C. elegans life cycle and developmental stages

<p><strong>A.</strong> <em>C. elegans</em> life cycle at 25 ˚C. Worms are drawn approximately to scale. Modified from Altun and Hall (2012). <strong>B.</strong> Micrographs of laid eggs, larval stages and adults. Modified from Fielenbach and Antebi (2008).</p> <p><strong>References:</strong></p> <p>Z. F. Altun and D. H. Hall (2012) Handbook of <em>C. elegans</em> Anatomy. In WormAtlas. http://www.wormatlas.org/hermaphrodite/hermaphroditehomepage.htm</p> <p>N. Fielenbach and A. Antebi (2008) <em>C. elegans</em> dauer formation and the molecular basis of plasticity. Genes and Development, 22(16):2149–2165</p

Custom reference transcriptome for transgenic mouse genome based on mm10

&lt;p&gt;&lt;span&gt;Reads were aligned to this custom reference genome, which was created based on the mouse mm10 reference genome v1.2.0 provided by 10x Genomics. Firstly, sequences for transgenes Sgcb1a1 (3&rsquo; of ER + 130 bp linker + 3&rsquo; UTR of Scgb1a1), Sftpc (rtTA-M2 coding sequence) and DTA were added to the reference genome FASTA file. Subsequently, the endogenous Esr1 (genomic position Chr10:4611989-5005614) and 3&rsquo; UTR of Scgb1a1 (genomic position Chr19:9083642-9083739) were masked from the genome. Then, three lines corresponding to the newly-added transgene sequences were added to the reference genome GTF file. Lastly, Cell Ranger was used to create the reference genome package from the modified FASTA and GTF files.&lt;/span&gt;&lt;/p&gt

Association between endometriosis and increased arterial stiffness

Background: Endometriosis is a common gynecologic disease associated with systemic inflammation and atherogenic risk factors. Therefore, women with endometriosis may have increased cardiovascular risk. Aims: We aimed to evaluate arterial stiffness using cardio–ankle vascular index (CAVI) in women with and without endometriosis. Methods: We enrolled 44 patients with endometriosis and 76 age‑matched controls without endometriosis.Endometriosis was diagnosed based on histopathologic examination or magnetic resonance imaging. Arterial stiffness was evaluated using CAVI in all study participants. Results: No differences were observed between patients and controls in terms of age (median [interquartile range, IQR], 30 [24.25–5] years and 26 years [24–35] years, respectively), body mass index (median [IQR], 23.31 [20.82–24.98] kg/m2 and 23.74 [21.13–26.78] kg/m2, respectively), or waist circumference (median [IQR], 69 [64–75] cm and 72 [65–81.25] cm, respectively). C‑reactive protein levels were higher in women with endometriosis than in controls (median [IQR], 0.27 [0.14–0.68] mg/dl vs 0.12 [0.06–0.24] mg/dl; P &lt; 0.001). Left ventricular ejection fraction, left ventricular mass index (LVMI), relative wall thickness, as well as systolic and diastolic blood pressures were similar in both groups. Women with endometriosis had higher CAVI than controls (mean [SD], 5.961 [0.644] vs 5.554 [0.654]; P = 0.001). Elevated arterial stiffness was observed in the endometriosis group also after adjustment for age and LVMI. Conclusions: Our results indicate increased arterial stiffness measured by CAVI in women with endometriosis. Therefore,clinicians should be aware that these patients may be at increased cardiovascular risk

Molecular Strategies of the <i>Caenorhabditis elegans</i> Dauer Larva to Survive Extreme Desiccation

<div><p>Massive water loss is a serious challenge for terrestrial animals, which usually has fatal consequences. However, some organisms have developed means to survive this stress by entering an ametabolic state called anhydrobiosis. The molecular and cellular mechanisms underlying this phenomenon are poorly understood. We recently showed that <i>Caenorhabditis elegans</i> dauer larva, an arrested stage specialized for survival in adverse conditions, is resistant to severe desiccation. However, this requires a preconditioning step at a mild desiccative environment to prepare the organism for harsher desiccation conditions. A systems approach was used to identify factors that are activated during this preconditioning. Using microarray analysis, proteomics, and bioinformatics, genes, proteins, and biochemical pathways that are upregulated during this process were identified. These pathways were validated via reverse genetics by testing the desiccation tolerances of mutants. These data show that the desiccation response is activated by hygrosensation (sensing the desiccative environment) via head neurons. This leads to elimination of reactive oxygen species and xenobiotics, expression of heat shock and intrinsically disordered proteins, polyamine utilization, and induction of fatty acid desaturation pathway. Remarkably, this response is specific and involves a small number of functional pathways, which represent the generic toolkit for anhydrobiosis in plants and animals.</p> </div

The Role of Phospholipid Headgroup Composition and Trehalose in the Desiccation Tolerance of <i>Caenorhabditis elegans</i>

Anhydrobiotic organisms have the remarkable ability to lose extensive amounts of body water and survive in an ametabolic state. Distributed to various taxa of life, these organisms have developed strategies to efficiently protect their cell membranes and proteins against extreme water loss. Recently, we showed that the dauer larva of the nematode <i>Caenorhabditis elegans</i> is anhydrobiotic and accumulates high amounts of trehalose during preparation to harsh desiccation (preconditioning). Here, we have used this genetic model to study the biophysical manifestations of anhydrobiosis and show that, in addition to trehalose accumulation, dauer larvae dramatically reduce their phosphatidylcholine (PC) content. The chemical composition of the phospholipids (PLs) has key consequences not only for their interaction with trehalose, as we demonstrate with Langmuir–Blodgett monolayers, but also, the kinetic response of PLs to hydration transients is strongly influenced as evidenced by time-resolved FTIR spectroscopy. PLs from preconditioned larvae with reduced PC content exhibit a higher trehalose affinity, a stronger hydration-induced gain in acyl chain free volume, and a wider spread of structural relaxation rates of their lyotropic transitions and sub-headgroup H-bond interactions. The different hydration properties of PC and phosphatidylethanolamine (PE) headgroups are crucial for the hydration-dependent rearrangement of the trehalose-mediated H-bond network. As a consequence, the compressibility modulus of PLs from preconditioned larvae is about 2.6-fold smaller than that from non-preconditioned ones. Thus, the biological relevance of reducing the PC:PE ratio by PL headgroup adaptation should be the preservation of plasma membrane integrity by relieving mechanical strain from desiccated trehalose-containing cells during fast rehydration

Novel DTR proteins and putative elements of the hygrosensation pathway involved in desiccation tolerance.

<p>Novel DTR proteins and putative elements of the hygrosensation pathway involved in desiccation tolerance.</p

Analysis of desiccation-induced DTR mRNAs.

<p>(A) Fold change clustering of upregulated (green area) and downregulated (pink area) genes. The very low FCC was discarded because the differential expression was too low. The number of genes (<i>n</i>) in each group is shown. (B) Hierarchical clustering of the 64 highly upregulated genes (blue region in panel A). Red/green column shows log₂ expression levels before (–) and after (+) preconditioning, cyan column shows log₂ fold changes for the genes indicated on the right. Color codes for the heat map are shown top left. Main branches of the dendrogram are labeled ‘a’ (light gray) and ‘b’ (dark gray, see the text for details). Highlighted genes reside in essential anhydrobiotic pathways shown in the legend with unique color codes, which are consistent in the following figures. (C) The trehalose biosynthesis pathway is upregulated in <i>C</i>. <i>elegans</i> upon desiccation stress. Enzymes that catalyze each reaction are shown with the corresponding differential expression values of their transcripts upon preconditioning. These fold changes are shown in green, red, and blue for upregulation, downregulation, and no change, respectively. Glucose-6-phosphate synthesis from lipids involves several steps; therefore, a dashed arrow is used. Highlighted genes are found in the high FCC (panel B). Glc, Glucose; Glc-6-P, glucose-6-phosphate; Glc-1-P, glucose-1-phosphate; UDP-Glc, UDP-glucose; Tre-6-P, trehalose-6-phosphate; Tre, trehalose.</p

Suggested model of the main strategies of desiccation tolerance in <i>C</i>.

<div><p><b><i>elegans</i></b>. </p> <p>The hypometabolic dauer larva senses a decrease in ambient humidity, perhaps via head neurons, and initiates a desiccation response at different levels. As a result of this, ROS and xenobiotics are eliminated, proteins and membranes are stabilized, and other essential functions are fulfilled. The ametabolic transition (anhydrobiosis) can only succeed under these conditions.</p></div