A practical reference on freeze-thaw: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-07-14. Anything still debated is marked as such rather than presented as settled.
The compound was designed at the Institute of Molecular Genetics of the Russian Academy of Sciences during the 1980s and 1990s. The stated design goal was to retain the immunomodulatory and central nervous system activity attributed to tuftsin while improving resistance to enzymatic breakdown. Adding a proline-rich tail to the short parent peptide was a deliberate strategy, because proline residues restrict the conformations available to many peptidases. The same laboratory produced Semax, an ACTH fragment analog, and both compounds were developed in parallel as short, enzymatically stabilized peptides intended for intranasal use.
Selank is not a naturally occurring peptide and has no known endogenous counterpart in human physiology. Russian-language sources frequently call it TP-7, while English-language sources use the name Selank almost exclusively. Database indexing is uneven, partly because early reports appeared in regional journals that are not widely cataloged. Some summaries describe the material as a tuftsin analog and others as a synthetic heptapeptide; the labels overlap rather than conflict. Citing the primary sequence resolves ambiguity more reliably than the research or trade name alone.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro, written TKPRPGP in one-letter notation. Its structure consists of the immunomodulatory tetrapeptide tuftsin, Thr-Lys-Pro-Arg, extended at the carboxyl terminus by a Pro-Gly-Pro segment. The molecular formula is commonly given as C33H57N11O9, corresponding to a monoisotopic mass near 751.4 Da and an average molecular mass near 751.9 Da. All seven residues are proteinogenic amino acids, and the molecule carries no modified side chains or non-natural linkages.
Published clinical evidence is limited. Most controlled trials were conducted in Russia, enrolled modest numbers of participants, and appeared in Russian-language journals, which restricts independent verification. Reported outcomes include lower anxiety scores, improved attention and memory measures, and changes in fatigue ratings. Reviews written in English note methodological limitations such as small samples and inconsistent endpoints. Whether the compound produces clinically meaningful benefit relative to established anxiolytics is therefore an open question rather than an established finding.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It was designed at the Institute of Molecular Genetics of the Russian Academy of Sciences as a structural analogue of tuftsin, a naturally occurring tetrapeptide fragment of the immunoglobulin heavy chain. The added Pro-Gly-Pro tail was intended to slow enzymatic degradation and extend biological activity. In Russia it is registered as an anxiolytic nasal preparation, while regulators elsewhere have not approved it for clinical use.
Proposed mechanisms centre on modulation of the GABAergic system, with reports of altered expression of genes related to GABA-A receptor subunits and changed monoamine turnover. Some studies describe inhibition of enkephalinase, the enzyme that degrades endogenous enkephalins, which may prolong opioid peptide signalling. Effects on brain-derived neurotrophic factor and on cytokine expression have also been reported. These findings come largely from animal models and small human studies, and the precise primary target remains unresolved.
| Property | Value | Notes |
|---|---|---|
| Peptide sequence | Thr-Lys-Pro-Arg-Pro-Gly-Pro | Seven residues; tuftsin plus a Pro-Gly-Pro tail |
| Molecular formula | C33H57N11O9 | Commonly reported value for the free peptide |
| Monoisotopic mass | Roughly 751.4 Da | Average molecular mass near 751.9 Da |
| Appearance | White to off-white powder | Typically supplied as a lyophilized solid |
| Solubility class | Freely soluble in water | Also dissolves in saline and other polar solvents |
Regulatory status differs sharply by region. Selank holds a Russian marketing authorization, where it is supplied mainly as nasal drops, while authorities elsewhere have not approved it for medical use. Material sold internationally is therefore usually labeled as a research chemical rather than a medicine. Peer-reviewed publications come predominantly from Russian laboratories, and sample sizes are generally small. Whether the compound produces comparable effects under independent, well-controlled replication remains an open question that the broader literature has not settled.
Selank is a synthetic heptapeptide developed in Russia as a structural analogue of tuftsin, a naturally occurring immunomodulatory tetrapeptide. Its sequence, Thr-Lys-Pro-Arg-Pro-Gly-Pro, keeps the tuftsin core at the N-terminus and appends a Pro-Gly-Pro tail. Researchers at the Institute of Molecular Genetics in Moscow synthesized the compound during the 1990s while searching for peptides with combined anxiolytic and immunomodulatory activity. The added tail was intended to resist enzymatic cleavage and prolong the molecule's presence in circulation.
Reported activity for Selank centers on anxiolytic and nootropic effects. Russian clinical reports describe use in anxiety and in cognitive or attention-related complaints. Most of this evidence comes from studies conducted by the same research groups that developed the peptide. Independent replication in other countries remains limited, and no major Western regulatory agency has approved the compound for any indication. The gap between local reports and external verification is a recurring point in discussions of the peptide.
Tuftsin, the parent structure, is a naturally occurring immunomodulatory tetrapeptide released from the Fc region of immunoglobulin G by spleen enzymes. Selank extends this four-residue sequence with three additional amino acids. The stated rationale is that the added tail slows enzymatic breakdown and may influence receptor interactions. How the full heptapeptide behaves at the molecular level is not firmly established, and proposed mechanisms often involve indirect modulation of neurotransmitter or immune signaling rather than a single defined target.
Selank is a synthetic heptapeptide developed in Russia. Its sequence is Thr-Lys-Pro-Arg-Pro-Gly-Pro, a seven-residue chain built around the natural tetrapeptide tuftsin. Researchers at the Institute of Molecular Genetics of the Russian Academy of Sciences first described the compound in the mid-1990s. The design combined the tuftsin core with an added Pro-Gly-Pro tail, a modification intended to extend the molecule's stability in biological fluids. Published work on the peptide has appeared mainly in Russian-language journals.
Reversed-phase high-performance liquid chromatography is the standard technique for estimating peptide purity. The result is a peak-area percentage, which describes how much of the detected material elutes as the main peak in one run. Mass spectrometry confirms the molecular mass and can reveal truncated, adducted, or otherwise modified species. Amino acid analysis or tandem mass spectrometry can address sequence fidelity when identity is in doubt. None of these measurements, taken alone, establishes that a sample is fit for any specific purpose.
Lyophilized selank is normally supplied as a dry powder and is considered stable for extended periods when kept cold and dry. Moisture uptake is the main practical threat, because absorbed water promotes both hydrolysis and aggregation in the solid state. Vials are usually warmed to room temperature before opening so that condensation does not form on the powder. Supplier documentation commonly specifies -20 °C for routine storage, with -80 °C used for material intended to be archived for years.
The epiphyseal arteries and osteogenic cells invade the epiphysis, depositing osteoclasts and osteoblasts which erode the cartilage and build bone, respectively. This occurs at both ends of long bones but only one end of digits and ribs.
Milk has probably been added to chocolate drinks wherever both ingredients were available. The first domesticated cattle were introduced to the Caribbean in 1493 by Christopher Columbus. Reciprocally, cocoa was introduced in Europe in the 1520s. The Natural History Museum of London lists Anglo-Irish botanist Hans Sloane as the inventor of drinking chocolate with milk. Sloane found the local Jamaican beverage consisting of cacao and water served to him in Jamaica unpalatable, but by adding milk to it, found it not as unacceptable as it was. However, according to historian James Delbourgo, the Jamaicans were brewing "a hot beverage brewed from shavings of freshly harvested cacao, boiled with milk and cinnamon" as far back as 1494. In the late 19th century, Swiss entrepreneur Daniel Peter developed a solid dehydrated version of chocolate milk so that it could be easily portioned, transported and conserved (fresh milk was rare in the cities). He eventually created milk chocolate in 1875.
==== Mosque ==== Ibelin's parish church was converted into a mosque, to which a minaret was added during the Mamluk period in 1337. The minaret is still standing, although the mosque itself (the former Crusader church) was blown up by the IDF in 1950.
=== Copper smelting === Exposure studies in the copper smelting industry are much more extensive and have established definitive links between arsenic, a by-product of copper smelting, and lung cancer via inhalation. Dermal and neurological effects were also increased in some of these studies. Although further occupational controls were introduced and workers were exposed to lower arsenic concentrations, the arsenic exposures measured in these studies range from about 0.05 to 0.3 mg/m3, significantly higher than usual airborne levels, ranging from 0 to 0.000003 mg/m3).
=== 2002–2005: Lilo & Stitch, The Ring, and television success === Chase's international profile expanded significantly in 2002. She was cast as the voice of Lilo Pelekai, a quirky and lonely Hawaiian girl who befriends a destructive alien fugitive, in the Walt Disney Animation Studios feature Lilo & Stitch. The film was a critical and commercial triumph, grossing over $273 million worldwide. Chase's voice performance was highly praised for its emotional authenticity and comedic timing; she was subsequently awarded the Outstanding Voice Acting in an Animated Feature at the 30th Annie Awards in 2003. She reprised the role of Lilo in the direct-to-video film Stitch! The Movie (2003) and the subsequent television series Lilo & Stitch: The Series, which aired on the Disney Channel from 2003 to 2006. Another voice acting role followed that year in Hayao Miyazaki's acclaimed animated fantasy film Spirited Away, that had a Disney-produced English-language dub where Chase provided the voice for protagonist Chihiro Ogino. Spirited Away later won the Academy Award for Best Animated Feature. Later in 2002, Chase starred as Samara Morgan in the supernatural horror film The Ring, a remake of the 1998 Japanese film Ring. Playing a malevolent, drowned child who curses a videotape, Chase required extensive prosthetic makeup and performed physically demanding stunt work in the role. Her portrayal gained wide notice in early 2000s pop culture, and the character of Samara became an iconic cinematic villain. At the 2003 MTV Movie Awards, Chase won the Best Villain award.
Sources: en.wikipedia.org
=== Cytokine modulation === An effective vaccine must induce an appropriate immune response for a given pathogen. DNA vaccines can polarise T-cell help towards TH1 or TH2 profiles and generate CTL and/or antibody when required. This can be accomplished by modifications to the form of antigen expressed (i.e. intracellular vs. secreted), the method and route of delivery or the dose. It can also be accomplished by the co-administration of plasmid DNA encoding immune regulatory molecules, i.e. cytokines, lymphokines or co-stimulatory molecules. These "genetic adjuvants" can be administered as a:
Instead, they reduce the release of excitatory neurotransmitters including glutamate, monoamine neurotransmitters and Substance P. Although not thought to be a major site of action, gabapentinoids such as gabapentin, but not pregabalin, have been found to activate Kv voltage-gated potassium channels (KCNQ). The endogenous α-amino acids L-leucine and L-isoleucine, which resemble the gabapentinoids in chemical structure (see figure) are ligands of the α2δ VDCC subunit with similar affinity as gabapentin and pregabalin (e.g., IC50 = 71 nM for L-isoleucine), and are present in human cerebrospinal fluid at micromolar concentrations (e.g., 12.9 μM for L-leucine, 4.8 μM for L-isoleucine). It has been hypothesized that they may be endogenous ligands of the subunit and that they may competitively antagonize the effects of gabapentinoids in brain tissues. In accordance, while gabapentin and pregabalin have nanomolar binding affinities for the α2δ subunit, their potencies in vivo are in the low micromolar range, and competition for binding by endogenous L-amino acids is likely responsible for this discrepancy. In one study, the affinity (Ki) values of gabapentinoids for the α2δ subunit expressed in rat brain were found to be 0.05 μM for gabapentin, 23 μM for (R)-phenibut, 39 μM for (S)-phenibut, and 156 μM for baclofen. Their affinities (Ki) for the GABAB receptor were >1 mM for gabapentin, 92 μM for (R)-phenibut, >1 mM for (S)-phenibut, 6 μM for Baclofen.
The opioid excess theory postulates that autism is the result of a metabolic disorder in which opioid peptides produced through metabolism of gluten and casein pass through an abnormally permeable intestinal membrane and then proceed to exert an effect on neurotransmission through binding with opioid receptors. Advocates of this hypothesis believe that autistic children are unusually sensitive to gluten, which results in small bowel inflammation in these children, which in turn allows these opioid peptides to enter the brain. However, mainstream reviews of existing studies have consistently determined there is insufficient evidence to validate the theory or prove that related alternative therapies have a measurable impact on core autistic traits.
== Evolutionary origins == Synovial joints have been found in the earliest jawed vertebrates (gnathostomes) 400 million years ago during the Silurian and Devonian. This finding overturns an earlier view that these joints first evolved in early tetrapods for terrestrial locomotion. Comparative studies find that synovial joints are present in all major groups of jawed vertebrates, including cartilaginous fishes (sharks, skates, and rays), bony fishes, and tetrapods. They are, however, absent in jawless vertebrates such as lampreys and hagfish. Cartilaginous fishes have true synovial joints with clear synovial cavities, articular cartilage lined by flattened chondrocytes, and express key developmental signaling molecules including growth differentiation factor-5 (Gdf5) and β-catenin, and require muscle contraction for proper joint cavitation. In contrast, cyclostomes have joints filled with tissue rather than fluid-filled cavities, with proteoglycans uniformly distributed across cartilages. Fossil evidence finds jawless osteostracans had pectoral fin connections filled with canals incompatible with fluid-filled joint cavities, while early jawed placoderms have reciprocally articulating surfaces separated by joint cavities. Synovial joints, it has been suggested, arose due to the high mechanical loads associated with predation and feeding and, as a result, allowed for the evolution of the complex skeletons of modern jawed vertebrates.
== Epidemiology == This condition occurs in association with denture wearing, and so those affected tend to be middle aged or older adults. 66-75% are estimated to occur in women. Epulis fissuratum is the third most common reactive lesion that occurs in the mouth, after peripheral giant cell granuloma and pyogenic granuloma.
Sources: en.wikipedia.org
Glutamate-5-semialdehyde is a non-proteinogenic amino acid involved in both the biosynthesis and degradation of proline and arginine (via ornithine), as well as in the biosynthesis of antibiotics, such as carbapenems. It is synthesized by the reduction of glutamyl-5-phosphate by glutamate-5-semialdehyde dehydrogenase. In solution in water, the aldehyde is in chemical equilibrium with (S)-1-pyrroline-5-carboxylic acid and this is the form in which many of its biochemical reactions occur.
After spending several days considering how to respond to the bill, President Truman vetoed Taft–Hartley with a strong message to Congress, calling the act a "dangerous intrusion on free speech." Labor leaders, meanwhile, derided the act as a "slave-labor bill". Despite Truman's all-out effort to prevent a veto override, Congress overrode his veto with considerable Democratic support, including 106 out of 177 Democrats in the House, and 20 out of 42 Democrats in the Senate.
A wide range of reproductive strategies have been noted in ant species. Females of many species are known to be capable of reproducing asexually through thelytokous parthenogenesis. Secretions from the male accessory glands in some species can plug the female genital opening and prevent females from re-mating. Most ant species have a system in which only the queen and breeding females have the ability to mate. Contrary to popular belief, some ant nests have multiple queens, while others may exist without queens. Workers with the ability to reproduce are called "gamergates" and colonies that lack queens are then called gamergate colonies; colonies with queens are said to be queen-right. In the ant Cataglyphis hispanica, workers are produced by hybridization of two distinct lineages while the male and female reproductives are produced through (asexual) parthenogenesis. The production of hybrid workers with the existence of non-hybrid queens and males has been termed as "social hybridogenesis". This has been noted in the genera Messor, Pogonomyrmex, Cataglyphis and Solenopsis. The use of sperm of another species by females has been termed as sperm parasitism. A more complex situation was discovered in 2025 where Messor ibericus queens were shown to lay some eggs that developed into workers which match genetically with a different species of ant, Messor structor. Although the two species overlap in some parts of their range, the colonies studied were on the island of Sicily where M. ibericus alone is found. Queen M. ibericus in this region were able to produce M.
His Imperial and Royal Apostolic Majesty, Francis Joseph I, by the Grace of God Emperor of Austria, King of Germany, King of Hungary, Bohemia, Lombardy–Venetia, Dalmatia, Croatia, Slavonia, Galicia, Lodomeria, Illyria, Serbia, Cumania, Bulgaria, Italy, Rama, Romania, King of Jerusalem, etc. etc.; Archduke of Austria; Grand Duke of Tuscany; Duke of Lorraine, Salzburg, Styria, Carinthia, Carniola and Bukovina; Grand Prince of Transylvania, Margrave of Moravia; Duke of Upper and Lower Silesia, of Modena, Parma, Piacenza and Guastalla, of Auschwitz and Zator, of Teschen, Friaul, Ragusa and Zara and Teck; Princely Count of Habsburg and Tyrol, of Kyburg, Gorizia and Gradisca; Prince of Trento and Brixen; Margrave of Upper and Lower Lusatia, Istria; Count of Hohenems, Feldkirch, Bregenz, Sonnenberg, etc. etc.; Lord of Trieste, of Cattaro and on the Windic March; Grand Voivode of the Voivodeship of Serbia, etc. etc.
Sources: en.wikipedia.org
The sequence is Thr-Lys-Pro-Arg-Pro-Gly-Pro, written TKPRPGP in one-letter code. It combines the tetrapeptide tuftsin with a carboxyl-terminal Pro-Gly-Pro extension. This full sequence identifies the molecule more precisely than the research name.
No peptide with this exact sequence has been identified as an endogenous substance. It is a laboratory-designed analog of tuftsin, a naturally occurring immunomodulatory tetrapeptide. The Pro-Gly-Pro extension has no known natural source.
Proline introduces conformational constraints that make a peptide less accessible to common peptidases. This is a standard stabilization strategy in peptide design. The added residues also increase the distance between the active tuftsin portion and typical cleavage sites.
It is a seven-amino-acid peptide, Thr-Lys-Pro-Arg-Pro-Gly-Pro, produced by chemical synthesis rather than extracted from biological tissue. Its design is based on tuftsin, a natural immunomodulatory tetrapeptide. The C-terminal Pro-Gly-Pro segment is a common stabilising motif in short regulatory peptides.