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Biology subjects

Ma, C.

Publications and source records attributed to Ma, C..

At least 199 records · Page 11Linked to original sources

Comparison of SARS-CoV-2 infections among 3 species of non-human primates

COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and New world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta, 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory samples reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis, the tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C. jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV-2 infection, followed by M. fascicularis and C. jacchus. One Sentence SummaryM. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus.

microbiology↗

Amino acid quality modifies the quantitative availability of protein for reproduction in Drosophila melanogaster

Diet composition, especially the relative abundance of key macronutrients, is well known to affect animal wellbeing by changing reproductive output, metabolism and length of life. However, less attention has been paid to the ways the quality of these nutrients modify these macronutrient interactions. Nutritional Geometry can be used to model the effects of multiple dietary components on life-history traits and to compare these responses when diet quality is varied. Previous studies have shown that dietary protein quality can be increased for egg production in Drosophila melanogaster by matching the dietary amino acid proportions to the balance of amino acids used by the sum of proteins in the flys in silico translated exome. Here, we show that dietary protein quality dramatically alters the effect of protein quantity on female reproduction across a broad range of diets varying in both protein and carbohydrate concentrations. These data show that when sources of ingredients vary, their relative value to the consumer can vastly differ and yield very different physiological outcomes. Such variations could be particularly important for meta analyses that look to draw generalisable conclusions from diverse studies.

physiology↗

Population sequencing enhances understanding of tea plant evolution

Tea is an economically important plant characterized by a large genome size and high heterozygosity and species diversity. In this study, we assembled a 3.26 Gb high-quality chromosome-scale genome for tea using the Longjing 43 cultivar of Camellia sinensis var. sinensis. Population resequencing of 139 tea accessions from around the world was used to investigate the evolution of tea and to reveal the phylogenetic relationships among tea accessions. With the spread of tea cultivation, hybridization has increased the heterozygosity and wide-ranging gene flow among tea populations. Population genetics and transcriptomics analyses revealed that during domestication, the selection for disease resistance and flavor in C. sinensis var. sinensis populations has been stronger than that in C. sinensis var. assamica populations. The data compiled in this study provide new resources for the marker assisted breeding of tea and are a basis for further research on the genetics and evolution of tea.

genomics↗

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) is the most common primary lung cancer, and increasing evidence indicates the clinical importance of the microenvironment in LUAD. Tumor-infiltrating immune cells play an important role in promoting or inhibiting tumor growth. This study aimed to identify immune-related prognostic genes that were associated with the LUAD microenvironment. MethodsWe used the "estimate" R package to calculate the immune/stromal scores of each sample of GSE72094 based on the ESTIMATE algorithm. Then we looked up relationships between patients characteristics and immune/stromal scores. After that, we divided the samples into two groups: high and low scores, identified the common differentially expressed genes (DEGs), and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) on the common DEGs. After conducting the overall survival analysis of the common DEGs, prognostic genes were harvested. Then we constructed the protein-protein interaction network and performed the enrichment of GO and KEGG for the prognostic genes. Crucial prognostic genes were obtained after validating in two independent data sources (GSE68465 and TIMER). Finally, we investigated the immune correlates of the crucial prognostic genes based on the TIMER. ResultsImmune scores did not vary with gender, age, smoking history, tumor stage, and EGFR status, but vary with the status of KRAS, STK11, and TP53. For the stromal scores, only the status of STK11 and TP53 mattered. Reduced immune score predicted poor prognosis of LUAD. 357 common DEGs were found, of which 108 were identified as prognostic genes after overall survival analysis. GO and KEGG analysis found that common DEGs and prognostic genes were both mainly involved in immune-related items. After validation in two independent data sources, 12 genes were validated to be crucial prognostic genes linked to prognosis. After investigated the TIMER, all 12 genes were correlated with the main immune cell types. Conclusion12 immune-related prognostic genes were discovered relating to the microenvironment in LUAD. These findings suggest that the composition of the tumor microenvironment affects the clinical outcomes of LUAD, and it may provide a basis for the development of novel prognostic biomarkers and immunotherapy for LUAD.

cancer biology↗

The Pathogenicity of 2019 Novel Coronavirus in hACE2 Transgenic Mice

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Kochs postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.

microbiology↗

Plastid EF-Tu Regulates Root Development through Both the ATM Pathway and GUN1

Impaired plastid translation affects various aspects of plant development, but the molecular mechanism remains elusive. Here, we described that the reduced function of plastid translation elongation factor EF-Tu encoded by RAB GTPASE HOMOLOG 8D (Rab8d) elicits defects in root development, including the reduced meristem size, programmed cell death (PCD) in the stem cell niche (SCN), and quiescent center (QC) division. We found that the ATAXIA-TELANGIECTASIA-MUTATED (ATM)-SUPPRESSOR OF GAMMA RESPONSE 1 module mediated overexpression of SIAMSE-RELATED 5 in the root meristem region is responsible for the reduced meristem size in the rab8d mutant through arresting the cell cycle. The QC activation in rab8d is dependent on ETHYLENE RESPONSE FACTOR 115, which expression is tightly associated with the PCD in SCN. We further found that Rab8d physically interacts with GENOME UNCOUPLED 1 (GUN1), and GUN1 is required for inducing PCD in the rab8d SCN. However, the loss of GUN1 function in rab8d severely impairs the root architecture, suggesting that the GUN1-mediated renewal of stem cells is essential for maintaining root growth. Our observations extend our knowledge on the roles of ATM and GUN1 in regulating root development through mediating plastid translation dependent signals. One-sentence summaryThe rab8d-dependent plastid signal mediated by ATM and GUN1 regulates the root meristem size and renewal of root stem cells, respectively.

plant biology↗

Regulating AMPK and insulin level by Vinegar, Swimming and Refeeding on High-Fat Diet Rats to Rebuild Lipid Homeostasis

Our aims were to explore the effects of dietary and behavior interventions on lipometabolism caused by unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks before being divided into 4 groups and intervened for another 4 weeks. 8 of them were classified into high-fat control group and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet with swimming group and 7 were just for refeeding normal diet group. Then the data of body weight was recorded and analyzed. Serum, pancreas, liver, cardiac tissues and epididymis adipose were sampled as required. Indexes of serum were tested by kits. AMPK, HNF1, CTRP6 from tissues were detected by western blot. According to our experiments, Swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by up-regulating the expression of pancreas AMPK. To be more specific, the refeeding rats showed lower T-CHO (P<0.001) and LDL-C (P<0.05), but higher weight gain (P<0.001),insulin level (P<0.01)and pancreas AMPK (P<0.01)than high-fat control rats. Compared with rats experimented by swimming or rice vinegar, they showed higher weight gain (P<0.001),insulin level (P<0.01)and HNF1, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.

molecular biology↗

Enhancing generating and collecting efficiency of single particle upconverting luminescence at low-level power excitation

Upconverting luminescent nanoparticles are photostable, non-blinking, and low chemically toxic fluorophores that are emerging as promising fluorescent probe at single-molecule level. High luminescence intensity upconversion nanoparticles (UCNPs) is achieved with highly doped rare-earth ions co-doped (20% Yb3+) using high excitation power (>2.5 MW/cm2). However, such particles are inadequate for in-vitro live-cell imaging and single-particle tracking since high excitation power can cause photodamage. Here, we compared UCNPs luminescence intensities with different dopants concentrations and presented a more efficient ([~]7x) UCNPs at low excitation power by increasing the concentrations of Yb3+ and Tm3+ dopants (NaYF4: 60% Yb3+, 8% Tm3+) and adding a core-shell structure.

biophysics↗

Finding ranges of optimal transcript expression quantification in cases of non-identifiability

Current expression quantification methods suffer from a fundamental but under-characterized type of error: the most likely estimates for transcript abundances are not unique. This means multiple estimates of transcript abundances generate the observed RNA-seq reads with equal likelihood, and the underlying true expression cannot be determined. This problem is called non-identifiability for probabilistic models, and is further exacerbated by incomplete reference transcriptome. That is, reads may be sequenced from unannotated expressed transcripts. Graph quantification is a generalization to transcript quantification, accounting for the reference incompleteness by allowing exponentially many unannotated transcripts to express reads. We propose methods to calculate a "confidence range of expression" for each transcript, representing its possible abundance across equally optimal estimates for both quantification models. This range informs both whether a transcript has potential estimation error due to non-identifiability and the extent of the error. Applying our methods to the Human Body Map data, we observe 35%-50% of transcripts potentially suffer from inaccurate quantification caused by non-identifiability. When comparing the expression between isoforms in one sample, we find that the degree of inaccuracy of 20%-47% transcripts can be so large that the ranking of expression between the transcript and its sibling isoforms cannot be determined. When comparing the expression of a transcript between two groups of RNA-seq samples in differential expression analysis, we observe that the majority of detected differentially expressed transcripts are reliable with a few exceptions after considering the ranges of the optimal expression estimates. The code for computing the range of expression is available at https://github.com/Kingsford-Group/subgraphquant. The code for the involved analyses is available at https://github.com/Kingsford-Group/subgraphquantanalysis.

bioinformatics↗

Estimating mutual information under measurement error

Mutual information is widely used to characterize dependence between biological signals, such as co-expression between genes or co-evolution between amino acids. However, measurement error of the biological signals is rarely considered in estimating mutual information. Measurement error is widespread and non-negligible in some cases. As a result, the distribution of the signals is blurred, and the mutual information may be biased when estimated using the blurred measurements. We derive a corrected estimator for mutual information that accounts for the distribution of measurement error. Our corrected estimator is based on the correction of the probability mass function (PMF) or probability density function (PDF, based on kernel density estimation). We prove that the corrected estimator is asymptotically unbiased in the (semi-) discrete case when the distribution of measurement error is known. We show that it reduces the estimation bias in the continuous case under certain assumptions. On simulated data, our corrected estimator leads to a more accurate estimation for mutual information when the sample size is not the limiting factor for estimating PMF or PDF accurately. We compare the uncorrected and corrected estimator on the gene expression data of TCGA breast cancer samples and show a difference in both the value and the ranking of estimated mutual information between the two estimators.

bioinformatics↗

A Priori Activation of Apoptosis Pathways of Tumor (AAAPT) Technology: Development of Targeted Apoptosis Initiators for Cancer Treatment.

Cancer cells develop tactics to circumvent the interventions by desensitizing themselves to interventions. The principle routes of desensitization include a) activation of survival pathways (e.g. NF-kB, PARP) and b) downregulation of cell death pathways (e.g. CD95/CD95L). As a result, it requires high therapeutic dose to achieve tumor regression which, in turn damages normal cells through the collateral damaging effects. Methods are needed to sensitize the low and non-responsive resistant tumor cells including cancer stem cells (CSCs) in order to evoke a better response from the current treatments. Current treatments including chemotherapy can induce cell death only in bulk cancer cells sparing CSCs and cancer resistant cells (CRCs) which are shown to be responsible for high recurrence of disease and low patient survival. Here, we report several novel tumor targeted sensitizers derived from the natural Vitamin E analogue (AMP-001-003). The drug design is based on a novel concept "A priori activation of apoptosis pathways of tumor technology (AAAPT) which is designed to activate specific cell death pathways and inhibit survival pathways simultaneously. Our results indicate that AMP-001-003 sensitize various types of cancer cells including MDA-MB-231 (triple negative breast cancer), PC3 (prostate cancer) and A543 (ling cancer) cells resulting in reducing the IC-50 of doxorubicin in vitro. At higher dose, AMP-001 acts as an anti-tumor agent on its own. The synergy between AMP-001 and doxorubicin could pave a new pathway to use AMP-001 as a neoadjuvant to chemotherapy to achieve a better efficacy and reduced off-target toxicity by the current treatments. Summary StatementA Priori Activation of Apoptosis Pathways of Tumor often referred to as "AAAPT" is a novel targeted tumor sensitizing technology which synergizes with chemotherapy to enhance the treatment efficacy.

cancer biology↗

A novel dynamic network imaging analysis method reveals aging-related fragmentation of cortical networks in mouse

Network analysis of large-scale neuroimaging data has proven to be a particularly challenging computational problem. In this study, we adapt a novel analytical tool, known as the community dynamic inference method (CommDy), which was inspired by social network theory, for the study of brain imaging data from an aging mouse model. CommDy has been successfully used in other domains in biology; this report represents its first use in neuroscience. We used CommDy to investigate aging-related changes in network parameters in the auditory and motor cortices using flavoprotein autofluorescence imaging in brain slices and in vivo. Analysis of spontaneous activations in the auditory cortex of slices taken from young and aged animals demonstrated that cortical networks in aged brains were highly fragmented compared to networks observed in young animals. Specifically, the degree of connectivity of each activated node in the aged brains was significantly lower than those seen in the young brain, and multivariate analyses of all derived network metrics showed distinct clusters of these metrics in young vs. aged brains. CommDy network metrics were then used to build a random-forests classifier based on NMDA-receptor blockade data, which successfully recapitulated the aging findings, suggesting that the excitatory synaptic substructure of the auditory cortex may be altered during aging. A similar aging-related decline in network connectivity was also observed in spontaneous activity obtained from the awake motor cortex, suggesting that the findings in the auditory cortex are reflections of general mechanisms that occur during aging. Therefore, CommDy therefore provides a new dynamic network analytical tool to study the brain and provides links between network-level and synaptic-level dysfunction in the aging brain.

neuroscience↗

Large-scale Analysis of 2,152 dataset reveals key features of B cell biology and the antibody repertoire

Antibody repertoire sequencing (Ig-seq) has been widely used in studying humoral responses, with promising results. However, the promise of Ig-seq has not yet been fully realized, and key features of the antibody repertoire remain elusive or controversial. To clarify these key features, we analyzed 2,152 high-quality heavy chain antibody repertoires, representing 582 donors and a total of 360 million clones. Our study revealed that individuals exhibit very similar gene usage patterns for germline V, D, and J genes and that 53 core V genes contribute to more than 99% of the heavy chain repertoire. We further found that genetic background is sufficient but not necessary to determine usage of V, D, and J genes. Although gene usage pattern is not affected by age, we observed a significant sex preference for 24 V genes, 9 D genes and 5 J genes, but found no positional bias for V-D and D-J recombination. In addition, we found that the number of observed clones that were shared between any two repertoires followed a linear model and noted that the mutability of hot/cold spots and single nucleotides within antibody genes suggested a strand-specific somatic hypermutation mechanism. This population-level analysis resolves some critical characteristics of the antibody repertoire and thus may serve as a reference for research aiming to unravel B cell-related biology or diseases. The metrics revealed here will be of significant value to the large cadre of scientists who study the antibody repertoire.

immunology↗

Identifying Sialylation Linkages at the Glycopeptide Level by Glycosyltransferase Labeling Assisted Mass Spectrometry (GLAMS)

Precise assignment of sialylation linkages at the glycopeptide level is of importance in bottom-up glycoproteomics, and is also an indispensable step to understand the function of glycoproteins in pathogen-host interactions and cancer progression. Even though some efforts have been dedicated to the discrimination of 2,3/2,6-sialylated isomers, unambiguous identification of sialoglycopeptide isomers is still needed. Herein, an innovative strategy of glycosyltransferase labeling assisted mass spectrometry (GLAMS) was developed. After specific enzymatic labeling, oxonium ions from higher-energy C-trap dissociation (HCD) fragmentation of 2,3-sailoglycopeptides generate unique reporters to distinctly differentiate those of 2,6-sailoglycopeptide isomers. Using this strategy, a total of 1,236 linkage-specific sialoglycopeptides were successfully identified from 161 glycoproteins in human serum.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC=\"FIGDIR/small/811554v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (20K):\norg.highwire.dtl.DTLVardef@eada4borg.highwire.dtl.DTLVardef@a1a7bdorg.highwire.dtl.DTLVardef@10b72d9org.highwire.dtl.DTLVardef@a11ebd_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Punishment insensitivity emerges from impaired contingency detection, not aversion insensitivity or reward dominance

Our behaviour is shaped by its consequences - we seek rewards and avoid harm. It has been reported that individuals vary markedly in their avoidance of detrimental consequences, i.e. in their sensitivity to punishment. The underpinnings of this variability are poorly understood; they may be driven by differences in aversion sensitivity, motivation for reward, and/or instrumental control. We examined these hypotheses by applying several analysis strategies to the behaviour of rats (n = 48; 18 female) trained in a task permitting concurrent assessment of punishment, reward-seeking, and Pavlovian fear. We show that punishment insensitivity is a unique phenotype, unrelated to differences in reward-seeking and Pavlovian fear, and due to a failure of instrumental control. Subjects insensitive to punishment are afraid of aversive events, they are simply unable to change their behaviour to avoid them.

neuroscience↗

Microscaled Proteogenomic Methods for Precision Oncology

Cancer proteogenomics integrates genomics, transcriptomics and mass spectrometry (MS)-based proteomics to gain insights into cancer biology and treatment efficacy. A proteogenomics approach was therefore developed for frozen core biopsies using tissue-sparing specimen processing with a \"microscaled\" proteomics workflow. For technical proof-of-principle, biopsies from ERBB2 positive breast cancers before and 48-72 hours after the first dose of neoadjuvant trastuzumab-based chemotherapy were analyzed. ERBB2 protein and phosphosite levels, as well as mTOR target phosphosites, were significantly more suppressed upon treatment in cases associated with pathological complete response, suggesting MS-based pharmacodynamics is achievable. Furthermore, integrated analyses indicated potential causes of treatment resistance including the absence of ERBB2 amplification (false-ERBB2 positive) and insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification (pseudo-ERBB2 positive). Candidate resistance features in true-ERBB2+ cases, including androgen receptor signaling, mucin expression and an inactive immune microenvironment were observed. Thus, proteogenomic analysis of needle core biopsies is feasible and clinical utility should be investigated.

cancer biology↗

Single-cell tracing of the first hematopoietic stem cell generation in human embryos

Tracing the emergence of the first hematopoietic stem cells (HSCs) in human embryos, particularly the scarce and transient precursors thereof, is so far challenging, largely due to technical limitations and material rarity. Here, using single-cell RNA sequencing, we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis. The transcriptomically defined HSC-primed hemogenic endothelial cells (ECs) were captured at Carnegie stage 12-14 in an unbiased way, showing an unambiguous arterial EC feature with the up-regulation of RUNX1, MYB and ANGPT1. Importantly, subcategorizing CD34+CD45- ECs into CD44+ population strikingly enriched hemogenic ECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed hemogenic ECs to hematopoietic stem progenitor cells, and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs, including EMCN, PROCR and RUNX1T1. We also uncovered another temporally and molecularly distinct intra-embryonic hemogenic EC population, which was detected mainly at earlier CS 10 and lacked the arterial feature. Finally, we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSC-primed hemogenic ECs. The cellular and molecular programs and interactions that underlie the generation of the first HSCs from hemogenic ECs in human embryos, together with distinguishing HSC-primed hemogenic ECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.

developmental biology↗

Discovery of powdery mildew resistance gene candidates from Aegilops biuncialis chromosome 2Mb based on transcriptome sequencing

Powdery mildew is one of the most widespread diseases of wheat. Breeding resistant varieties by utilization of resistance genes is considered as the most economic and effective method of controlling this disease. Previous study showed that the gene(s) at 2Mb in Chinese Spring (CS)-Aegilops biuncialis 2Mb disomic addition line TA7733 conferred high resistance to powdery mildew. In this study, 15 Bgt isolates prevalent in different regions of China were used to further test the resistance spectrum of TA7733. As a result, TA7733 was high resistance to all tested isolates, indicating that the gene(s) on chromosome 2Mb was broad-spectrum powdery mildew resistance. In order to mine resistance gene candidates and develop 2Mb-specific molecular markers to assist the transfer resistance gene(s) at chromosome 2Mb, RNA-seq of TA7733 and CS was conducted before and after Bgt-infection, generating a total of 158,953 unigenes. Of which, 7,278 unigenes were TA7733-specific which were not expressed in CS, and 295 out of these 7,278 unigenes were annotated as R genes. Based on Blastn against with CS Ref Seq v1.0, 61 R genes were further mapped to homoeologous group 2. Analysis of R gene-specific molecular markers designed from R gene sequences verified 40 out of 61 R genes to be 2Mb specific. Annotation of these 40 R genes showed most genes encoded nucleotide binding leucine rich repeat (NLR) protein, being most likely resistance gene candidates. The broad-spectrum powdery mildew resistance gene(s), disease resistance gene candidates, and functional molecular markers of 2Mb-specific in present study will not only lay foundations for transferring disease resistance gene(s) from 2Mb to common wheat by inducing CS-Ae. biuncialis homoeologous recombination, but also provide useful candidates for isolating and cloning resistance gene(s) and dissecting molecular and genetic mechanisms of disease resistance from 2Mb.

genetics↗