bluuebunny/crossref_metadata_2025 huggingface dataset:
Giants among Cnidaria: large nuclear genomes and rearranged mitochondrial genomes in siphonophores
Authors: Ahuja Namrata , Cao Xuwen , Schultz Darrin T. , Picciani Natasha , Lord Arianna , Shao Shengyuan , Burdick David R. , Haddock Steven H.D. , Li Yuanning , Dunn Casey W
Published: May 2023

Siphonophores (Cnidaria:Hydrozoa) are abundant predators found throughout the ocean and are important components in worldwide zooplankton. They range in length from a few centimeters to tens of meters. They are gelatinous, fragile, and difficult to collect, so many aspects of the biology of these 190 species remain poorly understood. To survey siphonophore genome diversity, we performed Illumina sequencing of 32 species sampled broadly across the phylogeny. Sequencing depth was sufficient to estimate nuclear genome size from k-mer spectra in 8 specimens, ranging from 0.7-4.8Gb. In 6 specimens we got heterozygosity estimates between 0.7-5.3%. Rarefaction analyses indicate k-mer peaks can be absent with as much as 30x read coverage, suggesting minimum genome sizes range from 1.0-3.8Gb in the remaining 27 samples without k-mer peaks. This work confirms most siphonophore nuclear genomes are large, but also identifies several with reduced size that are tractable targets for future siphonophore nuclear genome assembly projects. We also assembled mitochondrial genomes for 32 specimens from these new data, indicating a conserved gene order among Hydrozoa, Cystonectae and some Physonectae, also revealing the ancestral gene organization of siphonophores. There then was extensive rearrangement of mitochondrial genomes within other physonects and in Calycophorae, including the repeated loss of atp8. Though siphonophores comprise a small fraction of cnidarian species, this survey greatly expands our understanding of cnidarian genome diversity. This study further illustrates both the importance of deep phylogenetic sampling and the utility of Illumina genome skimming in understanding genomic diversity of a clade.

Significance

Descriptions of basic genome features, such as nuclear genome size and mitochondrial genome sequences, remain sparse across many clades in the tree of life, leading to over generalizations from very small sample sizes and often limiting selection of optimal species for genome assembly efforts. Here we use Illumina genome skimming to assess a variety of genome features across 35 siphonophores (Cnidaria). This deep dive within a single clade identifies six species that are optimal candidates of future genomic work, and reveals greater range in nuclear genome size and diversity of mitochondrial genome orders within siphonophores than had been described across all Cnidaria.
Hierarchical gradients of multiple timescales in the mammalian forebrain
Authors: Song Min , Shin Eun Ju , Seo Hyojung , Soltani Alireza , Steinmetz Nicholas A , Lee Daeyeol , Jung Min Whan , Paik Se-Bum
Published: May 2023

Many anatomical and physiological features of cortical circuits, ranging from the biophysical properties of synapses to the connectivity patterns among different neuron types, exhibit consistent variation along the hierarchical axis from sensory to association areas. Notably, the scale of temporal correlation of neural activity at rest, known as the intrinsic timescale, increases systematically along this hierarchy in both primates and rodents, analogous to the growing scale and complexity of spatial receptive fields. However, how the timescales for task-related activity vary across brain regions and whether their hierarchical organization appears consistently across different mammalian species remain unexplored. Here, we show that both the intrinsic timescale and the timescales of task-related activity follow a similar hierarchical gradient in the cortices of monkeys, rats, and mice. We also found that these timescales covary similarly in both the cortex and basal ganglia, whereas the timescales of thalamic activity are shorter than cortical timescales and do not conform to the hierarchical order predicted by their cortical projections. These results suggest that the hierarchical gradient of cortical timescales might be a universal feature of intra-cortical circuits in the mammalian brain.
Identification of Region-Specific Gene Isoforms in the Human Brain Using Long-Read Transcriptome Sequencing and Their Correlation with DNA Methylation
Authors: Shimada Mihoko , Omae Yosuke , Kakita Akiyoshi , Gabdulkhaev Ramil , Miyagawa Taku , Honda Makoto , Fujimoto Akihiro , Tokunaga Katsushi
Published: May 2023

Background

Site specificity is known in neuropsychiatric disorders, and differences in gene expression patterns could potentially explain this mechanism. However, studies using long-read transcriptome sequencing to analyze gene expression in different regions of the human brain have been limited, and none have focused on the hypothalamus, which plays a crucial role in regulating autonomic functions.

Results

We performed long-read RNA sequencing on 12 samples derived from three different brain regions of the same individuals; the cerebellum, hypothalamus, and temporal cortex. We found that, compared to other regions, many genes with higher expression levels in the cerebellum and temporal cortex were associated with neuronal pathways, whereas those with higher expression levels in the hypothalamus were primarily linked to immune pathways. In addition, we investigated genes with different major isoforms in each brain region, even with similar overall expression levels among regions, and identified several genes, such asGAS7, that express different major isoforms in different regions. Many of these genes are involved in “actin filament-based process” and “cell projection organization” pathways, suggesting that region-dependent isoforms may have distinct roles in dendritic spine and neuronal formation in each region. Furthermore, we investigated the involvement of DNA methylation in these isoforms and found that DNA methylation may be associated with isoforms that have different first exons.

Conclusions

Our results provide potentially valuable findings for future research on brain disorders and shed light on the mechanisms underlying isoform diversity in the human brain.
REPIC — an ensemble learning methodology for cryo-EM particle picking
Authors: Cameron Christopher JF , Seager Sebastian JH , Sigworth Fred J , Tagare Hemant D , Gerstein Mark B
Published: May 2023

Cryo-EM (cryogenic electron microscopy) particle identification from micrographs (i.e., picking) is challenging due to the low signal-to-noise ratio and lack of ground truth for particle locations. Moreover, current computational methods (“pickers”) identify different particle sets, complicating the selection of the best-suited picker for a protein of interest. Here, we present REPIC, an ensemble learning methodology that uses multiple pickers to find consensus particles. REPIC identifies consensus particles by framing its task as a graph problem and using integer linear programming to select particles. REPIC picks high-quality particles when the best picker is not known a priori and for known difficult-to-pick particles (e.g., TRPV1). Reconstructions using consensus particles achieve resolutions comparable to those from particles picked by experts, without the need for downstream particle filtering. Overall, our results show REPIC requires minimal (often no) manual picking and significantly reduces the burden on cryo-EM users for picker selection and particle picking.

Availability

https://github.com/ccameron/REPIC
Non-invasive optical synthetization of hearing sensation in non-genetically modified animal
Authors: Tamai Yuta , Uenaka Miku , Okamoto Aya , Hosokawa Keito , Ito Yuki , Toda Koji , Hiryu Shizuko , Kobayasi Kohta I.
Published: May 2023

Brain-machine interfaces are emerging devices that act as a medium for communication between the neural system and external software and hardware. Over the last decade, there has been a discussion on applying infrared laser stimulation to the brain-machine interfaces, including cochlear implants. Infrared lasers can selectively activate neural populations without introducing exogenous agents to tissues. This study presents the first demonstration that laser irradiation of the cochlea, a peripheral sensory organ, can elicit a clear behavioral auditory response. Mongolian gerbils (Meriones unguiculatus) were divided into two groups, each subjected to classical conditioning where a reward water delivery was predicted by either cochlear laser stimulation or sound stimulus. Laser-conditioned animals successfully learned licking behavior, with conditioned responses and behavioral properties comparable to auditory-conditioned animals. The laser-evoked response was significantly inhibited by auditory masking, and auditory-conditioned animals demonstrated stimulus generalization to laser stimulation. In a subsequent experiment, simultaneous presentation of auditory and laser stimulation induced nonlinear amplification in both auditory cortical and behavioral responses, suggesting that combining auditory and laser stimulation can enhance auditory perception beyond the effects of each stimulus alone. These findings indicate that infrared laser irradiation of the cochlea can potentially evoke and enhance auditory perception, making it a promising candidate for implementation in auditory prostheses.
Sleep-insomnia superposition: opposing brain signatures of sleep in task-based and resting-state conditions
Authors: Abdelhack Mohamed , Zhukovsky Peter , Milic Milos , Harita Shreyas , Wainberg Michael , Tripathy Shreejoy J , Griffiths John D , Hill Sean L , Felsky Daniel
Published: May 2023

Sleep and depression have a complex, bidirectional relationship, with sleep-associated alterations in brain dynamics and structure impacting a range of symptoms and cognitive abilities. Previous work describing these relationships has provided an incomplete picture by investigating only one or two types of sleep measures, depression, or neuroimaging modalities in parallel. We analyzed the correlations between task and resting-state brain-wide signatures of sleep, cognition, and depression in over 30,000 individuals. Neural signatures of insomnia and depression were negatively correlated with neural signatures of sleep duration in the task condition but positively correlated in the resting-state condition, showing that resting-state neural signatures of insomnia and depression resemble that of rested wakefulness. This was further supported by our finding of hypoconnectivity in task but hyperconnectivity in resting-state data in association with insomnia and depression This information disputes conventional assumptions about the neurofunctional manifestations of hyper– and hypo-somnia, and may explain inconsistent findings in the literature.
Skp1 proteins are structural components of the synaptonemal complex inC. elegans
Authors: Blundon Joshua , Cesar Brenda , Bae Jung Woo , Čavka Ivana , Haversat Jocelyn , Ries Jonas , Köhler Simone , Kim Yumi
Published: May 2023

The synaptonemal complex (SC) is a hallmark of meiotic prophase that plays a crucial role in regulating crossovers between homologous chromosomes. Here, we demonstrate that two Skp1-related proteins inC. elegans, SKR-1 and SKR-2, serve as structural components of the SC, independent of their canonical functions within the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex. SKR-1 and SKR-2 localize to the central region of the SC, and synapsis requires their dimerization through a hydrophobic interface that overlaps with the binding sites for CUL-1 and F-box proteins. Usingin vitroreconstitution andin vivoanalysis of mutant proteins, we show that SKR proteins interact with the other SC proteins using their C-terminal helices to form a soluble complex, which likely represents a basic building block for SC assembly. Our findings demonstrate how conserved Skp1 proteins are repurposed as part of the SC and may provide insight into how synapsis is coupled to cell cycle progression.
The androgen receptor does not directly regulate the transcription of DNA damage response genes
Authors: Hasterok Sylwia , Scott Thomas G. , Roller Devin G. , Spencer Adam , Dutta Arun B. , Sathyan Kizhakke M , Frigo Daniel E. , Guertin Michael J. , Gioeli Daniel
Published: May 2023

The clinical success of combined androgen deprivation therapy (ADT) and radiation therapy (RT) in prostate cancer (PCa) created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes in nascent RNA transcription in response to IR, the AR antagonist enzalutamide, or the combination of the two, we find that enzalutamide treatment significantly decreased expression of canonical AR target genes but had no effect on DDR gene sets in PCa cells. Surprisingly, we also found that the AR is not a primary regulator of DDR genes either in response to IR or at steady state in asynchronously growing PCa cells. Our data indicate that the clinical benefit of ADT and RT is not due to the direct regulation of DDR gene transcription by AR.
Spatial Tracking Across Time (STAT): Tracking Neurons Across In-Vivo Imaging Sessions through Optimizing Local Neighborhood Motion Consistency
Authors: Gu Shijie , Mackevicius Emily L. , Fee Michale S. , Zhou Pengcheng
Published: May 2023

Chronic calcium imaging has become a powerful and indispensable tool for analyzing the long-term stability and plasticity of neuronal activity. One crucial step of the data processing pipeline is to register individual neurons across imaging sessions, which usually extend over a few days or even months, and show various levels of spatial deformation of the imaged field of view (FOV). Previous solutions align FOVs of all sessions first and then register the same neurons according to their shapes and locations [1, 2]. However, the FOV registration is computational intensive, especially in the case of nonrigid case.

Here we propose a cell tracking method that does not require FOV image registration. Specifically, the algorithmSTAT(short forStayTogether,AlignTogether, and forSpatialTrackingAcrossTime) represents neurons from two sessions as two sets of neuronal centroids, uses point set registration (PSR) to find a spatially smooth transformation to align them while assigning correspondences. The optimization method iteratively updates between the general motion and individual neuron identity tracking, an idea seen in the computer vision literatures [3, 4]. Our method can be thought of as a specialization and simplification of these more general methods to calcium imaging neuron tracking.

We validate STAT on datasets with simulated nonrigid motion that is hard to motion correct without extensive manual intervention. Next, we test STAT on experimental data from singing birds collected on three different days, and observe stable song-locked activity across days. An example use case of this package is reference [5].
Hyperphosphorylated tau Inflicts Intracellular Stress Responses That Are Mitigated by Apomorphine
Authors: Song Zhenfeng , Wang Kuang-Wei , Hagar Hsiao-Tien Chien , Chen Hong-Ru , Kuan Chia-Yi , Zhang Kezhong , Kuo Min-Hao
Published: May 2023

Background

Abnormal phosphorylation of the microtubule-binding protein tau in the brain is a key pathological marker for Alzheimer’s disease and additional neurodegenerative tauopathies. However, how hyperphosphorylated tau causes cellular dysfunction or death that underlie neurodegeneration remains an unsolved question critical for the understanding of disease mechanism and the design of efficacious drugs.

Methods

Using a recombinant hyperphosphorylated tau protein (p-tau) synthesized by the PIMAX approach, we examined how cells responded to the cytotoxic tau and explored means to enhance cellular resistance to tau attack.

Results

Upon p-tau uptake, the intracellular calcium levels rose promptly. Gene expression analyses revealed that p-tau potently triggered endoplasmic reticulum (ER) stress, Unfolded Protein Response (UPR), ER stress-associated apoptosis, and pro-inflammation in cells. Proteomics studies showed that p-tau diminished heme oxygenase-1 (HO-1), an ER stress associated anti-inflammation and anti-oxidative stress regulator, while stimulated the accumulation of MIOS and other proteins. P-tau-induced ER stress-associated apoptosis and pro-inflammation are ameliorated by apomorphine, a brain-permeable prescription drug widely used to treat Parkinson’s disease symptoms, and by overexpression of HO-1.

Conclusion

Our results reveal probable cellular functions targeted by hyperphosphorylated tau. Some of these dysfunctions and stress responses have been linked to neurodegeneration in Alzheimer’s disease. The observations that the ill effects of p-tau can be mitigated by a small compound and by overexpressing HO-1 that is otherwise diminished in the treated cells inform new directions of Alzheimer’s disease drug discovery.
Hi-Fi fMRI: High-resolution, fast-sampled and sub-second whole-brain functional MRI at 3T in humans
Authors: Franceschiello Benedetta , Rumac Simone , Hilbert Tom , Nau Matthias , Dziadosz Martyna , Degano Giulio , Roy Christopher W. , Gaglianese Anna , Petri Giovanni , Yerly Jérôme , Stuber Matthias , Kober Tobias , van Heeswijk Ruud B. , Murray Micah M. , Fornari Eleonora
Published: May 2023

Functional magnetic resonance imaging (fMRI) is a methodological cornerstone of neuroscience. Most studies measure blood-oxygen-level-dependent (BOLD) signal using echo-planar imaging (EPI), Cartesian sampling, and image reconstruction with a one-to-one correspondence between the number of acquired volumes and reconstructed images. However, EPI schemes are subject to trade-offs between spatial and temporal resolutions. We overcome these limitations by measuring BOLD with a gradient recalled echo (GRE) with 3D radial-spiral phyllotaxis trajectory at a high sampling rate (28.24ms) on standard 3T field-strength. The framework enables the reconstruction of 3D signal time courses with whole-brain coverage at simultaneously higher spatial (1mm3) and temporal (up to 250ms) resolutions, as compared to optimized EPI schemes. Additionally, artifacts are corrected before image reconstruction; the desired temporal resolution is chosen after scanning and without assumptions on the shape of the hemodynamic response. By showing activation in the calcarine sulcus of 20 participants performing an ON-OFF visual paradigm, we demonstrate the reliability of our method for cognitive neuroscience research.
Paneth and Paneth-like cells undergoing necroptosis fuel intestinal epithelial cell proliferation following IFN-γ stimulation
Authors: Encarnacion-Garcia Maria R. , De la Torre-Baez Raul , Hernandez-Cueto Maria A. , Velázquez-Villegas Laura A. , Candelario-Martinez Aurora , Horta-López Perla H. , Montoya-García Armando , Jaimes-Ortega Gustavo Alberto , Lopez-Bailon Luis , Piedra-Quintero Zayda , Carrasco-Torres Gabriela , De Ita Marlon , del Pilar Figueroa-Corona Maria , Muñoz-Medina José Esteban , Sánchez-Uribe Magdalena , Meraz-Ríos Marco Antonio , Villa-Treviño Saúl , Garcia-Sierra Francisco , Cisneros Bulmaro , Schnoor Michael , Ortíz-Navarrete Vianney F. , Villegas-Sepúlveda Nicolás , Valle-Rios Ricardo , Medina-Contreras Oscar , Noriega Lilia G. , Nava Porfirio
Published: May 2023

The quality of life in patients with inflammatory bowel diseases (IBD) is strongly impaired. Alterations of intestinal epithelial homeostasis contribute to the development and establishment of IBD. Intestinal Paneth and Paneth-like cells produce and secrete luminal proteins sustaining epithelial homeostasis. Here we show that IFN-γ stimulates Paneth and Paneth-like cells degranulation that triggers the proliferation of intestinal epithelial cells (IEC) in a Wnt/β-catenin independent manner. Degranulation in Paneth and Paneth-like cells was mTORC1 and necroptosis dependent. Remarkably, lack of IFN-γ, inhibition of mTORC1, or impeding necroptosis reduces IEC proliferation cytokine-mediated. Our findings identify a new role for IFN-γ in stimulating IEC proliferation through inducing degranulation of Paneth and Paneth-like cells which is mTORC1 and necroptosis- dependent. In a mouse model of colitis, mTORC1 activation and necroptosis regulate Paneth and Paneth-like cell secretion. Furthermore, the colitogenic environment triggers PC metaplasia in the distal region of the large intestine to simulate cell proliferation.

Highlights:

IFN-γ stimulates proliferation,β-catenin independent.

IFN-γ enhances mitochondrial activity and proliferation

IFN-γ regulates PC biogenesis.

mTORC1-dependent necroptosis mediates secretion in Paneth and Paneth-like cells.
Immersive scene representation in human visual cortex with ultra-wide angle neuroimaging
Authors: Park Jeongho , Soucy Edward , Segawa Jennifer , Mair Ross , Konkle Talia
Published: May 2023

While humans experience the visual environment in a panoramic 220° view, traditional functional MRI setups are limited to display images like postcards in the central 10-15° of the visual field. Thus, it remains unknown how a scene is represented in the brain when perceived across the full visual field. Here, we developed a novel method for ultra-wide angle visual presentation and probed for signatures of immersive scene representation. To accomplish this, we bounced the projected image off angled-mirrors directly onto a custom-built curved screen, creating an unobstructed view of 175°. Scene images were created from custom-built virtual environments with a compatible wide field-of-view to avoid perceptual distortion. We found that immersive scene representation drives medial cortex with far-peripheral preferences, but surprisingly had little effect on classic scene regions. That is, scene regions showed relatively minimal modulation over dramatic changes of visual size. Further, we found that scene and face-selective regions maintain their content preferences even under conditions of central scotoma, when only the extreme far-peripheral visual field is stimulated. These results highlight that not all far-peripheral information is automatically integrated into the computations of scene regions, and that there are routes to high-level visual areas that do not require direct stimulation of the central visual field. Broadly, this work provides new clarifying evidence on content vs. peripheral preferences in scene representation, and opens new neuroimaging research avenues to understand immersive visual representation.
Trans-complementation by the RecB nuclease domain of RecBCD enzyme reveals new insight into RecA loading upon χ recognition
Authors: Pavankumar Theetha L. , Jason Wong C. , Wong Yun Ka , Spies Maria , Kowalczykowski Stephen C.
Published: May 2023

The loading of RecA onto ssDNA by RecBCD is an essential step of RecBCD-mediated homologous recombination. RecBCD facilitates RecA-loading onto ssDNA in a χ-dependent manner via its RecB nuclease domain (RecBn). Before recognition of χ, RecBnis sequestered through interactions with RecBCD. It was proposed that upon χ-recognition, RecBnundocks, allowing RecBnto swing out via a contiguous 70 amino acid linker to reveal the RecA-loading surface, and then recruit and load RecA onto ssDNA. We tested this hypothesis by examining the interactions between RecBn(RecB928–1180) and truncated RecBCD (RecB1–927CD) lacking the nuclease domain. The reconstituted complex of RecB1–927CD and RecBnis functionalin vitroandin vivo. Our results indicate that despite being covalently severed from RecB1–927CD, RecBncan still load RecA onto ssDNA, establishing that RecBndoes not function at the end of its flexible linker. Instead, RecBCD undergoes a χ-induced intramolecular rearrangement to reveal a RecA-loading surface.
Cancer-associated fibroblast ADAM17 mediates a feed-forward loop promoting cancer cell migration
Authors: Perciato Maria L , Whawell Simon A , Lambert Daniel W
Published: May 2023

One of the ways in which cancer associated fibroblasts (CAF) influence the tumour-microenvironment (TME) is by releasing soluble factors to elicit responses in nearby cells. These factors may be released by modification of the extracellular matrix (ECM), secretion from intracellular compartments, or proteolytic cleavage from the cell surface. A major mediator of proteolytic processing of cell surface proteins is the ‘a disintegrin and metalloproteinase’ (ADAM) family, commonly ADAM17. The role of ADAM17 in CAF, however, remains largely unknown.

Here, we show that expression of ADAM17 was induced in normal oral fibroblasts (NOF) and CAF by exposure to oral cancer cell-derived conditioned medium and depletion of ADAM17 reduced the ability of CAF to promote cancer cell migration by negatively regulating cancer cell-associated N-cadherin. Proteomic analysis of ADAM17-depleted CAF revealed changes in the expression of pro-tumorigenic proteins, including fibroblast growth factor 2 (FGF2). Inhibition of FGF2/FGFR1 signalling abrogated the pro-migratory effects of CAF by reducing cancer cell-associated N-cadherin, an effect rescued by addition of recombinant FGF2.

Taken together, these results indicate a novel molecular mechanism underpinning cancer cell migration in which tumour-derived factors induce ADAM17 expression in CAF, thus initiating a feed-forward loop wherein CAF release FGF2 to stimulate N-cadherin-dependent cancer cell migration.
Flight heights of Scopoli’s shearwatersCalonectris diomedeain the context of offshore wind farm developments
Authors: Courbin Nicolas , Besnard Aurélien , Boncourt Etienne , Grémillet David
Published: May 2023

Seabird face new risks through collisions with offshore wind turbines. Wind energy projects are emerging in the Mediterranean Sea, and unbiased knowledge on seabird flight altitudes are scarce in this area. Indeed, previous flight height observations were carried out from boats during daytime, and only in good weather conditions. We measured flight heights of 13 Scopoli’s shearwaters,Calonectris diomedea, one of the three endemic shearwater species in the Mediterranean, using highly precise barometric data loggers. The birds were equipped at the largest French colony of Scopoli’s shearwater in the Marseille archipelago. Birds from this location routinely visit forthcoming wind farm areas, within 50 km of their breeding site. We found that Scopoli’s shearwaters flew at very low altitudes with a mean flight height of 1.8 ± 2.7 m (± SD) above sea level. Birds therefore rarely (<0.02%) flew within the vertical envelop of collision risk with wind turbines. Ours results are coherent with field observations and the dynamic soaring flight technique used by shearwaters.

Nevertheless, collision risk may increase following behavioural modifications close to wind turbines.
3D organoid modeling identified that targeting IGF1R signaling may overcome drug resistance in breast cancer
Authors: Mittal Ekansh , Qian David
Published: May 2023

Breast cancer is the most frequently diagnosed cancer and the second largest cause of cancer deaths in women. However, drug resistance and poor response to treatments are common. Thus, there is an unmet need to identify new treatments and effective lab-based drug testing methods. Here we established a novel 3-dimensional organoid method by co-culturing cancer cells with healthy endothelial cells for longer-term testing of new drug combinations that combat drug resistance. As a proof-of-concept we showed that paclitaxel efficacy can be improved by combining it with AKT inhibitors. In addition, we identified a new triple combination of paclitaxel, HER2 inhibitor, and IGF1R inhibitor, which is more effective in increasing cell death and reducing organoid growth. Interestingly, many IGF1R pathway members are upregulated in breast cancer patients, and high expression is associated with poor survival, indicating that IGF1R is an attractive therapeutic target. Overall, using this novel organoid method, we can mimic more accurate culture conditions and identify new targets to be tested in clinical trials. Our approach is applicable to various cancers to improve patients’ outcomes.
Optimal reaching subject to computational and physical constraints reveals structure of the sensorimotor control system
Authors: Greene Patrick , Bastian Amy , Schieber Marc H. , Sarma Sridevi V.
Published: May 2023

Optimal feedback control provides an abstract framework describing the architecture of the sensorimotor system without prescribing implementation details such as what coordinate system to use, how feedback is incorporated, or how to accommodate changing task complexity. We investigate how such details are determined by computational and physical constraints by creating a model of the upper limb sensorimotor system in which all connection weights between neurons, feedback, and muscles are unknown. By optimizing these parameters with respect to an objective function, we find that the model exhibits a preference for an intrinsic (joint angle) coordinate representation of inputs and feedback and learns to calculate a weighted feedforward and feedback error. We further show that complex reaches around obstacles can be achieved by augmenting our model with a path-planner based on via points. The path-planner revealed “avoidance” neurons that encode directions to reach around obstacles, and “placement” neurons that make fine-tuned adjustments to via point placement. Our results demonstrate the surprising capability of computationally constrained systems and highlight new characteristics of the sensorimotor system.
Accessibility and activity of transcriptional regulatory elements during sea urchin embryogenesis and differentiation
Authors: Arenas-Mena Cesar , Akin Serhat
Published: May 2023

Transcriptional regulatory elements (TREs) are the primary nodes of the gene regulatory networks that control development. TREs are identified by PRO-seq and their accessibility by ATAC-seq during sea urchin embryonic development and differentiation. Our analysis identifies surprisingly early accessibility in 4-cell cleavage embryo TREs that is not necessarily followed by subsequent transcription, and an excess of ATAC-seq peaks transcriptionally disengaged during the stages analyzed. Embryonic accessibility shifts are driven by transcriptionally engaged TREs, and PRO-seq transcriptional differences at TREs provide more contrast among embryonic stages than ATAC-seq accessibility differences. TRE accessibility reaches a maximum around the 20-hour late blastula, which coincides with major embryo regionalizations. At the same time, a large number of distal TREs become transcriptionally disengaged, in support of an early Pol II primed model for developmental gene regulation that eventually resolves in transcriptional activation or silencing. A transcriptional potency model based on labile nucleosome TRE occupancy driven by DNA sequences and the prevalence of histone variants is proposed in order to explain the basal accessibility of transcriptionally inactive TREs during early embryogenesis.

Summary statement

Genomic profiles deciphering the location and activity of regulatory elements that control gene expression suggest general mechanisms of regulatory potency in early sea urchin embryos.
In vivo screening of tumor-hepatocyte interactions identifies Plexin B2 as a gatekeeper of liver metastasis
Authors: Borrelli Costanza , Roberts Morgan , Eletto Davide , Lafzi Atefeh , Kretz Jonas A. , Fazilaty Hassan , Hussherr Marie-Didiée , Guido Vinzoni Elena , Handler Kristina , Michler Jan , Adivarahan Srivathsan , Piscuoglio Salvatore , Ficht Xenia , Moor Andreas E.
Published: May 2023

It is estimated that only 0.02% of disseminated tumor cells are able to seed overt metastases1. While this indicates the presence of environmental constraints to metastatic seeding, the landscape of host factors controlling this process remains largely unknown. Combining transposon technology2and fluorescent niche labeling3, we developed anin vivoCRISPR activation screen to systematically investigate the influence of hepatocytes on metastatic seeding in the liver. Our approach enabled the identification of Plexin B2 as a critical host-derived regulator of metastasis. Plexin B2 upregulation in hepatocytes dramatically enhances grafting in colorectal and pancreatic cancer syngeneic models, and promotes seeding and survival of patient-derived organoids. Notably, ablation of Plexin B2 in hepatocytes prevents mesenchymal-to-epithelial transition of extravasated tumor cells and thereby almost entirely suppresses liver metastasis. We dissect a mechanism by which Plexin B2 interacts with class 4 semaphorins on tumor cells, activating Rac1 signaling and actin cytoskeleton remodeling, thereby promoting the acquisition of epithelial traits. Our findings highlight the essential role of signals from the liver parenchyma for the survival of disseminated tumor cells, prior to the establishment of a growth promoting niche. They further suggest that acquisition of epithelial traits is required for the adaptation of extravasated cells to their new tissue environment. Targeting of Plexin B2 on hepatocytes shields the liver from colonizing cells and thus presents an innovative therapeutic strategy for preventing metastasis. Finally, our screening technology, which evaluates host-derived extrinsic signals rather than tumor-intrinsic factors for their ability to promote metastatic seeding, is broadly applicable and lays a framework for the screening of environmental constraints on metastasis in other organs and cancer types.
On the dependence of creep-induced dislocation configurations on crystallographic orientation in pure Al and Al–Mg
Authors: Fernández Ricardo , Bokuchava Gizo , Bruno Giovanni , Serrano-Muñoz Itziar , González-Doncel Gaspar
Published: May 2023

The peak broadening in neutron diffraction experiments on tensile specimens of pure Al (99.8%) and an Al–Mg alloy pre-deformed at different creep strains is analysed. These results are combined with the kernel angular misorientation of electron backscatter diffraction data from the creep-deformed microstructures. It is found that differently oriented grains possess different microstrains. These microstrains vary with creep strain in pure Al, but not in the Al–Mg alloy. It is proposed that this behaviour can explain the power-law breakdown in pure Al and the large creep strain observed in Al–Mg. The present findings further corroborate a description of the creep-induced dislocation structure as a fractal, predicated on previous work.
Autism and social media: a systematic review of the user experience
Authors: Hudson Nicholas Andrew , Linnane Jake M. , Rayner-Smith Kelly
Published: May 2023

Purpose

Social media use in autistic people has been identified as a potential avenue for less pressured social contact. Given shifts towards online socialisation, this study aims to systematically review the available literature on how autistic people experience and use social media.

Design/methodology/approach

A systematic review was carried out using the preferred reporting items for systematic reviews and meta-analyses system, with relevant literature reviewed and synthesised using a narrative approach. Inclusion criteria included adults and/or adolescents as the sole sample, a focus on autism and social media use as the sole/main topic.

Findings

A total of 1,278 research studies were initially identified; following screening, 15 papers were reviewed. Studies demonstrated some support for the positive role social media can play and presented its use as a smart adaptation for the challenges of neurotypical socialising. For autistic people, social media may provide a balance between meeting the need to be connected to people without the pressure of managing aspects, such as tone of voice or body language.

Research limitations/implications

Most studies were questionnaire-based with substantial threats to validity. Samples were self-selecting, with autism status not always confirmed. Individual studies used a broad approach to the definition of social media, including online gaming and other online activities, precluding firm conclusions being made.

Practical implications

There may be a Goldilocks “just right” level of social media contact that could maximise connectedness to others without impacting negatively on mental health, offline relationships and activities of daily living.

Originality/value

This paper presents a novel account of research from case studies and larger scale questionnaire studies.
Corporate governance in the COVID-19 pandemic: current practices and potential improvement
Authors: Alshhadat Mohammad Q. , Al-Hajaya Krayyem
Published: May 2023

Purpose

The purpose of this paper is to analyse the effect of the COVID-19 pandemic on corporate governance and internal control in general. In addition, this paper attempts to develop a new corporate governance model that flexibly addresses conditions like those brought into the business environment by COVID-19.

Design/methodology/approach

Thirteen semi-structured interviews were conducted with chairpersons, CEOs and directors from companies listed on the FTSE 350.

Findings

This study suggests a corporate governance model, which we call Eunomia, which we believe will help businesses to navigate the unusual conditions resulting from COVID-19 and similar types of crises that lead to major disruption for businesses and society. The model includes five pillars that support governance, namely, flexibility, IT infrastructure, risk management, internal control and policies and procedures.

Practical implications

Implications for practice and policymakers. Based on the research outcomes, the authors suggest that the board of directors establishes policies that ensure supply diversity and that businesses do not rely on a single or limited number of suppliers, thereby making themselves vulnerable to supply chain disruption with those suppliers.

Originality/value

This paper presents an original contribution to the accounting literature relating to corporate governance and internal control systems, specifically in terms of how businesses can optimally operate under uncontrollable conditions resulting from pandemics, and similar situations.
The desire for employability and self-exploitation: concretizing Lacan's psychoanalysis on employability
Authors: Shah Muzammel
Published: May 2023

Purpose

Although commitment and employability are legitimized in the current world of work, they also have a dark side that has been ignored in the extant literature. To tackle this gap, the study developed and examined a comprehensive theoretical framework including learning, motivation, commitment, employability and self-exploitation. Limited research exists that explicitly examines this relationship or explores its potential implications. The author theorizes employability as a cultural fantasy that ends up in self-exploitation.

Design/methodology/approach

The study concretizes Lacan's (1977; 1981 and 1988) psychoanalysis, utilizing a sample of 658 subjects from eight industries. The hypothesized relationships were examined using structural equation modeling (SEM) in AMOS.

Findings

The findings provided support for the hypothesized relationships. Employability escorts to self-exploitation. Those employees who try to remain relevant to their firms continue to engage in employability activities end up being exploited in this process.

Research limitations/implications

The study provides a new roadmap to scholars of employability who wish to explore the domain further.

Practical implications

The theoretical knowledge from this research will inform practice. It will influence managers and policymakers in the organization as well as politicians. Although the macroaspects of the organizational environment are beyond the control of an organization, the development efforts of the organization should be real and should not estrange individuals from their true nature. The real intent should be to unite the individual with its true nature. This way, it will be real development and will empower individuals rather than exploitation.

Social implications

The finding that commitment is linked to self-exploitation via employability has implications for managers and policymakers. To avoid estrangement and exploitation, the organization should focus on employee real development. To have an ideal workplace, where employees unite with their nature, the organization should invest in employees, focus on their real needs, emphasize their career prospects and constantly provide them with learning and growth opportunities. In addition to material compensation, the organization should connect people with their true spirit. An organization that is concerned with people's real needs and real development will have a pool of human capital that will create real value for the organization and society as well.

Originality/value

The dark side of employability has been ignored in the extant literature. Limited research exists that explicitly examines this relationship or explores its potential implications. This study is an initiative for such debate.
LGBTQ+ in workplace: a systematic review and reconsideration
Authors: Maji Sucharita , Yadav Nidhi , Gupta Pranjal
Published: May 2023

Purpose

The inclusion of LGBTQ + persons (lesbian, gay, bisexual, transgender, queer and having other sexual orientations and gender identities) is a crucial step in improving gender diversity in the workplace; however, till date, it remains a significant challenge for human resource management professionals. The current study critically examines this issue of an inclusive workplace for LGBTQ + people through a systematic review of the existing research that has empirically studied their experiences at the workplace. It also examines the resistance and challenges organizations face in LGBTQ + diversity training and provides future research avenues.

Design/methodology/approach

For systematically reviewing the literature, Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) model has been used. A total of 101 empirical studies have been reviewed.

Findings

The result shows that LGBTQ + people encounter multiple negative workplace experiences, including proximal (hiring discrimination and housing discrimination) and distal workplace discrimination (unsafe work climate, microaggressions and harassment). These aversive experiences lead to work stress while also mandating that people manage their sexual identity and style of dressing. This stress, in turn, impacts their work–family outcomes, job satisfaction and decision-making with regard to their careers.

Originality/value

The paper provides a holistic understanding of the aversive workplace experiences encountered by sexual minorities.
Thriving in management innovation: an institutional perspective
Authors: Khosravi Pouria , Newton Cameron , Rezvani Azadeh , Ghanbarzadeh Reza , Akbari Morteza
Published: May 2023

Purpose

Management innovation is one of the most vital practices underpinning economic growth and is considered to be one of the fundamental components of gaining a superior business position in market conditions that are continually fluctuating. Drawing upon neo-institutional theory as well as absorptive capacity, the current empirical study unpacks the relationships between external institutional forces (i.e. regulative, mimetic and normative pressures) and management innovation through investigating the role of absorptive capacity as a mediator.

Design/methodology/approach

The research model is tested using survey data from Australian organisations. The study used Partial Least Squares (PLS), a component-based structural equation modelling (SEM) method, in order to perform the data analysis.

Findings

The results confirm that the various dimensions of institutional forces have diverse influences on management innovation. The authors found mimetic and normative pressures have positive influences on realised and potential absorptive capacity of an organisation. In addition, realised absorptive capacity mediates the relations between institutional forces and management innovation.

Originality/value

Dissimilar to preceding studies, this research shows that organisations not only innovate to pursue higher performance but sometimes strive for legitimacy. In addition, the significant associations between absorptive capacity and management innovation and the mediation role clearly signify that institutional forces and absorptive capacity play significant roles in the adoption of management innovation.
The role of bricolage in countering resource constraints and uncertainty in start-up business model innovation
Authors: Xu Sha , He Jie , Morrison Alastair M. , Su Xiaohua , Zhu Renhong
Published: May 2023

Purpose

Drawing from resource orchestration theory, this research proposed an integrative model that leverages insights into counter resource constraints and uncertainty in start-up business model innovation (BMI). It investigated the influences of entrepreneurial networks and effectuation on BMI through bricolage in uncertain environments.

Design/methodology/approach

The research surveyed 481 start-ups in China. LISREL 8.80 and SPSS 22.0 were employed to test the validity and reliability of key variables, respectively. Additionally, hypotheses were examined through multiple linear regression.

Findings

First, entrepreneurial networks and effectuation were positively related to BMI, and combining these two factors improved BMI for start-ups. Second, bricolage contributed to BMI and played mediating roles in translating entrepreneurial networks and effectuation into BMI. Third, environmental uncertainty weakened the linkage between bricolage and BMI.

Research limitations/implications

Future research should replicate the results in other countries because only start-ups in China were investigated in the study, and it is necessary to extend this research by gathering longitudinal data. This research emphasized the mediating effects of bricolage and the moderating influence of environmental uncertainty, and new potential mediating and moderating factors should be explored between resources and BMI.

Originality/value

There are three significant theoretical contributions. First, the findings enrich the literature on the complex antecedents of BMI by combining the impacts of entrepreneurial networks and effectuation. Second, an overarching framework is proposed explaining how bricolage (resource management) links entrepreneurial networks and effectuation and BMI. Third, it demonstrates the significance of environmental uncertainty in the bricolage–BMI linkage, deepening the understanding of the bricolage boundary condition.