Studies of the adduct formed on interacting cisplatin with human apotransferrin: Synthesis, in vitro binding kinetics, in vivo pharmacokinetics and biodistribution in the rat.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30716/1/0000362.pd

Transcriptome Prediction Performance Across Machine Learning Models and Diverse Ancestries

Transcriptome prediction methods such as PrediXcan and FUSION have become popular in complex trait mapping. Most transcriptome prediction models have been trained in European populations using methods that make parametric linear assumptions like the elastic net (EN). To potentially further optimize imputation performance of gene expression across global populations, we built transcriptome prediction models using both linear and non-linear machine learning (ML) algorithms and evaluated their performance in comparison to EN. We trained models using genotype and blood monocyte transcriptome data from the Multi-Ethnic Study of Atherosclerosis (MESA) comprising individuals of African, Hispanic, and European ancestries and tested them using genotype and whole-blood transcriptome data from the Modeling the Epidemiology Transition Study (METS) comprising individuals of African ancestries. We show that the prediction performance is highest when the training and the testing population share similar ancestries regardless of the prediction algorithm used. While EN generally outperformed random forest (RF), support vector regression (SVR), and K nearest neighbor (KNN), we found that RF outperformed EN for some genes, particularly between disparate ancestries, suggesting potential robustness and reduced variability of RF imputation performance across global populations. When applied to a high-density lipoprotein (HDL) phenotype, we show including RF prediction models in PrediXcan revealed potential gene associations missed by EN models. Therefore, by integrating other ML modeling into PrediXcan and diversifying our training populations to include more global ancestries, we may uncover new genes associated with complex traits

Synthesis and antitumor activity of bis-platinum complexes varying in the nature of the bridging diamine linker group.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29214/1/0000268.pd

Adrenocortical Challenge Response and Genomic Analyses in Scottish Terriers With Increased Alkaline Phosphate Activity

Scottish terriers (ST) frequently have increased serum alkaline phosphatase (ALP) of the steroid isoform. Many of these also have high serum concentrations of adrenal sex steroids. The study's objective was to determine the cause of increased sex steroids in ST with increased ALP. Adrenal gland suppression and stimulation were compared by low dose dexamethasone (LDDS), human chorionic gonadotropin (HCG) and adrenocorticotropic hormone (ACTH) response tests. Resting plasma pituitary hormones were measured. Steroidogenesis-related mRNA expression was evaluated in six ST with increased ALP, eight dogs of other breeds with pituitary-dependent hyperadrenocorticism (HAC), and seven normal dogs. The genome-wide association of single nucleotide polymorphisms (SNP) with ALP activity was evaluated in 168 ST. ALP (reference interval 8–70 U/L) was high in all ST (1,054 U/L) and HAC (985 U/L) dogs. All HAC dogs and 2/8 ST had increased cortisol post-ACTH administration. All ST and 2/7 Normal dogs had increased sex steroids post-ACTH. ST and Normal dogs had similar post-challenge adrenal steroid profiles following LDDS and HCG. Surprisingly, mRNA of hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2) was lower in ST and Normal dogs than HAC. HSD17B2 facilities metabolism of sex steroids. A SNP region was identified on chromosome 5 in proximity to HSD17B2 that correlated with increased serum ALP. ST in this study with increased ALP had a normal pituitary-adrenal axis in relationship to glucocorticoids and luteinizing hormone. We speculate the identified SNP and HSD17B2 gene may have a role in the pathogenesis of elevated sex steroids and ALP in ST

Commoning mobility:Towards a new politics of mobility transitions

Scholars have argued that transitions to more sustainable and just mobilities require moving beyond technocentrism to rethink the very meaning of mobility in cities, communities, and societies. This paper demonstrates that such rethinking is inherently political. In particular, we focus on recent theorisations of commoning practices that have gained traction in geographic literatures. Drawing on our global comparative research of low‐carbon mobility transitions, we argue that critical mobilities scholars can rethink and expand the understanding of mobility through engagement with commons–enclosure thinking. We present a new concept, “commoning mobility,” a theorisation that both envisions and shapes practices that develop fairer and greener mobilities and more inclusive, collaboratively governed societies. Our analysis introduces three “logics” of mobility transition projects. First, the paper discusses how a logic of scarcity has been a driver for mobility planning as the scarcity of oil, finance, space, and time are invoked across the world as stimuli for aspiring to greener, “smarter,” and cheaper mobilities. The paper then identifies two responses to the logic of scarcity: the logics of austerity and the logics of commoning. Austere mobilities are examined to problematise the distribution of responsibility for emissions and ensuing injustices and exclusion in low‐carbon transitions. The logics of commoning shows a potential to reassess mobility not only as an individual freedom but also as a collective good, paving the way for fairer mobility transitions and a collaborative tackling of sustainable mobility challenges.info:eu-repo/semantics/publishedVersio

What Pinnipeds Have to Say about Human Speech, Music, and the Evolution of Rhythm

Research on the evolution of human speech and music benefits from hypotheses and data generated in a number of disciplines. The purpose of this article is to illustrate the high relevance of pinniped research for the study of speech, musical rhythm, and their origins, bridging and complementing current research on primates and birds. We briefly discuss speech, vocal learning, and rhythm from an evolutionary and comparative perspective. We review the current state of the art on pinniped communication and behavior relevant to the evolution of human speech and music, showing interesting parallels to hypotheses on rhythmic behavior in early hominids. We suggest future research directions in terms of species to test and empirical data needed