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PubMed1998

Glycine and GABA receptors in the mammalian retina.

Molecular cloning has introduced an unexpected diversity of neurotransmitter receptors. In this study we review the types, the localization and possible synaptic function of the inhibitory neurotransmitter receptors in the mammalian retina. Glycine receptors (GlyRs) and their localization in the mammalian retina were analyzed immunocytochemically. Specific antibodies against the alpha 1 subunit of the GlyR (mAb2b) and against all subunits of the GlyR (mAb4a) were used. Both antibodies produced a punctate immunofluorescence, which was shown by electron microscopy to represent clustering of GlyRs at synaptic sites. Synapses expressing the alpha 1 subunit of the GlyR were found on ganglion cell dendrites and on bipolar cell axons. GlyRs were also investigated in the oscillator mutant mouse. The complete loss of the alpha 1 subunit was compensated for by an apparent upregulation of the other subunits of the GlyR. GABAA receptors (GABAARs) and their retinal distribution were studied with specific antibodies that recognize the alpha 1, alpha 2, alpha 3, beta 1, beta 2, beta 3, gamma 2 and delta subunits. Most antibodies produced a punctate immunofluorescence in the inner plexiform layer (IPL) which was shown by electron microscopy to represent synaptic clustering of GABAARs. The density of puncta varied across the IPL and different subunits were found in characteristic strata. This stratification pattern was analyzed with respect to the ramification of cholinergic amacrine cells. Using intracellular injection with Lucifer yellow followed by immunofluorescence, we found that GABAARs composed of different subunits were expressed by the same ganglion cell, however, they were clustered at different synaptic sites. The distribution of GABAC receptors was studied in the mouse and in the rabbit retina using an antiserum that recognizes the rho 1, rho 2 and rho 3 subunits. GABAC receptors were found to be clustered at postsynaptic sites. Most, if not all of the synapses were found on rod and cone bipolar axon terminals. In conclusion we find a great diversity of glycine and GABA receptors in the mammalian retina, which might match the plethora of morphological types of amacrine cells. This may also point to subtle differences in synaptic function still to be elucidated.

Animals↗
PubMed1975

Minimal brain Dysfunction.

Because of the prevalence in our society of children labeled with the term minimal brain dysfunction; physicians who treat children must develop a point of view toward the syndrome and a working procedure for assisting affected children. An approach to this problem can be divided into two parts: detection of somatic disorders and comprehensive management of school problems. The detection of somatic disorders that may have produced or substantially contributed to the school problem requires conventional medical skills for recognition and treatment. Comprehensive management of school problems requires a broader approach by the physician; including counseling of the parents regarding adverse family interactions, advice about educational resources and consideration of the question of drug therapy for behavioral disorders. In all instances parents should be able to rely on the physician to act as a scientific source of guidance on the merits of the plethora of therapies directed toward the child with learning disorders. The ability to function competently in all of these areas will enable the physician to provide a service for children and their families that may profoundly affect their lives.

Attention Deficit Disorder with Hyperactivity↗
PubMed1980

Genetic patterns in diabetes mellitus.

Diabetes comprises many syndromes whose only common feature is a high blood glucose level. Some are entirely genetic, some partially so, and others not at all. Perhaps the most important advance in the past 10 years is proof that insulin dependent diabetes is genetically different from the insulin independent form. Most progress has been made in unraveling the etiology of insulin dependent diabetes, although more information is needed before the mode of inheritance is finally settled. The last few years have produced a plethora of new facts about insulin dependent diabetes mellitus, providing geneticists, clinicians, and epidemiologists with the fascinating challenge of a disease with an apparently genetic susceptibility to external (environmental) triggers. Little progress has been made in the field of insulin independent diabetes, and one might safely predict that the diabetic syndrome will still produce some nightmares for researchers who take up the challenge of trying to unravel its various etiologies and methods of inheritance.

Adolescent↗
PubMed2003

The fluxes and transformations of suspended particles, carbon and nitrogen in the Humber estuarine system (UK) from 1994 to 1996: results from an integrated observation and modelling study.

Results from the first multi-constituent dynamic modelling study of the Humber estuarine system over seasonal time scales are presented. The model, constructed within the ECoS3 simulation software, has been calibrated using data obtained from 27 surveys of the Yorkshire Ouse and Humber estuaries during 1994-1996. The model is tidally averaged, and is one-dimensional in the vertical and in cross-section. Daily-varying longitudinal concentration profiles of SPM, POC, nitrate, nitrite and ammonium have been simulated, and these have been compared with the observations used for model calibration (model confirmation). The fits are generally good. The model captures the marked seasonal variability in concentrations of the particulate constituents (SPM, POC), and places the turbidity maximum in approximately the correct region of the estuary. There was a high degree of scatter in the SPM and POC concentrations measured due to tidal resuspension, which was not reproduced by the tidally averaged model. Comparisons between measured and simulated nitrate+nitrite are satisfactory, although for a number of surveys the modelled values are systematically too low in the lower Yorkshire Ouse and upper Humber. These discrepancies are not readily explained, but may be linked to inadequately characterised source terms for this nitrogen. The general trends in the concentrations and distributions of ammonium are reproduced by the model, despite the plethora of external inputs of this constituent, and significant modifications to ammonium transport by in situ nitrification and benthic exchange. The simulated concentrations and distributions have also been tested against independent data encapsulating axial transects in the Trent and Humber estuaries, and temporal variations at fixed sites on the Trent and Yorkshire Ouse estuaries. With some exceptions, the fits between the model results and these data are also good. The model has also been used to construct constituent budgets (external/internal sources and sinks) for each estuary for 1994, 1995 and 1996. Riverine inputs of SPM, POC, nitrate, nitrite and ammonium decreased over the 3 years, presumably reflecting changing patterns of terrestrial runoff coupled to a reduction in effluent inputs. This trend was also observed in the point discharges of these constituents direct to the estuary. The simulated estuary was a source of sediments to the North Sea during 1994 and 1996, but a sink during 1995. The difference has been ascribed to the exceptionally dry summer and autumn of 1995, in which up-estuary tidal 'pumping' of SPM was dominant over down-estuary flushing by river water. Fluvial inputs represent an important external source of POC to the model estuary (27-55%), as does the North Sea (26-58%). These inputs are exceeded by POC loss via bacterial remineralisation, suggesting that the estuarine bed is a net source of POC. Riverine inputs account for 76-77% of the external inputs of nitrate. This constituent behaves quasi-conservatively in the estuary, reflecting the dilution of nitrate-rich river waters with low-nitrate coastal water, although nitrification is a significant input (approx. 21%). Denitrification is small, and consequently all nitrate added to the estuary is lost to the North Sea. External loads of nitrite are small and ammonium nitrification accounts for approximately 93% of its annual input. Practically all of the nitrite is oxidised to nitrate, and little escapes to the North Sea. The fluvial and direct waste inputs of ammonium to the estuary are of similar size. Most of the ammonium in the model is nitrified (98-100%) and only a few tons are exported to the North Sea. In 1996 the estuary appears to have been a sink for coastal water ammonium. Constituent budgets are compared with independently evaluated fluxes. There is good agreement in a number of cases, but the comparison highlights the main uncertainties in the simulated fluxes. It is concluded that the model as currently formulated provides an excellent basis for heuristic studies of the Humber estuarine system.

Ammonia↗
PubMed1997

Hepatitis C virus infection and autoimmunity.

Hepatitis C virus (HCV) infection has been associated with a plethora of immune and autoimmune perturbations. We review serological and clinical autoimmune manifestations associated with HCV infection, discuss treatment regimens for HCV-related autoimmune diseases, and present a framework for understanding HCV-associated autoimmune disease by performing a computerized literature search from which representative articles were used and referenced. The immune response to HCV may include the development of cryoglobulins, rheumatoid factor, antinuclear antibodies (ANA), anticardiolipin, antithyroid, anti-liver/kidney/microsomal antibodies (anti-LKM), as well as HCV/anti-HCV immune complex formation and deposition. HCV infection is a significant cause of mixed essential cryoglobulinemia, which may then be complicated by cryoglobulinemic glomerulonephritis, vasculitis, or neuropathy. It has also been associated with membranous and membranoproliferative glomerulonephritis. Subsets of autoimmune hepatitis patients are infected with HCV and evidence suggests that HCV is a causative agent of antithyroid antibodies and autoimmune thyroid disease. Although cause-and-effect remain to be proved, there are reports of HCV infection preceding or coincident with polyarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and polymyositis/dermatomyositis (PM/DM). HCV-infected patients also have a high incidence of sialoadenitis, and reports of low-grade lymphoproliferative malignancies have emerged. However, HCV is not a major causative factor for most autoimmune diseases. Optimal treatment for HCV-related autoimmune disease remains to be determined. Interferon alpha (IFN alpha) has successfully reduced viremia/transaminitis, cryoglobulins, proteinuria, and nephritis, but recurrent disease manifestations are frequent after discontinuation of therapy. Moreover, IFN alpha may precipitate or exacerbate autoimmune disease symptoms. HCV-related autoimmune disease also has been treated successfully with corticosteroids, azathioprine, and cyclophosphamide, although HCV viremia persists and may worsen.

Antibodies, Viral↗
PubMed1997

Marine microorganisms as a source of new natural products.

Over the past decade, marine microorganisms have become recognized as an important and untapped resource for novel bioactive compounds. The oceans cover greater than 70% of the earth's surface and, taking this into account by volume, represent better than 95% of the biosphere. Given this fact, the oceans present themselves as an unexplored area of opportunity for the discovery of pharmacologically active compounds. In this review, data have been presented to illustrate the diversity of microorganisms living in the sea and the plethora of chemical compounds that have been discovered from them. However, it is important to pursue basic research on the marine environment in order to permit the continued isolation of unique microorganisms. There is still limited knowledge of the physiological requirements of most marine microorganisms, and a greater understanding of their conditions for growth will offer new insights into the complex world of marine microbiology. Clearly, a greater investment in the development of marine biotechnology will produce novel compounds that may contribute significantly toward drug development over the next decade.

Animals↗
PubMed2001

Retinoblastoma protein partners.

Studies of the retinoblastoma gene (Rb) have shown that its protein product (pRb) acts to restrict cell proliferation, inhibit apoptosis, and promote cell differentiation. The frequent mutation of the Rb gene, and the functional inactivation of pRb in tumor cells, have spurred interest in the mechanism of pRb action. Recently, much attention has focused on pRb's role in the regulation of the E2F transcription factor. However, biochemical studies have suggested that E2F is only one of many pRb-targets and, to date, at least 110 cellular proteins have been reported to associate with pRb. The plethora of pRb-binding proteins raises several important questions. How many functions does pRb possess, which of these functions are important for development, and which contribute to tumor suppression? The goal of this review is to summarize the current literature of pRb-associated proteins.

Carrier Proteins↗
PubMed2002

The myc oncogene: MarvelouslY Complex.

The activated product of the myc oncogene deregulates both cell growth and death check points and, in a permissive environment, rapidly accelerates the affected clone through the carcinogenic process. Advances in understanding the molecular mechanism of Myc action are highlighted in this review. With the revolutionary developments in molecular diagnostic technology, we have witnessed an unprecedented advance in detecting activated myc in its deregulated, oncogenic form in primary human cancers. These improvements provide new opportunities to appreciate the tumor subtypes harboring deregulated Myc expression, to identify the essential cooperating lesions, and to realize the therapeutic potential of targeting Myc. Knowledge of both the breadth and depth of the numerous biological activities controlled by Myc has also been an area of progress. Myc is a multifunctional protein that can regulate cell cycle, cell growth, differentiation, apoptosis, transformation, genomic instability, and angiogenesis. New insights into Myc's role in regulating these diverse activities are discussed. In addition, breakthroughs in understanding Myc as a regulator of gene transcription have revealed multiple mechanisms of Myc activation and repression of target genes. Moreover, the number of reported Myc regulated genes has expanded in the past few years, inspiring a need to focus on classifying and segregating bona fide targets. Finally, the identity of Myc-binding proteins has been difficult, yet has exploded in the past few years with a plethora of novel interactors. Their characterization and potential impact on Myc function are discussed. The rapidity and magnitude of recent progress in the Myc field strongly suggests that this marvelously complex molecule will soon be unmasked.

Animals↗
PubMed2007

Biomarker assay translation from discovery to clinical studies in cancer drug development: quantification of emerging protein biomarkers.

Many candidate biomarkers emerging from genomics and proteomics research have the potential to serve as predictive indexes for guiding the development of safer and more efficacious drugs. Research and development of biomarker discovery, selection, and clinical qualification, however, is still a relatively new field for the pharmaceutical industry. Advances in technology provide a plethora of analytical tools to discover and analyze mechanism-and-disease-specific biomarkers for drug development. In the discovery phase, differential proteomic analysis using mass spectrometry enables the identification of candidate biomarkers that are associated with a specific mechanism relevant to disease progression and affected by drug treatment. Reliable bioanalytical methods are then developed and implemented to select promising biomarkers for further studies in animals and humans. Quantitative analytical methods capable of generating reliable data constitute a solid basis for statistical assessment of the predictive utility of biomarkers. Biomarker method validation is diverse and for purposes that are very different from those of drug bioanalysis or diagnostic use. Besides being flexible, it should sufficiently demonstrate the method's ability to meet the study intent and the attendant regulatory requirements. Several papers have been published outlining specific requirements for successful biomarker method development and validation using a "Fit-for-Purpose" approach. Many of the challenges faced during biomarker discovery as well as during technology and process translation are discussed in this chapter, including preanalytical planning, assay development, and preclinical and clinical validation. Specific references to protein biomarkers for cancer drug development are also discussed.

Animals↗
PubMed2003

G protein-coupled receptors in invertebrates: a state of the art.

G protein-coupled receptors (GPCRs) constitute one of the largest and most ancient superfamilies of membrane-spanning proteins. We focus on neuropeptide GPCRs, in particular on those of invertebrates. In general, such receptors mediate the responses of signaling molecules that constitute the highest hierarchical position in the regulation of physiological processes. Until recently, only a few of these receptors were identified in invertebrates. However, the availability of a plethora of genomic information has boosted the discovery of novel members in several invertebrate species, such as Drosophila, in which 18 neuropeptide GPCRs have been characterized. The finalization of genomic projects in other invertebrates will lead to a similar expansion of GPCR understanding. Many new insights regarding neuropeptide regulation have followed from the discovery of their cognate receptors. Furthermore, information on GPCR signaling is still fragmentary and the elucidation of these pathways in model insects such as Drosophila will lead to further insights in other species, including mammals. In this review we present the current status of what is known about invertebrate GPCRs, discuss some novel perceptions that follow from the identified members, and, finally, present some future prospects.

Amino Acid Sequence↗
PubMed2004

Cell and molecular biology of nucleolar assembly and disassembly.

Nucleoli disassemble in prophase of the metazoan mitotic cycle, and they begin their reassembly (nucleologenesis) in late anaphase?early telophase. Nucleolar disassembly and reassembly were obvious to the early cytologists of the eighteenth and nineteenth centuries, and although this has lead to a plethora of literature describing these events, our understanding of the molecular mechanisms regulating nucleolar assembly and disassembly has expanded immensely just within the last 10-15 years. We briefly survey the findings of nineteenth-century cytologists on nucleolar assembly and disassembly, followed by the work of Heitz and McClintock on nucleolar organizers. A primer review of nucleolar structure and functions precedes detailed descriptions of modern molecular and microscopic studies of nucleolar assembly and disassembly. Nucleologenesis is concurrent with the reinitiation of rDNA transcription in telophase. The perichromosomal sheath, prenucleolar bodies, and nucleolar-derived foci serve as repositories for nucleolar processing components used in the previous interphase. Disassembly of the perichromosomal sheath along with the dynamic movements and compositional changes of the prenucleolar bodies and nucleolus-derived foci coincide with reactivation of rDNA synthesis within the chromosomal nucleolar organizers during telophase. Nucleologenesis is considered in various model organisms to provide breadth to our understanding. Nucleolar disassembly occurs at the onset of mitosis primarily as a result of the mitosis-specific phosphorylation of Pol I transcription factors and processing components. Although we have learned much regarding nucleolar assembly and disassembly, many questions still remain, and these questions are as vibrant for us today as early questions were for nineteenth- and early twentieth-century cytologists.

Animals↗
PubMed1995

The nuclear matrix: a structural milieu for genomic function.

While significant progress has been made in elucidating molecular properties of specific genes and their regulation, our understanding of how the whole genome is coordinated has lagged behind. To understand how the genome functions as a coordinated whole, we must understand how the nucleus is put together and functions as a whole. An important step in that direction occurred with the isolation and characterization of the nuclear matrix. Aside from the plethora of functional properties associated with these isolated nuclear structures, they have enabled the first direct examination and molecular cloning of specific nuclear matrix proteins. The isolated nuclear matrix can be used for providing an in vitro model for understanding nuclear matrix organization in whole cells. Recent development of high-resolution and three-dimensional approaches for visualizing domains of genomic organization and function in situ has provided corroborative evidence for the nuclear matrix as the site of organization for replication, transcription, and post-transcriptional processing. As more is learned about these in situ functional sites, appropriate experiments could be designed to test molecular mechanisms with the in vitro nuclear matrix systems. This is illustrated in this chapter by the studies of nuclear matrix-associated DNA replication which have evolved from biochemical studies of in vitro nuclear matrix systems toward three-dimensional computer image analysis of replication sites for individual genes.

Animals↗
PubMed2006

An introduction to BioArray Software Environment.

BioArray Software Environment (BASE) is a web-based software package for storing, searching, and analyzing locally generated microarray data and information surrounding microarray production. The workflow begins in sample management and, optionally, microtiter plate tracking and ends in visualization and analysis of entire experiments. The relative ease with which new analysis plug-ins can be added has given rise to a plethora of third-party tools, and the licensing terms (GNU GPL) encourage local modifications of the software. This introduction to BASE describes the basics of working with the software, both in general and in more detail for the various parts. It also provides some hints about more advanced usage and a section on what is needed to set up your own BASE server. The information is current as of BASE version 1.2.17b, which was released on November 6, 2005.

Animals↗
PubMedDate not supplied

Human proteomic databases: a powerful resource for functional genomics in health and disease.

Decoding of the genome information in terms of regulation and function will be the next great challenge in the life sciences in this millennium and indeed, today we are experiencing a rapid explosion of technology for the high throughput expression analysis of genes and their products (functional genomics). In particular, the field of proteomics is booming as proteins are often the functional molecules and represent important targets for the pharmaceutical industry. The proteomic technology is complex, and comprises a plethora of state-of-the-art techniques to resolve, identify and detect their interacting partners, as well as to store and communicate protein information in comprehensive two-dimensional polyacrylamide gel electrophoresis (2D PAGE) databases. Besides annotating the genome, these databases will offer a global approach to the study of gene expression both in health and disease. Here, we review the current status of human 2D PAGE databases that we are systematically constructing for the study of bladder cancer and skin ageing.

Databases, Protein↗
PubMed1999

The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction.

The ubiquitin system of intracellular protein degradation controls the abundance of many critical regulatory proteins. Specificity in the ubiquitin system is determined largely at the level of substrate recognition, a step that is mediated by E3 ubiquitin ligases. Analysis of the mechanisms of phosphorylation directed proteolysis in cell cycle regulation has uncovered a new class of E3 ubiquitin ligases called SCF complexes, which are composed of the subunits Skp1, Rbx1, Cdc53 and any one of a large number of different F-box proteins. The substrate specificity of SCF complexes is determined by the interchangeable F-box protein subunit, which recruits a specific set of substrates for ubiquitination to the core complex composed of Skp1, Rbx1, Cdc53 and the E2 enzyme Cdc34. F-box proteins have a bipartite structure--the shared F-box motif links F-box proteins to Skp1 and the core complex, whereas divergent protein-protein interaction motifs selectively bind their cognate substrates. To date all known SCF substrates are recognised in a strictly phosphorylation dependent manner, thus linking intracellular signalling networks to the ubiquitin system. The plethora of different F-box proteins in databases suggests that many pathways will be governed by SCF-dependent proteolysis. Indeed, genetic analysis has uncovered roles for F-box proteins in a variety of signalling pathways, ranging from nutrient sensing in yeast to conserved developmental pathways in plants and animals. Moreover, structural analysis has revealed ancestral relationships between SCF complexes and two other E3 ubiquitin ligases, suggesting that the combinatorial use of substrate specific adaptor proteins has evolved to allow the regulation of many cellular processes. Here, we review the known signalling pathways that are regulated by SCF complexes and highlight current issues in phosphorylation dependent protein degradation.

Amino Acid Sequence↗
PubMed1990

Excitotoxin-mediated neuron death in youth and old age.

Here I have discussed current issues in excitotoxicology (neurotoxicity of Glu and related agents) with special emphasis on the NMDA receptor and its possible role in neuropsychiatric disorders. I have briefly described several classes of anti-excitotoxic agents which are currently under study for their ability to protect neurons against excitotoxin-mediated neuronal degeneration. There is growing interest in the possibility that such agents, especially NMDA antagonists will prove useful in the clinical management of neurodegenerative disorders; however, neither their efficacy nor safety has been adequately established at present. With the plethora of new information about the NMDA receptor--ionophore complex, one tends to forget that non-NMDA receptors can also mediate excitotoxic events. Thus, although we know less about the physiology and make up of non-NMDA receptors, it seems likely that new information, as it becomes available, will reveal new links between endogenous excitotoxins and neuropsychiatric disease processes. In particular, since NMDA receptors are relatively more sensitive in early life and non-NMDA receptors more sensitive in adulthood, it is reasonable to postulate the greatest involvement of the former in developmental psychoneuropathology and the latter in neurodegenerative diseases of the elderly.

Aging↗
PubMed1992

5-lipoxygenase inhibitors and their anti-inflammatory activities.

A wide variety of agents have been reported as 5-LO inhibitors. The majority of the series appear to be lipophilic reducing agents, including phenols, partially saturated aromatics, and compounds containing heteroatom-heteroatom bonds. Many of these are not selective 5-LO inhibitors, but often affect CO and other LOs as well. In vivo systemic activity for many of these has been, in general, disappointing, probably because of poor bioavailability caused by lipophilicity and metabolic instability (oxidation, and conjugation of phenolic compounds). However, topically a number of agents have shown promise for skin inflammation, with Syntex's lonapalene the most advanced of these. Most results published to date appear more disappointing in the allergy/asthma field. More excitingly, a few structural types are selective 5-LO inhibitors which have shown systemic activity in vivo and in the clinic. Abbott's zileuton (136) appears to be one of the leading compounds in this category, along with other hydroxamates such as BW-A4C (129) from Burroughs-Wellcome. Recent selective non-reducing agents such as Wyeth-Ayerst's Wy-50,295 (143) and the similar ICI compounds such as ICI 216800 (145) also hold promise. The enantiospecific effects of (106) and (145) are especially interesting for the design of new inhibitors. If compounds like these validate the hypothesis that inhibition of 5-LO will have a significant anti-inflammatory effect, a redoubling of effort throughout the industry to find second- and third-generation selective agents may be expected. Part of the difficulty in interpreting and comparing the 5-LO literature is the plethora of test methods and activity criteria. As pointed out in the introduction, inhibition of product release from cells, often stimulated with A23187, has commonly been used to demonstrate 5-LO inhibition. However, this type of assay cannot be assumed to be diagnostic for 5-LO inhibition. Only if specificity for 5-LO product generation and (ideally) activity in cell-free enzymes is also shown should mechanistic interpretations be made. Recently, a new class of compounds was found at Merck which inhibited LT biosynthesis without inhibiting 5-LO, but apparently by a novel, specific mechanism. L-655,240 (169) and L-663,536 (MK-886) (170) were both active in human ISN, with IC50 values in the low micromolar range. Both also orally inhibited GPB (< 1 mg/kg). MK-886 was effective in Ascaris-induced asthma in squirrel monkeys, in rat carrageenan pleurisy, in rat Arthus pleurisy, and (topically) in guinea-pig ear oedema induced by A23187.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Thymosin beta 4 interactions.

Thymosin beta 4 is a small, 5-kDa protein with a diverse range of activities, including its function as an actin monomer sequestering protein, an antiinflammatory agent, and an inhibitor of bone marrow stem cell proliferation. Only the effects of thymosin beta 4 on the actin cytoskeleton have an explanation based on identified molecular interactions. Thymosin beta 4 is largely unfolded or perhaps completely unfolded in solution. Based on the paradigm introduced by Wright and Dyson (1999) that unfolded proteins may have multiple functions based on their ability to recognize numerous ligands, the flexible structure of thymosin beta 4 may facilitate the recognition of a variety of molecular targets, thus explaining the plethora of functions attributed to thymosin beta 4. Furthermore, if multiple ligands bind to thymosin beta 4, then it is possible that thymosin beta 4 has a unique integrative function that links the actin cytoskeleton to important immune and cell growth-signaling cascades.

Actins↗