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Biomedical subjects

Jun Xiao

Publications and source records attributed to Jun Xiao.

At least 19 recordsLinked to original sources

Integrative omics of the genetic basis for wheat WUE and drought resilience reveal the function of TaMYB7-A1.

Improving wheat drought resilience and water use efficiency (WUE) is critical for sustaining productivity under increasing water scarcity. Here, we integrate genome-wide association study (GWAS), expression quantitative trait locus (eQTL) mapping, population-transcriptome analysis, and summary-data-based mendelian randomization (SMR), followed by functional validation using indexed EMS mutants and transgenic lines, to systematically identify key WUE regulators. GWAS across water conditions in 228 accessions identifies 73 quantitative trait loci (QTLs) for WUE-traits. Transcriptome profiling of 110 diverse accessions reveals 28 drought-responsive modules. eQTL mapping uncovers 146,966 regulatory variants, including condition-specific hotspots associated with key drought-related pathways. Integrative analysis underscores 85 high-confidence candidate genes, notably TaMYB7-A1. Overexpression of TaMYB7-A1 enhances photosynthesis, WUE, root development, and grain yield under drought condition by activating TaPIP2;2-B1 (water transport), TaRD20-D1 (stomatal regulation), and TaABCB4-B1 (root growth), reflecting reduced water loss and improved physiological resilience. Our study presents a comprehensive regulatory map and robust targets for wheat drought adaptation and resilient cultivar breeding.

Triticum↗

Cyclin A but not cyclin D1 is essential for c-myc-modulated cell-cycle progression.

The proto-oncogene c-myc is a key player in cell-cycle regulation and is deregulated in a broad range of human cancers and cell proliferation disorders. Here we reported that overexpression of c-myc in human embryonic lung fibroblasts (HEL) that have low endogenous c-myc enriched S phase cells with increased expression of cyclin D3, E, A, Cdk2, and Cdk4, and decreased expression of p21 and p27. To the opposite, using RNAi to downregulate c-myc expression in A549 cells that have high endogenous c-myc enriched G1 phase cells with decreased expression of cyclin D3, E, A, Cdk2, Cdk4, and increased expression of p21 and p27. We found that cyclin A expression was the most susceptive to changes in c-myc levels and essential in c-myc-modulated cell cycle pathway via co-transfection, however, cyclin D1 showed no change between treated and control groups in either HEL or A549 cells. Our results indicated that upregulation of c-myc expression promotes cell cycling in HEL cells, whereas downregulation of c-myc expression causes G1 phase arrest in A549 cells, and the c-myc-mediated cell-cycle regulation pathway was dependent on cyclin A and involved cyclin D3, E, Cdk2, Cdk4, p21, and p27, but not cyclin D1.

Cell Cycle↗

[An improved operation approach for bipedal rat model construction].

OBJECTIVE: To explore an improved operation approach to make up the ethical deficiency of classical bipedal rat model. METHODS: 20 SD rats were randomly divided into an improved group and a traditional group averagely. Improved group were operated with plexus brachialis nerve amputation, while traditional group with forelimbs amputation close to shoulder joint. Forelimb and shoulder joint movements were observed and electromyography of the peripheral muscles around shoulder joint were recorded to make certain the paralytic scope. Operation duration and axillary artery hurt probability of both the improved and traditional operation were compared to evaluate the operation risk of improved approach. Mean total upright time on 2 d, 1 w, 2 w, 4 w and 6 w post-operation and upright posture on 6 w post-operation were recorded to evaluate the human-upright-posture-simulating effect of bipedal rats operated with improved approach. RESULTS: Compared with classical amputation approach, improved approach exhibited simpler operation procedure, shorter operation duration and lower axillary artery hurt probability. Electromyography revealed that all forelimb muscles and most shoulder-peripheral muscles were denervated, forelimbs of the improved bipedal rats were absolutely paralyzed and shoulder joint reserved only slight abduction function. The mean total upright time of improved bipedal rats was longer than the classical ones after 2 w post-operation, while upright posture showed no difference with classical bipedal rats. CONCLUSIONS: The improved operation approach not only simplified operation procedures, but also achieved even better effect than classical amputation operation and exempted bipedal rat model from the ethical shadow.

Animals↗

[Expressed genes related to adolescent idiopathic scoliosis in spinal facet].

OBJECTIVE: To construct a subtractive cDNA library from the spinal facets of adolescent idiopathic scoliosis (AIS) patient with suppression subtractive hybridization (SSH) technique and clone differentially expressed genes related to AIS in spinal facet. METHODS: mRNA was isolated separately from the convex side and concave side apical facets of an adolescent idiopathic scoliosis patient. Moreover, single-strand (ss) and double-strand (ds) cDNAs were synthesized in turn using SMART PCR cDNA synthesis technology. (ds) cDNAs then were digested with Rsa I and divided into two groups, and ligated to the specific adaptor 1 and adaptor 2R, respectively. After cDNAs were hybridized with each other twice and underwent two rounds of nested PCR, the PCR products were ligated with pDrive Cloning Vectors to set up the subtractive library. Sequence analysis was performed and the acquired data were aligned against the GeneBank nucleotide database. Furthermore, the spinal facets of 11 IS patients were collected. The techniques of immunohistochemistry and in situ hybridization were adopted in order to approve the gene expression difference. The images of immunohistochemistry and in situ hybridization were input to the image analysis system and were analyzed semi-quantitatively. RESULTS: A cDNA subtractive library of AIS in spinal facet was set up successfully with high subtractive efficiency. Beta2 Microglobulin (beta 2M) and calgranulin A (S100A8) were identified as highly differentially expressed genes in this study. CONCLUSION: All results confirm the effectiveness and sensitivity of SSH in detecting differentially expressed genes from a small amount of clinical samples. Information about such alterations in gene expression can be useful for elucidating the genetic events in the development of AIS.

Adolescent↗

The use of a novel and simple method of revealing neural fibers to show the regression of the lateral geniculate nucleus in the naked mole-rat (Heterocephalus glaber).

The lateral geniculate nucleus (LG) is an important subcortical nucleus in the visual system. It receives primary projections from the retina and relays these to central visual structures. Although there are studies on the retina and visual cortex of animals with regressed vision, little is known about the LG in such animals. The strictly subterranean naked mole-rat (Heterocephalus glaber) has markedly reduced visual acuity with concomitant pronounced changes in the visual cortex. We used a novel method to reveal myelinated neural fibers in a histological study assessing if the LG shows regressive changes commensurate with the level of reliance on vision by this rodent. Myelin detection here relies on significant differences in visible light reflection between neural fibers and the gray matter. Moreover, this simple method does not interfere with further staining for additional analyses. This method reveals that the contribution of the LG to brain volume in the naked mole-rat is less than a third of that of the rat. This shows that the retinogeniculocortical system in the naked mole-rat is considerably smaller than that of rodents that rely heavily on their visual system, but is nevertheless less regressed than that of the extensively studied blind mole-rat; this may facilitate limited responses to visual stimuli.

Animals↗

[Comparison of acute physiology and chronic health evaluation II, simplified acute physiology score II and Logistic organ dysfunction system on predicting outcome of critically ill patients in intensive care unit].

OBJECTIVE: To compare and evaluate the prognostic value of three prognostic systems namely acute physiology and chronic health evaluation II(APACHEII), simplified acute physiology score II(SAPSII), and Logistic organ dysfunction system (LODS),to predict mortality rate in intensive care unit (ICU). METHODS: APACHEII, SAPSII and LODS were used to assess probabilities of hospital mortality rate and to compare with actual outcome. The overall goodness-of-fit of three prognostic systems were assessed by using the areas under the receiver operating characteristic (ROC) curves and classification tables. Calibration curves and Lemeshow-Hosmer chi square statistics were used to test accuracy of prediction. RESULTS: Hospital mortality rate was basically equivalent to that predicted by APACHEII but higher than those predicted by SAPSII and LODS. The areas under the ROC curves were 0.881 for APACHEII, 0.904 for SAPSII and 0.875 for LODS, and 95% confidence interval (CI) were 0.858-0.904,0.884-0.924 and 0.851-0.898, respectively.The overall correct classification rates, applying the decision criterion of 50%, were 81.60% for APACHEII, 82.09% for SAPSII and 79.26% for LODS. Calibration of APACHEII(chi (2)=9.69) and SAPSII (chi (2)=13.50) were superior to that of LODS (chi (2)=87.22). CONCLUSION: The prognostic value of discrimination for APACHEII, SAPSII and LODS is good and basically equivalent, but calibration of acuity of APACHEII and SAPSII is much better than that of LODS.

APACHE↗

Neuronal correlates of movement dynamics in the dorsal and ventral premotor area in the monkey.

We investigated how neurons in the different motor areas of the frontal lobe reflect the movement dynamics, and how their neuronal activity undergoes plastic changes when monkeys adapt to perturbing forces (they learn new dynamics). Here we describe the results obtained in the dorsal premotor area (PMd) and ventral premotor area (PMv). Monkeys performed visually instructed, delayed reaching movements before, during and after exposure and adaptation to a viscous, curl force field. During movement planning (i.e., during an instructed delay that followed the cue and preceded the go signal), we found dynamics-related activity in PMd but not in PMv. A closer analysis revealed that the population of PMd reflected the dynamics of the upcoming movement increasingly over the course of the delay, starting from a kinematics-related signal. During movement execution, dynamics-related activity was present in both PMd and PMv. In this respect, the results for PMd were similar to that previously found for the supplementary motor area (SMA) whereas the results for PMv were more similar to that previously found for the primary motor cortex (M1). Plastic changes associated with the acquisition of new dynamics found in PMd and PMv were qualitatively similar to those previously observed in M1 and SMA. The ensemble of our experiments suggest a broader picture of the cortical control of movements, whereby multiple areas all contribute to the various sensorimotor processes, including "low" computations such as the movement dynamics, but also express a degree of specialization.

Action Potentials↗

Feedback connections to ferret striate cortex: direct evidence for visuotopic convergence of feedback inputs.

Interareal feedback connections are a fundamental aspect of cortical architecture, yet many aspects of their organization and functional relevance remain poorly understood. Previous studies have investigated the topography of feedback projections from extrastriate cortex to macaque area 17. We have extended this analysis to the ferret. We made restricted injections of cholera toxin B (CTb) into ferret area 17 and mapped the distribution of retrogradely labeled cells in extrastriate cortex. In addition to extensive label spreading within area 17, we found dense cell label in areas 18, 19, and 21 and the suprasylvian cortex and sparser connections from the lateral temporal and posterior parietal cortex. We made extensive physiological assessments of magnification factors in the extrastriate visual cortex and used these measures to convert the spread of labeled cortex in millimeters into a span in degrees of visual field. We also directly measured the visuotopic extents of receptive fields in the regions containing labeled cells in cases in which we made both CTb injections and physiological recordings in the same animals; we then compared the aggregate receptive field (ARF) of the labeled region in each extrastriate area with that of the injection site. In areas 18, 19, and 21, receptive fields of cells in regions containing labeled neurons overlapped those at the injection site but spanned a greater distance in visual space than the ARF of the injection site. The broad visuotopic extent of feedback connections is consistent with the suggestion that they contribute to response modulation by stimuli beyond the classical receptive field.

Animals↗

Syndecan-1 and E-cadherin expression in differentiated type of early gastric cancer.

AIM: To elucidate the role and alterations of syndecan-1 and E-cadherin expression in different cellular phenotypes of differentiated-type gastric cancers (DGCs). METHODS: A total of 120 DGCs at an early stage, and their adjacent mucosa, were studied both by immunohistochemistry. Syndecan-1 and E-cadherin were assessed by immunohistochemical staining with anti-syndecan-1 and anti-E-cadherin antibodies, respectively. Based on immunohistochemistry, DGCs and their surrounding mucosa were divided into four types: gastric type (G-type), ordinary type (O-type), complete-intestinal type (CI-type), and null type (N-type). RESULTS: Syndecan-1 expression was significantly lower in G-type cancers (29.4%) than in O-type (79.6%) and CI-type cancers (90%) (P<0.05, respectively), but E-cadherin did not show this result. In addition, syndecan-1 expression was significantly reduced in DGCs comprised partly of poorly differentiated adenocarcinoma or signet-ring cell carcinoma, compared to DGCs demonstrating papillary and/or tubular adenocarcinoma (P<0.05). G-type intestinal metaplasia (IM) surrounding the tumors was observed in 23.8% of G-type, 4.9% of O-type, and 6.7% of CI-type cancers (P<0.05; G-type vs O-type). Reduction of syndecan-1 expression was significant in G-type IM (25%) compared to non-G-type IM (75%; P<0.05). CONCLUSION: Loss of syndecan-1 plays a role in the growth of G-type cancers of DGCs at an early stage, and the reduction of syndecan-1 expression in IM surrounding the tumors may influence the growth of G-type cancer.

Adenocarcinoma↗

A new chamber method for mounting tissue sections.

We describe a method for mounting tissue sections onto slides that is faster and especially useful for those sections too thin or too large to be mounted easily by conventional methods. We have devised a chamber system for mounting tissue sections onto slides under buffer solution. Because of the buoyancy of sections in the buffer solution and the elimination of fluid surface tension, it is easy to move, turn, unfold, and spread even quite large or thin tissue sections. In-solution-mounting in this chamber also greatly reduces the force of the brush tip used to maneuver sections onto the slide, thus resulting in less damage to the tissue sections. This chamber greatly facilitates mounting multiple tissue sections onto a single slide. The new method is applicable to protocols that stain tissue sections either before (e.g. cytochrome oxidase) or after (e.g. cresyl violet) section mounting.

Animals↗

Premotor neuronal plasticity in monkeys adapting to a new dynamic environment.

Recent evidence indicates that premotor cortex (PM) in addition to their well-established motor functions, also play a role in nonmotor processes such as spatial attention and working memory. In the present study, neuronal activities in dorsal PM (PMd) and ventral PM (PMv) were recorded in a force field adaptation task. This study found that PM neurons show learning-related plasticity and that a neuron demonstrates either one type or multiple types of properties (i.e. kinematic, dynamic, and memory). The current study reveals that memory properties could be displayed by one or a combination of the cell activity parameters [i.e. average firing rate (AFR), dynamic range (DR), and preferred direction (PD)]. A predominant percentage of cells displayed memory properties with AFR or AFR plus other parameters. This study investigated the memory properties vs. the time sequence of the task trial [i.e. delay time (DT), movement time (MT), and target holding time (THT)] and found that: (i) most neurons display memory properties only in one time window; (ii) few neurons display memory properties in three time windows, and (iii) there are significantly more cells showing memory properties during MT than during any other time windows. There are cells that show memory I (changing their tuning curves in the force field and retaining those changes after the force field was removed), memory II (changing their tuning curves after the force field was removed), or both properties. Significantly more cells display one type of memory property (memory I or memory II) rather than both types of memory properties (memory I and memory II).

Adaptation, Physiological↗

Construction of a metastasis-associated gene subtracted cDNA library of human colorectal carcinoma by suppression subtraction hybridization.

AIM: To construct a differentially-expressed gene subtracted cDNA library from two colorectal carcinoma (CRC) cell lines with different metastatic phenotypes by suppression subtractive hybridization. METHODS: Two cell lines of human CRC from the same patient were used. SW620 cell line showing highly metastatic potential was regarded as tester in the forward subtractive hybridization, while SW480 cell line with lowly metastatic potential was treated as tester in the reverse hybridization. Suppression subtractive hybridization (SSH) was employed to obtain cDNA fragments of differentially expressed genes for the metastasis of CRC. These fragments were ligated with T vectors, screened through the blue-white screening system to establish cDNA library. RESULTS: After the blue-white screening, 235 white clones were picked out from the positive-going hybridization and 232 from the reverse. PCR results showed that 200-700 bp inserts were seen in 98% and 91% clones from the forward and reverse hybridizations, respectively. CONCLUSIONS: A subtractive cDNA library of differentially expressed genes specific for metastasis of CRC can be constructed with SSH and T/A cloning techniques.

Cell Line, Tumor↗

[Genetic damage in peripheral blood lymphocyte of coke oven workers].

OBJECTIVE: To investigate DNA and chromosome damage in peripheral blood lymphocyte of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: One hundred and thirty-seven coke oven workers and 50 controls without occupational PAHs exposure were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate DNA and chromosomal damage levels in peripheral blood lymphocyte. Urinary 1-hydroxypyrene level was used to assess the personal internal PAHs exposure dose. Personal information including occupational history, age, sex, smoking and drinking status was collected by questionnaire. RESULTS: Urinary 1-hydroxypyrene level in coke oven workers [(5.76 +/- 1.04) micro mol/mol Cr] was significantly higher than that in controls [(0.70 +/- 0.32) micro mol/mol Cr]. The rate of CBMN and comet tail moment of lymphocyte in coke oven workers [8.0 per thousand (0.0 per thousand - 30.0 per thousand ) and 2.09 (0.31 - 75.41), respectively] were higher than those in controls [3.5 per thousand (0.0 per thousand - 13.0 per thousand ) and 1.05 (0.11 - 6.63), P < 0.05]. In controls, the comet moment in smokers was significantly higher than that in non-smokers [1.44 (0.23 - 6.63) vs 0.81 (0.11 - 3.47), P < 0.05]. According to the length of work, 137 coke oven workers were classified into 3 groups i.e. 0.5 yrs , 16.0 yrs and 22.0 yrs group, and the comet moments were 1.34 (0.31 - 37.84), 2.32 (0.49 - 52.97) and 3.20 (0.45 - 75.41) respectively after adjusting the age, sex, smoking, drinking and level of urinary 1-hydroxy-pyrene. There was a rising tendency along with the increase in length of work. CONCLUSION: Under present PAHs exposure levels, both comet assay and Cytokinesis-block micronucleus test could detect PAHs-induced genotoxicity in coke oven workers, and comet assay is more suitable to assess the cumulative damage effect on DNA.

Adult↗

[A study on the inherited susceptibility of chromosomal damage in peripheral blood lymphocytes among coke oven workers].

OBJECTIVE: To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers. METHODS: One hundred and fourty-nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study. Urinary 1-hydroxypyrene levels were measured as the internal dose of PAH exposure. The 6 per 1 000 of micronucleus value was used as the cut-off value to determine whether the individual's chromosomal damage was positive. The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene-gene interaction. RESULTS: In 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2.01, 95% CI = 1.03 -3.91). Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR = 3.18, 95% CI = 1.18 - 8.62). The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR = 0.40, 95% CI = 0.19 - 0.88). No significant associations were found for other gene polymorphisms and chromosomal damage risk. In addition, the gene-gene interactions were also found among GSTM1, NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk. CONCLUSION: Significant associations between genetic polymorphisms in GSTM1, NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH-exposed workers, which related to the mechanism of PAH carcinogenesis.

Adult↗

[Differential screening of novel human metastasis-associated genes of colorectal carcinoma].

OBJECTIVE: To clone novel metastasis-associated genes of colorectal carcinoma and provide clues for the molecular mechanisms of metastasis of colorectal carcinoma. METHODS: By suppression subtractive hybridization (SSH), a pair of colorectal carcinoma cell lines with different metastatic potentials derived from the same parental cell line was used to construct two subtractive cDNA library specific for metastasis-accelerating genes or metastasis-suppressor genes. Partial positive clones in the two libraries were selected randomly and differentially screened, and the differentially expressed gene fragments obtained were sequenced and analyzed with BLAST software. The mRNA expressions of several new genes were confirmed by Northern blot analysis. RESULTS: Two subtractive cDNA libraries had 235 and 232 white clones respectively and more than 90% of the white clones had the inserts. About 200 positive clones selected randomly were differentially screened, and 29 differentially expressed genes were obtained. Fifteen unknown genes were found by sequence and BLAST analysis and had been collected by the GenBank dbEST database with the entry number of CD485499 to CD485513, among which 6 novel genes were located in the fifth chromosome. CONCLUSION: SSH is a reliable strategy for screening novel genes differentially expressed in metastasis of colorectal carcinoma. The fifth chromosome may harbor many new genes related with metastasis of colorectal carcinoma, and identified new genes can be cloned for their full length for further study of their functions.

Base Sequence↗

[Relationship of polycyclic aromatic hydrocarbon exposure with peripheral blood lymphocyte DNA damage in coke oven workers].

OBJECTIVE: To investigate the relationship between lymphocyte DNA damage and polycyclic aromatic hydrocarbons (PAHs) exposure in coke oven workers. METHODS: Two hundred and thirty-five coke oven workers and 30 controls were selected in this study. Alkaline single-cell gel electrophoresis was used to evaluate the lymphocyte DNA damage, HPLC was employed to measure 1-hydroxypyrene levels in spot urine samples which were obtained at the end of a workweek (4 days of 8 hours/day) and personal information including occupational exposure, age, sex, smoking and drinking status was collected by the questionnaire. RESULTS: The lymphocyte DNA damage level expressed as olive moment in coke oven workers was significantly higher than that of controls [2.47 (0.22 approximately 46.68) vs 0.94 (0.42 approximately 4.21), P < 0.01], and correlation between urinary 1-hydroxypyrene concentrations and olive moment was found (Spearman Partial correlation coefficient = 0.22, P < 0.01) in coke oven workers. The 1.9 of olive moment value was used as the limit to determine whether the subject DNA damage was positive. The coke oven workers had significantly higher risk in DNA damage (adjusted OR = 5.38, 95% CI = 2.07 approximately 14.08) than did controls, and dose-response relationships were also found between external exposure (exposure category) or internal doses (urinary 1-hydroxypyrene) and DNA damage. CONCLUSION: There are dose-effect and dose-response relationships between PAHs exposure and lymphocyte DNA damage in coke oven workers.

Adult↗

Localization of PIP2 activation gate in inward rectifier K+ channels.

Ion channels respond to changes in transmembrane voltage or ligand concentration by opening or closing an activation gate. In voltage-gated K+ channels, this gate has been localized to an intracellular bundle crossing. Here we examined whether this bundle crossing, or the more internal cytoplasmic pore, acts as a gate for PIP2 activation of inward rectifier K+ (Kir) channels expressed in Xenopus laevis oocytes. We studied the open/closed state-dependence of the accessibility of intracellular cationic modifiers to a position (residue Ile176 in the TM2 helix of Kir2.1) more external to the bundle crossing. Cd2+ blocked I176C mutant channels much more weakly in the closed state than in the open state, but Ag+ and sulfhydryl-specific methanethiosulfonate reagents modified the channels with similar rates in both states. These results suggest that the TM2 helices undergo conformation changes upon PIP2 binding/unbinding, but neither they nor the cytoplasmic pore close fully to form a physical gate for K+ conduction.

Amino Acid Sequence↗

[Application of suppression subtractive hybridization technique in the investigation of heat adaptation mechanism].

OBJECTIVE: To understand whether there are genes differentially expressed in association with heat adaptation in resting heat-adapted rats at normal temperature, and to evaluate the feasibility of investigating heat adaptation mechanism in light of gene differential expression. METHODS: The mRNAs were extracted from rat liver tissues and reverse transcripted into double-strand cDNAs. Suppression subtractive hybridization (SSH) was applied to compare the gene expression profiles between heat adaptation group and normal temperature control group, and cDNA subtraction libraries of the differentially expressed genes were constructed. PCR-selective differential screening technique was used to identify the differentially expressed genes. RESULTS: Six cDNA fragments were identified in the preliminary experiment to be differentially expressed. CONCLUSIONS: There are genes differentially expressed in the liver of resting heat-adapted rats in association with heat adaptation at normal temperature, and these genes may be involved in maintaining heat adaptation. This study also indicates the feasibility of investigating heat adaptation mechanism by isolating differentially expressed genes associated with heat adaptation.

Adaptation, Physiological↗