Knocking Down NOx: Examining the Effects of Transportation Electrification on Urban Ozone Production in the South Coast Air Basin

With last year’s commitment to all in-state sales of new passenger cars and trucks being zero-emission by 2035 (California Executive Order N-79-20), California is leading the charge for transportation electrification in the United States. Despite being at the forefront of climate change management and mitigation, California has some of the worst air quality in the nation. While primarily motivated by a desire to reduce carbon dioxide emissions and reliance on fossil fuels, transportation electrification will also have a significant impact on local air quality. The goal of this study is to quantify and qualify this impact in the context of urban ozone production. From robust studies of the weekend ozone effect, we know that reductions in vehicle emissions on weekend days can actually increase urban ozone concentrations. By examining data from eight ground monitoring stations in California’s South Coast Air Basin (SoCAB) over a period of 40 years, we show that this region is a volatile organic compound (VOC)-limited system in which the weekend ozone effect is a clear trend. Additionally, these data reveal that despite a significant decline in average annual nitrogen oxides (NOx) emissions, mean ozone levels have changed very little. With this in mind, the question looking forward becomes: how will local atmospheric chemistry and air quality evolve as transportation electrification accelerates? To investigate this question, VOC-NOx ratios are modeled for varying rates of light and heavy-duty vehicle electrification in order to gauge how urban ozone production will be affected. While it is clear that vehicle electrification will ultimately improve air quality and help mitigate climate change, this study provides a unique perspective into the less understood transient impacts of electrification

The neural correlates of speech motor sequence learning

Speech is perhaps the most sophisticated example of a species-wide movement capability in the animal kingdom, requiring split-second sequencing of approximately 100 muscles in the respiratory, laryngeal, and oral movement systems. Despite the unique role speech plays in human interaction and the debilitating impact of its disruption, little is known about the neural mechanisms underlying speech motor learning. Here, we studied the behavioral and neural correlates of learning new speech motor sequences. Participants repeatedly produced novel, meaningless syllables comprising illegal consonant clusters (e.g., GVAZF) over 2 days of practice. Following practice, participants produced the sequences with fewer errors and shorter durations, indicative of motor learning. Using fMRI, we compared brain activity during production of the learned illegal sequences and novel illegal sequences. Greater activity was noted during production of novel sequences in brain regions linked to non-speech motor sequence learning, including the BG and pre-SMA. Activity during novel sequence production was also greater in brain regions associated with learning and maintaining speech motor programs, including lateral premotor cortex, frontal operculum, and posterior superior temporal cortex. Measures of learning success correlated positively with activity in left frontal operculum and white matter integrity under left posterior superior temporal sulcus. These findings indicate speech motor sequence learning relies not only on brain areas involved generally in motor sequencing learning but also those associated with feedback-based speech motor learning. Furthermore, learning success is modulated by the integrity of structural connectivity between these motor and sensory brain regions.R01 DC007683 - NIDCD NIH HHS; R01DC007683 - NIDCD NIH HH

University American Sign Language Learners: Longitudinal Self- and Faculty Evaluation Ratings

Students who are Deaf or hard of hearing (D/HH) represent a small yet diverse population of students with individual needs who often receive educational services provided by sign language interpreters and teachers of the Deaf/hard of hearing (D/HH). Many interpreters and teachers appear unprepared to model fluent American Sign Language (ASL) skills when working with D/HH students who use sign language for communication and instruction. We investigated the ASL skills of 19 interpreting and Deaf education candidates within one university preparation program at two points in time: the end of ASL I class (Time 1) and a year later at the end of ASL IV (Time 2). We used video recordings of candidates’ signed renditions of a picture book, a rubric of 12 sign language indicators with five levels of proficiency across each indicator, and ratings conducted independently by the candidates and the five authors. Four of these authors were university professors in two different Deaf education/interpreting preparation programs and the fifth was a teacher at a residential school for the Deaf. Three have typical hearing and use ASL as a secondary language; two are Deaf and use ASL as their primary language. We compared candidates’ self-ratings to those of the five authors. We found that candidates tended to over-estimate their skills at T1; self-ratings and author ratings increased from T1 to T2, and candidates had higher agreement with most authors at T2 compared to T1. In addition, we found differences among ratings between the university faculty and the high school teacher. We discuss these differences in our findings and address implications for evaluating and improving university candidates’ ASL skills

Transformation of animal agriculture should be evidence-driven and respectful of livestock’s benefits and contextual aspects

Non peer reviewe

Animal board invited review: Animal source foods in healthy, sustainable, and ethical diets – An argument against drastic limitation of livestock in the food system

Animal source foods are evolutionarily appropriate foods for humans. It is therefore remarkable that they are now presented by some as unhealthy, unsustainable, and unethical, particularly in the urban West. The benefits of consuming them are nonetheless substantial, as they offer a wide spectrum of nutrients that are needed for cell and tissue development, function, and survival. They play a role in proper physical and cognitive development of infants, children, and adolescents, and help promote maintenance of physical function with ageing. While high-red meat consumption in the West is associated with several forms of chronic disease, these associations remain uncertain in other cultural contexts or when consumption is part of wholesome diets. Besides health concerns, there is also widespread anxiety about the environmental impacts of animal source foods. Although several production methods are detrimental (intensive cropping for feed, overgrazing, deforestation, water pollution, etc.) and require substantial mitigation, damaging impacts are not intrinsic to animal husbandry. When well-managed, livestock farming contributes to ecosystem management and soil health, while delivering high-quality foodstuffs through the upcycling of resources that are otherwise non-suitable for food production, making use of marginal land and inedible materials (forage, by-products, etc.), integrating livestock and crop farming where possible has the potential to benefit plant food production through enhanced nutrient recycling, while minimising external input needs such as fertilisers and pesticides. Moreover, the impacts on land use, water wastage, and greenhouse gas emissions are highly contextual, and their estimation is often erroneous due to a reductionist use of metrics. Similarly, whether animal husbandry is ethical or not depends on practical specificities, not on the fact that animals are involved. Such discussions also need to factor in that animal husbandry plays an important role in culture, societal well-being, food security, and the provision of livelihoods. We seize this opportunity to argue for less preconceived assumptions about alleged effects of animal source foods on the health of the planet and the humans and animals involved, for less top-down planning based on isolated metrics or (Western) technocratic perspectives, and for more holistic and circumstantial approaches to the food system.Peer reviewe

Behavioral and neural correlates of speech motor sequence learning in stuttering and neurotypical speakers: an fMRI investigation

Stuttering is a neurodevelopmental disorder characterized by impaired production of coordinated articulatory movements needed for fluent speech. It is currently unknown whether these abnormal production characteristics reflect disruptions to brain mechanisms underlying the acquisition and/or execution of speech motor sequences. To dissociate learning and control processes, we used a motor sequence learning paradigm to examine the behavioral and neural correlates of learning to produce novel phoneme sequences in adults who stutter (AWS) and neurotypical controls. Participants intensively practiced producing pseudowords containing non-native consonant clusters (e.g., “GVAZF”) over two days. The behavioral results indicated that although the two experimental groups showed comparable learning trajectories, AWS performed significantly worse on the task prior to and after speech motor practice. Using functional magnetic resonance imaging (fMRI), the authors compared brain activity during articulation of the practiced words and a set of novel pseudowords (matched in phonetic complexity). FMRI analyses revealed no differences between AWS and controls in cortical or subcortical regions; both groups showed comparable increases in activation in left-lateralized brain areas implicated in phonological working memory and speech motor planning during production of the novel sequences compared to the practiced sequences. Moreover, activation in left-lateralized basal ganglia sites was negatively correlated with in-scanner mean disfluency in AWS. Collectively, these findings demonstrate that AWS exhibit no deficit in constructing new speech motor sequences but do show impaired execution of these sequences before and after they have been acquired and consolidated.Published versio

Transcriptional diversity of long-term glioblastoma survivors

BACKGROUND: Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. METHODS: We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival \u3e48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal characteristics of these LTSs. RESULTS: The median overall survival of our cohort was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n = 2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identities. The majority of the MSKCC LTSs (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was found to be differentially expressed in the MSKCC and TCGA LTSs. CONCLUSIONS: While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression

Estimating survival in patients with gastrointestinal cancers and brain metastases: An update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA).

BackgroundPatients with gastrointestinal cancers and brain metastases (BM) represent a unique and heterogeneous population. Our group previously published the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with GI cancers (GI-GPA) (1985-2007, n = 209). The purpose of this study is to update the GI-GPA based on a larger contemporary database.MethodsAn IRB-approved consortium database analysis was performed using a multi-institutional (18), multi-national (3) cohort of 792 patients with gastrointestinal (GI) cancers, with newly-diagnosed BM diagnosed between 1/1/2006 and 12/31/2017. Survival was measured from date of first treatment for BM. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. These factors were incorporated into the updated GI-GPA.ResultsMedian survival (MS) varied widely by primary site and other prognostic factors. Four significant factors (KPS, age, extracranial metastases and number of BM) were used to formulate the updated GI-GPA. Overall MS for this cohort remains poor; 8 months. MS by GPA was 3, 7, 11 and 17 months for GPA 0-1, 1.5-2, 2.5-3.0 and 3.5-4.0, respectively. >30% present in the worst prognostic group (GI-GPA of ≤1.0).ConclusionsBrain metastases are not uncommon in GI cancer patients and MS varies widely among them. This updated GI-GPA index improves our ability to estimate survival for these patients and will be useful for therapy selection, end-of-life decision-making and stratification for future clinical trials. A user-friendly, free, on-line app to calculate the GPA score and estimate survival for an individual patient is available at brainmetgpa.com

In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice

Background: Mosaicism, the presence of genetically distinct cell populations within an organism, has emerged as an important contributor to disease. Mutational events occurring during embryonic development can cause mosaicism in any tissue, but the influence of environmental factors on levels of mosaicism is unclear. Objectives: We investigated whether in utero exposure to the widespread environmental mutagen benzo[a]pyrene (BaP) has an impact on the burden and distribution of mutations in adult mice. Methods: We used the Muta™Mouse transgenic rodent model to quantify and characterize mutations in the offspring of pregnant mice exposed to BaP during postconception days 7 through 16, covering the major period of organogenesis in mice. Next-generation DNA sequencing was then used to determine the spectrum of mutations induced in adult mice that were exposed to BaP during fetal development. Results: Mutation frequency was significantly increased in the bone marrow, liver, brain, and sperm of first filial generation (F1) males. Developing embryos accumulated more mutations and exhibited higher proportions of mosaicism than exposed adults, particularly in the brain. Decreased sperm count and motility revealed additional negative impacts on the reproductive function of F1 males. Conclusion: In utero exposure to environmental mutagens contributes to somatic and germline mosaicism, permanently affecting both the genetic health of the F1 and the population gene pool. Citation: Meier MJ, O’Brien JM, Beal MA, Allan B, Yauk CL, Marchetti F. 2017. In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice

Cas9 gRNA engineering for genome editing, activation and repression

We demonstrate that by altering the length of Cas9-associated guide RNA(gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits with combined transcriptional regulation and kill functions governed by a single multifunctional Cas9 protein.National Human Genome Research Institute (U.S.) (P50 HG005550)United States. Department of Energy (DE-FG02-02ER63445)Wyss Institute for Biologically Inspired EngineeringUnited States. Army Research Office (DARPA W911NF-11-2-0054)National Science Foundation (U.S.)United States. National Institutes of Health (5R01CA155320-04)United States. National Institutes of Health (P50 GM098792)National Cancer Institute (U.S.) (5T32CA009216-34)Massachusetts Institute of Technology. Department of Biological EngineeringHarvard Medical School. Department of GeneticsDefense Threat Reduction Agency (DTRA) (HDTRA1-14-1-0006