Observations from a systematic review of pharmacist- led research in solid organ transplantation: An opinion paper of the American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network

IntroductionThe contributions of transplant pharmacists to clinical and translational research in the United States are ill- defined and have not been systematically reviewed.ObjectivesThe American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network conducted a systematic review of available pharmacist- led research publications involving solid organ transplantation with the intent to quantify and describe pharmacist- led research endeavors and their changes over time.MethodsAn electronic search of Scopus was conducted to identify publications in the field of solid organ transplantation by pharmacist authors between January 1, 1975 and May 25, 2017. Articles were excluded if they were written in non- English languages or originated from non- US countries. Review articles, case reports, surveys, basic science research, pre- clinical studies, and non- transplant research were further excluded. Studies were categorized as one of four phases on the clinical and translational research spectrum, adapted from the Harvard Clinical and Translational Science Center description of a T1 to T4 classification system.ResultsA total of 10- 354 publications were identified by the systematic search with 547 full- text English- language publications included in the analysis. Pharmacists served as the first author in 87% of the articles and as the senior author in 67% of the articles. A total of 71% of the articles included more than one pharmacist author. Transplant pharmacists published more studies that employed a retrospective or observational study design (55% and 78%, respectively). A total of 37% of studies were funded. On the spectrum of clinical and translation research, pharmacists were most involved in T3 (translation to practice) research (72%), followed by T2 (translation to patients) research (23%).ConclusionsTransplant pharmacists are increasingly represented in the US literature and frequently published across domains. Further demonstrating the relevance of pharmacist- delivered interventions and outcomes is a critical area of practice focus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163590/2/jac51294.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163590/1/jac51294_am.pd

Historical perspective on: Femtosecond transition-state spectroscopy of iodine—From strongly bound to repulsive surface dynamics [Volume 161, Issues 4–5, 22 September 1989, Pages 297–302]

Summary by J.L. Herek. Nobel prize-winner: Professor Ahmed Zewail. In the spring of 1990, I was a young liberal arts student soon to graduate from Lawrence University in Wisconsin, dreaming of a career in chemical physics. Thanks to an elective course on applications of lasers in chemistry and physics, which also required a literature study and report, I had found that a revolution in chemical physics was underway, with many groups clamouring to conquer new territory in the study of chemical reactions: the elusive and fleeting transition state. My interest in this emerging field dictated my choices of potential graduate schools, with Caltech and the group of Ahmed Zewail at the top of my list

Heat-shock responsive genes identified and validated in Atlantic cod (Gadus morhua) liver, head kidney and skeletal muscle using genomic techniques

Background: Daily and seasonal changes in temperature are challenges that fish within aquaculture settings cannot completely avoid, and are known to elicit complex organismal and cellular stress responses. We conducted a large-scale gene discovery and transcript expression study in order to better understand the genes that are potentially involved in the physiological and cellular aspects of stress caused by heat-shock. We used suppression subtractive hybridization (SSH) cDNA library construction and characterization to identify transcripts that were dysregulated by heat-shock in liver, skeletal muscle and head kidney of Atlantic cod. These tissues were selected due to their roles in metabolic regulation, locomotion and growth, and immune function, respectively. Fish were exposed for 3 hours to an 8°C elevation in temperature, and then allowed to recover for 24 hours at the original temperature (i.e. 10°C). Tissue samples obtained before heat-shock (BHS), at the cessation of heat-shock (CS), and 3, 12, and 24 hours after the cessation of heat-shock (ACS), were used for reciprocal SSH library construction and quantitative reverse transcription - polymerase chain reaction (QPCR) analysis of gene expression using samples from a group that was transferred but not heat-shocked (CT) as controls.Results: We sequenced and characterized 4394 ESTs (1524 from liver, 1451 from head kidney and 1419 from skeletal muscle) from three "forward subtracted" libraries (enriched for genes up-regulated by heat-shock) and 1586 from the liver "reverse subtracted" library (enriched for genes down-regulated by heat-shock), for a total of 5980 ESTs. Several cDNAs encoding putative chaperones belonging to the heat-shock protein (HSP) family were found in these libraries, and "protein folding" was among the gene ontology (GO) terms with the highest proportion in the libraries. QPCR analysis of HSP90α and HSP70-1 (synonym: HSPA1A) mRNA expression showed significant up-regulation in all three tissues studied. These transcripts were more than 100-fold up-regulated in liver following heat-shock. We also identified HSP47, GRP78 and GRP94-like transcripts, which were significantly up-regulated in all 3 tissues studied. Toll-like receptor 22 (TLR22) transcript, found in the liver reverse SSH library, was shown by QPCR to be significantly down-regulated in the head kidney after heat-shock.Conclusion: Chaperones are an important part of the cellular response to stress, and genes identified in this work may play important roles in resistance to thermal-stress. Moreover, the transcript for one key immune response gene (TLR22) was down-regulated by heat-shock, and this down-regulation may be a component of heat-induced immunosuppression

Expression and functional profiling reveal distinct gene classes involved in fatty acid metabolism

Cells respond to fatty acid exposure by metabolic reorganization and proliferation of peroxisomes. Described here is the development and application of a genome-wide screen to identify nonessential yeast genes necessary for efficient metabolism of myristic and oleic acids. Comparison of the resultant fitness data set with an integrated data set of genes transcriptionally responsive to fatty acids revealed very little overlap between the data sets. Furthermore, the fitness data set enriched for genes involved in peroxisome biogenesis and other processes related to cell morphology, whereas the expression data set enriched for genes related to metabolism. These data suggest that in response to fatty acid exposure, transcriptional control is biased towards metabolic reorganization, and structural changes tend to be controlled post-transcriptionally. They also suggest that fatty acid responsive metabolic networks are more robust than those related to cell structure. Statistical analyses of these and other global data sets suggest that the utilization of distinct control mechanisms for the execution of morphological versus metabolic responses is widespread

Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMP

The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication-dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat cis elements within the bidirectional histone3–histone4 promoter direct HLB formation in Drosophila. In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X chromosome. Therefore, CLAMP binding to GA repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome

Use of terrestrial field studies in the derivation of bioaccumulation potential of chemicals

Field-based studies are an essential component of research addressing the behavior of organic chemicals, and a unique line of evidence that can be used to assess bioaccumulation potential in chemical registration programs and aid in development of associated laboratory and modeling efforts. To aid scientific and regulatory discourse on the application of terrestrial field data in this manner, this article provides practical recommendations regarding the generation and interpretation of terrestrial field data. Currently, biota-to-soil-accumulation factors (BSAFs), biomagnification factors (BMFs), and bioaccumulation factors (BAFs) are the most suitable bioaccumulation metrics that are applicable to bioaccumulation assessment evaluations and able to be generated from terrestrial field studies with relatively low uncertainty. Biomagnification factors calculated from field-collected samples of terrestrial carnivores and their prey appear to be particularly robust indicators of bioaccumulation potential. The use of stable isotope ratios for quantification of trophic relationships in terrestrial ecosystems needs to be further developed to resolve uncertainties associated with the calculation of terrestrial trophic magnification factors (TMFs). Sampling efforts for terrestrial field studies should strive for efficiency, and advice on optimization of study sample sizes, practical considerations for obtaining samples, selection of tissues for analysis, and data interpretation is provided. Although there is still much to be learned regarding terrestrial bioaccumulation, these recommendations provide some initial guidance to the present application of terrestrial field data as a line of evidence in the assessment of chemical bioaccumulation potential and a resource to inform laboratory and modeling efforts

Aerial Seismology Using Balloon-Based Barometers

Seismology on Venus has long eluded planetary scientists due to extreme temperature and pressure conditions on its surface, which most electronics cannot withstand for mission durations required for ground-based seismic studies. We show that infrasonic (low-frequency) pressure fluctuations, generated as a result of ground motion, produced by an artificial seismic source known as a seismic hammer, and recorded using sensitive microbarometers deployed on a tethered balloon, are able to replicate the frequency content of ground motion. We also show that weak, artificial seismic activity thus produced may be geolocated by using multiple airborne barometers. The success of this technique paves the way for balloon-based aero-seismology, leading to a potentially revolutionary method to perform seismic studies from a remote airborne station on the earth and solar system objects with substantial atmospheres such as Venus and Titan

Ozone-CO Correlations Determined by the TES Satellite Instrument in Continental Outflow Regions

Collocated measurements of tropospheric ozone (O3) and carbon monoxide (CO) from the Tropospheric Emission Spectrometer (TES) aboard the EOS Aura satellite provide information on O3-CO correlations to test our understanding of global anthropogenic influence on O3. We examine the global distribution of TES O3-CO correlations in the middle troposphere (618 hPa) for July 2005 and compare to correlations generated with the GEOS-Chem chemical transport model and with ICARTT aircraft observations over the eastern United States (July 2004). The TES data show significant O3-CO correlations downwind of polluted continents, with dO3/dCO enhancement ratios in the range 0.4–1.0 mol mol−1 and consistent with ICARTT data. The GEOS-Chem model reproduces the O3-CO enhancement ratios observed in continental outflow, but model correlations are stronger and more extensive. We show that the discrepancy can be explained by spectral measurement errors in the TES data. These errors will decrease in future data releases, which should enable TES to provide better information on O3-CO correlations.Earth and Planetary SciencesEngineering and Applied Science

Ozone-CO Correlations Determined by the TES Satellite Instrument in Continental Outflow Regions

Collocated measurements of tropospheric ozone (O3) and carbon monoxide (CO) from the Tropospheric Emission Spectrometer (TES) aboard the EOS Aura satellite provide information on O3-CO correlations to test our understanding of global anthropogenic influence on O3. We examine the global distribution of TES O3-CO correlations in the middle troposphere (618 hPa) for July 2005 and compare to correlations generated with the GEOS-Chem chemical transport model and with ICARTT aircraft observations over the eastern United States (July 2004). The TES data show significant O3-CO correlations downwind of polluted continents, with dO3/dCO enhancement ratios in the range 0.4–1.0 mol mol−1 and consistent with ICARTT data. The GEOS-Chem model reproduces the O3-CO enhancement ratios observed in continental outflow, but model correlations are stronger and more extensive. We show that the discrepancy can be explained by spectral measurement errors in the TES data. These errors will decrease in future data releases, which should enable TES to provide better information on O3-CO correlations.Earth and Planetary SciencesEngineering and Applied Science