Friedmantucker8057

Ultracold preservation is widely used for storage of genetic stocks of Caenorhabditis elegans Current cryopreservation protocols are vulnerable to refrigeration failures, which can result in the loss of stock viability due to damage during re-freezing. Here we present a method for preserving worms in a dehydrated and frozen form that retains viability after multiple freeze-thaw cycles. After dehydration in the presence of trehalose or glycerol, C. elegans stocks can be frozen and thawed multiple times while maintaining viability. While both dauer and non-dauer larvae survive desiccation and freezing, the dauer defective mutant daf-16 does not survive desiccation. Our technique is useful for storing stocks in a manner robust to freezer failures, and potentially for shipping strains between laboratories.The aim of the current study was to evaluate the effect of sustained physiologic increase of ∼50 mg/dL in plasma glucose concentration on insulin secretion in normal glucose-tolerant (NGT) subjects. Twelve NGT subjects without family history of type 2 diabetes mellitus (T2DM; FH-) and 8 NGT with family history of T2DM (FH+) received an oral glucose tolerance test and two-step hyperglycemic clamp (100 and 300 mg/dL) followed by intravenous arginine bolus before and after 72-h glucose infusion. Fasting plasma glucose increased from 94 ± 2 to 142 ± 4 mg/dL for 72 h. First-phase insulin secretion (0-10 min) increased by 70%, while second-phase insulin secretion during the first (10-80 min) and second (90-160 min) hyperglycemic clamp steps increased by 3.8-fold and 1.9-fold, respectively, following 72 h of physiologic hyperglycemia. Insulin sensitivity during hyperglycemic clamp declined by ∼30% and ∼55% (both P less then 0.05), respectively, during the first and second hyperglycemic clamp steps. Insulin secretion/insulin resistance (disposition) index declined by 60% (second clamp step) and by 62% following arginine (both P less then 0.005) following 72-h glucose infusion. The effect of 72-h glucose infusion on insulin secretion and insulin sensitivity was similar in subjects with and without FH of T2DM. Following 72 h of physiologic hyperglycemia, metabolic clearance rate of insulin was markedly reduced (P less then 0.01). AP-III-a4 molecular weight These results demonstrate that sustained physiologic hyperglycemia for 72 h 1) increases absolute insulin secretion but impairs β-cell function, 2) causes insulin resistance, and 3) reduces metabolic clearance rate of insulin.The causal genetic underpinnings of congenital heart diseases, which are often complex and multigenic, are still far from understood. Moreover, there are also predominantly monogenic heart defects, such as cardiomyopathies, with known disease genes for the majority of cases. In this study, we identified mutations in myomesin 2 (MYOM2) in patients with Tetralogy of Fallot (TOF), the most common cyanotic heart malformation, as well as in patients with hypertrophic cardiomyopathy (HCM), who do not exhibit any mutations in the known disease genes. MYOM2 is a major component of the myofibrillar M-band of the sarcomere, and a hub gene within interactions of sarcomere genes. We show that patient-derived cardiomyocytes exhibit myofibrillar disarray and reduced passive force with increasing sarcomere lengths. Moreover, our comprehensive functional analyses in the Drosophila animal model reveal that the so far uncharacterized fly gene CG14964 [herein referred to as Drosophila myomesin and myosin binding protein (dMnM)] may be an ortholog of MYOM2, as well as other myosin binding proteins. Its partial loss of function or moderate cardiac knockdown results in cardiac dilation, whereas more severely reduced function causes a constricted phenotype and an increase in sarcomere myosin protein. Moreover, compound heterozygous combinations of CG14964 and the sarcomere gene Mhc (MYH6/7) exhibited synergistic genetic interactions. In summary, our results suggest that MYOM2 not only plays a critical role in maintaining robust heart function but may also be a candidate gene for heart diseases such as HCM and TOF, as it is clearly involved in the development of the heart.This article has an associated First Person interview with Emilie Auxerre-Plantié and Tanja Nielsen, joint first authors of the paper.

Nausea and vomiting are common symptoms for patients with advanced cancer. While there is evidence for acupuncture point stimulation for treatment of these symptoms for patients having anticancer treatment, there is little for when they are not related to such treatment.

To determine whether acupressure at the pericardium 6 site can help in the treatment of nausea and vomiting suffered by palliative care patients with advanced cancer.

Double blind randomised controlled trial-active versus placebo acupressure wristbands. In-patients with advanced cancer in two specialist palliative care units who fitted either or both of the following criteria were approached Nausea that was at least moderate; Vomiting daily on average for the prior 3 days.

57 patients were randomised to have either active or placebo acupressure wristbands. There was no difference in any of the outcome measures between the two groups change from baseline number of vomits; Visual Analogue Scale for 'did acupressure wristbands help you to feel better?'; total number of as needed doses of antiemetic medication; need for escalation of antiemetics.

In contrast to a previously published feasibility study, active acupressure wristbands were no better than placebo for specialist palliative care in-patients with advanced cancer and nausea and vomiting.

In contrast to a previously published feasibility study, active acupressure wristbands were no better than placebo for specialist palliative care in-patients with advanced cancer and nausea and vomiting.Rapid plant genome evolution is crucial to adapt to environmental changes. Chromosomal rearrangements and gene copy number variation (CNV) are two important tools for genome evolution and sources for the creation of new genes. However, their emergence takes many generations. In this study, we show that in Arabidopsis thaliana, a significant loss of ribosomal RNA (rRNA) genes with a past history of a mutation for the chromatin assembly factor 1 (CAF1) complex causes rapid changes in the genome structure. Using long-read sequencing and microscopic approaches, we have identified up to 15 independent large tandem duplications in direct orientation (TDDOs) ranging from 60 kb to 1.44 Mb. Our data suggest that these TDDOs appeared within a few generations, leading to the duplication of hundreds of genes. By subsequently focusing on a line only containing 20% of rRNA gene copies (20rDNA line), we investigated the impact of TDDOs on 3D genome organization, gene expression, and cytosine methylation. We found that duplicated genes often accumulate more transcripts.