Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “dosage balance”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Why Specialized Metabolism Recurrently Emerges in Plants: Chemical and Genomic Biases in Metabolic Diversification.

Specialized metabolism plays a central role in mediating ecological interactions and adaptive responses in plants, while leaving enduring signatures in genome structure and evolution. Here, we synthesize advances in genomics, biochemistry, and evolutionary biology into a metabolite-driven genetic diversification (MGD) framework, in which metabolite chemistry biases the generation, retention, and reuse of genetic variation. When metabolic flux produces reactive, inhibitory, or otherwise costly intermediates, pathways handling these liabilities recurrently recruit gene dosage changes, duplication, and divergence at catalytic and regulatory choke points. These biases do not impose deterministic outcomes; instead, they shape which genomic variants are preferentially sampled and retained under selection, giving rise to predictable patterns of genomic change. Genome multiplication-through whole-genome duplication, allopolyploidy, and cell type-specific endoreduplication-amplifies these effects by altering dosage balance, regulatory context, and retention trajectories. Integrating MGD with genome-scale dosage dynamics explains why specialized metabolism repeatedly converges on similar solutions across plant lineages, even amid extensive genomic turnover and chemical diversity.

Journal Article↗
PubMed2026

Genome-wide identification, structural characterization, and evolutionary analysis of growth-related gene families in African catfish (Clarias gariepinus).

The somatotropic axis encompassing growth hormone (GH), insulin-like growth factor (IGF), myostatin (MSTN), and prolactin (PRL) signalling cascades is the master regulator of somatic growth, metabolism, and development in vertebrates. African catfish (Clarias gariepinus), a commercially pivotal aquaculture species, now possesses a chromosome-level reference genome (CGAR_prim_01v2); however, a systematic, genome-wide characterization spanning all five interconnected growth-related gene families has not previously been undertaken in this species. Here, we identified and characterized 15 growth-related genes spanning gh1, ghra, ghrb, Igf1, Igf2a, Igf2b, igf1ra, Igf1rb, Igf2r, Mstna, Mstnb, prl, prlra, prlrb, and smtlb distributed across 13 chromosomes. Complete one-to-one orthology with zebrafish confirmed strong dosage-balance conservation across >120 million years of teleost divergence. Physicochemical analysis resolved a clear biochemical dichotomy between compact, basic secreted ligands (19.88-45.81 kDa; pI up to 10.02) and large, acidic, heavily glycosylated membrane receptors (56.82-270.80 kDa; pI 4.85-5.97). Phylogenetic analysis confirmed 3R whole-genome duplication origins for all paralog pairs, while synteny analysis revealed a disruption of the ancestral gh1-prl chromosomal block in C. gariepinus, a finding that warrants further comparative and functional investigation. This genomic atlas provides the sequence and structural information including exon-intron boundaries, domain architecture, and chromosomal coordinates needed as a prerequisite for future marker-assisted selection and CRISPR-based myostatin-editing efforts in African catfish aquaculture, though translation into applied breeding outcomes will require subsequent functional and expression studies.

Animals↗
PubMed1977

[Glucose and K+ balance during high-dosage intravenous glucose infusion].

Intravenous infusion of glucose in high dosage was given to 42 tumor patients, attaining a hyperglycemia of about 40 mg/100 ml over a period of 24 hours. This hyperglycemia is a part of the so-called "cancer-multistep-therapie". During the period of glucose-infusion a water-turnover of about 6,000 ml can be registered which is connected with a requirement of glucose of about 2,000 g. Only 1/3 of this amount is loosing by renal excretion, but 2/3 are metabolised to correspond with a glucose-uptake of 0,94 g and a glucosuria of 0,32 g per kg bodyweight and hour. Requirement of glucose and glucose uptake are in inverse proportion to the age of the patients and to the duration of hyperglycemia. Further a "glucose-potassium-equivalent" existed: about 10 mval potassium per 100 g infused glucose, whereas the netto uptake of potassium is 0,049 mval per g of metabolised glucose. Acid-base-equilibrium and red blood-picture did not show any relevant variations while typical deviations of some other parameters (cardiac-frequency, body-temperature), white blood-picture) are can be associated with the so-called "general adaptation syndrom". The findings are discussed in view of their general importance for the parenteral application of glucose.

Acid-Base Equilibrium↗
PubMed2026

Mixed Evidence that Dosage Sensitive Genes Drive Global Dosage Compensation in Flour Beetles.

Heteromorphic sex chromosomes create inherent gene dosage differences between males and females because one sex carries a single copy of the X chromosome while the other carries two. Many species have evolved mechanisms that equalize X-linked gene expression between the sexes and, in some cases, restore ancestral autosomal levels, a process known as dosage compensation. Although chromosome-wide compensation is common in male heterogametic (XY) insects, regulatory outcomes vary across taxa and sex chromosome systems, leaving the evolutionary forces shaping sex chromosome regulation unresolved. One hypothesis proposes that the extent to which genes are sensitive to changes in gene dose determines whether complete compensation evolves. We tested predictions of this insensitive sex chromosome hypothesis (ISCH) across five flour beetle species using comparative transcriptomics and genome-wide RNAi-derived measures of gene-by-gene sensitivity. Including an X-autosome fusion in Tribolium confusum allowed direct assessment of expression evolution following a transition from a diploid autosome to a hemizygous Neo-X. Across all five species, we detect complete chromosome-wide dosage compensation and balance between the sexes in somatic tissues, including the Neo-X region. Consistent with ISCH predictions, neither the ancestral Shared-X nor the Neo-X is depleted of genes that are sensitive to RNAi-based expression disruption. However, contrary to expectations, at the level of individual genes, we find little evidence that more sensitive genes exhibit reduced expression divergence. These results suggest that chromosome-wide compensation can be maintained by global regulatory mechanisms that persist through sex chromosome turnover, even when gene-by-gene constraints are weak. Understanding the molecular basis of these mechanisms remains a central challenge in sex chromosome evolution.

Animals↗
PubMed2025

Overcoming gene dosage barriers in mammalian development: An imprinting balancing act.

Genomic imprinting ensures parent-of-origin gene expression and prevents uniparental development. In this issue of Cell Stem Cell, Li et al.1 extensively engineered androgenic haploid embryonic stem cells to overcome imprinting barriers, producing adult bi-paternal mice, albeit with low efficiency, and providing insights into roles of imprinted genes in development.

Genomic Imprinting↗
PubMed1977

[Gentamycin in distributive balance between serum, perilymph and liquor in guinea-pig after dosage in therapeutical range (author's transl)].

Dosage of gentamycin in therapeutical range just as in higher doses results in a distributive balance between serum, perilymph and liquor under the condition of steady serum levels. After high doses the perilymph levels compared to the serum levels are relatively lower than after less doses. The distributive balance is reached after about 7 h in doses, which lead to concentrations of the serum levels of the supposed ototoxic critical range. Afterwards the concentration in the inner ear doesn't increase. In steady state, the concentration in serum is always higher than in perilymph, whereas the perilymph concentration is always higher than the one in liquor.

Animals↗
PubMed1977

Effects of levodopa on the renin-aldosterone system.

Plasma renin activity and plasma aldosterone, supine and erect, and urinary aldosterone levels were measured in 18 patients on normal sodium diets and 11 patients on low sodium diets, all of whom also were on long-term levodopa therapy. Of the 230 hormone measurements, 185 were normal, 11 were high, and 34 were low. Most of the low levels were in 3 patients who had recently received fludrocortisone for orthostatic hypotension, and the renin-aldosterone systems might have been suppressed by it. In another phase of this study, 4 subjects were maintained on a constant diet for 6 wk, while the effect of gradually increasing dosages of levodopa on mineral balance and renin-aldosterone was determined. In 3 of the 4 patients there was a mild natriuretic effect of levodopa (previously demonstrated for acute levodopa therapy). There were no significant consistent changes in renin or aldosterone levels while levodopa was being administered. These studies indicate that levodopa does not usually suppress the elements of the renin-aldosterone system and that such a mechanism is unlikely to be the cause of orthostatic hypotension during the course of levodopa therapy. Since levodopa may induce natriuresis, in this situation unchanged lvels of renin and aldosterone may, however, represent an inappropriately low set of this hormonal system.

Aldosterone↗
PubMed2026

LINE-1 repeats are a defining feature of the Xce.

During early development, female mammals inactivate one X chromosome to balance their X-linked gene dosage with males. While allelic choice is random in inbred mouse populations, choice can be significantly skewed in interstrain hybrids. The genetic basis of skewing has long been attributed to the mysterious "X chromosome controlling element(s)" (Xce) with different strengths among species, subspecies, and strains. When two X-chromosomes with different Xce strengths are inherited by offspring, the X chromosome with the stronger Xce will have a higher probability of remaining active. Here, we provide evidence that L1Tf repeats-a subfamily of long interspersed nuclear elements 1-plays a role in determining Xce strength. L1Tf elements form a condensed core within the inactive X (Xi) territory. Mouse strains with varying Xce strengths differ in the L1Tf copy number on the X chromosome, with the strength of the Xce allele being inversely related to L1Tf copy number. L1Tf expression mediates the Xce effect. However, in contrast to a prior report, L1Tf RNA does not coat the Xi. Rather, L1Tf promotes condensation of the Xi core. Intriguingly, L1Tfs recruit and sequester YY1 from active genes, accelerating XCI in cis. Thus, L1Tf copy number, expression, and binding of YY1 are key defining features of the Xce. We propose a model in which the Xce influences the choice of Xist alleles by promoting YY1 binding to the nucleation site for the initiation of Xist spreading.

Animals↗
PubMed1978

Plasma concentrations of diazepam, noradiazepam and amylobarbitone after short-term treatment of anxious patients.

Twenty-four anxious inpatients were treated with diazepam, amylobarbitone and placebo, each given in flexible dosage for one week, according to a fully-balanced design. Plasma concentrations of diazepam and of its metabolite nordiazepam and of amylobarbitone were determined after two, four and seven days of treatment. Clinical and psychological assessments were made after seven days of each treatment by means of psychiatrist rating scales, patient's self-rating and a comprehensive battery of performance measures. Diazepam and nordiazepam but not amylobarbitone were accumulating over the seven days of treatment. In patients on diazepam without previous amylobarbitone, nordiazepam accumulated more rapidly than diazepam over the week so that the ratio of diazepam to nordiazepam was 2.21 after two days but only 1.14 after seven days; those with previous amylobarbitone on the other hand always had nordiazepam concentrations higher than those of the administered drug and both were accumulating equally. Diazepam and nordiazepam were still detectable in most patients two weeks after the interruption of treatment. No correlations were found between drug concentrations and clinical and psychological effects.

Adult↗
PubMed1975

Long-term therapy of viramin D-resistant richets with 25-hydroxycholecalciferol.

The long-term effects of the vitamin D metabolite, 25-hydroxycholecalciferol (25-HCC), were evaluated in 2 children with hypophosphatemic vitamin D-resistant rickets. Serial total balance studies demonstrated an apparent lack of correlation between the effects of the vitamin on intestinal absorption of calcium and phosphorus and both the onset of healing in 1 of the 2 patients treated with 5,000 to 7,500 u of the metabolite and the absence of demonstrable radiologic improvement in another patient in whom the final dosage was 20,000 u. per day. At first, the metabolite induced a positive calcium balance in both patients resulting largely from a reduction in intestinal calcium excretion. Despite a continued positive calcium balance, 1 of the 2 patients did not demonstrate further healing, while in the other patient healing was noted even when total calcium balance was negative. Serum phosphate levels did not return to normal in either patient, nor was phosphate excretion altered by 25-HCC. Serum alkaline phosphatase remained elevated in both. Serum immunoassayable parathyroid hormone levels were consistently normal to high-normal in the 2 patients throughout more than 24 months of observation. No instances of hypercalcemia and only occasional hypercalciuric episodes were noted.

Alkaline Phosphatase↗
PubMed1975

[4 cases of osteomalacia during anticonvulsant or sedative treatment].

The authors report osteomalacia in 3 cases of epilepsy and one case of coronary heart disease treated with phenobarbitone, either alone or associated with other anticonvulsants. There were clinical signs in all cases and typical radiological signs in 3 cases, a characteristic laboratory syndrome in 4 cases. In the 3 cases where it was estimated, serum levels of parathormone were high. Finally, in 3 cases where it was measured, daily urinary excretion of glucaric D acid was increased. The bony histological signs studied in 3 cases, were similar to those in deficiency osteomalacia. A study of Ca45 metabolism in one case, showed the characteristic changes found in osteomalacia. Finally, a study of the metabolism of tritiated vitamin D, or tritiated 25 OH CC, carried out in 3 cases, gave 3 different patterns; only one of them was characteristic of enzyme induction under the dependency of anticonvulsant. Started in 2 cases, treatment with 125 OH2CC, brought about a rapid fall in blood PTH levels which then rose again before falling progressively in one case, under treatment with 25 OH CC. The bony histological signs of hyperparathyroidism then regressed whilst serum PTH levels remained high. Phosphorous and calcium balance improved in only one case. Treatment with 25 OH CC in high dosage brought about clinical, radiological and laboratory cure of osteomalacia in both cases, reducing the frequency of fits in the epileptic patient.

Adult↗
PubMed1978

[Possibilities and limitations of peripheral-venous parenteral feeding].

The possibilities of peripheral-venous nutrition as regards its substrate dosage are limited due to the vein tolerance (osmolarity) of the infusion mixtures. It is, therefore, imperative to achieve an optimum composition of the solution for obtaining the most favourable utilization rate for the organism. We have shown that a dosage below 0.6 g amino acids/kg BW per day does not have a positive influence on the nitrogen balance in comparison to a control group not nourished. The situation of a patient in the post-aggression phase results in 30 to 40% of the supplied amino acids being utilized in the energy metabolism and excreted as urea, in spite of a sufficient simultaneous energy supply. Not only does this uneconomical loss alone necessitate a higher amino acid dosage, but also the additionally increased catabolism of endogenous protein reserves in the post-operative phase. It remains to be tested whether the sole substitution of amino acids in a solution without carbohydrates over a short infusion period constitutes a compromise between the intended peripheral-venous tolerance and an effect on the nitrogen balance.

Amino Acids↗
PubMed1978

Cholesterol metabolism in diabetes. I. The effect of diabetic control on sterol balance.

To evaluate the effect of diabetic control on sterol balance, five subjects (one with fasting chylomicronemia) were studied when they had little control of blood glucose (period I) and, continuously, when increased insulin dosage improved diabetic control (period II). The four subjects with no chylomicronemia showed a diminished fecal bile acid (FBA) excretion. Although fecal neutral steroid excretion increased variably, the total steroid balance was unchanged. The results support the concept that good control of diabetes shifts the fecal steroid excretion towards diminished FBA, but steroid balance methods did not reveal an effect of insulin on total steroid balance.

Adult↗
PubMed1977

The role of different components of balanced anaesthesia in tolerance to endotracheal intubation.

In order to demonstrate the role of anaesthesia, analgesia and muscle paralysis in suppressing the responses to nociceptive stimuli during balanced anaesthesia, the effect of tolerance to endotracheal intubation was used as a model during recovery from a suxamethonium block after different combinations of thiopental and fentanyl. The induction groups were: Thiopental, 4, 6 or 8 mg/kg, and thiopental, 4 mg/kg, supplemented with fentanyt, either 1 microgram/kg or 2 microgram/kg. All 107 patients received suxamethonium 1.5 mg/kg, after precurarization and recovery of muscle strength had been recorded by measuring the twitch tension of thumb adduction caused by indirect supramaximal stimulation of the ulnar nerve. With 4 mg/kg thiopental 60% of the patients reacted against the tube before the suxamethonium block had subsided. Increasing the dose to 8 mg/kg or supplementing the 4 mg/kg thiopental with 1 microgram/kg fentanyl reduced the reactions to about 30%. After supplementing with 2 microgram/kg fentanyl, 90% of the patients tolerated the tube. Reactions against the tube, if any, usually occurred before the twitch tension had recovered by more than 30%. After 4 and 6 mg/kg thiopental, about 10% of the patients started reacting before there were signs of recovery of twitch tension. The results show that if bucking or coughing are used as an indication of inadequate muscle paralysis overcurarization can easily occur. Tolerance to the endotracheal tube is more rationally achieved by small doses of narcotic analgesics (e.g. fentanyl, 0.5 to 1 microgram/kg) than by increasing the dosage of thiopental. This simple model has been found useful in demonstrating the basic principles of balanced anaesthesia at the beginning of training in the specialty.

Adult↗
PubMed1979

A comparison of the clinical and psychological effects of diazepam and amylobarbitone in anxious patients.

1. Twenty-four anxious inpatients were treated with diazepam, amylobarbitone sodium and placebo in flexible dosage for 1 week. They each received all three treatments according to a fully-balanced design, using double-blind procedures. 2. The clinical and the psychological effects of the drugs were assessed by the comprehensive battery of psychiatrist's ratings, subjective and psychological tests before treatment and at the end of each week of treatment. The tests included self-rating of anxiolytic and hypnotic effects, reaction-time, card sorting, coding and cancellation tasks, arithmetic and tappin. 3. Diazepam improved significantly subjective anxiety and insomnia, while amylobarbitone improved only the self-rated quality of sleep. Occasion effects were absent on clinical measures, indicating that the patients did not respond to non-specific temporal factors. Performance on motor tasks improved over time because of the expected practice effect, but an impairment relative to placebo was detected on two motor tests after the barbiturate and on four other tests with a cognitive component after the benzodiazepine.

Adult↗
PubMed1978

[Thienylic acid, a new drug with saluretic and uricosuric activity. Preliminary data].

The effects of ticrynafen (250-500 mg) on salt-water and uric acid metabolism have been studied in 18 patients with no haemodinamic abnormalities or salt-water repletion (cardiac failure, oedema). The main results are: -- an effective natriuresis is observed in the first days and is attenuated thereafter. In subjects with a reduced GFR, a negative salt balance is obtained altough the volume of diuresis is not significantly increased. -- The potassium loss is variable according to dosage (maximum at 500 mg), renal function (low when reduced). -- The increase of urinary uric acid excretion and the lowering of blood uric acid concentration are rapid and prolonged. In conclusion, we confirm the effective natriuretic and uricosuric properties of ticrynafen.

Adult↗