bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new high-resolution three-dimensional retinal implant: System design and preliminary human results
Authors: Yanovitch Leonid , Raz-Prag Dorit , Hanein Yael 
Published: September 2022

AbstractThe NR600 retinal prosthetic device is a unique newly developed implant intended to restore visual perception to people who lost their vision due to retinal degenerative diseases. The miniature implant captures the visual image in place of the damaged photoreceptor cells and creates the electrical stimulation required to activate the preserved retinal cell layers. The NR600 system transduces visual signal into electrical signals that are delivered to the retina via an array of needle shaped electrodes to minimize electrical activation levels and improve stimulation localization. NR600 consists of two components: A miniature implantable chip and eyeglasses set worn by the patient. The eyeglasses deliver power and control the implantable device. In this report, we present the NR600 system design, its optical, electrical, and electro-chemical characteristics, and preliminary results from human subjects.
P3HT-GRAPHENE DEVICE FOR THE RESTORATION OF VISUAL PROPERTIES IN A RAT MODEL OF RETINITIS PIGMENTOSA
Authors: Francia Simona , Marco Stefano Di , DiFrancesco Mattia L. , Ferrari Davide V. , Shmal Dmytro , Cavalli Alessio , Pertile Grazia , Attanasio Marcella , Maya-Vetencourt José Fernando , Manfredi Giovanni , Lanzani Guglielmo , Benfenati Fabio , Colombo Elisabetta 
Published: September 2022

ABSTRACTRetinal degeneration is one of the prevalent causes of blindness worldwide, for which no effective treatment has yet been identified. Inorganic photovoltaic devices have been investigated for visual restoration in advanced stage Retinitis pigmentosa (RP), although lack of implant flexibility and foreign-object reactions have limited their application. Organic photoactive retinal prostheses may overcome these limitations, being biomimetic and tissue friendly. Inspired by organic photovoltaic strategies involving graphene, a hybrid retinal prosthesis was recently engineered consisting of a dual poly-3-hexylthiophene (P3HT) and graphene layer onto a flexible substrate. Here, this hybrid prosthesis was subretinally implanted in vivo in 5-month-old Royal College of Surgeons (RCS) rats, a rodent model of RP. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses. Moreover, the analysis of the physical-mechanical properties after prolonged permanence in the eye showed excellent biocompatibility and robustness of the device. Overall, the results demonstrate that graphene-enhanced organic photovoltaic devices can be suitably employed for the rescue of retinal dystrophies and supports the translation of the organic strategy into the medical practice.TABLE OF CONTENTSInspired by organic photovoltaic, a hybrid retinal prosthesis consisting of poly-3-hexylthiophene (P3HT) and graphene on a flexible substrate was subretinally implanted in vivo in Royal College of Surgeons (RCS) rats, a model of Retinitis pigmentosa. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses.
Comparison of Transcriptomic Changes in Younger and Older Multiple Myeloma Patients from the MMRF-CoMMpass Study RNA-Seq Data
Authors: Keskin Merve 
Published: September 2022

AbstractBackgroundAge-related differences in Multiple Myeloma (MM) are studied in clinical and genomic context, however, transcriptome changes have not yet been determined. The aim of this study is to identify the genes that are expressed differently in young and old patient groups and to examine the relationship of these genes with biological pathways and the drugs that can be used.MethodsThe MMRF CoMMpass cohort RNA-Seq data (n=634) was used to analyze differentially expressed genes between young and old patients. GO term and KEGG gene-set enrichment analysis were conducted using R packages. Drug-gene interactions were detected using DGIdb.ResultsGlobally, 523 genes (366 upregulated, 157 downregulated) were differentially expressed (p < 0.05) in young patients. Totally 220 GO terms, mostly related to immune regulation pathways were enriched. “Cytokine-cytokine receptor interaction” gene-set was enriched in KEGG GSEA. Among the highest expression difference, genes involved in immune regulation (FCGR1A, FCER1G, TLR2), known proto-oncogenic genes (BCL2, FGR) and genes under investigation for association with various cancers (RGL4, MT-RNR1, ETS2, ENPP3, FUT7, NTNG2, PRAM1) were identified. Drugs associated with the pathways affected by these genes were identified.ConclusionsFurther investigation of differentially expressed genes in young patients may shed light on new treatment options.
Cancer cells communicate with macrophages to prevent T cell activation during development of cell cycle therapy resistance
Authors: Griffiths Jason I. , Cosgrove Patrick A. , Castaneda Eric Medina , Nath Aritro , Chen Jinfeng , Adler Frederick R. , Chang Jeffrey T. , Khan Qamar J. , Bild Andrea H. 
Published: September 2022

AbstractCancer cells evolve, acquire resistance to therapy and change their environment. One resistance mechanism involves altering communication with non-malignant cells in the tumor microenvironment (TME). By corrupting the signals for growth and survival, evolving cancer cells can engineer a pro-tumor TME. However, the specific interactions between malignant and non-malignant cells that predispose drug resistance and their changes during treatment remain widely unknown. Here we examine the composition, communication, and phenotypic diversity of tumor-associated cell populations in serial biopsies from early-stage ER+ breast cancers. These patients received either endocrine therapy (letrozole) alone or in combination with a CDK4/6 cell cycle inhibitor ribociclib, and were analyzed using single-cell RNA sequencing (scRNAseq). Our analyses reveal cancer cells from ribociclib resistant tumors stimulate macrophage differentiation towards an immune-suppressive phenotype through upregulation of a broad diversity of cytokines and growth factors. This shift in phenotype leads to reduced macrophage cell IL-15/-18 crosstalk with CD8+ T-cell via IL-2/15RA/18R receptors, resulting in diminished T-cell activation and recruitment. Thus, cancer communication promoting an immune-cold TME predispose tumors to develop CDK4/6 inhibitor resistance, and that the beneficial effects of cell cycle inhibitors through blocking cancer cell proliferation must be balanced against their known inhibitory effect on immune cell division and activation. An optimal treatment strategy will require coupling the prevention of cancer division with activation of an effective cytotoxic T-cell response.
When complex movement yields simple dispersal: behavioural heterogeneity, spatial spread and parasitism in groups of micro-wasps
Authors: Burte Victor , Cointe Melina , Perez Guy , Mailleret Ludovic , Calcagno Vincent 
Published: September 2022

AbstractUnderstanding how behavioural dynamics, inter-individual variability and individual interactions scale-up to shape the spatial spread and dispersal of animal populations is a major challenge in ecology. For biocontrol agents, such as the microscopic Trichogramma parasitic wasps, an understanding of movement strategies is also critical to predict pest-suppression performance in the field.We experimentally studied the spatial propagation of groups of parasitoids and their patterns of parasitism. We investigated whether population spread is density-dependent, how it is affected by the presence of hosts, and whether the spatial distribution of parasitism (dispersal kernel) can be predicted from the observed spread of individuals.Using a novel experimental device and high-throughput imaging techniques, we continuously tracked the spatial spread of groups of parasitoids over large temporal and spatial scales (eight hours; and six metres, ca. 12,000 body lengths). We could thus study how population density, the presence of hosts and their spatial distribution impacted the rate of population spread, the spatial distribution of individuals during population expansion, the overall rate of parasitism and the dispersal kernel (position of parasitism events).Higher population density accelerated population spread, but only transiently: the rate of spread reverted to low values after four hours, in a “tortoise-hare” effect. Interestingly, the presence of hosts suppressed this transiency and permitted a sustained high rate of population spread. Importantly, we found that population spread did not obey classical diffusion, but involved dynamical switches between resident and explorer movement modes. Population distribution was therefore not Gaussian, though surprisingly the distribution of parasitism (dispersal kernel) was.Even homogenous asexual groups of animals were shown to develop behavioral heterogeneties over a few hours. Explorer individuals were responsible for most parasitism and dispersal, and determined spatial spread and density-dependent dispersal. We showed that simple Gaussian dispersal did not emerge from simple diffusion, but rather from the interplay of several non-linearities at individual level. This suggests expectations from classical diffusion theory may not hold generally to active dispersers. These results highlight the need to take into account behaviour and inter-individual heterogeneity to understand population spread in animals.
Dual-Coil Transcranial Magnetic Stimulation Reveals Temporal Dynamics of Bilateral Corticomotor Excitability During Response Inhibition
Authors: Ratcliffe Chantelle E. , McAllister Craig J. , MacDonald Hayley J. 
Published: September 2022

AbstractA changing environment may suddenly require some parts of a multi-component response to be cancelled, while others continue. Such partial cancellation consistently produces a behavioural delay in the remaining component. This delay may reflect a three-step process of non-selective neural inhibition of all response components, functional uncoupling of components, and selective initiation of the remaining response. However, most neurophysiological evidence supporting this hypothesis has been recorded from muscles of a single hand, without direct comparison between response components. We aimed to simultaneously record - and therefore directly compare - corticomotor excitability (CME) in the cancelled and responding hands using a dual-coil technique not yet applied in this context. Human participants received transcranial magnetic stimulation to both primary motor cortices 1ms apart while performing a bimanual response inhibition task. Motor evoked potentials (MEPs) were recorded from both first dorsal interosseous (FDI) muscles as a measure of CME during partial cancellation. An equivalent reduction in CME was evident for both the responding and cancelled FDI muscles 175 ms after the stop cue during successful partial cancellation. The responding FDI subsequently exhibited an increase in CME above levels in the cancelled hand, leading to the unimanual response. This study reveals, for the first time, the temporal dynamics of CME for both response components simultaneously during a bimanual response inhibition task. Our results provide strong evidence that neural modulation during sudden partial cancellation can be viewed in light of the stop-change framework as a sequential non-selective stop, uncouple and switch, then selectively go process.
Differences in self-reported benefits for student-artist versus faculty experiences in a virtual artist-in-residence program
Authors: Cuevas Skylar , Liu Qi (Kathy) , Qian Helen , Joffe Max E. , Calvitti Karisa , Schladt Megan , Skaar Eric P. , Oliver Kendra H. 
Published: September 2022

ABSTRACTThe value of science communication in engaging the public has been well established. While many new programs bridge the arts and sciences, conducting comprehensive examination of exiting art-science programs can produce more efficient training and program development guidance for improving visual communications in the sciences. Here, we recruited a variety of scientists and artists to collaborate in creating visual science communication products over three summers. Using survey data, we performed qualitative and quantitative analyses to define sources for negative and positive experiences and outcomes from the Vanderbilt Institute for Infection, Immunology, and Inflammation (VI4) Artist-in-Residence (AiR) program. Further, we analyze responses from participants, student-artists and faculty, to specify areas for improvement and areas successful in producing a positive experience and outcome in an AiR program. We found that time and virtual delivery of the program could be modified to improve the experience. Additionally, we found that student participants had more positive responses about “learning something new” from the program than faculty members. However, the most surprising aspect of our analysis suggests that for both “way of thinking” and “science communication to the public or general audience,” there may be more significant beneficial gains for faculty compared to students. We conclude this analysis with suggestions to enhance the benefits and outcomes of an AiR program and ways to minimize the difficulties, such as communication and collaboration, faced by participants and program designers.
Revisiting the bad luck hypothesis: Cancer risk and aging are linked to replication-driven changes to the epigenome
Authors: Minteer Christopher J. , Thrush Kyra , Niimi Peter , Rozowsky Joel , Liu Jason , Frank Mor , McCabe Thomas , Hofstatter Erin , Rozenblit Mariya , Pusztai Lajos , Beckman Kenneth , Gerstein Mark , Levine Morgan E. 
Published: September 2022

AbstractAging is the leading risk factor for cancer. While it’s been proposed that the age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. Here, we show that both aging and cancer share a common epigenetic replication signature, which we modeled from DNA methylation data in extensively passaged immortalized human cellsin vitroand tested on clinical tissues. This epigenetic signature of replication – termed CellDRIFT – increased with age across multiple tissues, distinguished tumor from normal tissue, and was escalated in normal breast tissue from cancer patients. Additionally, within-person tissue differences were correlated with both predicted lifetime tissue-specific stem cell divisions and tissue-specific cancer risk. Overall, our findings suggest that age-related replication drives epigenetic changes in cells, pushing them towards a more tumorigenic state.One sentence summaryCellular replication leaves an epigenetic fingerprint that may partially underly the age-associated increase in cancer risk.
Age-related complexity of the resting state MEG signals: a multiscale entropy analysis
Authors: Makani Armin , Akhavan Amir , Shahbazi Farhad , Noruzi Mohammad , Zare Marzieh 
Published: September 2022

AbstractThe effects of aging on the brain can be studied by examining the changes in complexity of brain signals and fluid cognitive abilities. This paper is a relatively large-scale study in which the complexity of the resting-state MEG (rsMEG) signal was investigated in 602 healthy participants (298 females and 304 males) aged 18 to 87. In order to quantify the brain signals’ complexity, the multiscale entropy is applied. This study investigates the relationship between age and fluid intelligence with brain complexity and the variations of the complexity asymmetry between the left-right brain hemispheres across the life span. In the analysis of the brain signals, the gender difference was considered. The results showed that the complexity of rsMEG decreases across the lifespan. However, the complexity difference between the left-right brain hemispheres positively correlates with age. Furthermore, the results demonstrated that fluid intelligence and age have a positive correlation. Finally, the frequency analysis revealed a significant increase in the relative power of low and high gamma rhythms in females compared to males in all age groups.
Optogenetic Instruction of Cell Fate by Temporal Patterning of Mechanobiological Signals
Authors: Sampayo Rocío G. , Sakamoto Mason , Kumar Sanjay , Schaffer David V. 
Published: September 2022

AbstractDuring the intricate process by which cells give rise to tissues, embryonic and adult stem cells are exposed to diverse mechanical signals from the extracellular matrix (ECM) that influence their fate. Cells can sense these cues in part through dynamic generation of protrusions, modulated and controlled by cyclic activation of Rho GTPases. However, it remains unclear how extracellular mechanical signals regulate Rho GTPase activation dynamics and how such rapid, transient activation dynamics are integrated to yield long-term, irreversible cell fate decisions. Here, we report that ECM stiffness cues alter not only the magnitude but also the temporal frequency of RhoA and Cdc42 activation in adult neural stem cells (NSCs). Using optogenetics to control the frequency of RhoA and Cdc42 activation, we further demonstrate that these dynamics are functionally significant, where high- or low-frequency activation of RhoA and Cdc42 drives astrocytic or neuronal differentiation, respectively. In addition, high-frequency Rho GTPase activation induces sustained phosphorylation of the TGFβ pathway effector SMAD1, which in turn promotes astrocytic differentiation. By contrast, under low-frequency Rho GTPase stimulation, cells fail to accumulate SMAD1 phosphorylation and undergo neurogenesis. Our findings reveal the temporal patterning of Rho GTPase signaling and the resulting accumulation of a SMAD1 signal as a critical mechanism through which ECM stiffness cues regulate NSC fate.
Advanced Feedback Enhances Sensorimotor Adaptation
Authors: Wang Tianhe , Avraham Guy , Tsay Jonathan S. , Thummala Tanvi , Ivry Richard B. 
Published: September 2022

AbstractIt is widely recognized that sensorimotor learning is enhanced when the feedback is provided throughout the movement compared to when it is provided at the end of the movement. However, the source of this advantage is unclear: Continuous feedback is more ecological, dynamic, and available earlier than endpoint feedback. Here we assess the relative merits of these factors using a method that allows us to manipulate feedback timing independent of actual hand position. By manipulating the onset time of ‘endpoint’ feedback, we found that adaptation was modulated in a non-monotonic manner, with the peak of the function occurring in advance of the hand reaching the target. Moreover, at this optimal time, learning was of similar magnitude as that observed with continuous feedback. By varying movement duration, we demonstrate that this optimal time occurs at a relatively fixed time after movement onset, an interval we hypothesize corresponds to when the comparison of the sensory prediction and feedback generates the strongest error signal.
Differential modularity of the mammalian Engrailed 1 enhancer network directs eccrine sweat gland development
Authors: Aldea Daniel , Kokalari Blerina , Atsuta Yuji , Dingwall Heather L. , Zheng Ying , Nace Arben , Cotsarelis George , Kamberov Yana G. 
Published: September 2022

SummaryEnhancers are context-specific regulators of expression that drive biological complexity and variation through the redeployment of conserved genes. An example of this is the enhancer-mediated control of the transcription of Engrailed 1 (EN1), a pleiotropic gene whose expression is required for the specification of eccrine sweat glands in mammals. We have previously identified an enhancer, ECE18 that has been highly and repeatedly derived on the human lineage to potentiate ectodermal EN1 and induce our species’ uniquely high eccrine gland density. Intriguingly, ECE18 quantitative activity is negligible outside of primates and ECE18 is not required for En1 regulation and eccrine gland specification in mice, raising the possibility that distinct enhancers have evolved to modulate the same trait. Here we report the identification of the ECE20 enhancer and show it has conserved functionality in mouse and human developing skin ectoderm. Unlike ECE18, knock-out of ECE20 in mice reduces ectodermal En1 and eccrine gland number. Notably, we find ECE20, but not ECE18, is also required for En1 expression in the embryonic mouse brain, demonstrating that ECE20 is a pleiotropic En1 enhancer. Finally, that ECE18 deletion does not potentiate the eccrine phenotype of ECE20 knockout mice supports the secondary incorporation of ECE18 into the regulation of this trait in primates. Our findings reveal that the mammalian En1 regulatory machinery diversified to incorporate both shared and lineage-restricted enhancers to regulate the same phenotype, and also have implications for understanding the forces that shape the robustness and evolvability of developmental traits.
Dictys: dynamic gene regulatory network dissects developmental continuum with single-cell multi-omics
Authors: Wang Lingfei , Trasanidis Nikolaos , Wu Ting , Dong Guanlan , Hu Michael , Bauer Daniel E. , Pinello Luca 
Published: September 2022

AbstractGene regulatory networks (GRNs) are key determinants of cell function and identity and are dynamically rewired during development and disease. Despite decades of advancement, challenges remain in GRN inference: dynamic rewiring, causal inference, feedback-loop modeling, and context specificity. To address them, we develop Dictys, a dynamic GRN inference and analysis method which leverages multi-omic single-cell assays of chromatin accessibility and gene expression, context specific transcription factor (TF) footprinting, stochastic process network, and efficient probabilistic modeling of scRNA-seq read counts. Dictys improves GRN reconstruction accuracy and reproducibility and enables the inference and comparative analysis of context specific and dynamic GRNs across developmental contexts. Dictys’ network analyses recover unique insights in human blood and mouse skin development with cell-type specific and dynamic GRNs. Its dynamic network visualizations enable time-resolved discovery and investigation of developmental driver TFs and their regulated targets. Dictys is available as a free, open source, and user-friendly Python package.
Genomic architecture of migration timing in a long-distance migratory songbird
Authors: de Greef Evelien , Suh Alexander , Thorstensen Matt J. , Delmore Kira E. , Fraser Kevin C. 
Published: September 2022

AbstractThe impact of climate change on spring phenology poses risks to migratory birds, as migration timing is controlled predominantly by endogenous mechanisms. Despite numerous studies on internal cues controlling migration, the underlying genetic basis of migration timing remains largely unknown. We investigated the genetic architecture of migration timing in a long-distance migratory songbird (purple martin, Progne subis subis) by integrating genomic data with an extensive dataset of direct migratory tracks. Our findings show migration has a predictable genetic basis in martins and maps to a region on chromosome 1. This region contains genes that could facilitate nocturnal flights and act as epigenetic modifiers. Additionally, we found that genomic variance explained a higher proportion of historic than recent environmental spring phenology data, which may suggest a reduction in the adaptive potential of migratory behavior in contemporary populations. Overall, these results advance our understanding of the genomic underpinnings of migration timing and could provide context for conservation action.