bluuebunny/crossref_metadata_2025 huggingface dataset:
The Specific Genetic Markers to Diagnose Xanthomonads Infecting Pepper and Tomato Plants
Authors: Can Ahmet , Abdul-Baasit Abdul-Nasır , Belen Ilayda Nur , Capar Umran , Sener Burak , Basaran Ceyda C. , Sulu Serap Melike , Kusek Mustafa , Silme Ragip Soner , Baysal Omur
Published: January 2025

We have improved a marker system to examine the genetic diversity in Xanthomonads species by using whole genome sequence analysis and repetitive regions in the bacterial genome. Specifically, we amplified microsatellite regions using PCR, and the resulting fragments were digested with specific enzymes. These fragment profiles served as molecular markers. Consequently, a more precise marker for bacterial identification was developed by combining the microsatellite and RFLP methods to differentiate Xanthomonads species. In Addition, we analysed the ancestral ordering of variousXanthomonasspecies’ genomes available in NCBI using Progressive Mauve Alignment. The data revealed unique collinear regions characteristic ofXanthomonasspecies. These regions were also associated with cut genomic fragments used as markers, enabling the discrimination ofXanthomonasspecies infecting tomato and pepper. We propose that these findings contribute to understanding the genetic diversity ofXanthomonasand rapidly diagnosis.
Carbon monoxide exposure stimulates growth and activity of primary producers in diverse soil ecosystems
Authors: Xu Yongfeng , Teng Ying , Liao Jing , Leung Pok Man , Dai Shixiang , Sun Yi , Hu Wenbo , Wang Hongzhe , Li Yanning , Huang Yuqi , Guo Zhiying , Pan Xianzhang , Dong Xiyang , Luo Yongming , Greening Chris
Published: January 2025

Carbon monoxide (CO) is both a potent poison for many aerobic organisms and a desirable energy source for diverse microorganisms. Atmospheric emissions of this gas have increased since industrialization and their levels are highly elevated in many urban and natural environments; however, it is unresolved whether elevated levels of CO at environmentally relevant concentrations are primarily stimulatory or inhibitory to soil microbial communities. Here, we showed that CO exposure minimally affects microbial abundance, richness, and composition in diverse ecosystem soils, suggesting most microbes are tolerant of this gas. Genome-resolved metagenomic profiling showed that these soils harbored diverse bacteria capable of using CO an electron donor for aerobic respiration and carbon fixation. CO stimulated the growth of several of these putative CO-oxidizing bacteria in a dose-dependent manner, especially widespread proteobacterial and actinobacterial lineages. Additionally, we found a strong relationship between CO oxidation and carbon fixation and observed an enrichment of several carboxydotrophic MAGs capable of carbon fixation in most soil types. These findings highlight that environmentally relevant CO levels do not inhibit soil microbes, but instead foster the growth of distinct carboxydotrophic bacteria, suggesting a robust soil CO sink that could help mitigate anthropogenic CO emissions and contribute to carbon cycling in terrestrial ecosystems.
Multi-omics reveals global signaling rewiring and identifies Activin A-induced dysregulation of FOS/Activator Protein 1 as a novel target in Fibrodysplasia ossificans progressiva
Authors: Wits Marius , Gómez-Suárez Nerea , López Alexandre Deber , Farfán Nicole , Bekedam Fjodor , Sampadi Bharath , Rotman Sarah , López Daniel Rubiera , Márquez Judit Bestilleiro , Arendzen Christiaan , Freund Christian , Veelen Peter van , Valldeperas Aida Llucià , Man Frances de , Ventura Francesc , Goumans Marie-José , Sanchez-Duffhues Gonzalo
Published: January 2025

Background

Fibrodysplasia ossificans progressiva (FOP) is caused by an activating mutation (p.R206H) in the type I BMP receptor ALK2, leading to heterotopic ossification (HO) in soft connective tissues. While aberrant Activin A-induced SMAD signaling is central in FOP pathogenesis, global signaling alterations remain poorly understood.

Methods

We performed phosphoproteomics, transcriptomics and biochemical analyses in mesenchymal cells (MSCs) overexpressing wild-type ALK2WTor mutant ALK2R206Hreceptors and in induced-MSCs derived from FOP patient iPSCs. Findings were validated in vivo using FOP-like mouse models and in vitro via pharmacological interventions.

Results

Multi-omics analyses revealed previously unrecognized signaling networks in ALK2R206Hcells, including enhanced MAPK, mTOR, RUNX2 and RHO-mediated mechanotransduction pathways. Notably, we identified dysregulated Activator Protein-1 (AP-1) expression and function as a novel contributor to FOP. AP-1 factors were highly enriched in HO lesions in FOP-like animals. Pharmacological inhibition of AP-1 significantly reduced osteochondrogenic differentiation in vitro.

Conclusion

This study highlights global signaling dysregulation in FOP and identifies AP-1 as a critical driver and potential therapeutic target for FOP.
Telemetry validation of dorsal scute microchemistry: complementary tools reconstruct the migratory life-history of an endangered population of Atlantic Sturgeon
Authors: Ingram Evan C. , Altenritter Matthew E. , Wilson Kylee B. , Frisk Michael G. , McCartin Kellie R.
Published: January 2025

An understanding of age-specific habitat requirements and the timing of critical ontogenetic transitions is essential to inform conservation and recovery efforts for Atlantic Sturgeon (Acipenser oxyrinchus). However, these are often difficult to assess due to the species’ cryptic nature and the consequent lack of temporal and spatial habitat data across life stages. Sampling and microchemistry analysis of dorsal scute apical spines (i.e., dorsal scutes) represents an innovative methodology to reconstruct past life-history events of endangered populations of Atlantic Sturgeon. Here, we establish the broad potential of dorsal scute sampling for wild-caught Atlantic Sturgeon and compare age-estimates and trace-element ratio patterns from dorsal scute with those from pectoral fin spines. We also evaluate microchemistry signatures from both structures to infer past habitat use and age at initial entry into marine waters and, importantly, validate these interpretations using known locations from acoustic telemetry detections. Major ontogenetic shifts in habitat use detected in the microchemistry signatures suggest our methodology was appropriate to identify the timing of initial juvenile migration into marine habitat, while providing additional information regarding the timing of transitions between freshwater and marine habitats that are essential to the management and conservation of this endangered species. As such, the collection of dorsal scute samples is suggested to complement ongoing research efforts for wild-populations and provides additional data points beyond those available from conventional tag-recapture methods alone, allowing researchers and managers to retrospectively identify environmental transitions and habitat use that occur prior to sampling encounters or outside of monitored areas.
PI3K regulates TAZ/YAP and mTORC1 axes that can be synergistically targeted
Authors: Garcia Keith C. , Khan Ali A. , Ghosh Krishnendu , Sinha Souradip , Scalora Nicholas , DeWane Gillian , Fullenkamp Colleen , Merritt Nicole , Drebot Yuliia , Yu Samuel , Leidinger Mariah , Henry Michael D. , Breheny Patrick , Chimenti Michael S. , Tanas Munir R.
Published: January 2025

Abstract/Summary

Purpose

Sarcomas are a heterogeneous group of cancers with few shared therapeutic targets. PI3K signaling is activated in various subsets of sarcomas, representing a shared oncogenic signaling pathway. Oncogenic PI3K signaling has been challenging to target therapeutically. An integrated view of PI3K and Hippo pathway signaling is examined to determine if this could be leveraged therapeutically.

Experimental design

A tissue microarray containing sarcomas of various histological types was evaluated for PTEN loss and correlated with levels of activated TAZ and YAP. PI3K and Hippo pathways were dissected in sarcoma cell lines. The role of TAZ and YAP were evaluated in a PI3K-driven mouse model. The efficacy of mTORC1 inhibition and TEAD inhibition were evaluated in sarcoma cell lines andin vivo.

Results

PI3K signaling is frequently activated in sarcomas due to PTEN loss (in 30-60%), representing a common therapeutic target. TAZ and YAP are transcriptional co-activators regulated by PI3K and drive a transcriptome necessary for tumor growth in a PI3K-driven sarcoma mouse model. Combination therapy using IK-930 (TEAD inhibitor) and everolimus (mTORC1 inhibitor) synergistically diminished proliferation and anchorage independent growth of PI3K-activated sarcoma cell lines at low, physiologically achievable doses. Furthermore, this combination therapy showed a synergistic effectin vivo, reducing tumor proliferation and size.

Conclusions

TAZ and YAP are transcriptional co-activators downstream of PI3K signaling, a pathway that has lacked a well-defined oncogenic transcription factor. This PI3K-TAZ/YAP axis exists in parallel to the known PI3K-Akt-mTORC1 axis allowing for synergistic combination therapy targeting the TAZ/YAP-TEAD interaction and mTORC1 in sarcomas.
CHD2 Dosage Ties Autolysosomal Pathway to Cortical Maturation in Disease and Evolution
Authors: Leonardi Oliviero , Lewerissa Elly , Aprile Davide , Barakat Tahsin Stefan , Culotta Lorenza , Deng Ruizhi , Haazen Linda , Linda Katrin , Majoie Marian , Mordelt Annika , Ortale Aurelio , Oudakker Astrid , Prazzoli Filippo , Puvogel Sofia , Scheefhals Nicky , Schelhaas Helenius J , Schoenmaker Chantal , van Hugte Eline , van Bokhoven Hans , Verhoeven Judith , Vitriolo Alessandro , Boeckx Cedric , Testa Giuseppe , Kasri Nael Nadif
Published: January 2025

The relatively slow pace of cortical development in humans has long been a topic of investigation. Studies seeking to understand the underlying mechanisms have mostly focused on neurogenetic comparisons with extant species. Here we ask if developmental tempo differences may have also existed between us and our extinct relatives for whom genomes are available. To do so, we nominate asapiens-specific derived allele, virtually fixed in contemporary populations, which resides in an enhancer region active during early cortical development. The single nucleotide variant is predicted to significantly affect CHD2 expression, a chromatin remodeler known to play an important role in neural development and for which haploinsufficiency is associated with epilepsy and autism. We leverage patient induced pluripotent stem lines (iPSC) and engineered iPSCs in which we reintroduced the ancestral allele and generated heterozygous loss-of-function mutations. We reveal that CHD2 deficiency impairs lysosomal acidification and autophagosome flux. In contrast, ancestralized lines, which we find express higher levels of CHD2, exhibit enhanced lysosomal function and consequently accelerated autophagosome flux, consistent with our observations in chimpanzee and bonobo lines. This set of findings demonstrates that CHD2 dosage critically regulates the autolysosomal pathway. Through deep phenotyping of cortical organoid and neuron cultures, we show that the CHD2-modulated autolysosomal pathway impacts the timing of developmental programs, acquisition of neuronal functional properties and circuit maturation. Finally, we validate an estrogen-dependent rewiring of CHD2 regulation in the evolution of our lineage, providing a mechanistic understanding of how a single nucleotide variant in a regulatory region contributed to the modern pace of neuronal development and maturation. Together, our findings establish CHD2 as a regulator in setting neurodevelopmental tempo via the autolysosomal pathway.
Spatial Frequency Maps in Human Visual Cortex: A Replication and Extension
Authors: Ha Jiyeong , Broderick William F. , Kay Kendrick , Winawer Jonathan
Published: January 2025

In a step toward developing a model of human primary visual cortex, a recent study introduced a model of spatial frequency tuning in V1 (Broderick, Simoncelli, & Winawer, 2022). The model is compact, using just 9 parameters to predict BOLD response amplitude for locations across all of V1 as a function of stimulus orientation and spatial frequency. Here we replicated this analysis in a new dataset, the ‘nsdsynthetic’ supplement to the Natural Scenes Dataset (Allen et al., 2022), to assess generalization of model parameters. Furthermore, we extended the analyses to extrastriate maps V2 and V3. For each retinotopic map in the 8 NSD subjects, we fit the 9-parameter model. Despite many experimental differences between NSD and the original study, including stimulus size, experimental design, and MR field strength, there was good agreement in most model parameters. The dependence of preferred spatial frequency on eccentricity in V1 was similar between NSD and Broderick et al. Moreover, the effect of absolute stimulus orientation on spatial frequency maps was similar: higher preferred spatial frequency for horizontal and cardinal orientations compared to vertical and oblique orientations in both studies. The extension to extrastriate maps revealed that the biggest change in tuning between maps was in bandwidth: the bandwidth in spatial frequency tuning increased by 70% from V1 to V2 and 100% from V1 to V3, paralleling known increases in receptive field size. Together, the results show robust reproducibility and bring us closer to a systematic characterization of spatial encoding in the human visual system.
Distinct Genetic Populations and Resistance Backgrounds of the Malaria VectorAnopheles funestusin Tanzania
Authors: Odero Joel O. , Nambunga Ismail H. , Bwanary Hamis , Mkandawile Gustav , Paliga John M. , Mapua Salum A. , Mwinyi Sophia H. , Ngowo Halfan S. , Govella Nicodem J. , Kaindoa Emmanuel W. , Tripet Frédéric , Hernandez-Koutoucheva Anastasia , Ferguson Heather M. , Clarkson Chris S. , Miles Alistair , Weetman David , Baldini Francesco , Okumu Fredros O. , Dennis Tristan P. W.
Published: January 2025

Population genetic analysis of mosquitoes is becoming increasingly important for understanding the distribution of insecticide resistance alleles, devising sustainable insecticide-based vector control approaches, and how malaria vector populations are structured in space.Anopheles funestusis the dominant malaria vector in Tanzania and most parts of East and Southern Africa. To better understand its population genomic structure in Tanzania, we sequenced the genomes of 334 individualAn. funestusmosquitoes from 11 administrative regions. We found two genetically differentiated populations; one inland and at high altitude (found in Katavi, Kagera, Kigoma, and Mwanza) and a second coastal, at low altitude (found in Pwani, Morogoro, Tanga, Ruvuma, Mtwara, Dodoma, and Lindi), with differences in genetic diversity and inbreeding. We found asynchronous selective sweeps, associated with insecticide resistance phenotypes, at theCyp9k1gene, andCyp6pgene cluster, with distinct copy number-variant profiles between the coastal and inland populations. These results suggest that inland and coastalAn. funestuspopulations have divergent histories, with the arid, central region of Tanzania, which also contains the Rift Valley being a possible barrier to gene flow. Such population disconnectedness should be considered for insecticide deployment, resistance management, and the rollout of novel genetic- based vector control approaches. These findings provide the most detailed study of TanzanianAn. funestuspopulation structure and resistance genetics to date. Future research should examine the epidemiological relevance of this discontinuity in gene flow and whether these populations have different malaria transmission abilities.
Defining epithelial stem cell heterogeneity through undulating structures of the skin and oral mucosa
Authors: Ishikawa Mizuho , Ngo Yen Xuan , Nishikawa Ikuto , Kato Hiroko , Maeda Ryo , Mizuno Ryosuke , Mizuno Jun , Izumi Kenji , Yanagisawa Hiromi , Sada Aiko
Published: January 2025

Epithelial stem cells exhibit heterogeneity, with distinct stem cell populations occupying specific tissue regions. The human skin displays a characteristic undulating structure at the epidermal-dermal junction, which supports mechanical strength and influences the spatial organization of epithelial stem cells. Unlike human skin, mouse skin lacks these undulations, complicating studies into the effects of tissue architecture on stem cell distribution. Here, we leverage the mouse oral mucosa, which possesses an undulating structure similar to human skin, to characterize stem cell division dynamics and long-term fatein vivo. Using a combination of H2B-GFP pulse-chase analysis and lineage tracing with Dlx1-CreER and Slc1a3-CreER models, we demonstrate that slow-and fast-cycling stem cells localize to distinct anatomical regions relative to the undulating structure and maintain their respective compartments during tissue homeostasis. A three-dimensional culture model using micropatterned collagen scaffolds that recapitulate the undulating structuresin vitroreveals that the mechanical environment generated by the undulating structures partially induces proliferative heterogeneity in epithelial stem cells. This study proposes tissue undulating surface structure as a common principle as a niche component that defines the localization of compartmentalized stem cell populations across different epithelial tissues.

Abstract Figure
A robust platform streamlining aromatic noncanonical amino acid biosynthesis and genetic code expansion inEscherichia coli
Authors: Zhang Jingxuan , Yu Keying , Xu Yali , Zhao Wushuang , Li Yulian , Wang Ying , Seebeck Florian P. , Chen Xiaohua , Liao Cangsong
Published: January 2025

Genetic code expansion has significantly enhanced the diversity and functionality of proteins in the biological world, leading to a wide range of applications in catalysis, biology, and medicine. Despite the extraordinary advances in genetic code expansion over the past years, the availability and cost of noncanonical amino acids (ncAAs) remain one of the major obstacles, particularly for large-scale industrial production.In situbiosynthesis of ncAAs from commercially available precursors offers a promising solution to this challenge, yet only a few biosynthetic pathways for specific amino acids have been reported to date. To address this gap, we present a robust platform that couples the biosynthesis of aromatic amino acids with genetic code expansion inE. coli, enabling the production of proteins and peptides containing incorporated ncAAs. Forty amino acids with diverse functional groups were synthesized from aryl aldehydes by a biosynthetic pathway comprising two heterologously expressed enzymes and one endogenous enzyme. Nineteen of these amino acids were successfully incorporated into superfolder GFP (sfGFP) using three classic orthogonal translation systems. The platform’s versatility was further demonstrated by the production of macrocyclic peptides and antibodies containing functional ncAAs, such aspara-azidophenylalanine andpara-boronophenylalanine. We envision that the simplicity, efficiency, compatibility, and broad applicability of this biosynthetic pathway and the platform will greatly facilitate the production of peptides, enzymes, and antibodies containing ncAAs, thereby accelerating their use in various applications.

Graphical abstract
Mechanical signalling through collagen I regulates cholangiocyte specification and tubulogenesis during liver development
Authors: Thelwall Iona G. , Morell Carola M. , Dziedzicka Dominika , Cabriales Lucia , Hodgson Andrew , Roos Floris J.M. , Elfari Louis , Vallier Ludovic , Chalut Kevin J.
Published: January 2025

Cholangiocyte dysfunction accounts for a third of liver transplantations, access to which is limited by a shortage of healthy donor organs. A promising alternative is the therapeutic use of human induced pluripotent stem cell (hiPSC)-derived cholangiocytes. However, the use of hiPSCs is impeded by a lack of knowledge regarding intrahepatic cholangiocyte development, limiting the generation of fully functional cells. In this study, we generate hiPSC-derived tubular cholangiocytes using an approach based in synthetic hydrogels. These hydrogels exert control over stiffness and extracellular matrix (ECM) composition and stability, allowing us to address a critical gap in understanding cholangiocyte development. Our findings reveal that stable collagen I functionalisation, particularly on a soft substrate, enhances cholangiocyte differentiation, largely irrespective of substrate stiffness. Furthermore, high collagen I stability on a soft substrate suppresses hepatic identity whilst promoting biliary identity and duct morphogenesis. Our findings highlight the importance of collagen I mechanical signalling in regulating hepatoblast fate determination. Overall, we propose a mechanism by which the ECM modulates cholangiocyte and bile duct development and present a scalable platform for future clinical applications in the understanding and treatment of cholangiopathies.
Follicular mural granulosa cells stockpile glycogen to fuel corpus luteum pre-vascularization
Authors: Liao Jianning , Liu Qinghua , Liu Cong , Liu Guiqiong , Li Xiang , Wang Xiaodong , Wang Yaqin , Liu Ruiyan , Wu Hao , Shi Hongru , Zhao Yongheng , Ke Wenkai , Ran Zaohong , Wu Zian , Tan Bowen , Wang Chaoli , Jiang Xunping , Wang Quanfeng , Xie Qingzhen , Liu Guoshi , He Changjiu
Published: January 2025

The differentiation of follicular mural granulosa cells (fGCs) into luteal cells involves a rapid progesterone synthesis surge and the vascular network development. However, progesterone elevation occurs before vascularization, leaving luteinizing fGCs temporarily devoid of blood supply. The mechanism of how fGCs fuel increased progesterone synthesis during this avascular phase remains unclear. Our research, utilizing integrative single-cell/spatial transcriptomics analysis and in vivo/ex vivo experiments, revealed that upon receiving the ovulatory/luteinization signal, fGCs transition to a low-energy state, reducing metabolic activity and storing glucose as glycogen. This process is governed by the LH (hCG)-Ras/Raf/Mek/Erk-RUNX1-Insulin signaling cascade. By mobilizing glycogen storage pre-vascularization, fGCs are fueled for enhanced progesterone synthesis. Supplementing glucose enhanced glycogen storage, leading to heightened progesterone secretion in corpora lutea. Implementing this technique, we enhanced luteal function in mice, sheep, and humans, resulting in increased litter rate in mice and improved pregnancy rates in sheep. Our study introduces the innovative concept of “fGC energy storage” and establishes the “Luteal Function Enhancement Technique”, contributing to the theoretical basis of reproductive physiology and displaying substantial clinical implications.
Fos expression in the periaqueductal gray, but not the ventromedial hypothalamus, is correlated with psychosocial stress-induced cocaine-seeking behavior in rats
Authors: Hinds Nicole M. , Wojtas Ireneusz D. , Pulley Desta M. , McDonald Stephany J. , Spencer Colton D. , Sudarikov Milena , Hubbard Nicole E. , Kulick-Soper Colin M. , de Guzman Samantha , Hayden Sara , Debski Jessica J. , Patel Bianca , Fox Douglas P. , Manvich Daniel F.
Published: January 2025

Psychosocial stressors are known to promote cocaine craving and relapse in humans but are infrequently employed in preclinical relapse models. Consequently, the underlying neural circuitry by which these stressors drive cocaine seeking has not been thoroughly explored. Using Fos expression analyses, we sought to examine whether the ventromedial hypothalamus (VMH) or periaqueductal gray (PAG), two critical components of the brain’s hypothalamic defense system, are activated during psychosocial stress-induced cocaine seeking. Adult male and female rats self-administered cocaine (0.5 mg/kg/inf IV, fixed-ratio 1 schedule, 2 h/session) over 20 sessions. On sessions 11, 14, 17, and 20, a tactile cue was present in the operant chamber that signaled impending social defeat stress (n=16, 8/sex), footshock stress (n=12, 6/sex), or a no-stress control condition (n=12, 6/sex) immediately after the session’s conclusion. Responding was subsequently extinguished, and rats were tested for reinstatement of cocaine seeking during re-exposure to the tactile cue that signaled their impending stress/no-stress post-session event. All experimental groups displayed significant reinstatement of cocaine seeking, but Fos analyses indicated that neural activity within the rostrolateral PAG (rPAGl) was selectively correlated with cocaine-seeking magnitude in the socially-defeated rats. rPAGl activation was also associated with active-defense coping behaviors during social defeat encounters and with Fos expression in prelimbic prefrontal cortex and orexin-negative cells of the lateral hypothalamus/perifornical area in males, but not females. These findings suggest a potentially novel role for the rPAGl in psychosocial stress-induced cocaine seeking, perhaps in a sex-dependent manner.
Endothelial Slit2 guides the Robo1-positive sympathetic innervation during heart development
Authors: Zhao Juanjuan , Bruche Susann , Lekkos Konstantinos , Carr Carolyn , Vieira Joaquim M. , Parnavelas John G. , Andrews William D. , Mommersteeg Mathilda T.M.
Published: January 2025

Axon guidance cues direct nerves in the heart during development, disease and regeneration. These cues determine cardiac innervation patterning by regulating the balance between chemo-attraction and chemo-repulsion. However, the role of one of the most crucial ligand-receptor combinations among axon guidance molecules, the Slit chemo-active ligands and their Roundabout (Robo) transmembrane receptors, remains unknown during cardiac innervation patterning. To test if Slit-Robo signalling is important for cardiac innervation guidance, we analysed Slit and Robo mouse knock-outs. ConstitutiveSlit2-/-ventricles showed significantly reduced innervation, whileSlit3-/-hearts showed temporary increased levels of innervation compared to wild-type littermate controls. Whereas innervation was not affected inRobo2-/-mice, the phenotype seen inSlit2-/-ventricles was recapitulated inRobo1-/-mice. Detailed expression analysis identified expression of Slit2 ligand in the endothelium of the coronary vessels, while Slit3 was highly present in the coronary smooth muscle wall and in the innervation. Both the Robo1 and Robo2 receptors were present in the nerves and at low levels in the vessels. Knocking outSlit2specifically in the endothelium recapitulated the defects seen in the constitutiveSlit2-/-hearts.Ex vivoaxon guidance cultures showed that attraction of axons extending from the ganglia was strongly reduced in ventricles with absence of endothelial Slit2 compared to wild-type controls. In absence of endothelial Slit2, adult mice showed reduced response to challenging the sympathetic innervation. In conclusion, we have identified an important new chemo-active Slit2-Robo1 pathway required for correct cardiac innervation development.
The Binary Cellular Biology of Human Growth: I. Quantifying the Creation and Growth of the Body and its Parts
Authors: Chodrow Philip , Su Jessica , Lee Daniel , He Neil , De Man Ruben , Tiwari Ankur , Mannherz William , Citi Luca , Gupta Rashi , Gu Zifan , Cantonwine David E , McElrath Thomas F , Tiemeier Henning , Michaelson James Selib
Published: January 2025

Assessing and understanding theGrowthandDevelopmentof animals generally, and of human fetuses specifically, provides essential information for the management of the health of the newborn and its mother. Here we show that a consideration of the formation of the body, in units of numbers of cells,N, and the change in these numbers by the binary either/or decisions of cells to divide or not, an approach we callBinary Cellular Analysis, provides new insights and new equations for quantifying the growth and development of the body and its parts. These equations include: 1) TheBinary Cellular Universal Growth Equation, which captures growth from conception to adulthood, and provides a method for biologically-based, data-driven,Growth Curves; 2) TheBinary Cellular Universal Mitotic Fraction Equation, which lies within theBinary Cellular Universal Growth Equation, and captures the mechanism of growth to adult size, control of cell division; 3) TheBinary Cellular Allometric Growth Equation, which captures the creation and growth of theTissues, Organs, andAnatomical Structuresof the body, and how the embryo creates eachBody Partfrom aSingle Founder Cell; and, 4)Binary Cellular Estimated Fetal Weight Equations, derived from theBinary Cellular Allometric Growth Equation, which captures the relationship betweenUltrasound Measurementand theSizeof the body as a whole. These equations capture the developmental process ofCellular Selection, resulting fromDifferential Cellular Proliferation, which molds the formation of the body from a single fertilized ovum into a multicellular animal. The parameters of these equations both capture the differences inSizeandGrowthbetween animals across the taxonomic spectrum, and between human fetuses, as well as identify the individual mechanisms of mitosis that driveGrowthandDevelopment. From theBinary Cellular Universal Growth Equation, theGrowthof human fetuses can be measured, thus providing a much-needed tool for understanding the biological forces that cause a fetus to grow toSmall, Average, orLarge Sizeat birth, for providing the basis of biologically-based, data-driven,Growth Curves, and for assisting the management of the obstetric care of the fetus and its mother.
Tau mediated regulation of Rho1- cytoskeletal dynamics in shaping renal tubule development inDrosophila
Authors: Tiwari Neha , Tapadia Madhu G.
Published: January 2025

The present study explored the significance of the microtubule-associated protein Tau in the morphogenesis and physiological processes of Malpighian tubules (MTs) inDrosophila melanogaster. Employing genetic manipulation techniques and microscopy, we established that Tau plays a crucial role in MTs development and function. Genetic ablation and RNAi-mediated suppression of Tau led to pronounced structural abnormalities, including cystic formations, non-uniform tubule diameters, and disorganized epithelial architecture. These aberrations are accompanied by perturbations in the cytoskeletal arrangement, compromised cellular polarity, and ionic imbalances. Functional analyses revealed deficiencies in salt homeostasis and fluid secretion within Tau-deficient tubules. Attenuation of Rho1 expression mitigated the structural defects observed in Tau mutants, highlighting the importance of Tau in modulating Rho1-mediated actin-microtubule dynamics suggesting a genetic interplay between Tau and Rho1 GTPase in orchestrating tubule morphogenesis The phenotypic parallels between Tau-deficient MTs and mammalian models of polycystic kidney disease implies an evolutionarily conserved function of Tau in tubular organ biology.

Graphical Abstract
Automatic detection of fluorescently labeled synapses in volumetric in vivo imaging data
Authors: Chen Zhining , Coste Gabrielle I. , Li Evan , Huganir Richard L. , Graves Austin R. , Charles Adam S.
Published: January 2025

Synapses are submicron structures that connect and enable communication between neurons. Many forms of learning are thought to be encoded by synaptic plasticity, wherein the strength of specific synapses is regulated by modulating expression of neurotransmitter receptors. For instance, regulation of AMPA-type glutamate receptors is a central mechanism controlling the formation and recollection of long-term memories. A critical step in understanding how synaptic plasticity drives behavior is thus to directly observe, i.e., image, fluorescently labeled synapses in living tissue. However, due to their small size and incredible density — with one ∼0.5 µm diameter synapse every cubic micron — accurately detecting individual synapses and segmenting each from its closely abutting neighbors is challenging. To overcome this, we trained a convolutional neural network to simultaneously detect and separate densely labeled synapses. These tools significantly increased the accuracy and scale of synapse detection, enabling segmentation of hundreds of thousands of individual synapses imaged in living mice.
Mef2c Controls Postnatal Callosal Axon Targeting by Regulating Sensitivity to Ephrin Repulsion
Authors: Sudarsanam Sriram , Guzman-Clavel Luis , Dar Nyle , Ziak Jakub , Shahid Naseer , Jin Xinyu O. , Kolodkin Alex L.
Published: January 2025

Cortical connectivity is contingent on ordered emergence of neuron subtypes followed by the formation of subtype-specific axon projections. Intracortical circuits, including long-range callosal projections, are crucial for information processing, but mechanisms of intracortical axon targeting are still unclear. We find that the transcription factor Myocyte enhancer factor 2-c (Mef2c) directs the development of somatosensory cortical (S1) layer 4 and 5 pyramidal neurons during embryogenesis. During early postnatal development,Mef2cexpression shifts to layer 2/3 callosal projection neurons (L2/3 CPNs), and we find a novel function forMef2cin targeting homotopic contralateral cortical regions by S1-L2/3 CPNs. We demonstrate, using functional manipulation of EphA-EphrinA signaling inMef2c-mutant CPNs, that Mef2c downregulatesEphA6 to desensitize S1-L2/3 CPN axons to EphrinA5-repulsion at their contralateral targets. Our work uncovers dual roles forMef2cin cortical development: regulation of laminar subtype specification during embryogenesis, and axon targeting in postnatal callosal neurons.

HIGHLIGHTS

Mef2c is required for the development of L4 and L5 neurons in the embryonic neocortex

Postnatally,Mef2cis enriched in L2/3 neurons and is required for axon targeting

L2/3-specificMef2cdeletion leads toEphA6upregulation

Mef2cdeletion in L2/3 neurons sensitizes them to EfnA5 repulsion in the contralateral cortex
LIN28-mediated gene regulatory loops synchronize developmental transitions throughout organogenesis
Authors: Thevarajan Indhujah , Osuna Maria F. , Lewey Sonia Fuentes , Sauceda Eustolia , Briseno Sayra , Griffin Caylah , Kim Bareun , Rowe R. Grant , da Rocha Edroaldo Lummertz , Osborne Jihan K.
Published: January 2025

Precise control of the intervals between self-renewal, proliferation, and differentiation of stem/progenitor cells are coordinated by developmental regulators, comprised of both microRNAs (miRNAs) and proteins, termed heterochronic genes. These heterochronic factors make up a unique subset of evolutionarily conserved genes that regulate the developmental rate and timing of metazoans from worms to mammals. We and others have shown critical roles for the RNA-binding proteins (RBPs) Lin28 during pluripotency, reprogramming, and organogenesis. There has been much investigation into the negative feedback loop between the Lin28-RBPs and the miRNAs–Let-7during development and disease. Albeit there are fewer investigations into how positive feedback loops between mammalian Lin28-RBPs and mRNAs order mammalian spatiotemporal transitions of progenitors from specification to organogenesis. Screening for factors that activate luciferase reporters of the humanLIN28AandLIN28Bpromoters, in combination with genetic mouse models, we demonstrate positive feedforward loops between key developmental transcription factors such as B-Catenin, Sox2, Sox9, and Lin28-RBPs. Furthermore, we demonstrate heterochronic regulation of morphogenesis and ultimately differentiation is not only genetically moderated but also molecularly fine-tuned via position-dependent sequences in the 5’ and/or 3’ untranslated regions.
Complete Next-to-Leading Order QCD Corrections to
ZZ
Production in Gluon Fusion
Authors: Agarwal Bakul , Jones Stephen , Kerner Matthias , von Manteuffel Andreas
Published: January 2025

We calculate the complete next-to-leading order (NLO) QCD corrections to loop-induced gg→ZZ production including full top-quark mass effects. The two-loop virtual corrections are obtained by combining analytic results for the massless, Higgs-mediated, and one-loop factorizable contributions with numerically computed amplitudes containing the top-quark mass. We show that the choice of subtraction scheme for the virtual contribution impacts the precision with which the virtual contribution must be evaluated in order to obtain sufficiently precise phenomenological predictions. For direct production through a massive top-quark loop, we observe that the relative NLO corrections are large. The direct massive and Higgs-mediated contributions individually increase relative to the massless production at high diboson invariant mass, but interfere destructively with each other. At the Large Hadron Collider, the NLO corrections to the gluon channel give a sizable contribution to the pp→ZZ+X cross section at N3LO.

Published by the American Physical Society
2025
Controlling beam trajectory and transport in a tapered helical undulator
Authors: Fisher A. , Jin J. , Musumeci P.
Published: January 2025

In this paper we present a detailed discussion of the helical undulator system developed for high extraction efficiency experiments in the tapered-enhanced stimulated superradiant amplification regime. The design is based on permanent magnet technology and comprises two Halbach arrays orthogonally oriented and shifted by 90° with respect to each other. When used in low energy beamlines for THz generation, the electron beam trajectory and transport are particularly sensitive to the undulator off-axis fields so that it becomes important to complement on-axis field measurements with analysis and tuning of the higher-order field components. Here we describe how the pulsed wire measurement technique can be effectively used to retrieve on- and off-axis magnetic field characteristics of the undulator. A simple two-dipole model is developed to guide the final adjustments to the permanent magnet positions along the array to tune the quadrupole and sextupole components of the field.
Determinants of resilience in local food systems: insights from world agriculture heritage sites
Authors: Vafadari Kazem , Khoshkam Mana , Yotsumoto Yukio , Bielik Peter , Ferraris Alberto
Published: January 2025

Purpose

This study delves into the relationship between local food systems and food tourism destinations, with a specific focus on resilience. Drawing on stimulus-organism-response (S-O-R) theory, we investigate the determinants of this relationship such as destination food image (DFI), food authenticity (FA), food culture (FC), food experience (FE), food traditional value (FTV), local food products (LFPs) and resilient food system (RFS) as crucial components influencing the resilience of the food system.

Design/methodology/approach

The data were collected in Oita Prefecture, Japan. The domestic, international tourists and local communities of six cities in this area were part of the surveys. A partial least squares approach (Smart-PLS 3.2.9) was used to analyse the data collected.

Findings

The results revealed that a destination’s food image, shaped by authenticity, traditional value and experiences, positively impacts the resilience of the food system, benefiting both the local community and tourists. The findings extend the literature by explaining the resilience of food systems in tourist destinations.

Originality/value

The study provides direction for policymakers and stakeholders to bolster the sustainability and resilience of local food systems as part of tourism.
Religiosity role on Islamic bank consumers’ self-esteem, mortal salience and social responsibility (CnSR): a terror management theory (TMT) perspective
Authors: Rahmawati Rahmawati , Junaidi Junaidi , Sabri Sabri , Mustika Ita , Sumardin Sumardin
Published: January 2025

Purpose

This study explores the impact of religiosity on self-esteem and mortality salience, subsequently influencing Indonesia’s Islamic banking consumers’ social responsibility (CnSR).

Design/methodology/approach

In total, 613 participants, Indonesia’s Islamic bank consumers, were recruited, and structural equation modelling (SEM) was used to examine research frameworks.

Findings

The empirical findings show that religiosity levels have a significant effect on self-esteem and mortality salience. Furthermore, mortality salience is less influential on CnSR than self-esteem. Furthermore, self-esteem and mortality salience partially bridge the relationship between religiosity and CnSR.

Research limitations/implications

Future studies need to examine the correlation between religiosity and CnSR in other contexts and theories, such as conventional banks and companies across the globe, to provide comprehensive insights into the mindset and actions of CnSR.

Practical implications

The recent study clarified the primary operations of Islamic bank customers in the context of business, religion and CnSR. Hence, increasing attention to customers’ social responsibility and religiosity is required from both the government and the Shariah Supervisory Board.

Originality/value

The result of the current study contributes to extending knowledge on terror management theory (TMT). In addition, it creates a fresh perspective on the factors affecting customers’ decision-making.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-02-2024-0105
Fostering altruistic prosocial tendencies in young leaders: the role of inclusive leadership and internalized values
Authors: Sholikhah Zahrotush , Nastiti Tur , Kismono Gugup
Published: January 2025

Purpose

In the contemporary globalized era, where conscientious and inclusive leadership (IL) are increasingly valued, cultivating altruistic prosocial tendencies (APT) among future leaders becomes critical. However, a significant gap persists in understanding the optimal approach for assisting young leaders with commendable social sensitivity. This study aims to examine the connection between IL and a leader’s APT and focuses on the moderating role of internalized values (IV) among young leaders in Indonesia.

Design/methodology/approach

The research adopted a quantitative methodology, using an online survey to gather data from 12.584 participants in the “Kampus Mengajar” program. The data analysis is conducted using structural equation modeling.

Findings

The study highlights the significant association between IL and APT among leaders, emphasizing the importance of inclusive approaches in fostering prosocial behavior. Additionally, it reveals the moderating impact of IVs, indicating that leaders who embrace values promoting societal belongingness are more inclined toward altruistic actions. This nuanced insight contributes to theoretical discourse and offers practical implications for organizations and educational institutions aiming to cultivate socially conscious leadership among young leaders.

Originality/value

This study advances scholarly understanding by exploring how IL shapes APT among young leaders, integrating insights from Role Identity and Role Identity Salience theory. By examining the moderating role of IVs, the study offers nuanced insights into the conditions that enhance this relationship.
Research on the rapid diagnosis method for hunting of high-speed trains
Authors: Xie Wanru , Zhao Yixin , Zhao Gang , Yang Fei , Wei Zilong , Liu Jinzhao
Published: January 2025

Purpose

High-speed turnouts are more complex in structure and thus may cause abnormal vibration of high-speed train car body, affecting driving safety and passenger riding experience. Therefore, it is necessary to analyze the data characteristics of continuous hunting of high-speed trains passing through turnouts and propose a diagnostic method for engineering applications.

Design/methodology/approach

First, Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) is performed to determine the first characteristic component of the car body’s lateral acceleration. Then, the Short-Time Fourier Transform (STFT) is performed to calculate the marginal spectra. Finally, the presence of a continuous hunting problem is determined based on the results of the comparison calculations and diagnostic thresholds. To improve computational efficiency, permutation entropy (PE) is used as a fast indicator to identify turnouts with potential problems.

Findings

Under continuous hunting conditions, the PE is less than 0.90; the ratio of the maximum peak value of the signal component to the original signal peak value exceeded 0.7, and there is an energy band in the STFT time-frequency map, which corresponds to a frequency distribution range of 1–2 Hz.

Originality/value

The research results have revealed the lateral vibration characteristics of the high-speed train’s car body during continuous hunting when passing through turnouts. On this basis, an effective diagnostic method has been proposed. With a focus on practical engineering applications, a rapid screening index for identifying potential issues has been proposed, significantly enhancing the efficiency of diagnostic processes.
Probing (2D) thin-film temperature sensors: materials and fabrication perspective
Authors: Devaraj Lakshmi , S. Thaarini , R.R. Athish , Ashokan Vallimanalan
Published: January 2025

Purpose

This study aims to provide a comprehensive overview of thin-film temperature sensors (TTS), focusing on the interplay between material properties and fabrication techniques. It evaluates the current state of the art, addressing both low- and high-temperature sensors, and explores the potential applications across various fields. The study also identifies challenges and highlights emerging trends that may shape the future of this technology.

Design/methodology/approach

This study systematically examines existing literature on TTS, categorizing the materials and fabrication methods used. The study compares the performance metrics of different materials, addresses the challenges encountered in thin-film sensors and reviews the case studies to identify successful applications. Emerging trends and future directions are also analyzed.

Findings

This study finds that TTS are integral to various advanced technologies, particularly in high-performance and specialized applications. However, their development is constrained by challenges such as limited operational range, material degradation, fabrication complexities and long-term stability. The integration of nanostructured materials and the advancement of wireless, self-powered and multifunctional sensors are poised to drive significant advancements in this field.

Originality/value

This study offers a unique perspective by bridging the gap between material science and application engineering in TTS. By critically analyzing both established and emerging technologies, the study provides valuable insights into the current state of the field and proposes pathways for future innovation in terms of interdisciplinary approaches. The focus on emerging trends and multifunctional applications sets this review apart from existing literature.
Business Model Innovation through AI Adaptation: The Role of Strategic Human Resources Management
Authors: Roy Sanjit K. , Dey Bidit L. , Brown David M. , Abid Aman , Apostolidis Chrysostomos , Christofi Michael , Tarba Shlomo
Published: January 2025

While artificial intelligence (AI) requires business model innovation, it simultaneously poses persistent operational, regulatory and strategic challenges, highlighting the importance of researching AI adaptation to appropriate organizational value. AI adaptation is not monolithic, and its nature and consequent value appropriation processes may vary due to external factors and an organization's strategic approach to innovation and resource management. Accordingly, a taxonomy of AI adaptation and its link with value appropriation can yield a theoretical understanding and practical implications of why and how organizations vary in leveraging strategic human resource management to shape business innovation led by AI adaptation. In this paper, we address this issue by applying adaptive structuration theory and conducting interviews with top management personnel from 51 companies based in India. Based on our findings, we develop a novel taxonomy of AI adaptation (exploitive, exploratory, emancipatory and expedient), structured within a 2 × 2 matrix and a robust model of value appropriation within a dynamic business environment.