13 Works

Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases

Johannes Reiter, Wei-Ting Hung, I-Hsiu Lee, Shriya Nagpal, Peter Giunta, Sebastian Degner, Gang Liu, Emma Wassenaar, William Jeck, Martin Taylor, Alexander Farahani, Hetal Marble, Simon Knott, Onno Kranenburg, Jochen Lennerz & Kamila Naxerova
Genetic diversity among metastases is poorly understood but contains important information about disease evolution at secondary sites. Here we investigate inter- and intra-lesion heterogeneity for two types of metastases that associate with different clinical outcomes: lymph node and distant organ metastases in human colorectal cancer. We develop a rigorous mathematical framework for quantifying metastatic phylogenetic diversity. Distant metastases are typically monophyletic and genetically similar to each other. Lymph node metastases, in contrast, display high levels...

Cerebral Vasoregulation in Diabetes

Vera Novak & Laura Mendez
This observational study evaluated the effects of type 2 diabetes on cerebral vasoregulation and functional outcomes, measured by blood flow responses to hypocapnia and hypercapnia, Valsalva maneuver, head-up tilt, and sit-to-stand test. This dataset contains 37 diabetic participants and 49 controls (aged 55 to 75 years) with continuous measurements of cerebral blood flow using transcranial Doppler and MRI, heart rate, blood pressure, and respiratory parameters, balance, walking, laboratory and retinopathy measures.

Seasonal patterns of melatonin alter aggressive phenotypes of female Siberian hamsters

Nikki Rendon, Christopher Petersen, Kathleen Munley, Andrea Amez, Daniel Boyes, Marcy Kingsbury & Gregory Demas
Many animal species exhibit year-round aggression, a behaviour that allows individuals to compete for limited resources in their environment (e.g., food and mates). Interestingly, this high degree of territoriality persists during the non-breeding season, despite low levels of circulating gonadal steroids (i.e., testosterone [T] and oestradiol [E2]). Our previous work suggests that the pineal hormone melatonin mediates a ‘seasonal switch’ from gonadal to adrenal regulation of aggression in Siberian hamsters (Phodopus sungorus); solitary, seasonally breeding...

The Landscape of Connected Cancer Symptom Management in Rural America

Ming-Yuan Chih, Anna McCowan, Sadie Whittaker, Melinda Krakow, David K. Ahern, Eliah Aronoff-Spencer, Bradford W. Hesse, Timothy W. Mullett & Robin C. Vanderpool
Background: The 2016 President’s Cancer Panel called for projects focusing on improving cancer symptom management using connected health technologies (broadband and telecommunications). However, rural communities, like those in Appalachia, may experience a “double burden” of high cancer rates and lower rates of broadband access and adoption necessary for connected health solutions. Purpose: To better understand the current landscape of connected health in the management of cancer symptoms in rural America. Methods: A literature search was...

Risk factors for cardiovascular disease (CVD) in adults with type 1 diabetes: findings from prospective real-life T1D exchange registry

Nicole Foster, Viral N Shah, Ryan Bailey, Mengdi Wu, Rodica Pop-Busui, Michelle Katz, Jill Crandall, Fida Bacha, Kristen Nadeau, Ingrid Libman, Paul Hiers, Kara Mizokami-Stout, Linda A DiMeglio, Jennifer Sherr, Richard Pratley, Shivani Agarwal, Janet Snell-Bergeon, Eda Cengiz, Sarit Polsky & Sanjeev N Mehta
Context Cardiovascular disease (CVD) is a major cause of mortality in adults with type 1 diabetes. Objective We prospectively evaluated CVD risk factors in a large, contemporary cohort of adults with type 1 diabetes living in the United States. Design Observational study of CVD and CVD risk factors over a median of 5.3 years. Setting The T1D Exchange clinic network. Patients Adults (age ≥18 years) with type 1 diabetes and without known CVD diagnosed before...

Cell-autonomous light sensitivity via Opsin3 regulates fuel utilization in brown adipocytes

Mari Sato, Tadataka Tsuji, Kunyan Yang, Jonathan Dreyfuss, Tian Lian Huang, Chih-Hao Wang, Farnaz Shamsi, Luiz Leiria, Matthew Lynes, Yu-Hua Tseng, Xiaozhi Ren & King-Wai Yau
Opsin3 (Opn3) is a transmembrane heptahelical G-protein-coupled receptor (GPCR) with the potential to produce a non-visual photoreceptive effect. Interestingly, anatomical profiling of GPCRs reveals that Opn3 mRNA is highly expressed in adipose tissue. The photosensitive functions of Opn3 in mammals are poorly understood, and whether Opn3 has a role in fat is entirely unknown. In this study, we found that Opn3-knockout (Opn3-KO) mice were prone to diet-induced obesity and insulin-resistance. At the cellular level, Opn3-KO...

Data from: Age influences the thermal suitability of Plasmodium falciparum transmission in the Asian malaria vector Anopheles stephensi

Courtney Murdock, Kerri Miazgowicz, Erin Mordecai, Sadie Ryan, Richard Hall, Harry Owen, Temitayo Adanlawo, Kavya Balaji, Marta Shocket, Oswaldo Villena, Leah Johnson, Blanka Tesla, Leah Demakovsky, Matt Bonds, Calistus Ngonghala & Melinda Brindley
Models predicting disease transmission are vital tools for long-term planning of malaria reduction efforts, particularly for mitigating impacts of climate change. We compared temperature-dependent malaria transmission models when mosquito life history traits were estimated from a truncated portion of the lifespan (a common practice) to traits measured across the full lifespan. We conducted an experiment on adult female Anopheles stephensi, the Asian urban malaria mosquito, to generate daily per capita values for mortality, egg production,...

Data from: TAS2R20 variants confer dietary adaptation to high-quercitrin bamboo leaves in Qinling giant pandas

Xiangxu Hu, Guan Wang, Lei Shan, Shuyan Sun, Yibo Hu & Fuwen Wei
Sensitivity to bitter tastes provides animals with an important means of interacting with their environment and thus, influences their dietary preferences. Genetic variants encoding functionally distinct receptor types contribute to variation in bitter taste sensitivity. Our previous study showed that two nonsynonymous sites, A52V and Q296H, in the TAS2R20 gene are directionally selected in giant pandas from the Qinling Mountains, which are speculated to be the causative base-pair changes of Qinling pandas for the higher...

Regulation of olfactory-based sex behaviors in the silkworm by genes in the sex-determination cascade

Jun Xu
Insect courtship and mating depend on integration of olfactory, visual, and tactile cues. Compared to other insects, Bombyx mori, the domesticated silkworm, has relatively simple sexual behaviors as it cannot fly. Here by using CRISPR/Cas9 and electrophysiological techniques we found that courtship and mating behaviors are regulated in male silk moths by mutating genes in the sex determination cascade belonging to two conserved pathways. Loss of Bmdsx gene expression significantly reduced the peripheral perception of...

Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo: RNAseq dataset

Eben Estell, Phuong T Le, Yosta Vegting, Hyeonwoo Kim, Christiane Wrann, Mary L Bouxsein, Kenichi Nagano, Roland Baron, Bruce M Spiegelman & Clifford J Rosen
Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. In vitro, irisin (2–10 ng/mL) increased osteoclast differentiation in C57BL/6J mouse bone marrow progenitors; however, this increase was blocked by a neutralizing antibody to integrin αVβ5. Irisin also increased bone resorption on several substrates in situ. RNAseq revealed differential gene expression induced by irisin including...

Rural Appalachia Battling the Intersection of Two Crises

Margaret Miller, Rebekah Rollston, Kate E. Beatty & Michael Meit
During the COVID-19 pandemic, rural Appalachia is at great risk of unforeseen side effects including increased mortality from substance use disorders (SUDs). People living with SUDs are at increased risk for both exposure to and poor outcomes from COVID infection. The economic impacts of COVID-19 must also be considered. As rural Appalachia combats the substance use crisis amidst the COVID-19 pandemic, the geographic economic, health and social inequities within our region must be considered. As...

cGAS suppresses genomic instability as a decelerator of replication forks

Hao Chen
The cyclic GMP-AMP synthase (cGAS), a sensor of cytosolic DNA, is critical for the innate immune response. Here, we show that loss of cGAS in untransformed and cancer cells results in uncontrolled DNA replication, hyperproliferation, and genomic instability. While the majority of cGAS is cytoplasmic, a fraction of cGAS associates with chromatin. cGAS interacts with replication fork proteins in a DNA binding–dependent manner, suggesting that cGAS encounters replication forks in DNA. Independent of cGAMP and...

Data from: Evidence for normal novel object recognition abilities in developmental prosopagnosia

Regan Fry, Jeremy Wilmer, Isabella Xie, Mieke Verfaellie & Joseph DeGutis
The issue of the face specificity of recognition deficits in developmental prosopagnosia (DP) is fundamental to the organisation of high-level visual memory and has been increasingly debated in recent years. Previous DP investigations have found some evidence of object recognition impairments, but have almost exclusively used familiar objects (e.g., cars), where performance may depend on acquired object-specific experience and related visual expertise. An object recognition test not influenced by experience could provide a better, less...

Registration Year

  • 2020

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  • Harvard Medical School
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  • University of Florida
  • Beth Israel Deaconess Medical Center
  • Cornell University
  • University of Pennsylvania
  • University of Colorado System
  • University of Michigan-Ann Arbor
  • University of Georgia
  • University of California, San Diego