Povidone
Substance P
Macromolecular Substances
Receptors, Neurokinin-1
Molecular chaperones: small heat shock proteins in the limelight. (1/19184)
Small heat shock proteins have been the Cinderellas of the molecular chaperone world, but now the crystal structure of a small heat shock protein has been solved and mutation of two human homologues implicated in genetic disease. Intermediate filaments appear to be one of the key targets of their chaperone activity. (+info)Association of snRNA genes with coiled bodies is mediated by nascent snRNA transcripts. (2/19184)
BACKGROUND: Coiled bodies are nuclear organelles that are highly enriched in small nuclear ribonucleoproteins (snRNPs) and certain basal transcription factors. Surprisingly, coiled bodies not only contain mature U snRNPs but also associate with specific chromosomal loci, including gene clusters that encode U snRNAs and histone messenger RNAs. The mechanism(s) by which coiled bodies associate with these genes is completely unknown. RESULTS: Using stable cell lines, we show that artificial tandem arrays of human U1 and U2 snRNA genes colocalize with coiled bodies and that the frequency of the colocalization depends directly on the transcriptional activity of the array. Association of the genes with coiled bodies was abolished when the artificial U2 arrays contained promoter mutations that prevent transcription or when RNA polymerase II transcription was globally inhibited by alpha-amanitin. Remarkably, the association was also abolished when the U2 snRNA coding regions were replaced by heterologous sequences. CONCLUSIONS: The requirement for the U2 snRNA coding region indicates that association of snRNA genes with coiled bodies is mediated by the nascent U2 RNA itself, not by DNA or DNA-bound proteins. Our data provide the first evidence that association of genes with a nuclear organelle can be directed by an RNA and suggest an autogenous feedback regulation model. (+info)Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. (3/19184)
The vacuolar protein sorting (VPS) pathway of Saccharomyces cerevisiae mediates transport of vacuolar protein precursors from the late Golgi to the lysosome-like vacuole. Sorting of some vacuolar proteins occurs via a prevacuolar endosomal compartment and mutations in a subset of VPS genes (the class D VPS genes) interfere with the Golgi-to-endosome transport step. Several of the encoded proteins, including Pep12p/Vps6p (an endosomal target (t) SNARE) and Vps45p (a Sec1p homologue), bind each other directly [1]. Another of these proteins, Vac1p/Pep7p/Vps19p, associates with Pep12p and binds phosphatidylinositol 3-phosphate (PI(3)P), the product of the Vps34 phosphatidylinositol 3-kinase (PI 3-kinase) [1] [2]. Here, we demonstrate that Vac1p genetically and physically interacts with the activated, GTP-bound form of Vps21p, a Rab GTPase that functions in Golgi-to-endosome transport, and with Vps45p. These results implicate Vac1p as an effector of Vps21p and as a novel Sec1p-family-binding protein. We suggest that Vac1p functions as a multivalent adaptor protein that ensures the high fidelity of vesicle docking and fusion by integrating both phosphoinositide (Vps34p) and GTPase (Vps21p) signals, which are essential for Pep12p- and Vps45p-dependent targeting of Golgi-derived vesicles to the prevacuolar endosome. (+info)Four dimers of lambda repressor bound to two suitably spaced pairs of lambda operators form octamers and DNA loops over large distances. (4/19184)
Transcription factors that are bound specifically to DNA often interact with each other over thousands of base pairs [1] [2]. Large DNA loops resulting from such interactions have been observed in Escherichia coli with the transcription factors deoR [3] and NtrC [4], but such interactions are not, as yet, well understood. We propose that unique protein complexes, that are not present in solution, may form specifically on DNA. Their uniqueness would make it possible for them to interact tightly and specifically with each other. We used the repressor and operators of coliphage lambda to construct a model system in which to test our proposition. lambda repressor is a dimer at physiological concentrations, but forms tetramers and octamers at a hundredfold higher concentration. We predict that two lambda repressor dimers form a tetramer in vitro when bound to two lambda operators spaced 24 bp apart and that two such tetramers interact to form an octamer. We examined, in vitro, relaxed circular plasmid DNA in which such operator pairs were separated by 2,850 bp and 2,470 bp. Of these molecules, 29% formed loops as seen by electron microscopy (EM). The loop increased the tightness of binding of lambda repressor to lambda operator. Consequently, repression of the lambda PR promoter in vivo was increased fourfold by the presence of a second pair of lambda operators, separated by a distance of 3,600 bp. (+info)Stable remodeling of tailless nucleosomes by the human SWI-SNF complex. (5/19184)
The histone N-terminal tails have been shown previously to be important for chromatin assembly, remodeling, and stability. We have tested the ability of human SWI-SNF (hSWI-SNF) to remodel nucleosomes whose tails have been cleaved through a limited trypsin digestion. We show that hSWI-SNF is able to remodel tailless mononucleosomes and nucleosomal arrays, although hSWI-SNF remodeling of tailless nucleosomes is less effective than remodeling of nucleosomes with tails. Analogous to previous observations with tailed nucleosomal templates, we show both (i) that hSWI-SNF-remodeled trypsinized mononucleosomes and arrays are stable for 30 min in the remodeled conformation after removal of ATP and (ii) that the remodeled tailless mononucleosome can be isolated on a nondenaturing acrylamide gel as a novel species. Thus, nucleosome remodeling by hSWI-SNF can occur via interactions with a tailless nucleosome core. (+info)Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity. (6/19184)
Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand. (+info)Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A. (7/19184)
The small G protein Rab3A plays an important role in the regulation of neurotransmitter release. The crystal structure of activated Rab3A/GTP/Mg2+ bound to the effector domain of rabphilin-3A was solved to 2.6 A resolution. Rabphilin-3A contacts Rab3A in two distinct areas. The first interface involves the Rab3A switch I and switch II regions, which are sensitive to the nucleotide-binding state of Rab3A. The second interface consists of a deep pocket in Rab3A that interacts with a SGAWFF structural element of rabphilin-3A. Sequence and structure analysis, and biochemical data suggest that this pocket, or Rab complementarity-determining region (RabCDR), establishes a specific interaction between each Rab protein and its effectors. RabCDRs could be major determinants of effector specificity during vesicle trafficking and fusion. (+info)Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. (8/19184)
The U1, U2, U4/U6, and U5 small nuclear ribonucleoprotein particles (snRNPs) involved in pre-mRNA splicing contain seven Sm proteins (B/B', D1, D2, D3, E, F, and G) in common, which assemble around the Sm site present in four of the major spliceosomal small nuclear RNAs (snRNAs). These proteins share a common sequence motif in two segments, Sm1 and Sm2, separated by a short variable linker. Crystal structures of two Sm protein complexes, D3B and D1D2, show that these proteins have a common fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel beta sheet, and the D1D2 and D3B dimers superpose closely in their core regions, including the dimer interfaces. The crystal structures suggest that the seven Sm proteins could form a closed ring and the snRNAs may be bound in the positively charged central hole. (+info)Povidone, also known as PVP or polyvinylpyrrolidone, is not a medication itself but rather a pharmaceutical ingredient used in various medical and healthcare products. It is a water-soluble synthetic polymer that has the ability to bind to and carry other substances, such as drugs or iodine.
In medical applications, povidone is often used as a binder or coating agent in pharmaceutical tablets and capsules. It can also be found in some topical antiseptic solutions, such as those containing iodine, where it helps to stabilize and control the release of the active ingredient.
It's important to note that while povidone is a widely used pharmaceutical ingredient, it is not typically considered a medication on its own.
Substance P is an undecapeptide neurotransmitter and neuromodulator, belonging to the tachykinin family of peptides. It is widely distributed in the central and peripheral nervous systems and is primarily found in sensory neurons. Substance P plays a crucial role in pain transmission, inflammation, and various autonomic functions. It exerts its effects by binding to neurokinin 1 (NK-1) receptors, which are expressed on the surface of target cells. Apart from nociception and inflammation, Substance P is also involved in regulating emotional behaviors, smooth muscle contraction, and fluid balance.
Macromolecular substances, also known as macromolecules, are large, complex molecules made up of repeating subunits called monomers. These substances are formed through polymerization, a process in which many small molecules combine to form a larger one. Macromolecular substances can be naturally occurring, such as proteins, DNA, and carbohydrates, or synthetic, such as plastics and synthetic fibers.
In the context of medicine, macromolecular substances are often used in the development of drugs and medical devices. For example, some drugs are designed to bind to specific macromolecules in the body, such as proteins or DNA, in order to alter their function and produce a therapeutic effect. Additionally, macromolecular substances may be used in the creation of medical implants, such as artificial joints and heart valves, due to their strength and durability.
It is important for healthcare professionals to have an understanding of macromolecular substances and how they function in the body, as this knowledge can inform the development and use of medical treatments.
Substance-related disorders, as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), refer to a group of conditions caused by the use of substances such as alcohol, drugs, or medicines. These disorders are characterized by a problematic pattern of using a substance that leads to clinically significant impairment or distress. They can be divided into two main categories: substance use disorders and substance-induced disorders. Substance use disorders involve a pattern of compulsive use despite negative consequences, while substance-induced disorders include conditions such as intoxication, withdrawal, and substance/medication-induced mental disorders. The specific diagnosis depends on the type of substance involved, the patterns of use, and the presence or absence of physiological dependence.
Neurokinin-1 (NK-1) receptors are a type of G protein-coupled receptor that bind to the neuropeptide substance P, which is a member of the tachykinin family. These receptors are widely distributed in the central and peripheral nervous systems and play important roles in various physiological functions, including pain transmission, neuroinflammation, and emesis (vomiting).
NK-1 receptors are activated by substance P, which binds to the receptor's extracellular domain and triggers a signaling cascade that leads to the activation of various intracellular signaling pathways. This activation can ultimately result in the modulation of neuronal excitability, neurotransmitter release, and gene expression.
In addition to their role in normal physiological processes, NK-1 receptors have also been implicated in a number of pathological conditions, including pain, inflammation, and neurodegenerative disorders. As such, NK-1 receptor antagonists have been developed as potential therapeutic agents for the treatment of these conditions.
Substance abuse treatment centers are healthcare facilities that provide a range of services for individuals struggling with substance use disorders (SUDs), including addiction to alcohol, illicit drugs, prescription medications, and other substances. These centers offer comprehensive, evidence-based assessments, interventions, and treatments aimed at helping patients achieve and maintain sobriety, improve their overall health and well-being, and reintegrate into society as productive members.
The medical definition of 'Substance Abuse Treatment Centers' encompasses various levels and types of care, such as:
1. **Medical Detoxification:** This is the first step in treating substance abuse, where patients are closely monitored and managed for withdrawal symptoms as their bodies clear the harmful substances. Medical detox often involves the use of medications to alleviate discomfort and ensure safety during the process.
2. **Inpatient/Residential Treatment:** This level of care provides 24-hour structured, intensive treatment in a controlled environment. Patients live at the facility and receive various therapeutic interventions, such as individual therapy, group counseling, family therapy, and psychoeducation, to address the underlying causes of their addiction and develop coping strategies for long-term recovery.
3. **Partial Hospitalization Programs (PHP):** Also known as day treatment, PHPs offer structured, intensive care for several hours a day while allowing patients to return home or to a sober living environment during non-treatment hours. This level of care typically includes individual and group therapy, skill-building activities, and case management services.
4. **Intensive Outpatient Programs (IOP):** IOPs provide flexible, less intensive treatment than PHPs, with patients attending sessions for a few hours per day, several days a week. These programs focus on relapse prevention, recovery skills, and addressing any co-occurring mental health conditions.
5. **Outpatient Treatment:** This is the least restrictive level of care, where patients attend individual or group therapy sessions on a regular basis while living at home or in a sober living environment. Outpatient treatment often serves as step-down care after completing higher levels of treatment or as an initial intervention for those with milder SUDs.
6. **Aftercare/Continuing Care:** Aftercare or continuing care services help patients maintain their recovery and prevent relapse by providing ongoing support, such as 12-step meetings, alumni groups, individual therapy, and case management.
Each treatment modality has its unique benefits and is tailored to meet the specific needs of individuals at various stages of addiction and recovery. It's essential to consult with a healthcare professional or an addiction specialist to determine the most appropriate level of care for each person's situation.