This is a working overview of deamidation, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2026-03-18 and is reviewed periodically as new material appears.
Interpretation depends on study phase and duration. Phase 2 programs are powered for weight and safety signals, not for cardiovascular or renal outcomes, which require event-driven designs. Gastrointestinal events such as nausea, diarrhea, vomiting, and constipation are the most frequently reported adverse effects and tend to cluster around dose escalation. Small increases in heart rate have been described. Because follow-up after treatment discontinuation is limited, questions about weight regain and durability are open rather than answered.
Trial reports for this compound rely on a small set of repeated measures. Body weight is normally expressed as percent change from baseline at a fixed week, with absolute kilograms given secondarily. Glycemic endpoints include HbA1c, fasting glucose, and, in some protocols, continuous glucose monitoring summaries. Imaging endpoints such as MRI-derived proton density fat fraction quantify liver fat. Standardization matters because a percent change and a categorical responder analysis can tell different stories about the same dataset.
Body composition is assessed with dual-energy X-ray absorptiometry or comparable methods, which separate fat mass from lean mass. Reported losses include both compartments, and the ratio between them is a subject of ongoing analysis rather than a settled result. Waist circumference, blood pressure, and lipid panels are collected as supporting measures. Resting energy expenditure and substrate oxidation are measured in smaller mechanistic studies, where glucagon receptor activity is expected to matter. These substudies are typically short and small, so their findings carry wide uncertainty.
Solid peptide is generally held as a lyophilised powder at low temperature to slow degradation, with desiccant to limit moisture uptake. Reconstituted solutions are less stable and are usually kept refrigerated and protected from light for short periods. Repeated freeze-thaw cycles are avoided because they encourage aggregation. Laboratory handling includes work in a fume hood or laminar flow cabinet to limit inhalation and contamination. Weighing and transfer steps are performed with antistatic tools to reduce static-driven loss of fine powder.
Characterising a peptide of this size relies on a combination of chromatographic and mass spectrometric techniques. Reversed-phase high-performance liquid chromatography separates the intact molecule from related impurities, while electrospray mass spectrometry confirms molecular mass and detects truncation or oxidation products. Peptide mapping after enzymatic digestion verifies the amino acid sequence and locates modified residues. Because the molecule carries a lipid chain, assays must also distinguish the correctly conjugated product from incompletely acylated species.
Peptides in this class degrade mainly through hydrolysis, oxidation, and aggregation. The lipid modification improves plasma residence time but can also promote self-association in aqueous solution at higher concentrations. Oxidation of methionine and deamidation of asparagine residues are common chemical liabilities that accumulate during storage. Stability studies therefore track purity loss, aggregate formation, and changes in receptor-binding potency over time under defined temperature and humidity conditions.
| Property | Value | Notes |
|---|---|---|
| Trial design | Randomized, double-blind, placebo-controlled | Frequently includes dose-escalation arms |
| Weight endpoint | Percent change from baseline | Reported at a prespecified week |
| Liver fat endpoint | MRI proton density fat fraction | Non-invasive imaging measure |
| Body composition method | Dual-energy X-ray absorptiometry | Separates fat mass from lean mass |
| Common adverse events | Nausea, diarrhea, vomiting | Reported most often during dose escalation |
== Uses == Controlled clinical trials of mepiprazole in patients with irritable bowel syndrome (IBS) were also carried out and suggested some benefits of the drug in relieving symptoms of IBS in some patients. Similarly to other phenylpiperazines like trazodone, nefazodone, and etoperidone, mepiprazole produces mCPP as an active metabolite.
=== Reemergence === The technologies of the bankrupt or struggling companies were often bought by other companies which continued the development under more conservative business models. Examples of companies who sold their products after folding were Curis and Intercytex. Many of the companies abandoned their long-term goals of developing fully functional organs in favor of products and technologies that could turn a profit in the short run. Examples of these kinds of products are products in the cosmetic and testing industry. In other cases such as in the case of Advanced Tissue Sciences, the founders started new companies. In the 2010s the regulatory framework also started to facilitate faster time to market especially in the US as new centres and pathways were created by the FDA specifically aimed at products coming from living cells such as the Center for Biologics Evaluation and Research.
== Fictional history == In this fictional universe, the Culture exists concurrently with human society on Earth. The time frame for the published Culture stories is from 1267 CE to roughly 2970 CE, with Earth being contacted around 2100 CE, though the Culture had covertly visited the planet in the 1970s in The State of the Art. The Culture itself is described as having been created when several humanoid species and machine sentiences reached a certain social level, and took not only their physical, but also their civilisational evolution into their own hands. In The Player of Games, the Culture is described as having existed as a space-faring society for eleven thousand years. In The Hydrogen Sonata, one of these founding civilisations was named as the Buhdren Federality.
== Further reading == Edwards, Clive A. (ed.) Earthworm Ecology. Boca Raton: CRC Press, 2004. Second revised edition. ISBN 0-8493-1819-X Lee, Keneth E. Earthworms: Their Ecology and Relationships with Soils and Land Use. Academic Press. Sydney, 1985. ISBN 0-12-440860-5 Stewart, Amy. The Earth Moved: On the Remarkable Achievements of Earthworms. Chapel Hill, N.C.: Algonquin Books, 2004. ISBN 1-56512-337-9
Rejuva is a gene therapy which is under development for the treatment of obesity and diabetes. It is an adeno-associated virus (AAV)-based gene therapy which involves an engineered variant of human insulin promotor and which aims to permanently increase nutrient-responsive secretion glucagon-like peptide-1 (GLP-1) by pancreatic β-cells. The therapy is administered via a 25-gauge needle delivery system guided by endoscopic ultrasound in a one-time outpatient treatment. It is intended as a permanent alternative to GLP-1 agonists like semaglutide. Rejuva is under development by Fractyl Health and is in the preclinical research stage of development.
Sources: en.wikipedia.org
=== Pray Codex === An image in the medieval manuscript of the Pray Codex (c. 1192–1195) has generated a debate among some believers since 1978. Although the Pray Codex predates the Shroud of Turin, some of the assumed features of the drawing, including the four L-shaped holes on the coffin lid, have pointed some people towards a possible attempted representation of the linen cloth. However the image on the Pray Codex has crosses on what may be one side of the supposed shroud, an interlocking step pyramid pattern on the other, and no image of Jesus. Critics point out that it may not be a shroud at all, but rather a rectangular tombstone, as seen on other sacred images. A crumpled cloth can be seen discarded on the coffin, and the text of the codex fails to mention any miraculous image on the codex shroud.
== Epidemiology == The prevalence of hemoglobin H disease mirrors that of the hemoglobinopathies. As a whole, they are most prevalent in individuals of Asian, African, and Mediterranean decent. There is a protective effect against malaria for individuals carrying thalassemia genes, which explains the high frequency of thalassemia within the worldwide population.
== History == The syndrome was first recognized in Royal Melbourne Hospital, Australia in an affected family by Denborough et al. in 1962. Denborough did much of his subsequent work on the condition at the Royal Canberra Hospital. Similar reactions were found in pigs. The efficacy of dantrolene as a treatment was discovered by South African anesthesiologist Gaisford Harrison and reported in a 1975 article published in the British Journal of Anaesthesia. After further animal studies corroborated the possible benefit from dantrolene, a 1982 study confirmed its usefulness in humans. In 1981, the Malignant Hyperthermia Association of the United States (MHAUS) hotline was established to provide telephone support to clinical teams treating patients with suspected malignant hyperthermia. The hotline became active in 1982 and since that time MHAUS has provided continuous access to board-certified anesthesiologists to assist teams in treatment.
UIP pattern: Honeycombing, with or without peripheral traction bronchiectasis; or bronchiolectasis (dilatation of the terminal bronchioles) Predominantly subpleural and basal Often heterogenous distribution, being occasionally diffuse, and may be asymmetrical There may be superimposed CT features such as mild ground-glass opacity, reticular pattern and pulmonary ossification.
== Etymology == The word sirloin derives from the Middle English surloine, itself derived from the Old French word surloigne (variant of surlonge), that is, sur for 'above' and longe for 'loin'. Therefore, a sirloin is the cut from above the loin. In Modern French, the cut of meat is called aloyau or faux-filet. A fictitious etymology recounts that a king of England knighted the loin of beef as "Sir Loin." Although the pun is reported as early as 1630, and the notion of a king knighting it dates to 1655, the name predates any of the many kings (Henry VIII, James VI and I, Charles II) mentioned in versions of the anecdote. The story at most influenced the spelling sir rather than sur.
Sources: en.wikipedia.org
=== Terminology === Because of concerns around stigma, and because of a move away from the original theoretical basis for the term (see history), there is ongoing debate about renaming borderline personality disorder. While some clinicians agree with the current name, others argue that it should be changed, since many who are labelled with borderline personality disorder find the name unhelpful, stigmatizing, or inaccurate. Alternative suggestions for names include emotional regulation disorder or emotional dysregulation disorder. Impulse disorder and interpersonal regulatory disorder are other valid alternatives, according to John G. Gunderson of McLean Hospital in the United States. Another term suggested by psychiatrist Carolyn Quadrio is post-traumatic personality disorganization (PTPD), reflecting the condition's status as (often) both a form of chronic post-traumatic stress disorder (PTSD) as well as a personality disorder. However, although many with BPD do have traumatic histories, some do not report any traumatic event, which suggests that BPD is not necessarily a trauma spectrum disorder. The Treatment and Research Advancements National Association for Personality Disorders (TARA-APD) campaigned unsuccessfully to change the name and designation of BPD in DSM-5, published in May 2013, in which the name "borderline personality disorder" remains unchanged, and it is not considered a trauma- and stressor-related disorder.
Digoxin (wherein it may result in increased serum digoxin levels) Insulin or anti-diabetic medication (wherein it may enhance the effects of a hypoglycemic treatment) Drugs that prolong the QT interval such as methadone, and other arrhythmogenic drugs, as hydroxychloroquine prolongs the QT interval and may increase the risk of inducing serious abnormal heart rhythms (ventricular arrhythmias) if used concurrently. Mefloquine and other drugs known to lower the seizure threshold (co-administration with other antimalarials known to lower the convulsion threshold may increase risk of convulsions) Antiepileptics (concurrent use may impair the antiepileptic activity) Methotrexate (combined use is unstudied and may increase the frequency of side effects) Cyclosporin (wherein an increased plasma cyclosporin level was reported when used together).
== Eukaryotic == The process of transcriptional termination is less understood in eukaryotes, which have extensive post-transcriptional RNA processing, and each of the three types of eukaryotic RNA polymerase have a different termination system. In RNA polymerase I, Transcription termination factor, RNA polymerase I binds downstream of the pre-rRNA coding regions, causing the dissociation of the RNA polymerase from the template and the release of the new RNA strand. In RNA polymerase II, the termination occurs via a polyadenylation/cleaving complex. The 3' tail on the ending of the strand is bound at the polyadenylation site, but the strand will continue to code. The newly synthesised ribonucleotides are removed one at a time by the cleavage factors CSTF and CPSF, in a process that is still not fully understood. The remainder of the strand is disengaged by a 5′-exonuclease when the transcription is finished. RNA polymerase III terminates after a series of uracil polymerization residues in the transcribed mRNA. Unlike in bacteria and in polymerase I, the termination RNA hairpin needs to be upstream to allow for correct cleaving.
Mary McNab won a by-election in Glasgow on 22 November, but failed to comply with legislation requiring her to stand down from her Glasgow City Council job the next working day. A Second World War veteran who has moved to Canada says she is "angry" and "heartbroken" after a meeting with minister Emma Reynolds regarding the freezing of pensions for some pensioners who now live overseas. Charities call for urgent support from both the UK and Scottish governments to prevent public services from collapse. 4 December – The Organisation for Economic Co-operation and Development (OECD) has forecast that UK interest rates will fall less quickly over the next two years because of the budget. Secretary of State for Housing, Communities and Local Government Angela Rayner insists that councils must meet the government's housing target after local authorities called them impossible to meet. Secretary of State for Transport Heidi Alexander announces that South Western Railway, c2c and Abellio Greater Anglia would be nationalised by autumn 2025 pending new legislation. Defence minister Alistair Carns says that British Armed Forces could be wiped out in six months if they were forced to fight a war on the scale of the Ukraine conflict. The former prime minister, Boris Johnson, accuses Starmer of misleading the House of Commons and says he should correct the record immediately.
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and release of cortisol and androgens by the zona fasciculata and zona reticularis, respectively. ACTH is also related to the circadian rhythm in many organisms. Deficiency of ACTH is an indicator of secondary adrenal insufficiency (suppressed production of ACTH due to an impairment of the pituitary gland or hypothalamus, cf. hypopituitarism) or tertiary adrenal insufficiency (disease of the hypothalamus, with a decrease in the release of corticotropin releasing hormone (CRH)). Conversely, chronically elevated ACTH levels occur in primary adrenal insufficiency (e.g. Addison's disease) when adrenal gland production of cortisol is chronically deficient. In Cushing's disease, a pituitary tumor leads to excessive production of ACTH, which stimulates the adrenal cortex to produce high levels of cortisol.
Sources: en.wikipedia.org
A responder analysis counts participants who cross a threshold, such as five or ten percent weight loss. It complements average percent change by showing how widely results are distributed. The two measures can diverge when a subset of participants loses a large amount.
Mechanistic measures such as energy expenditure and liver fat change come from small substudies and should be read as preliminary. Long-term clinical outcomes are not yet available. Average weight loss figures are better supported than explanations for how the loss is achieved.
Endpoints reported at different weeks, in different baseline BMI ranges, or under different dose-escalation schedules are not directly comparable. Studies in type 2 diabetes often show smaller weight changes than studies in obesity without diabetes. Reporting the population alongside the number keeps comparisons honest.
Mass spectrometry provides the most direct confirmation of molecular mass. Reversed-phase chromatography adds a retention-time signature that supports identity when compared against a reference standard. No single method is sufficient on its own.