bluuebunny/crossref_metadata_2025 huggingface dataset:
The development of Future Health Today: piloting a new platform for identification and management of chronic disease in general practice
Authors: Hunter Barbara , Alexander Karyn , Biezen Ruby , Hallinan Christine Mary , Wood Anna , Nelson Craig , Manski-Nankervis Jo-Anne
Published: November 2022

Chronic disease identification and management is a significant issue in Australia, with general practice being the primary contact point for those at risk of, or living with, chronic disease. However, there is a well-described gap between guideline recommendations for chronic disease management and translation in the general practice setting. In 2018, a group of researchers, clinicians and software developers collaborated to develop a tool to support the identification and management of chronic disease in general practice, with the aim to create a platform that met the needs of general practice. The co-design process drew together core principles and expectations for the establishment of a technological platform, called Future Health Today (FHT), which would sit alongside the electronic medical record (EMR) management system within general practice. FHT used algorithms applied to EMR data to identify patients with, or at risk of, chronic disease and requiring review. Using chronic kidney disease as a clinical focus, the FHT prototype was piloted in a large, metropolitan general practice, and a large regional general practice. Based on user feedback, the prototype was further developed and improved. This paper provides a report on the key features and functionalities that participants identified and implemented in practice.
Rapid homeostatic modulation of transsynaptic nanocolumn rings
Authors: Muttathukunnel Paola , Frei Patrick , Perry Sarah , Dickman Dion , Müller Martin
Published: November 2022

Robust neural information transfer relies on a delicate molecular nano-architecture of chemical synapses. Neurotransmitter release is controlled by a specific arrangement of proteins within presynaptic active zones. How the specific presynaptic molecular architecture relates to postsynaptic organization and how synaptic nano-architecture is transsynaptically regulated to enable stable synaptic transmission remain enigmatic. Using time-gated stimulated emission-depletion microscopy at the
Drosophila
neuromuscular junction, we found that presynaptic nanorings formed by the active-zone scaffold Bruchpilot (Brp) align with postsynaptic glutamate receptor (GluR) rings. Individual rings harbor approximately four transsynaptically aligned Brp-GluR nanocolumns. Similar nanocolumn rings are formed by the presynaptic protein Unc13A and GluRs. Intriguingly, acute GluR impairment triggers transsynaptic nanocolumn formation on the minute timescale during homeostatic plasticity. We reveal distinct phases of structural transsynaptic homeostatic plasticity, with postsynaptic GluR reorganization preceding presynaptic Brp modulation. Finally, homeostatic control of transsynaptic nano-architecture and neurotransmitter release requires the auxiliary GluR subunit Neto. Thus, transsynaptic nanocolumn rings provide a substrate for rapid homeostatic stabilization of synaptic efficacy.
IGF2BP2 promotes cancer progression by degrading the RNA transcript encoding a v-ATPase subunit
Authors: Latifkar Arash , Wang Fangyu , Mullmann James J. , Panizza Elena , Fernandez Irma R. , Ling Lu , Miller Andrew D. , Fischbach Claudia , Weiss Robert S. , Lin Hening , Cerione Richard A. , Antonyak Marc A.
Published: November 2022

IGF2BP2 binds to a number of RNA transcripts and has been suggested to function as a tumor promoter, although little is known regarding the mechanisms that regulate its roles in RNA metabolism. Here we demonstrate that IGF2BP2 binds to the 3′ untranslated region of the transcript encoding ATP6V1A, a catalytic subunit of the vacuolar ATPase (v-ATPase), and serves as a substrate for the NAD
+
-dependent deacetylase SIRT1, which regulates how IGF2BP2 affects the stability of the ATP6V1A transcript. When sufficient levels of SIRT1 are expressed, it catalyzes the deacetylation of IGF2BP2, which can bind to the ATP6V1A transcript but does not mediate its degradation. However, when SIRT1 expression is low, the acetylated form of IGF2BP2 accumulates, and upon binding to the ATP6V1A transcript recruits the XRN2 nuclease, which catalyzes transcript degradation. Thus, the stability of the ATP6V1A transcript is significantly compromised in breast cancer cells when SIRT1 expression is low or knocked-down. This leads to a reduction in the expression of functional v-ATPase complexes in cancer cells and to an impairment in their lysosomal activity, resulting in the production of a cellular secretome consisting of increased numbers of exosomes enriched in ubiquitinated protein cargo and soluble hydrolases, including cathepsins, that together combine to promote tumor cell survival and invasiveness. These findings describe a previously unrecognized role for IGF2BP2 in mediating the degradation of a messenger RNA transcript essential for lysosomal function and highlight how its sirtuin-regulated acetylation state can have significant biological and disease consequences.
Genetic algorithms reveal profound individual differences in emotion recognition
Authors: Binetti Nicola , Roubtsova Nadejda , Carlisi Christina , Cosker Darren , Viding Essi , Mareschal Isabelle
Published: November 2022

Emotional communication relies on a mutual understanding, between expresser and viewer, of facial configurations that broadcast specific emotions. However, we do not know whether people share a common understanding of how emotional states map onto facial expressions. This is because expressions exist in a high-dimensional space too large to explore in conventional experimental paradigms. Here, we address this by adapting genetic algorithms and combining them with photorealistic three-dimensional avatars to efficiently explore the high-dimensional expression space. A total of 336 people used these tools to generate facial expressions that represent happiness, fear, sadness, and anger. We found substantial variability in the expressions generated via our procedure, suggesting that different people associate different facial expressions to the same emotional state. We then examined whether variability in the facial expressions created could account for differences in performance on standard emotion recognition tasks by asking people to categorize different test expressions. We found that emotion categorization performance was explained by the extent to which test expressions matched the expressions generated by each individual. Our findings reveal the breadth of variability in people’s representations of facial emotions, even among typical adult populations. This has profound implications for the interpretation of responses to emotional stimuli, which may reflect individual differences in the emotional category people attribute to a particular facial expression, rather than differences in the brain mechanisms that produce emotional responses.
Community-level evolutionary processes: Linking community genetics with replicator-interactor theory
Authors: Lean Christopher H. , Doolittle W. Ford , Bielawski Joseph P.
Published: November 2022

Understanding community-level selection using Lewontin’s criteria requires both community-level inheritance and community-level heritability, and in the discipline of community and ecosystem genetics, these are often conflated. While there are existing studies that show the possibility of both, these studies impose community-level inheritance as a product of the experimental design. For this reason, these experiments provide only weak support for the existence of community-level selection in nature. By contrast, treating communities as interactors (in line with Hull’s replicator-interactor framework or Dawkins’s idea of the “extended phenotype”) provides a more plausible and empirically supportable model for the role of ecological communities in the evolutionary process.
Plastic deformation of superionic water ices
Authors: Matusalem Filipe , Santos Rego Jéssica , de Koning Maurice
Published: November 2022

Due to their potential role in the peculiar geophysical properties of the ice giants Neptune and Uranus, there has been a growing interest in superionic (SI) phases of water ice. So far, however, little attention has been given to their mechanical properties, even though plastic deformation processes in the interiors of planets are known to affect long-term processes, such as plate tectonics and mantle convection. Here, using density functional theory calculations and machine learning techniques, we assess the mechanical response of high-pressure/temperature solid phases of water in terms of their ideal shear strength (ISS) and dislocation behavior. The ISS results are well described by the renormalized Frenkel model of ideal strength and indicate that the SI ices are expected to be highly ductile. This is further supported by deep neural network molecular dynamics simulations for the behavior of lattice dislocations for the SI face-centered cubic (fcc) phase. Dislocation velocity data indicate effective shear viscosities that are orders of magnitude smaller than that of Earth’s lower mantle, suggesting that the plastic flow of the internal icy layers in Neptune and Uranus may be significantly faster than previously foreseen.
Nano-positioning and tubulin conformation contribute to axonal transport regulation of mitochondria along microtubules
Authors: Van Steenbergen Valérie , Lavoie-Cardinal Flavie , Kazwiny Youcef , Decet Marianna , Martens Tobie , Verstreken Patrik , Boesmans Werend , De Koninck Paul , Vanden Berghe Pieter
Published: November 2022

Correct spatiotemporal distribution of organelles and vesicles is crucial for healthy cell functioning and is regulated by intracellular transport mechanisms. Controlled transport of bulky mitochondria is especially important in polarized cells such as neurons that rely on these organelles to locally produce energy and buffer calcium. Mitochondrial transport requires and depends on microtubules that fill much of the available axonal space. How mitochondrial transport is affected by their position within the microtubule bundles is not known. Here, we found that anterograde transport, driven by kinesin motors, is susceptible to the molecular conformation of tubulin in neurons both in vitro and in vivo. Anterograde velocities negatively correlate with the density of elongated tubulin dimers like guanosine triphosphate (GTP)-tubulin. The impact of the tubulin conformation depends primarily on where a mitochondrion is positioned, either within or at the rim of microtubule bundle. Increasing elongated tubulin levels lowers the number of motile anterograde mitochondria within the microtubule bundle and increases anterograde transport speed at the microtubule bundle rim. We demonstrate that the increased kinesin velocity and density on microtubules consisting of elongated dimers add to the increased mitochondrial dynamics. Our work indicates that the molecular conformation of tubulin contributes to the regulation of mitochondrial motility and as such to the local distribution of mitochondria along axons.
IER3IP1 is critical for maintaining glucose homeostasis through regulating the endoplasmic reticulum function and survival of β cells
Authors: Yang Jing , Zhen Jinyang , Feng Wenli , Fan Zhenqian , Ding Li , Yang Xiaoyun , Huang Yumeng , Shu Hua , Xie Jing , Li Xin , Qiao Jingting , Fan Yuxin , Sun Jinhong , Li Na , Liu Tengli , Wang Shusen , Zhang Xiaona , Arvan Peter , Liu Ming
Published: November 2022

Recessive mutations in IER3IP1 (immediate early response 3 interacting protein 1) cause a syndrome of microcephaly, epilepsy, and permanent neonatal diabetes (MEDS). IER3IP1 encodes an endoplasmic reticulum (ER) membrane protein, which is crucial for brain development; however, the role of IER3IP1 in β cells remains unknown. We have generated two mouse models with either constitutive or inducible IER3IP1 deletion in β cells, named IER3IP1-βKO and IER3IP1-iβKO, respectively. We found that IER3IP1-βKO causes severe early-onset, insulin-deficient diabetes. Functional studies revealed a markedly dilated β-cell ER along with increased proinsulin misfolding and elevated expression of the ER chaperones, including PDI, ERO1, BiP, and P58IPK. Islet transcriptome analysis confirmed by qRT-PCR revealed decreased expression of genes associated with β-cell maturation, cell cycle, and antiapoptotic genes, accompanied by increased expression of antiproliferation genes. Indeed, multiple independent approaches further demonstrated that IER3IP1-βKO impaired β-cell maturation and proliferation, along with increased condensation of β-cell nuclear chromatin. Inducible β-cell IER3IP1 deletion in adult (8-wk-old) mice induced a similar diabetic phenotype, suggesting that IER3IP1 is also critical for function and survival even after β-cell early development. Importantly, IER3IP1 was decreased in β cells of patients with type 2 diabetes (T2D), suggesting an association of IER3IP1 deficiency with β-cell dysfunction in the more-common form of diabetes. These data not only uncover a critical role of IER3IP1 in β cells but also provide insight into molecular basis of diabetes caused by IER3IP1 mutations.
Oceanic nutrient rise and the late Miocene inception of Pacific oxygen-deficient zones
Authors: Wang Xingchen Tony , Wang Yuwei , Auderset Alexandra , Sigman Daniel M. , Ren Haojia , Martínez-García Alfredo , Haug Gerald H. , Su Zhan , Zhang Yi Ge , Rasmussen Birger , Sessions Alex L. , Fischer Woodward W.
Published: November 2022

The modern Pacific Ocean hosts the largest oxygen-deficient zones (ODZs), where oxygen concentrations are so low that nitrate is used to respire organic matter. The history of the ODZs may offer key insights into ocean deoxygenation under future global warming. In a 12-My record from the southeastern Pacific, we observe a >10‰ increase in foraminifera-bound nitrogen isotopes (
15
N/
14
N) since the late Miocene (8 to 9 Mya), indicating large ODZs expansion. Coinciding with this change, we find a major increase in the nutrient content of the ocean, reconstructed from phosphorus and iron measurements of hydrothermal sediments at the same site. Whereas global warming studies cast seawater oxygen concentrations as mainly dependent on climate and ocean circulation, our findings indicate that modern ODZs are underpinned by historically high concentrations of seawater phosphate.
Adult neurogenesis acts as a neural regularizer
Authors: Tran Lina M. , Santoro Adam , Liu Lulu , Josselyn Sheena A. , Richards Blake A. , Frankland Paul W.
Published: November 2022

New neurons are continuously generated in the subgranular zone of the dentate gyrus throughout adulthood. These new neurons gradually integrate into hippocampal circuits, forming new naive synapses. Viewed from this perspective, these new neurons may represent a significant source of “wiring” noise in hippocampal networks. In machine learning, such noise injection is commonly used as a regularization technique. Regularization techniques help prevent overfitting training data and allow models to generalize learning to new, unseen data. Using a computational modeling approach, here we ask whether a neurogenesis-like process similarly acts as a regularizer, facilitating generalization in a category learning task. In a convolutional neural network (CNN) trained on the CIFAR-10 object recognition dataset, we modeled neurogenesis as a replacement/turnover mechanism, where weights for a randomly chosen small subset of hidden layer neurons were reinitialized to new values as the model learned to categorize 10 different classes of objects. We found that neurogenesis enhanced generalization on unseen test data compared to networks with no neurogenesis. Moreover, neurogenic networks either outperformed or performed similarly to networks with conventional noise injection (i.e., dropout, weight decay, and neural noise). These results suggest that neurogenesis can enhance generalization in hippocampal learning through noise injection, expanding on the roles that neurogenesis may have in cognition.
Spatiotemporally mapping temperature dynamics of lysosomes and mitochondria using cascade organelle-targeting upconversion nanoparticles
Authors: Di Xiangjun , Wang Dejiang , Su Qian Peter , Liu Yongtao , Liao Jiayan , Maddahfar Mahnaz , Zhou Jiajia , Jin Dayong
Published: November 2022

The intracellular metabolism of organelles, like lysosomes and mitochondria, is highly coordinated spatiotemporally and functionally. The activities of lysosomal enzymes significantly rely on the cytoplasmic temperature, and heat is constantly released by mitochondria as the byproduct of adenosine triphosphate (ATP) generation during active metabolism. Here, we developed temperature-sensitive LysoDots and MitoDots to monitor the in situ thermal dynamics of lysosomes and mitochondria. The design is based on upconversion nanoparticles (UCNPs) with high-density surface modifications to achieve the exceptionally high sensitivity of 2.7% K
−1
and low uncertainty of 0.8 K for nanothermometry to be used in living cells. We show the measurement is independent of the ion concentrations and pH values. With Ca
2+
ion shock, the temperatures of both lysosomes and mitochondria increased by ∼2 to 4 °C. Intriguingly, with chloroquine (CQ) treatment, the lysosomal temperature was observed to decrease by up to ∼3 °C, while mitochondria remained relatively stable. Lastly, with oxidative phosphorylation inhibitor treatment, we observed an ∼3 to 7 °C temperature increase and a thermal transition from mitochondria to lysosomes. These observations indicate different metabolic pathways and thermal transitions between lysosomes and mitochondria inside HeLa cells. The nanothermometry probes provide a powerful tool for multimodality functional imaging of subcellular organelles and interactions with high spatial, temporal, and thermal dynamics resolutions.
Scaling of Berry-curvature monopole dominated large linear positive magnetoresistance
Authors: Zhang Shen , Wang Yibo , Zeng Qingqi , Shen Jianlei , Zheng Xinqi , Yang Jinying , Wang Zhaosheng , Xi Chuanying , Wang Binbin , Zhou Min , Huang Rongjin , Wei Hongxiang , Yao Yuan , Wang Shouguo , Parkin Stuart S. P. , Felser Claudia , Liu Enke , Shen Baogen
Published: November 2022

The linear positive magnetoresistance (LPMR) is a widely observed phenomenon in topological materials, which is promising for potential applications on topological spintronics. However, its mechanism remains ambiguous yet, and the effect is thus uncontrollable. Here, we report a quantitative scaling model that correlates the LPMR with the Berry curvature, based on a ferromagnetic Weyl semimetal CoS
2
that bears the largest LPMR of over 500% at 2 K and 9 T, among known magnetic topological semimetals. In this system, masses of Weyl nodes existing near the Fermi level, revealed by theoretical calculations, serve as Berry-curvature monopoles and low-effective-mass carriers. Based on the Weyl picture, we propose a relation

MR
=

e
ℏ

B

Ω

F

, with
B
being the applied magnetic field and

Ω

F

the average Berry curvature near the Fermi surface, and further introduce temperature factor to both MR/
B
slope (MR per unit field) and anomalous Hall conductivity, which establishes the connection between the model and experimental measurements. A clear picture of the linearly slowing down of carriers, i.e., the LPMR effect, is demonstrated under the cooperation of the
k
-space Berry curvature and real-space magnetic field. Our study not only provides experimental evidence of Berry curvature–induced LPMR but also promotes the common understanding and functional designing of the large Berry-curvature MR in topological Dirac/Weyl systems for magnetic sensing or information storage.
The structured organization of
Deinococcus radiodurans
’ cell envelope
Authors: Farci Domenica , Haniewicz Patrycja , Piano Dario
Published: November 2022

Surface layers (S-layers) are highly ordered coats of proteins localized on the cell surface of many bacterial species. In these structures, one or more proteins form elementary units that self-assemble into a crystalline monolayer tiling the entire cell surface. Here, the cell envelope of the radiation-resistant bacterium
Deinococcus radiodurans
was studied by cryo-electron microscopy, finding the crystalline regularity of the S-layer extended into the layers below (outer membrane, periplasm, and inner membrane). The cell envelope appears to be highly packed and resulting from a three-dimensional crystalline distribution of protein complexes organized in close continuity yet allowing a certain degree of free space. The presented results suggest how S-layers, at least in some species, are mesoscale assemblies behaving as structural and functional scaffolds essential for the entire cell envelope.
Two intrinsic timing mechanisms set start and end times for dendritic arborization of a nociceptive neuron
Authors: Suzuki Nobuko , Zou Yan , Sun HaoSheng , Eichel Kelsie , Shao Meiyu , Shih Mushaine , Shen Kang , Chang Chieh
Published: November 2022

Choreographic dendritic arborization takes place within a defined time frame, but the timing mechanism is currently not known. Here, we report that the precisely timedlin-4-lin-14regulatory circuit triggers an initial dendritic growth activity, whereas the precisely timedlin-28-let-7-lin-41regulatory circuit signals a subsequent developmental decline in dendritic growth ability, hence restricting dendritic arborization within a set time frame. Loss-of-function mutations in thelin-4microRNA gene cause limited dendritic outgrowth, whereas loss-of-function mutations in its direct target, thelin-14transcription factor gene, cause precocious and excessive outgrowth. In contrast, loss-of-function mutations in thelet-7microRNA gene prevent a developmental decline in dendritic growth ability, whereas loss-of-function mutations in its direct target, thelin-41tripartite motif protein gene, cause further decline.lin-4andlet-7regulatory circuits are expressed in the right place at the right time to set start and end times for dendritic arborization. Replacing thelin-4upstream cis-regulatory sequence at thelin-4locus with a late-onsetlet-7upstream cis-regulatory sequence delays dendrite arborization, whereas replacing thelet-7upstream cis-regulatory sequence at thelet-7locus with an early-onsetlin-4upstream cis-regulatory sequence causes a precocious decline in dendritic growth ability. Our results indicate that thelin-4-lin-14and thelin-28-let-7-lin-41regulatory circuits control the timing of dendrite arborization through antagonistic regulation of the DMA-1 receptor level on dendrites. The LIN-14 transcription factor likely directly repressesdma-1gene expression through a transcriptional means, whereas the LIN-41 tripartite motif protein likely indirectly promotesdma-1gene expression through a posttranscriptional means.
Omics analyses of a somaticTrp53R245W/+breast cancer model identify cooperating driver events activating PI3K/AKT/mTOR signaling
Authors: Yu Xiaojie , Zhang Yun , Xiong Shunbin , McDaniel Joy M. , Sun Chang , Chau Gilda P. , Gencel-Augusto Jovanka , Chachad Dhruv , Morrissey Rhiannon L. , Rao Xiayu , Wang Jing , Lozano Guillermina
Published: November 2022

Alterations of the tumor suppressorTP53, one of the most common events in cancer, alone are insufficient for tumor development but serve as drivers of transformation. We sought to identify cooperating events through genomic analyses of a somaticTrp53R245Wmouse model (equivalent to theTP53R248Whot spot mutation in human cancers) that recapitulates metastatic breast–cancer development. We identified cooperating lesions similar to those found in human breast cancers. Moreover, we identified activation of the Pi3k/Akt/mTOR pathway in most tumors via mutations inPten,Erbb2,Kras, and/or a recurrentPip5k1cmutation that stabilizes the Pip5k1c protein and activates Pi3k/Akt/mTOR signaling. AnotherPIP5K1Cfamily member,PIP5K1A, is coamplified withPI4KBin 18% of human breast cancer patients; both encode kinases that are responsible for production of the PI3K substrate, phosphatidylinositol 4,5-bisphosphate. Thus, theTP53R248Wmutation and PI3K/AKT/mTOR signaling are major cooperative events driving breast-cancer development. Additionally, a combination of two US Food and Drug Administration (FDA)-approved drugs, tigecycline and metformin, which target oxidative phosphorylation downstream of PI3K signaling, inhibited tumor cell growth and may be repurposed for breast-cancer treatment. These findings advance our understanding of how mutant p53 drives breast-tumor development and pinpoint the importance of PI3K/AKT/mTOR signaling, expanding combination therapies for breast-cancer treatment.
Long-term depression–inductive stimulation causes long-term potentiation in mouse Purkinje cells with a mutant thyroid hormone receptor
Authors: Ninomiya Ayane , Amano Izuki , Kokubo Michifumi , Takatsuru Yusuke , Ishii Sumiyasu , Hirai Hirokazu , Hosoi Nobutake , Koibuchi Noriyuki
Published: November 2022

Thyroid hormones (THs) regulate gene expression by binding to nuclear TH receptors (TRs) in the cell. THs are indispensable for brain development. However, we have little knowledge about how congenital hypothyroidism in neurons affects functions of the central nervous system in adulthood. Here, we report specific TH effects on functional development of the cerebellum by using transgenic mice overexpressing a dominant-negative TR (Mf-1) specifically in cerebellar Purkinje cells (PCs). Adult Mf-1 mice displayed impairments in motor coordination and motor learning. Surprisingly, long-term depression (LTD)–inductive stimulation caused long-term potentiation (LTP) at parallel fiber (PF)–PC synapses in adult Mf-1 mice, although there was no abnormality in morphology or basal properties of PF–PC synapses. The LTP phenotype was turned to LTD in Mf-1 mice when the inductive stimulation was applied in an extracellular high-Ca
2+
condition. Confocal calcium imaging revealed that dendritic Ca
2+
elevation evoked by LTD-inductive stimulation is significantly reduced in Mf-1 PCs but not by PC depolarization only. Single PC messenger RNA quantitative analysis showed reduced expression of SERCA2 and IP
3
receptor type 1 in Mf-1 PCs, which are essential for mGluR1-mediated internal calcium release from endoplasmic reticulum in cerebellar PCs. These abnormal changes were not observed in adult-onset PC-specific TH deficiency mice created by adeno-associated virus vectors. Thus, we propose the importance of TH action during neural development in establishing proper cerebellar function in adulthood, independent of its morphology. The present study gives insight into the cellular and molecular mechanisms underlying congenital hypothyroidism–induced dysfunctions of central nervous system and cerebellum.
Magnetosome-inspired synthesis of soft ferrimagnetic nanoparticles for magnetic tumor targeting
Authors: Ma Kun , Xu Shuai , Tao Tongxiang , Qian Junchao , Cui Qiqi , Rehman Sajid ur , Zhu Xiaoguang , Chen Ruiguo , Zhao Hongxin , Wang Changhao , Qi Ziping , Dai Han , Zhang Xin , Xie Can , Lu Yang , Wang Hongzhi , Wang Junfeng
Published: November 2022

Magnetic targeting is one of the most promising approaches for improving the targeting efficiency by which magnetic drug carriers are directed using external magnetic fields to reach their targets. As a natural magnetic nanoparticle (MNP) of biological origin, the magnetosome is a special “organelle” formed by biomineralization in magnetotactic bacteria (MTB) and is essential for MTB magnetic navigation to respond to geomagnetic fields. The magnetic targeting of magnetosomes, however, can be hindered by the aggregation and precipitation of magnetosomes in water and biological fluid environments due to the strong magnetic attraction between particles. In this study, we constructed a magnetosome-like nanoreactor by introducing MTB Mms6 protein into a reverse micelle system. MNPs synthesized by thermal decomposition exhibit the same crystal morphology and magnetism (high saturation magnetization and low coercivity) as natural magnetosomes but have a smaller particle size. The DSPE-mPEG–coated magnetosome-like MNPs exhibit good monodispersion, penetrating the lesion area of a tumor mouse model to achieve magnetic enrichment by an order of magnitude more than in the control groups, demonstrating great prospects for biomedical magnetic targeting applications.
Delay effects on the stability of large ecosystems
Authors: Pigani Emanuele , Sgarbossa Damiano , Suweis Samir , Maritan Amos , Azaele Sandro
Published: November 2022

The common intuition among the ecologists of the midtwentieth century was that large ecosystems should be more stable than those with a smaller number of species. This view was challenged by Robert May, who found a stability bound for randomly assembled ecosystems; they become unstable for a sufficiently large number of species. In the present work, we show that May’s bound greatly changes when the past population densities of a species affect its own current density. This is a common feature in real systems, where the effects of species’ interactions may appear after a time lag rather than instantaneously. The local stability of these models with self-interaction is described by bounds, which we characterize in the parameter space. We find a critical delay curve that separates the region of stability from that of instability, and correspondingly, we identify a critical frequency curve that provides the characteristic frequencies of a system at the instability threshold. Finally, we calculate analytically the distributions of eigenvalues that generalize Wigner’s as well as Girko’s laws. Interestingly, we find that, for sufficiently large delays, the eigenvalues of a randomly coupled system are complex even when the interactions are symmetric.
Reduced surface accumulation of swimming bacteria in viscoelastic polymer fluids
Authors: Cao Ding , Dvoriashyna Mariia , Liu Song , Lauga Eric , Wu Yilin
Published: November 2022

Surface-associated bacterial communities flourish in nature and in the body of animal hosts with abundant macromolecular polymers. It is unclear how the endowed viscoelasticity of polymeric fluids influences bacterial motile behavior in such environments. Here, we combined experiment and theory to study near-surface swimming of flagellated bacteria in viscoelastic polymer fluids. In contrast to the swimming behavior in Newtonian fluids, we discovered that cells swim in less curved trajectories and display reduced near-surface accumulation. Using a theoretical analysis of the non-Newtonian hydrodynamic forces, we demonstrated the existence of a generic lift force acting on a rotating filament near a rigid surface, which arises from the elastic tension generated along curved flow streamlines. This viscoelastic lift force weakens the hydrodynamic interaction between flagellated swimmers and solid surfaces and contributes to a decrease in surface accumulation. Our findings reveal previously unrecognized facets of bacterial transport and surface exploration in polymer-rich environments that are pertinent to diverse microbial processes and may inform the design of artificial microswimmers capable of navigating through complex geometries.
Structure of an amorphous calcium carbonate phase involved in the formation of
Pinctada margaritifera
shells
Authors: Grünewald Tilman A. , Checchia Stefano , Dicko Hamadou , Le Moullac Gilles , Sham Koua Manaarii , Vidal-Dupiol Jeremie , Duboisset Julien , Nouet Julius , Grauby Olivier , Di Michiel Marco , Chamard Virginie
Published: November 2022

Some mollusc shells are formed from an amorphous calcium carbonate (ACC) compound, which further transforms into a crystalline material. The transformation mechanism is not fully understood but is however crucial to develop bioinspired synthetic biomineralization strategies or accurate marine biomineral proxies for geoscience. The difficulty arises from the simultaneous presence of crystalline and amorphous compounds in the shell, which complicates the selective experimental characterization of the amorphous fraction. Here, we use nanobeam X-ray total scattering together with an approach to separate crystalline and amorphous scattering contributions to obtain the spatially resolved atomic pair distribution function (PDF). We resolve three distinct amorphous calcium carbonate compounds, present in the shell of
Pinctada margaritifera
and attributed to: interprismatic periostracum, young mineralizing units, and mature mineralizing units. From this, we extract accurate bond parameters by reverse Monte Carlo (RMC) modeling of the PDF. This shows that the three amorphous compounds differ mostly in their Ca–O nearest-neighbor atom pair distance. Further characterization with conventional spectroscopic techniques unveils the presence of Mg in the shell and shows Mg–calcite in the final, crystallized shell. In line with recent literature, we propose that the amorphous-to-crystal transition is mediated by the presence of Mg. The transition occurs through the decomposition of the initial Mg-rich precursor into a second Mg-poor ACC compound before forming a crystal.
Embryonic microRNAs are essential for bovine preimplantation embryo development
Authors: Paulson Erika E. , Fishman Emily L. , Ma Jun , Schultz Richard M. , Ross Pablo J.
Published: November 2022

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression after transcription. miRNAs are present in transcriptionally quiescent full-grown oocytes and preimplantation embryos that display a low level of transcription prior to embryonic genome activation. The role of miRNAs, if any, in preimplantation development is not known. The temporal pattern of expression of miRNAs during bovine preimplantation development was determined by small RNA-sequencing using eggs and preimplantation embryos (1-cell, 2-cell, 4-cell, 8-cell, 16-cell, morula, and blastocyst). Embryos cultured in the presence of α-amanitin, which permitted the distinguishing of maternal miRNAs from embryonic miRNAs, indicated that embryonic miRNA expression was first detected at the two-cell stage but dramatically increased during the morula and blastocyst stages. Targeting
DGCR8
by a small-interfering RNA/morpholino approach revealed a role for miRNAs in the morula-to-blastocyst transition. Knockdown of DGCR8 not only inhibited expression of embryonically expressed miRNAs but also inhibited the morula-to-blastocyst transition. In addition, RNA-sequencing identified an increased relative abundance of messenger RNAs potentially targeted by embryonic miRNAs in DGCR8-knockdown embryos when compared with controls. Results from these experiments implicate an essential role for miRNAs in bovine preimplantation embryo development.
Anti-PF4 antibodies associated with disease severity in COVID-19
Authors: Liu Qingbo , Miao Huiyi , Li Shuai , Zhang Peng , Gerber Gloria F. , Follmann Dean , Ji Hongkai , Zeger Scott L. , Chertow Daniel S. , Quinn Thomas C. , Robinson Matthew L. , Kickler Thomas S. , Rothman Richard E. , Fenstermacher Katherine Z. J. , Braunstein Evan M. , Cox Andrea L. , Farci Patrizia , Fauci Anthony S. , Lusso Paolo
Published: November 2022

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)–polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.
Chromophore hydrolysis and release from photoactivated rhodopsin in native membranes
Authors: Hong John D. , Salom David , Kochman Michał Andrzej , Kubas Adam , Kiser Philip D. , Palczewski Krzysztof
Published: November 2022

For sustained vision, photoactivated rhodopsin (Rho*) must undergo hydrolysis and release of all-
trans
-retinal, producing substrate for the visual cycle and apo-opsin available for regeneration with 11-
cis
-retinal. The kinetics of this hydrolysis has yet to be described for rhodopsin in its native membrane environment. We developed a method consisting of simultaneous denaturation and chromophore trapping by isopropanol/borohydride, followed by exhaustive protein digestion, complete extraction, and liquid chromatography–mass spectrometry. Using our method, we tracked Rho* hydrolysis, the subsequent formation of
N
-retinylidene-phosphatidylethanolamine (
N
-ret-PE) adducts with the released all-
trans
-retinal, and the reduction of all-
trans
-retinal to all-
trans
-retinol. We found that hydrolysis occurred faster in native membranes than in detergent micelles typically used to study membrane proteins. The activation energy of the hydrolysis in native membranes was determined to be 17.7 ± 2.4 kcal/mol. Our data support the interpretation that metarhodopsin II, the signaling state of rhodopsin, is the primary species undergoing hydrolysis and release of its all-
trans
-retinal. In the absence of NADPH, free all-
trans
-retinal reacts with phosphatidylethanolamine (PE), forming a substantial amount of
N
-ret-PE (∼40% of total all-
trans
-retinal at physiological pH), at a rate that is an order of magnitude faster than Rho* hydrolysis. However,
N
-ret-PE formation was highly attenuated by NADPH-dependent reduction of all-
trans
-retinal to all-
trans
-retinol. Neither
N
-ret-PE formation nor all-
trans
-retinal reduction affected the rate of hydrolysis of Rho*. Our study provides a comprehensive picture of the hydrolysis of Rho* and the release of all-
trans
-retinal and its reentry into the visual cycle, a process in which alteration can lead to severe retinopathies.
Generation of genome-edited chicken and duck lines by adenovirus-mediated in vivo genome editing
Authors: Lee Joonbum , Kim Dong-Hwan , Karolak Madeline C. , Shin Sangsu , Lee Kichoon
Published: November 2022

Conventional avian genome editing is mediated by isolation, culture, and genome editing of primordial germ cells (PGCs); screening and propagating the genome-edited PGCs; and transplantation of the PGCs into recipient embryos. The PGC-mediated procedures, however, are technically difficult, and therefore, the conventional method has previously been utilized only in chickens. Here, we generated germline mosaic founder chicken and duck lines without the PGC-mediated procedures by injecting an adenovirus containing the CRISPR-Cas9 system into avian blastoderms. Genome-edited chicken and duck offspring produced from the founders carried different insertion or deletion mutations without mutations in the potential off-target sites. Our data demonstrate successful applications of the adenovirus-mediated method for production of genome-edited chicken and duck lines.
Flexible integration of continuous sensory evidence in perceptual estimation tasks
Authors: Esnaola-Acebes Jose M. , Roxin Alex , Wimmer Klaus
Published: November 2022

Temporal accumulation of evidence is crucial for making accurate judgments based on noisy or ambiguous sensory input. The integration process leading to categorical decisions is thought to rely on competition between neural populations, each encoding a discrete categorical choice. How recurrent neural circuits integrate evidence for continuous perceptual judgments is unknown. Here, we show that a continuous bump attractor network can integrate a circular feature, such as stimulus direction, nearly optimally. As required by optimal integration, the population activity of the network unfolds on a two-dimensional manifold, in which the position of the network’s activity bump tracks the stimulus average, and, simultaneously, the bump amplitude tracks stimulus uncertainty. Moreover, the temporal weighting of sensory evidence by the network depends on the relative strength of the stimulus compared to the internally generated bump dynamics, yielding either early (primacy), uniform, or late (recency) weighting. The model can flexibly switch between these regimes by changing a single control parameter, the global excitatory drive. We show that this mechanism can quantitatively explain individual temporal weighting profiles of human observers, and we validate the model prediction that temporal weighting impacts reaction times. Our findings point to continuous attractor dynamics as a plausible neural mechanism underlying stimulus integration in perceptual estimation tasks.
Combined effect and mechanism of thermal behaviour and flow characteristic on microstructure and mechanical property of oscillation laser-welded of IN718
Authors: Yan Shenghong , Meng Zheng , Chen Bo , Tan Caiwang , Song Xiaoguo , Wang Guodong
Published: November 2022

An oscillation laser beam was conducted to enhance the mechanical property of Inconel 718 joints. The dynamic behaviours of molten pool on the microstructure and mechanical property of joints were investigated. The results showed that the improvement of Laves phase and the tensile property depended on the flow and thermal behaviours of molten pool. Compared with conventional laser welding, the maximum flow velocity on the surface of molten pool increased by 375.5%(150 Hz), which indicated the dendrites received greater bending stress to break more easily, resulting in the homogenisation of element. In addition, the oscillation laser beam decreased the temperature gradient from 218.5°C/mm to 73°C/mm, and the cooling rate of 150 Hz in the centre and edge of molten pool increased by 64.4% and 111.9%, which hindered the segregation phenomenon during the element diffusion to restrain the formation of Laves phase in the eutectic reaction.
The multimodal motion along a solid–liquid interface of a soft microrobot driven by compound magnetic fields
Authors: Gao Jian , Rong Weibin , Gao Peng , Li Dongjie , Wang Lefeng , Sun Lining
Published: November 2022

In recent years, soft microrobots based on flexible materials have received increasing attention. Most of the current studies on soft microrobots have implemented only one motion mode, and because the motion environment is often set inside liquid, the strategies of multimodal motion control near the solid–liquid interface are insufficient. In this study, we present a 4 mm × 1 mm × 0.2 mm sheet-like soft microrobot bent into a ring shape and magnetized so that it can move in multiple modes along the solid–liquid interface and can be driven by different types of magnetic fields. The deformation amplitude and the total magnetic moment of the robot under the external magnetic field were obtained with the help of finite element simulations. Three different periodic magnetic field driving modes along the solid–liquid interface, namely rolling mode, walking mode, and hopping mode, were realized, and the robot’s motion speed and direction under various motion modes were adjusted by additional magnetic field strengths and magnetic field gradients. This research can enhance the adaptability of soft microrobots to various motion environments and further expand their application prospects.
Acoustic charge transport in organic semiconductor films
Authors: Mishra Himakshi , Bhattacharjee Paromita , Nemade Harshal B
Published: November 2022

We demonstrate the acoustic charge transport of optically induced excitons in two organic semiconductors, P3HT and MEH-PPV, up to a distance of 3 mm. The device consists of a surface acoustic wave (SAW) resonator transmitting SAW through a polymer layer where acoustic charge transport takes place and a polymer diode at the end to collect the charges. The voltage excitation is provided using an interdigital transducer (IDT) on a piezoelectric YZ lithium niobate substrate producing Rayleigh SAW at 42 MHz. Optical illumination up to 15 mW cm−2 intensity is applied to induce excitons in the polymer layer deposited on the lithium niobate substrate. The photogenerated excitons in the polymer are ionized by SAW field resulting in free carriers that are transported to the polymer diode by the travelling SAW. A surge in photovoltaic current in the diode is observed in the presence of SAW when the carriers are optically generated away from the diode. The maximum charge capacity and transfer efficiency of the acoustic transport are calculated for various SAW power and illumination intensities. A theoretical analysis of charge carrier dynamics in the presence of a moving SAW field is also performed using a semi-classical Hamiltonian of the system.
A novel terahertz integrated sensor for liquid samples detections based on metamaterial and embedded microfluidic channels
Authors: Li Xue , Jiao Hengyuan , Zhu Mingqiang , Deng Tao , Sun Jingye
Published: November 2022

THz metamaterial (MM) microfluidic sensors, which can be utilized for the detection of small volume liquid specimen, have attracted much attention in biosensing applications. In this paper, we propose a novel microfluidic channel embedded terahertz MM sensor, which employs split ring resonators (SRRs) and asymmetric two-gap SRRs for the detection of liquid samples. Unlike currently reported THz MM microfluidic sensors utilizing microfluidic superstrate-metal-substrate structure, our approach combines the microfluidic superstrate with substrate, by designing micro-channels underneath the gap of the SRRs within the polydimethylsiloxane substrate. It could be easily fabricated by standard photolithography techniques. The simulated results show that the performance of the sensor is dependent on the spacing angle between two gaps, the orientation of the gaps, as well as the polarization of electric fields. Furthermore, maximum Q factors of 9.5 and 44 are achieved for dipole resonance, with corresponding figure of merits of 0.63 and 2.89 RIU−1 for transmission and reflection scenarios. Thus, this concept and method not only provides sensitive biosensing for liquid-based samples, but also can be applied to other MM structures to further improve the sensitivity.
Tunable anomalous Hall and Nernst effects in MM′X compounds
Authors: Samathrakis Ilias , Fortunato Nuno , Singh Harish K , Shen Chen , Zhang Hongbin
Published: November 2022

Based on first-principles calculations, the anomalous Hall conductivity (AHC) and anomalous Nernst conductivities (ANCs) of the XMnP (X = Ti, Zr, Hf) compounds are evaluated, and the possibility to tailor such properties in compounds susceptible to changing the magnetization directions is also investigated. We observe large changes in the calculated AHC and ANC for different magnetization directions that are originating from changes in the band structure all over the whole Brillouin zone. Our study gives a promising clue on engineering magnetic intermetallic compounds for tunable transverse thermoelectric applications.