scholarly journals Adipose transcriptome analysis provides novel insights into molecular regulation of prolonged fasting in northern elephant seal pups

2018 ◽  
Vol 50 (7) ◽  
pp. 495-503 ◽  
Author(s):  
Bridget Martinez ◽  
Jane Khudyakov ◽  
Kim Rutherford ◽  
Daniel E. Crocker ◽  
Neil Gemmell ◽  
...  
Keyword(s):  
Marine Mammals ◽  
Energy Homeostasis ◽  
De Novo ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Elephant Seal ◽  
Prolonged Fasting ◽  
Northern Elephant Seal ◽  
Data Set

The physiological and cellular adaptations to extreme fasting in northern elephant seals ( Mirounga angustirostris, NES) are remarkable and may help to elucidate endocrine mechanisms that regulate lipid metabolism and energy homeostasis in mammals. Recent studies have highlighted the importance of thyroid hormones in the maintenance of a lipid-based metabolism during prolonged fasting in weaned NES pups. To identify additional molecular regulators of fasting, we used a transcriptomics approach to examine changes in global gene expression profiles before and after 6–8 wk of fasting in weaned NES pups. We produced a de novo assembly and identified 98 unique protein-coding genes that were differentially expressed between early and late fasting. Most of the downregulated genes were associated with lipid, carbohydrate, and protein metabolism. A number of downregulated genes were also associated with maintenance of the extracellular matrix, consistent with tissue remodeling during weight loss and the multifunctional nature of blubber tissue, which plays both metabolic and structural roles in marine mammals. Using this data set, we predict potential mechanisms by which NES pups sustain metabolism and regulate adipose stores throughout the fast, and provide a valuable resource for additional studies of extreme metabolic adaptations in mammals.

scholarly journals Comprehensive Clinical and Molecular Characterization of KRASG12C-Mutant Colorectal Cancer

2021 ◽  
pp. 613-621
Author(s):  
Jason T. Henry ◽  
Oluwadara Coker ◽  
Saikat Chowdhury ◽  
John Paul Shen ◽  
Van K. Morris ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
De Novo ◽  
Expression Profiles ◽  
Single Gene ◽  
Gene Expression Profiles ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Data Set ◽  
External Data

PURPOSE KRAS p.G12C mutations occur in approximately 3% of metastatic colorectal cancers (mCRC). Recently, two allosteric inhibitors of KRAS p.G12C have demonstrated activity in early phase clinical trials. There are no robust studies examining the behavior of this newly targetable population. METHODS We queried the MD Anderson Cancer Center data set for patients with colorectal cancer who harbored KRAS p.G12C mutations between January 2003 and September 2019. Patients were analyzed for clinical characteristics, overall survival (OS), and progression-free survival (PFS) and compared against KRAS nonG12C. Next, we analyzed several internal and external data sets to assess immune signatures, gene expression profiles, hypermethylation, co-occurring mutations, and proteomics. RESULTS Among the 4,632 patients with comprehensive molecular profiling, 134 (2.9%) were found to have KRAS p.G12C mutations. An additional 53 patients with single gene sequencing were included in clinical data but excluded from prevalence analysis allowing for 187 total patients. Sixty-five patients had de novo metastatic disease and received a median of two lines of chemotherapy without surgical intervention. For the first three lines of chemotherapy, the median PFS was 6.4 months (n = 65; 95% CI, 5.0 to 7.4 months), 3.9 months (n = 47; 95% CI, 2.9 to 5.9 months), and 3.0 months (n = 21; 95% CI, 2.0 to 3.4 months), respectively. KRAS p.G12C demonstrated higher rates of basal EGFR activation compared with KRAS nonG12C. When compared with an internal cohort of KRAS nonG12C, KRAS p.G12C patients had worse OS. CONCLUSION PFS is poor for patients with KRAS p.G12C metastatic colorectal cancer. OS was worse in KRAS p.G12C compared with KRAS nonG12C patients. Our data highlight the innate resistance to chemotherapy for KRAS p.G12C patients and serve as a historical comparator for future clinical trials.

A new perspective on adiposity in a naturally obese mammal

2001 ◽  
Vol 281 (6) ◽  
pp. E1347-E1351 ◽  
Author(s):  
Rudy M. Ortiz ◽  
Dawn P. Noren ◽  
Beate Litz ◽  
C. Leo Ortiz
Keyword(s):  
Body Fat ◽  
Marine Mammals ◽  
Tritiated Water ◽  
Elephant Seal ◽  
Mirounga Angustirostris ◽  
Prolonged Fasting ◽  
Northern Elephant Seal ◽  
Fat Stores ◽  
New Perspective ◽  
Water Dilution

Many mammals seasonally reduce body fat due to inherent periods of fasting, which is associated with decreased leptin concentrations. However, no data exist on the correlation between fat mass (FM) and circulating leptin in marine mammals, which have evolved large fat stores as part of their adaptation to periods of prolonged fasting. Therefore, FM was estimated (by tritiated water dilution), and serum leptin and cortisol were measured in 40 northern elephant seal ( Mirounga angustirostris) pups early (<1 wk postweaning) and late (6–8 wk postweaning) during their natural, postweaning fast. Body mass (BM) and FM were reduced late; however, percent FM (early: 43.9 ± 0.5, late: 45.5 ± 0.5%) and leptin [early: 2.9 ± 0.1 ng/ml human equivalents (HE), late: 3.0 ± 0.1 ng/ml HE] did not change. Cortisol increased between early (9.2 ± 0.5 μg/dl) and late (16.3 ± 0.9 μg/dl) periods and was significantly and negatively correlated with BM ( r = 0.426; P < 0.0001) and FM ( r = 0.328; P = 0.003). FM and percent FM were not correlated ( P > 0.10) with leptin at either period. The present study suggests that these naturally obese mammals appear to possess a novel cascade for regulating body fat that includes cortisol. The lack of a correlation between leptin and FM may reflect the different functions of fat between terrestrial and marine mammals.

scholarly journals Use of relevancy and complementary information for discriminatory gene selection from high-dimensional cancer data

2020 ◽  
Author(s):  
Md Nazmul Haque ◽  
Sadia Sharmin ◽  
Amin Ahsan Ali ◽  
Abu Ashfaqur Sajib ◽  
Mohammad Shoyaib
Keyword(s):  
Gene Expression ◽  
Gene Selection ◽  
De Novo ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Poor Performance ◽  
Global Gene Expression ◽  
Biological Information ◽  
Classification Rate ◽  
Cancer Data

AbstractWith the advent of high-throughput technologies, life sciences are generating a huge amount of biomolecular data. Global gene expression profiles provide a snapshot of all the genes that are transcribed or not in a cell or in a tissue at a particular moment under a particular condition. The high-dimensionality of such gene expression data (i.e., very large number of features/genes analyzed in relatively much less number of samples) makes it difficult to identify the key genes (biomarkers) that are truly and more significantly attributing to a particular phenotype or condition, such as cancer or disease, de novo. With the increase in the number of genes, simple feature selection methods show poor performance for both selecting the effective and informative features and capturing biological information. Addressing these issues, here we propose Mutual information based Gene Selection method (MGS) for selecting informative genes and two ranking methods based on frequency (MGSf) and Random Forest (MGSrf) for ranking the selected genes. We tested our methods on four real gene expression datasets derived from different studies on cancerous and normal samples. Our methods obtained better classification rate with the datasets compared to recently reported methods. Our methods could also detect the key relevant pathways with a causal relationship to the phenotype.

scholarly journals In-air hearing in Hawaiian monk seals: implications for understanding the auditory biology of Monachinae seals

2021 ◽  
Author(s):  
Brandi Ruscher ◽  
Jillian M. Sills ◽  
Beau P. Richter ◽  
Colleen Reichmuth
Keyword(s):  
Marine Mammals ◽  
Elephant Seal ◽  
Critical Ratio ◽  
Mirounga Angustirostris ◽  
Northern Elephant Seal ◽  
Hearing Ability ◽  
Highly Sensitive ◽  
Monk Seals ◽  
Management And Conservation ◽  
Hearing Abilities

AbstractThe auditory biology of Monachinae seals is poorly understood. Limited audiometric data and certain anatomical features suggest that these seals may have reduced sensitivity to airborne sounds compared to related species. Here, we describe the in-air hearing abilities of a Hawaiian monk seal (Neomonachus schauinslandi) trained to participate in a psychophysical paradigm. We report absolute (unmasked) thresholds for narrowband signals measured in quiet conditions across the range of hearing and masked thresholds measured in the presence of octave-band noise at two frequencies. The behavioral audiogram indicates a functional hearing range from 0.1 to 33 kHz and poor sensitivity, with detection thresholds above 40 dB re 20 µPa. Critical ratio measurements are elevated compared to those of other seals. The apparently reduced terrestrial hearing ability of this individual—considered with available auditory data for a northern elephant seal (Mirounga angustirostris)—suggests that hearing in Monachinae seals differs from that of the highly sensitive Phocinae seals. Exploration of phylogenetic relationships and anatomical traits support this claim. This work advances understanding of the evolution of hearing in amphibious marine mammals and provides updated information that can be used for management and conservation of endangered Hawaiian monk seals.

scholarly journals Granulosa cells from human primordial and primary follicles show differential global gene expression profiles

2018 ◽  
Vol 33 (4) ◽  
pp. 666-679 ◽  
Author(s):  
E H Ernst ◽  
S Franks ◽  
K Hardy ◽  
P Villesen ◽  
K Lykke-Hartmann
Keyword(s):  
Gene Expression ◽  
Granulosa Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression

scholarly journals Integrative Genomics with Mediation Analysis in a Survival Context

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Szilárd Nemes ◽  
Toshima Z. Parris ◽  
Anna Danielsson ◽  
Zakaria Einbeigi ◽  
Gunnar Steineck ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genomic Analysis ◽  
Mrna Levels ◽  
Integrative Genomics ◽  
Asymptotic Results ◽  
Data Set ◽  
Cancer Data ◽  
Dna And Rna ◽  
Altered Gene

DNA copy number aberrations (DCNA) and subsequent altered gene expression profiles may have a major impact on tumor initiation, on development, and eventually on recurrence and cancer-specific mortality. However, most methods employed in integrative genomic analysis of the two biological levels, DNA and RNA, do not consider survival time. In the present note, we propose the adoption of a survival analysis-based framework for the integrative analysis of DCNA and mRNA levels to reveal their implication on patient clinical outcome with the prerequisite that the effect of DCNA on survival is mediated by mRNA levels. The specific aim of the paper is to offer a feasible framework to test the DCNA-mRNA-survival pathway. We provide statistical inference algorithms for mediation based on asymptotic results. Furthermore, we illustrate the applicability of the method in an integrative genomic analysis setting by using a breast cancer data set consisting of 141 invasive breast tumors. In addition, we provide implementation in R.

scholarly journals Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape

2020 ◽  
Author(s):  
Gustavo Deco ◽  
Kevin Aquino ◽  
Aurina Arnatkevičiūtė ◽  
Stuart Oldham ◽  
Kristina Sabaroedin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Brain Regions ◽  
Biophysical Model ◽  
Neuronal Dynamics ◽  
Regional Heterogeneity ◽  
Magnetic Resonance Imaging Mri

AbstractBrain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles and MRI-derived estimates of myeloarchitecture. We further show that regional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional activity timescales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptional data to constrain models of large-scale brain function.

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