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"Michael D. White"
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Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma
Brain metastases from lung adenocarcinoma (BM-LUAD) frequently cause patient mortality. To identify genomic alterations that promote brain metastases, we performed whole-exome sequencing of 73 BM-LUAD cases. Using case-control analyses, we discovered candidate drivers of brain metastasis by identifying genes with more frequent copy-number aberrations in BM-LUAD compared to 503 primary LUADs. We identified three regions with significantly higher amplification frequencies in BM-LUAD, including
MYC
(12 versus 6%),
YAP1
(7 versus 0.8%) and
MMP13
(10 versus 0.6%), and significantly more frequent deletions in
CDKN2A/B
(27 versus 13%). We confirmed that the amplification frequencies of
MYC
,
YAP1
and
MMP13
were elevated in an independent cohort of 105 patients with BM-LUAD. Functional assessment in patient-derived xenograft mouse models validated the notion that
MYC
,
YAP1
or
MMP13
overexpression increased the incidence of brain metastasis. These results demonstrate that somatic alterations contribute to brain metastases and that genomic sequencing of a sufficient number of metastatic tumors can reveal previously unknown metastatic drivers.
Whole-exome sequencing of human brain metastases from lung adenocarcinoma uncovers new drivers by comparison of somatic alteration frequencies in brain metastasis cases to those in primary lung adenocarcinomas.
Journal Article
Landscape position mediates drought vulnerability in California valley oak (Quercus lobata)
Future climate change will exacerbate drought stress in water-limited ecosystems. However, topography can alter the fine-scale climatic and hydrologic conditions that mediate plant response to meteorological drought. Here, with six new valley oak ( Quercus lobata ) tree-ring width chronologies, we assess how topography acts as a mediating factor on tree growth and drought sensitivity. Because valley oaks are known to be highly dependent on subsurface water, we predicted that trees growing in riparian sites would be less sensitive to precipitation variability due to greater access to groundwater. Trees were sampled in the Tehachapi Mountains of California across a landscape gradient of sites ranging from 375–1650 m elevation and across upland (55–69 m mean height above nearest drainage) and riparian (2–6 m mean height above the nearest drainage) hillslope positions. Interannual tree growth patterns and drought sensitivity varied substantially in association with hillslope position and elevation. Valley oak radial growth showed a consistently weaker response to precipitation at riparian sites. The influence of hillslope position on drought sensitivity varied with elevation, such that the riparian buffering effect was weakest at sites higher in the watershed and strengthened, progressively, toward the lower elevation sites with greater climatic water deficit. Upland tree growth exhibited a strong response to high-frequency interannual precipitation variability at the high elevation site, whereas trees at lower elevation upland sites responded more to low-frequency decadal trends in precipitation, possibly reflecting hydrogeological processes by which precipitation feeds groundwater lower in the watershed. Our results are consistent with groundwater-dependence of valley oak and indicate that riparian habitats are the most likely refugia for the species during prolonged drought.
Journal Article
Assessing the utility of metabarcoding for diet analyses of the omnivorous wild pig (Sus scrofa)
Wild pigs (Sus scrofa) are an invasive species descended from both domestic swine and Eurasian wild boar that was introduced to North America during the early 1500s. Wild pigs have since become the most abundant free‐ranging exotic ungulate in the United States. Large and ever‐increasing populations of wild pigs negatively impact agriculture, sport hunting, and native ecosystems with costs estimated to exceed $1.5 billion/year within the United States. Wild pigs are recognized as generalist feeders, able to exploit a broad array of locally available food resources, yet their feeding behaviors remain poorly understood as partially digested material is often unidentifiable through traditional stomach content analyses. To overcome the limitation of stomach content analyses, we developed a DNA sequencing‐based protocol to describe the plant and animal diet composition of wild pigs. Additionally, we developed and evaluated blocking primers to reduce the amplification and sequencing of host DNA, thus providing greater returns of sequences from diet items. We demonstrate that the use of blocking primers produces significantly more sequencing reads per sample from diet items, which increases the robustness of ascertaining animal diet composition with molecular tools. Further, we show that the overall plant and animal diet composition is significantly different between the three areas sampled, demonstrating this approach is suitable for describing differences in diet composition among the locations. We developed a DNA sequencing‐based protocol to describe the plant and animal diet composition of wild pigs from three eco‐regions within the United States: California, Texas, and Florida. We show that the overall plant and animal diet composition is significantly different between these eco‐regions. By applying the protocol, we describe here, assessing the diet composition of wild pigs through DNA analysis will increase management efficacy by allowing control efforts to be focused in landscapes supporting seasonally preferred diet items.
Journal Article
Stop and Frisk
No policing tactic has been more controversial than \"stop and frisk,\" whereby police officers stop, question and frisk ordinary citizens, who they may view as potential suspects, on the streets. As Michael White and Hank Fradella show inStop and Frisk, the first authoritative history and analysis of this tactic, there is a disconnect between our everyday understanding and the historical and legal foundations for this policing strategy. First ruled constitutional in 1968, stop and frisk would go on to become a central tactic of modern day policing, particularly by the New York City Police Department. By 2011 the NYPD recorded 685,000 'stop-question-and-frisk' interactions with citizens; yet, in 2013, a landmark decision ruled that the police had over- and mis-used this tactic.Stop and Frisktells the story of how and why this happened, and offers ways that police departments can better serve their citizens. They also offer a convincing argument that stop and frisk did not contribute as greatly to the drop in New York's crime rates as many proponents, like former NYPD Police Commissioner Ray Kelly and Mayor Michael Bloomberg, have argued.
While much of the book focuses on the NYPD's use of stop and frisk, examples are also shown from police departments around the country, including Philadelphia, Baltimore, Chicago, Newark and Detroit. White and Fradella argue that not only does stop and frisk have a legal place in 21st-century policing but also that it can be judiciously used to help deter crime in a way that respects the rights and needs of citizens. They also offer insight into the history of racial injustice that has all too often been a feature of American policing's history and propose concrete strategies that every police department can follow to improve the way they police. A hard-hitting yet nuanced analysis,Stop and Friskshows how the tactic can be a just act of policing and, in turn, shows how to police in the best interest of citizens.
eBook
An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation
Atypical protein kinase C (aPKC) isoforms have been implicated in cell polarisation and migration through association with Cdc42 and Par6. In distinct migratory models, the Exocyst complex has been shown to be involved in secretory events and migration. By RNA interference (RNAi) we show that the polarised delivery of the Exocyst to the leading edge of migrating NRK cells is dependent upon aPKCs. Reciprocally we demonstrate that aPKC localisation at the leading edge is dependent upon the Exocyst. The basis of this inter-dependence derives from two-hybrid, mass spectrometry, and co-immunoprecipitation studies, which demonstrate the existence of an aPKC-Exocyst interaction mediated by Kibra. Using RNAi and small molecule inhibitors, the aPKCs, Kibra, and the Exocyst are shown to be required for NRK cell migration and it is further demonstrated that they are necessary for the localized activation of JNK at the leading edge. The migration associated control of JNK by aPKCs determines JNK phosphorylation of the plasma membrane substrate Paxillin, but not the phosphorylation of the nuclear JNK substrate, c-jun. This plasma membrane localized JNK cascade serves to control the stability of focal adhesion complexes, regulating migration. The study integrates the polarising behaviour of aPKCs with the pro-migratory properties of the Exocyst complex, defining a higher order complex associated with the localised activation of JNK at the leading edge of migrating cells that determines migration rate.
Journal Article
Patient perception of spinal cord injury through social media: An analysis of 703 Instagram and 117 Twitter posts
ABSTRACT
Introduction:
Social media has developed exponentially over the last decade as a means for individuals and patients to connect to others and has provided a unique opportunity for physicians to provide broader information to the general public to attempt to positively modify health behavior. The purpose of this study was to assess the patient's perception of spinal cord injury (SCI) on social media.
Methods:
Instagram and Twitter social media platforms were analyzed to determine posts written by patients with SCI. The initial search for Instagram posts tagged with \"#spinalcordinjury\" yielded over 270,000 posts in April 2021. Posts pertaining to the patient's experience were retrospectively collected from January 2020 to April 2021. Twitter posts that included \"#spinalcordinjury,\" \"@spinalcordinjury,\" and \"spinal cord injury\" were retrospectively collected in April 2021. One hundred seventeen tweets were found that were directly from a patient with SCI. Themes associated with patients' experiences living with SCI were coded.
Results:
The most common theme on Instagram was spreading positivity and on Twitter was the appearance of the wheelchair (75.8% and 37.3%, respectively). Other common themes on Instagram were the appearance of a wheelchair (71.8%), recovery or rehabilitation (29.9%), and life satisfaction (29.0%). Prevalent themes on Twitter included spreading positivity (23.2%) and recovery or rehabilitation (21.3%).
Conclusion:
The prevalence of themes of positivity and awareness may indicate the utilization of social media as a support mechanism for patients living with SCI. Identification of prevalent themes is important for the holistic treatment of SCI survivors.
Journal Article
Leveraging Body-Worn Camera Footage to Better Understand Opioid Overdoses and the Impact of Police-Administered Naloxone
Objectives. To investigate what transpires at opioid overdoses where police administer naloxone and to identify the frequency with which concerns about police-administered naloxone are observed. Methods. We reviewed body-worn camera (BWC) footage of all incidents where a Tempe, Arizona police officer administered naloxone or was present when the Tempe Fire Medical Rescue (TFMR) administered it, from February 3, 2020 to May 7, 2021 (n = 168). We devised a detailed coding instrument and employed univariate and bivariate analysis to examine the frequency of concerns regarding police-administered naloxone. Results. Police arrived on scene before the TFMR in 73.7% of cases. In 88.6% of calls the individual was unconscious when police arrived, but 94.6% survived the overdose. The primary concerns about police-administered naloxone were rarely observed. There were no cases of improper naloxone administration or accidental opioid exposure to an officer. Aggression toward police from an overdose survivor rarely occurred (3.6%), and arrests of survivors (3.6%) and others on scene (1.2%) were infrequent. Conclusions. BWC footage provides a unique window into opioid overdoses. In Tempe, the concerns over police-administered naloxone are overstated. If results are similar elsewhere, those concerns are barriers that must be removed. (Am J Public Health. 2022;112(9):1326–1332. https://doi.org/10.2105/AJPH.2022.306918 )
Journal Article
