scholarly journals Serum Proteomic Analyses Suggest That the HMGB1 and Other Inflammatory Pathways Are Operational in MBL and Are Less in Overt CLL

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2625-2625
Author(s):  
Florencia Palacios ◽  
Gonzalo Blanco ◽  
Kamala Vanarsa ◽  
Poojitha Dugyala ◽  
Steven L Allen ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Immune Suppression ◽  
Cell Movement ◽  
Immune Dysfunction ◽  
P Value ◽  
Immune Stimulation ◽  
Serum Samples ◽  
Protein Levels ◽  
Immune Alterations ◽  
Equity Ownership

Abstract Background. CLL-like monoclonal B-ceII lymphocytosis (MBL) is considered a requisite precursor of CLL, with 1-2% of subjects annually progressing to CLL requiring therapy. The role of immune alterations leading to and operating in MBL and controlling progression to CLL is not well characterized. Since an increased frequency of immune-related conditions associated with immune dysfunction exists prior to CLL diagnosis (Landgren et al, Br J Haematol 2007 and Blood 2007; Andersen et al, Leukemia 2020), immune alterations likely exist in MBL. We have examined the serum protein profiles of MBL and CLL in search of clues linking immune dysfunction with malignant transformation. Objectives. 1. Characterize the serum proteomic profiles of MBL individuals, IGHV-mutated CLL (M-CLL) and IGHV-unmutated CLL (U-CLL) patients, and age-matched healthy controls (HC). 2. Compare the serum proteomic profiles between the groups. 3. Assess the effect of IGHV mutation status on serum proteomic profiles in CLL. Methods. A total of 12 MBL, 12 M-CLL, 12 U-CLL and 12 age-matched HC were studied. Patients were cared for at Northwell Health, New York (n=25) and Hospital del Mar, Barcelona (n=11). All patients were treatment naive except for one U-CLL patient who was treated one year beforehand. Serum samples were collected, and their protein levels measured employing SOMAmers (modified single-stranded DNA aptamers; SomaLogic) to quantify relative levels of 1,310 proteins. P-values <0.05 were used to define significantly different protein levels between groups. Ingenuity Pathway Analysis (IPA; QIAGEN) was employed to evaluate potential protein interactions and pathways. IPA pathways with P-value <0.05 and Z-score ≥2 or ≤-2 were considered to be activated or inhibited, respectively. Results. Overall, the levels of 862 proteins differed significantly between groups: MBL vs. HC: 10 downregulated (d) and 24 upregulated (u); M-CLL vs. HC: 206d and 6u; U-CLL vs. HC: 54d and 40u; M-CLL vs. MBL: 384d and 5u; U-CLL vs. MBL: 74d and 24u; and M-CLL vs. U-CLL: 35d and 0u. IPA highlighted a role for the pro-inflammatory HMGB1 pathway in several comparisons. First, an activated HMGB1 pathway was predicted in MBL compared to HC, together with activation of phagocytes, and an inhibition of the systemic immune suppressor TGF-β. Second and consistent with the former, U-CLL patients displayed an activated HMGB1 pathway compared to HC, along with other signs of immune stimulation (activated NFkB and Th1 pathways, maturation of dendritic cells, and inhibition of TGF-β) and leukemic progression (activated progression of tumor, and leukocyte extravasation). Third and contrary to the above, the HMGB1 pathway was inhibited when comparing M-CLL to HC, in line with a global immune suppression signature (inhibited PRR, GM-CSF, FcεRI, IL1, IL8, TNF, Th1, STAT3 and NFkB pathways, in addition to inhibited cell movement, viability and activation). Notably, inhibition of immune pathways was predicted for both M-CLL and U-CLL compared to MBL (diminished TNF and IL6 signaling, and reduced cell movement), although the greatest differences were seen for M-CLL vs. MBL comparison, including blockade of the HMGB1 pathway in M-CLL. Finally, the M-CLL vs. U-CLL comparison suggested inhibited INFγ, IL2, IL3, IL4, NFkB, and decreased T lymphocyte stimulation and movement of tumor cells in M-CLL patients. Conclusions. An increased pro-inflammatory signature with involvement of the HMGB1 pathway was identified in MBL and U-CLL compared with HC, whereas the opposite was seen for M-CLL. Since MBL most often exhibit mutated IGHV (91% of cases in our cohort), these findings suggest immune stimulation as a characteristic feature in the pre-leukemic and U-CLL leukemic stage that surprisingly is not operative in M-CLL. Consistent with this, M-CLL displayed a global immune suppression (HMGB1 pathway inhibition), whereas U-CLL exhibited signs of immune stimulation (HMGB1 pathway activation) compared to HC which may relate to distinct capabilities of the two subtypes to interact with the microenvironment. Lastly, the increased inflammatory signature identified in MBL, which are mainly IGHV-mutated, was lessened in CLL, mainly in M-CLL patients. This is consistent with a decreased influence of immune imbalance and the HMGB1 pathway associated with IGHV-mutated clonal expansions. Acknowledgments. GB is supported by a grant from Fundación Alfonso Martín Escudero. Disclosures Allen: Alexon: Research Funding; Bristol Myers Squibb: Other: Equity Ownership; C4 Therapeutics: Other: Equity Ownership; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees. Rhodes: Conquer Cancer Foundation Young Investigator Award: Other: Grant/Research Support; AbbVie, Genentech, Pharmacyclics, TG Therapeutics: Other: Consultant.

scholarly journals miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 274-283
Author(s):  
Peng Yang ◽  
Jianhua Han ◽  
Shigeng Li ◽  
Shaoning Luo ◽  
Xusheng Tu ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Aberrant Expression ◽  
Protein Levels ◽  
Apoptosis And Inflammation ◽  
Hk2 Cells

Abstract Background Sepsis is a systemic inflammatory response that can lead to the dysfunction of many organs. The aberrant expression of miRNAs is associated with the pathogenesis of sepsis. However, the biological functions of miR-128-3p in sepsis remain largely unknown, and its mechanism should be further investigated. This study aimed to determine the regulatory network of miR-128-3p and TGFBR2 in lipopolysaccharide (LPS)-induced sepsis. Methods The expression levels of miR-128-3p and transforming growth factor beta receptors II (TGFBR2) were detected by quantitative polymerase chain reaction (qPCR). The protein levels of TGFBR2, Bcl-2, Bax, cleaved caspase 3, Smad2, and Smad3 were measured by western blot. Cell apoptosis was analyzed by flow cytometry. Cytokine production was detected by enzyme-linked immunosorbent assay (ELISA). The binding sites of miR-128-3p and TGFBR2 were predicted by Targetscan online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results The level of miR-128-3p was decreased, and TGFBR2 expression was increased in serum samples of sepsis patients and LPS-induced HK2 cells. Overexpression of miR-128-3p or knockdown of TGFBR2 ameliorated LPS-induced inflammation and apoptosis. Moreover, TGFBR2 was a direct target of miR-128-3p, and its overexpression reversed the inhibitory effects of miR-128-3p overexpression on inflammation and apoptosis in LPS-induced HK2 cells. Besides, overexpression of miR-128-3p downregulated TGFBR2 to suppress the activation of the Smad signaling pathway. Conclusion miR-128-3p could inhibit apoptosis and inflammation by targeting TGFBR2 in LPS-induced HK2 cells, which might provide therapeutic strategy for the treatment of sepsis.

scholarly journals Integrated Analysis of Global DNA Methylation and Transcription Reveals a Leukemia Subtype with Extreme Hypermethylation Associated with Silencing of Regulators of Differentiation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2608-2608
Author(s):  
Claudia Gebhard ◽  
Roger Mulet-Lazaro ◽  
Lucia Schwarzfischer ◽  
Dagmar Glatz ◽  
Margit Nuetzel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Promoter Methylation ◽  
Research Funding ◽  
Promoter Hypermethylation ◽  
Ctcf Binding ◽  
P Value ◽  
Global Dna Methylation ◽  
Employment Equity ◽  
Equity Ownership

Abstract Acute myeloid leukemia (AML) represents a highly heterogeneous myeloid stem cell disorder classified based on various genetic defects. Besides genetic alterations, epigenetic changes are recognized as an additional mechanism contributing to leukemogenesis, but insight into the latter process remains minor. Using a combination of Methyl-CpG-Immunoprecipitation (MCIp-chip) and MALDI-TOF analysis of bisulfite-treated DNA in a cohort of 196 AML patients we previously demonstrated that (cyto)genetically defined AML subtypes, including CBFB-MYH11, AML-ETO, NPM1-mut, CEBPA-mut or IDH1/2-mut subtypes, express specific DNA-methylation profiles (Gebhard et al, Leukemia, 2018). A fraction of AML patients (5/196) displayed a unique abnormal hypermethylation profile that was completely distinct from any other AML subtype. These patients present immature leukemia (FAB M0, M1) with various chromosomal aberrations but very few mutations (e.g. no IDH1/2, KRAS, DNMT3A) that might explain the CpG island methylator phenotype (CIMP) phenotype. The CIMP patients showed high resemblance with a recently reported CEBPA methylated subgroup (Wouters et al, 2007 and Figueroa et al, 2009), which we confirmed by MCIp-chip and MALDI-TOF analysis. To explore the whole range of epigenetic alterations in the CIMP-AML patients we performed in-depth global DNA methylation and gene expression analyses (MCIp-seq and RNA-seq) in 45 AML and 12 CIMP patients from both studies. Principle component analysis and t-distributed stochastic neighbor embedding (t-SNE) revealed that CIMP patients express a unique DNA-methylation and gene-expression signature that separated them from all other AMLs. We could discriminate promoter methylation from non-promoter methylation by selecting MCIp-seq peaks within 3kb around TSS. Promoter hypermethylation was highly associated with repression of genes (PCC = -0.053, p-value = 0.00075). Hypermethylation of non-promoter regions was more strongly associated with upregulation of genes (PCC = 0.046, p-value = 4.613e-06). Interestingly, differentially methylated regions also showed a positive association with myeloid lineage CTCF binding sites (27% vs 18% expected, p-value < 2.2e-16 in a chi-square test of independence). Methylation of CTCF sites causes loss of CTCF binding, which has been reported to disrupt boundaries between so-called topologically associated domains (TADs), allowing enhancers located in a particular TAD to become accessible to genes in adjacent TADs and affect their transcription. Whether this is the case is under investigation. In this study we particularly focused on the role of hypermethylation of promoters in CIMP-AMLs. Promoters of many transcriptional regulators that are involved in the differentiation of myeloid lineages of which several are frequently mutated in AML were hypermethylated and repressed, including CEBPA, CEBPD, IRF8, GATA2, KLF4, MITF or MAFB. Notably, HMGA2, a critical regulator of myeloid progenitor expansion, exhibited the largest degree of CIMP promoter hypermethylation compared to the other AMLs, accompanied by a reduction in gene expression. Moreover, multiple members of the HOXB family and KLF1 (erythroid differentiation) were methylated and repressed as well. In addition, these patients frequently showed hypermethylation of many chromatin factors (e.g. LMNA, CHD7 or TET2). Hypermethylation of the TET2 promoter could result in a loss of maintenance DNA demethylation and therefore successive hypermethylation at CpG islands. We carried out regulome-capture-bisulfite sequencing on CIMP-AMLs compared to other AML samples and normal blood cell controls and confirmed methylation of the same transcription and chromatin factor promoters. We conclude that these leukemias represent very primitive HSCPs which are blocked in differentiation into multiple hematopoietic lineages, due to the absence of regulators of these lineages. Although the underlying cause for the extreme hypermethylation signature is still subject to ongoing studies, the consequence of promoter hypermethylation is silencing of key lineage regulators causing the differentiation arrest in these cells. We argue that these patients may particularly benefit from therapies that revert DNA methylation. Disclosures Ehninger: Cellex Gesellschaft fuer Zellgewinnung mbH: Employment, Equity Ownership; GEMoaB Monoclonals GmbH: Employment, Equity Ownership; Bayer: Research Funding. Thiede:AgenDix: Other: Ownership; Novartis: Honoraria, Research Funding.

scholarly journals Circulation of Toscana Virus in a Sample Population of Corsica, France

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 39
Author(s):  
Shirley Masse ◽  
Nazli Ayhan ◽  
Lisandru Capai ◽  
Rémi Charrel ◽  
Alessandra Falchi
Keyword(s):  
Blood Donors ◽  
Cross Sectional Study ◽  
P Value ◽  
Healthy Population ◽  
Sample Population ◽  
Surveillance Systems ◽  
Toscana Virus ◽  
Serum Samples ◽  
Cross Sectional ◽  
Study Participants

Sandfly-borne phleboviruses pathogenic to humans, such as Toscana virus (TOSV) and sandfly fever Sicilian virus (SFSV), are endemic in the Mediterranean region. In France, several autochthonous cases of TOSV infection have been described which cause either meningitis or encephalitis. The aim of the present study was to estimate the seroprevalence of TOSV and SFSV antibodies in a healthy population from Corsica. In this cross-sectional study, participants were enrolled from the medical staff at University of Corsica Pasquale Paoli (UCPP) and from general practitioners of the Corsican Sentinelles Network. The seroprevalence study was based on virus microneutralization (MN). A total of 240 patients were tested for TOSV and SFSV. Altogether, 54 serum samples were confirmed for TOSV infection (seroprevalence = 22.5%). None of the samples were positive for SFSV (0/240). The main place of residence was significantly associated with TOSV seropositivity (p-value = 0.005). The overall rate of TOSV antibody seroprevalence observed in our study suggests a more intense circulation of TOSV in Corsica, with a rate significantly higher than the 8.7% reported in Corsica in 2007 from blood donors. The absence of seropositivity to SFSV seems to confirm the low circulation of this virus in Corsica and in continental France. The increasing circulation of TOSV reported here should encourage the implementation of surveillance systems to control phlebovirus infection.

scholarly journals Analysis of RAS protein interactions in living cells reveals a mechanism for pan-RAS depletion by membrane-targeted RAS binders

2020 ◽  
Vol 117 (22) ◽  
pp. 12121-12130
Author(s):  
Yao-Cheng Li ◽  
Nikki K. Lytle ◽  
Seth T. Gammon ◽  
Luke Wang ◽  
Tikvah K. Hayes ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Developmental Disorders ◽  
Degradation Pathway ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Ras Proteins ◽  
Ras Protein ◽  
Protein Levels ◽  
Ras Family ◽  
Ras Isoforms

HRAS, NRAS, and KRAS4A/KRAS4B comprise the RAS family of small GTPases that regulate signaling pathways controlling cell proliferation, differentiation, and survival. RAS pathway abnormalities cause developmental disorders and cancers. We found that KRAS4B colocalizes on the cell membrane with other RAS isoforms and a subset of prenylated small GTPase family members using a live-cell quantitative split luciferase complementation assay. RAS protein coclustering is mainly mediated by membrane association-facilitated interactions (MAFIs). Using the RAS–RBD (CRAF RAS binding domain) interaction as a model system, we showed that MAFI alone is not sufficient to induce RBD-mediated RAS inhibition. Surprisingly, we discovered that high-affinity membrane-targeted RAS binding proteins inhibit RAS activity and deplete RAS proteins through an autophagosome–lysosome-mediated degradation pathway. Our results provide a mechanism for regulating RAS activity and protein levels, a more detailed understanding of which should lead to therapeutic strategies for inhibiting and depleting oncogenic RAS proteins.

scholarly journals Frequency of antibodies and risk factors associated with Toxoplasma gondii infection in backyard pig production in the city of Mossoró, state of Rio Grande do Norte, Brazil

2019 ◽  
Vol 28 (3) ◽  
pp. 508-513 ◽  
Author(s):  
Isabela Maria Campanelli dos Santos ◽  
Alexandro Iris Leite ◽  
Maria Eduarda Chiaradia Furquim ◽  
Diego Carlos de Souza Zanatto ◽  
Simone de Jesus Fernandes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rio Grande ◽  
Female Gender ◽  
Immunofluorescence Assay ◽  
P Value ◽  
Serum Samples ◽  
Igg Antibody ◽  
Source Of Infection ◽  
Antibody Titers ◽  
Toxoplasma Gondii Infection

Abstract Toxoplasmosis is an important zoonosis for pregnant women and immunosuppressed people. The pig population also becomes infected by this pathogen, and undercooked or raw meat is an important source of infection for humans. The aims of the present study were to evaluate the rate of exposure of pigs to T. gondii in the municipality of Mossoró, Rio Grande do Norte and seek to identify associations with possible risk factors. Blood samples were collected from 412 pigs and were analyzed using the immunofluorescence assay. Among these 412 serum samples, 40.7% were seropositive for T. gondii. The IgG antibody titers were 64 (56 specimens), 128 (32), 256 (37), 512 (23), 1024 (14), 2048 (5) and 4046 (1). Seropositivity for T. gondii was found to be related (p-value < 0.05) to the following factors: female gender, semi-confined rearing system, use of well water, dewormed animals, presence of cats, goats, sheep, mice and vultures on the farm and carcasses left on the ground. In contrast, seropositivity was not related (p-value < 0.05) to the age of the pigs, type of facility or feeding with human food remains. Preventive measures need to be adopted on the farms studied here, with the aim of decreasing the animals’ intake of sporulated oocysts.

In Silico Recognition of Protein-Protein Interaction

2011 ◽  
pp. 248-268
Author(s):  
Byung-Hoon Park ◽  
Phuongan Dam ◽  
Chongle Pan ◽  
Ying Xu ◽  
Al Geist ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Regulatory Networks ◽  
Machine Learning Techniques ◽  
Translation Regulation ◽  
Future Research ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Protein Levels ◽  
Protein Functions ◽  
Model Protein

Protein-protein interactions are fundamental to cellular processes. They are responsible for phenomena like DNA replication, gene transcription, protein translation, regulation of metabolic pathways, immunologic recognition, signal transduction, etc. The identification of interacting proteins is therefore an important prerequisite step in understanding their physiological functions. Due to the invaluable importance to various biophysical activities, reliable computational methods to infer protein-protein interactions from either structural or genome sequences are in heavy demand lately. Successful predictions, for instance, will facilitate a drug design process and the reconstruction of metabolic or regulatory networks. In this chapter, we review: (a) high-throughput experimental methods for identification of protein-protein interactions, (b) existing databases of protein-protein interactions, (c) computational approaches to predicting protein-protein interactions at both residue and protein levels, (d) various statistical and machine learning techniques to model protein-protein interactions, and (e) applications of protein-protein interactions in predicting protein functions. We also discuss intrinsic drawbacks of the existing approaches and future research directions.

scholarly journals Relationship between serum-based biomarkers & Magnetic Resonance Imaging measures following mild traumatic brain injury in collegiate athletes post return to play

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S25.1-S25
Author(s):  
Taylor Susa ◽  
Marguerite Moore ◽  
Joshua Carlson
Keyword(s):  
Gray Matter Volume ◽  
Collegiate Athletes ◽  
Positive Association ◽  
Time Frame ◽  
Return To Play ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Samples ◽  
Protein Levels ◽  
Mri Scans

ObjectiveThis study analyzed MRI and serum samples from 30 participants across two groups to explore the relationship between protein levels and MRI scans in post return-to-play collegiate athletes following concussion.BackgroundRecently, there has been an increase in concussion research on their effects on different protein levels in serum (a derived portion of blood) between concussed and control groups. Recent research examining serum biomarkers in concussion have found elevated levels of many proteins, but overall have mixed results in correlation with MRI. However, these studies have not focused on the lingering effects that exist in post return-to-play.Design/MethodsThe first group (n = 15) consisted of recently cleared to return-to-play collegiate athletes after experiencing a sports-related concussion. The second group (n = 15) was collegiate athlete controls matched on age, sex, and sport. Serum samples were collected to assess the levels of proteins following post return-to-play. These proteins were evaluated using Enzyme-Linked Immunosorbent Assay kits (ELIASA).ResultsAn overall BDNF effect was observed between groups (p < 0.05), the concussed group exhibited significantly higher levels of serum BDNF compared to the control group. A positive association between BDNF and gray matter volume (GMV) was observed at a 250 voxel cluster level in both the right (pFDR = 0.015) and left cerebellum region (pFDR = 0.045) across groups. A negative association between BDNF and GMV in both groups was observed in the brainstem (p = 0.029) and the precuneus (p = 0.017) areas. A differential relationship between group and BDNF on GMV was observed (p = 0.022) in the prefrontal cortex.ConclusionsPrevious research has not examined the post return-to-play effects in neuroplasticity specific proteins, nor the time frame of injury in comparison to controls with MRI. Serum-based biomarkers and MRI grant a better depiction of what is occurring during post return-to-play.

scholarly journals Serum Aminoacyl-tRNA Synthetase-Interacting Multifunctional Protein-1 Can Predict Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Pilot Monocentric Study

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Sung Soo Ahn ◽  
Jin-Ock Kim ◽  
Taejun Yoon ◽  
Jason Jungsik Song ◽  
Yong-Beom Park ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Multivariate Logistic Regression Analysis ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Population Based ◽  
Trna Synthetase ◽  
Aminoacyl Trna Synthetase ◽  
Serum Samples ◽  
Cross Sectional ◽  
Multifunctional Protein ◽  
Protein Levels

We investigated whether serum aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) could predict severe cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on the Birmingham vasculitis activity score (BVAS). Sixty-one patients with AAV were selected for inclusion from our prospective AAV cohort. AAV-specific indices and clinical manifestations were assessed, and laboratory tests were performed on the day of blood sampling. Patients with severe AAV were defined as those with a BVAS higher than the lower limit of the highest tertile of BVAS (BVAS ≥ 12). We measured serum AIMP1 levels of the stored serum samples. A total of 20 (32.8%) and 41 (67.2%) patients were classified as having severe and nonsevere AAV according to the cut-off of BVAS ≥ 12. Patients with severe AAV showed higher frequencies of general and renal manifestations, along with ANCA positivity, and exhibited a higher mean neutrophil count, erythrocyte sedimentation rate, and C-reactive protein levels, but lower mean haemoglobin and serum albumin levels than those with nonsevere AAV. The mean serum AIMP1 level in patients with severe AAV was significantly higher than that of patients with nonsevere AIMP1 (351.1 vs. 98.4 pg/mL, p = 0.006). Multivariate logistic regression analysis including variables showing significance in univariate analyses revealed that only serum AIMP1 exhibited a significant association with severe AAV (odds ratio 1.004, p = 0.031). When we set the optimal cut-off of serum AIMP1 for severe AAV to 50.28 pg/mL, patients with severe AAV more frequently had AIMP1 levels above the cut-off than those with nonsevere AAV (80.0% vs. 31.7%, relative risk 8.615, p < 0.001). The results from our study suggest that serum AIMP1 can be used to estimate the cross-sectional severe AAV population based on the BVAS.

scholarly journals Molecular signatures of cell migration in C. elegans Q neuroblasts

2009 ◽  
Vol 185 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Guangshuo Ou ◽  
Ronald D. Vale
Keyword(s):  
Cell Migration ◽  
Fluorescent Protein ◽  
Cell Movement ◽  
Live Animal ◽  
Α Subunit ◽  
C Elegans ◽  
Protein Levels ◽  
Neuroblast Migration ◽  
Green Fluorescent

Metazoan cell movement has been studied extensively in vitro, but cell migration in living animals is much less well understood. In this report, we have studied the Caenorhabditis elegans Q neuroblast lineage during larval development, developing live animal imaging methods for following neuroblast migration with single cell resolution. We find that each of the Q descendants migrates at different speeds and for distinct distances. By quantitative green fluorescent protein imaging, we find that Q descendants that migrate faster and longer than their sisters up-regulate protein levels of MIG-2, a Rho family guanosine triphosphatase, and/or down-regulate INA-1, an integrin α subunit, during migration. We also show that Q neuroblasts bearing mutations in either MIG-2 or INA-1 migrate at reduced speeds. The migration defect of the mig-2 mutants, but not ina-1, appears to result from a lack of persistent polarization in the direction of cell migration. Thus, MIG-2 and INA-1 function distinctly to control Q neuroblast migration in living C. elegans.

Factors contributing to high levels of plasma iodide in brook trout, Salvelinus fontinalis (Mitchill)

1975 ◽  
Vol 53 (3) ◽  
pp. 267-277 ◽  
Author(s):  
Linda A. Gregory ◽  
J. G. Eales
Keyword(s):  
Protein Interactions ◽  
Brook Trout ◽  
Plasma Proteins ◽  
Iodine Concentration ◽  
High Plasma ◽  
Natural Food ◽  
Storage Site ◽  
Tissue Storage ◽  
Commercial Diet ◽  
Protein Levels

The influences of dietary iodine, ambient iodide, tissue storage of iodide, and iodide binding to plasma proteins have been related to the high plasma iodide in laboratory brook trout.Plasma iodide exceeded 1800 μg/100 ml (μg%) for trout acclimated at 13 °C and fed an Ewos commercial diet. This was largely due to (i) efficient iodide absorption from the gut, and (ii) an iodine concentration in Ewos food (31–35 μg I/g dry wt.) that was 20–78 times greater than that of four other artificial foods or that of several natural food items.Ambient iodide ranged seasonally from 1.26 to2.21 μg I/liter. This source probably contributed little to the high plasma iodide, but helped to maintain plasma levels during starvation or use of low-iodide diets.No major extrathyroidal iodide storage site was found in 15 organs or tissues examined.Iodide binds to brook trout plasma proteins, but the concentration of binding sites is less than that reported for other species. This binding aids maintenance of plasma iodide, particularly when iodide intake is low. Variation in plasma iodide between individual fish was not clearly related to variations in iodide–protein interactions nor to variations in plasma protein levels.

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