Aib substitution comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Updated 2025-08-13. Numbers and descriptions here follow the published literature rather than marketing material.
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
Clinical studies of semaglutide generally measure glycated hemoglobin, fasting plasma glucose, body weight, and composite cardiovascular endpoints. The SUSTAIN program enrolled adults with type 2 diabetes, while the STEP program focused on obesity without diabetes. Administration follows a stepwise escalation schedule designed to limit gastrointestinal effects during the first weeks. Reported outcomes include mean percentage weight change, the proportion of participants reaching defined weight-loss thresholds, and rates of nausea, vomiting, and diarrhea. Long-term data on durability after treatment stops are still limited and remain a topic of ongoing research.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, developed by Novo Nordisk and first approved in 2017 for type 2 diabetes. It belongs to the incretin mimetic class, a group of agents that reproduce the glucose-dependent actions of endogenous GLP-1. The molecule was engineered to resist degradation by dipeptidyl peptidase-4 and to bind serum albumin, extending its half-life from minutes to roughly one week. Approval for chronic weight management followed in 2021, based on large cardiovascular and obesity outcome trials.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Acylated GLP-1 receptor agonist | 31-residue synthetic peptide |
| Molecular formula | C187H291N45O59 | established for the free peptide |
| Appearance | White to off-white powder | as supplied before formulation |
| Solubility | Freely soluble in water | aqueous buffers near neutral pH |
| Typical storage | 2 to 8 degrees Celsius, protected from light | powder and solution forms differ in shelf life |
Receptor activation follows the canonical Gs pathway: binding increases intracellular cyclic AMP, which promotes protein kinase A activity. In pancreatic beta cells this amplifies glucose-dependent insulin release, so secretion rises when blood glucose is high and changes little when it is low. The same signalling suppresses glucagon release from alpha cells and slows gastric emptying. Receptors in the hypothalamus and brainstem are thought to contribute to reduced appetite and lower energy intake. Which of these effects dominates clinical outcomes remains an area of active study.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released by intestinal L cells after food intake. The natural hormone acts on pancreatic and central receptors but is degraded within minutes by dipeptidyl peptidase-4 and other peptidases. Semaglutide belongs to the class of long-acting GLP-1 receptor agonists, a group distinguished by structural changes that slow breakdown and extend circulation time. Its development followed earlier short-acting analogues and reflects a general strategy in peptide drug design: preserve receptor activity while blocking proteolytic clearance.
Three structural changes define the molecule. At position 8 an alpha-aminoisobutyric acid residue replaces alanine, which blocks dipeptidyl peptidase-4 cleavage. At position 34 arginine replaces lysine, and at position 26 a lysine carries a C18 fatty diacid attached through a short linker. The fatty chain binds serum albumin, and this albumin association reduces renal filtration and enzymatic attack. The unchanged backbone retains the receptor contacts that produce signalling. The free base has the formula C187H291N45O59 and a molecular weight near 4114 daltons.
Receptor activation occurs at GLP-1 receptors distributed across pancreatic islets, the hypothalamus, and the gastrointestinal tract. Binding triggers G protein signaling that raises cyclic AMP and enhances glucose-dependent insulin release. Because the effect depends on prevailing glucose levels, insulin secretion does not rise when blood sugar is already low. Signaling in the brain and gut also influences appetite and gastric emptying, which is why the compound appears in both metabolic and weight-related research literature.
Development began in the early 2010s with the goal of extending GLP-1 activity beyond the brief window achieved by native peptide infusion. The earliest approved formulation was a subcutaneous injection given once weekly. A later oral tablet pairs the peptide with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, usually shortened to SNAC. That carrier lowers local pH and helps the peptide cross gastric tissue. Both routes deliver the same active molecule.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, a gut hormone released after meals. Its backbone retains the GLP-1 sequence but incorporates two substitutions that slow enzymatic breakdown by dipeptidyl peptidase-4. A short polyethylene glycol linker and a C18 fatty diacid are attached to the peptide chain, allowing the molecule to bind serum albumin and remain in circulation far longer than the native hormone. The result is a circulating half-life measured in days rather than the minutes typical of endogenous GLP-1.
The semaglutide sequence is a 31-residue analogue of human GLP-1, altered at three positions relative to the parent hormone. Aminoisobutyric acid replaces alanine at position 8, arginine replaces lysine at position 34, and a lipophilic diacid is attached to lysine 26 through a short linker. These features are reported consistently in the structural literature. The position 8 substitution blocks recognition by dipeptidyl peptidase-4, while the attached chain drives strong, reversible association with a carrier protein in blood.
Receptor activation raises intracellular cyclic AMP through Gs coupling, which promotes glucose-dependent insulin release and suppresses glucagon secretion when blood glucose is elevated. Effects outside the pancreas include slower gastric emptying and altered appetite signalling in the hypothalamus and hindbrain. The relative contribution of each tissue to overall metabolic outcomes remains an area of active investigation. Central mechanisms in particular are inferred mainly from animal models and indirect human measures rather than direct observation.
Material described as research-grade is not necessarily manufactured to pharmaceutical standards, and purity figures depend on the method used to obtain them. A certificate of analysis states the measured purity, the analytical technique, and the batch identifier, but the underlying data are not always included. Independent testing by a second laboratory is a common way to confirm identity and purity. Uncertainties remain about how storage history affects long-term stability, and about how well results from one laboratory transfer to another. Documentation of handling conditions supports comparison between batches.
Peptides are sensitive to temperature, light, oxygen, and repeated freeze-thaw cycles. Semaglutide in dry form is generally held at refrigerated temperatures, while reconstituted solutions require a defined short-term storage window. Vials should be kept in secondary packaging to limit photodegradation, and exposure to alkaline conditions is avoided because it accelerates chemical degradation. Adsorption to glass and some plastics can reduce the measured concentration of dilute solutions, so low-binding polypropylene containers are preferred for analytical work. Each transfer step introduces a small risk of contamination, and closed handling practices reduce that risk.
== Plot == Joe Huff is an Alabama cop who has been suspended for excessive violence. After stopping a supermarket robbery, he is summoned by FBI agent Lance Dockery, who takes him to meet with special agent Frank Cunningham. Cunningham blackmails Joe by threatening to turn Joe's three-week suspension into six months without pay. Cunningham wants Joe to go undercover in Mississippi and infiltrate The Brotherhood, a white supremacist biker gang linked to the murders of government officials and suspected of dealing drugs to the mafia. The Brotherhood is led by Chains Cooper. Joe goes undercover as "John Stone". Tasked with killing a Bolivian man as his initiation, Joe enlists the FBI's help to fake the murder and is accepted into the Brotherhood. However, Chains' right-hand man, Ice Hensley, does not trust Joe and tries to expose him, leading to Ice's death in a high-speed motorcycle chase. Joe learns that the Brotherhood's goal is to eliminate Brent "The Whip" Whipperton, a district attorney running for Governor of Mississippi, who has promised to crack down on crime. They plan to use stolen military weapons to storm the Supreme Court at the Mississippi State Capitol, where Trouble Owens, one of their own, is on trial for murder, to assassinate Whipperton and the judges. When Chains' girlfriend, Nancy, accidentally learns about Joe's identity, he offers her immunity if she cooperates with the FBI. Though reluctant at first, Nancy accepts his offer, but they are discovered when the Bolivian man Joe had supposedly killed as an initiation returns.
== See also == Advanced Landing Ground – a type of semi-permanent bases in Kent, France, Belgium, Netherlands and occupied Germany Air Ministry Experimental Station Chain Home – radar defence system developed during the Second World War Class A airfield – airfields constructed to Air Ministry specifications during the Second World War List of Battle of Britain airfields List of North African airfields during World War II List of Royal Air Force stations, current MoD and RAF stations List of Royal Air Force Satellite Landing Grounds List of V Bomber dispersal bases
Arrestins are elongated molecules, in which several intra-molecular interactions hold the relative orientation of the two domains. Unstimulated cell arrestins are localized in the cytoplasm in a basal inactive conformation. Active phosphorylated GPCRs recruit arrestin to the plasma membrane. Receptor binding induces a global conformational change that involves the movement of the two arrestin domains and the release of its C-terminal tail that contains clathrin and AP2 binding sites. Increased accessibility of these sites in receptor-bound arrestin targets the arrestin-receptor complex to the coated pit. Arrestins also bind microtubules (part of the cellular skeleton), where they assume yet another conformation, different from both free and receptor-bound form. Microtubule-bound arrestins recruit certain proteins to the cytoskeleton, which affects their activity and/or redirects it to microtubule-associated proteins. Arrestins shuttle between cell nucleus and cytoplasm. Their nuclear functions are not fully understood, but it was shown that all four mammalian arrestin subtypes remove some of their partners, such as protein kinase JNK3 or the ubiquitin ligase Mdm2, from the nucleus. Arrestins also modify gene expression by enhancing transcription of certain genes.
All nuclear data not otherwise stated is from the standard source: Twenty isotopes of californium are known with mass number ranging from 237 to 256; the most stable are 251Cf with half-life 898 years, 249Cf with half-life 351 years, 250Cf at 13.08 years, and 252Cf at 2.645 years. All other isotopes have half-life shorter than a year, and most of these have half-lives less than 20 minutes. 249Cf is formed by beta decay of berkelium-249, and heavier californium isotopes are made by subjecting berkelium to intense neutron radiation in a nuclear reactor. Though californium-251 has the longest half-life, its production yield is relatively low due to its rapid depletion by reaction with another neutron (high neutron cross section). 252Cf is a very strong neutron emitter, which makes it an extremely hazardous radioactive isotope. 252Cf, 96.9% of the time, alpha decays to curium-248; the other 3.1% of decays are spontaneous fission. One microgram of 252Cf emits 2.3 million neutrons per second (about 3.7 neutrons per fission). The other main isotopes of californium (248-251) also alpha decay to those of curium, with a much smaller fraction of fission.
The lambda particle is a type of subatomic particle in subatomic particle physics. Lambda is the set of logical axioms in the axiomatic method of logical deduction in first-order logic. Uppercase Lambda is often used as a stylized form of uppercase A, especially in science fiction. There is a poetical allusion to the use of Lambda as a shield blazon by the Spartans. Lambda is the von Mangoldt function in mathematical number theory. Lambda denotes the de Bruijn–Newman constant which is closely connected with Riemann's hypothesis. In statistics, lambda is used for the likelihood ratio. In statistics, Wilks's lambda is used in multivariate analysis of variance (MANOVA analysis) to compare group means on a combination of dependent variables. In the spectral decomposition of matrices, lambda indicates the diagonal matrix of the eigenvalues of the matrix. In computer science, lambda is the time window over which a process is observed for determining the working memory set for a digital computer's virtual memory management. In astrophysics, lambda represents the likelihood that a small body will encounter a planet or a dwarf planet leading to a deflection of a significant magnitude. An object with a large value of lambda is expected to have cleared its neighbourhood, satisfying the current definition of a planet. In crystal optics, lambda is used to represent a lattice period. In electrochemistry, lambda denotes the "equivalent conductance" of an electrolyte solution.
Sources: en.wikipedia.org
Kallistatin is a protein that in humans is encoded by the SERPINA4 gene. Kallistatin consists of three folded ß segments and eight helical structures and contains two functional domains, an active site and a heparin-binding site. Kallistatin signals through several receptors, including integrin ß3, lipoprotein receptor-related protein 6 (LRP6), nucleolin, and Krüppel-like factor 4 (KLF4).
Dashi is a family of stocks in Japanese cooking, typically made by briefly simmering a variety of kelp called kombu in nearly boiling water, often with other ingredients such as katsuobushi or shiitake. Myeolchi yuksu is a stock in Korean cooking made by briefly cooking dried anchovies with kelp in nearly boiling water. Glace de viande is stock, usually made from veal, that is highly concentrated by reduction. Ham stock, common in Cajun cooking, is made from ham hocks. Master stock is a Chinese stock used primarily for poaching meats, flavored with soy sauce, sugar, ginger, garlic, and other aromatics. Prawn stock is made from boiling prawn shells. It is used in Southeast Asian dishes such as laksa. Remouillage is a second stock made from the same set of bones. Bran stock is bran boiled in water. It can be used to thicken meat soups, used as a stock for vegetable soups or made into soup itself with onions, vegetables and molasses.
== Diagnosis == Genetic testing for the m.3243A>G mutation in mitochondrial DNA is commonly used to isolate the diagnosis of MELAS syndrome from other mitochondrial disorders. This mutation is an adenine to guanine point mutation at base pair 3,243 in the mitochondrial genome. A minimum amount of mtDNA must be mutated to generate the MELAS phenotype, known as the "threshold effect". Due to mitochondrial heteroplasmy, urine and blood testing is preferable to blood alone. PCR and ARMS-PCR are commonly used, reliable, rapid, and cost-effective techniques for the diagnosis of MELAS. Magnetic-resonance imaging (MRI) is a common imaging test used to identify the presence of stroke-like lesions. These lesions are multifocal infarct-like areas of cortical edema in different stages of ischemic evolution, yet do not commonly conform to any known vascular territory, distinguishing them from a stroke. Initial lesions often occur in the occipital or parietal lobes with eventual involvement of the cerebellum, cerebral cortex, basal ganglia, and thalamus. The occipital lobe is thought to be a region prone to stroke-like lesions due to the high energy requirements of the visual cortex. Lactate levels are often elevated in serum and cerebrospinal fluid. Magnetic resonance spectroscopy (MRS) may show an elevated lactate peak in affected and even unaffected brain areas. Muscle biopsy shows ragged red fibers. However, genetic evaluation should be done first, which eliminates the need for muscle biopsy in most cases. Diagnosis may be molecular or clinical:
The radioactive substance used clinical practices in PET scanning is a simple sugar called fluorodeoxyglucose (FDG). Many different tracers may be used for research or clinical investigations various imaging purposes, depending on the target process within the body, such as:
== Function == The compressive forces applied to the foot are distributed along five rays, three medial (side of big toe) and two lateral (side of little toe). The lateral rays stretch over the cuboid bone to the heel bone and the medial rays over the three cuneiform bones and the navicular bone to the ankle bone. Because the ankle bone is placed over the heel bone, these rays are adjacent near the toes but overriding near the heel, and together they form the arches of the foot that are optimized to distributed compressive forces across an uneven terrain. In this context the heel thus forms the posterior point of support that together with the balls of the large and little toes bear the brunt of the loads.
Sources: en.wikipedia.org
== Society and culture == Depictions of heart attacks in popular media often include collapsing or loss of consciousness which are not common symptoms; these depictions contribute to widespread misunderstanding about the symptoms of myocardial infarctions, which in turn contributes to people not getting care when they should.
== History == 1979-1988: Research scientist and Senior research scientist of First Institute of Biochemistry, Semmelweis University Medical School and Hungarian Academy of Sciences 1988-1994: Head of Peptide Research Laboratory, Associate Professor of Biochemistry, Joint Research Organization of the Hungarian Academy of Sciences and Semmelweis University Medical School, The First Institute of Biochemistry 1994-2008: Head of Peptide Biochemistry Research Group and Rational Drug Design Laboratory, Professor of Biochemistry, Department of Medicinal Chemistry, Semmelweis Medical University 1992-1999: Scientific advisor of Sugen 1999-2005: Scientific advisor of Axxima Pharmaceuticals 1999–present: CEO and CSO of Vichem Chemie Research Ltd. 2001-2012: Chairman of Rational Drug Design Laboratories Co-operation Research Center, Semmelweis University 2002-2008: Curator of Office for Subsidised Research Units of Hungarian Academy of Sciences 2008-2012: Head of Signal Transduction Therapy Laboratory at Semmelweis University 2012–present: Head of Pathobiochemistry Research Group of Hungarian Academy of Sciences at Semmelweis University, Department of Medical Chemistry
The optical lens has been playing a critical role in almost all areas of science and technology since its invention about 3000 years ago. With the advances in micro- and nanofabrication techniques, continued miniaturization of the conventional optical lenses has always been requested for various applications such as communications, sensors, data storage and a wide range of other technology-driven and consumer-driven industries. Specifically, ever smaller sizes, as well as thinner thicknesses of micro lenses, are highly needed for subwavelength optics or nano-optics with extremely small structures, particularly for visible and near-IR applications. Also, as the distance scale for optical communications shrinks, the required feature sizes of micro lenses are rapidly pushed down. Recently, the excellent properties of newly discovered graphene oxide provide novel solutions to overcome the challenges of current planar focusing devices. Specifically, giant refractive index modification (as large as 10^-1), which is one order of magnitude larger than the current materials, between graphene oxide (GO) and reduced graphene oxide (rGO) have been demonstrated by dynamically manipulating its oxygen content using the direct laser writing (DLW) method. As a result, the overall lens thickness can be potentially reduced by more than ten times. Also, the linear optical absorption of GO is found to increase as the reduction of GO deepens, which results in transmission contrast between GO and rGO and therefore provides an amplitude modulation mechanism.
2024 Conservative Party leadership election: Nominations open for the first round of the leadership election. July 2024 Welsh Labour leadership election: Eluned Morgan is elected unopposed as the new leader of Welsh Labour after nominations close at midday. The Senedd will be recalled on 6 August to choose a new First Minister of Wales following the resignation of Vaughan Gething and the subsequent Welsh Labour leadership election. 25 July – Conservative Party leadership election: Tom Tugendhat and Robert Jenrick enter the race to become the next Conservative leader. 26 July – Labour peer Lord Falconer introduces the Assisted Dying Bill into the House of Lords. The bill would allow anyone with a terminal illness and less than six months left to live to get medical assistance to end their life. Following a critical report on the Care Quality Commission, Health Secretary Wes Streeting describes the body as not fit for purpose. Conservative Party leadership election: Former Work and Pensions Secretary Mel Stride becomes the fourth candidate to announce his intention to run for the Conservative Party leadership election. 27 July – Conservative Party leadership election: Priti Patel becomes the fifth candidate to put their name forward for the election, standing as a unity candidate. 28 July – Labour accuses the previous Conservative government of "covering up" "catastrophic" problems in the public sector and creating a multi-billion pound gap in public finances.
Sources: en.wikipedia.org
Native GLP-1 is degraded within minutes by dipeptidyl peptidase-4 and neutral endopeptidases. Semaglutide carries a non-natural amino acid at position eight that blocks that cleavage, and a fatty diacid side chain that binds albumin. The result is a much longer duration of action than the native hormone.
The fatty diacid chain associates strongly with serum albumin, which keeps the peptide in circulation and shields it from rapid renal clearance. Bound peptide is released gradually, producing a sustained receptor signal. This mechanism also reduces the peak-to-trough variation seen with shorter-acting analogues.
The balance between peripheral receptor activation and signalling in the central nervous system is not fully resolved. The extent to which slowed gastric emptying accounts for reduced energy intake, compared with direct effects on appetite circuits, is debated. Long-term effects on lean mass and on tissues outside the gut and brain are still under study.
It is given either as a once-weekly subcutaneous injection or as an oral tablet taken once daily. The two forms use different absorption strategies, so they are not interchangeable on a milligram-for-milligram basis.