bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible graphene-based neurotechnology for high-precision deep brain mapping and neuromodulation in Parkinsonian rats
Authors: Ria Nicola , Eladly Ahmed , Masvidal Eduard , Illa Xavi , Guimerà Anton , Hills K. , Garcia Ramon , Flaherty Samuel , Prokop Michal , Wykes Rob. C , Kostarelos Kostas , Garrido Jose A.
Published: September 2024

Deep brain stimulation (DBS) is a neuroelectronic therapy for the treatment of a broad range of neurological disorders, including Parkinson’s disease. Current DBS technologies face important limitations that impact their efficacy, such as large electrode size, invasiveness, and lack of adaptive therapy based on biomarker monitoring. The use of novel electrode materials is expected to contribute to overcome these limitations. In a previous study, we reported that nanoporous reduced graphene oxide (rGO) is a promising electrode material due to its high charge injection capacity and low impedance. Here, we investigate the potential benefits of using the rGO technology in DBS. To this end, we implant a flexible high-density array of rGO microelectrodes in the subthalamic nucleus (STN) of healthy and hemi-parkinsonian rats to investigate specific electrophysiological Parkinsonian biomarkers and to assess the effect of microscale stimulation. We demonstrate that these microelectrodes record action potentials with high signal-to-noise ratios (SNR > 6), allowing the precise localization of deep brain structures like the STN, and the tracking of multiunit-based biomarkers such as STN bursts. The bidirectional capability to deliver high-density focal stimulation and to record high-fidelity signals unlocks the visualization of the local neuromodulation of the multiunit biomarker. These findings demonstrate the potential of bidirectional high-resolution neural interfaces to investigate the mechanisms around DBS in preclinical models and suggest new avenues for the use of adaptive closed-loop operation based on electrophysiological biomarkers monitoring.
CX3CR1 modulates migration of resident microglia towards brain injury
Authors: Wagner Jens , Hoyer Cornelia , Antony Henrike , Lundgrén Kristiina , Soliymani Rabah , Crux Sophie , Justus Lena , Keppler Kevin , Steffen Julia , Kurts Christian , Engel Daniel R. , Herms Jochen , Łałowski Maciej , Fuhrmann Martin
Published: September 2024

Microglia are innate immune cells of the central nervous system (CNS). They extend their processes towards and migrate towards injuriesin vivo. However, whether the fractalkine receptor (CX3CR1) influences microglial migration remains unknown. Label-free proteomic profiling predicted changes in RHO-signaling activity that hint at dysregulated cytoskeleton signaling inCx3cr1-deficient murine cortex tissue. To further investigate microglial migration, we carried out 4-hour interval two-photonin vivoimaging for 72 hours after a laser lesion in the cortex.Cx3cr1-deficient microglia showed enhanced migration towards the lesion. Additionally, length and velocity of microglial fine processes extending towards the lesion were increased inCx3cr1-deficient microglia. Migration remained unchanged inCcr2-deficient mice, indicating that monocyte-derived macrophages/microglia did not contribute to microglia accumulation around the lesion. These results demonstrate microglia migration towards CNS injury and suggest CX3CR1 as a modulator of this. Manipulating microglia migration via CX3CR1 therefore is a potential target for treatment of CNS-injury.
Identification and Diagnostic Potential of Pyroptosis-Related Genes in Endometriosis: A Novel Bioinformatics Analysis
Authors: Teng Piaopiao , Wang Li , Ding Caiyun , Gu Kaili , Luo Xianchen , Su Chang , Ni Guantai , Lyu Yuanyuan , Ding Jin
Published: September 2024

Objective

This study aimed to identify and analyze potential signatures of pyroptosis-related genes in EMs.

Methods

Transcriptomic datasets related to endometriosis were retrieved from the GEO databases (GSE7305, GSE7307, and GSE11691). Differential gene expression analysis was performed to identify pyroptosis-related differentially expressed genes (PRDEGs) by intersecting DEGs with a curated list of PRGs. Various bioinformatics tools were employed to explore the biological functions and pathways associated with PRDEGs.

Results

We identified 26 PRDEGs from combined datasets and constructed an EMs diagnostic model using LASSO regression based on pyroptosis scores. The model included 5 DEGs: KIF13B, BAG6, MYO5A, HEATR, and AK055981. Additionally, 21 Key Module Genes (KMGs) were identified, leading to the classification of 3 distinct EMs subtypes. These subtypes were analyzed for immune cell infiltration, revealing a complex immune landscape in EMs.

Conclusions

This study reveals pyroptosis’ crucial role in EMs and offers a novel diagnostic model based on pyroptosis-related genes. Modulating pyroptosis may provide a new therapeutic approach for managing EMs.
Building plumbing influences the microdiversity and community assembly of the drinking water microbiome
Authors: He Huanqi , Huo Linxuan , Oosthuizen-Vosloo Solize , Pieper Kelsey J. , Stubbins Aron , Yoon Byungman , Pinto Ameet J.
Published: September 2024

Building plumbing microbial communities can significantly influence water quality at the point of use, particularly during periods of stagnation. Thus, a fine-scale understanding of factors governing community membership and structure, as well as environmental and ecological factors shaping building plumbing microbial communities is critical. In this study, we utilized full-length 16S ribosomal RNA (rRNA) gene sequencing to investigate the microdiversity and spatial-temporal dynamics of microbial communities in commercial and residential building plumbing systems. Bacterial operational taxonomic units (OTUs) within commercial buildings exhibited much lower microdiversity relative to the same OTUs in residential buildings. Microdiversity was associated with higher persistence and relative abundance of OTUs. Interestingly, amplicon sequencing variants within the same OTUs exhibited habitat preferences based on the building type while also demonstrating varying temporal turnover patterns. Dispersal limitation disproportionately governed community assembly in commercial buildings, whereas heterogeneous selection was the dominant ecological mechanism shaping the microbial community in residential buildings. Dispersal limitation in commercial buildings is consistent with larger building sizes and greater periods of water stagnation. Interestingly, the inability to explain the extent of heterogeneous selection-driven community assembly in residential locations using measured water chemistry may suggest a disproportionately large effect of fine-scale variation in plumbing characteristics on community assembly in residential locations.
Eavesdropping on Herbivores: Using contact microphones to quantify Plant-Insect Interactions
Authors: Mehrotra Dev , Still Laurence , Agrawal Vidit , Gibson Kimberly , Crall James D. , Bick Emily N.
Published: September 2024

Herbivorous insects are major crop pests whose feeding often results in significant economic damage. Detecting and monitoring insect herbivory is crucial for effective pest management, but manual methods can be time-consuming, inefficient, and destructive. This study investigates the use of contact microphones as a non-invasive and efficient tool for detecting, identifying, and monitoring insects feeding on plants.

Approach and methods: Contact microphones connected to a Raspberry Pi were clipped onto plant stems and programmed to record sounds made by the feeding insects. Three combinations of herbivorous insects and plants were evaluated: tobacco hornworm (Manduca sextaLinnaeus) on tobacco, Colorado potato beetle (Leptinotarsa decemlineataSay) on potato, and European corn borer (Ostrinia nubilalisHübner) and Northern corn rootworm (Diabrotica barberiSmith & Lawrence) on corn (Zea maysLinnaeus). Sound recordings were analyzed to determine the presence and absence of insects and to quantify differences in feeding activity between different insects. The laboratory study was repeated in a corn field to observe corn rootworms (Diabroticaspp.).

Main results: Contact microphones successfully detected insect herbivory on the tobacco, potato, and corn plants in the lab and field, demonstrating the use of substrate-born acoustic signals for detecting both large and small-bodied insect pests. The recordings also revealed differences in the feeding patterns, frequency, and amplitude between insect species. Field experiments indicate low background noise relative to lab experiments.

Conclusions and implications: Contact microphones offer a promising cost-effective, non-destructive, and efficient method for monitoring insect herbivory. This approach has the potential to improve scientific observations of insect herbivores and pest management strategies by enabling early pest detection and measuring the success of interventions. Early field results indicate the viability of this approach under realistic conditions in the field. The results highlight the importance of considering the acoustic environment in agricultural ecosystems, suggesting sound can be used to better understand the behavior of insects and their interactions with plant hosts. Contact microphones could have widespread applications in agriculture and ecology by providing a simple and effective tool for detecting and monitoring insect activity.
PDZ-directed substrate recruitment is the primary determinant of specific 4E- BP1 dephosphorylation by PP1-Neurabin
Authors: Fedoryshchak Roman O , El-Bouri Karim , Joshi Dhira , Mouilleron Stephane , Treisman Richard
Published: September 2024

Protein Phosphatase 1 (PP1) relies on association with PP1-interacting proteins (PIPs) to generate substrate-specific PIP/PP1 holoenzymes, but the lack of well-defined substrates has hindered elucidation of the mechanisms involved. We previously demonstrated that the Phactr1 PIP confers sequence specificity on the Phactr1/PP1 holoenzyme by remodelling the PP1 hydrophobic substrate groove. Phactr1 defines a group of “RVxF-ΦΦ-R-W” PIPs that all interact with PP1 in a similar fashion. Here we use a PP1-PIP fusion approach to address sequence specificity and identify substrates of the RVxF-ΦΦ-R-W family PIPs. We show that the four Phactr proteins confer identical sequence specificities on their holoenzymes. We identify the 4E-BP and p70 S6K translational regulators as substrates for the Neurabin/Spinophilin PIPs, implicated in neuronal plasticity, pointing to a role for their holoenzymes in mTORC1-dependent translational control. Biochemical and structural experiments show that in contrast to the Phactrs, substrate recruitment and catalytic efficiency of the PP1-Neurabin and PP1-Spinophilin fusions is primarily determined by substrate interaction with the PDZ domain adjoining their RVxF-ΦΦ-R-W motifs, rather than by recognition of the remodelled PP1 hydrophobic groove. Thus, even PIPs that interact with PP1 in a similar manner use different mechanisms to ensure substrate selectivity.
Whisker deprivation triggers a distinct form of cortical homeostatic plasticity that is impaired in theFmr1KO
Authors: Lakhani Alishah , Huang Washington , Rodgers Chris C. , Wenner Peter
Published: September 2024

Mouse models of Fragile X Syndrome (FXS) have demonstrated impairments in excitatory and inhibitory sensory-evoked neuronal firing. Homeostatic plasticity, which encompasses a set of mechanisms to stabilize baseline activity levels, does not compensate for these changes in activity. Previous work has shown that impairments in homeostatic plasticity are observed in FXS, including deficits in synaptic scaling and intrinsic excitability. Here, we aimed to examine how homeostatic plasticity is alteredin vivoin anFmr1KO mouse model following unilateral whisker deprivation (WD). We show that WD in the wild type leads to an increase in the proportion of L5/6 somatosensory neurons that are recruited, but this does not occur in the KO. In addition, we observed a change in the threshold of excitatory neurons at a later developmental stage in the KO. Compromised homeostatic plasticity in development could influence sensory processing and long-term cortical organization.
Versatile Cell Penetrating Peptide for Multimodal CRISPR Gene Editing in Primary Stem Cells
Authors: Graham Josh P. , Castro Jose Gabriel , Werba Lisette C. , Fardone Luke C. , Francis Kevin P. , Ramamurthi Anand , Layden Michael , McCarthy Helen O. , Gonzalez-Fernandez Tomas
Published: September 2024

CRISPR gene editing offers unprecedented genomic and transcriptomic control for precise regulation of cell function and phenotype. However, delivering the necessary CRISPR components to therapeutically relevant cell types without cytotoxicity or unexpected side effects remains challenging. Viral vectors risk genomic integration and immunogenicity while non-viral delivery systems are challenging to adapt to different CRISPR cargos, and many are highly cytotoxic. The arginine-alanine-leucine-alanine (RALA) cell penetrating peptide is an amphiphilic peptide that self-assembles into nanoparticles through electrostatic interactions with negatively charged molecules before delivering them across the cell membrane. This system has been used to deliver DNAs, RNAs, and small anionic molecules to primary cells with lower cytotoxicity compared to alternative non-viral approaches. Given the low cytotoxicity, versatility, and competitive transfection rates of RALA, we aimed to establish this peptide as a new CRISPR delivery system in a wide range of molecular formats across different editing modalities. We report that RALA was able to effectively encapsulate and deliver CRISPR in DNA, RNA, and ribonucleic protein (RNP) formats to primary mesenchymal stem cells (MSCs). Comparisons between RALA and commercially available reagents revealed superior cell viability leading to higher numbers of transfected cells and the maintenance of cell proliferative capacity. We then used the RALA peptide for the knock-in and knock-out of reporter genes into the MSC genome as well as for the transcriptional activation of therapeutically relevant genes. In summary, we establish RALA as a powerful tool for safer and effective delivery of CRISPR machinery in multiple cargo formats for a wide range of gene editing strategies.
The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles
Authors: Straub Verena M. , Barti Benjamin , Tandar Sebastian T. , Stevens A. Floor , van der Wel Tom , Zhu Na , Rüegger Joel , van der Horst Cas , Heitman Laura H. , Li Yulong , Stella Nephi , van Hasselt J. G. Coen , Katona István , van der Stelt Mario
Published: September 2024

While it is known that endocannabinoids (eCB) modulate multiple neuronal functions, the molecular mechanism governing their release and transport remains elusive. Here, we propose an “on-demand release” model, wherein the formation of microvesicles, a specific group of extracellular vesicles (EVs) containing the eCB, 2-arachidonoylglycerol (2-AG), is the rate-limiting step. A co-culture model system that combines a reporter cell line expressing the fluorescent eCB sensor, GRABeCB2.0, and neuronal cells revealed that neurons release EVs containing 2-AG, but not anandamide, in a stimulus-dependent process regulated by PKC, DAGL, Arf6, and which was sensitive to inhibitors of eCB facilitated diffusion. A vesicle contained approximately 2000 2-AG molecules. Accordingly, hippocampal eCB-mediated synaptic plasticity was modulated by Arf6 and transport inhibitors. This “on demand release” model, supported by mathematical analysis, offers a cohesive framework for understanding eCB signaling at the molecular level and suggests that microvesicles carrying signaling lipids regulate neuronal functions in parallel to canonical synaptic vesicles.
Cytotoxicity of Activator Expression in CRISPR-based Transcriptional Activation Systems
Authors: Maddineni Aakaanksha , Liang Ziyan , Jambardi Shreya , Roy Subrata , Tycko Josh , Patil Ajinkya , Manzano Mark , Gottwein Eva
Published: September 2024

CRISPR-based transcriptional activation (CRISPRa) has extensive research and clinical potential. Here, we show that commonly used CRISPRa systems can exhibit pronounced cytotoxicity. We demonstrate the toxicity of published and new CRISPRa vectors expressing the activation domains (ADs) of the transcription factors p65 and HSF1, components of the synergistic activation mediator (SAM) CRISPRa system. Based on our findings for the SAM system, we extended our studies to additional ADs and the p300 acetyltransferase core domain. We show that the expression of potent transcriptional activators in lentiviral producer cells leads to low lentiviral titers, while their expression in the transduced target cells leads to cell death. Using inducible lentiviral vectors, we could not identify an activator expression window for effective SAM-based CRISPRa without measurable toxicity. The toxicity of current SAM-based CRISPRa systems hinders their wide adoption in biomedical research and introduces selection bottlenecks that may confound genetic screens. Our results suggest that the further development of CRISPRa technology should consider both the efficiency of gene activation and activator toxicity.
Identification of a crucialINO2allele for enhancing ethanol resistance in an industrial fermentation strain ofSaccharomyces cerevisiae
Authors: Albillos-Arenal Sonia , Alonso del Real Javier , Lairón-Peris María , Barrio Eladio , Querol Amparo
Published: September 2024

Ethanol toxicity is a major challenge forS. cerevisiaeduring fermentation, affecting its growth and influencing the process. This study investigated the molecular mechanisms of ethanol tolerance using transcriptomic analysis of threeS. cerevisiaestrains with varying ethanol resistance. We identified distinct responses in membrane lipid synthesis genes, particularly in ergosterol biosynthesis, regulated by the Ino2p transcription factor. A variant of Ino2p with V263I and H86R amino acid replacements was exclusive to ethanol-tolerant strains. CRISPR-Cas9-mediated point mutations in theINO2gene of the highly tolerant strain AJ4 resulted in decreased ethanol tolerance. Our findings demonstrate the crucial role of Ino2p in ethanol tolerance through regulation of lipid synthesis and membrane composition, highlighting the complex interplay of trans elements in strain-specific ethanol resistance

IMPORTANCE

This study provides critical insights into the molecular basis of ethanol tolerance inS. cerevisiae, a key trait for improving industrial fermentation processes. By identifying specific genetic variants in the Ino2p transcription factor and their impact on ethanol resistance, we reveal potential targets for enhancing yeast strain performance in high-ethanol environments. Our findings not only contribute to the fundamental understanding of stress response mechanisms in yeast but also offer practical implications for strain engineering in the biotechnology and beverage industries. The unexpected magnitude of the Ino2p variants’ effect on ethanol tolerance underscores the importance of considering strain-specific genetic backgrounds in metabolic engineering strategies
Absent, but not glucocorticoid-modulated, corticotropin-releasing hormone (Crh) regulates anxiety-like behaviors in mice
Authors: Friedman Hannah R. , Gaston Lindsey S. , Chan Li F. , Majzoub Joseph A.
Published: September 2024

The hypothalamic-pituitary-adrenal (HPA) axis is a well characterized endocrine response system. Hypothalamic Crh in the paraventricular nucleus of the hypothalamus (PVH) initiates HPA axis signaling to cause the release of cortisol (or corticosterone in rodents) from the adrenal gland. PVH-specific deletion ofCrhreduces anxiety-like behaviors in mice. Here we report that manipulation of PVHCrhexpression in primary adrenal insufficiency or by dexamethasone (DEX) treatment do not alter mouse anxiety behaviors. In Experiment 1, we compared wildtype (WT) mice to those with primary adrenal insufficiency (MrapKO) or global deletion of Crh (CrhKO). We analyzed behaviors using open field (OF) and elevated plus maze (EPM), PVH Crh mRNA expression by spatial transcriptomics, and plasma ACTH and corticosterone after a 15-minute restraint test with ELISAs. EPM analysis showedCrhKO mice were less anxious than WT andMrapKO mice, andMrapKO mice had no distinguishing behavioral phenotype. In Experiment 2, we evaluated HPA axis habituation to chronically elevatedCrhexpression by comparing mice treated with 5-8 weeks of DEX with those similarly treated followed by DEX withdrawal for 1 week. All mice regardless of genotype and treatment showed no significant behavioral differences. Our findings suggest that reduced anxiety associated with lowCrhexpression requires extreme deficiency, perhaps outside of those PVH Crh neurons negatively regulated by glucocorticoids. If these findings extend to humans, they suggest that increases in Crh expression with primary adrenal insufficiency, or decreases with exogenous glucocorticoid therapy, may not alter anxiety behaviors via modulation of Crh expression.
The role of vibration amplitude in the escape hatching response of red-eyed treefrog embryos
Authors: Jung Julie , Caldwell Michael S. , McDaniel J. Gregory , Warkentin Karen M.
Published: September 2024

The function and adaptive significance of defensive behaviors depend on the contexts in which they naturally occur. Amplitude properties of predator cues are widely used by prey to assess predation risk, yet rarely studied in the context of the stimuli relevant to defensive decisions in nature. Red-eyed treefrog embryos,Agalychnis callidryas, hatch precociously in response to attacks on their arboreal egg clutches by snakes and wasps. They use vibrations excited during attacks to detect predators, but wind and rainstorms also excite intense vibrations. Past work has demonstrated that to avoid costly decision errors,A. callidryasnon-redundantly combine information from the temporal and frequency properties of clutch vibrations. Here we demonstrate that embryos also use absolute amplitude and fine-scale amplitude modulation information to refine their hatching decision. We used vibration recordings to characterize the amplitude properties of the most common predator and benign-source disturbances toA. callidryasegg clutches in nature and tested whether embryos at three ages across the onset of mechanosensory-cued hatching (4–6 days) respond to amplitude variation during playback of synthetic vibrations to eggs. Older embryos responded to much lower-amplitude vibrations, reflecting a >88-fold decrease in response threshold from 4 to 5 days. To assess how embryos combine amplitude with other vibration properties, we played embryos recorded exemplars of snake attack and rain vibrations of varying amplitudes and patterns of amplitude modulation. The amplitude response curve was steeper for snake recordings than for rain. While amplitude information alone is insufficient to discriminate predator attack from benign-source vibrations,A. callidryasemploy an impressively complex strategy combining absolute amplitude, amplitude modulation, temporal, and frequency information for their hatching decision.
Quorum sensing orchestrates parallel cell death pathways inVibrio choleraevia Type 6 secretion dependent and independent mechanisms
Authors: Mashruwala Ameya A. , Bassler Bonnie L.
Published: September 2024

Quorum sensing (QS) is a cell-to-cell communication process that enables bacteria to coordinate group behaviors. InVibrio choleraecolonies, a program of spatial-temporal cell death is among the QS-controlled traits. Cell death occurs in two phases, first along the colony rim, and subsequently, at the colony center. Both cell death phases are driven by the type VI secretion system (T6SS). Here, we show that HapR, the master QS regulator, does not controlt6ssgene expression nor T6SS-mediated killing activity. Nonetheless, a ΔhapRstrain displays no cell death at the colony rim. RNA-Seq analyses reveal that HapR activates expression of an operon containing four genes of unknown function,vca0646-0649. Epistasis and overexpression studies show that two of the genes,vca0646andvca0647, are required to drive cell death in both a ΔhapRand a ΔhapRΔt6ssstrain. Thus,vca0646-0649are regulated by HapR but act independently of the T6SS machinery to cause cell death, suggesting that a second, parallel pathway to cell death exists inV. cholerae.

Significance

Cell death is a fundamental biological process. In mammals, cell death sculpts tissues during development, enables injury recovery, and regulates immunity. In bacteria, cell death mechanisms remain little explored. Recently, colonies formed by the pathogenVibrio choleraewere demonstrated to undergo a spatio-temporal program of cell death. The program is controlled by quorum sensing (QS) and driven by the Type VI secretion system. Here, we discover QS-controlled genes, calledvca0646-0649, that cause cell death inV. choleraecolonies independently of the Type VI secretion system. These findings indicate that a second cell death pathway exists inV. cholerae. The results expand our understanding of bacterial cell death mechanisms and provide insight into how cell death shapes bacterial community structure.
Identification of Intrinsic Features for Cortical Separability of Human and Mouse Neurons
Authors: Yun Zhixi , Ye Wen , Ji Nan , Wang Yujin , Rong Jing , Li Tian , Wang Ruilong , Li Yingxin , Zhang Hairuo , Xu Hao , Mo Nan , Song Binghua , Chen Xin , Wang Yi , Mai Yiying , Ding Ming , Ding Song-Lin , Liu Lijuan , Zhang Liwei , Peng Hanchuan
Published: September 2024

This work introduces a novel framework for holistic comparative analysis of cortical regions in mouse and human brains at single-neuron resolution, with a primary focus on the morphological and molecular characteristics of neurons. To do so, we generated one of the largest dendritic reconstruction datasets of cortical neurons to date, comprising 2,363 human neurons and 16,011 mouse neurons from the frontal, parietal, and temporal lobes, followed by establishing a rigorous procedure to identify anatomically and functionally corresponding brain regions with minimal variability in brain mapping. Additionally, we leveraged single nucleus/cell transcriptomic data from independent groups to validate the molecular correspondence of the brain regions identified in this study. The significance of these anatomically, functionally, and molecularly corresponding mouse-human region pairs is highlighted by examining the intrinsic features of their respective cortical regions. Our findings reveal that human neuron branching patterns differ dramatically from those in mouse brains, particularly in terms of dendritic branching frequency and normalized dendritic branching intervals. This difference is pronounced in the frontal and temporal lobes, underscoring the distinct neuronal architectures between the two species. At the single-neuron level, we found that neurons from the human frontal and parietal lobes are six times more separable than those from the same regions in mouse brains. This heightened separability is also observed between the frontal and temporal lobes, as well as between the parietal and temporal lobes in humans. We thoroughly explored the entire morphological feature space, along with its characteristic subspaces, and consistently found this distinct separability. Remarkably, this neuronal separability can be partially recapitulated when examining the global functional states of these brain lobes-using newly acquired Electroencephalography (EEG) and Magnetoencephalography (MEG) signals as physiological measures-as well as their global metabolic states, molecular profiles, and cortical geometry. These findings suggest that our comparative analysis of single-neuron intrinsic features could serve as a valuable foundation for future comprehensive studies of cross-species brain structures and functions.
Distinct Disruptions in CA1 and CA3 Place Cell Function in Alzheimer’s Disease Mice
Authors: Park Sanggeon , Park Mijeong , Kim Eun Joo , Kim Jeansok J. , Huh Yeowool , Cho Jeiwon
Published: September 2024

The hippocampus, a critical brain structure for spatial learning and memory, is susceptible to neurodegenerative disorders such as Alzheimer’s disease (AD). The APPswe/PSEN1dE9 (APP/PS1) transgenic mouse model is widely used to study the pathology of AD. Although previous research has established AD-associated impairments in hippocampal-dependent learning and memory, the neurophysiological mechanisms underlying these cognitive dysfunctions remain less understood. To address this gap, we investigated the activities of place cells in both CA1 and CA3 hippocampal subregions, which have distinct yet complementary computational roles. Behaviorally, APP/PS1 mice demonstrated impaired spatial recognition memory compared to wild-type (WT) mice in the object location test. Physiologically, place cells in APP/PS1 mice showed deterioration in spatial representation compared to WT. Specifically, CA1 place cells exhibited significant reductions in coherence and spatial information, while CA3 place cells displayed a significant reduction in place field size. Both CA1 and CA3 place cells in APP/PS1 mice also showed significant disruptions in their ability to stably encode the same environment. Furthermore, the burst firing properties of these cells were altered to forms correlated with reduced cognition. Additionally, the theta rhythm was significantly attenuated in CA1 place cells of APP/PS1 mice compared to WT. Our results suggest that distinct alteration in the physiological properties of CA1 and CA3 place cells, coupled with disrupted hippocampal theta rhythm in CA1, may collectively contribute to impaired hippocampal-dependent spatial learning and memory in AD.
Jaeger: an accurate and fast deep-learning tool to detect bacteriophage sequences
Authors: Wijesekara Yasas , Wu Ling-Yi , Beeloo Rick , Rozwalak Piotr , Hauptfeld Ernestina , Doijad Swapnil P. , Dutilh Bas E. , Kaderali Lars
Published: September 2024

Viruses are integral to every biome on Earth, yet we still need a more comprehensive picture of their identity and global distribution. Global metagenomics sequencing efforts revealed the genomic content of tens of thousands of environmental samples, however identifying the viral sequences in these datasets remains challenging due to their vast genomic diversity. Here, we address identifying bacteriophage sequences in unlabeled sequencing data. In a recent benchmarking paper, we observed that existing deep-learning tools show a high true positive rate, but may also produce many false positives when confronted with divergent sequences. To tackle this challenge, we introduce Jaeger, a novel deep-learning method designed specifically for identifying bacteriophage genome fragments. Extensive benchmarking on the IMG/VR database and real-world metagenomes reveals Jaeger’s consistent high sensitivity (0.87) and precision (0.92). Applying Jaeger to over 16,000 metagenomic assemblies from the MGnify database yielded over five million putative phage contigs. On average, Jaeger is around 20 times faster than the other state-of-the-art methods. Jaeger is available athttps://github.com/MGXlab/Jaeger.
The electrogenicity of the Na+/K+-ATPase poses challenges for computation in highly active spiking cells
Authors: Weerdmeester Liz , Schleimer Jan-Hendrik , Schreiber Susanne
Published: September 2024

1

The evolution of the Na+/K+-ATPase laid the foundation for ion homeostasis and electrical signalling. While not required for restoration of ionic gradients, the electrogenicity of the pump (resulting from its 3:2 stoichiometry) is useful to prevent runaway activity. As we show here, electrogenicity also comes with disadvantageous side effects: (1) an activity-dependent shift in a cell’s baseline firing and (2) interference with computation, disturbing network entrainment when inputs change strongly. We exemplify these generic effects in a mathematical model of the weakly electric fish electrocyte, which spikes at hundreds of Hz and is exposed to abrupt rate changes when producing behaviourally-relevant communication signals. We discuss biophysical strategies allowing cells to mitigate the consequences of electrogenicity at additional metabolic cost and postulate an interesting role for a voltage-dependence of the Na+/K+-ATPase. Our work shows that the pump’s electrogenicity opens an additional axis of vulnerability that is likely to play a role in brain disease.
A genome-wide CRISPR screen inAnophelesmosquito cells identifies essential genes and required components of clodronate liposome function
Authors: Mameli Enzo , Samantsidis George-Rafael , Viswanatha Raghuvir , Kwon Hyeogsun , Hall David R. , Butnaru Matthew , Hu Yanhui , Mohr Stephanie E. , Perrimon Norbert , Smith Ryan C.
Published: September 2024

Anophelesmosquitoes are the sole vector of human malaria, the most burdensome vector-borne disease worldwide. Strategies aimed at reducing mosquito populations and limiting their ability to transmit disease show the most promise for disease control. Therefore, gaining an improved understanding of mosquito biology, and specifically that of the immune response, can aid efforts to develop new approaches that limit malaria transmission. Here, we use a genome-wide CRISPR screening approach for the first time in mosquito cells to identify essential genes inAnophelesand identify genes for which knockout confers resistance to clodronate liposomes, which have been widely used in mammals and arthropods to ablate immune cells. In the essential gene screen, we identified a set of 1280Anophelesgenes that are highly enriched for genes involved in fundamental cell processes. For the clodronate liposome screen, we identified several candidate resistance factors and confirm their roles in the uptake and processing of clodronate liposomes throughin vivovalidation inAnopheles gambiae, providing new mechanistic detail of phagolysosome formation and clodronate liposome function. In summary, we demonstrate the application of a genome-wide CRISPR knockout platform in a major malaria vector and the identification of genes that are important for fitness and immune-related processes.
Dual roles of EGO-1 and RRF-1 in regulating germline exo-RNAi efficiency inCaenorhabditis elegans
Authors: Dejima Katsufumi , Yoshida Keita , Mitani Shohei
Published: September 2024

RNA interference (RNAi) is widely used in life science research and is critical for diverse biological processes, such as germline development and antiviral defense. InCaenorhabditis elegans, RNA-dependent RNA polymerases, with redundant involvement of EGO-1 and RRF-1, facilitate small RNA amplification in germline exogenous RNAi (exo-RNAi). However, their coordination during the regulation of exo-RNAi processes in the germline remains unclear. Here, we examined non-null mutants of theego-1gene and found thatego-1(S1198L)animals exhibited germline exo-RNAi defects with normal fertility, abnormalities in germ granules, and synthetic temperature-dependent sterility withrrf-1. The exo-RNAi defects inego-1(S1198L)were partially restored by inhibitinghrde-1,cde-1, andznfx-1. Similar defects were observed in wild-type andego-1(S1198L)heterozygous descendants derived fromego-1(S1198L), but these were suppressed by ancestral inhibition ofrrf-1. These data reveal a dual role for EGO-1 in the positive regulation of germline exo-RNAi: it not only mediates target silencing through its RNA-dependent RNA polymerase activity, but also fine-tunes germ granule function or downstream processes, which are antagonized by RRF-1.
Motor preparation tracks decision boundary crossing in temporal decision-making
Authors: Ofir Nir , Landau Ayelet N.
Published: September 2024

Interval timing, the ability of animals to estimate the passage of time, is thought to involve diverse neural processes rather than a single central “clock” (Paton & Buonomano, 2018). Each of the different processes engaged in interval timing follows a different dynamic path, according to its specific function. For example, attention tracks anticipated events, such as offsets of intervals (Rohenkohl & Nobre, 2011), while motor processes control the timing of the behavioral output (De Lafuente et al., 2024). Hence, different processes provide complimentary perspectives on mechanisms of time perception. The temporal bisection task, where participants categorize intervals as “long” or “short”, is thought to rely on the same mechanisms as other perceptual decisions (Balcı & Simen, 2014). In line with this hypothesis, we previously described an EEG potential that tracks the formation of decision following the end of the timed interval (Ofir & Landau, 2022). Here, we track the dynamics of motor preparation to investigate the formation of decision within the timed interval. In contrast to typical perceptual decisions, where motor plans for all response alternatives are prepared simultaneously (Shadlen & Kiani, 2013), we find that different temporal decisions develop sequentially. While preparation for “long” responses was already underway before interval offset, no preparation was found for “short” responses. Furthermore, within intervals categorized as “long”, motor preparation was stronger at interval offset for faster responses. Our findings shed light on the unique dynamics of temporal decisions and demonstrate the importance of considering neural activity in timing tasks from multiple perspectives.
Neff
as a new physics probe in the precision era of cosmology
Authors: Du Yong
Published: September 2024

We perform a global fit to the electroweak vertices and four-fermion operators of the standard model effective field theory in this work using Neff from cosmological probes, as well as datasets from colliders and low-energy experiments. We find Neff, both its current measurement and future projections, can only marginally improve the fit in both the flavor universal and the most general flavor scenarios. The resulting 1σ bound on Neff is significantly improved from the global fit and becomes comparable to its current theoretical uncertainty, such that the latter will become important for this study at next generation experiments like future lepton colliders. Neff from the global fit is also adopted to predict the primordial helium abundance YP, which significantly reduces the parameter space on the YP−Neff plane. Through error propagation, we also conclude that reducing the experimental uncertainty of YP from metal-poor galaxies down below 0.2% could play an important role in deepening our understanding of the free neutron lifetime anomaly.

Published by the American Physical Society
2024
High-fidelity macroscopic superposition states via shortcut to adiabaticity
Authors: Aslani Mehdi , Salari Vahid , Abdi Mehdi
Published: September 2024

A shortcut to an adiabatic scheme is proposed for preparing a massive object in a macroscopic spatial superposition state. In this scheme we propose to employ counterdiabatic driving to maintain the system in the ground state of its instantaneous Hamiltonian while the trap potential is tuned from a parabola to a double well. This, in turn, is performed by properly ramping a control parameter. We show that a few counterdiabatic drives are enough for most practical cases. A hybrid electromechanical setup in superconducting circuits is proposed for the implementation. The efficiency of our scheme is benchmarked by numerically solving the system dynamics in the presence of noises and imperfections. The results show that a mechanical resonator with very-high-fidelity spatially distinguishable cat states can be prepared with our protocol. Furthermore, the protocol is robust against noises and imperfections. We also discuss a method for verifying the final state via spectroscopy of a coupled circuit electrodynamical cavity mode. Our work can serve as the ground work to feasibly realize and verify macroscopic superposition states in future experiments.

Published by the American Physical Society
2024
Crystal structure and Hirshfeld surface analysis of trichlorido(1,10-phenanthroline-κ2
N,N′)phenyltin(IV)
Authors: Benlatreche Tarek , Bensegueni Mohamed Abdellatif , Dénès Georges , Golhen Stéphane , Merazig Hocine
Published: September 2024

The title compound, [Sn(C6H5)Cl3(C12H8N2)], which was obtained by the reaction between 1,10-phenanthroline and phenyltin trichloride in methanol, exhibits intramolecular hydrogen-bonding interactions involving the chlorine and hydrogen atoms. Crystal cohesion is ensured by intermolecular C—H...Cl hydrogen bonds, as well as Y—X...π and π-stacking interactions involving three different aromatic rings with centroid–centroid distances of 3.6605 (13), 3.9327 (14) and 3.6938 (12) Å]. Hirshfeld surface analysis and the associated two-dimensional fingerprint plots reveal significant contributions from H...H (30.7%), Cl...H/H...Cl (32.4%), and C...H/H...C (24.0%) contacts to the crystal packing while the C...C (6.2%), C...Cl/Cl...C (4.1%), and N...H/H...N (1.7%) interactions make smaller contributions.
8-Hydroxyquinolinium trichlorido(pyridine-2,6-dicarboxylic acid-κ3
O,N,O′)copper(II) dihydrate
Authors: Nazarov Yusufjon Eshkobilovich , Turaev Khayit Khudainazarovich , Suyunov Jabbor Ruziboevich , Alimnazarov Bekmurod Khurramovich , Rasulov Abdusamat Abdujabborovich , Ibragimov Bakhtiyar Tulyaganovich , Ashurov Jamshid Mengnorovich
Published: September 2024

The title compound, (C9H8NO)[CuCl3(C7H5NO4)]·2H2O, was prepared by reacting CuII acetate dihydrate, solid 8-hydroxyquinoline (8-HQ), and solid pyridine-2,6-dicarboxylic acid (H2pydc), in a 1:1:1 molar ratio, in an aqueous solution of dilute hydrochloric acid. The CuII atom exhibits a distorted CuO2NCl3 octahedral geometry, coordinating two oxygen atoms and one nitrogen atom from the tridentate H2pydc ligand and three chloride atoms; the nitrogen atom and one chloride atom occupy the axial positions with Cu—N and Cu—Cl bond lengths of 2.011 (2) Å and 2.2067 (9) Å, respectively. In the equatorial plane, the oxygen and chloride atoms are arranged in a cis configuration, with Cu—O bond lengths of 2.366 (2) and 2.424 (2) Å, and Cu—Cl bond lengths of 2.4190 (10) and 2.3688 (11) Å. The asymmetric unit contains 8-HQ+ as a counter-ion and two uncoordinated water molecules. The crystal structure features strong O—H...O and O—H...Cl hydrogen bonds as well as weak interactions including C—H...O, C—H...Cl, Cu—Cl...π, and π–π, which result in a three-dimensional network. A Hirshfeld surface analysis indicates that the most important contributions to the crystal packing involving the main residues are from H...Cl/Cl...H interactions, contributing 40.3% for the anion. Weak H...H contacts contribute 13.2% for the cation and 28.6% for the anion.
Corrosion resistance of MWCNTs-nanoZnO composite reinforced chromium-free Zn-Al coating
Authors: Fu Yu , Zhao Junwen , Li Xujia , Peng Yiwen
Published: September 2024

Purpose

This paper aims to prepare high corrosion-resistant chromium-free zinc-aluminum (Zn–Al) coatings reinforced with multi-walled carbon nanotubes (MWCNTs) and nano-ZnO particle composites.

Design/methodology/approach

The morphology, composition and corrosion resistance of the coatings were analyzed by electrochemical tests, water contact angle tests, immersion tests, scanning electron microscopy/energy dispersive spectrometer and X-ray diffraction.

Findings

The composite coating with 0.3% MWCNTs and 0.5% nano-ZnO particles demonstrated both high shielding performance and cathodic protection performance, which was attributed to the porosity filling of MWCNTs and nano-ZnO particles together with the electrical connection of MWCNTs between the zinc and aluminum powders.

Originality/value

This work laid an experimental foundation for the preparation and corrosion mechanism of high corrosion-resistant chromium-free Zn–Al coating reinforced with MWCNTs and nano-ZnO particles.
Actor opportunism, social capital and coping strategies in the sharing economy: drivers, outcomes and marketing implications
Authors: Saravade Swapnil , Felix Reto
Published: September 2024

Purpose

This paper aims to provide a conceptual understanding of the drivers and outcomes of actor opportunism in the context of the three key actors of the sharing economy – the service provider, the platform and the consumer.

Design/methodology/approach

The research uses a conceptual approach by drawing on literature from within and outside of marketing.

Findings

The current research introduces a conceptual framework of opportunism in the sharing economy with seven underlying propositions. The framework posits a U-shaped moderating effect of social capital for the relationship between opportunism and its drivers, actor vulnerability and asset specificity. Furthermore, a 2 × 2 matrix consisting of two types of opportunistic behaviors (active and passive) and two coping strategies by other actors (defensive and nondefensive) suggests that passive opportunism tends to lead to value codestruction independently of the coping strategies employed by other actors. Counterintuitively, the combination of active opportunism and defensive coping strategy presents an opportunity for value cocreation due to its potential to break up older structures and generate new ones.

Research limitations/implications

While our research provides a higher-level understanding of opportunism pertaining to platform, consumers and service providers in the sharing economy, future research could situate our framework within specific regulatory environments, incorporate the role of competitors and examine individual interaction effects between type of opportunism and coping strategies.

Practical implications

The framework enables service providers, platforms and consumers to identify drivers of opportunistic behaviors of their partners and discern instances in which opportunistic behaviors lead to value codestruction for all actors.

Originality/value

This research transcends prior work on the bright and dark sides of the sharing economy by identifying its dynamic nature and examining the contributing role of opportunism.
Developmentalism, technocracy and legitimacy crises of humanities: A Third World perspective
Authors: Bhattacharyya Sanchari , Sanasam Reena
Published: September 2024

Purpose

The visible ill-effects of the developmental enterprises in the ex-colonies and the tendency towards technocratic totalitarianism, in many ways, have altered the way modern humans perceived the idea of “progress” and “development” historically since the Cold War. This paper presents a deconstructive-transdisciplinary critique of the pervasive ideology by focusing on three nodal points in the stages of “development”: (1) the rise of technocratic modern science; (2) the making of the Third World; and (3) de-legitimisation of its indigenous knowledge paradigms.

Design/methodology/approach

Drawing on the first-hand accounts of the researchers, social scientists, activists and environmentalists, this paper presents an extensive critique of the violence involved in the development enterprises and recommends possible ways to move beyond the developmental hegemony. This paper is a theoretical investigation that adopts an interpretative, pluralistic, transdisciplinary approach, in order to deconstruct the development ideology and analyse the ramifications of the developmental propaganda and practice as they unfolded in the Global South.

Findings

This paper highlights the need to decondition the social imaginary from the hegemony of developmentalism and its by-product scientism and “technological rationality” for an inclusive, pluralistic, democratic social order.

Research limitations/implications

The focal area of this work is India in particular and Global South in general. It studies the era between the 1950s and 1980s when the major development enterprises took place and studies the consequences they entailed.

Social implications

The scope of this paper encompasses every socio-economic, ecological and epistemological domain affected by the detrimental effects of the developmental enterprises in the Global South.

Originality/value

The originality of this work lies in its transdisciplinary approach. The scope of this paper is extensive and covers nearly every domain of human existence that has been affected by the development debacle and technocratic totalitarianism in the post-War era.