Pennsylvania Folklife Vol. 34, No. 4

• Coverlets • Sign Painting • Reverse Painting on Glass • Kites • Snake Lore • Horncraft • Weathervanes and Country Signs • Festival Focus • Sheep Shearing & Natural Knits • Bread Baking Among the Pennsylvania Dutch • The Craft of Rushing • Toy Soldier Casting • Pennsylvania Dutch Humor • Fireside Brooms and Whirligigs • Springerlehttps://digitalcommons.ursinus.edu/pafolklifemag/1108/thumbnail.jp

Bioavailability of Macro and Micronutrients Across Global Topsoils: Main Drivers and Global Change Impacts

Understanding the chemical composition of our planet\u27s crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro- and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome-dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling-atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world

Effectiveness and Utilization of Cardiac Rehabilitation Among People With CKD

Introduction: Cardiac rehabilitation (CR) is a proven therapy for reducing cardiovascular death and hospitalization. Whether CR participation is associated with improved outcomes in patients with chronic kidney disease (CKD) is unknown. Methods: We obtained data on all adult patients in Calgary, Alberta, Canada with angiographically proven coronary artery disease from 1996 to 2016 referred to CR from The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and TotalCardiology Rehabilitation. An estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or kidney replacement therapy defined CKD. Predictors of CR use were estimated with multinomial logistic regression. The association between starting versus not starting and completion versus noncompletion of CR and clinical outcomes were estimated using multivariable Cox proportional hazards models. Results: Of 23,215 patients referred to CR, 12,084 were eligible for inclusion. Participants with CKD (N = 1322) were older, had more comorbidity, lower exercise capacity on graded treadmill testing, and took longer to be referred and to start CR than those without CKD. CKD predicted not starting CR: odds ratio 0.73 (95% confidence interval [CI] 0.64–0.83). Over a median 1 year follow-up, there were 146 deaths, 40 (0.3%) from CKD and 106 (1.0%) not from CKD. Similar to those without CKD, the risk of death was lower in CR completers (hazard ratio [HR] 0.24 [95% CI 0.06–0.91) and starters (HR 0.56 [95% CI 0.29– 1.10]) with CKD. Conclusion: CR participation was associated with comparable benefits in people with moderate CKD as those without who survived to CR. Lower rates of CR attendance in this high-risk population suggest that strategies to increase CR utilization are needed

Deletion of Dystrophin In-Frame Exon 5 Leads to a Severe Phenotype: Guidance for Exon Skipping Strategies.

Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease. Exceptions to the dystrophin reading frame rule are usually resolved after molecular diagnosis on muscle RNA. We report a moderate/severe Becker muscular dystrophy patient with an in-frame genomic deletion of DMD exon 5. This mutation has been reported by others as resulting in Duchenne or Intermediate muscular dystrophy, and the loss of this in-frame exon in one patient led to multiple splicing events, including omission of exon 6, that disrupts the open reading frame and is consistent with a severe phenotype. The patient described has a deletion of dystrophin exon 5 that does not compromise recognition of exon 6, and although the deletion does not disrupt the reading frame, his clinical presentation is more severe than would be expected for classical Becker muscular dystrophy. We suggest that the dystrophin isoform lacking the actin-binding sequence encoded by exon 5 is compromised, reflected by the phenotype resulting from induction of this dystrophin isoform in mouse muscle in vivo. Hence, exon skipping to address DMD-causing mutations within DMD exon 5 may not yield an isoform that confers marked clinical benefit. Additional studies will be required to determine whether multi-exon skipping strategies could yield more functional dystrophin isoforms, since some BMD patients with larger in-frame deletions in this region have been reported with mild phenotypes

Additional file 2: of Incidence of sudden cardiac death in adults with end-stage renal disease: a systematic review and meta-analysis

Includes a table describing the characteristics of the included studies. (DOC 96 kb

Dystrophin and spectrin expression in patient and normal muscle.

<p><b>(a)</b> Dystrophin immunofluorescence using Novocastra Laboratories antibodies, NCL DYS-1 (upper row, specific for the rod domain) NCL DYS-2 (upper middle row, specific for the carboxy-terminus) and NCL-DYS 3 (lower middle row, specific for the amino-terminus) and spectrin (lower row) on patient (left panel) and normal human muscle (right panel) cryosections. Nuclei are stained with DAPI. (Bar = 100μm). (b) Western blot using NCL-DYS 1 to detect dystrophin in normal and patient muscle sample. (c) Sequencing of the <i>DMD</i> RT-PCR exon 1–10 amplicon from the exon 5-deletion patient showing the junction of <i>DMD</i> exons 4 and 6.</p

Antisense oligomer induced skipping of <i>DMD</i> exon 6 in patient and normal myogenic cells.

<p>Normal and <i>DMD exon 5 deletion</i> patient fibroblasts, forced into the myogenic lineage by transfection with the MyoD expressing adenovirus, were transfected with an AO designed to excise <i>DMD</i> exon 6. Dystrophin exons 1–10 were amplified from RNA prepared from control and oligomer (H6A(+69+91))-treated normal and patient RNA samples by nested RT-PCR. The full-length amplicon is 1157 bp, the amplicon derived by RT-PCR of patient RNA, missing exon 5, is 1064 bp. The induced amplicons missing exon 6 (normal) are 984 bp and 891 (patient). The RT-PCR generating the amplicons from the 100 nM transfection of patient cells was not efficient due to low RNA yields, but both full-length and skipped products are evident.</p

<i>DMD</i> deletion breakpoint characterization.

<p>(a) Amplification of patient and normal DNA with HIn4 F4 and the reverse primer targeted to exon 6 (HEx6ROuter), across the predicted <i>DMD</i> breakpoint location. A 1 kb DNA ladder was used as a marker to estimate amplicon sizes. (b) Alignment of nucleotide sequences from introns 4 and 5 showing the precise deletion breakpoint in the <i>DMD</i> exon 5 deletion patient. The size of the deletion is estimated, relative to the reference sequence <u>NG_012232.1</u>. (c) Representation of three <i>DMD</i> exon 5 deletions, showing deletion breakpoints. The patient described in the current study has the largest genomic deletion, 10.8 kb and the breakpoint downstream of exon 5 is located between the breakpoints in previously reported individuals, with 3.4 and 7.78 kb deletions [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145620#pone.0145620.ref013" target="_blank">13</a>].</p

AO-mediated induction of <i>Dmd</i> exon 5 deletion dystrophin isoform in wild type mice.

<p><b>(a)</b> Cryosections from diaphragm of <i>5-PPMOk</i> and sham treated C57BL10 mice, and sham treated <i>mdx</i> mice were stained to reveal dystrophin carboxy terminus (NCL DYS-2), β-dystroglycan (β-Dys), neuronal nitric oxide synthase (nNOS) and developmental myosin heavy chain (NCL-MHCd). Picro sirius red was used to stain collagen, as an indicator of fibrosis, and muscle architecture is revealed by hematoxylin and eosin (H&E) staining. (Bar = 200μm) (b) RT-PCR across <i>Dmd</i> exons 1–7 on RNA extracted from diaphragm of <i>5-PPMOk (n = 5)</i> and sham treated C57BL10 mice, and sham treated <i>mdx</i> mice. The percentage of induced amplicon (exon 5 deleted) as a percentage of the total transcript product is indicated. (c) Western blot on protein extracts (7.5μg total protein per lane) from diaphragm of <i>5-PPMOk (n = 5)</i> and sham treated C57BL10 mice, and sham treated <i>mdx</i> mice. Dystrophin was detected using NCL-Dys2 (Novocastra Laboratories) and Western Breeze (Life Technologies/Thermo Fisher Scientific). The percentage of dystrophin, relative to the wild type control, was assessed by densitometry after normalization to myosin heavy chain expression.</p