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At least 37 records · Page 2Linked to original sources
PubMed1976

Substrate-specific enzyme variation in natural populations of Drosophila pseudoobscura.

By using a number of different alcohols as substrates, eight alcohol dehydrogenase loci were discovered in Drosophila pseudoobscura. Each of these loci can take more than one substrate. Several of these loci differed in their tissue specificities and activity patterns during development. The genic variation in natural populations was studied at four of these loci and three of them were polymorphic. A quantitative study of substrate-specific differences among alleles of the same locus produced negative results. This result appears to be typical of most studies done on this aspect. From this it was concluded that the substrate specificity of enzymes is not an important factor in determining the greater amount of genic variation at Group II loci than at Group I loci, as proposed by KOJIMA, GILLESPIE and TOBARI (1970). There are several observations which suggest a different explanation for the differences in the genic variability at Group I and Group II loci: (1) There are, on an average, more isozyme loci (loci with similar substrate specificity) for enzymes in Group II than in Group I; (2) The null alleles are far more common at Group II loci than at Group I loci; (3) There is significant heterogeneity in the number of alleles and the heterozygosities at loci within each of these two groups of enzymes; (4) Relatively higher levels of genic variation are observed at Group II loci even in populations which appear to be living in homogeneous environments; and (5) Some loci (e.g. esterases) are highly polymorphic in most species investigated by gel electrophoresis techniques. Based on these general observations, it is proposed that (1) the substrate-specific differences are between isozyme loci and not between alleles of a given locus, and (2) neutral alleles are proportionately far more common at loci at Group II than at loci in Group I, because the former is under less selection constraint than the latter.

Alcohol Oxidoreductases↗
PubMed2025

The Arabidopsis TIRome informs the design of artificial TIR (Toll/interleukin-1 receptor) domain proteins.

The TIR (Toll/interleukin-1 receptor) domain is an ancient protein module that functions in immune and cell death responses across the Tree of Life. TIR domains encoded by plants and prokaryotes function as enzymes to produce diverse small molecule immune signals. Plant genomes can encode hundreds of TIR-domain containing proteins-many of which confer important agricultural disease resistance as TIR-NLR (nucleotide-binding, leucine-rich repeat) immune receptors. Despite their importance, how natural variation influences TIR enzymatic output and immunity-associated cell death is largely unexplored. We assayed a complete collection of the TIR domains of Arabidopsis thaliana Col-0 (the "AtTIRome") to explore variation in TIR metabolite production and cell death signaling. Roughly half of the AtTIRome triggered cell death in transient assays. Artificial TIR proteins designed based on consensus sequences of the AtTIRome's cell death phenotypic classes revealed polymorphisms controlling variation in TIR cell death elicitation and metabolite production. Structure-function analyses of artificial TIRs revealed that natural variation in the "BB-loop", a flexible region overlying the catalytic pocket, determines differences in function across Arabidopsis TIR-containing proteins. We further demonstrate that artificial TIRs are functional on an NLR chassis and that BB-loop variation can tune the activity of a natural TIR-NLR protein. These findings shed light on the diversity of TIR outputs and reveal methods to design and engineer TIR-based immune receptors.

Arabidopsis↗
PubMed2026

Mapping the regulatory architecture of circadian clock adaptation: A genome-wide eQTL analysis in Drosophila melanogaster.

The circadian clock enables organisms to align internal daily rhythms with environmental cues, with major consequences for survival and fitness. Although the molecular framework of this system in Drosophila melanogaster is well characterized through transcription translation feedback loops involving ten core clock genes, the genetic basis of natural variation in their expression remains poorly understood. Here, we used natural expression variation to identify expression quantitative trait loci (eQTLs) through genome-wide association mapping. Using the Drosophila Genetic Reference Panel, we measured relative expression of all core clock genes at a single time point two hours after light onset. We identified 109 significant SNPs and 28 indels associated with expression variation across the clock network. Expression levels varied widely, with Pdp1ε showing the greatest variation (an 86-fold difference between extreme lines) and cyc the least (11.3-fold). Only three significant SNPs were located within clock genes themselves, all in Clk, whereas most associations represented trans-eQTLs in genes with diverse molecular functions. Candidate regulators included transcription factors such as Abd-B, tai, and E5; RNA binding proteins including Pum, Bru-3, and Mbl; and several long noncoding and antisense RNAs. Variants were also detected in gbb and the BMP pathway transcription factor Mad. Consistent with this, Mad knockdown reduced vri expression. Together, these results reveal a complex regulatory architecture underlying natural variation in circadian gene expression.

Journal Article↗
PubMed1979

Fate of vasoactive biogenic amines and activity of enzyme phenylethanolamine-N-methyltransferase in rat adrenal gland during the course of pregnancy, parturition and postpartum.

Influence of pregnancy, parturition and postparturition upon natural evolution of adrenaline, dopamine and enzyme of adrenaline synthesis, phenylethanolamine-N-methyltransferase in the adrenal gland was studied. Adrenaline content of the adrenal gland showed a progressive decrease from the 14th to the 18th day postcoitum. The mean values for adrenaline remained lower than the value of day 14 throughout the course of pregnancy up to day 21 postcoitum. At parturition (0 to 4 h) adrenaline declined again to its minimum value but was accompanied by an increase in the adrenal adrenaline level 24 h postpartum. The activity of enzyme phenylethanolamine-N-methyltransferase followed a similar pattern of evolution as that of adrenaline during pregnancy and postpartum. Dopamine concentration of the adrenal gland showed nonsignificant increases during days 14--18 postcoitum. At day 20 postcoitum adrenal dopamine was decreased to its minimum value and this decrease persisted up to day 21 postcoitum. At day 22 postcoitum, adrenal dopamine increased sharply to its maximum value but was again back to the level of day 21 at 0 h parturition. At 24 h postpartum, dopamine content decreased maximally again. The results presented here suggest that the content of vasoactive biogenic amines and the enzyme of adrenaline synthesis go through important natural variations during pregnancy, parturition and postpartum from day 14 postcoitum to 24 h postpartum. This phenomenon does not seem to be merely a cyclic effect. All these variations can be attributed to modified endocrine activity of the pregnant animals by correlating natural variations in steroid hormone levels with the observed changes in biogenic amines, since it is well established that most of the hormonal and nonhormonal steroids affect catecholamine regulation. The observed changes in amine levels could have important influence for the termination of pregnancy.

Adrenal Glands↗
PubMed1976

Unimodality, symmetry and the step-state hypothesis of electrophoretic variation in natural populations.

The population frequency distributions of electromorphs of polymorphic loci, when ordered by electrophoretic mobility, tend strongly and significantly to be both unimodal and symmetrical. Such distributions are predicted by all step-change models and their generality in published data can be construed as supportive of the step-change hypothesis. On the other hand, unimodality and symmetry might also be due to artifactual "unit perception" biases that affect the interpretation and reporting of electrophoretic data. In any case, it appears that perceived electromorphs are highly heterogeneous.

Alleles↗
PubMed1979

Alterations in activity of enzyme catechol-O-methyltransferase in central and peripheral regions of the rat and rabbit during pregnancy, parturition, and the postpartum period.

Natural variations in the activity of the enzyme catechol-O-methyltransferase in central and peripheral regions of the rat and rabbit during pregnancy and parturition were observed. All of the organs of the rat showed a decrease in enzyme activity up to the twenty-first day of pregnancy. Rabbit tissues also demonstrated a decrease in catechol-O-methyltransferase activity during Days 24 to 30 after coitus. Increases in activity of the rat ovary, brain, and hypothalamus took place from during Day 21 after coitus to the onset of parturition. The enzyme activity in the rat hypothalamus reached its maximum level at four hours post partum from the Day 21 value, but the rabbit hypothalamus showed the maximum activity at 0 hour parturition. During post partum hours, rat brain catechol-O-methyltransferase activity was very high but the rabbit brain showed a very low level of activity. Rabbit uterine activity reached its minimum value at Day 31 after coitus, but at the comparable intervals the situation was inversed in the rat. Results show an important modification of monoamine degradation by 3-O-methylation during midgestation in the central and peripheral regions. These modifications may be attributed to the natural variations in endocrine activity taking place during pregnancy.

Adrenal Glands↗
PubMed2025

Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to the benzimidazole (BZ) drug class is nearly ubiquitous in many species and is associated with mutations in beta-tubulin genes. However, mutations in beta-tubulin alone do not fully explain all BZ resistance. We performed a genome-wide association study using a genetically diverse panel of Caenorhabditis elegans strains to identify loci that contribute to resistance to the BZ drug thiabendazole (TBZ). We identified a quantitative trait locus (QTL) on chromosome V independent of all beta-tubulin genes and overlapping with two promising candidate genes, the cytochrome P450 gene cyp-35D1 and the nuclear hormone receptor nhr-176. Both genes were previously demonstrated to play a role in TBZ metabolism. NHR-176 binds TBZ and induces the expression of CYP-35D1, which metabolizes TBZ. We generated single gene deletions of cyp-35D1 and nhr-176 and found that both genes play a role in TBZ response. A predicted high-impact lysine-to-glutamate substitution at position 267 (K267E) in CYP-35D1 was identified in a sensitive strain, and reciprocal allele replacement strains in different genetic backgrounds were used to show that the lysine allele conferred increased TBZ resistance. Using competitive fitness assays, we found that neither allele was deleterious, but the lysine allele was selected in the presence of TBZ. Additionally, we found that the lysine allele significantly increased the rate of TBZ metabolism compared to the glutamate allele. Moreover, yeast expression assays showed that the lysine version of CYP-35D1 had twice the enzymatic activity of the glutamate allele. To connect our results to parasitic nematodes, we analyzed four Haemonchus contortus cytochrome P450 orthologs but did not find variation at the 267 position in fenbendazole-resistant populations. Overall, we confirmed that variation in this cytochrome P450 gene is the first locus independent of beta-tubulin to play a role in BZ resistance.

Animals↗
PubMed2026

Integrating GWAS and Transcriptome Analysis Identifies Candidate Genes for Kernel Starch Quality Traits in Maize.

Maize (Zea mays L.) starch quality is a complex trait with significant implications for grain processing and industrial applications. However, the genetic basis underlying starch quality, particularly for gelatinization and thermodynamic properties, remains poorly understood. In this study, we evaluated 12 starch quality traits, including seven gelatinization characteristics, four thermodynamic traits, and kernel starch content (KSC) in a diverse panel of 335 maize inbred lines. Considerable phenotypic variation was observed for all traits. A total of 228 quantitative trait loci (QTLs) were significantly associated with 12 starch quality traits through genome-wide association studies (GWAS). By integrating a dynamic transcriptome analysis of two maize inbred lines with contrasting starch quality, we identified 60 candidate genes. One gene, waxy1, encoding a starch synthase, was found to be associated with enthalpy of gelatinization (ΔHgel) and pasting temperature (Ptemp). Six variants in waxy1 contributed to natural variation in ΔHgel and Ptemp, and a cost-effective InDel and two PARMS-based molecular markers were developed and validated in 144 maize inbred lines, enabling efficient marker-assisted selection. Our findings provide key genes and molecular markers for high-quality maize breeding with improved starch properties.

Zea mays↗
PubMed1977

[Variability of Act. noursei, the producer of nystatin, under the influence of the separate and combined actions of hydrogen peroxide and UV rays].

The lethal and mutagenic effect of hydrogen dioxide used alone and in combination with UV light on the nystatin-producing strain 408 of Act. noursei was studied. The spore survival decreased with an increase in the hydrogen dioxide concentration and the irradiation dose. When the above mutagens were used in combination the lethality was close to the expected one on the summation effect. Under the effect of hydrogen dioxide and most of its combinations with UV light the morphological variation of strain 408 was close to the natural variation or somewhat lower. This phenomenon was possibly associated with significant lethal effect of hydrogen dioxide on the morphologically changed forms of the strain. Variation of the nystatin-roducing strain with respect to nystatin production increased mainly at the account of higher rate of low active variants especially under combined effect of the mutagens. The lethal and mutagenic effect of the combined use of hydrogen dioxide and UV light on the nystatin-producing organism did not depend on the exposure sequence.

Dose-Response Relationship, Drug↗
PubMed1979

Skeletal concentrations of lead in ancient Peruvians.

The level of biologic lead (expressed as the ratio of atomic lead to atomic calcium) in bones of Peruvians buried 1600 years ago was found to be 3 x 10(-8), as compared to 2100 to 3500 x 10(-8) in the bones of present-day residents of England and the United States. The ratio of barium to calcium was 2 to 3 x 10(-6) in bones of ancient Peruvians and present-day Americans. Barium and lead have similar morphologic distributions in organisms, so this discrepancy for lead must result from overexposure of present-day people to industrial lead and not from natural variations. The magnitude of this discrepancy has been confirmed by two different lines of investigation not reported in this article. This new evidence suggests that natural interactions of lead in human cells have not yet been determined because reagents, nutrients and controls used in laboratory and field studies have been contaminated with lead far in excess of naturally occurring levels.

Adult↗
PubMed1976

Na+ transport by rabbit urinary bladder, a tight epithelium.

By in vitro experiments on rabbit bladder, we reassessed the traditional view that mammalian urinary bladder lacks ion transport mechanisms. Since the ratio of actual-to-nominal membrane area in folded epithelia is variable and hard to estimate, we normalized membrane properties to apical membrane capacitance rather than to nominal area (probably 1 muF approximately 1 cm2 actual area). A new mounting technique that virtually eliminates edge damage yielded resistances up to 78,000 omega muF for rabbit bladder, and resistances for amphibian skin and bladder much higher than those usually reported. This technique made it possible to observe a transport-related conductance pathway, and a close correlation between transepithelial conductance (G) and short-circuit current (Isc) in these tight epithelia. G and Isc were increased by mucosal (Na+) [Isc approximately 0 when (Na+) approximately 0], aldosterone, serosal (HCO-3) and high mucosal (H+); were decreased by amiloride, mucosal (Ca++), ouabain, metabolic inhibitors and serosal (H+); and were unaffected by (Cl-) and little affected by antidiuretic hormone (ADH). Physiological variation in the rabbits' dietary Na+ intake caused variations in bladder G and Isc similar to those caused by the expected in vivo changes in aldosterone levels. The relation between G and Isc was the same whether defined by diet changes, natural variation among individual rabbits, or most of the above agents. A method was developed for separately resolving conductances of junctions, basolateral cell membrane, and apical cell membrane from this G--Isc relation. Net Na+ flux equalled Isc. Net Cl- flux was zero on short circuit and equalled only 25% of net Na+ flux in open circuit. Bladder membrane fragments contained a Na+-K+-activated, ouabain-inhibited ATPase. The physiological significance of Na+ absorption against steep gradients in rabbit bladder may be to maintain kidney-generated ion gradients during bladder storage of urine, especially when the animal is Na+-depleted.

Adenosine Triphosphatases↗
PubMed2026

Rice LSD1-like Genes: Genome-Wide Characterization and Evidence Linking OsLSD3 to Plant Height.

LSD1-like zinc-finger proteins participate in programmed cell death, redox homeostasis, and stress responses in plants, but their functional diversification and contributions to agronomic variation in rice remain poorly defined. This study aimed to characterize the rice LSD1-like gene family and evaluate the potential agronomic roles of selected members, with particular emphasis on OsLSD3. Genome-wide analyses were integrated with OsLSD3 natural variation and haplotype analyses in 4666 rice accessions, CRISPR/Cas9 mutant phenotyping in the ZH11 background, and subcellular localization assays. Seven LSD1-like genes were identified and showed substantial divergence in protein architecture, gene organization, promoter cis-element profiles, and tissue- and stress-responsive expression. OsLSD3 formed six population-structured haplotypes, and two common Japonica haplotypes differed significantly in plant height. Consistently, two independent oslsd3 mutant lines were taller than the wild type, whereas additional changes in grain-related traits were line-specific. OsLSD2 and OsLSD3 localized mainly to the nucleus, while OsLSD4 was predominantly nuclear with weak cytoplasmic localization. These results identify OsLSD3 as the strongest candidate among the examined members for further investigation of plant height- and grain-related traits, while OsLSD2 and OsLSD4 represent additional candidates for grain-trait regulation. Further validation using additional alleles and environments is required.

LSD1-like↗
PubMed2025

Long-Read Sequencing of the MUC1 VNTR: Genomic Variation, Mutational Landscape, and Its Impact on ADTKD Diagnosis and Progression.

BACKGROUND: ADTKD-MUC1 is caused by frameshift mutations in MUC1 gene that produce a frameshifted protein (MUC1fs) toxic to kidney cells. The gene's variable number of tandem repeats (VNTR), with high GC content, makes it largely inaccessible to standard sequencing. As a result, both the reference sequence and natural variation in this region remain poorly defined, complicating mutation detection and data interpretation. Standard methods also fail to pinpoint the exact VNTR unit affected, limiting insight into mutation mechanisms and genotype-phenotype correlations. METHODS: We employed Single Molecule, Real-Time (SMRT) sequencing and characterized the genomic sequence of MUC1 in 300 individuals including 279 individuals from 143 families suspected of having ADTKD-MUC1. We compared these results to those obtained using the CLIA-approved mass spectrometry-based probe extension (PE) assay, which specifically detect the most prevalent 59dupC mutation. We correlated the structural features of the MUC1 VNTR with the rate of kidney function decline in affected individuals. RESULTS: We identified MUC1 consensus sequences for 205 unique VNTR alleles, with 9 distinct types of frameshift mutations present on 52 distinct mutated VNTR alleles. MUC1 frameshift mutations were identified in 71 of 143 families (50%) with suspected ADTKD, comprising 135 genetically affected individuals (48%). The SMRT assay exhibited complete concordance and revealed that the PE assay is capable of detecting frameshift mutations in approximately 85% of affected families. The constellation of VNTR structures supports a genotype-progression model, in which fast progressors exhibit a significantly lower number of repeat units on the wild-type allele and a higher number of repeats on the mutation-bearing allele, including an increased number of frameshifted repeat units. CONCLUSIONS: SMRT sequencing outperforms current diagnostic methods for ADTKD-MUC1 and reveals the prognostic value of VNTR structures. Although their contribution to disease progression is modest (~6% variance explained), it remains biologically and clinically meaningful.

Autosomal Dominant Tubulointerstitial Kidney Disea↗