH dysregulation as the underlying defect. We suggest that NHE6 is a component of GLUT4 storage vesicles where it regulates proteostasis. These findings establish NHE6 as a novel contributor to glucose homeostasis and energy metabolism with implications for Christianson syndrome patients who carry loss of function mutations in theSLC9A6gene.

Graphical Abstract
Context-invariant beliefs are supported by dynamic reconfiguration of single unit functional connectivity in prefrontal cortex
Authors: Noel Jean-Paul , Balzani Edoardo , Savin Cristina , Angelaki Dora E.
Published: July 2023

Natural behaviors occur in closed action-perception loops and are supported by dynamic and flexible beliefs abstracted away from our immediate sensory milieu. How this real-world flexibility is instantiated in neural circuits remains unknown. Here we have macaques navigate in a virtual environment by primarily leveraging sensory (optic flow) signals, or by more heavily relying on acquired internal models. We record single-unit spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and the dorso-lateral prefrontal cortex (dlPFC). Results show that while animals were able to maintain adaptive task-relevant beliefs regardless of sensory context, the fine-grain statistical dependencies between neurons, particularly in 7a and dlPFC, dynamically remapped with the changing computational demands. In dlPFC, but not 7a, destroying these statistical dependencies abolished the area’s ability for cross-context decoding. Lastly, correlation analyses suggested that the more unit-to-unit couplings remapped in dlPFC, and the less they did so in MSTd, the less were population codes and behavior impacted by the loss of sensory evidence. We conclude that dynamic functional connectivity between prefrontal cortex neurons maintains a stable population code and context-invariant beliefs during naturalistic behavior with closed action-perception loops.
Chitosan stimulates root hair callose deposition and inhibits root hair growth
Authors: Drs Matěj , Haluška Samuel , Škrabálková Eliška , Krupař Pavel , Potocká Andrea , Brejšková Lucie , Muller Karel , Serrano Natalia , Voxeur Aline , Vernhettes Samantha , Ortmannová Jitka , Caldarescu George , Fendrych Matyáš , Potocký Martin , Žárský Viktor , Pečenková Tamara
Published: July 2023

Although angiosperm plants have a general capacity to react after the immunity elicitor chitin or chitosan treatment by the cell wall callose deposition, this response in particular cell types and its evolutionary conservation is not understood. Here we show that also the growing root hairs (RHs) of Arabidopsis can respond to a mild (0.001%) chitosan treatment by the callose deposition and by a deceleration of the RH growth. We demonstrate that the glucan synthase-like 5 (GSL5)/PMR4 is vital for chitosan-induced callose deposition but not for RH growth inhibition. Upon the higher chitosan concentration (0.01%) treatment, RHs do not deposit callose, while growth inhibition is prominent. To understand the specificities of the low and high concentration chitosan treatments, we analysed the corresponding PTI signalling components, gene expression, and RH cellular endomembrane and cytoskeleton modifications. Importantly, chitosan-induced callose deposition is also present in the functionally analogous and evolutionarily only distantly related RH-like structures rhizophores (lycophytes) and rhizoids (bryophytes). Our results point to the RH callose deposition as a conserved strategy of soil-anchoring plant cells (rhizoids/rhizophores/RHs) to deal with mild biotic stress. At the same time, high chitosan concentration prominently disturbs intracellular dynamics, tip-localised endomembrane compartments and RH growth, precluding callose deposition.
Mobile retroelements induced by hypomethylating agents are restricted to transpose in myeloid malignancies
Authors: Pavlová Šárka , Krzyžánková Marcela , Volakhava Anastasiya , Smirnova Anastasia , Grigoreva Tatiana , Jašková Zuzana , Synáčková Hana , Wahl Dennis , Bohúnová Michaela , Červinek Libor , Pospíšilová Šárka , Mamedov Ilgar , Plevová Karla
Published: July 2023

Retroelements (RE) present in the human genome are silenced via multiple mechanisms, including DNA methylation, to prevent their potentially mutagenic effect. RE activity, demonstrated by their expression and somatic retrotransposition events, is deregulated in multiple tumor types but not in leukemia. We hypothesized that treatment with hypomethylating agents (HMA), commonly used in myelodysplastic syndromes and acute myeloid leukemia, could lead to increased RE activity and somatic retrotranspositions, and contribute to disease progression. We induced expression of ORF1p protein encoded by long interspersed nuclear element-1 (L1) after 72h treatment with HMA in DAMI and HL-60 cell lines. ORF1p was predominantly localized in the cytoplasm, as evidenced by fluorescent microscopy of the DAMI cell line. To study whether long-term HMA therapy may induce somatic retrotranspositions, we (i) treated both cell lines for four weeks, (ii) analyzed a cohort of 17 MDS patients before and on treatment with HMA. Using a previously established sensitive NGS-based method, no RE events were identified. To conclude, we show that although HMA induces the expression of L1-encoded proteins in tumor myeloid cell lines,de novosomatic retrotransposition events do not arise during the long-term treatment of MDS patients and myeloid cell lines with these agents.
Spatial Omics Driven Crossmodal Pretraining Applied to Graph-based Deep Learning for Cancer Pathology Analysis
Authors: Azher Zarif , Fatemi Michael , Lu Yunrui , Srinivasan Gokul , Diallo Alos , Christensen Brock , Salas Lucas , Kolling Fred , Perreard Laurent , Palisoul Scott , Vaickus Louis , Levy Joshua
Published: July 2023

Graph-based deep learning has shown great promise in cancer histopathology image analysis by contextualizing complex morphology and structure across whole slide images to make high quality downstream outcome predictions (ex: prognostication). These methods rely on informative representations (i.e., embeddings) of image patches comprising larger slides, which are used as node attributes in slide graphs. Spatial omics data, including spatial transcriptomics, is a novel paradigm offering a wealth of detailed information. Pairing this data with corresponding histological imaging localized at 50-micron resolution, may facilitate the development of algorithms which better appreciate the morphological and molecular underpinnings of carcinogenesis. Here, we explore the utility of leveraging spatial transcriptomics data with a contrastive crossmodal pretraining mechanism to generate deep learning models that can extract molecular and histological information for graph-based learning tasks. Performance on cancer staging, lymph node metastasis prediction, survival prediction, and tissue clustering analyses indicate that the proposed methods bring improvement to graph based deep learning models for histopathological slides compared to leveraging histological information from existing schemes, demonstrating the promise of mining spatial omics data to enhance deep learning for pathology workflows.
Metagenomic ecosystem monitoring of soft scale and mealybug infestations in Australian vineyards
Authors: Ward Chris M. , Onetto Cristobal A. , Van Den Heuvel Steven , Dixon Robyn , Borneman Anthony R.
Published: July 2023

Soft scale insects and mealybugs are phloem feeding Hemipterans that are considered majors pests in agricultural and horticultural settings throughout the world. Viticulturally, scale are a major issue due to their ability to secrete honeydew, which facilitates the development of sooty mould and for their propensity as transmission vectors for several viral diseases of grapevine. To facilitate the rapid identification and quantification of vineyard-associated insects a metagenomic-based bioinformatic pipeline was developed for generalised ecosystem monitoring that automated the assembly and classification of insect mitochondrial genomes from shotgun sequencing data using the Barcode of Life Database API.Parthenolecanium corni(European fruit scale), which was thought to be absent from Australian grapevines, was identified as the dominant coccid species infesting all vines sampled, along with secondary infestation byPseudococcus viburni(obscure mealybug) andPseudo. longispinus(long-tailed mealybug). In addition, parisitoidism byCoccophagus scutellaris(Aphelinidae) wasps was also detected. The discovery ofParth. cornias a significant member of scale infestations in Australia has significant implications for the development of effective control strategies for this important group of pests.
ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota
Authors: Cheng Mingyang , Xu Bin , Sun Yu , Wang Junhong , Lu Yiyuan , Shi Chunwei , Pan Tianxu , Zhao Wenhui , Li Xiaoxu , Song Xiaomei , Wang Jianzhong , Wang Nan , Yang Wentao , Jiang Yanlong , Huang Haibin , Yang Guilian , Zeng Yan , Yang Dongqin , Wang Chunfeng , Cao Xin
Published: July 2023

E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Here we systematically identify the E3 ligase ASB3 as a facilitative regulator in the development and progression of IBD. ASB3-/-mice are resistant to DSS-induced colitis. IκBα phosphorylation levels and production of proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in colonic tissues of ASB3-/-mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotic clearance of the microbiota. Mechanistically, ASB3 specifically catalyzes K48-linked polyubiquitination of TRAF6 in IECs. In contrast, in ASB3-deficient organoids, the integrity of the TRAF6 protein is shielded, consequently decelerating the onset of intestinal inflammation. Taken together, Our findings demonstrates that ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors production by disrupting the TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis.
Identification of Sequence Determinants for the ABHD14 Enzymes
Authors: Vaidya Kaveri , Rodrigues Golding , Gupta Sonali , Devarajan Archit , Yeolekar Mihika , Madhusudhan M. S. , Kamat Siddhesh S.
Published: July 2023

Over the course of evolution, enzymes have developed remarkable functional diversity in catalyzing important chemical reactions across various organisms, and understanding how new enzyme functions might have evolved remains an important question in modern enzymology. To systematically annotate functions, based on protein sequences and available biochemical studies, enzymes with similar catalytic mechanisms and/or aspects of catalysis have been clustered together into an enzyme superfamily. Typically, enzymes within a superfamily have similar overall three-dimensional structures, conserved key catalytic residues, but large variations in substrate recognition sites and residues to accommodate the diverse biochemical reactions that are catalyzed within the superfamily. The serine hydrolases are an excellent example of such an enzyme superfamily, that based on known enzymatic activities and protein sequences, is split almost equally into the serine proteases and metabolic serine hydrolases. Within the metabolic serine hydrolases, are two outlying members, ABHD14A and ABHD14B, that have high sequence similarity, but their functions remained cryptic till recently. While ABHD14A still lacks any functional annotation to date, we recently showed that ABHD14B functions as a lysine deacetylase in mammals. Given their high sequence similarity, automated databases wrongly assign ABHD14A and ABHD14B as the same enzyme, and therefore, annotating functions to them in various organisms maybe problematic. In this paper, we present a bioinformatics study coupled to biochemical experiments, that identifies key sequence determinants for both ABHD14A and ABHD14B, and enables better classification for them. Additionally, we map these enzymes on an evolutionary timescale, and provide a resource in studying these interesting enzymes in different organisms.
NetVA: An R Package for Network Vulnerability and Influence Analysis
Authors: Kumar Swapnil , Pauline Grace , Vindal Vaibhav
Published: July 2023

In biological network analysis, identifying key molecules plays a decisive role in the development of potential diagnostic and therapeutic candidates. Among various approaches of network analysis, network vulnerability analysis is quite important, as it assesses significant associations between topological properties and the functional essentiality of a network. Further, some node centralities are also used to screen out key molecules. Among these node centralities, escape velocity centrality (EVC), and its extended version (EVC+) outperform others,viz., Degree, Betweenness, and Clustering coefficient. Keeping this in mind, we aimed to develop a first-of-its-kind R package named NetVA, which analyzes networks to identify key molecular players through network vulnerability and EVC+-based approaches. To demonstrate the application and relevance of our package in network analysis, previously published and publicly available protein-protein interactions (PPIs) data of human breast cancer were analyzed. This resulted in identifying some most important proteins. These included essential proteins, non-essential proteins, hubs, and bottlenecks, which play vital roles in breast cancer development. Thus, the NetVA package, available athttps://github.com/kr-swapnil/NetVAwith a detailed tutorial to download and use, assists in predicting potential candidates for therapeutic and diagnostic purposes by exploring various topological features of a disease-specific PPIs network.
Nanoscale analysis of human G1 and metaphase chromatinin situ
Authors: Chen Jon Ken , Liu Tingsheng , Cai Shujun , Ruan Weimei , Ng Cai Tong , Shi Jian , Surana Uttam , Gan Lu
Published: July 2023

The structure of chromatin at the nucleosome level inside cells is mysterious. Here we presentin situelectron cryotomography analyses of chromatin in both G1 and metaphase RPE-1 cells. G1 nucleosomes are concentrated in globular chromatin domains and metaphase nucleosomes are concentrated in the chromatids. Classification analysis reveals that canonical mononucleosomes, ordered stacked dinucleosomes, and mononucleosomes with a disordered gyre-proximal density are abundant in both cell-cycle states. Class averages that have more than two stacked nucleosomes or that have side-by-side dinucleosomes are not detected, suggesting that groups of more than two nucleosomes are heterogeneous. Large multi-megadalton structures are abundant in G1 nucleoplasm, but not found in G1 chromatin domains and metaphase chromatin. The macromolecular phenotypes studied here represent a starting point for the comparative analysis of compaction in normal and unhealthy human cells, other cell-cycle states, other organisms, andin vitrochromatin assemblies.
A transcriptome-based single-cell biological age model and resource for tissue-specific aging measures
Authors: Mao Shulin , Su Jiayu , Wang Longteng , Bo Xiaochen , Li Cheng , Chen Hebing
Published: July 2023

Accurately measuring biological age is crucial for improving healthcare for the elderly population. However, the complexity of aging biology poses challenges in how to robustly estimate aging and interpret the biological significance of the traits used for estimation. Here we present SCALE, a statistical pipeline that quantifies biological aging in different tissues using explainable features learned from literature and single-cell transcriptomic data. Applying SCALE to the “Mouse Aging Cell Atlas” (Tabula Muris Senis) data, we identified tissue-level transcriptomic aging programs for more than 20 murine tissues and created a multitissue resource of mouse quantitative aging-associated genes. We observe that SCALE correlates well with other age indicators, such as the accumulation of somatic mutations, and can distinguish subtle differences in aging even in cells of the same chronological age. We further compared SCALE with other transcriptomic and methylation “clocks” in data from aging muscle stem cells, Alzheimer's disease, and heterochronic parabiosis. Our results confirm that SCALE is more generalizable and reliable in assessing biological aging in aging-related diseases and rejuvenating interventions. Overall, SCALE represents a valuable advancement in our ability to measure aging accurately, robustly, and interpretably in single cells.
Structures of rac-2,4:3,5-dimethylene xylitol derivatives
Authors: Satlow Michael , Williard Paul G.
Published: July 2023

The structures of three racemic (tetrahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl)methanol derivatives are reported, namely, 4-[(methylsulfonyloxy)methyl]-2,4,4a,6,8,8a-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxine, C8H14O7S, 1, 4-[(benzyloxy)methyl]-2,4,4a,6,8,8a-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxine, C14H18O5, 2, and 4-[(anilinocarbonyl)methyl]-2,4,4a,6,8,8a-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxine, C14H17NO6, 3. Mesylate ester 1 at 173 K has triclinic P\overline{1} symmetry and both benzyl ether 2 at 173 K and phenyl urethane 3 have monoclinic P21/c symmetry. These structures are of interest because of the conformation of the cis-fused tetraoxadecalin ring system. This cis-bicyclo[4.4.0]decane ring system, i.e. cis-decalin, can undergo conformational equilibration. In the two most stable conformers, both six-membered rings adopt a chair conformation. However, there are significant consequences in these two stable conformers, with heteroatom substitution at the 1,3,5,7-ring positions as described. Only one conformation, denoted as `concave' or `inside', is found in these crystal structures. This is consistent with previously reported structures of the 1,1-geminal dihydroxy aldehyde and tosylate analogs.
Aeroengine gas trajectory prediction using time-series analysis auto regressive integrated moving average
Authors: Mary Victoria Florence M. , Priyadarshini E.
Published: July 2023

Purpose

This study aims to propose the use of time series autoregressive integrated moving average (ARIMA) models to predict gas path performance in aero engines. The gas path is a critical component of an aero engine and its performance is essential for safe and efficient operation of the engine.

Design/methodology/approach

The study analyzes a data set of gas path performance parameters obtained from a fleet of aero engines. The data is preprocessed and then fitted to ARIMA models to predict the future values of the gas path performance parameters. The performance of the ARIMA models is evaluated using various statistical metrics such as mean absolute error, mean squared error and root mean squared error. The results show that the ARIMA models can accurately predict the gas path performance parameters in aero engines.

Findings

The proposed methodology can be used for real-time monitoring and controlling the gas path performance parameters in aero engines, which can improve the safety and efficiency of the engines. Both the Box-Ljung test and the residual analysis were used to demonstrate that the models for both time series were adequate.

Research limitations/implications

To determine whether or not the two series were stationary, the Augmented Dickey–Fuller unit root test was used in this study. The first-order ARIMA models were selected based on the observed autocorrelation function and partial autocorrelation function.

Originality/value

Further, the authors find that the trend of predicted values and original values are similar and the error between them is small.
Clients as drivers of innovation in the infrastructure sector: implications of hard and soft project management approaches
Authors: Guerrero Jacob , Engström Susanne
Published: July 2023

Purpose

By adopting the “hard” and “soft” project management (PM) approaches from the PM-literature, this paper aims to problematize the expected role of client organizations in driving innovation in the transport infrastructure sector.

Design/methodology/approach

Addressing a large public client in Sweden, a case study design was initially applied to provide in-depth insights and perspectives of client project managers’ views and experiences of managing projects expected to drive innovation. In this paper, the concepts of “hard” and “soft” are used to discuss empirical findings on challenges associated with adopting a PM-approach for driving innovation in projects. The empirical material consists of interview data, complemented with observations and archival data.

Findings

Findings reveal challenges associated with combining hard and soft approaches, frequently demonstrating difficulties in balancing short-term project expectations with the promotion of innovation. In line with the literature, project managers note that there is a need for soft approaches to promote development and drive innovation. Yet, findings reflect a situation in which operational success criteria predominate, whereas soft approaches are not sufficiently used to create the grounds required for fostering innovation.

Originality/value

Insights are provided into how PM-approaches may impact construction innovation in the infrastructure sector, demonstrating a need for further research on the challenges and implications of applying and combining hard and soft PM-approaches.
Innovation as a firm-level factor of the gender wage gap
Authors: Masso Jaan , Vahter Priit
Published: July 2023

Purpose

This paper investigates the relationship of both technological (product and process) and non-technological (organizational and marketing) innovation with the gender wage gap at firms.

Design/methodology/approach

Using employer–employee level data from Estonia, the authors estimate Mincerian wage equations, in order to show how innovation at the firm level is associated with the gender wage gap. Next, the authors use propensity score matching (PSM) to study the effects of the movement of men and women into innovative firms, how this shapes the gender wage gap at firms.

Findings

The authors find that both technological and non-technological innovation are associated with a larger gender wage gap at firms. The relationship between innovation and the contemporaneous gender wage gap at firms reflects to a significant extent the different selection of men and women with different time-invariant characteristics to innovative firms. Further, the authors find that movement of men and women to work at innovative firms is in longer term associated with larger gains in wages for men. The authors also observe that the relationship of innovation with gender wage gap is stronger in the case of women with children.

Originality/value

Much of the prior analysis focuses on the effects of technological innovation on gender-related labour market outcomes. The authors show here that the relationship of innovation at firms with higher gender wage gap is not only specific to technological innovation, but is more general, and is observed across different types of innovation indicators, including non-technological innovation. This study's results suggest that the effects of innovation on gender wage gap may reflect to an extent the higher demand for flexibility of employees for work purposes at innovative firms, which may increase the gender wage gap, especially between men and women with children.
A new perspective on behavior-based sales control system and salespersons’ job outcomes: an outbound pharmaceutical sales perspective
Authors: Khan Faheem Ahmad , Ahmad Maria , Saeed Tahir
Published: July 2023

Purpose

This study aims to investigate the direct effect of the behavior-based sales control system on job outcomes: salesperson’s performance and turnover intentions. The current study also intends to integrate these two streams by conceptualizing work engagement as a mediating variable between behavior-based sales control systems and salespersons’ job outcomes in the pharmaceutical sales context.

Design/methodology/approach

Data was collected through multi-stage stratified random sampling from a sample of 619 salespersons working in 20 pharmaceutical firms (multinational and national) through self-administered questionnaires.

Findings

The structural equation model yielded results indicating that the behavior-based sales control system was positively related to salespersons’ work engagement and negatively to turnover intentions while the relationship between the behavior-based sales control system and salespersons’ job outcomes was mediated by work engagement.

Originality/value

Two relatively separate lines of investigation have appeared in academic literature. The first line centered on sales force control systems and salespersons’ related consequences, whereas the second line of investigation emphasizes work engagement and its consequences. Although both lines are important, a diminutive research effort has been made to join these two different lines of investigation in sales management, specifically, in the pharmaceutical context. Focusing on this, the current research explores the role of an unexplored construct of work engagement in a pharmaceutical sales context. Second, it addresses the need to identify additional mediating variables to clarify the inconsistent relationship between sales control systems and job outcomes, such as job performance and turnover intentions.
Dismissing uncertainties about open innovation constraints to organizational agility in emerging markets: is knowledge hiding a perfect storm?
Authors: Urresta-Vargas Daniela , Carvajal-Vargas Valeria , Arias-Pérez José
Published: July 2023

Purpose

As a key driver of organizational agility, open innovation allows for improving time-to-market and complexity, which are the mechanisms that most significantly lower the risk of knowledge expropriation in emerging markets. For this reason, there is concern about the negative impacts of hiding knowledge in the context of inter-organizational collaborative work. Therefore, the research goal is to analyze the moderating effect of the three types of knowledge hiding (playing dumb, evasive hiding and rationalized hiding) on the relationship between open innovation (both inbound and outbound) and agility.

Design/methodology/approach

The research model was tested with survey data from a sample of 248 companies located in an emerging country, mostly from sectors of high turbulence in demand and technology.

Findings

None of the three types of knowledge hiding has a negative effect on the relationship between open innovation and agility. Surprisingly, evasive hiding has a positive and significant effect, specifically on the relationship between inbound open innovation and agility.

Originality/value

The study contributes to the discussion on the contradictory influence of knowledge hiding. Although the presence of knowledge hiding in business relationships with their external partners is undeniable, this research makes clear that, when faced with the particular need to be agile, businesses recognize that the benefits of open innovation in terms of time-to-market improvement and complexity outweigh the protectionism underlying hiding. Moreover, the study results suggest evasive hiding is essential for the inbound process to use time effectively and avoid wasting it in discussions that do not promote agility.
Is there an optimum way for the commercial property market to adjust to the changing circumstances?
Authors: Banytė Jurgita , Mulhearn Christopher
Published: July 2023

Purpose

This article seeks to offer an answer. It explores the criteria on which commercial property market participants can develop strategies in hugely challenging circumstances. For this purpose, a survey-based approach was developed with work conducted with property-market professional in the United Kingdom (UK), France, Germany and Sweden to produce a criteria-based tool supporting adaption to changing market circumstances.

Design/methodology/approach

The data have been analyzed using statistical analysis. The data's statistical analysis included Cronbach's alpha's application to evaluate the respondents' replies' reliability. A entral tendency test was used to identify the means of relevance of the criteria. The Mann–Whitney U test was used to determine potential material differences between the UK and other countries with Bonferroni corrections applied to minimize type-I errors.

Findings

Thirty characteristics have been identified that impact the dynamics of the commercial property market. Their relevance to the commercial property market was determined using a survey. The literature analysis showed that the researchers paid more attention to quantitative criteria and their comparison. The survey showed that the relevance of criteria to the commercial property market dynamics is unequal. However, the survey results showed that it is most important to pay attention to emotional criteria to adapt to uncertainty changing conditions. The problem of the environment has been on the agenda for the last four decades. Therefore, the fact that the results of the study showed that the environmental criteria are the least significant is unexpected.

Research limitations/implications

The study involved economically developed countries of Europe. Extending the study's geographical scope would be valuable in revealing whether the same differences exist in other geographical areas (such as Australia or the USA).

Practical implications

The practical implication of the analysis may be to facilitate the decision-making process of either selecting a country for commercial property investment or selecting the most sensitive and relevant criteria for the decision-making.

Originality/value

Criteria for commercial property market performance which promote successful property investment have been developed. Moreover, the criteria affecting the commercial property market have been weighted by their relevance to the market and their sequence of relevance has been established. And finally, the developed criteria have been placed into five groups that could serve as a foundation for a macro-level assessment of commercial property market dynamics.
Population density affects sexual selection in an insect model
Authors: Winkler Lennart , Eilhardt Ronja , Janicke Tim
Published: July 2023

Understanding the impact of demographic and ecological factors on the strength of sexual selection is pivotal to predict eco‐evolutionary dynamics in populations facing environmental change. Density is expected to show pervasive intra‐ and interspecific variation in natural populations, but its effect on sexual selection remains largely unexplored.

We tested experimentally the effect of density on standardized metrics of sexual selection in male and female red flour beetles. Specifically, we explored density effects during mating by manipulating the size of mating groups and the mating arena.

We found that higher densities imposed by a larger group size amplified the opportunity for pre‐copulatory sexual selection in females and, to a smaller extent, also in males. Moreover, in males, we detected a higher opportunity for post‐copulatory sexual selection in larger groups. By contrast, higher densities imposed by differences in the size of the mating arena resulted in a steeper male sexual selection gradient.

Overall, these data suggest that density is an important environmental factor contributing to the tremendous variation in the strength of sexual selection within and among species.

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Silicon supplementation and jasmonate activation synergistically increase phenolic defences against a legume herbivore
Authors: Ryalls J. M. W. , Gherlenda A. N. , Rowe R. C. , Moore B. D. , Johnson S. N.
Published: July 2023

The accumulation of silicon (Si) is widely reported to have anti‐herbivore defensive properties in grasses. There is emerging, but fragmentary, evidence that Si could play a similar role in legumes.

Here, we sought to understand the effects of Si supplementation on anti‐herbivore defensive properties in lucerne (Medicago sativa), especially in relation to other potential defences (i.e. phenolics) and the phytohormone that regulates anti‐herbivore defences, jasmonic acid or jasmonate (JA), which is also linked to Si accumulation.

We determined how growth, root nodulation and chemistry (carbon, nitrogen and phenolic concentrations) of four genotypes of lucerne responded to Si supplementation, with and without the application of JA, and we used feeding assays to determine the subsequent effects on the feeding success of adult Sitona discoideus weevils.

Si supplementation increased plant mass and root nodulation of M. sativa by 61% and 227%, respectively, and reduced relative consumption (RC) and frass production by S. discoideus by 38% and 30% respectively. Si supplementation had no effect on foliar nitrogen concentrations, most likely due to the dilution effects of increased plant growth and foliar carbon. Phenolic concentrations were negatively correlated with leaf RC; RC also decreased by 34% when JA was applied to plants. When Si was combined with JA application, phenolics were significantly enhanced, demonstrating the potential to stimulate multiple anti‐herbivore properties in M. sativa. Overall, the Si‐ and JA‐induced phytochemical and herbivore feeding responses were consistent between the four lucerne genotypes tested.

Synthesis. The novel findings suggest that Si accumulation may play a more important role in legume resistance to herbivorous animals than previously thought. The ubiquity of soil Si and its emerging functional role in plant biology, including plant–animal interactions, suggest that these patterns could be common among legumes.