bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light-regulated pro-angiogenic engineered living materials
Authors: Dhakane Priyanka , Tadimarri Varun Sai , Sankaran Shrikrishnan 
Published: October 2022

I.AbstractDespite their promise, the application of growth factors in regenerative medicine is limited by their poor stability in the body, high costs of production/storage and need for localized and tightly controlled delivery to minimize adverse side effects. In this study, a unique strategy to overcome these limitations is explored based on engineered living materials (ELMs). These are an emerging class of composite materials, which contain live microorganisms that can be engineered to produce and secrete proteins in response to external stimuli. Herein, the development of an ELM that light-responsively releases a pro-angiogenic protein is described. This is achieved by optogenetically engineering bacteria to synthesize and secrete a fusion protein containing a vascular endothelial growth factor peptidomimetic linked to a collagen-binding domain. The bacteria are securely encapsulated in bilayer hydrogel constructs that support bacterial functionality but prevent their escape from the ELM. The possibility to switch protein release ON and OFF with light and to tune the amount released with different light intensities is demonstrated. Finally, it is shown that the released protein is active through its ability to bind to collagen and promote angiogenic network formation in human vascular endothelial cell cultures, indicating the regenerative potential of these ELMs.
A Common Resequencing-Based Genetic Marker Dataset for Global Maize Diversity
Authors: Grzybowski Marcin W. , Mural Ravi V. , Xu Gen , Turkus Jonathan , Yang Jinliang , Schnable James C. 
Published: October 2022

ABSTRACTMaize (Zea mays ssp. mays) populations exhibit vast amounts of genetic and phenotypic diversity. As sequencing costs have declined, an increasing number of projects have sought to measure genetic differences between and within maize populations using whole genome resequencing strategies, identifying millions of segregating single-nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). Unlike older genotyping strategies like microarrays and genotyping by sequencing, resequencing should, in principle, frequently identify and score common genetic variants. However, in practice, different projects frequently employ different analytical pipelines, often employ different reference genome assemblies, and consistently filter for minor allele frequency within the study population. This constrains the potential to reuse and remix data on genetic diversity generated from different projects to address new biological questions in new ways. Here we employ resequencing data from 1,276 previously published maize samples and 239 newly resequenced maize samples to generate a single unified marker set of ∼366 million segregating variants and ∼46 million high confidence variants scored across crop wild relatives, landraces as well as tropical and temperate lines from different breeding eras. We demonstrate that the new variant set provides increased power to identify known causal flowering time genes using previously published trait datasets, as well as the potential to track changes in the frequency of functionally distinct alleles across the global distribution of modern maize.
LTP-like noninvasive striatal brain stimulation enhances striatal activity and motor skill learning in humans
Authors: Wessel Maximilian J. , Beanato Elena , Popa Traian , Windel Fabienne , Vassiliadis Pierre , Menoud Pauline , Beliaeva Valeriia , Violante Ines R. , Abderrahmane Hedjoudje , Dzialecka Patrycja , Park Chang-Hyun , Maceira-Elvira Pablo , Morishita Takuya , Cassara Antonino , Steiner Melanie , Grossman Nir , Neufeld Esra , Hummel Friedhelm C. 
Published: October 2022

AbstractThe stimulation of deep brain structures has thus far been possible only with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here, we show for the first time successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, fMRI studies and behavioral evaluations. Theta-burst patterned, LTP-like striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor learning capacity, especially in healthy older participants, who have lower natural learning capacity than younger subjects. These findings suggest exciting methods for noninvasively targeting deep brain structures in humans, thus enhancing our understanding of their functional roles. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders, in which deep brain structures play key pathophysiological roles.
Cytotoxicity, Mutagenicity and Genotoxicity of Electronic Cigarettes Emission Aerosols Compared to Cigarette Smoke: the REPLICA project
Authors: Emma Rosalia , Fuochi Virginia , Distefano Alfio , Rust Sonja , Zadjali Fahad , Tobi Mohammed Al , Zadjali Razan , Alharthi Zaina , Pulvirenti Roberta , Furneri Pio Maria , Polosa Riccardo , Caruso Massimo , Volti Giovanni Li 
Published: October 2022

AbstractDuring the last decade electronic cigarettes (e-cigarettes) have been studied as an alternative devices to the tobacco cigarette, but with better safety for the health of smokers, so as to create a new approach to smoking addiction, such as the “smoking harm reduction”. This new approach, suggested by a part of the scientific world, aroused interest and debates in the regulatory field, involving all the major regulatory bodies and often creating divergences from nation to nation on the rules driving the production, distribution and consumption of these alternative products. Many studies have been conducted both in vitro and in vivo, to clarify the effects of the e-cigarette compared to the classic one. In this context, the Center of Excellence for the Acceleration of HArm Reduction (CoEHAR) was established within the University of Catania (Italy) and the multi-center project, created under its leadership, the REPLICA project, which aims to replicate in vitro studies originally conducted by tobacco and e-cigarette manufacturers, in order to verify the robustness and replicability of the data. In this work the REPLICA Team replicated part of the work published by Rudd and colleagues in 2020, which aims to establish the aerosol-induced cytotoxicity, mutagenesis and genotoxicity of a pod system e-cigarette aerosol compared to tobacco cigarette smoke. As in the original paper, we performed Neutral Red Test (NRU) for the evaluation of cytotoxicity, AMES test for the evaluation of mutagenesis and In Vitro Micronuclei (IVM) assay for the evaluation of genotoxicity on cells treated with cigarette smoke or e-cigarette aerosol. The results obtained showed high cytotoxicity, mutagenicity and genotoxicity induced by cigarette smoke, but slight or no cytotoxic, mutagenic and genotoxic effects induced by the e-cigarette aerosol. The data obtained support those previously presented by Rudd and colleagues, although we have highlighted some methodological flaws of their work. Overall, we can affirm that the results obtained by Rudd and colleagues have been established and our data also confirm the idea that e-cigarette aerosol is much safer and less harmful than cigarette smoking, making it a useful device in smoking harm reduction.
Mutations inNAKED-ENDOSPERMIDD genes reveal functional interactions withSCARECROWand a maternal influence on leaf patterning in C4grasses
Authors: Hughes Thomas E. , Sedelnikova Olga , Thomas Mimi , Langdale Jane A. 
Published: October 2022

ABSTRACTLeaves comprise a number of different cell-types that are patterned in the context of either the epidermal or inner cell layers. In grass leaves, two distinct anatomies develop in the inner leaf tissues depending on whether the leaf carries out C3or C4photosynthesis. In both cases a series of parallel veins develops that extends from the leaf base to the tip but in ancestral C3species veins are separated by a greater number of intervening mesophyll cells than in derived C4species. We have previously demonstrated that the GRAS transcription factor SCARECROW (SCR) regulates the number of photosynthetic mesophyll cells that form between veins in the leaves of the C4species maize, whereas it regulates the formation of stomata in the epidermal leaf layer in the C3species rice. Here we show that SCR is required for inner leaf patterning in the C4speciesSetaria viridisbut in this species the presumed ancestral stomatal patterning role is also retained. Through a comparative mutant analysis between maize, setaria and rice we further demonstrate that loss of NAKED-ENDOSPERM (NKD) INDETERMINATE DOMAIN (IDD) protein function exacerbates loss of functionscrphenotypes in the inner leaf tissues of maize and setaria but not rice. Specifically, in both setaria and maize,scr;nkdmutants exhibit an increased proportion of fused veins with no intervening mesophyll cells, whereas inner leaf tissues are patterned normally inscr;nkdmutants of rice. Thus, combined action of SCR and NKD may control how many mesophyll cells are specified between veins in the leaves of C4but not C3grasses. Finally, we identified a maternal effect in maize in which maternally derived NKD can affect patterning of cells in leaf primordia that are initiated during embryogenesis. Together our results provide insight into the evolution of cell patterning in grass leaves, demonstrate a novel patterning role for IDD genes in C4leaves and suggest that NKD can influence embryonic leaf development non-cell autonomously from the surrounding maternal tissue.Summary statementMutations inNKDIDD genes enhance loss of functionscrphenotypes in the leaves of C4grasses maize andSetaria viridisbut not in the C3grass rice, and reveal a maternal effect on cell-type patterning in leaves that are initiated during embryogenesis.
Concurrent maintenance of both veridical and transformed working memory representations within unique coding schemes
Authors: Kandemir Güven , Wolff Michael J. , Karabay Aytaç , Stokes Mark G. , Axmacher Nikolai , Akyürek Elkan G. 
Published: October 2022

AbstractIn the dynamic environment we live in, the already limited information that human working memory can maintain needs to be constantly updated to optimally guide behaviour. Indeed, previous studies showed that leading up to a response, representations maintained in working memory representations are transformed continuously. This goes hand-in-hand with the removal of task-irrelevant items. However, does such removal also include the representations of stimuli as they were originally, prior to transformation? Here we assessed the neural representation of task-relevant transformed representations, and the no-longer-relevant veridical representations they originated from. We applied multivariate pattern analysis to electroencephalographic data during maintenance of orientation gratings with and without mental rotation. During maintenance, we perturbed the representational network by means of a visual impulse stimulus, and were thus able to successfully decode veridical as well as imaginary, transformed orientation gratings from impulse-driven activity. The impulse response reflected only task-relevant (cued), but not task-irrelevant (uncued) items, suggesting that the latter were quickly discarded from working memory. By contrast, even though the original cued orientation gratings were also no longer task-relevant after mental rotation, these items continued to be represented next to the rotated ones, in different representational formats. This seemingly inefficient use of scarce working memory capacity was associated with reduced probe response times and may thus serve to increase precision and flexibility in guiding behaviour in dynamic environments.
Co-option of the transcription factorSALL1in mole ovotestis formation
Authors: Schindler Magdalena , Osterwalder Marco , Harabula Izabela , Wittler Lars , Tzika Athanasia C. , Dechmann Dina , Vingron Martin , Visel Axel , Haas Stefan , Real Francisca M. 
Published: October 2022

ABSTRACTChanges in gene expression represent an important source for phenotypical innovation. Yet, how such changes emerge and impact the evolution of traits remains elusive. Here, we explore the molecular mechanisms associated with the development of masculinizing ovotestes in female moles. By performing comparative analyses of epigenetic and transcriptional data in mole and mouse, we identifiedSALL1as a co-opted gene for the formation of testicular tissue in mole ovotestes. Chromosome conformation capture analyses highlight a striking conservation of the 3D organization at theSALL1locus, but a prominent evolutionary turnover of enhancer elements. Interspecies reporter assays support the capability of mole-specific enhancers to activate transcription in urogenital tissues. Through overexpression experiments in transgenic mice, we further demonstrate the capability ofSALL1to induce the ectopic gene expression programs that are a signature of mole ovotestes. Our results highlight the co-option of gene expression, through changes in enhancer activity, as a prominent mechanism for the evolution of traits.
Assistive loading promotes goal-directed tuning of stretch reflex gains
Authors: Torell Frida , Franklin Sae , Franklin David W. , Dimitriou Michael 
Published: October 2022

AbstractVoluntary movements are prepared before they are executed. Preparatory activity has been observed across the CNS and recently documented in first order neurons of the human PNS i.e., in muscle spindles. The changes seen in these sensory organs suggest that the independent modulation of stretch reflex gains may represent an important component of movement preparation. The aim of the current study was to further investigate the preparatory modulation of short- and long-latency stretch reflex responses (‘SLR’ and ‘LLR’) of the dominant upper limb. Specifically, we investigated how different target parameters (target distance and direction) affect the preparatory tuning of stretch reflex gains in the context of goal-directed reaching, and whether any such tuning depends on preparation duration and the direction of background loads. We found that target distance produced only small variations in reflex gains. In contrast, both SLR and LLR gains were strongly modulated as a function of target direction, in a manner that facilitated the upcoming voluntary movement. This goal-directed tuning of SLR and LLR gains was present or enhanced when the preparatory delay was sufficiently long (>250 ms) and the homonymous muscle was unloaded i.e., when a background load was first applied in the direction of homonymous muscle action (assistive loading). The results extend further support for a relatively slow-evolving process in reach preparation that functions to modulate reflexive muscle stiffness, likely via the independent control of fusimotor neurons. Such control can augment voluntary goal-directed movement and is triggered or enhanced when the homonymous muscle is unloaded.Significance StatementIt is well-known that movement preparation improves motor performance. That is, briefly delaying the onset of a goal-directed movement can significantly benefit the overall quality of movement. However, the mechanisms underlying movement preparation remain unclear. In this study we examined the preparatory modulation of short- and long-latency stretch reflex responses in the dominant upper limb. We found that goal-directed tuning of stretch reflex gains is consistently triggered or enhanced in cases where preparation is sufficiently long (>250 ms) and a background -‘assistive’- load is first applied in the direction of homonymous muscle action. A better understanding of movement preparation will likely also benefit the development of rehabilitation regimes and movement augmentation devices.
Temporary knockdown of p53 during focal limb irradiation increases the development of sarcomas
Authors: Daniel Andrea R. , Lee Chang-Lung , Su Chang , Williams Nerissa T. , Li Zhiguo , Huang Jianguo , Lopez Omar , Luo Lixia , Ma Yan , De Silva Campos Lorraine , Selitsky Sara R. , Modliszewski Jennifer L. , Liu Siyao , Mowery Yvonne M. , Cardona Diana M. , Kirsch David G. 
Published: October 2022

AbstractBackgroundApproximately half of all cancer patients receive radiotherapy and, as cancer survivorship rates increase with more effective therapies, the very low rate of radiation-associated sarcomas is rising. Radiation-associated sarcomas are life-threatening cancers, and radiation exposure is a primary risk factor for sarcoma development. During radiotherapy or other genotoxic cancer therapy forp53mutant cancers, pharmacological inhibition of p53 has been proposed to ameliorate acute injury of normal tissues. However, enhancing the survival of normal cells that sustain DNA damage by temporarily inhibiting p53 has the potential to increase the risk of cancer development. Here, we usein vivoshRNA technology to examine the consequences of temporarily reducing p53 expression on radiation-induced sarcoma development.MethodsWe utilized a mouse model of radiation-induced sarcoma where mice express a doxycycline (dox)-inducible p53 shRNA to temporarily and reversibly reduce p53 expression. Mice were placed on a dox diet 10 days prior to receiving 30 or 40 Gy hind limb irradiation in a single fraction and then returned to normal chow. Mice were examined weekly for sarcoma development and scored for radiation-induced normal tissue injuries. Radiation-induced sarcomas were harvested and subjected to RNA sequencing.ResultsFollowing single high-dose irradiation, 21% of temporary p53 knockdown animals developed a sarcoma in the radiation field compared to 2% of control animals. Mice with more severe acute injuries in the first 3 months after irradiation had a significantly increased risk of developing late persistent wounds in the soft tissue and bone. Chronic radiation-induced wounds were associated with sarcomagenesis. Examination of muscle stem cells by flow cytometry following hind limb irradiation indicated p53 knockdown preserves muscle stem cells in the irradiated limb, supporting the notion that temporary p53 knockdown at the time of irradiation reduces death of cells with DNA damage which may then persist to develop into a sarcoma. We performed RNA sequencing on 16 radiation-induced sarcomas compared to normal muscle controls. Gene set enrichment analysis revealed upregulation in the sarcomas of genes related to translation, epithelial mesenchymal transition (EMT), inflammation, and the cell cycle versus downregulation of genes related to myogenesis and tumor metabolism. Furthermore, genes with increased copy number such asMetandCdk4were overexpressed in tumors.ConclusionsTemporary reduction of p53 during high-dose irradiation increases late effects including tissue injuries and sarcoma development.
Biological Sex Influences the Contribution of Sign-Tracking and Anxiety-Like Behaviour toward Remifentanil Self-Administration
Authors: Zumbusch Alicia , Samson Ana , Chernoff Chloe , Coslovich Brandi , Hynes Tristan 
Published: October 2022

AbstractMost people sample addictive drugs, but use becomes disordered in only a small minority. Two important factors that influence susceptibility to addiction are individual differences in personality traits and biological sex. The influence of traits on addiction-like behaviour is well characterized in preclinical models of cocaine self-administration, but less is understood in regards to opioids. How biological sex influences trait susceptibility to opioid self-administration is likewise less studied than psychostimulants. Thus, we sought to elucidate how biological sex and several addiction-relevant traits interact with the propensity to self-administer the opioid remifentanil. We first screened female (n=19) and male (n=19) rats for four addiction-relevant traits: impulsivity, novelty place-preference, anxiety-like behaviour, and attribution of incentive value to reward cues. Rats were then trained to self-administer remifentanil in a “conflict model” of drug self-administration. Rats had to endure a mild electric shock to access the response manipulandum that triggered an intravenous infusion of remifentanil. In male rats, high anxiety-like behaviour was positively correlated with the number of drug infusions if the shock level was low or completely absent. In females, sign-tracking was predictive of greater resistance to punishment during drug seeking; an effect that was mediated by anxiety-like behaviour. Females consumed more remifentanil under all conditions, and their drug seeking persisted in the face of significantly greater current than males. These findings demonstrate that the influence of behavioural traits over the propensity to self-administer opioids is dependent upon biological sex.
Comprehensive multi-omics characterization of gut microbiome extracellular vesicles reveals a connection to gut-brain axis signaling
Authors: Sultan Salma , Yousuf Basit , Yeo JuDong , Ahmed Tamer , Bouhlel Nour Elhouda , Hassan Heba , Minic Zoran , Mottawea Walid , Hammami Riadh 
Published: October 2022

AbstractMicrobiota-gut-brain axis is an evident pathway of host-microbiota crosstalk that is linked to multiple brain disorders. Microbiota released extracellular vesicles (MEVs) has emerged as a key player in intercellular signaling in host microbiome communications. However, their role in gutbrain axis signaling is poorly investigated. Here, we performed a deep multi-omics profiling of MEVs content generated ex vivo and from stool samples in order to get some insights on their role in gut-brain-axis signaling. Metabolomics profiling identified a wide array of metabolites embedded in MEVs, including lipids, carbohydrates, amino acids, vitamins, and organic acids. Interestingly, many neurotransmitter-related compounds were detected inside MEVs, including arachidonyl-dopamine (NADA), gabapentin, glutamate and N-acylethanolamines. Next, we aimed to identify commensal microbes with psychobiotic activity. We isolated 58Bacteroidesstrains assigned to four genera, 11 species, and 4 new species based on 16S rDNA sequencing. We performed whole genome sequencing of 18 representative isolates, followed by a comparative analysis of the structure of polysaccharide utilization loci (PUL) and glutamate decarboxylase (GAD), a genetic system involved in GABA production. Quantifying GABA was done using competitive ELISA, wherein three isolates (B. finegoldii, B. faecis, andB. caccae) showed high GABA production (4.5-7 mM range) in supernatant whereas 2.2 to 4 uM GABA concentration was detected inside microvesicles extracted using ultracentrifugation. To test the biodistribution of MEVs from the gut to other parts of the body, CACO-2, RIN-14 B, and hCMEC/D3 cells showed a capacity to internalize labeled MEVs through an endocytic mechanism. Additionally, MEVs exhibited a dose dependent paracellular transport through CACO-2 intestinal cells and hCMEC/D3 brain endothelial cells. In vivo results showed biodistribution of MEVs to liver, stomach and spleen. Overall, our results reveal the capabilities of MEVs to cross the intestinal and blood brain barriers to deliver their cargoes of neuroactive molecules to the brain as a new signaling mechanism in microbiota-gut-brain axis communications.