scholarly journals Migration-related changes in gene expression in leg muscle of the Christmas Island red crab Gecarcoidea natalis: seasonal preparation for long-distance walking

2010 ◽  
Vol 213 (10) ◽  
pp. 1740-1750 ◽  
Author(s):  
U. Postel ◽  
F. Thompson ◽  
G. Barker ◽  
M. Viney ◽  
S. Morris
Keyword(s):  
Gene Expression ◽  
Long Distance ◽  
Christmas Island ◽  
Leg Muscle ◽  
Gecarcoidea Natalis

scholarly journals Long-Distance Control of Origin Choice and Replication Timing in the Human β-Globin Locus Are Independent of the Locus Control Region

2000 ◽  
Vol 20 (15) ◽  
pp. 5581-5591 ◽  
Author(s):  
Daniel M. Cimbora ◽  
Dirk Schübeler ◽  
Andreas Reik ◽  
Joan Hamilton ◽  
Claire Francastel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Control Region ◽  
Globin Gene ◽  
Replication Timing ◽  
S Phase ◽  
Chromatin Conformation ◽  
Erythroid Cells ◽  
Long Distance ◽  
Targeted Deletion ◽  
Globin Gene Expression

ABSTRACT DNA replication in the human β-globin locus is subject to long-distance regulation. In murine and human erythroid cells, the human locus replicates in early S phase from a bidirectional origin located near the β-globin gene. This Hispanic thalassemia deletion removes regulatory sequences located over 52 kb from the origin, resulting in replication of the locus from a different origin, a shift in replication timing to late S phase, adoption of a closed chromatin conformation, and silencing of globin gene expression in murine erythroid cells. The sequences deleted include nuclease-hypersensitive sites 2 to 5 (5′HS2-5) of the locus control region (LCR) plus an additional 27-kb upstream region. We tested a targeted deletion of 5′HS2-5 in the normal chromosomal context of the human β-globin locus to determine the role of these elements in replication origin choice and replication timing. We demonstrate that the 5′HS2-5-deleted locus initiates replication at the appropriate origin and with normal timing in murine erythroid cells, and therefore we conclude that 5′HS2-5 in the classically defined LCR do not control replication in the human β-globin locus. Recent studies also show that targeted deletion of 5′HS2-5 results in a locus that lacks globin gene expression yet retains an open chromatin conformation. Thus, the replication timing of the locus is closely correlated with nuclease sensitivity but not globin gene expression.

scholarly journals Modeling transcriptional regulation using gene regulatory networks based on multi-omics data sources

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neel Patel ◽  
William S. Bush
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Prediction Models ◽  
Long Distance ◽  
Chromatin Looping ◽  
Gene Regulatory ◽  
The Impact

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

scholarly journals Lower leg muscle structure and function are altered in long-distance runners with medial tibial stress syndrome: a case control study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Joshua Mattock ◽  
Julie R. Steele ◽  
Karen J. Mickle
Keyword(s):  
Lower Leg ◽  
Structure And Function ◽  
Flexor Hallucis Longus ◽  
Plantar Flexor ◽  
Distance Runners ◽  
Long Distance ◽  
Cross Sectional ◽  
Muscle Structure ◽  
Leg Muscle ◽  
And Function

Abstract Background Medial tibial stress syndrome (MTSS) is a common lower leg injury experienced by runners. Although numerous risk factors are reported in the literature, many are non-modifiable and management of the injury remains difficult. Lower leg muscle structure and function are modifiable characteristics that influence tibial loading during foot-ground contact. Therefore, this study aimed to determine whether long-distance runners with MTSS displayed differences in in vivo lower leg muscle structure and function than matched asymptomatic runners. Methods Lower leg structure was assessed using ultrasound and a measure of lower leg circumference to quantify muscle cross-sectional area, thickness and lean lower leg girth. Lower leg function was assessed using a hand-held dynamometer to quantify maximal voluntary isometric contraction strength and a single leg heel raise protocol was used to measure ankle plantar flexor endurance. Outcome variables were compared between the limbs of long-distance runners suffering MTSS (n = 20) and matched asymptomatic controls (n = 20). Means, standard deviations, 95 % confidence intervals, mean differences and Cohen’s d values were calculated for each variable for the MTSS symptomatic and control limbs. Results MTSS symptomatic limbs displayed a significantly smaller flexor hallucis longus cross-sectional area, a smaller soleus thickness but a larger lateral gastrocnemius thickness than the control limbs. However, there was no statistical difference in lean lower leg girth. Compared to the matched control limbs, MTSS symptomatic limbs displayed deficits in maximal voluntary isometric contraction strength of the flexor hallucis longus, soleus, tibialis anterior and peroneal muscles, and reduced ankle plantar flexor endurance capacity. Conclusions Differences in lower leg muscle structure and function likely render MTSS symptomatic individuals less able to withstand the negative tibial bending moment generated during midstance, potentially contributing to the development of MTSS. The clinical implications of these findings suggest that rehabilitation protocols for MTSS symptomatic individuals should aim to improve strength of the flexor hallucis longus, soleus, tibialis anterior and peroneal muscles along with ankle plantar flexor endurance. However, the cross-sectional study design prevents us determining whether between group differences were a cause or effect of MTSS. Therefore, future prospective studies are required to substantiate the study findings.

scholarly journals Systematic functional characterization of antisense eRNA of protocadherin α composite enhancer

2021 ◽  
Vol 35 (19-20) ◽  
pp. 1383-1394
Author(s):  
Yuxiao Zhou ◽  
Siyuan Xu ◽  
Mo Zhang ◽  
Qiang Wu
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Single Cells ◽  
Functional Characterization ◽  
Three Dimensional ◽  
Elongation Factor ◽  
Locked Nucleic Acid ◽  
Loop Formation ◽  
Long Distance ◽  
Enhancer Region

Enhancers generate bidirectional noncoding enhancer RNAs (eRNAs) that may regulate gene expression. At present, the eRNA function remains enigmatic. Here, we report a 5′ capped antisense eRNA PEARL (Pcdh eRNA associated with R-loop formation) that is transcribed from the protocadherin (Pcdh) α HS5-1 enhancer region. Through loss- and gain-of-function experiments with CRISPR/Cas9 DNA fragment editing, CRISPRi, and CRISPRa, as well as locked nucleic acid strategies, in conjunction with ChIRP, MeDIP, DRIP, QHR-4C, and HiChIP experiments, we found that PEARL regulates Pcdhα gene expression by forming local RNA–DNA duplexes (R-loops) in situ within the HS5-1 enhancer region to promote long-distance chromatin interactions between distal enhancers and target promoters. In particular, increased levels of eRNA PEARL via perturbing transcription elongation factor SPT6 lead to strengthened local three-dimensional chromatin organization within the Pcdh superTAD. These findings have important implications regarding molecular mechanisms by which the HS5-1 enhancer regulates stochastic Pcdhα promoter choice in single cells in the brain.

EXERCISE IN THE TERRESTRIAL CHRISTMAS ISLAND RED CRAB GECARCOIDEA NATALIS - BLOOD GAS TRANSPORT

1994 ◽  
Vol 188 (1) ◽  
pp. 235-256 ◽  
Author(s):  
A Adamczewska ◽  
S Morris
Keyword(s):  
Gas Transport ◽  
Lactate Production ◽  
Circulatory System ◽  
Indirect Evidence ◽  
Blood Gas ◽  
Christmas Island ◽  
Exercise Period ◽  
Gas Measurements ◽  
Gecarcoidea Natalis ◽  
O2 Delivery

The respiratory and circulatory physiology of the terrestrial Christmas Island red crab Gecarcoidea natalis was investigated with respect to exercise in the context of its annual breeding migration. Red crabs were allowed to walk for predetermined periods of up to 45 min. During this exercise period, blood gas measurements were made on venous, pulmonary and arterial samples to assess the function of the lungs in gas exchange and the performance of the circulatory system in gas transport and to determine the role and importance of the haemocyanin. The lungs of G. natalis were very efficient at O2 uptake, pulmonary blood being 80­90 % saturated throughout the 45 min exercise period. The maximum O2-carrying capacity was 1.1 mmol l-1, and haemocyanin (Hc) delivered 86 % of oxygen in resting crabs and 97 % during exercise. Oxygen delivery to the tissues was diffusion-limited during exercise. Indirect evidence, from the changes in haemolymph pH during transit through the lungs, suggested that the lung is the site of CO2 excretion. The Bohr shift was high at high pH (pH 7.8­7.5, phi=-1.23) but decreased at low pH (pH 7.1­6.8, phi=-0.48). The decreased Hc affinity for O2 during the exercise period facilitated O2 delivery to the tissues without impairing O2 loading at the lungs. The decrease in pH was sufficient to explain the change of affinity of Hc for O2 during the exercise period. The marked acidosis (0.8 pH unit decrease) was largely metabolic in origin, especially during sustained locomotion, but less than could be predicted from concomitant lactate production.

Homeobox NKX2-3 Is Over-Expressed in Human B-Cell Lymphomas and Drives Marginal Zone B-Cell Lymphomagenesis in Mice

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 260-260
Author(s):  
Eloy F Robles ◽  
Beatriz Aldaz ◽  
Takashi Akasaka ◽  
Laura Macri Pellizzeri ◽  
Eduardo Martinez-Anso ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Molecular Cloning ◽  
B Lymphocytes ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
B Cell Lymphomas ◽  
Long Distance

Abstract Abstract 260 While the molecular study of the common immunoglobulin (IG) translocations, hallmarks of B-cell lymphomas, led to the discovery of seminal cancer genes such as MYC and BCL2, cloning of other less frequent rearrangements has also identified genes with critical biological functions, including BCL10 and BCL11A. Therefore, molecular cloning of rare IG-related translocations may still pinpoint genes with unappreciated roles in lymphomagenesis. We identified a novel chromosomal translocation t(10;14)(q24;q32) involving the IGH locus in a case of mature B-cell lymphoma in leukemic phase. Molecular cloning by long-distance inverse PCR revealed involvement of NKX2-3. Subsequent screening of lymphoma cases with 10q chromosome breaks using fluorescence in situ hybridization identified a t(10;14)(q24;q12) translocation fusing NKX2-3 with TCRA. Both cases were classified as atypical low-grade mature B-cell lymphoma and exhibited increased expression of NKX2-3 with respect to normal B lymphocytes. In addition, NKX2-3 over-expression using quantitative RT-PCR and immunohistochemistry was detected in 42 of 166 (25%) primary mature B-cell lymphoma samples, including 15 of 29 (51%) splenic marginal zone lymphomas (SMZL), 14 of 46 (30%) mucosa-associated lymphoid tissue (MALT) lymphomas, and 13 of 42 (31%) diffuse large B-cell lymphomas (DLBCLs), but not in follicular lymphomas (0 of 18), mantle cell lymphomas (0 of 8) or chronic B-cell lymphocytic leukemias (0 of 23). NKX2-3 belongs to the NKX family of homeodomain transcription factors that regulate cell-specific gene expression during differentiation and development. In mice, Nkx2-3 is essential for spleen and MALT development by regulating lymphocyte migration and homing to these sites. To determine whether NKX2-3 might, like some other family members, play an oncogenic role in hematopoietic neoplasms, Eμ-NKX2-3 transgenic mice were generated in which the EμSR enhancer drove restricted expression of human NKX2-3 to lymphocytes. Mice were fertile and developed normally. However, from 4 months of age, a progressive block in the pro-B (B220+CD19+Kit+) to pre-B cell (B220+CD25+) transition was detected in the bone marrow (BM), accompanied by a decrease in the number of circulating B220+IgM+B lymphocytes. Notably, an expansion of CD21highCD23low marginal-zone splenic B cells was identified, which correlated with progressive spleen enlargement upon ultrasound monitoring of transgenic animals. From ∼12 months of age, mice started to develop clinical signs of disease and were euthanized, showing massive splenomegaly (5–10 times larger than normal controls) in all cases (n=46). Histolopathological analysis of enlarged spleens revealed a complete red pulp infiltration of large and irregular nodules composed of cells with a biphasic morphology comprising an inner zone of small lymphocytes and a peripheral zone of larger lymphoid cells. Immunohistochemical studies showed that the infiltrating cells were mature CD20+IgM+IgD− B lymphocytes, with reactive CD3+ T lymphocytes, results that were concordant with flow cytometry studies. In 55% of the mice, additional extranodal tumors involving the lungs, liver and kidneys were detected, showing infiltrates of small mature B lymphocytes. Study of Igh, Igk and Igl rearrangements by PCR and sequencing revealed that most lymphomas were of clonal origin. Using gene expression microarray analysis, a significant overlap was found between the transcriptional signatures of the mouse NKX2-3 splenic lymphomas and human SMZLs, including genes known to be involved in human SMZL pathogenesis such as Notch2, Jun, Junb, Cyclin-D2, Ikzf3, Cxcr4, Traf5 and Maml2, as well as other genes implicated in mature B-cell lymphoma development such as Bcl3, Pax5, Bcl11a, Foxo3, Cebpb, Litaf, Socs1, IL10, Ccl5 and Cdkn1a. Taken together, these data indicate that the murine tumors closely resembled human splenic and extranodal marginal-zone (MALT) lymphomas. Furthermore, analysis of splenic and extranodal lymphomas from mice older than 18 months revealed areas of high-grade transformation to DLBCL, further highlighting the parallelism between splenic and human lymphomas. In conclusion, NKX2-3 protein is over-expressed in a subset of patients with SMZL, MALT lymphoma and DLBCL, and that the ectopic expression of NKX2-3 in mouse B lymphocytes recapitulates the main features of the human lymphoma counterparts. Disclosures: Siebert: Abbott/Vysis: Speakers Honorarium.

scholarly journals Reprogramming of the Wheat Transcriptome in Response to Infection with Claviceps Purpurea, the Causal Agent of Ergot

2020 ◽  
Author(s):  
Lesley A. Boyd ◽  
Eleni Tente ◽  
Nelzo Ereful ◽  
Anyela Camargo Rodriguez ◽  
Paul Grant ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Early Stage ◽  
Receptor Protein ◽  
Claviceps Purpurea ◽  
Long Distance ◽  
Transmitting Tissue ◽  
Significant Differential Expression ◽  
Differential Gene ◽  
Wheat Transcriptome

Abstract Background: Ergot, caused by the fungal pathogen Claviceps purpurea, infects the female flowers of a range of cereal crops, including wheat. To understand the interaction between C. purpurea and hexaploid wheat we undertook an extensive examination of the reprogramming of the wheat transcriptome in response to C. purpurea infection through floral tissues (i.e. the stigma, transmitting and base ovule tissues of the ovary) and over time. Results: C. purpurea hyphae were observed to have grown into and down the stigma at 24 hours (H) after inoculation. By 48H hyphae had grown through the transmitting tissue into the base, while by 72H hyphae had surrounded the ovule. By 5 days (D) the ovule had been replaced by fungal tissue. Significant differential gene expression was first observed at 1H in the stigma tissue. Many of the wheat genes differentially transcribed in response to C. purpurea infection were associated with plant hormones and included the ethylene (ET), auxin, cytokinin, gibberellic acid (GA), salicylic acid and jasmonic acid (JA) biosynthetic and signaling pathways. Hormone-associated genes were first detected in the stigma and base tissues at 24H, but not in the transmitting tissue. Genes associated with GA and JA pathways were seen in the stigma at 24H, while JA and ET-associated genes were identified in the base at 24H. In addition, several defence-associated genes were differential expressed in response to C. purpurea infection, including antifungal proteins, endocytosis/exocytosis-related proteins, NBS-LRR class proteins, genes involved in programmed cell death, receptor protein kinases and transcription factors. Of particular interest was the identification of significant differential expression of wheat genes in the base tissue well before the appearance of fungal hyphae, suggesting that a mobile signal, either pathogen or plant-derived, is delivered to the base prior to colonisation.Conclusions: Multiple host hormonal biosynthesis and signalling pathways were significantly perturbed from an early stage in the wheat – C. purpurea interaction. Significant differential gene expression at the base of the ovary, ahead of arrival of the pathogen, indicated the potential presence of a long-distance signal modifying host gene expression.

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