Effects of elevated carbon dioxide on primary productivity in a Mojave Desert ecosystem

Growth and gas exchange are predicted to be most responsive to future atmospheric CO2 concentrations within and ecosystems. It is hypothesized that elevated CO2 will result in enhanced seasonal growth, increased leaf area and extension of the growing season via increased water-use efficiency (WUE). Greater WUE could result in increased survivorship and productivity of desert shrubs, and may increase the importance of this biome in the global carbon budget. Elevated CO2 is also expected to influence future species distribution and abundance, which could alter structure and function, especially in arid ecosystems. For these reasons, we measured aboveground production, gas exchange, and water relations of species from different functional types in order to evaluate how future atmospheric CO2 concentrations may affect desert shrubs. Elevated CO2 significantly enhanced growth and gas exchange of the dominant evergreen perennial during an exceptionally wet year, but had less effect on spring- and summer-active drought-deciduous shrubs. During dry years, growth and seasonal carbon assimilation rates were much reduced across all functional types. Overall it appears that water availability strongly interacts with CO2 concentration to affect growth and gas exchange. As such, unpredictable and infrequent rainfall patterns typical of the desert southwest may prevent significant CO2 affects on growth in dry years. However, predictions of increased atmospheric CO 2 concentrations and rainfall in the desert southwest may have important implications for the future productivity of the region

Mice with endogenous TDP‐43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis

TDP-43 (encoded by the gene TARDBP) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP-43 function at physiological levels both in vitro and in vivo. Interestingly, we find that mutations within the C-terminal domain of TDP-43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP-43 loss- and gain-of-function effects. TDP-43 gain-of-function effects in these mice reveal a novel category of splicing events controlled by TDP-43, referred to as "skiptic" exons, in which skipping of constitutive exons causes changes in gene expression. In vivo, this gain-of-function mutation in endogenous Tardbp causes an adult-onset neuromuscular phenotype accompanied by motor neuron loss and neurodegenerative changes. Furthermore, we have validated the splicing gain-of-function and skiptic exons in ALS patient-derived cells. Our findings provide a novel pathogenic mechanism and highlight how TDP-43 gain of function and loss of function affect RNA processing differently, suggesting they may act at different disease stages. Keywords: ALS; cryptic exon; skiptic exon; splicing; TDP-4

Could antiretrovirals be treating EBV in MS? A case report

We present the case of an HIV-negative patient clinically diagnosed with relapsing-remitting MS who achieved significant disease improvement on Combivir (zidovudine/lamivudine). Within months of treatment, the patient reported complete resolution of previously unremitting fatigue and paresthesiae, with simultaneous improvements in lesion burden detected by MRI. All improvements have been sustained for more than three years. This response may be related to the action of zidovudine as a known inhibitor of EBV lytic DNA replication, suggesting future directions for clinical investigation. Keywords: Multiple sclerosis, Epstein-Barr viru

Lead toxicity and genetics in Flint, MI

It has been well established that lead poisoning, as defined by the CDC as blood lead levels (BLLs) at or above 5 μg/dl, can lead to long-term neurotoxic effects in children and requires immediate treatment. As such, the CDC has long recommended clinicians’ assess to all patients for lead exposure and test BLLs for all at-risk patients. Furthermore, it is increasingly recognised that there is no safe level of lead for children due to the irreversible lifelong detrimental effects of lead exposure.2,3 Since the disaster of lead contaminated drinking water in Flint, MI has been uncovered, action has been taken to test children for lead poisoning. However, when children are tested and results show that lead levels are below the 5 μg/dl criteria no further follow-up is conducted with these children, as they are deemed ‘healthy’. This practice is problematic, given that other studies have shown that blood lead levels, even at rates lower than the poison range can be detrimental to a child’s health. The estimated population of Flint is ~99,002, with about 27% of the residents categorised as children under the age of 18 years. Therefore, more than ~26,730 children, of whom 60% are African Americans (N=16,038), have been exposed to environmental lead in the drinking water.National Institute of Nursing Research (U.S.) (Grant NR013520

A perspective for sequencing familial hypercholesterolaemia in African Americans

African Americans suffer disproportionately from poor cardiovascular health outcomes despite similar proportions of African Americans and Americans of European ancestry experiencing elevated cholesterol levels. Some of the variation in cardiovascular outcomes is due to confounding effects of other risk factors, such as hypertension and genetic influence. However, genetic variants found to contribute to variation in serum cholesterol levels in populations of European ancestry are less likely to replicate in populations of African ancestry. To date, there has been limited follow-up on variant discrepancies or on identifying variants that exist in populations of African ancestry. African and African-American populations have the highest levels of genetic heterogeneity, which is a factor that must be considered when evaluating genetic variants in the burgeoning era of personalised medicine. Many of the large published studies identifying genetic variants associated with disease risk have evaluated populations of mostly European ancestry and estimated risk in other populations based on these findings. The purpose of this paper is to provide a perspective, using familial hypercholesterolaemia as an exemplar, that studies evaluating genetic variation focused within minority populations are necessary to identify factors that contribute to disparities in health outcomes and realise the full utility of personalised medicine

A. E. Housman: Fragment grške tragedije

Alfred Edward Housman (1859–1936), ki je kasneje postal angleški pesnik in eden največjih filologov svojega časa, je svoj zafrkantski »fragment« objavil pri triindvajsetih, leta 1883, v reviji Bromsgrovian. Revijo je izdajala Bromsgrove School, kjer se je šolal kot najstnik (1870–77); na šolo, ki je prva prepoznala njegov jezikovni in pesniški talent, se je za kratek čas (1881–82) vrnil kot pomožni učitelj po ne­pričakovanem študijskem porazu na Oxfordu. Kot ugotavlja Ralph Marcellino, ni naključje, da besedilo paro­dira predvsem Ajshila, ki je bil Housmanov najljubši pesnik. V njem odzvanja Oresteja, zlasti drami Agamemnon in Prinašalke pitnih darov, verjetno zato, ker so ju dijaki na šoli, kjer je poučeval, pri pouku največ brali. Prav ta ciljna publika je znala ceniti norčevanje iz retoričnih figur ter sintaktičnih konstrukcij, ki jim jih je njihov pomožni učitelj vbijal v glavo

Genome Sequencing Technologies and Nursing

Background Advances in DNA sequencing technology have resulted in an abundance of personalized data with challenging clinical utility and meaning for clinicians. This wealth of data has potential to dramatically impact the quality of healthcare. Nurses are at the focal point in educating patients regarding relevant healthcare needs; therefore, an understanding of sequencing technology and utilizing these data are critical. Aim The objective of this study was to explicate the role of nurses and nurse scientists as integral members of healthcare teams in improving understanding of DNA sequencing data and translational genomics for patients. Approach A history of the nurse role in newborn screening is used as an exemplar. Discussion This study serves as an exemplar on how genome sequencing has been utilized in nursing science and incorporates linkages of other omics approaches used by nurses that are included in this special issue. This special issue showcased nurse scientists conducting multi-omic research from various methods, including targeted candidate genes, pharmacogenomics, proteomics, epigenomics, and the microbiome. From this vantage point, we provide an overview of the roles of nurse scientists in genome sequencing research and provide recommendations for the best utilization of nurses and nurse scientists related to genome sequencing

Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues

We have analyzed the intracellular localization of transcripts from the myotonin protein kinase (Mt-PK) gene in fibroblasts and muscle biopsies from myotonic dystrophy patients and normal controls. In affected individuals, a trinucleotide expansion in the gene results in the phenotype, the severity of which is proportional to the repeat length. A fluorochrome-conjugated probe (10 repeats of CAG) hybridized specifically to this expanded repeat. Mt-PK transcripts containing CTG repeat expansions were detected in the nucleus as bright foci in DM patient fibroblasts and muscle biopsies, but not from normal individuals. These foci represented transcripts from the Mt-PK gene since they simultaneously hybridized to fluorochrome-conjugated probes to the 5\u27-end of the Mt-PK mRNA. A single oligonucleotide probe to the repeat and the sense strand each conjugated to different fluorochromes revealed the gene and the transcripts simultaneously, and indicated that these focal concentrations (up to 13 per nucleus) represented predominately posttranscriptional RNA since only a single focus contained both the DNA and the RNA. This concentration of nuclear transcripts was diagnostic of the affected state, and may represent aberrant processing of the RNA

Gene expression studies for the analysis of domoic acid production in the marine diatom Pseudo-nitzschia multiseries

Background: Pseudo-nitzschia multiseries Hasle (Hasle) (Ps-n) is distinctive among the ecologically important marine diatoms because it produces the neurotoxin domoic acid. Although the biology of Ps-n has been investigated intensely, the characterization of the genes and biochemical pathways leading to domoic acid biosynthesis has been limited. To identify transcripts whose levels correlate with domoic acid production, we analyzed Ps-n under conditions of high and low domoic acid production by cDNA microarray technology and reverse-transcription quantitative PCR (RT-qPCR) methods. Our goals included identifying and validating robust reference genes for Ps-n RNA expression analysis under these conditions. Results: Through microarray analysis of exponential- and stationary-phase cultures with low and high domoic acid production, respectively, we identified candidate reference genes whose transcripts did not vary across conditions. We tested eleven potential reference genes for stability using RT-qPCR and GeNorm analyses. Our results indicated that transcripts encoding JmjC, dynein, and histone H3 proteins were the most suitable for normalization of expression data under conditions of silicon-limitation, in late-exponential through stationary phase. The microarray studies identified a number of genes that were up- and down-regulated under toxin-producing conditions. RT-qPCR analysis, using the validated controls, confirmed the up-regulation of transcripts predicted to encode a cycloisomerase, an SLC6 transporter, phosphoenolpyruvate carboxykinase, glutamate dehydrogenase, a small heat shock protein, and an aldo-keto reductase, as well as the down-regulation of a transcript encoding a fucoxanthin-chlorophyll a-c binding protein, under these conditions. Conclusion: Our results provide a strong basis for further studies of RNA expression levels in Ps-n, which will contribute to our understanding of genes involved in the production and release of domoic acid, an important neurotoxin that affects human health as well as ecosystem function.Plymouth State University Graduate Programs OfficeWoods Hole Oceanographic Institution Academic Programs OfficeNew Hampshire IDeA Network of Biological Research Excellence (NH-INBRE)National Center for Research Resources (U.S.) (Grant 5P20RR030360-03)National Institute of General Medical Sciences (U.S.) (Grant 8P20GM103506-03