Biology subjects

Huang, J.

Publications and source records attributed to Huang, J..

At least 415 records · Page 23Linked to original sources

bioRxiv2022

Durable alveolar engraftment of PSC-derived lung epithelial cells into immunocompetent mice

Durable reconstitution of the injured distal lung epithelium with pluripotent stem cell (PSC) derivatives, if realized, would represent a promising potential therapy for diseases that result from alveolar damage. Here we differentiate murine PSCs in vitro into self-renewing lung epithelial progenitors able to engraft into the injured distal lung epithelium of immunocompetent, syngeneic mouse recipients. Emulating the roadmap of the developing embryo, we generate transplantable PSC-derived Nkx2-1+/Sox9+ lung epithelial progenitors that are highly similar to cultured primary embryonic distal lung bud tip progenitors. These cells display a stable phenotype after frozen archiving or extensive expansion in culture, providing a nearly inexhaustible source of cells that can be engrafted into syngeneic injured mouse lungs without the need for immunosuppression. After transplantation PSC-derived tip-like progenitors downregulate Sox9 and mature in the distal lung, upregulating alveolar type 2 cell markers or assuming the flat morphology and molecular phenotype of terminally differentiated alveolar type 1 cells. After months in vivo, donor-derived cells retain their alveolar epithelial type 2-like and type 1-like phenotypes, as characterized by single cell RNA sequencing, ultrastructural analyses, in vivo histologic profiling, and ex vivo organoid assays that demonstrate continued capacity of the engrafted cells to proliferate and differentiate. These results indicate durable reconstitution of the distal lungs facultative progenitor and differentiated epithelial cell compartments in vivo with PSC-derived cells, thus establishing a novel model for pulmonary cell therapy which can be utilized to better understand the mechanisms and utility of engraftment prior to future clinical studies.

cell biology↗

bioRxiv2022

SiPLATZ12 transcript factor regulates multiple yield traits and salt tolerance in foxtail millet (Setaria italica)

Grain yield and salt tolerance are critical for crop production. However, the genetic and biochemical basis underlying the trade-off of these characters remain poorly described in crops. We show here that SiPLATZ12 transcription factor positively regulates multiple elite yield traits at the expense of salt tolerance in foxtail millet. SiPLATZ12 overexpression increases seed size, panicle length, and stem diameter, while reduces plant height and salt tolerance of foxtail millet. A 9-bp insertion in the SiPLATZ12 promoter has significant effects on the different expression of SiPLATZ12, multiple yield traits, and salt tolerance between foxtail millet and its wild ancestor, green foxtail. Moreover, SiPLATZ12 upregulates the expression of genes involved in seed development, but repressing the transcription of most NHX, SOS, and CBL genes to regulate Na+, K+ and pH homeostasis. Therefore, our results uncover a domesticated site that could be used to improve grain yield and salt tolerance in foxtail millet.

molecular biology↗

bioRxiv2022

A Novel Selective ERK1/2 Inhibitor, Laxiflorin B, Targets EGFR Mutation Subtypes in Non-small-cell Lung Cancer

Extracellular regulated protein kinases 1/2 (ERK1/2) are key members of multiple signaling pathways including the ErbB axis. ERK1/2 ectopic activation is responsible for various types of cancer, especially drug resistance to inhibitors of RTK, RAF and MEK, but specific ERK1/2 inhibitors are scarce. In this study, we identified a potential novel ERK covalent inhibitor, Laxiflorin B, a herbal compound with anticancer activity. However, Laxiflorin B is present at low levels in herbs; therefore, we adopted a semi-synthetic process for the efficient production of Laxiflorin B to improve the yield. Laxiflorin B induced mitochondria-mediated apoptosis via BAD activation in non-small-cell lung cancer (NSCLC) cells, especially in EGFR mutant subtypes. Transcriptomic analysis suggested that Laxiflorin B inhibits amphiregulin (AREG) and epiregulin (EREG) expression through ERK inhibition, and suppressed the activation of their receptors, ErbBs, via a positive feedback loop. More importantly, mass spectrometry combined with computer simulation analysis revealed that Laxiflorin B binds covalently to Cys-183 in the ATP-binding pocket of ERK1 through D-ring, and Cys-178 of ERK1 though non-inhibitory binding of A-ring, respectively. Laxiflorin B also exhibited strong tumor suppressive effects with low toxicity in a NSCLC tumor xenograft model in nude mice, and AREG and EREG were identified as biomarkers of Laxiflorin B efficacy. Finally, Laxiflorin B-4, a C-6 modification of Laxiflorin B, exhibited higher affinity for ERK1/2 and stronger tumor suppression. These findings provide a new approach to tumor inhibition using natural anticancer compounds.

pharmacology and toxicology↗

bioRxiv2022

Determination of expression profiles for Drosophila ovarian Follicle Stem Cells (FSCs) using single-cell RNA sequencing

Drosophila ovarian Follicle Stem Cells (FSC) present an excellent paradigm for understanding how a community of active stem cells maintained by population asymmetry is regulated. Here we describe single-cell RNA sequencing studies of a pre-sorted population of cells that include FSCs and the neighboring cell types, Escort Cells (ECs) and Follicle Cells (FCs), which they support. Cell-type assignment relies on anterior-posterior (AP) location within the germarium. We clarify the previously determined location of FSCs and use spatially targeted lineage studies as further confirmation. The scRNA profiles among four clusters are consistent with an AP progression from anterior ECs through posterior ECs and then FSCs, to early FCs. Several genes with graded profiles from ECs to FCs are highlighted as candidate effectors of the inverse gradients of the two principal signaling pathways, Wnt and JAK-STAT, that guide FSC differentiation and division.

developmental biology↗

bioRxiv2022

Spatial Atlas of the Mouse Central Nervous System at Molecular Resolution

Spatially charting molecular cell types at single-cell resolution across the three-dimensional (3D) volume of the brain is critical for illustrating the molecular basis of the brain anatomy and functions. Single-cell RNA sequencing (scRNA-seq) has profiled molecular cell types in the mouse brain1, 2, but cannot capture their spatial organization. Here, we employed an in situ sequencing technique, STARmap PLUS3, 4, to map more than one million high-quality cells across the whole adult mouse brain and the spinal cord, profiling 1,022 genes at subcellular resolution with a voxel size of 194 X 194 X 345 nm in 3D. We developed computational pipelines to segment, cluster, and annotate 231 molecularly defined cell types and 64 tissue regions with single-cell resolution. To create a transcriptome-wide spatial atlas, we further integrated the STARmap PLUS measurements with a published scRNA-seq atlas1, imputing 11,844 genes at the single-cell level. Finally, we engineered a highly expressed RNA barcoding system to delineate the tropism of a brain-wide transgene delivery tool, AAV-PHP.eB5, 6, revealing its single-cell resolved transduction efficiency across the molecular cell types and tissue regions of the whole mouse brain. Together, our datasets and annotations provide a comprehensive, high-resolution single-cell resource that integrates a spatial molecular atlas, cell taxonomy, brain anatomy, and genetic manipulation accessibility of the mammalian central nervous system (CNS).

neuroscience↗

bioRxiv2022

Efficacy of Parainfluenza Virus 5 (PIV5)-vectored Intranasal COVID-19 Vaccine as a Single Dose Vaccine and as a Booster against SARS-CoV-2 Variants

Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has greatly reduced coronavirus disease 2019 (COVID-19)-related deaths and hospitalizations, but waning immunity and the emergence of variants capable of immune escape indicate the need for novel SARS-CoV-2 vaccines. An intranasal parainfluenza virus 5 (PIV5)-vectored COVID-19 vaccine CVXGA1 has been proven efficacious in animal models and blocks contact transmission of SARS-CoV-2 in ferrets. CVXGA1 vaccine is currently in human clinical trials in the United States. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccines expressing additional antigen SARS-CoV-2 nucleoprotein (N) or SARS-CoV-2 variant spike (S) proteins of beta, delta, gamma, and omicron variants against homologous and heterologous challenges in hamsters. A single intranasal dose of CVXGA1 induces neutralizing antibodies against SARS-CoV-2 WA1 (ancestral), delta variant, and omicron variant and protects against both homologous and heterologous virus challenges. Compared to mRNA COVID-19 vaccine, neutralizing antibody titers induced by CVXGA1 were well-maintained over time. When administered as a boost following two doses of a mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive neutralizing antibodies compared to three doses of a mRNA vaccine. In addition to the S protein, the N protein provides added protection as assessed by the highest body weight gain post-challenge infection. Our data indicates that PIV5-vectored COVID-19 vaccines, such as CVXGA1, can serve as booster vaccines against emerging variants. ImportanceWith emerging new variants of concern (VOC), SARS-CoV 2 continues to be a major threat to human health. Approved COVID-19 vaccines have been less effective against these emerging VOCs. This work demonstrates the protective efficacy, and strong boosting effect, of a new intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters.

microbiology↗

bioRxiv2022

Neural mechanisms underlying distractor suppression guided by spatial cues

A growing body of research demonstrates that distracting inputs can be proactively suppressed via spatial cues, nonspatial cues, or experience, which are governed by more than one top-down mechanism of attention. However, how the neural mechanisms underlying spatial distractor cues guide proactive suppression of distracting inputs remains unresolved. Here, we recorded electroencephalography signals from 110 subjects in three experiments to identify the role of alpha activity in proactive distractor suppression induced by spatial cues and its influence on subsequent distractor inhibition. Behaviorally, we found novel spatial changes in spatial distractor cues: cueing distractors far away from the target improves search performance for the target while cueing distractors close to the target hampers performance. Crucially, we found dynamic characteristics of spatial representation for distractor suppression during anticipation. This result was further verified by alpha power increased relatively contralateral to the cued distractor. At both the between- and within-subjects levels, we found that these activities further predicted the decrement of subsequent PD component, which was indicative of reduced distractor interference. Moreover, anticipatory alpha activity and its link with subsequent PD component were specific to the high predictive validity of distractor cue. Together, these results provide evidence for the existence of proactive suppression mechanisms of spatial distractors, support the role of alpha activity as gating by proactive suppression and reveal the underlying neural mechanisms by which cueing the spatial distractor may contribute to reduced distractor interference. (235). SignificanceIn space, the attention-capturing distractors are obstacles to successfully identifying targets. How to sidestep task-irrelevant distractors that stand between the target and our focus in advance is essential but still unclear. This research investigated how dynamic spatial cues can help us proactively eliminate attention-capturing distractors. Using three cue-distractor tasks that manipulate the predictive validity of distractor occurrence, we provide a series of evidence for the presence of alpha power activity related to distractor anticipation. Critically, this was the first study linking cue-elicited alpha power and distractor-elicited PD, indicating that spatial modulation of alpha power may reduce distractor interference. These findings delineate the neural mechanisms of proactive suppression for spatial distractors. (109)

neuroscience↗

bioRxiv2022

MADET: A Manually Curated Knowledgebase for Microbiomic Effects on Efficacy and Toxicity of Anticancer Treatments

A plethora of studies have reported the associations between microbiota and multiple diseases, leading to at least four databases to demonstrate microbiota-disease associations, i.e., gutMDisorder, mBodyMap, GMrepo and Amadis. Moreover, gut microbiota also mediates drug efficacy and toxicity, whereas a comprehensive database to elucidate the microbiota-drug associations is lacking. Here we report an open-access knowledgebase, MADET (Microbiomics of Anticancer Drug Efficacy and Toxicity), which harbors 453 manually annotated microbiota-drug associations from 24 papers. MADET provides user-friendly functions allowing users to freely browse, search, and download the data conveniently from the database. Users can customize their search filters in MADET using different types of keywords, including bacterial name (e.g., Akkermansia muciniphila), anticancer treatment (e.g., anti-PD-1 therapy) or cancer type (e.g., lung cancer) with different types of experimental evidence of microbiota-drug association and causation. We have also enabled user submission to further enrich the data document in MADET. The MADET database is freely available at https://www.madet.info. We anticipate that MADET will serve as a useful resource for a better understanding of the microbiota-drug associations and facilitate the future development of novel biomarkers and live biotherapeutic products for anticancer therapies.

microbiology↗

bioRxiv2022

Complexity of enhancer networks predicts cell identity and disease genes revealed by single-cell multi-omics analysis

Many enhancers exist as clusters in the genome and control cell identity and disease genes; however, the underlying mechanism remains largely unknown. Here, we introduce an algorithm, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression profiles. Enhancer network is a gene regulation model we proposed that not only delineates the mapping between enhancers and target genes, but also quantifies the underlying regulatory relationships among enhancers. The complexity of enhancer networks is assessed by two metrics: the number of enhancers and the frequency of predicted enhancer interactions (PEIs) based on chromatin co-accessibility. We apply eNet algorithm to a human blood dataset and find cell identity and disease genes tend to be regulated by complex enhancer networks. The network hub enhancers (enhancers with frequent PEIs) are the most functionally important in enhancer networks. Compared with super-enhancers, enhancer networks show better performance in predicting cell identity and disease genes. The establishment of enhancer networks drives gene expression during lineage commitment. Applying eNet in various datasets in human or mouse tissues across different single-cell platforms, we demonstrate eNet is robust and widely applicable. Thus, we propose a model of enhancer networks containing three modes: Simple, Multiple and Complex, which are distinguished by their complexity in regulating gene expression. Taken together, our work provides an unsupervised approach to simultaneously identify key cell identity and disease genes and explore the underlying regulatory relationships among enhancers in single cells, without requiring the cell type identity in advance. HighlightsO_LIeNet, a computational method to build enhancer network based on scATAC-seq and scRNA-seq data C_LIO_LICell identity and disease genes tend to be regulated by complex enhancer networks, where network hub enhancers are functionally important C_LIO_LIEnhancer network outperforms the existing models in predicting cell identity and disease genes, such as super-enhancer and enhancer cluster C_LIO_LIWe propose a model of enhancer networks in gene regulation containing three modes: Simple, Multiple and Complex C_LI

bioinformatics↗

bioRxiv2022

Highly efficient healing of critical sized articular cartilage defect in situ using a chemically nucleoside-modified mRNA-enhanced cell therapy

Critical sized cartilage defects heal poorly and MSC-based therapies holds promise functional cartilage regeneration either used alone or in combination with growth factors. However, Recombinant protein growth factors were proven to have minimal benefits while to have adverse side effects and high cost. Nonviral mRNA delivery provides a promising, alternative approach to delivering therapeutic proteins within defect lesion for an extended period of time. Despite successful therapeutic outcome in bone and other vascularized tissues, the therapeutic application of mRNA in poorly vascularized tissues such as cartilage is still facing many challenges and rarely studied. We report here using chemically modified messenger RNA encoding TGF-{beta}3(TGF-{beta}3 cmRNA) to enhance the therapeutic efficacy of BMSCs to efficient repair of cartilage defect. Local administration of TGF-{beta}3 cmRNA enhanced BMSCs therapy restored critical-sized cartilage defects in situ in a rat model within 6 weeks with structural and molecular markers similar to its nature counterparts. In addition, the development of osteoarthritis caused by cartilage damage was prevented by this mRNA-enhanced BMSCs therapy evidenced by minimal late-stage OA pharmacological presentations. This novel mRNA enhanced-MSC technology extend the development of new therapeutic approaches for treating functional cartilage repair.

synthetic biology↗

bioRxiv2022

Temporal PHATE: A multi-view manifold learningmethod for brain state trajectories

1The complexity and intelligence of the brain give the illusion that measurements of brain activity will have intractably high dimensionality, rife with collection and biological noise. Nonlinear dimensionality reduction methods like UMAP and t-SNE have proven useful for high-throughput biomedical data. However, they have not been used extensively for brain imaging data such as from functional magnetic resonance imaging (fMRI), a noninvasive, secondary measure of neural activity over time containing redundancy and co-modulation from neural population activity. Here we introduce a nonlinear manifold learning algorithm for timeseries data like fMRI, called temporal potential of heat-diffusion for affinity-based transition embedding (T-PHATE). In addition to recovering a lower intrinsic dimensionality from timeseries data, T-PHATE exploits autocorrelative structure within the data to faithfully denoise dynamic signals and learn activation manifolds. We empirically validate T-PHATE on three human fMRI datasets, showing that T-PHATE significantly improves data visualization, classification, and segmentation of the data relative to several other state-of-the-art dimensionality reduction benchmarks.These notable improvements suggest many potential applications of T-PHATE to other high-dimensional datasets of temporally-diffuse processes.

neuroscience↗

bioRxiv2022

Covalent Docking and Molecular Dynamics Simulations Reveal the Specificity-Shifting Mutations Ala237Arg and Ala237Lys in TEM Beta-Lactamase

The rate of modern drug discovery using experimental screening methods still lags behind the rate at which pathogens mutate, underscoring the need for fast and accurate predictive simulations of protein evolution. Multidrug-resistant bacteria evade our defenses by expressing a series of proteins, the most famous of which is the 29-kilodalton enzyme, TEM {beta}-lactamase. Considering these challenges, we applied a covalent docking heuristic to measure the effects of all possible alanine 237 substitutions in TEM due to this codons importance for catalysis and effects on the binding affinities of commercially-available {beta}-lactam compounds. In addition to the usual mutations that reduce substrate binding due to steric hindrance, we identified two distinctive specificity-shifting TEM mutations, Ala237Arg and Ala237Lys, and their respective modes of action. Notably, we discovered and verified through minimum inhibitory concentration assays that, while these mutations and their bulkier side chains lead to steric clashes that curtail ampicillin binding, these same groups foster salt bridges with the negatively-charged side-chain of the cephalosporin cefixime, widely used in the clinic to treat multi-resistant bacterial infections. To measure the stability of these unexpected interactions, we used molecular dynamics simulations and found the binding modes to be stable despite the application of biasing forces. Finally, we found that both TEM mutants also bind strongly to other drugs containing negatively-charged R-groups, such as carumonam and ceftibuten. As with cefixime, this increased binding affinity stems from a salt bridge between the compounds negative moieties and the positively-charged side chain of the arginine or lysine, suggesting a shared mechanism. In addition to reaffirming the power of using simulations as molecular microscopes, our results can guide the rational design of next-generation {beta}-lactam antibiotics and bring the community closer to retaking the lead against the recurrent threat of multidrugresistant pathogens. Author SummaryResistance to antibiotics is a major public health threat. Microorganisms are able to resist commonly used drugs by evolving and expressing enzymes capable of neutralizing antibiotics. Understanding the relationships between structural elements in these enzymes and their drug-clearing functions can lead to crucial insights for the discovery of next-generation antibiotics. In this study, we have used cutting-edge computational modeling methods to predict the effects of all naturally-occurring variations of an important region of the binding site of TEM {beta}-lactamase, one of the major resistance-granting enzymes in bacteria. In an effort to identify patterns that could be useful for drug discovery, our simulations sought to understand how chemical changes in the tested region can affect resistance against a collection of over 90 widely used antibiotics. Crucially, through our simulations, we have identified a pathway for bacterial resistance against {beta}-lactam antibiotics containing a negatively-charged moiety. We have also elucidated the mechanism behind the gain of resistance, which involves strong interactions between the drugs negative moieties and the positively-charged chemical shifts resulting from the mutation. Finally, we validated our predictions against fitness experiments for two commonly used antibiotics, which qualitatively corroborated our most important findings.

bioinformatics↗

bioRxiv2022

Prenatal development of neonatal vocalizations

Human and non-human primates produce rhythmical sounds as soon as they are born. These early vocalizations are important for soliciting the attention of caregivers. How they develop, remains a mystery. The orofacial movements necessary for producing these vocalizations have distinct spatiotemporal signatures. Therefore, their development could potentially be tracked over the course of prenatal life. We densely and longitudinally sampled fetal head and orofacial movements in marmoset monkeys using ultrasound imaging. We show that orofacial movements necessary for producing rhythmical vocalizations differentiate from a larger movement pattern that includes the entire head. We also show that signature features of marmoset infant contact calls emerge prenatally as a distinct pattern of orofacial movements. Our results establish that aspects of the sensorimotor development necessary for vocalizing occur prenatally, even before the production of sound.

neuroscience↗

bioRxiv2022

Self-avoidance alone does not explain the function of Dscam1 in mushroom body axonal wiring

Alternative splicing of Drosophila Dscam1 into 38,016 isoforms provides neurons with a unique molecular code for self-recognition and self-avoidance. A canonical model suggests that homophilic binding of identical Dscam1 isoforms on sister branches of mushroom body (MB) axons supports segregation with high fidelity, even when only a single isoform is expressed. Here we generated a series of mutant flies with a single exon 4, 6, or 9 variant, encoding 1,584, 396, or 576 potential isoforms, respectively. Surprisingly, most of the mutants in the latter two groups exhibited obvious defects in the growth, branching, and segregation of MB axonal sister branches. This demonstrates that repertoires of 396 and 576 Dscam1 isoforms were not sufficient for normal patterning of axonal branches. Moreover, reducing Dscam1 levels largely reversed the defects caused by reduced isoform diversity, suggesting a functional link between Dscam1 expression levels and isoform diversity. Taken together, these results indicate that canonical self-avoidance alone does not explain the function of Dscam1 in MB axonal wiring.

neuroscience↗

bioRxiv2022

Cis mutagenesis in vivo reveals extensive noncanonical functions of Dscam1 isoforms in neuronal wiring

Drosophila Dscam1 encodes ten thousand of cell recognition molecules via alternative splicing, which is required for nervous function. However, the underlying mechanism has not fully understood. Here we revealed extensive noncanonical functions of Dscam1 isoform diversity in neuronal wiring. We generated a series of allelic cis mutations in Dscam1, encoding normal number of isoforms albeit with altered isoform composition. Despite normal dendritic self-avoidance and self/non-self discrimination in da neurons, which is consistent with canonical self-avoidance model, these mutants exhibited strikingly distinct spectra of phenotypic defects in three classes of neurons: up to [~]60% defects in mushroom bodies, a significantly increased branching and growth in da neurons, and mild axonal branching defects in mechanosensory neurons. These data suggest that proper Dscam1 isoform composition is required for axon and dendrite growth in diverse neurons. This unprecedented splicing-tuned regulation unlocks new insights into the molecular mechanisms that Dscam1 isoform diversity is engaged in.

neuroscience↗

bioRxiv2022

Comparative analysis about the structure of complete chloroplast genomes in genus Mangifera and accuracy verification about phylogenetic analysis based on gene ycf2 in genus level

Mango is an evergreen plant belonging to the genus Mangifera of the Anacardiaceae family. Genus Mangifera has 69 species of Mangifera around the world that are mainly distributed in tropical and subtropical countries, including India, Indonesia, the Malay Peninsula, Thailand, and South China. It is a popular tropical fruit known as the "King of Tropical Fruits". However, the study of the structure information of the complete chloroplast genome of Mangifera was microscopic, there was no report about the comparison of SSR, Ka/Ks, codons analysis and RNA editing, so in this study, we sequenced the 6 Mangifera samples and used three different ways to analyze the relationship of 6 species of Mangifera. Then we got some results, through the RNA editing and Ka/Ks calculating, we found the species could be divided into two groups, and the difference between the two groups was protein-coding gene ccsA. Moreover, all RNA editing occurred conversion of C to T and the gene ndhB had the most RNA editing sites in all species. In Ka/Ks analysis, the gene atpB, cemA, clpP, ndhD, petD, petB and ycf15 would be suffered from the positive selection after divergence. We also find the IR regions in these seven samples were very conservation through IR contraction and expansion and Sequence Divergence Analysis. Finally, we tried to confirm the relationship between 7 samples of Mangifera in Angiosperms in 3 different ways. Then we got that ML210 and MP090 had a closer relationship than others, MS796 had a closer relationship with ML210 and MP090 than others. At the same time, the method of phylogenetic analysis based on the gene ycf2 was not more accurate at the genus level than the method based on complete cp genome and proteincoding genes.

molecular biology↗

bioRxiv2022

PeerPub: A device for concurrent operant oral self-administration by multiple rats

The social environment has long been recognized to play an important role in substance abuse disorders (SUD). Operant conditioning is the most widely used rodent model of SUD. However, most operant chambers do not accommodate more than one rat at a time. Here, we introduce PeerPub - a novel social operant chamber. PeerPub uses a touch sensor to record the number of licks on drinking spouts. It then delivers a drop of solution with a fixed volume as the reward to the tip of the spout when the number of licks meets the requirement of a reinforcement schedule. A radio-frequency identification (RFID) chip implanted on top of each rats skull tracks the identity of the rat. The system is controlled by a Raspberry Pi computer. We tested PeerPub using male Wistar Kyoto rats in daily one-hour sessions where supersac, a solution containing glucose and saccharin, was delivered under a fixed ratio 5 schedule. We found that male rats consumed more supersac in group housing rather than in isolated conditions. These data demonstrated the utility of PeerPub in modeling the interaction between motivated behavior and social context. We anticipate devices like PeerPub will help demonstrate the role of the social environment in SUD phenotypes. The design of PeerPub is available at http://github.com/nijie321/PeerPub

animal behavior and cognition↗

bioRxiv2022

Mutational footprint of platinum chemotherapy in a secondary thyroid cancer

Although papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor with a generally excellent prognosis, a patient developed a clinically aggressive PTC eleven years after receiving platinum chemotherapy for ovarian endometrioid adenocarcinoma. Germline and somatic analyses of multi-temporal and multi-regional molecular profiles indicated that ovarian and thyroid tumors did not share common genetic alterations. PTC tumors had driver events associated with aggressive PTC behavior, an RBPMS-NTRK3 fusion and a TERT promoter mutation. Spatial and temporal genomic heterogeneity analysis indicated a close link between anatomical locations and molecular patterns of PTC. Mutational signature analyses demonstrated a molecular footprint of platinum exposure, and that aggressive molecular drivers of PTC were linked to prior platinum-associated mutagenesis. This case provides a direct association between platinum chemotherapy exposure and secondary solid tumor evolution, in specific aggressive thyroid carcinoma, and suggests that uniform clinical assessments for secondary PTC after platinum chemotherapy may warrant further evaluation.

genomics↗