bluuebunny/crossref_metadata_2025 huggingface dataset:
Interdependence between SEB-3 and NLP-49 peptides shifts across predator-induced defensive behavioral modes inCaenorhabditis elegans
Authors: Quach Kathleen T , Hughes Gillian A , Chalasani Sreekanth H
Published: May 2024

Prey must balance the need to avoid predators with the need to feed, a dilemma central to prey refuge theory. Additionally, prey must also assess predatory imminence, or how close predator threats are in space and time. Predatory imminence theory classifies defensive behaviors into three defense modes—pre-encounter, post-encounter, and circa-strike—each corresponding to increasing levels of predatory imminence—suspecting a predator, detecting a predator, and contact with a predatory attack. Although prey often simultaneously face variations in predatory imminence and spatial distribution of predation risks, research on how these factors intersect to influence defensive behaviors has been limited. Integrating these factors into a complex, naturalistic environment could enable comprehensive analysis of multiple defense modes in consistent conditions within the same study, unlike laboratory tests designed to examine only one mode at a time. Here, we combine prey refuge and predatory imminence theories to develop a model system of nematode defensive behaviors, withCaenorhabditis elegansas prey andPristionchus pacificusas predator. We show thatC. elegansinnately exhibits circa-strike behaviors in a foraging environment comprised of a food-rich, high-risk patch and a food-poor, predator-free refuge. However, after extended experience in this environment,C. elegansacquires post- and pre-encounter behaviors that proactively anticipate threats rather than merely reacting to attacks. We also demonstrate that these defense modes are potentiated by increasingly harmful predators, with only life-threatening predators capable of eliciting all three defense modes. Finally, our model system reveals that SEB-3 receptors and NLP-49 peptides, key to stress response regulation, vary in their impact and interdependence across defense modes. We find that SEB-3 has a greater impact on the highest-imminence defense mode, while NLP-49 peptides have a stronger effect on the lowest-imminence defense mode. Overall, our model system reveals detailed and comprehensive insights into how stress-related molecular signaling affects behavioral responses to threats.
Replay without sharp wave ripples in a spatial memory task
Authors: Widloski John , Foster David J.
Published: May 2024

Sharp-wave ripples in the hippocampus are believed to be a fundamental mechanism for the consolidation of episodic memories. During ripples, hippocampal neurons are re-activated in sequences called replay, which have been hypothesized to reflect episodic memory content. Ripples and replay are usually reported to co-occur, and are commonly thought to reflect the same process. Here we report that, in rats performing an open field spatial memory task, replays readily occur in the complete absence of ripples. Moreover, the occurrence of ripple-less and ripple-containing replays is not random, but precisely organized in terms of virtual space: Ripples are confined to “ripple fields”, which are spatially-restricted areas defined over the virtual locations depicted during replay and independent of the actual location of the animal. Similar to allocentric coding by place fields, ripple fields are independent of the direction of travel, and stable throughout the recording session. Ripple fields track changes to environmental structure caused by the addition or subtraction of barriers to movement, consistent with ripples conveying information about the incorporation of novel experiences. Moreover, ripple fields were matched across different rats experiencing the same barrier configuration, highlighting the robustness of the ripple field spatial code. We hypothesize a new relationship between ripples and replay, in which a subset of replays that is particularly relevant to learning or novelty is paired with ripples, in order to promote its selective broadcast to the rest of the brain for consolidation.
Sex-dependent effects of amyloidosis on functional network hub topology is associated with downregulated neuronal gene signatures in the APPswe/PSEN1dE9 double transgenic mouse
Authors: Simon Zachary D , McFarland Karen N , Golde Todd E , Chakrabarty Paramita , Febo Marcelo
Published: May 2024

Extracellular beta-amyloid (Aβ) is thought to cause impairments in brain-wide functional connectivity, although mechanisms linking Aβ to broader functional network processing remain elusive. In the present study, we evaluated the effects of Aβ on fear memory and functional connectome measures in male and female mice. Middle-aged (9-11mo) double transgenic APP-PS1 mice and age and sex-matched controls were tested on a fear conditioning protocol and then imaged at 11.1 Tesla. Brains were harvested and processed for analysis of Aβ plaques and Iba1 immunolabeling in neocortical areas, hippocampus, and basolateral amygdala. Additional RNA sequencing data from separate age, strain, and sex-matched mice were analyzed for differentially expressed genes (DEGs) and weighted gene co-expression networks. In both male and female mice, we observed increased functional connectivity in a dorsal striatal/amygdala network as a result of Aβ. Increased functional connectivity within this network was matched by increases in APP gene expression, Aβ and Iba1 immunolabeling, and an upregulated cluster of DEGs involved in the immune response. Conversely, the network measure representing node hubness, eigenvector centrality, was increased in prefrontal cortical brain regions, but only in female APP-PS1 mice. This female-specific effect of amyloid was associated with down-regulation of a cluster of DEGs involved in cortical and striatal GABA transmission, anxiogenic responses, and motor activity, in female APP-PS1 mice, but not males. Our results contribute to a growing literature linking between Aβ, immune activation, and functional network connectivity. Furthermore, our results reveal outcomes of Aβ on gene expression patterns in female mice that may contribute to amyloidosis-induced dysregulation of non-cognitive circuitry.
Active Microtubule-Actin Crosstalk Mediated by a Nesprin-2G-Kinesin Complex
Authors: Sahabandu Natalie , Okada Kyoko , Khan Aisha , Elnatan Daniel , Starr Daniel A. , Ori-McKenney Kassandra M. , Luxton G.W. Gant , McKenney Richard J.
Published: May 2024

Nesprins are integral membrane proteins that physically couple the nucleus and cytoskeleton. Nesprin-2 Giant (N2G) stands out for its extensive cytoplasmic domain, which contains tandem N-terminal actin-binding calponin-homology domains followed by >50 spectrin repeats and a C-terminal outer nuclear membrane-spanning KASH domain. N2G’s KASH domain interacts with the inner nuclear membrane, lamina-binding SUN proteins within the perinuclear space, forming a linker of nucleoskeleton and cytoskeleton (LINC) complex. Additionally, N2G contains a conserved W-acidic LEWD motif that enables the direct interaction with kinesin-1’s light chain, indicating N2G’s involvement with both actin and microtubules. The absence of N2G leads to embryonic lethality in mice, while cellular assays highlight N2G’s role in nuclear positioning across diverse biological contexts. However, the precise mechanisms underlying N2G-mediated nucleocytoskeletal coupling remain unclear. Here we study N2G’s interactions with F-actin and kinesin-1, revealing its functions as an F-actin bundler, a kinesin-1-activating adapter, and a mediator of active cytoskeletal crosstalk. Along with MAP7 proteins, N2G directly links active kinesin-1 motors to F-actin, facilitating actin transport along microtubule tracks. These findings shed light on N2G’s dynamic role as a crosslinker between actin and microtubule cytoskeletons, offering insights into nuclear movement, a fundamental cellular process.
Cortical Dynamics during Contour Integration
Authors: He Dongcheng , Yang Angeline , Coates Daniel R. , Ogmen Haluk , Chung Susana TL
Published: May 2024

Integrating visual elements into contours is important for object recognition. Previous studies emphasized the role that the primary visual cortex (V1) plays in this process. However, recent evidence suggests that contour integration relies on the coordination of hierarchical substrates of cortical regions through recurrent connections. Many previous studies presented the contour at the same onset-time as the trial, which caused the subsequent neural imaging data to incorporate both visual evocation and contour integration activities, and thus confounding the two. In this study, we varied both the contour onset-time and contour fidelity and used EEG to examine the cortical activities under these conditions. Our results suggest that the temporal N300 represents the grouping and integration of visual elements into contours. Before this signature, we observed interhemispheric connections between lateral frontal and posterior parietal regions that were contingent on the contour location and peaked at around 150ms after contour appearance. Also, the magnitudes of connections between medial frontal and superior parietal regions were dependent on the timing of contour onset and peaked at around 250ms after contour onset. These activities appear to be related to the bottom-up and top-down attentional processing during contour integration, respectively, and shed light on how these processes cooperate dynamically during contour integration.
Phylogenetic study of local patterns influenza A(H3N2) virus transmission in a semi-isolated population in a remote island in Japan between 2011-2013
Authors: Han Su Myat , Shiino Teiichiro , Masuda Shingo , Furuse Yuki , Yasaka Takahiro , Kanda Satoshi , Komori Kazuhiri , Saito Nobuo , Kubo Yoshiano , Smith Chris , Endo Akira , Robert Alexis , Baguelin Marc , Ariyoshi Koya
Published: May 2024

Background

The spatial spread and importation risk of influenza A viruses in rural settings remains unclear due to the sparsity of representative spatiotemporal sequence data.

Methods

Nasopharyngeal (NPS) samples of Rapid Influenza Diagnostic Test (RIDT) positive individuals in Kamigoto Island, Japan, were confirmed using quantitative polymerase chain reaction (RT-PCR). The confirmed influenza A positive samples were processed for whole- genome sequencing. Time-resolved phylogenetic trees were built from HA sequences to classify the circulating clades, with events of introductions and local clustering. Spatio-temporal transmission patterns were then analyzed for the largest local clusters.

Results

We obtained 178 whole-genome sequences of influenza A/H3N2 collected during 2011/12 and 2012/13 influenza seasons. The time-resolved phylogenetic tree identified at least six independent introduction events in 2011/12 and 2012/13. Majority of Kamigoto strains are closely related to strains from mainland Japan. All 2011/12 strains were identified as clade 3 C.2 (n=29), while 2012/13 strains fell into two clades: clade 3C.2 (n=129), and 3C.3a (n=20). No local persistence over one year was observed for Kamigoto strains. The spatio-temporal analysis of the largest cluster revealed that the first case and a large number of cases came from the busiest district of the island and spread towards the other parts of the island.

Conclusion

Influenza A(H3N2) virus outbreaks in Kamigoto island were marked by multiple introductions and fueled by local transmission. All the identified clusters in 2012/13 season circulate simultaneously. These cases may be misinterpreted as part of the same cluster without sequencing data, highlighting the importance of genomic surveillance. The results of this study are based on a two-year analysis of influenza sequences from the island; repeated analyzes for different influenza seasons and geographic locations will help us better understand detailed transmission patterns.
Variability in mineral composition of Canadian lentil cultivars
Authors: Vargas Ana , Podder Rajib , Subedi Maya , Bett Kirstin E. , Vandenberg Albert
Published: May 2024

Lentils are a good source of essential minerals for the proper functioning of the human body. We evaluated 34 cultivars and elite lentil lines representing the breadth of the Canadian breeding program. Trials were established in 10 site-years across Saskatchewan Province. Concentrations of 27 minerals were quantified with an inductive coupled argon plasma emission spectrometer in whole and dehulled lentil seeds. Li, V, Cr, Co, As, Ag, Cd, Sn, La, Hg, and Pb had concentrations below the quantification limit and were excluded from further analysis. The effects of site year, tissue type (whole and dehulled), and lentil genotypes were analyzed using a mixed model. Mineral concentrations of Na, K, Ca, Mg, Cu, B, and Ba were stable across site years. Na, Zn, P, Cu, Se, and Mo had similar concentrations in whole and dehulled seeds. Ca, Fe, Mg, Mn, B, Al, and Ba were more concentrated in whole seeds, while K, S, and Ni were higher in dehulled seeds. Several lentil genotypes had outstanding concentrations of several minerals. Lentil genotypes with a higher composition of several minerals could be a starting point for enhancing mineral composition in lentils.
Dietary preservatives alter the gut microbiotain vitroandin vivowith sex-specific consequences for host metabolic development
Authors: Schell Laura D. , Chadaideh Katia S. , Allen-Blevins Cary R. , Venable Emily M. , Carmody Rachel N.
Published: May 2024

Antibiotics in early life can promote adiposity via interactions with the gut microbiota. However, antibiotics represent only one possible route of antimicrobial exposure. Dietary preservatives exhibit antimicrobial activity, contain chemical structures accessible to microbial enzymes, and alter environmental conditions favoring specific microbial taxa. Therefore, preservatives that retain bioactivity in the gut might likewise alter the gut microbiota and host metabolism. Here we conductin vitro, ex vivo, and in vivoexperiments in mice to test the effects of preservatives on the gut microbiota and host physiology. We screened common dietary preservatives against a panel of human gut isolates and whole fecal communities, finding that preservatives strongly altered microbial growth and community structure. We exposed mice to diet-relevant doses of 4 preservatives [acetic acid, BHA (butylated hydroxyanisole), EDTA (ethylenediaminetetraacetic acid) and sodium sulfite], which each induced compound-specific changes in gut microbiota composition. Finally, we compared the long-term effects of early-life EDTA and low-dose antibiotic (ampicillin) exposure. EDTA exposure modestly reduced nutrient absorption and cecal acetate in both sexes, resulting in lower adiposity in females despite greater food intake. Females exposed to ampicillin also exhibited lower adiposity, along with larger brains and smaller livers. By contrast, in males, ampicillin exposure generally increased energy harvest and decreased energy expenditure, resulting in higher adiposity. Our results highlight the potential for everyday doses of common dietary preservatives to affect the gut microbiota and impact metabolism differently in males and females. Thus, despite their generally-regarded-as-safe designation, preservatives could have unintended consequences for consumer health.

SIGNIFICANCE

Early-life exposure to antibiotics can alter the gut microbiota and shape adult metabolic health. Here we show that dietary preservatives can have analogous effects. Common dietary preservatives altered gut microbiota compositionin vitro,ex vivoandin vivo. Early-life EDTA exposure had long-term, sex-specific consequences for energy metabolism. Simultaneously, we deliver new mechanistic understanding of early-life antimicrobial-induced effects on adiposity via evidence that low-dose ampicillin treatment increases energy harvest while conserving energy expenditure in males, promoting adiposity, while EDTA treatment dampens energy harvest, promoting leanness in females. Overall, our results emphasize that early-life gut microbiome disruptions can be triggered by diverse antimicrobial exposures, with previously unappreciated metabolic consequences that differ for males and females.
Asymmetric Engagement of Dimeric CRL3KBTBD4by the Molecular Glue UM171 Licenses Degradation of HDAC1/2 Complexes
Authors: Yeo Megan JR , Zhang Olivia , Xie Xiaowen , Nam Eunju , Payne Neil Connor , Gosavi Pallavi M , Kwok Hui Si , Iram Irtiza , Lee Ceejay , Li Jiaming , Chen Nicholas J , Jiang Hanjie , Wang Zhipeng A , Lee Kwangwoon , Mao Haibin , Harry Stefan A , Barakat Idris A , Takahashi Mariko , Waterbury Amanda L , Barone Marco , Mattevi Andrea , Bar-Peled Liron , Cole Philip A , Mazitschek Ralph , Liau Brian B , Zheng Ning
Published: May 2024

UM171 is a potent small molecule agonist of ex vivo human hematopoietic stem cell (HSC) self-renewal, a process that is tightly controlled by epigenetic regulation. By co-opting KBTBD4, a substrate receptor of the CULLIN3-RING E3 ubiquitin ligase complex, UM171 promotes the degradation of members of the CoREST transcriptional corepressor complex, thereby limiting HSC attrition. However, the direct target and mechanism of action of UM171 remain unclear. Here, we reveal that UM171 acts as a molecular glue to induce high-affinity interactions between KBTBD4 and HDAC1 to promote the degradation of select HDAC1/2 corepressor complexes. Through proteomics and chemical inhibitor studies, we discover that the principal target of UM171 is HDAC1/2. Cryo-electron microscopy (cryo-EM) analysis of dimeric KBTBD4 bound to UM171 and the LSD1-HDAC1-CoREST complex unveils an unexpected asymmetric assembly, in which a single UM171 molecule enables a pair of KBTBD4 KELCH-repeat propeller domains to recruit HDAC1 by clamping on its catalytic domain. One of the KBTBD4 propellers partially masks the rim of the HDAC1 active site pocket, which is exploited by UM171 to extend the E3-neo-substrate interface. The other propeller cooperatively strengthens HDAC1 binding via a separate and distinct interface. The overall neomorphic interaction is further buttressed by an endogenous cofactor of HDAC1-CoREST, inositol hexakisphosphate, which makes direct contacts with KBTBD4 and acts as a second molecular glue. The functional relevance of the quaternary complex interaction surfaces defined by cryo-EM is demonstrated by in situ base editor scanning of KBTBD4 and HDAC1. By delineating the direct target of UM171 and its mechanism of action, our results reveal how the cooperativity offered by a large dimeric CRL E3 family can be leveraged by a small molecule degrader and establish for the first time a dual molecular glue paradigm.
TheNeosartorya (Aspergillus) fischeriantifungal protein NFAP2 has low potential to trigger resistance development inCandida albicans in vitro
Authors: Bende Gábor , Zsindely Nóra , Laczi Krisztián , Kristóffy Zsolt , Papp Csaba , Farkas Attila , Tóth Liliána , Sáringer Szabolcs , Bodai László , Rákhely Gábor , Marx Florentine , Galgóczy László
Published: May 2024

Due to the increase in the number of drug-resistantCandida albicansstrains, new antifungal compounds with limited potential for development of resistance are urgently needed. NFAP2, an antifungal protein (AFP) secreted byNeosartorya(Aspergillus)fischeri, is a promising candidate. We investigated the ability ofC. albicansto develop resistance to NFAP2 in a microevolution experiment compared with generic fluconazole (FLC).C. albicansadapted to only 1 × minimum inhibitory concentration (MIC) of NFAP2 compared with 32 × MIC of FLC. Genome analysis revealed non-silent mutations in only two genes in NFAP2-resistant strains and in several genes in FLC-resistant strains. Resistance development to NFAP2 did not influence cell morphology. The susceptibility of NFAP2-resistant strains did not change to FLC, amphotericin B, micafungin, terbinafine. These strains did not show altered susceptibility to AFPs fromPenicillium chrysogenum, except one which had less susceptibility toP. chrysogenumantifungal protein B. FLC-resistant strains had decreased susceptibility to terbinafine and NFAP2, but not to other drugs and AFPs fromP. chrysogenum. NFAP2- and FLC-resistant strains showed decreased and increased NFAP2 binding and uptake, respectively. The development of resistance to NFAP2 decreased tolerance to cell wall, heat, and UV stresses. The development of FLC resistance increased tolerance to cell wall stress and decreased tolerance to heat and UV stresses. Resistance to NFAP2 did not have significant metabolic fitness cost and could not increase virulence, compared with resistance to FLC.

Importance

Due to the increasing number of (multi)drug-resistant strains, only a few effective antifungal drugs are available to treat infections caused by opportunisticCandidaspecies. Therefore, the incidence of hard-to-treat candidiasis has increased dramatically in the past decade, and the demand to identify antifungal compounds with minimal potential to trigger resistance is substantial. The features of NFAP2 make it a promising candidate for the topical treatment ofCandidainfection. Data on the development of resistance to AFPs inC. albicansare lacking. In this study, we provide evidence that NFAP2 has low potential to trigger resistance inC. albicans in vitroand the developed resistance mechanisms to NFAP2 are not associated with severe phenotypic changes compared with development of resistance to generic FLC. These results suggest the slow emergence of NFAP2-resistantCandidastrains and that NFAP2 can reliably be used long-term in the clinic.
TRBP regulates poly(I:C)-mediated apoptotic pathway by modulating miRNA biogenesis
Authors: Azuma Shota , Nakano Yuko , Takahashi Tomoko , Onomoto Koji , Haraguchi Takeshi , Suzuki Yutaka , Iba Hideo , Yoneyama Mitsutoshi , Asano Yoshimasa , Ui-Tei Kumiko
Published: May 2024

Interferon (IFN) response is usually triggered by the invasion of viral RNAs, and is known to suppress RNA silencing triggered by microRNAs (miRNAs). However, the detailed mechanism regulating RNA silencing during IFN response has not been elucidated. We previously reported that a virus sensor protein, LGP2, which is an upregulated protein during IFN response, interacts with an RNA-binding protein, TRBP. Since TRBP is an RNA-binding protein which enhances miRNA biogenesis in collaboration with Dicer, the interaction of TRBP with LGP2 inhibits the interaction with Dicer and suppresses the TRBP-mediated miRNA biogenesis. During Sendai virus infection, we found that the inhibition of miRNA maturation caused by TRBP depletion resulted in the induction of apoptosis. However, the global gene expression network regulated by miRNAs during viral infection is not understood. In this study, we analyzed comprehensive data from RNA-sequencing and small RNA-sequencing during the antiviral response induced by poly(I:C) transfection, and investigated how TRBP regulates expression profiles of miRNAs and the downstream mRNAs. A group of miRNAs, including miRNAs preferably bind to TRBP, were downregulated by poly(I:C) transfection. Although about 60 % of miRNAs were situated in the introns of their host genes, the expression levels of mature miRNAs were not correlated with those of host genes. Therefore, the downregulation of the expression levels of mature miRNAs was considered to be not caused by transcriptional inhibition of host genes but by the inhibition of TRBP-mediated miRNA processing. Target prediction analysis suggested that the downregulated miRNAs in the presence of TRBP but not in the absence of TRBP mainly targeted transcription factors. Furthermore, these transcription factors were included in the regulators of apoptosis- and cell cycle-related factors. Some of these regulators were also predicted to be the direct targets of downregulated miRNAs in the presence of TRBP. Thus, it was revealed that the downregulation of miRNAs in the presence of TRBP regulates the expression of apoptosis- and cell cycle-related genes either directly or indirectly through adjusting the expression levels of transcription factors. These results suggest that TRBP has a pivotal role in the determination of cell fates during viral infection regulating the miRNA-mRNA regulatory networks through modifying miRNA biogenesis.
Quantifying uncertainty in RNA velocity
Authors: Zhang Huizi , Bochkina Natalia , Wade Sara
Published: May 2024

The concept of RNA velocity has made it possible to extract dynamic information from single-cell RNA sequencing data snapshots, attracting considerable attention and inspiring various extensions. Nonetheless, existing approaches lack uncertainty quantification and many adopt unrealistic assumptions or employ complex black-box models that are difficult to interpret. In this paper, we present a Bayesian hierarchical model to estimate RNA velocity, which leverages a time-dependent transcription rate and non-trivial initial conditions, allowing for well-calibrated uncertainty quantification. The proposed method is validated in a comprehensive simulation study that covers various scenarios, and benchmarked against a widely embraced and commonly recognized approach for RNA velocity on single-cell RNA sequencing data from mouse embryonic stem cells. We demonstrate that our model surpasses this widely used, state-of-the-art method, offering enhanced interpretation of cell velocity and cell orders. Additionally, it supports the estimation of a unified gene-shared latent time, providing a valuable resource for downstream analysis.
Neural Processing of Naturalistic Audiovisual Events in Space and Time
Authors: Hu Yu , Mohsenzadeh Yalda
Published: May 2024

Our brain seamlessly integrates distinct sensory information to form a coherent percept. However, when real-world audiovisual events are perceived, the specific brain regions and timings for processing different levels of information remain less investigated. To address that, we curated naturalistic videos and recorded fMRI and EEG data when participants viewed videos with accompanying sounds. Our findings reveal early asymmetrical cross-modal interaction, with acoustic information represented in both early visual and auditory regions, while visual information only identified in visual cortices. The visual and auditory features were processed with similar onset but different temporal dynamics. High-level categorical and semantic information emerged in multi-modal association areas later in time, indicating late cross-modal integration and its distinct role in converging conceptual information. Comparing neural representations to a two-branch deep neural network model highlighted the necessity of early fusion to build a biologically plausible model of audiovisual perception. With EEG-fMRI fusion, we provided a spatiotemporally resolved account of neural activity during the processing of naturalistic audiovisual stimuli.
Common patterns of spatial selectivity in early visual cortex and face-selective brain regions
Authors: Morsi Anisa Y. , Chow-Wing-Bom Hugo T , Schwarzkopf D. Sam , Goffaux Valerie , Dekker Tessa M , Greenwood John A
Published: May 2024

Face recognition is widely considered to be "special", involving dedicated brain regions with unique patterns of selectivity. This contrasts with increasing evidence for common patterns of 'visuospatial coding', where even high-level category-selective areas share the spatial properties of earlier brain regions. Here we examined whether the retinotopic properties of face-selective areas vary around the visual field in a similar fashion to those of early visual cortex, and whether these spatial properties could explain variations in face perception around the visual field. We carried out retinotopic mapping of early (V1-V3) and face-selective cortical regions (OFA, pFus, mFus) using large-field bars of faces (21° eccentricity), with spatial selectivity measured via population receptive field (pRF) analysis. While pRFs were considerably larger in face-selective regions than in V1-V3, their size did not vary consistently either across areas or in line with behavioural anisotropies. However, both early cortex and face-selective areas show a greater number of pRFs and a concomitant increase in visual field coverage along the horizontal vs. vertical meridian and in the lower vs. upper field. Variations in our face-recognition abilities around the visual field could thus be driven by these differences in sampling. We also show that pRF numbers (and subsequent coverage) in mFus were typically greater for upright than inverted faces, suggesting these properties could similarly support the perceptual advantage for upright faces, at least in part. The commonality of these variations in visual field sampling between face-selective cortex and earlier visual regions further support a hierarchical model whereby the spatial selectivity of higher-level areas is built upon the selectivity of lower regions, even for specialised face processing.
Amyloid beta glycation leads to 1 neuronal mitochondrial dysfunction and Alzheimer’s pathogenesis through VDAC1-dependent mtDNA efflux
Authors: Akhter Firoz , Akhter Asma , Schiff Hillary , Maffei Arianna , Zhu Xiongwei , Douglas Justin , Zhao Zhen , Zhu Donghui
Published: May 2024

Amyloid beta (Aβ), a stable protein, undergoes posttranslational glycation, forming glycated Aβ (gAβ), an advanced glycation end product (AGE) observed in Alzheimer’s disease (AD), yet the pathological role of gAβ remains understudied. This work explores gAβ’s role in inducing neuronal mitochondrial DNA (mtDNA) efflux in a VDAC1-dependent manner and in activating the innate immune cGAS-STING pathway in AD. Findings demonstrate cGAS-mtDNA binding induced by gAβ in neuro-cytoplasm, along with cGAS-STING activation in aged AD mice and human AD brains. Knockdown of RAGE, cGAS, or STING protects APP mice from mitochondrial dysfunction and AD-like pathology, as does inhibiting VDAC1. Moreover, RAGE inhibition in APP knock-in mice, coupled with spatially enhanced resolution omics-sequencing, confirms downregulation of innate immune responses and disease-associated genes in AD. Therefore, this study identifies a crucial link between gAβ and innate immunity, indicating therapeutic targeting of VDAC1, RAGE, or cGAS-STING may enhance resilience against gAβ-related pathological insults in AD.
Melanopsin ganglion cells in the mouse retina independently evoke pupillary light reflex
Authors: Bohl Jeremy Matthew , Hassan Abdul Rhman , Sharpe Zachary J. , Kola Megi , Ayub Mahnoor , Pandey Yamini , Shehu Angela , Ichinose Tomomi
Published: May 2024

Purpose

The pupillary light reflex (PLR) is crucial for protecting the retina from bright light. The intrinsic photosensitive ganglion cells (ipRGCs) in the retina mediate the PLR, which directly sense light and receive inputs from rod/cone photoreceptors. Previous work used genetic knockout mice to reveal that rod/cone photoreceptors drive transient constriction, and ipRGCs drive the sustained component. We acutely ablated photoreceptors by a chemical injection to examine the role of rod and cone photoreceptors in PLR.

Methods

PLR and the multiple electrode array (MEA) recording were conducted with C57BL6/J (wildtype: WT) and Cnga3-/-; Gnat1-/-(rod/cone dysfunctional) mice. n-Nitroso-n-methylurea (MNU) was applied to C57 mice by intraperitoneal injection, and PLR was conducted after 5-7 days of injection. Three different light levels (mesopic, low photopic, and high photopic) were tested. Immunohistochemistry was conducted using the anti-Gnat1 and anti-melanopsin antibodies with DAPI.

Results

PLR was induced by all light levels we tested, and the level of constriction increased as the light level increased. After the MNU injection, PLR was not induced at mesopic light stimulus, but was fully induced by high light. The level of PLR was identical between WT and MNU mice, suggesting that ipRGCs fully contributed to the PLR at this light level. Immunohistochemistry revealed that photoreceptors were ablated by the MNU injection, but ipRGCs were preserved. The MEA recording revealed that a population of ipRGCs generated fast and robust spikes in MNU-injected retinal tissues inex vivo.

Conclusions

Contrary to previous observations, our results demonstrate that ipRGCs are the major contributor to the PLR induced by high light.
Beyond the Triple Helix: Exploration of the Hierarchical Assembly Space of Collagen-like Peptides
Authors: Yu Le Tracy , Kreutzberger Mark A. B. , Hancu Maria C. , Bui Thi H. , Farsheed Adam C. , Egelman Edward H. , Hartgerink Jeffrey D.
Published: May 2024

Thede novodesign of self-assembling peptides has garnered significant attention in scientific research. While alpha-helical assemblies have been extensively studied, exploration of polyproline type II (PPII) helices, such as those found in collagen, remains relatively limited. In this study, we focused on understanding the sequence-structure relationship in hierarchical assemblies of collagen-like peptides, using defense collagen SP-A as a model. By dissecting the sequence derived from SP-A and synthesizing short collagen-like peptides, we successfully constructed a discrete bundle of hollow triple helices. Mutation studies pinpointed amino acid sequences, including hydrophobic and charged residues that are critical for oligomer formation. These insights guided thede novodesign of collagen-like peptides, resulting in the formation of diverse quaternary structures, including discrete and heterogenous bundled oligomers, 2D nanosheets, and pH-responsive nanoribbons. Our study represents a significant advancement in the understanding and harnessing of collagen higher-order assemblies beyond the triple helix.
Dicarboxylic acids synergize with yeast and human Hsp60/10 systems to mimic GroEL/ES
Authors: Gautam Deepika , Aaquib Mohammad , Kochar Manisha , Chakraborty Kausik
Published: May 2024

GroEL/ES has been the archetype to understand the function of the class I chaperonins (Hsp60/10 systems). While very similar in structure, the human or yeast mitochondrial one has diminished negative charge density in the central cavity. These chaperones had also lost their ability to assist a substrate ofE.coliGroEL/ES. Here, we show that the eukaryotic Hsp60/10 systems can synergize with dicarboxylic acids in vitro at the physiological concentration of these metabolites to mimic the activity ofE. coliGroEL/ES. Combining these Hsp60/10s and metabolites effectively alters the folding landscape like GroEL/ES; this is specific for the eukaryotic chaperonins and not the prokaryotic homologs with less negatively charged cavities. Thus, we identify a potential cooperation between molecular and chemical chaperones that may have important physiological implications linking metabolism to proteostasis.
A new target of multiple lysine methylation in bacteria
Authors: Inoue Shori , Yoshimoto Shogo , Hori Katsutoshi
Published: May 2024

The methylation of ε-amino groups in protein lysine residues is known to be an important posttranslational modification in eukaryotes. This modification plays a pivotal role in the regulation of diverse biological processes, including epigenetics, transcriptional control, and cellular signaling. Although less studied in prokaryotes, recent research has begun to reveal the potential role of methylation in modulating bacterial immune evasion and adherence to host cells. In this study, we analyzed the cell surface proteins of the toluene-degrading bacteriumAcinetobactersp. Tol 5 by label-free liquid chromatography‒mass spectrometry (LC‒MS) and found that the lysine residues of its trimeric autotransporter adhesin (TAA), AtaA, are methylated. Over 130 lysine residues of AtaA, consisting of 3,630 amino acids and containing 232 lysine residues, were methylated. We identified the outer membrane protein lysine methyltransferase (OM PKMT) of Tol 5, KmtA, which specifically methylates the lysine residues of AtaA. In the KmtA-deficient mutant, most lysine methylations on AtaA were absent, indicating that KmtA is responsible for the methylation of multiple lysine residues throughout AtaA. Bioinformatic analysis revealed that the OM PKMT genes were widely distributed among gram-negative bacteria, including pathogens with TAAs that promote infectivity, such asBurkholderia malleiandHaemophilus influenzae. Although KmtA has sequence similarities to the OM PKMTs ofRickettsiainvolved in infectivity, KmtA-like PKMTs formed a distinct cluster from those of theRickettsiatype according to the clustering analysis, suggesting that they are new types of PKMTs. Furthermore, the deletion of Tol 5 KmtA led to an increase in AtaA on the cell surface and enhanced bacterial adhesion, resulting in slower growth.

Significance

Methylation of lysine residues is a posttranslational modification that plays diverse physiological roles in eukaryotes. In prokaryotes however, lysine methylation has been studied only in a limited number of pathogenic bacteria. In this study, we found novel lysine methylation across multiple residues of an outer membrane protein and its methyltransferase, KmtA, in a bacterium from activated sludge. KmtA, along with rickettsial outer membrane protein lysine methyltransferases, which are known to be involved in bacterial pathogenicity, exists in many species of gram-negative bacteria. This finding suggests that methylations are ubiquitous in prokaryotes and are involved in a variety of functions, offering potential strategies for controlling bacterial infections and enhancing the functions of beneficial bacteria for biotechnological applications.
Intravenous Immunization with Triple Auxotrophs ofMycobacterium tuberculosis: A novel vaccine strategy against tuberculosis
Authors: Vilchèze Catherine , Rajagopalan Saranathan , Jacobs William R.
Published: May 2024

Tuberculosis, caused byMycobacterium tuberculosis(Mtb), remains a leading infectious cause of mortality worldwide despite widespread use of the BCG vaccine and the availability of sterilizing pharmacopoeia. Recent research indicates that the intravenous administration of BCG confers sterilizing immunity againstMtbpulmonary challenge in non-human primates. However, while BCG is relatively safe, complications such as disseminated BCGosis have been observed in immunocompromised individuals. Double auxotrophic mutants ofMtblacking the ability to synthesize leucine and pantothenate are safe and sterilized in immunocompromised mice and SIV-infected Rhesus macaques. We examined how immunization with aMtbtriple auxotrophic strain, mc27902, which cannot synthesize leucine, pantothenate, and arginine, protects immunocompetent mice from a virulentMtbinfection. The route of immunization was a crucial factor for protection with mc27902 with intravenous immunization being 100 times more effective in protecting immunocompetent mice fromMtbchallenge when compared to conventional subcutaneous vaccination with BCG. To further increase the safety of the attenuated auxotroph for vaccine purposes, the type VII secretion system Esx1 responsible for BCG attenuation was deleted in mc27902. When tested by prime-boost immunization of immunocompetent mice followed by aerosol challenge with virulentMtb, mc27902 Δesx1provided similar protection to mc27902. This robust protection againstMtbinfection conferred by mc27902 and mc27902 Δesx1in a mouse model paves the way for new TB vaccine development using highly attenuated, auxotrophicMtbstrains.
Enhancing thermal stability of optimal magnetization reversal in nanoparticles
Authors: Badarneh Mohammad H. A. , Kwiatkowski Grzegorz J. , Bessarab Pavel F.
Published: May 2024

Energy-efficient switching of nanoscale magnets requires application of a time-varying magnetic field characterized by microwave frequency. At finite temperatures, even weak thermal fluctuations induce perturbations in the magnetization that can accumulate in time, disrupt the phase locking between the magnetization and the applied field, and eventually compromise magnetization switching. It is demonstrated here that the magnetization reversal is mostly disturbed by unstable perturbations arising in a certain domain of the configuration space of a nanomagnet. The instabilities can be suppressed and the probability of magnetization switching enhanced by applying an additional stimulus such as a weak longitudinal magnetic field that ensures bounded dynamics of the perturbations. Application of the stabilizing longitudinal field to a uniaxial nanomagnet makes it possible to reach a desired probability of magnetization switching even at elevated temperatures. The principle of suppressing instabilities provides a general approach to enhancing thermal stability of magnetization dynamics.

Published by the American Physical Society
2024
Aging behavior difference between aqueous coatings and solvent coatings in sulfuric acid environment
Authors: Wang He , Li Zhiguo , Zhou Haifei , Zhou Zhengqiang , Lu Wei , Wang Pengzhen , Zhang Jiagang , Gao Jin , Yi Pan
Published: May 2024

Purpose

This paper aims to compare the aging behavior of water-based coatings and solvent-based coatings in sulfuric acid environments and to discuss the related mechanism.

Design/methodology/approach

A sulfuric acid solution with a concentration of 5 Wt.% was selected for immersion test at 23°C. The failure behavior of the coating was studied by combining the transformation rules of the macroscopic morphology and basic properties with the results of electrochemical impedance spectrum analysis.

Findings

The results showed that the surface smoothness of the water-based coating was lower than that of the solvent-based coating. The glossiness, thickness and hardness of the water-based coating exhibited more significant changes. The electrochemical test also indicated that the water-based coating was infiltrated by a large number of corrosive media, which may have induced corrosion under the coating. In contrast, the solvent-based coating showed good shielding properties, but the adhesion was seriously affected by the corrosive medium.

Originality/value

This work clarified the difference of failure behavior and mechanism between water-based coatings and solvent-based coatings in acidic environment and provided a theoretical basis for the selection and mechanism research of anticorrosive coatings.
Benefits and challenges with blockchain technology in global food supply chains: views from the practice
Authors: Beveridge Ivana , Angelis Jannis , Mihajlov Martin
Published: May 2024

Purpose

Although technologies such as blockchain (BCT) hold great potential to improve global food supply chains (GFSCs), our understanding of BCT use in GFSCs remains limited. The purpose of this study is to broaden BCT discussions by exploring its benefits and challenges across the entire GFSC.

Design/methodology/approach

Qualitative interviews with 23 industry experts were used to identify and comprehend the nuanced issues with BCT application in GFSCs.

Findings

The study identifies 21 perceived benefits and challenges with BCT use in GFSCs, including the benefit of broader data incentives beyond BCT use and the challenge of reluctance to assume dominant roles among the GFSC actors.

Originality/value

While prior studies mostly focused on BCT use for traceability and food safety in the GFSC midstream, this study extends the scope to include upstream and midstream actors. It highlights socio-economic benefits for traditionally disadvantaged farmers in the upstream and normative challenges to its adoption in the GFSC midstream and downstream. It also identifies three paradoxes emerging with BCT use in the GFSCs including the paradoxes of food technology, transparency and de-centralization.
Networks perceptions and job satisfaction: the mediating role of perceived organizational support for women’s work contribution
Authors: Pinnington Ashly H. , Aldabbas Hazem , Mirshahi Fatemeh , Brown Mary L.
Published: May 2024

Purpose

This study investigates the relationship between women’s networks perceptions and job satisfaction. It also examines the mediating effects of perceived organizational support (POS) for women’s work contributions on the relationship between networks perceptions and job satisfaction.

Design/methodology/approach

The participants are female employees working in Scotland (n = 247). The data were collected using a survey questionnaire. PROCESS macro (model 4, Hayes, 2018) was used to test the proposed model.

Findings

The results revealed that (controlling for work time, age and sector) there is a significant relationship between women’s networks perceptions and job satisfaction. In addition, POS for women’s work contribution mediates the relationship between networks perceptions and job satisfaction. These findings show the significant effects of networks perceptions on employees’ job, satisfaction directly and through POS for women’s work contributions. Therefore, understanding the networks perceptions of employees and organizational factors will assist in improving job satisfaction.

Originality/value

This study is unique for examining the role of POS for women’s work contribution in the relationship between employees’ networks perceptions and job satisfaction. It addresses gender inequality in the workplace in terms of women’s career advancement and job satisfaction. In addition, this research offers insight into the development of a seven-item measurement scale related to networks perceptions.
Investigation of lightweight gypsum based on montmorillonite nanoclay with enhanced insulation properties
Authors: Anjomshoa Erfan
Published: May 2024

Purpose

Nowadays, thermal comfort plays a prominent role in contemporary construction practices. Appropriate thermal insulation not only offers energy efficiency benefits in buildings but also enhances occupant well-being, comfort, and productivity. Therefore, a comprehensive understanding of the thermal properties of building materials is essential. This research aims to prepare and investigate a lightweight gypsum-based composite incorporating nano montmorillonite with advanced thermal insulation properties, considering both quality and cost-effectiveness while ensuring environmental compatibility.

Design/methodology/approach

This study adopts a laboratory experimental approach. A gypsum sample (without additives) and seven samples of gypsum combined with varying percentages of sodium and calcium montmorillonite nanoclays undergo extensive testing and analysis. Subsequently, the properties of these samples are compared.

Findings

The results indicate that adding montmorillonite nanoclays to gypsum composites reduces the density of the tested samples and increases their porosity. Moreover, the thermal conductivity coefficient decreases in these samples, significantly improving the thermal insulation properties of the lightweight gypsum plaster. This improvement is more pronounced in samples containing sodium montmorillonite nanoclay compared to calcium-based samples. Additionally, the investigations reveal that compressive strength decreases with the addition of montmorillonite to the samples.

Originality/value

In this research, laboratory experiments were conducted to investigate the physical and mechanical properties of gypsum plaster with varying percentages of sodium and calcium montmorillonite nanoclays. The studied properties include density, porosity, thermal conductivity coefficient, and compressive strength. Additionally, stress-strain diagrams, elastic modulus, and initial and secondary critical stresses were analyzed for each specimen.