Pro-(carboxypeptidases A) from whole pig pancreas. Their mass, size, shape and solvation.
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ABSTRACT:
SUBMITTER: Martinez MC
PROVIDER: S-EPMC1152359 | biostudies-other | 1983 Oct
REPOSITORIES: biostudies-other
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Project description:ContextIndividuals with type 1 diabetes (T1D) have a smaller pancreas, but longitudinal changes in pancreas size and shape are unclear.ObjectiveWe monitored changes in pancreas size and shape after diagnosis with T1D.DesignWe conducted a prospective cohort study at an academic medical center between 2014 and 2022.Patients and healthy controlsIndividuals with T1D (n = 91) or controls (n = 90) underwent magnetic resonance imaging (MRI) of the pancreas, including longitudinal MRI in 53 individuals with new-onset T1D.InterventionInterventions included MRI and continuous glucose monitoring (CGM).Main outcome measuresPancreas size and shape were measured from MRI. For participants who used CGM, measures of glycemic variability were calculated.ResultsOn longitudinal imaging, pancreas volume and pancreas volume index normalized for body weight declined during the first year after diagnosis. Pancreas volume index continued to decline through the fifth year after diagnosis. A cross-sectional study of individuals with diabetes duration up to 60 years demonstrated that pancreas size in adults negatively correlated with age and disease duration, whereas pancreas volume and pancreas volume index remained stable in controls. Pancreas volume index correlated inversely with low blood glucose index, a measure of risk for hypoglycemia. Pancreas shape was altered in individuals with T1D and further diverged from controls over the first 5 years after diagnosis. Pancreas size and shape are altered in nondiabetic individuals at genetic risk for T1D. Combined pancreas size and shape analysis better distinguished the pancreas of individuals with T1D from controls than size alone.ConclusionsPancreas size declines most rapidly near the clinical diagnosis of T1D and continues to decline throughout adulthood. Declines in pancreas size are accompanied by changes in pancreas shape.
| S-EPMC10505530 | biostudies-literature
Project description:A method is reported for the preparative isolation of the two forms of pro-(carboxypeptidase A) from pig pancreas: the monomer and the binary complex with pro-(proteinase E). This method, which is mainly based on chromatography on DEAE-Sepharose at pH 5.7, allows these proenzymes to be prepared more quickly and in safer conditions than with other reported methods. Undegraded and homogeneous carboxypeptidase A1 and A2 species (peptidyl-L-amino acid hydrolase, EC 3.4.17.1), in monomeric forms with high specific activity, are also obtained in high yield by controlled trypsin activation of either of the pro-(carboxypeptidases A) followed by chromatography on DEAE-Sepharose at pH 5.8 under dissociating conditions (7 M-urea).
| S-EPMC1145102 | biostudies-other
Project description:UNLABELLED:Peptidoglycan (PG) is an essential structural component of the bacterial cell wall and maintains the integrity and shape of the cell by forming a continuous layer around the cytoplasmic membrane. The thin PG layer of Escherichia coli resides in the periplasm, a unique compartment whose composition and pH can vary depending on the local environment of the cell. Hence, the growth of the PG layer must be sufficiently robust to allow cell growth and division under different conditions. We have analyzed the PG composition of 28 mutants lacking multiple PG enzymes (penicillin-binding proteins [PBPs]) after growth in acidic or near-neutral-pH media. Statistical analysis of the muropeptide profiles identified dd-carboxypeptidases (DD-CPases) that were more active in cells grown at acidic pH. In particular, the absence of the DD-CPase PBP6b caused a significant increase in the pentapeptide content of PG as well as morphological defects when the cells were grown at acidic pH. Other DD-CPases (PBP4, PBP4b, PBP5, PBP6a, PBP7, and AmpH) and the PG synthase PBP1B made a smaller or null contribution to the pentapeptide-trimming activity at acidic pH. We solved the crystal structure of PBP6b and also demonstrated that the enzyme is more stable and has a lower Km at acidic pH, explaining why PBP6b is more active at low pH. Hence, PBP6b is a specialized DD-CPase that contributes to cell shape maintenance at low pH, and E. coli appears to utilize redundant DD-CPases for normal growth under different conditions. IMPORTANCE:Escherichia coli requires peptidoglycan dd-carboxypeptidases to maintain cell shape by controlling the amount of pentapeptide substrates available to the peptidoglycan synthetic transpeptidases. Why E. coli has eight, seemingly redundant dd-carboxypeptidases has remained unknown. We now show that one of these dd-carboxypeptidases, PBP6b, is important for cell shape maintenance in acidic growth medium, consistent with the higher activity and stability of the enzyme at low pH. Hence, the presence of multiple dd-carboxypeptidases with different enzymatic properties may allow E. coli to maintain a normal cell shape under various growth conditions.
| S-EPMC4916385 | biostudies-literature
Project description:Two different forms of procarboxypeptidase A (I and II) were obtained from pig pancreas extracts. The Mr values, the pattern found on polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate, and the sedimentation coefficients indicate that form I is a binary complex formed by two different subunits, whereas form II is a monomer. The carboxypeptidase A-precursor subunit of form I and the form II monomer are very similar with respect to Mr value, amino acid composition and fragmentation by CNBr and iodosobenzoic acid. The activation process of both forms is unspecific with respect to the activating enzyme, the peptide released during activation is unusually long (Mr approx.sor subunit of form I and the form II monomer are very similar with respect to Mr value, amino acid composition and fragmentation by CNBr and iodosobenzoic acid. The activation process of both forms is unspecific with respect to the activating enzyme, the peptide released during activation is unusually long (Mr approx.sor subunit of form I and the form II monomer are very similar with respect to Mr value, amino acid composition and fragmentation by CNBr and iodosobenzoic acid. The activation process of both forms is unspecific with respect to the activating enzyme, the peptide released during activation is unusually long (Mr approx. 12500) and, in the case of the binary complex, the activation with trypsin follows a rather complex pattern, suggesting that the accompanying subunit of form I might play a modulating role in the activation process. Although the appearance of enzymic activity is rather slow, a protein with an Mr equivalent to that of active carboxypeptidase A is found very early in the activation process. Both zymogens are glycoproteins (so far no carbohydrate has been reported in any procarboxypeptidase A) and both contain two strongly bound Zn2+ ions/molecule. Other chemical and physical properties were also determined.
| S-EPMC1163063 | biostudies-other
Project description:Improving our understanding of mammalian pancreas development is crucial for the development of more effective cellular therapies for diabetes. Most of what we know about mammalian pancreas development stems from mouse genetics. We have learnt that a unique set of transcription factors controls endocrine and exocrine cell differentiation. Transgenic mouse models have been instrumental in studying the function of these transcription factors. Mouse and human pancreas development are very similar in many respects, but the devil is in the detail. To unravel human pancreas development in greater detail, in vitro cellular models (including directed differentiation of stem cells, human beta cell lines and human pancreatic organoids) are used; however, in vivo validation of these results is still needed. The current best 'model' for studying human pancreas development are individuals with monogenic forms of diabetes. In this review, we discuss mammalian pancreas development, highlight some discrepancies between mouse and human, and discuss selected transcription factors that, when mutated, cause permanent neonatal diabetes. Graphical abstract.
| S-EPMC7476910 | biostudies-literature
Project description:Cluster-size-resolved ultrafast dynamics of the solvated electron in neutral water clusters with n = 3 to ∼200 molecules are studied with pump-probe time-of-flight mass spectrometry after below band gap excitation. For the smallest clusters, no longer-lived (>100-200 fs) hydrated electrons were detected, indicating a minimum size of n ∼ 14 for being able to sustain hydrated electrons. Larger clusters show a systematic increase of the number of hydrated electrons per molecule on the femtosecond to picosecond time scale. We propose that with increasing cluster size the underlying dynamics is governed by more effective electron formation processes combined with less effective electron loss processes, such as ultrafast hydrogen ejection and recombination. It appears unlikely that any size dependence of the solvent relaxation dynamics would be reflected in the observed time-resolved ion yields.
| S-EPMC8237264 | biostudies-literature
Project description:The large size of human tissues requires a practical stereological approach to perform a comprehensive analysis of the whole organ. We have developed a method to quantitatively analyze the whole human pancreas, as one of the challenging organs to study, in which endocrine cells form various sizes of islets that are scattered unevenly throughout the exocrine pancreas. Furthermore, the human pancreas possesses intrinsic characteristics of intra-individual variability, i.e. regional differences in endocrine cell/islet distribution, and marked inter-individual heterogeneity regardless of age, sex and disease conditions including obesity and diabetes. The method is built based on large-scale image capture, computer-assisted unbiased image analysis and quantification, and further mathematical analyses, using widely-used software such as Fiji/ImageJ and MATLAB. The present study includes detailed protocols of every procedure as well as all the custom-written computer scripts, which can be modified according to specific experimental plans and specimens of interest.
| S-EPMC5034323 | biostudies-literature
Project description:ObjectivesAdult body mass (MB) empirically scales as height (Ht) squared (MB ∝ Ht(2) ), but does regional body mass and body composition as a whole also scale as Ht(2) ? This question is relevant to a wide range of biological topics, including interpretation of body mass index (BMI).MethodsDual-energy X-ray absorptiometry (DXA) was used to quantify regional body mass [head (MH), trunk, arms, and legs] and whole-body composition [fat, lean soft tissue (LST), and bone mineral content (BMC)] in non-Hispanic (NH) white, NH black, Mexican American, and Korean adults participating in the National Health and Nutrition Examination Survey (NHANES; n = 17,126) and Korean NHANES (n = 8,942). Regression models were developed to establish Ht scaling powers for each measured component with adjustments for age and adiposity.ResultsExploratory analyses revealed a consistent scaling pattern across men and women of the four population groups: regional mass powers, head (∼0.8-1) < arms and trunk (∼1.8-2.3) < legs (∼2.3-2.6); and body composition, LST (∼2.0-2.3) < BMC (∼2.1-2.4). Small sex and population differences in scaling powers were also observed. As body mass scaled uniformly across the eight sex and population groups as Ht(∼2) , tall and short subjects differed in body shape (e.g., MH/MB ∝ Ht(-∼1) ) and composition.ConclusionsAdult human body shape and relative composition are a function of body size as represented by stature, a finding that reveals a previously unrecognized phenotypic heterogeneity as defined by BMI. These observations provide new pathways for exploring mechanisms governing the interrelations between adult stature, body morphology, biomechanics, and metabolism.
| S-EPMC4638414 | biostudies-literature
Project description:Aerobic metabolism generates 15-20 times more energy (ATP) than anaerobic metabolism, which is crucial in maintaining energy budgets in animals, fueling metabolism, activity, growth and reproduction. For ectothermic water-breathers such as fishes, low dissolved oxygen may limit oxygen uptake and hence aerobic metabolism. Here, we assess, within a phylogenetic context, how abiotic and biotic drivers explain the variation in hypoxia tolerance observed in fishes. To do so, we assembled a database of hypoxia tolerance, measured as critical oxygen tensions (Pcrit ) for 195 fish species. Overall, we found that hypoxia tolerance has a clear phylogenetic signal and is further modulated by temperature, body mass, cell size, salinity and metabolic rate. Marine fishes were more susceptible to hypoxia than freshwater fishes. This pattern is consistent with greater fluctuations in oxygen and temperature in freshwater habitats. Fishes with higher oxygen requirements (e.g. a high metabolic rate relative to body mass) also were more susceptible to hypoxia. We also found evidence that hypoxia and warming can act synergistically, as hypoxia tolerance was generally lower in warmer waters. However, we found significant interactions between temperature and the body and cell size of a fish. Constraints in oxygen uptake related to cellular surface area to volume ratios and effects of viscosity on the thickness of the boundary layers enveloping the gills could explain these thermal dependencies. The lower hypoxia tolerance in warmer waters was particularly pronounced for fishes with larger bodies and larger cell sizes. Previous studies have found a wide diversity in the direction and strength of relationships between Pcrit and body mass. By including interactions with temperature, our study may help resolve these divergent findings, explaining the size dependency of hypoxia tolerance in fish.
| S-EPMC9542040 | biostudies-literature
Project description:Understanding historical range shifts and population size variation provides an important context for interpreting contemporary genetic diversity. Methods to predict changes in species distributions and model changes in effective population size (N e) using whole genomes make it feasible to examine how temporal dynamics influence diversity across populations. We investigate N e variation and climate-associated range shifts to examine the origins of a previously observed latitudinal heterozygosity gradient in the bumble bee Bombus vancouverensis Cresson (Hymenoptera: Apidae: Bombus Latreille) in western North America. We analyze whole genomes from a latitude-elevation cline using sequentially Markovian coalescent models of N e through time to test whether relatively low diversity in southern high-elevation populations is a result of long-term differences in N e. We use Maxent models of the species range over the last 130,000 years to evaluate range shifts and stability. N e fluctuates with climate across populations, but more genetically diverse northern populations have maintained greater N e over the late Pleistocene and experienced larger expansions with climatically favorable time periods. Northern populations also experienced larger bottlenecks during the last glacial period, which matched the loss of range area near these sites; however, bottlenecks were not sufficient to erode diversity maintained during periods of large N e. A genome sampled from an island population indicated a severe postglacial bottleneck, indicating that large recent postglacial declines are detectable if they have occurred. Genetic diversity was not related to niche stability or glacial-period bottleneck size. Instead, spatial expansions and increased connectivity during favorable climates likely maintain diversity in the north while restriction to high elevations maintains relatively low diversity despite greater stability in southern regions. Results suggest genetic diversity gradients reflect long-term differences in N e dynamics and also emphasize the unique effects of isolation on insular habitats for bumble bees. Patterns are discussed in the context of conservation under climate change.
| S-EPMC9889631 | biostudies-literature