Temporal resolution measurement of 128-slice dual source and 320-row area detector computed tomography scanners in helical acquisition mode using the impulse method

PurposeTo analyse the temporal resolution (TR) of modern computed tomography (CT) scanners using the impulse method, and assess the actual maximum TR at respective helical acquisition modes.MethodsTo assess the actual TR of helical acquisition modes of a 128-slice dual source CT (DSCT) scanner and a 320-row area detector CT (ADCT) scanner, we assessed the TRs of various acquisition combinations of a pitch factor (P) and gantry rotation time (R).ResultsThe TR of the helical acquisition modes for the 128-slice DSCT scanner continuously improved with a shorter gantry rotation time and greater pitch factor. However, for the 320-row ADCT scanner, the TR with a pitch factor of <1.0 was almost equal to the gantry rotation time, whereas with pitch factor of >1.0, it was approximately one half of the gantry rotation time. The maximum TR values of single- and dual-source helical acquisition modes for the 128-slice DSCT scanner were 0.138 (R/P = 0.285/1.5) and 0.074 s (R/P = 0.285/3.2), and the maximum TR values of the 64 × 0.5- and 160 × 0.5-mm detector configurations of the helical acquisition modes for the 320-row ADCT scanner were 0.120 (R/P = 0.275/1.375) and 0.195 s (R/P = 0.3/0.6), respectively.ConclusionBecause the TR of a CT scanner is not accurately depicted in the specifications of the individual scanner, appropriate acquisition conditions should be determined based on the actual TR measurement.     

Modulation of the extracellular matrix patterning of thrombospondins by actin dynamics and thrombospondin oligomer state

Thrombospondins (TSPs) are evolutionarily-conserved, secreted glycoproteins that interact with cell surfaces and extracellular matrix (ECM) and have complex roles in cell interactions. Unlike the structural components of the ECM that form networks or fibrils, TSPs are deposited into ECM as arrays of nanoscale puncta. The cellular and molecular mechanisms for the patterning of TSPs in ECM are poorly understood. In the present study, we investigated whether the mechanisms of TSP patterning in cell-derived ECM involves actin cytoskeletal pathways or TSP oligomer state. From tests of a suite of pharmacological inhibitors of small GTPases, actomyosin-based contractility, or actin microfilament integrity and dynamics, cytochalasin D and jasplakinolide treatment of cells were identified to result in altered ECM patterning of a model TSP1 trimer. The strong effect of cytochalasin D indicated that mechanisms controlling puncta patterning depend on global F-actin dynamics. Similar spatial changes were obtained with endogenous TSPs after cytochalasin D treatment, implicating physiological relevance. Under matched experimental conditions with ectopically-expressed TSPs, the magnitude of the effect was markedly lower for pentameric TSP5 and Drosophila TSP, than for trimeric TSP1 or dimeric Ciona TSPA. To distinguish between the variables of protein sequence or oligomer state, we generated novel, chimeric pentamers of TSP1. These proteins accumulated within ECM at higher levels than TSP1 trimers, yet the effect of cytochalasin D on the spatial distribution of puncta was reduced. These findings introduce a novel concept that F-actin dynamics modulate the patterning of TSPs in ECM and that TSP oligomer state is a key determinant of this process.     

Energy metabolism by splanchnic tissues of mature sheep fed varying levels of lucerne hay cubes

The objective of this study was to determine the pattern of energy metabolites net flux across the portal-drained viscera (PDV) and total splanchnic tissues (TSP) in mature sheep fed varying levels of lucerne hay cubes. Four Suffolk mature sheep (61.4 ± 3.6 kg BW) surgically fitted with multi-catheters were fed four levels of dry matter intake (DMI) of lucerne hay cubes ranging from 0.4- to 1.6-fold the metabolizable energy (ME) requirements for maintenance. Six sets of blood samples were simultaneously collected from arterial and venous catheters at 30-min intervals. With increasing DMI, apparent total tract digestibility increased linearly and quadratically for dry matter (P < 0.05), quadratically (P < 0.05) with a linear tendency (P < 0.1) for organic matter and tended to increase quadratically (P < 0.1) for NDF. PDV release of volatile fatty acids (VFA) and β-hydroxybutyric acid was relatively low at 0.4 M and then linearly increased (P < 0.05) with increasing DMI. Net PDV flux of non-esterified fatty acids showed curvilinear decrease from 0.4 to 1.2 M and then increased at 1.6 M. The respective proportions of each VFA appearing in the portal blood differed (P < 0.05) with DMI and this difference was more obvious from 0.4 to 0.8 M than from 0.8 to 1.6 M. Heat production, as a percentage of ME intake (MEI), decreased linearly (P < 0.05) with increasing DMI accounting for 37%, 21%, 16% and 13% for PDV and 62%, 49%, 33% and 27% for TSP at 0.4, 0.8, 1.2 and 1.6 M, respectively. As a proportion of MEI, total energy recovery including heat production, decreased linearly with increasing DMI (P < 0.05) accounting for 113%, 83%, 62% and 57% for PDV and 140%, 129%, 86% and 83% for TSP at 0.4, 0.8, 1.2 and 1.6 M, respectively. Regression analysis revealed a linear response between MEI (MJ/day per kg BW) and total energy release (MJ/day per kg BW) across the PDV and TSP, respectively. However, respective contributions of energy metabolites to net energy release across the PDV and TSP were highly variable among treatments and did not follow the same pattern of changes in DMI.     

Modulation of thrombospondin expression during differentiation of embryonal carcinoma cells

The thrombospondins (TSPs) are a family of extracellular glycoproteins that display distinct patterns of temporal and spatial expression during development. In this study, we investigated the expression of two of the TSPs–TPS1 and TSP2– during the course of differentiation of embryonal carcinoma cells in vitro. We report that both TSP1 and TSP2 mRNA and protein synthesis are induced during the differentiation of P19EC cells into neurons, glial cells, and fibroblasts. Immunofluorescence studies indicate that TSP1 displays a fibrillar pattern of staining, characteristic of an extracellular matrix protein, in differentiated P19EC cells. In contrast, TSP2 is cell-associated and is present on differentiated P19EC cells and on primary neurons and glial cells obtained from a 17-day embyronic mouse cerebral cortex. Interestingly, although both TSP1 and TSP2 are more prevalent in areas of differentiated cells, they display distinct patterns of deposition. These observations suggest that TSP1 and TSP2 may function differently during neurogenesis. The response of TSP1 and TSP2 to differentiation of P19EC cells indicates that this cell system will serve as a valuable model for the study of TSP expression and function during neurogenesis. © 1994 Wiley-Liss, Inc.     

Temperature-shift analysis of conidial development in Aspergillus nidulans

Temperature-shift experiments have been performed on spore-originated colonies of 11 thermosensitive aconidial mutants of Aspergillus nidulans in order to determine the latest time of shift to the restrictive temperature that prevents the initiation of conidiation. This time defines the beginning of the thermosensitive period (TSP) of the mutant. Eight of the mutants have TSPs that begin in the 7-hour period (32–39 hr) just prior to the first appearance of conidia-bearing structures, while 3 of the mutants have TSPs that begin later and very close to the time of onset of conidiation (45 hr). Thus no mutant of the set has a TSP that begins during the first 32 hr of vegetative growth of spore-originated colonies. For all mutants, an upshift performed after the beginning of the TSP allows initiation of conidiation at close to the normal time and at the normal rate, but results in an abrupt cessation of conidiation at some fixed time after upshift, characteristic of the mutant. The mutant whose TSP begins the earliest (aco-49) is exceptional in that, if conidiation is suppressed by growth of colonies in submerged culture, this mutant becomes thermoinsensitive during vegetative submerged growth; in contrast, the remaining 10 mutants become thermoinsensitive only after the suppressive condition has been relieved. We discuss the possibility that this exceptional mutant is defective in a function required for initiation of the process that ultimately results in the formation of conidia.     

Solution Structure,Membrane Interactions,and Protein Binding Partners of the Tetraspanin Sm-TSP-2, a Vaccine Antigen from the Human Blood Fluke Schistosoma mansoni

The tetraspanins (TSPs) are a family of integral membrane proteins that are ubiquitously expressed at the surface of eukaryotic cells. TSPs mediate a range of processes at the surface of the plasma membrane by providing a scaffold for the assembly of protein complexes known as tetraspanin-enriched microdomains (TEMs). We report here the structure of the surface-exposed EC2 domain from Sm-TSP-2, a TSP from Schistosoma mansoni and one of the better prospects for the development of a vaccine against schistosomiasis. This is the first solution structure of this domain, and our investigations of its interactions with lipid micelles provide a general model for interactions between TSPs, membranes, and other proteins. Using chemical cross-linking, eight potential protein constituents of Sm-TSP-2-mediated TEMs were also identified. These include proteins important for membrane maintenance and repair, providing further evidence for the functional role of Sm-TSP-2- and Sm-TSP-2-mediated TEMs. The identification of calpain, Sm29, and fructose-bisphosphate aldolase, themselves potential vaccine antigens, suggests that the Sm-TSP-2-mediated TEMs could be disrupted via multiple targets. The identification of further Sm-TSP-2-mediated TEM proteins increases the available candidates for multiplex vaccines and/or novel drugs targeting TEMs in the schistosome tegument.     

Temperature-sensitive mutations in Drosophila melanogaster. 8. Temperature-sensitive periods of the lethal and morphological phenotypes of selected combinations of notch-locus mutations

Temperature-shift experiments were performed on five Notch-locus genotypes with temperature-sensitive phenotypes. The results show that temperature-sensitive periods (TSPs) for lethality may occur at any developmental stage: (1) $\text{N}{}^{\mathrm{g11}}\text{N}{}^{\mathrm{g11}}$;Dp^51b7 having a short embryonic TSP for lethality, (2) $\text{Ax}{}^{16172}\text{N}{}^{\mathrm{?40}}$ having a second-instar TSP for lethality, and (3) $\text{N}{}^{\mathrm{?103}}\text{fa}{}^{\mathrm{no}}$ with a long, possibly polyphasic, TSP, beginning in the embryonic stage and ending in the pupal stage. On the other hand, TSPs for adult morphological phenotypes appear to be restricted to the third larval instar: (1) $\text{Ax}{}^{16172}\text{N}{}^{\mathrm{?40}}$ having third-instar TSPs for wing vein gapping and ocellar bristle loss, and (2) $\text{N}{}^{\mathrm{?103}}\text{spl}$ having third-instar TSPs for eye facet disarray, wing notching, bristle number variation, and fusion of tarsal segments. The significance of these results is discussed in terms of the role of the Notch locus in development.     

Thrombospondins 1 and 2 function as inhibitors of angiogenesis.

Thrombospondins (TSPs) 1 and 2 are matricellular proteins with the well-characterized ability to inhibit angiogenesis in vivo, and the migration and proliferation of cultured microvascular endothelial cells (ECs). Angiogenesis in developing tumors and in various models of wound healing is diminished or delayed by the presence of TSP1 or 2. Sequences within the type I repeats of TSP1 and 2 have been demonstrated to mediate the anti-migratory effects of TSPs on microvascular EC, although, paradoxically, sequences in the N- and C-terminal domains have pro-angiogenic effects. A scavenger receptor, CD36, recognizes the active sequences in the type I repeats, and is required for the anti-angiogenic effects of TSP1 in the corneal neovascularization assay. However, interactions of TSPs with growth factors, proteases, histidine-rich glycoprotein, and other cell-surface receptors on EC have the potential to modulate CD36-mediated effects. Binding of TSP1 to CD36 has been shown to activate apoptosis by inducing p38 and Jun N-terminal kinase, members of the mitogen-activated protein kinase superfamily, and subsequently the cell-surface expression of FasL. Ligation of Fas by FasL then induces a caspase cascade and apoptotic cell death. However, we have recently shown that inhibition of proliferation of microvascular EC by TSPs can occur in the absence of cell death. This finding raises the possibility that TSPs can activate separate cell death and anti-proliferative pathways.     

Thrombospondins: structure and regulation of expression.

Thrombospondin (TSP) is a large, trimeric, modular glycoprotein that is a major constituent of platelet alpha granules. TSP is also secreted by a wide variety of epithelial and mesenchymal cells in patterns that reflect developmental changes in the embryo and response to injury in the adult. In addition to its role in blood coagulation, TSP has been reported to serve both adhesive and anti-adhesive functions, to foster neurite outgrowth, stimulate and inhibit cell growth and migration, and inhibit angiogenesis. Although this diversity in apparent function can be attributed, in part, to the ability of a single TSP to interact with several different cell-surface receptors, it is now known that the TSPs are encoded by at least three homologous genes in both human and mouse. TSP1, the commonly recognized protein isolated from platelets, is similar to TSP2 in structure. Both proteins contain NH2-terminal, COOH-terminal, and procollagen homology domains, and type I (TSP or properdin), type II (EGF-like), and type III (Ca(2+)-binding) repeats. However, the two TSPs differ in amino acid sequence and in the regulation of their expression. TSP1 is rapidly induced by serum and growth factors. An SRE and a binding site for NF-Y have been shown to mediate the serum response of the human TSP1 gene. On the other hand, TSP2 is far less responsive to serum than TSP1 and lacks the promoter elements that mediate the serum responsiveness of TSP1. TSP3 resembles TSP1 and TSP2 in its COOH-terminal domain and type III repeats, but contains four rather than three type II repeats and lacks type I repeats and a procollagen homology. The NH2-terminal domain of TSP3 also differs from that of either TSP1 or TSP2. All three TSPs demonstrate characteristic patterns of expression in the developing and adult mouse. It is therefore likely that each protein subserves a discrete function. In the future it will be necessary to distinguish among the three TSPs in addressing the function of these proteins.     

Thrombospondins as key regulators of synaptogenesis in the central nervous system

Thrombospondins (TSPs) are a family of large, oligomeric multidomain glycoproteins that participate in a variety of biological functions as part of the extracellular matrix (ECM). Through their associations with a number of binding partners, TSPs mediate complex cell-cell and cell-matrix interactions in such diverse processes as angiogenesis, inflammation, osteogenesis, cell proliferation, and apoptosis. It was recently shown in the developing central nervous system (CNS) that TSPs promote the formation of new synapses, which are the unique cell-cell adhesions between neurons in the brain. This increase in synaptogenesis is mediated by the interaction between astrocyte-secreted TSPs and their neuronal receptor, calcium channel subunit α2δ-1. The cellular and molecular mechanisms that underlie induction of synaptogenesis via this interaction are yet to be fully elucidated. This review will focus on what is known about TSP and synapse formation during development, possible roles for TSP following brain injury, and what the previously established actions of TSP in other biological tissues may tell us about the mechanisms underlying TSP's functions in CNS synaptogenesis.     

Two examples of indication specific radiation dose calculations in dental CBCT and Multidetector CT scanners

PurposeTo calculate organ doses and estimate the effective dose for justification purposes in patients undergoing orthognathic treatment planning purposes and temporal bone imaging in dental cone beam CT (CBCT) and Multidetector CT (MDCT) scanners.MethodsThe radiation dose to the ICRP reference male voxel phantom was calculated for dedicated orthognathic treatment planning acquisitions via Monte Carlo simulations in two dental CBCT scanners, Promax 3D Max (Planmeca, FI) and NewTom VGi evo (QR s.r.l, IT) and in Somatom Definition Flash (Siemens, DE) MDCT scanner. For temporal bone imaging, radiation doses were calculated via MC simulations for a CBCT protocol in NewTom 5G (QR s.r.l, IT) and with the use of a software tool (CT-expo) for Somatom Force (Siemens, DE). All procedures had been optimized at the acceptance tests of the devices.ResultsFor orthognathic protocols, dental CBCT scanners deliver lower doses compared to MDCT scanners. The estimated effective dose (ED) was 0.32 mSv for a normal resolution operation mode in Promax 3D Max, 0.27 mSv in VGi-evo and 1.18 mSv in the Somatom Definition Flash. For temporal bone protocols, the Somatom Force resulted in an estimated ED of 0.28 mSv while for NewTom 5G the ED was 0.31 and 0.22 mSv for monolateral and bilateral imaging respectively.ConclusionsTwo clinical exams which are carried out with both a CBCT or a MDCT scanner were compared in terms of radiation dose. Dental CBCT scanners deliver lower doses for orthognathic patients whereas for temporal bone procedures the doses were similar.     

Functions of the conserved thrombospondin carboxy-terminal cassette in cell-extracellular matrix interactions and signaling

Thrombospondins (TSPs) are extracellular, multidomain, calcium-binding glycoproteins that function at cell surfaces, in extracellular matrix (ECM) and as bridging molecules in cell-cell interactions. TSPs are multifunctional and modulate cell behavior during development, wound-healing, immune response, tumor growth and in the homeostasis of adult tissues. TSPs are assembled as oligomers that are composed of homologous polypeptides. In all the TSP polypeptides, the most highly-conserved region is the carboxyl-region, which contains a characteristic set of domains comprising EGF domains, TSP type 3 repeats and a globular carboxy-terminal domain. This large region is termed here the thrombospondin carboxy-terminal cassette (TSP-CTC). The strong conservation of the TSP-CTC suggests that it may mediate ancestral functions that are shared by all TSPs. This review summarizes the current knowledge of the TSP-CTC and areas of future interest.     

Control of cell motility by interaction of gangliosides, tetraspanins, and epidermal growth factor receptor in A431 versus KB epidermoid tumor cells

Growth of epidermoid carcinoma cell lines, A431 and KB, has been known to be controlled by the interaction of epidermal growth factor (EGF) and its receptor (EGFR) with tyrosine kinase. Ganglioside GM3 was previously found to interact with EGFR and to inhibit EGFR tyrosine kinase. However, motility of these cells, controlled by EGFR and ganglioside, was not studied. The present study is focused on the control mechanism of the motility of these cells through interaction of ganglioside, tetraspanin (TSP), and EGFR. Key results are as follows: (i) The level of EGFR expressed in A431 cells is 6 times higher than that expressed in KB cells, and motility of A431 cells is also much higher than that of KB cells, yet growth of A431 cells is either not affected or is inhibited by EGF. In contrast, growth of KB cells is enhanced by EGF. (ii) Levels of TSPs (CD9, CD82, and CD81) expressed in A431 cells are much higher than those expressed in KB cells, and TSPs expressed in A431 cells are reduced by treatment of cells with EtDO-P4, which inhibits the synthesis of glycosphingolipids (GSLs) and gangliosides. (iii) These TSPs are co-immunoprecipitated with EGFR in both A431 and KB cells, indicating that TSPs are closely associated with EGFR. (iv) High motility of A431 cells is greatly reduced, while low motility of KB cells is not affected, by treatment of cells with EtDO-P4. These results, taken together, suggest that there is a close correlation between high motility of A431 cells and high expression of EGFR and TSPs, and between ganglioside GM3/GM2 and TSP. A similar correlation was suggested between the low motility of KB cells and low levels of EGFR and TSP. The correlation between high motility and high level of EGFR with the ganglioside–TSP complex in A431 cells is unique. This is in contrast to our previous studies that indicate that motility of many types of tumor cells is inhibited by a high level of CD9 or CD82, together with growth factor receptors and integrins.     

National Survey of Radiation Dose and Image Quality in Adult CT Head Scans in Taiwan

Introduction

The purpose of the present study was to evaluate the influence of different variables on radiation dose and image quality based on a national database.

Materials and Methods

Taiwan’s Ministry of Health and Welfare requested all radiology departments to complete a questionnaire for each of their CT scanners. Information gathered included all scanning parameters for CT head scans. For the present analysis, CT machines were divided into three subgroups: single slice CT (Group A); multi-detector CT (MDCT) with 2-64 slices (Group B); and MDCT with more than 64 slices (Group C). Correlations between computed tomography dose index (CTDI) and signal-to-noise ratio (SNR) with cumulated tube rotation number (CTW(n)) and cumulated tube rotation time (CTW(s)), and sub group analyses of CTDI and SNR across the three groups were performed.

Results

CTDI values demonstrated a weak correlation (r = 0.33) with CTW(n) in Group A. SNR values demonstrated a weak negative correlation (r = -0.46) with CTW(n) in Group C. MDCT with higher slice numbers used more tube potential resulting in higher effective doses. There were both significantly lower CTDI and SNR values in helical mode than in axial mode in Group B, but not Group C.

Conclusion

CTW(n) and CTW(s) did not influence radiation output. Helical mode is more often used in MDCT and results in both lower CTDI and SNR compared to axial mode in MDCT with less than 64 slices.     

Disulfide connectivity of recombinant C-terminal region of human thrombospondin 2

The thrombospondin (TSP) family of extracellular glycoproteins consists of five members in vertebrates, TSP1 to -4 and TSP5/cartilage oligomeric matrix protein, and a single member in Drosophila. TSPs are modular multimeric proteins. The C-terminal end of a monomer consists of 3-6 EGF-like modules; seven tandem 23-, 36-, or 38-residue aspartate-rich, Ca(2+)-binding repeats; and an approximately 230-residue C-terminal sequence. The Ca(2+)-binding repeats and C-terminal sequence are spaced almost exactly the same in different TSPs and share many blocks of identical residues. We studied the C-terminal portion of human TSP2 from the third EGF-like module through the end of the protein (E3CaG2). E3CaG2, CaG2 lacking the EGF module, and Ca2 composed of only the Ca(2+)-binding repeats were expressed using recombinant baculoviruses and purified from conditioned media of insect cells. As previously described for intact TSP1, E3CaG2 bound Ca(2+) in a cooperative manner as assessed by equilibrium dialysis, and its circular dichroism spectrum was sensitive to the presence of Ca(2+). Mass spectrometry of the recombinant proteins digested with endoproteinase Asp-N revealed that disulfide pairing of the 18 cysteines in the Ca(2+)-binding repeats and C-terminal sequence is sequential, i.e. a 1-2, 3-4, 5-6, etc., pattern.     

Control of organization and function of muscle and tendon by thrombospondin-4

Thrombospondins (TSPs) are multifunctional proteins that are deposited in the extracellular matrix where they directly affect the function of vascular and other cell types. TSP-4, one of the 5 TSP family members, is expressed abundantly in tendon and muscle. We have examined the effect of TSP-4 deficiency on tendon collagen and skeletal muscle morphology and function.In Thbs4^−/− mice, tendon collagen fibrils are significantly larger than in wild-type mice, and there is no compensatory over-expression of TSP-3 and TSP-5, the two TSPs most highly homologous to TSP-4, in the deficient mice. TSP-4 is expressed in skeletal muscle, and higher levels of TSP-4 protein are associated with the microvasculature of red skeletal muscle with high oxidative metabolism. Lack of TSP-4 in medial soleus, red skeletal muscle with predominant oxidative metabolism, is associated with decreased levels of several specific glycosaminoglycan modifications, decreased expression of a TGFβ receptor beta-glycan, decreased activity of lipoprotein lipase, which associates with vascular cell surfaces by binding to glycosaminoglycans, and decreased uptake of VLDL. The soleus muscle is smaller and hind- and fore-limb grip strength is reduced in Thbs4^−/− mice compared to wild-type mice. These observations suggest that TSP-4 regulates the composition of the ECM at major sites of its deposition, tendon and muscle, and the absence of TSP-4 alters the organization, composition and physiological functions of these tissues.     

Structure of intermediate filaments

Recent amino acid sequence data have revealed that the microfibrils in hard α-keratin contain proteins with highly significant homologies and closely similar structural characteristics to the intermediate filament (IF) proteins known as desmin and vimentin. This result implies that microfibrils in hard α-keratin may be classified as a member of the IF and that the major features of these various filamentous structures are the same. Consequently, data obtained using X-ray diffraction, electron microscopy, amino acid sequence structural analysis and physicochemical techniques have been collated from the hitherto diverse fields of keratin and IF structure and used to formulate a more detailed model for the 7–8 nm diameter filaments than has previously been possible. Two models consisting of four-chain units arranged with the helical symmetry deduced for hard α-keratin¹ (Fraser et al. J. Mol. Biol. 1976, 108, 435–452) are in accord with the data. The structural unit comprises an oppositely directed pair of molecules each consisting of a two-stranded parallel-chain coiled-coil rope of length ～45 nm stabilized by both interchain and intermolecular ionic interactions. For a perfectly regular structure the filament may be likened either to a seven-stranded cable with a supercoil pitch length of about 345 nm (pitch angle ～2.9°), or a ten-stranded cable (Fraser, R. D. B. and MacRae, T. P. Polymer 1973, 14, 61–67) with a supercoil pitch length of about 1293 nm (pitch angle ～0.8°). The models also provide some insight into the self-assembly mechanism of the IF.     

Invoking the power of thrombospondins: Regulation of thrombospondins expression

Increasing evidence suggests critical functions of thrombospondins (TSPs) in a variety of physiological and pathological processes. With the growing understanding of the importance of these matricellular proteins, the need to understand the mechanisms of regulation of their expression and potential approaches to modulate their levels is also increasing. The regulation of TSP expression is multi-leveled, cell- and tissue-specific, and very precise. However, the knowledge of mechanisms modulating the levels of TSPs is fragmented and incomplete. This review discusses the known mechanisms of regulation of TSP levels and the gaps in our knowledge that prevent us from developing strategies to modulate the expression of these physiologically important proteins.