Biology subjects

Lu, K.

Publications and source records attributed to Lu, K..

41 records · Page 3Linked to original sources

bioRxiv2019

Becoming a better parent: mice learn sounds that improve a stereotyped maternal behavior

While mothering is often instinctive and stereotyped in species-specific ways, evolution can favor genetically "open" behavior programs that allow experience to shape infant care. Among experience-dependent maternal behavioral mechanisms, sensory learning about infants has been hard to isolate from motivational changes arising from sensitization with infants. We developed a paradigm where sensory learning of an infant-associated cue improves a stereotypical maternal behavior in female mice. Mice instinctively employed a spatial memory-based strategy when engaged repetitively in a pup search and retrieval task. However, by playing a sound from a T-maze arm to signal where a pup will be delivered for retrieval, mice learned within 7 days and retained for at least 2 weeks the ability to use this specific cue to guide a more efficient search strategy. The motivation to retrieve pups also increased, but that alone did not sufficiently explain the shift in search strategy. Bilaterally silencing auditory cortical activity significantly impaired the new strategy without changing the motivation to retrieve pups. Finally, motherhood as compared to infant-care experience alone accelerated how quickly the new sensory-based strategy was acquired, suggesting a role for the maternal hormonal state. By rigorously establishing that newly formed sensory associations can improve the performance of a natural maternal behavior, this work facilitates future studies into the neurochemical and circuit mechanisms that mediate novel sensory learning in the maternal context, as well as more learning-based mechanisms of parental behavior in rodents.

neuroscience↗

bioRxiv2019

Adapterama II: Universal amplicon sequencing on Illumina platforms (TaggiMatrix)

Next-generation sequencing (NGS) of amplicons is used in a wide variety of contexts. Most NGS amplicon sequencing remains overly expensive and inflexible, with library preparation strategies relying upon the fusion of locus-specific primers to full-length adapter sequences with a single identifying sequence or ligating adapters onto PCR products. In Adapterama I, we presented universal stubs and primers to produce thousands of unique index combinations and a modifiable system for incorporating them into Illumina libraries. Here, we describe multiple ways to use the Adapterama system and other approaches for amplicon sequencing on Illumina instruments. In the variant we use most frequently for large-scale projects, we fuse partial adapter sequences (TruSeq or Nextera) onto the 5 end of locus-specific PCR primers with variable-length tag sequences between the adapter and locus-specific sequences. These fusion primers can be used combinatorially to amplify samples within a 96-well plate (eight forward primers + 12 reverse primers yield 8 x 12 = 96 combinations), and the resulting amplicons can be pooled. The initial PCR products then serve as template for a second round of PCR with dual-indexed iTru or iNext primers (also used combinatorially) to make full-length libraries. The resulting quadruple-indexed amplicons have diversity at most base positions and can be pooled with any standard Illumina library for sequencing. The number of sequencing reads from the amplicon pools can be adjusted, facilitating deep sequencing when required or reducing sequencing costs per sample to an economically trivial amount when deep coverage is not needed. We demonstrate the utility and versatility of our approaches with results from six projects using different implementations of our protocols. Thus, we show that these methods facilitate amplicon library construction for Illumina instruments at reduced cost with increased flexibility. A simple web page to design fusion primers compatible with iTru primers is available at: http://baddna.uga.edu/tools-taggi.html. A fast and easy to use program to demultiplex amplicon pools with internal indexes is available at: https://github.com/lefeverde/Mr_Demuxy.

genomics↗

bioRxiv2019

Adaptive efficient coding of correlated acoustic properties

Natural sounds such as vocalizations often have co-varying acoustic attributes where one acoustic feature can be predicted from another, resulting in redundancy in neural coding. It has been proposed that sensory systems are able to detect such covariation and adapt to reduce redundancy, leading to more efficient neural coding. Results of recent psychoacoustic studies suggest that, following passive exposure to sounds in which temporal and spectral attributes covaried in a correlated fashion, the auditory system adapts to efficiently encode the two co-varying dimensions as a single dimension, at the cost of lost sensitivity to the orthogonal dimension. Here we explore the neural basis of this psychophysical phenomenon by recording single-unit responses from primary auditory cortex (A1) in awake ferrets exposed passively to stimuli with two correlated attributes in the temporal and spectral domain similar to that utilized in the psychoacoustic experiments. We found that: (1) the signal-to-noise (SNR) ratio of spike rate coding of cortical responses driven by sounds with correlated attributes was reduced along the orthogonal dimension; while the SNR ratio remained intact along the exposure dimension; (2) Mutual information of spike temporal coding increased only along the exposure dimension; (3) correlation between neurons tuned to the two covarying attributes decreased after exposure; (4) these exposure effects still occurred if sounds were correlated along two acoustic dimensions, but varied randomly along a third dimension. These neurophysiological results are consistent with the Efficient Learning Hypothesis and may deepen our understanding of how the auditory system represents acoustic regularities and covariance. SignificanceIn the Efficient Coding (EC) hypothesis, proposed by Barlow in 1961, the neural code in sensory systems efficiently encodes natural stimuli by minimizing the number of spikes to transmit a sensory signal. Results of recent psychoacoustic studies are consistent with the EC hypothesis, showing that following passive exposure to stimuli with correlated attributes, the auditory system adapts so as to more efficiently encode the two co-varying dimensions as a single dimension. In the current neurophysiological experiments, using a similar stimulus design and experimental paradigm to the psychoacoustic studies of Stilp and colleagues (2010, 2011, 2012, 2016), we recorded responses from single neurons in the auditory cortex of the awake ferret, showing adaptive efficient neural coding of correlated acoustic properties.

neuroscience↗

bioRxiv2018

Penaeidins are a novel family of antiviral effectors against WSSV in shrimp

Penaeidins are members of a family of key effectors with broad anti-bacterial activities in penaeid shrimp. However, the function of penaeidins in antiviral immunity is rarely reported and remains largely unknown. Herein, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV). Firstly, RNAi in vivo mediated knockdown of each penaeidin from four identified penaeidins from Litopenaeus vannamei resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, whilst the phenotype of survival rate in penaeidin-silenced shrimp can be rescued via the injection of recombinant penaeidin proteins. Moreover, pull-down assays demonstrated the conserved PEN domain of penaeidin was able to interact with WSSV structural proteins. Furthermore, we observed that colloidal gold-labeled penaeidins were located on the outer surface of the WSSV virion. By infection-blocking assay, we observed that hemocytes had lower viral infection rates in the group of WSSV preincubated with penaeidins than those of control group. Phagocytic activity analysis further showed that penaeidins were able to inhibit phagocytic activity of hemocytes against WSSV Taken together, these results suggest that penaeidins specifically binds to WSSV virion by interacting with its structural proteins, thus preventing viral infection that confers host against WSSV. In addition, dual-luciferase assay and EMSA assay demonstrated that penaeidins were regulated by Dorsal and Relish, two transcription factors of the canonical Toll and IMD pathway, respectively. To our best knowledge, this is the first report on uncovering the antiviral function of penaeidins in the innate immune system of shrimp.\n\nImportancesWhite spot syndrome, caused by white spot syndrome virus (WSSV), is the most serious disease in shrimp aquaculture, which has long been a scourge of cultured shrimp industry. Herein, we provided some substantial evidences to indicate that penaeidins are a novel family of effectors with antiviral activity against WSSV in shrimp. Penaeidins such as BigPEN, PEN2 and PEN3 were able to interact with the outer surface of WSSV virion via binding to viral structural proteins, and thus preventing viral entry host cells. In addition, we demonstrated that the Toll and IMD signaling pathways can regulate the transcriptional expression of penaeidins, which may suggest an important role of the conserved innate signaling pathways in antiviral immunity. This is the first report of the antiviral mechanism of penaeidins in shrimp, which may provide some new insights into strategies to control WSSV infection in shrimp farms.

immunology↗

bioRxiv2018

Systematic Discovery of the Functional Impact of Somatic Genome Alterations in Individual Tumors through Tumor-specific Causal Inference

We report a tumor-specific causal inference (TCI) framework, which discovers causative somatic genome alterations (SGAs) through inferring causal relationships between SGAs and molecular phenotypes (e.g., transcriptomic, proteomic, or metabolomic changes) within an individual tumor. We applied the TCI algorithm to tumors from The Cancer Genome Atlas (TCGA) and identified those SGAs that causally regulate the differentially expressed genes (DEGs) within each tumor. Overall, TCI identified 634 SGAs that cause cancer-related DEGs in a significant number of tumors, including most of the previously known drivers and many novel candidate cancer drivers. The inferred causal relationships are statistically robust and biologically sensible, and multiple lines of experimental evidence support the predicted functional impact of both well-known and novel candidate drivers. By identifying major candidate drivers and revealing their functional impact in a tumor, TCI shed light on disease mechanisms of each tumor, providing useful information for advancing cancer biology and precision oncology.\n\nSignificance statementsCancer is mainly caused by SGAs. Precision oncology involves identifying and targeting tumor-specific aberrations resulting from causative SGAs. TCI is a novel computational framework for discovering the causative SGAs and their impact on oncogenic processes, thus revealing tumor-specific disease mechanisms. This information can be used to guide precision oncology.

cancer biology↗