Monosynaptic targets of utricular afferents in the larval zebrafish

The larval zebrafish acquires a repertoire of vestibular-driven behaviors that aid survival early in development. These behaviors rely mostly on the utricular otolith, which senses inertial (tilt and translational) head movements. We previously characterized the known central brainstem targets of utricular afferents using serial-section electron microscopy of a larval zebrafish brain. Here we describe the rest of the central targets of utricular afferents, focusing on the neurons whose identities are less certain in our dataset. We find that central neurons with commissural projections have a wide range of predicted directional tuning, just as in other vertebrates. In addition, somata of central neurons with inferred responses to contralateral tilt are located more laterally than those with inferred responses to ipsilateral tilt. Many dorsally located central utricular neurons are unipolar, with an ipsilateral dendritic ramification and commissurally projecting axon emerging from a shared process. Ventrally located central utricular neurons tended to receive otolith afferent synaptic input at a shorter distance from the soma than in dorsally located neurons. Finally, we observe an unexpected synaptic target of utricular afferents: afferents from the medial (horizontal) semicircular canal. Collectively, these data provide a better picture of the gravity-sensing circuit. Furthermore, we suggest that vestibular circuits important for survival behaviors develop first, followed by the circuits that refine these behaviors

Monosynaptic targets of utricular afferents in the larval zebrafish

The larval zebrafish acquires a repertoire of vestibular-driven behaviors that aid survival early in development. These behaviors rely mostly on the utricular otolith, which senses inertial (tilt and translational) head movements. We previously characterized the known central brainstem targets of utricular afferents using serial-section electron microscopy of a larval zebrafish brain. Here we describe the rest of the central targets of utricular afferents, focusing on the neurons whose identities are less certain in our dataset. We find that central neurons with commissural projections have a wide range of predicted directional tuning, just as in other vertebrates. In addition, somata of central neurons with inferred responses to contralateral tilt are located more laterally than those with inferred responses to ipsilateral tilt. Many dorsally located central utricular neurons are unipolar, with an ipsilateral dendritic ramification and commissurally projecting axon emerging from a shared process. Ventrally located central utricular neurons tended to receive otolith afferent synaptic input at a shorter distance from the soma than in dorsally located neurons. Finally, we observe an unexpected synaptic target of utricular afferents: afferents from the medial (horizontal) semicircular canal. Collectively, these data provide a better picture of the gravity-sensing circuit. Furthermore, we suggest that vestibular circuits important for survival behaviors develop first, followed by the circuits that refine these behaviors

SIDE: Self-supervised Intermediate Domain Exploration for Source-free Domain Adaptation

Domain adaptation aims to alleviate the domain shift when transferring the knowledge learned from the source domain to the target domain. Due to privacy issues, source-free domain adaptation (SFDA), where source data is unavailable during adaptation, has recently become very demanding yet challenging. Existing SFDA methods focus on either self-supervised learning of target samples or reconstruction of virtual source data. The former overlooks the transferable knowledge in the source model, whilst the latter introduces even more uncertainty. To address the above issues, this paper proposes self-supervised intermediate domain exploration (SIDE) that effectively bridges the domain gap with an intermediate domain, where samples are cyclically filtered out in a self-supervised fashion. First, we propose cycle intermediate domain filtering (CIDF) to cyclically select intermediate samples with similar distributions over source and target domains. Second, with the aid of those intermediate samples, an inter-domain gap transition (IDGT) module is developed to mitigate possible distribution mismatches between the source and target data. Finally, we introduce cross-view consistency learning (CVCL) to maintain the intrinsic class discriminability whilst adapting the model to the target domain. Extensive experiments on three popular benchmarks, i.e. Office-31, Office-Home and VisDA-C, show that our proposed SIDE achieves competitive performance against state-of-the-art methods.Comment: code at https://github.com/se111/SID

Engineering Yeast for Production of Benzophenones and Xanthones as Precursors of Polycyclic Polyprenylated Acylphloroglucinols

Polycyclic polyprenylated acylphloroglucinols (PPAPs) exhibit a broad range of biological activities, such as antidepressant, antibacterial, antiviral and antitumor properties. The content of PPAPs in the producing plants is often quite low, and their complex structures make total chemical synthesis difficult and economically impractical. Progresses in synthetic biology provide an alternative approach for the production of these valuable compounds. Here we present our results on reconstruction of the biosynthetic pathways of PPAP precursors in yeast. Based on our previous works on the biosynthesis of PPAPs, genes involved in the formation of benzophenones and xanthones from Hypericum sp. and other organisms were expressed in yeast either episomally or by integration into the genome. The production of the expected products reached around 0.5 mg/l, which is high enough to be the substrate for enzymes of subsequent biosynthetic steps. The yeast strains will be further engineered by introducing various prenyltransferase enzymes to reconstruct the full biosynthetic pathways of PPAPs

Refining orthologue groups at the transcript level

<p>Abstract</p> <p>Background</p> <p>Orthologues are genes in different species that are related through divergent evolution from a common ancestor and are expected to have similar functions. Many databases have been created to describe orthologous genes based on existing sequence data. However, alternative splicing (in eukaryotes) is usually disregarded in the determination of orthologue groups and the functional consequences of alternative splicing have not been considered. Most multi-exon genes can encode multiple protein isoforms which often have different functions and can be disease-related. Extending the definition of orthologue groups to take account of alternate splicing and the functional differences it causes requires further examination.</p> <p>Results</p> <p>A subset of the orthologous gene groups between human and mouse was selected from the InParanoid database for this study. Each orthologue group was divided into sub-clusters, at the transcript level, using a method based on the sequence similarity of the isoforms. Transcript based sub-clusters were verified by functional signatures of the cluster members in the InterPro database. Functional similarity was higher within than between transcript-based sub-clusters of a defined orthologous group. In certain cases, cancer-related isoforms of a gene could be distinguished from other isoforms of the gene. Predictions of intrinsic disorder in protein regions were also correlated with the isoform sub-clusters within an orthologue group.</p> <p>Conclusions</p> <p>Sub-clustering of orthologue groups at the transcript level is an important step to more accurately define functionally equivalent orthologue groups. This work appears to be the first effort to refine orthologous groupings of genes based on the consequences of alternative splicing on function. Further investigation and refinement of the methodology to classify and verify isoform sub-clusters is needed, particularly to extend the technique to more distantly related species.</p

Refining orthologue groups at the transcript level

<p>Abstract</p> <p>Background</p> <p>Orthologues are genes in different species that are related through divergent evolution from a common ancestor and are expected to have similar functions. Many databases have been created to describe orthologous genes based on existing sequence data. However, alternative splicing (in eukaryotes) is usually disregarded in the determination of orthologue groups and the functional consequences of alternative splicing have not been considered. Most multi-exon genes can encode multiple protein isoforms which often have different functions and can be disease-related. Extending the definition of orthologue groups to take account of alternate splicing and the functional differences it causes requires further examination.</p> <p>Results</p> <p>A subset of the orthologous gene groups between human and mouse was selected from the InParanoid database for this study. Each orthologue group was divided into sub-clusters, at the transcript level, using a method based on the sequence similarity of the isoforms. Transcript based sub-clusters were verified by functional signatures of the cluster members in the InterPro database. Functional similarity was higher within than between transcript-based sub-clusters of a defined orthologous group. In certain cases, cancer-related isoforms of a gene could be distinguished from other isoforms of the gene. Predictions of intrinsic disorder in protein regions were also correlated with the isoform sub-clusters within an orthologue group.</p> <p>Conclusions</p> <p>Sub-clustering of orthologue groups at the transcript level is an important step to more accurately define functionally equivalent orthologue groups. This work appears to be the first effort to refine orthologous groupings of genes based on the consequences of alternative splicing on function. Further investigation and refinement of the methodology to classify and verify isoform sub-clusters is needed, particularly to extend the technique to more distantly related species.</p

Organization of the gravity-sensing system in zebrafish

Motor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion is linked to both developmental sequence and neuronal temporal dynamics. Early-born pathways carrying phasic information preferentially excite fast escape circuits, whereas later-born pathways carrying tonic signals excite slower postural and oculomotor circuits. These results demonstrate that vestibular circuits are organized by tuning direction and dynamics, aligning them with downstream motor circuits and behaviors

Construction and validation of a prognostic model for hepatocellular carcinoma: Inflammatory ferroptosis and mitochondrial metabolism indicate a poor prognosis

BackgroundAn increasing number of innovations have been discovered for treating hepatocellular carcinoma (HCC or commonly called HCC) therapy, Ferroptosis and mitochondrial metabolism are essential mechanisms of cell death. These pathways may act as functional molecular biomarkers that could have important clinical significance for determining individual differences and the prognosis of HCC. The aim of this study was to construct a stable and reliable comprehensive model of genetic features and clinical factors associated with HCC prognosis.MethodsIn this study, we used RNA-sequencing (fragments per kilobase of exon model per million reads mapped value) data from the Cancer Genome Atlas (TCGA) database to establish a prognostic model. We enrolled 104 patients for further validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses (KEGG) analysis were used for the functional study of differentially expressed genes. Pan-cancer analysis was performed to evaluate the function of the Differentially Expressed Genes (DEGs). Thirteen genes were identified by univariate and least absolute contraction and selection operation (LASSO) Cox regression analysis. The prognostic model was visualized using a nomogram.ResultsWe found that eight genes, namely EZH2, GRPEL2, PIGU, PPM1G, SF3B4, TUBG1, TXNRD1 and NDRG1, were hub genes for HCC and differentially expressed in most types of cancer. EZH2, GRPEL2 and NDRG1 may indicate a poor prognosis of HCC as verified by tissue samples. Furthermore, a gene set variation analysis algorithm was created to analyze the relationship between these eight genes and oxidative phosphorylation, mitophagy, and FeS-containing proteins, and it showed that ferroptosis might affect inflammatory-related pathways in HCC.ConclusionEZH2, GRPEL2, NDRG1, and the clinical factor of tumor size, were included in a nomogram for visualizing a prognostic model of HCC. This nomogram based on a functional study and verification by clinical samples, shows a reliable performance of patients with HCC

The two-component system CpxAR is required for the high potassium stress survival of Actinobacillus pleuropneumoniae

IntroductionActinobacillus pleuropneumoniae is an important respiratory pathogen, which can cause porcine contagious pleuropneumonia and lead to great economic losses to worldwide swine industry. High potassium is an adverse environment for bacteria, which is not conducive to providing turgor pressure for cell growth and division. Two-component system CpxAR is an important regulatory system of bacteria in response to environmental changes, which is involved in a variety of biological activities, such as antibiotic resistance, periplasmic protein folding, peptidoglycan metabolism and so on.MethodsHowever, little is known about the role of CpxAR in high potassium stress in A. pleuropneumoniae. Here, we showed that CpxAR is critical for cell division of A. pleuropneumoniae under high potassium (K+) stress.ResultsqRT-PCR analysis found that CpxAR positively regulated the cell division genes ftsEX. In addition, we also demonstrated that CpxR-P could directly bind the promoter region of the cell division gene ftsE by EMSA.DiscussionIn conclusion, our results described a mechanism where CpxAR adjusts A. pleuropneumoniae survival under high-K+ stress by upregulating the expression of the cell division proteins FtsE and FtsX. These findings are the first to directly demonstrate CpxAR-mediated high-K+ tolerance, and to investigate the detailed molecular mechanism

Study on Water Resource Carrying Capacity of Zhengzhou City Based on DPSIR Model

Based on the driving force–pressure–state–impact–response (DPSIR) model, a comprehensive evaluation index system is constructed. The index weight is determined by the combination weighting method in combination with the data of 2010–2019. The TOPSIS model is used to comprehensively analyze the water resource carrying capacity of Zhengzhou as the central city in China with a developed economy and relatively short water resources. The study results are as follows. (1) During the sample period, the comprehensive evaluation value of water resources carrying capacity of Zhengzhou increases from 0.4183 in 2010 to 0.5560 in 2019, with an overall fluctuating rise. Simultaneously, the water resource carrying capacity grade improves from Grade III (normal carrying capacity) to Grade II (good carrying capacity). (2) The contribution of each subsystem to the comprehensive evaluation value increases year by year. Among them, S subsystem and I subsystem make the largest contribution to the comprehensive carrying capacity. R subsystem makes a relatively stable contribution to the overall carrying capacity. Affected by GDP growth rate and uneven temporal–spatial distribution of water resources in Zhengzhou, the D subsystem and P subsystem of water resource carrying capacities show the fluctuating change. Finally, based on the above conclusions, this paper puts forward the countermeasures and suggestions to improve the level of water resource carrying capacity of Zhengzhou