Energy expenditure and weight-related behaviors in youth with Down syndrome: a protocol

BackgroundThe consequences of obesity are ominous, yet healthcare professionals are not adequately preventing or treating obesity in youth with Down syndrome (DS). Total daily energy expenditure (TDEE) is the energy expended in 24 h through physical activity and life-sustaining physiologic processes. An individual's TDEE is essential for determining the daily caloric intake needed to maintain or change body weight. Successful prevention and treatment of obesity in youth with DS is severely compromised by the lack of data on TDEE and information on weight-related behaviors for this high-risk population. This manuscript describes the protocol for the federally funded study that is in process to determine daily energy expenditure in a large cohort of children with DS.MethodsThis observational cross-sectional study will include a national sample of 230 youth with DS, stratified by age (5–11 and 12–18 years of age) and sex. Doubly Labeled Water analysis will provide the criterion body fat%, fat-free mass, and TDEE. To increase accessibility and decrease the burden on participants, the entire study, including obtaining consent and data collection, is conducted virtually within the participant's home environment on weekdays and weekends. The study team supervises all data collection via a video conferencing platform, e.g., Zoom. This study will (1) examine and determine average TDEE based on age and sex, (2) develop a prediction equation based on measured TDEE to predict energy requirements with a best-fit model based on fat-free mass, sex, age, and height and/or weight, and (3) use 24-hour dietary recalls, a nutrition and physical activity screener, wearable devices, and sleep questionnaire to describe the patterns and quality of dietary intake, sleep, and physical activity status in youth with DS.DiscussionThe lack of accurate information on energy expenditure and weight-related behaviors in youth with DS significantly impedes the successful prevention and treatment of obesity for this vulnerable population. The findings of this study will provide a further understanding of weight-related behaviors as obesity risk factors, currently not well understood for this population. This study will advance the science of weight management in individuals with disabilities and shift clinical practice paradigms

SLI-1 Cbl Inhibits the Engulfment of Apoptotic Cells in C. elegans through a Ligase-Independent Function

The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway, which includes the small GTPase CED-10 Rac and the cytoskeletal regulator ABI-1, acts to rearrange the cytoskeleton of the engulfing cell. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The second pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Cbl, the mammalian homolog of the C. elegans E3 ubiquitin ligase and adaptor protein SLI-1, interacts with Rac and Abi2 and modulates the actin cytoskeleton, suggesting it might act in engulfment. Our genetic studies indicate that SLI-1 inhibits apoptotic cell engulfment and DTC migration independently of the CED-10 Rac and CED-1 pathways. We found that the RING finger domain of SLI-1 is not essential to rescue the effects of SLI-1 deletion on cell migration, suggesting that its role in this process is ubiquitin ligase-independent. We propose that SLI-1 opposes the engulfment of apoptotic cells via a previously unidentified pathway.National Cancer Institute (U.S.) (Award K08CA104890

Orbits of promotion and rowmotion on order ideal

In this paper, we study operations known as promotion and rowmotion,\ud which act on the linear extensions and order ideals of a poset. In particular, we are interested in the orbits of these operations on various types of posets. The orbit structure of promotion is in some cases better understood than that of rowmotion,\ud so we can learn about rowmotion by connecting it to promotion. We give a\ud correspondence between the action of promotion on posets that are the direct sum of two chains and the action of rowmotion on posets that are the product of two\ud chains, and show that their orbit structures are the same. Then, we generalize this\ud correspondence to connect the operations on more general classes of posets. Finally, we study the orbit structure of rowmotion on products of three chains

Labeling DNA replication foci to visualize chromosome territories in vivo

<p>First larval stage (L1) worms were anaesthetized and viewed using DIC microscopy. The numbers of cell corpses in the heads were counted. s.d., standard deviation. <i>p-</i>Values refer to comparisons between the double mutant and accompanying triple mutant strains.</p

Core molecular pathways required for the engulfment of apoptotic cells.

<p>Proteins of the CED-10 Rac pathway are labeled in yellow. Proteins of the CED-1 pathway are labeled in green. <i>C. elegans</i> protein names are indicated above and their mammalian homologs below. The Wave Regulatory Complex (WRC) contains ABI-1, GEX-2, GEX-3, WVE-1 and NUO-3. The dashed arrow from CED-6 to CED-10 indicates that CED-1, CED-6 and CED-7 might also signal through CED-10 <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003115#pgen.1003115-Kinchen1" target="_blank">[6]</a>. The CED-1 pathway is required for engulfment only, whereas the CED-10 Rac pathway is required for both engulfment and DTC migration.</p

<i>sli-1</i> does not affect the timing of deaths or morphology of cell corpses.

<p>(A) The number and time of appearance of apoptotic cell corpses that occurred from the first cell death to the comma stage were recorded at 3-min intervals in wild-type and <i>sli-1(sy143)</i> animals using time-lapse DIC microscopy (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003115#s4" target="_blank">Materials and Methods</a>). Mean numbers of corpses at each time point were calculated from three embryos for both wild-type and <i>sli-1(sy143)</i> animals. Statistical analysis was by the Wilcoxon rank-sum test. The curves are similar (<i>p</i>>0.05). (B) The duration of cell-corpse visibility is similar in wild-type and <i>sli-1(sy143)</i> embryos. The percentage of cell corpses visible for a given period was recorded. The duration of appearance of all cell corpses recorded from three wild-type (n = 159 cell corpses) and three <i>sli-1(sy143)</i> (n = 154) embryos was analyzed. Statistical analysis was by the Wilcoxon rank-sum test. The curves are similar (p>0.5). (C) The morphology of cell corpses in wild-type and <i>sli-1(sy143)</i> embryos are similar. Arrowheads, apoptotic corpses. Embryos were at similar stages of development, approximately six minutes prior to the comma stage. Bar = 5 microns.</p

Overexpression of <i>sli-1</i> reverses the effect of <i>sli-1(sy143)</i> on engulfment in <i>ced-10(n1993); sli-1(sy143)</i> animals.

<p><i>ced-10(n1993); sli-1(sy143)</i> embryos containing the transgenes indicated above were heat shocked at 33°C for 1 hour and then allowed to recover for 3–3.5 hours at 20°<i>C.</i> The numbers of cell corpses in the heads of anaesthetized first larval stage (L1) worms were counted using DIC microscopy within 0.5 h of hatching. The number of persistent corpses was determined from two independent transgenic lines for each transgene except for P<i>_hspsli-1ΔRING</i> (see text for explanation). s.d., standard deviation.</p

A <i>let-60</i> Ras gain-of-function mutation does not affect apoptotic cell engulfment.

<p>A <i>let-60</i> Ras gain-of-function mutation does not affect apoptotic cell engulfment.</p

Loss of <i>sli-1</i> function suppresses engulfment and DTC migration defects in an <i>abi-1</i> loss-of-function mutant.

<p>(A) The heads of <i>ced-1(e1735)</i> L1 animals with or without the <i>sli-1(sy143)</i> mutation and with or without treatment with <i>abi-1</i> feeding RNAi were scored for engulfment defects using DIC microscopy. The mean ± standard deviation (s.d.) is indicated within each bar. Error bars are sd. <i>p</i> values derived using Student's t test are shown. At least 15 animals were analyzed for each genotype. (B) The heads of <i>ced-5(n1812)</i> L1 animals with or without the <i>sli-1(sy143)</i> and/or <i>abi-1(tm494)</i> mutations were scored as in (A). At least 15 animals were analyzed for each genotype. (C) The gonads of <i>ced-5(n1812)</i> young adult worms with and without mutations in <i>sli-1(sy143)</i> and/or <i>abi-1(tm494)</i> were scored for morphology using DIC microscopy. More than 80 gonad arms were scored for all genotypes. <i>p</i> values derived using Fisher's exact test are shown.</p

The TKB domain of <i>sli-1</i> is required for its cell migration function.

<p>(A) Truncation minigene <i>sli-1</i> constructs used in this study. Red lines represent proline-rich areas. L, conserved linker domain between the TKB domain (composed of the 4H, EF hand and SH2 domains) and the RING finger. (B) The gonads of <i>ced-10(n1993); sli-1(sy143)</i> young adult animals with or without transgenic arrays containing the genes shown in (A) were scored for abnormal morphology after heat shock. 200 gonad arms in two independent strains were analyzed per genotype. <i>p</i> values derived using Fisher's exact test are shown.</p