Biology subjects

Lin, Y.-J.

Publications and source records attributed to Lin, Y.-J..

At least 19 recordsLinked to original sources

bioRxiv2026

Artificial hibernation uncovers distinct interaction dynamics in functional and pathological state change

Neural population activity can reorganize without disrupting function, but how such changes differ from those associated with pathology remains unknown. Artificial hibernation, Q-neuron-induced hypothermia and hypometabolism (QIH), causes extensive synaptic remodeling in the hippocampus without erasing established memories, allowing us to examine how extensive network reorganization can occur without lasting functional impairment. Longitudinal calcium imaging showed that hippocampal activity recovered after QIH without returning to its pre-hibernation population configuration. Instead, QIH reorganized neuronal activity patterns and coactivity beyond representational drift. Electrophysiological recordings revealed that this reorganization of neuronal interactions depended on the preceding network state. In mice subjected to kainic acid-induced status epilepticus, QIH reduced seizure-associated increases in neuronal interactions and spike coactivity during sharp-wave ripples. Over the following 50 days, the divergence of hippocampal LFP trajectories was constrained, and the progressive development of electrophysiological and histological pathology was attenuated. These findings suggest that controlled, extensive reorganization of neural population activity can prevent the progression toward pathological network states, with changes in neuronal interactions, particularly sharp-wave ripple-associated coactivity, accompanying this process.

neuroscience↗

bioRxiv2026

A fine-tuned genomic language model adds complementary nucleotide-context information to missense variant interpretation

Missense variant interpretation remains a major challenge in clinical genomics. Existing missense variant impact predictors achieve strong performance, but they emphasize protein-level consequences and often share overlapping annotation priors. A missense annotation specifies the encoded amino-acid substitution, but the underlying nucleotide change may also act through nucleotide sequence context that protein-centric predictors overlook. Whether genomic language models capture distinctive nucleotide-level information beyond established missense variant impact predictors remains unclear. Through a comprehensive comparison of model backbones, embedding aggregation strategies, classifier heads, and adaptation regimes, we developed GLM-Missense, a genomic language model fine-tuned for missense variant impact prediction. Variant-position embeddings, multi-species pretraining, and low-rank adaptation were the design choices most critical to its performance. GLM-Missense contributed information complementary to established missense variant impact predictors. It showed low concordance with AlphaMissense, ESM1b, REVEL, CADD, SIFT and PolyPhen-2. We then asked whether this divergence was predictive rather than noise: after accounting for the other predictors, GLM-Missense retained the strongest unique association with variant pathogenicity. Finally, in MetaMissense, an XGBoost ensemble of all seven predictors, GLM-Missense ranked among the most informative features, indicating that its nucleotide-context signal carries information the ensemble uses to predict pathogenicity. A subset of the variants GLM-Missense resolved were annotated as missense but carried ClinVar splicing-related evidence for pathogenicity. This suggests GLM-Missense captures splicing-relevant signal. However, substituting SpliceAI for GLM-Missense in the ensemble failed to recapitulate its feature importance, suggesting that GLM-Missense captures additional sequence-derived information beyond splicing context alone. Together, these results demonstrate that GLM-Missense, a fine-tuned genomic language model, captures nucleotide-level information overlooked by established missense variant impact predictors.

bioinformatics↗

bioRxiv2026

Engineering a performance-improved, axon-targeted kalium channelrhodopsin for optogenetic neuropathway inhibition

Optogenetic neuropathway inhibition is a powerful approach for dissecting circuit functions. This strategy, however, frequently encounters practical challenges due to insufficient expression or performance of the optogenetic silencer on axonal projections/terminals. HcKCR1, a light-gated potassium-selective channel from Hyphochytrium catenoides, has shown great promise for optogenetic inhibition. Unfortunately, the application of HcKCR1 in neuropathway manipulations is hindered by its unsatisfactory gating properties and poor axonal trafficking. To overcome these hurdles, we first engineered a performance-improved HcKCR1 (piKCR) that allowed more reliable neuronal inhibition at low intensities of green or red light. We next engineered an axon-targeted piKCR (piKCR.AT) that demonstrated long-range axonal trafficking and optical presynaptic inhibition in the mouse hippocampus. When piKCR.AT was expressed in the cerebellar Purkinje Cells (PCs), optical manipulation of PC outputs to the deep cerebellar nuclei robustly disrupted mouse movement on the balance beam. With enhanced performance and axonal distribution, piKCR.AT may provide new opportunities for elucidating neuropathway functions in health and diseases.

bioengineering↗

bioRxiv2025

Artificial hibernation uncovers distinct synaptic engram architecture for memory retention

The memory trace at the neuronal and synaptic levels remains controversial. Stable, larger spines are thought to support memory, but the high turnover of dendritic spines and the drifting of neuronal representations following memory formation suggest alternative possibilities. To elucidate a structural trace underlying memory retention, we utilize a mouse model of artificial hibernation. During hibernation, hippocampal neurons exhibited a substantial reduction in their activity and an extensive elimination of dendritic spines and synapses. Despite these changes, their memory and associated hippocampal neuronal representations are intact after arousal. We find that a subset of spines is maintained during hibernation. These spatially clustered engram-engram synapses are exclusively protected from elimination and characterized by synaptic contacts with multi-synaptic boutons. These findings suggest that synaptic engram architecture, rather than larger spines per se, is resilient to network remodeling and underlies long-term memory retention.

neuroscience↗

bioRxiv2025

Effects of arginine on the interfacial behavior of proteins

HypothesisProtein adsorption at fluid-fluid interfaces can induce conformational rearrangements and promote aggregation. Arginine, as an amino acid is known to attenuate protein-protein interactions and lower the viscosity of protein formulations. Given its surface-active properties, we hypothesize that arginine may be effective in limiting aggregation at fluid-fluid interfaces. ExperimentsInterfacial rheology of Etanercept (Enbrel), Immunoglobulin G1 (IgG1), and Bovine Serum Albumin (BSA) was characterized across a range of concentrations, with and without L-arginine Hydrochloride. The interfacial response was examined in both linear and nonlinear regimes.{zeta} -potential was also measured for selected formulations to evaluate the relationship between electrostatic characteristics and the rheological outcomes. FindingsBased on both linear and nonlinear interfacial rheology results, arginine generally weakened protein-protein interactions; however, the effect depends on protein identity and concentration. In arginine-containing formulations, Enbrel and BSA displayed only minor variation in interfacial viscoelasticity between 0.01 and 1 mg/mL, particularly during prolonged aging; in contrast, IgG1 showed larger concentration-dependent differences. These results strengthen predictive frameworks for interfacial stability and guide the rational design of protein-amino acid biopharmaceutical formulations. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/674647v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@10a0bc8org.highwire.dtl.DTLVardef@8b9be7org.highwire.dtl.DTLVardef@1a88e43org.highwire.dtl.DTLVardef@113d5a9_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2024

Variant Impact Predictor database (VIPdb), version 2: Trends from 25 years of genetic variant impact predictors

BackgroundVariant interpretation is essential for identifying patients disease-causing genetic variants amongst the millions detected in their genomes. Hundreds of Variant Impact Predictors (VIPs), also known as Variant Effect Predictors (VEPs), have been developed for this purpose, with a variety of methodologies and goals. To facilitate the exploration of available VIP options, we have created the Variant Impact Predictor database (VIPdb). ResultsThe Variant Impact Predictor database (VIPdb) version 2 presents a collection of VIPs developed over the past 25 years, summarizing their characteristics, ClinGen calibrated scores, CAGI assessment results, publication details, access information, and citation patterns. We previously summarized 217 VIPs and their features in VIPdb in 2019. Building upon this foundation, we identified and categorized an additional 186 VIPs, resulting in a total of 403 VIPs in VIPdb version 2. The majority of the VIPs have the capacity to predict the impacts of single nucleotide variants and nonsynonymous variants. More VIPs tailored to predict the impacts of insertions and deletions have been developed since the 2010s. In contrast, relatively few VIPs are dedicated to the prediction of splicing, structural, synonymous, and regulatory variants. The increasing rate of citations to VIPs reflects the ongoing growth in their use, and the evolving trends in citations reveal development in the field and individual methods. ConclusionsVIPdb version 2 summarizes 403 VIPs and their features, potentially facilitating VIP exploration for various variant interpretation applications. AvailabilityVIPdb version 2 is available at https://genomeinterpretation.org/vipdb

bioinformatics↗

bioRxiv2024

Label-Free Optical Mapping for Large-Area Biomechanical Dynamics of Multicellular Systems

Mapping cellular activities over large areas is crucial for understanding the collective behaviors of multicellular systems. Biomechanical properties, such as cellular traction force, serve as critical regulators of physiological states and molecular configurations. However, existing technologies for mapping large-area biomechanical dynamics are limited by the small field of view and scanning nature. To address this, we propose a novel platform that utilizes a vast number of optical diffractive elements for mapping large-area biomechanical dynamics. This platform achieves a field-of-view of 10.6 mm X 10.6 mm, a three-orders-of-magnitude improvement over traditional traction force microscopy. Transient mechanical waves generated by monolayer neonatal rat ventricular myocytes were captured with high spatiotemporal resolution (130 fps and 20 {micro}m for temporal and spatial resolution, respectively). Furthermore, its label-free nature allows for long-term observations extended to a week, with minimal disruption of cellular functions. Finally, simultaneous measurements of calcium ions concentrations and biomechanical dynamics are demonstrated.

bioengineering↗

bioRxiv2023

Massively Concurrent Sub-Cellular Traction Force Videography enabled by Single-Pixel Optical Tracers (SPOTs)

We report a large field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13mm2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells mechanical traction stress into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave. One-Sentence SummaryAn optical platform for fast, concurrent measurements of cell mechanics at 83 frames per second, over a large area of 13mm2.

bioengineering↗

bioRxiv2022

Neutralization of SARS-CoV-2 Omicron BA.4/BA.5 subvariant by a booster dose of bivalent adjuvanted subunit vaccine containing Omicron BA.4/BA.5 and BA.1 subvariants

The dominance of SARS-CoV-2 variants of concern (VoC), such as the Omicron subvariants, is a threat to the current vaccination scheme due to increased resistance to immune neutralization and greater transmissibility. To develop the next generation of prefusion SARS-CoV-2 spike protein (S-2P) subunit vaccine adjuvanted with CpG1018 and aluminum hydroxide, mice immunized with two doses of the adjuvanted ancestral Wuhan strain (W) followed by the third dose of the W or Omicron variants (BA.1 or BA.4/BA.5) S-2P, or a combination of the above bivalent S-2Ps. Antisera from mice were tested against pseudovirus neutralization assay of ancestral SARS-CoV-2 (WT) and Omicron BA.4/BA.5 subvariant. Boosting with bivalent mixture of Omicron BA.4/BA.5 and W S-2P achieved the highest neutralizing antibody titers against BA.4/BA.5 subvariant pseudovirus compared to other types of S-2P as boosters.

immunology↗

bioRxiv2022

Intranasal Nanoemulsion Adjuvanted S-2P Vaccine Demonstrates Protection in Hamsters and Induces Systemic, Cell-Mediated and Mucosal Immunity in Mice

With the rapid progress made in the development of vaccines to fight the SARS-CoV-2 pandemic, almost >90% of vaccine candidates under development and a 100% of the licensed vaccines are delivered intramuscularly (IM). While these vaccines are highly efficacious against COVID-19 disease, their efficacy against SARS-CoV-2 infection of upper respiratory tract and transmission is at best temporary. Development of safe and efficacious vaccines that are able to induce robust mucosal and systemic immune responses are needed to control new variants. In this study, we have used our nanoemulsion adjuvant (NE01) to intranasally (IN) deliver stabilized spike protein (S-2P) to induce immunogenicity in mouse and hamster models. Data presented demonstrate the induction of robust immunity in mice resulting in 100% seroconversion and protection against SARS-CoV-2 in a hamster challenge model. There was a significant induction of mucosal immune responses as demonstrated by IgA- and IgG-producing memory B cells in the lungs of animals that received intranasal immunizations compared to an alum adjuvanted intramuscular vaccine. The efficacy of the S-2P/NE01 vaccine was also demonstrated in an intranasal hamster challenge model with SARS-CoV-2 and conferred significant protection against weight loss, lung pathology, and viral clearance from both upper and lower respiratory tract. Our findings demonstrate that intranasal NE01-adjuvanted vaccine promotes protective immunity against SARS-CoV-2 infection and disease through activation of three arms of immune system: humoral, cellular, and mucosal, suggesting that an intranasal SARS-CoV-2 vaccine may play a role in addressing a unique public health problem and unmet medical need.

immunology↗

bioRxiv2022

Protection of Hamsters Challenged with SARS-CoV-2 after Two Doses of MVC-COV1901 Vaccine Followed by a Single Intranasal Booster with Nanoemulsion Adjuvanted S-2P Vaccine

Intramuscular vaccines have greatly reduced hospitalization and death due to severe COVID-19. However, most countries are experiencing a resurgence of infection driven predominantly by the Delta and Omicron variants of SARS-CoV-2. In response, booster dosing of COVID-19 vaccines has been implemented in many countries to address waning immunity and reduced protection against the variants. However, intramuscular boosting fails to elicit mucosal immunity and therefore does not solve the problem of persistent viral carriage and transmission, even in patients protected from severe disease. In this study, two doses of stabilized prefusion SARS-CoV-2 spike (S-2P)-based intramuscular vaccine adjuvanted with Alum/CpG1018, MVC-COV1901, were used as a primary vaccination series, followed by an intranasal booster vaccination with nanoemulsion (NE01)-adjuvanted S-2P vaccine in a hamster model to demonstrate immunogenicity and protection from viral challenge. Here we report that this vaccination regimen resulted not only in the induction of robust immunity and protection against weight loss and lung pathology following challenge with SARS-CoV-2, but also led to increased viral clearance from both upper and lower respiratory tracts. Our findings showed that intramuscular MVC-COV1901 vaccine followed by a booster with intranasal NE01-adjuvanted vaccine promotes protective immunity against both viral infection and disease, suggesting that this immunization protocol may offer a solution in addressing a significant, unmet medical need for both the COVID-19 and future pandemics.

immunology↗

bioRxiv2021

Genomes of keystone Mortierella species lead to better in silico prediction of soil mycobiome functions from Taiwan's offshore islands

The ability to correlate the functional relationship between microbial communities and their environment is critical to understanding microbial ecology. There is emerging knowledge on island biogeography of microbes but how island characteristics influence functions of microbial community remain elusive. Here, we explored soil mycobiomes from nine islands adjacent to Taiwan using ITS2 amplicon sequencing. Geographical distances and island size were positively correlated to dissimilarity in mycobiomes, and we identified 56 zero-radius operational taxonomic units (zOTUs) that were ubiquitously present across all islands, and as few as five Mortierella zOTUs dominate more than half of mycobiomes. Correlation network analyses revealed that seven of the 45 hub species were part of the ubiquitous zOTUs belonging to Mortierella, Trichoderma, Aspergillus, Clonostachys and Staphylotrichum. We sequenced and annotated the genomes of seven Mortierella isolates, and comparative predictions of KEGG orthologues using PICRUSt2 database updated with new genomes increased sequence reads coverage by 62.9% at the genus level. In addition, genes associated with carbohydrate and lipid metabolisms were differentially abundant between islands which remained undetected in the original database. Predicted functional pathways were similar across islands despite their geographical separation, difference in differentially abundant genes and composition. Our approach demonstrated the incorporation of the key taxa genomic data can improve functional gene prediction results and can be readily applied to investigate other niches of interests.

genomics↗

bioRxiv2021

Protection of Hamsters Challenged with SARS-CoV-2 Variants of Concern by Two Doses of MVC-COV1901 Vaccine Followed by a Single Dose of Beta Variant Version of MVC-COV1901

The current fight against COVID-19 is compounded by the Variants of Concern (VoCs), which can diminish the effectiveness of vaccines and potentially increase viral transmission and severity of disease. MVC-COV1901 is a protein subunit vaccine based on the prefusion SARS-CoV-2 spike protein (S-2P) and is adjuvanted with CpG 1018 and aluminum hydroxide. In this study, we used the Delta variant to challenge hamsters inoculated with S-2P from the Wuhan wildtype and the Beta variant in two-dose or three-dose regimens. Two doses of wildtype S-2P followed by the third dose of Beta variant was shown to induce the highest neutralizing antibody titer against live SARS-CoV-2 of the wildtype and all current VoCs, as well as improved neutralization against Omicron variant pseudovirus compared to three doses of wildtype S-P. All regimens of vaccination were able to protect hamsters from SARS-CoV-2 Delta variant challenge and resulted in reduced lung live virus titer and pathology. Three doses of vaccination also significantly reduced lung viral RNA titer, regardless of whether the wildtype or Beta variant S-2P was used as the third dose. Based on the immunogenicity and viral challenge data, two doses of wildtype S-2P followed by the third dose of Beta variant S-2P induced potent antibody immune responses against the VoCs.

immunology↗

bioRxiv2021

TMS entrains occipital alpha activity: Individual alpha frequency predicts the strength of entrained phase-locking

Parieto-occipital alpha rhythms (8-12 Hz) underlie cortical excitability and influence visual performance. Whether the synchrony of intrinsic alpha rhythms in the occipital cortex can be entrained by transcranial magnetic stimulation (TMS) is an open question. We applied 4-pulse, 10-Hz rhythmic TMS to entrain intrinsic alpha oscillators targeting right V1/V2, and tested four predictions with concurrent electroencephalogram (EEG): (1) progressive enhancement of entrainment across time windows, (2) output frequency specificity, (3) dependence on the intrinsic oscillation phase, and (4) input frequency specificity to individual alpha frequency (IAF) in the neural signatures. Two control conditions with an equal number of pulses and duration were arrhythmic-active and rhythmic-sham stimulation. The results confirmed the first three predictions. Rhythmic TMS bursts significantly entrained local neural activity. Near the stimulation site, evoked oscillation amplitude and inter-trial phase coherence (ITPC) were increased for 2 and 3 cycles, respectively, after the last TMS pulse. Critically, ITPC following entrainment positively correlated with IAF rather than with the degree of similarity between IAF and the input frequency (10 Hz). Thus, we entrained alpha-band activity in occipital cortex for ~3 cycles (~300 ms), and IAF predicts the strength of entrained occipital alpha phase synchrony indexed by ITPC.

neuroscience↗

bioRxiv2021

CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge

The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 {micro}g or 5 {micro}g of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 g or 5 g of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.

microbiology↗

bioRxiv2020

GAMYB modulates bHLH142 and is homeostatically regulated by TDR during rice anther tapetal and pollen development

GAMYB, UDT1, TIP2/bHLH142, TDR, and EAT1/DTD are important transcription factors (TFs) that play a crucial role during rice pollen development. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a "hub" in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of bHLH142 promoter during early stage of pollen development; while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. The up- and down-regulation of TFs highlights the importance that a tight, precise, and coordinated regulation among these TFs is essential for normal pollen development. Most notably, this study illustrates the regulatory pathways of GAMYB and UDT1 that rely on bHLH142 in a direct and an indirect manner, respectively, and function in different tissues with distinct biological functions during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development. HighlightGAMYB can directly modulate the transactivation of the bHLH142, but the modulation is repressed by TDR to keep the homeostasis of bHLH142 gene expression to ensure normal pollen development.

molecular biology↗

bioRxiv2020

Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 is a worldwide health emergency. The immense damage done to public health and economies has prompted a global race for cures and vaccines. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein by adding two proline substitutions at the top of the central helix (S-2P). To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P was combined with various adjuvants, including CpG 1018, and administered to mice to test its effectiveness in eliciting anti-SARS-CoV-2 neutralizing antibodies. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of spike-specific antibodies in sera of immunized mice. The neutralizing abilities in pseudotyped lentivirus reporter or live wild-type SARS-CoV-2 were measured with reciprocal inhibiting dilution (ID50) titers of 5120 and 2560, respectively. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th-1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens with up to 50 g of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018/alum as a candidate vaccine to prevent COVID-19 disease.

immunology↗

bioRxiv2020

The genome of low-chill Chinese plum 'Sanyueli' (Prunus salicina Lindl.) provides insights into the regulation of chilling requirement of flower bud

Chinese plum (Prunus salicina Lindl.) is a stone fruit that belongs to the Prunus genus and plays an important role in the global production of plum. In this study, we report the genome sequence of the Chinese plum Sanyueli, which is known to have a low-chill requirement for flower bud break. The assembled genome size was 308.06 Mb, with a contig N50 of 815.7 kb. A total of 30,159 protein-coding genes were predicted from the genome and 56.4% (173.39 Mb) of the genome was annotated as repetitive sequence. Bud dormancy is influenced by chilling requirement in plum and partly controlled by DORMANCY ASSOCIATED MADS-box (DAM) genes. Six tandemly arrayed PsDAM genes were identified in the assembled genome. Sequence analysis of PsDAM6 in Sanyuelirevealed the presence of large insertions in the intron and exon regions. Transcriptome analysis indicated that the expression of PsDAM6 in the dormant flower buds of Sanyueli was significantly lower than that in the dormant flower buds of the high chill requiring Furongli plum. In addition, the expression of PsDAM6 was repressed by chilling treatment. The genome sequence of Sanyueli plum provides a valuable resource for elucidating the molecular mechanisms responsible for the regulation of chilling requirements, and is also useful for the identification of the genes involved in the control of other important agronomic traits and molecular breeding in plum.

genomics↗