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Liu, H.-C.

Publications and source records attributed to Liu, H.-C..

8 recordsLinked to original sources

A dynamical attractor computes reward prediction in the basal forebrain

Phasic ensemble bursting in subcortical neuromodulatory systems such as the basal forebrain (BF) provides a powerful format for broadcasting reward-prediction signals. These bursts encode reward prediction by varying population amplitude, yet their internal structure, reflected in cell-to-cell amplitude relationships, remains conserved. How neural circuits reconcile these competing constraints remains unknown. Here we show that BF bursting is generated by a dynamical attractor: burst structure is imposed not by feedforward inputs but by recurrent circuit dynamics, while burst amplitude is determined by approximately linear integration across concurrent inputs. Optogenetic activation of BF neurons expressing natriuretic peptide receptor 3 (Npr3) outside the behavioral task reproduced the low-dimensional dynamics of natural cue-evoked bursting, preserving the temporal envelope and cell-to-cell amplitude relationships across stimulation patterns. Critically, unilateral activation of non-overlapping Npr3 populations in either hemisphere recruited the full bilateral ensemble into the same native trajectory, showing that restricted inputs can nevertheless recruit the full ensemble. Matched ipsilateral and contralateral onset latencies exceeding 25 ms implicated recurrent interactions beyond the BF. Despite the conserved structure, population burst amplitude varied with stimulation strength and summed approximately linearly across concurrent unilateral inputs. This linear summation extended to natural sensory input during behavior: adding Npr3 stimulation to auditory cues increased cue-evoked burst amplitude, improved detection, and reduced subsequent reward responses, consistent with stronger reward prediction producing smaller reward prediction errors. Thus, a low-dimensional dynamical attractor preserves a shared BF burst structure across diverse inputs while integrating concurrent inputs into a scalar burst amplitude that encodes reward prediction.

neuroscience↗

Mismatch repair and homologous recombination are yin-yang partners in hybrid zygote meiosis

Rad51 and meiosis-specific Dmc1 catalyze homologous recombination (HR) between maternal and paternal chromosomes during meiosis in many sexual eukaryotes, generating three interhomolog (IH) recombination products: noncrossovers (NCOs), class I crossovers (COs), and class II COs. Some COs form chiasmata, which physically connect homologous chromosomes and ensure proper chromosome segregation during meiosis I. Meiosis is highly relevant to speciation, with the mismatch repair (MMR) system believed to prevent IH-HR, leading to postzygotic isolation between closely related species. We report that several Saccharomyces cerevisiae HR proteins exhibit anti-MMR activities, including Rad51, Rad54, and synapsis-promoting ZMM proteins (Mer3, Zip1, Zip4, and Msh4) in SK1/S288c hybrid zygotes. Srs2 (an ortholog of Escherichia coli helicase UvrD) facilitates MMR by dissembling Rad51-ssDNA presynaptic filaments. Rad51 antagonizes MMR and Srs2 to catalyze D-loop formation. Rad54s anti-MMR activity acts after Srs2 and outcompetes its pro-HR function to promote Rad51-mediated IH-HR in hybrid zygotes. Dmc1 does not possess anti-MMR activity, but exhibits better mismatch tolerability than Rad51. Following D-loop formation mediated by Dmc1 and/or Rad51, ZMM proteins promote class I IH-CO formation while limiting MMR to promote NCO formation by Sgs1 (an ortholog of E. coli RecQ helicase) and prevent class II IH-CO formation by the Mms4*Mus81 endonuclease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/636946v2_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@db6794org.highwire.dtl.DTLVardef@6d5947org.highwire.dtl.DTLVardef@1004489org.highwire.dtl.DTLVardef@938403_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMMR and HR antagonize each other in intraspecies hybrid zygotes. C_LIO_LIThe HR proteins Rad51, Rad54, and ZMM exhibit anti-MMR activities. C_LIO_LIMMR overrides HR in hybrid zygotes with anti-MMR mutations, causing hybrid sterility. C_LI

genetics↗

Sex-biased zinc responses modulate ribosome biogenesis, protein synthesis and social defects in Cttnbp2 mutant mice

Autism spectrum disorders (ASD) are neurodevelopmental conditions influenced by genetic mutations, dietary factors, and sex-specific mechanisms, yet the interplay of these factors remains elusive. Here, we investigate the sex-biased responses of mutant mice carrying an ASD-associated mutation in Cttnbp2 to dietary zinc supplementation using behavioral assays, proteomic and bioinformatic analyses, and puromycin pulse labeling to assess protein synthesis. Our results demonstrate that zinc supplementation enhances ribosome biogenesis and increases the density and size of dendritic spines in male Cttnbp2 mutant mice, alleviating male-biased social deficits. Analyses of neuronal cultures further revealed that neurons, not astrocytes, respond to zinc to enhance protein synthesis. In contrast, female Cttnbp2 mutants exhibit resilience to differential zinc intake, even under zinc deprivation. Elevated mTOR phosphorylation and increased protein levels of translational initiation factors in female brains may provide a protective mechanism, reducing their sensitivity to zinc deficiency. Cttnbp2 mutations heighten male vulnerability to zinc deprivation, impairing social behaviors. These findings highlight zinc-regulated ribosome biogenesis and protein synthesis as critical mediators of sex-specific ASD phenotypes, offering new insights into dietary interventions.

neuroscience↗

EZH2/ hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression

BackgroundChondrosarcomas are primary cancers of cartilaginous tissue and capable of alteration to highly aggressive, metastatic, and treatment-refractory states, leading to a poor prognosis with a five-year survival rate at 11 months for the dedifferentiated subtype. At present, the surgical resection of chondrosarcoma is the only effective treatment, and no other treatment options including targeted therapies, conventional chemotherapies, or immunotherapies are available for these patients. MethodsA non-biased ChIP sequence, cDNA microarray analysis, and validation of chondrosarcoma cell lines identified sulfatase 1(SULF1) as the top EZH2-targeted gene to regulate chondrosarcoma progression. Receptor tyrosine kinase (RTK) array of chondrosarcoma cells with vector control or ectopically expressed SULF1 revealed that cMET was the downstream signal. The regulation of the EZH2/SULF1/cMET axis was further validated in mice and patient samples with mice models and chondrosarcoma tissue array, respectively. ResultsThe EZH2/SULF1/cMET axis is identified, which contributes to the malignancy of chondrosarcoma and provides a potential therapeutic option for the disease. Ectopically expressed SULF1 or pharmaceutical inhibition of the cMET pathway significantly retards the chondrosarcoma growth and extends mice survival. ConclusionsThe results not only established a signal pathway promoting the malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma.

cancer biology↗

HSFA1 proteins mediate heat-induced accumulation of CPT7-derived polyprenols affecting thylakoid organization

Polyprenols are ubiquitous isoprenoid compounds that accumulate in large quantities in plant photosynthetic tissues. While our knowledge of polyprenol biochemistry is constantly expanding, the regulation of their biosynthesis as well as the molecular basis of their cellular action are still poorly understood. In Arabidopsis, the polyprenols Pren-9, -10 and -11, synthesized by cis-prenyltransferase 7 (CPT7), are localized in plastidial membranes and affect the photosynthetic performance of chloroplasts. In this report we present evidence that plastidial polyprenols are among the major constituents of thylakoid membranes. Disturbances in polyprenol level, caused by alterations in CPT7 expression, change chloroplast ultrastructure, affect aggregation of LHCII complexes and modulate non-photochemical quenching (NPQ). Moreover, we show that Arabidopsis responds to high temperature by upregulating expression of CPT7 and increasing the accumulation of CPT7-derived polyprenols. These heat-induced changes in polyprenol biosynthesis are mediated by Heat Shock Transcription Factors of the HSFA1 family, the master regulators of heat stress response. Collectively, results presented in this report bring us closer to understanding the mechanisms by which polyprenols affect plant physiology and provide an additional link between chloroplast biology and plant responses to changing environmental conditions. One sentence summaryHeat Shock Transcription Factors induce biosynthesis of polyprenols - isoprenoid compounds that affect the organization and function of chloroplasts.

plant biology↗

Intrinsic disorder codes for leaps of protein expression

Serine(S)/threonine(T)-glutamine(Q) cluster domains (SCDs), polyglutamine (polyQ) tracts and polyglutamine/asparagine (polyQ/N) tracts are Q-rich motifs found in many proteins. SCDs often are intrinsically disordered regions that mediate protein phosphorylation and protein-protein interactions. PolyQ and polyQ/N tracts are structurally flexible sequences that trigger protein aggregation. We report that due to their high percentages of STQ or STQN amino acid content, four SCDs and three prion-causing Q/N-rich motifs of yeast proteins possess autonomous protein expression-enhancing activities. Since these Q-rich motifs can endow proteins with structural and functional plasticity, we suggest that they represent useful toolkits for evolutionary novelty. Comparative Gene Ontology (GO) analyses of the near-complete proteomes of 27 representative model eukaryotes reveal that Q-rich motifs prevail in proteins involved in specialized biological processes, including Saccharomyces cerevisiae RNA-mediated transposition and pseudohyphal growth, Candida albicans filamentous growth, ciliate peptidyl-glutamic acid modification and microtubule-based movement, Tetrahymena thermophila xylan catabolism and meiosis, Dictyostelium discoideum development and sexual cycles, Plasmodium falciparum infection, and the nervous systems of Drosophila melanogaster, Mus musculus and Homo sapiens. We also show that Q-rich-motif proteins are expanded massively in ten ciliates with reassigned TAAQ and TAGQ codons. Notably, the usage frequency of CAGQ is much lower in ciliates with reassigned TAAQ and TAGQ codons than in organisms with expanded and unstable Q runs (e.g., D. melanogaster and H. sapiens), indicating that the use of noncanonical stop codons in ciliates may have coevolved with codon usage biases to avoid triplet repeat disorders mediated by CAG/GTC replication slippage.

biochemistry↗

An allometric scaling approach to estimate epiphytic bryophyte biomass in tropical montane cloud forests

Epiphytic bryophytes (EB) are some of the most commonly found plant species in tropical montane cloud forests, and they play a disproportionate role in influencing the terrestrial hydrological and nutrient cycles. However, it is difficult to estimate the abundance of EB due to the nature of their "epiphytic" habitat. This study proposes an allometric scaling approach to measure EB biomass, implemented in 16,773 ha tropical montane cloud forests of northeastern Taiwan. A general allometry was developed to estimate EB biomass of 100 cm2 circular-shaped mats (n = 131) and their central depths. A point-intercept instrument was invented to measure the depths of EB along tree trunks (n = 210) below 3-m from the ground level (sampled stem surface area [SSA]) in twenty-one 30 x 30 m plots. Biomass of EB of each point measure was derived using the general allometry and was aggregated across each SSA, and its performance was evaluated. Total EB biomass of a tree was estimated by referring to an in-situ conversion model and was interpolated for all trees in the plots (n = 1451). Finally, we assessed EB biomass density at the plot scale and preliminarily estimated EB biomass of the study region. The general EB biomass-depth allometry showed that the depth of an EB mat was a salient variable for biomass estimation (R2 = 0.72, p < 0.001). The performance of upscaling from mats to SSA was satisfactory, which allowed us to further estimate mean ({+/-} standard deviation) EB biomass of the 21 plots (272 {+/-} 104 kg ha-1) and to provide preliminary estimation of the total EB biomass of 4562 Mg for the study region. Since a significant relationship between tree size and EB abundance is commonly found, regional EB biomass may be mapped by integrating our method and three-dimensional airborne data.

ecology↗

Differences in in vitro responses of the hypothalamo-pituitary-gonadal hormonal axis between low and high egg producing turkey hens

Low egg producing hens (LEPH) ovulate less frequently than high egg producing hens (HEPH) and exhibit differences in mRNA levels for components of the hypothalamo-pituitary-gonadal (HPG) axis, suggesting differential responsiveness to trophic stimulation. Ovulation frequency is governed by the production and feedback of pituitary gonadotropins and ovarian follicle steroid hormones, which are regulated by HPG axis stimulation and inhibition at the hypothalamic level. Pituitary and follicle cells from LEPH and HEPH were subjected to in vitro hormonal treatments to stimulate or inhibit the HPG axis, followed by expression analysis of mRNA levels for HPG axis genes and radioimmunoassays for steroid hormone production. Statistical analysis was performed using the mixed models procedure of SAS. Pituitary cells from HEPH showed up-regulation of genes associated with ovulation stimulation, whereas LEPH cells showed up-regulation of genes associated with inhibition of ovulation. HEPH follicle cells displayed a higher sensitivity and responsiveness to gonadotropin treatment. Level of egg production impacted ovulation-related gene expression in pituitary cells as well as steroid hormone production in follicle cells, with HEPH displaying a greater positive response to stimulation. These findings indicate that differences in egg production among turkey hens likely involve differential responsiveness of the cells within the HPG axis.

physiology↗