A barrier in the children’s environmental health field has been the lack of early-warning systems to identify risks of childhood illness and developmental disorders. We aimed to develop a methodology to identify an accessible biomarker measured in a small amount of blood to distinguish newborns at elevated risk from a toxic prenatal exposure, using air pollutants as a case study. Because air pollutants are associated with altered DNA methylation, we developed a pipeline using DNA methylation signatures measured in umbilical cord blood, which could be used as predictors of prenatal exposure. We used air pollution indicators, including modelled trimester-specific and pregnancy average NO2 and PM2.5, and DNA methylation signatures from Illumina arrays measured in two New York City-based longitudinal birth cohorts from the Columbia Centre for Children’s Environmental Health. We developed a screening plus three-part pipeline that incorporates selection, testing, and validation to identify whether DNA methylation can be used to predict exposure to prenatal air pollution indicators, NO2 and PM2.5. Exarafenib Applying this pipeline, we found that cord blood DNA methylation could be used to predict high vs. low average pregnancy NO2 (AUC = 0.60, 95% CI 0.52-0.68, with validation AUC = 0.60). Similar results were found for high vs. low third trimester NO2. In this proof of concept study using air pollutants as an example, we provide an approach (with a generalizable analytic pipeline) that can be used for prediction of prenatal exposure to contaminants. This approach has potential to identify children at risk of developmental disorders and illness resulting from prenatal exposure.Genotoxic insult causes nuclear and mitochondrial DNA damages with macroautophagy/autophagy induction. The role of mitochondrial DNA (mtDNA) damage in the requirement of autophagy for nuclear DNA (nDNA) stability is unclear. Using site-specific DNA damage approaches, we show that specific nDNA damage alone does not require autophagy for repair unless in the presence of mtDNA damage. We provide evidence that after IR exposure-induced mtDNA and nDNA damages, autophagy suppression causes non-apoptotic mitochondrial permeability, by which mitochondrial ENDOG (endonuclease G) is released and translocated to nuclei to sustain nDNA damage in a TET (tet methylcytosine dioxygenase)-dependent manner. Furthermore, blocking lysosome function is sufficient to increase the amount of mtDNA leakage to the cytosol, accompanied by ENDOG-free mitochondrial puncta formation with concurrent ENDOG nuclear accumulation. We proposed that autophagy eliminates the mitochondria specified by mtDNA damage-driven mitochondrial permeabilit mtDNA mitochondrial DNA; nDNA nuclear DNA; 4-OHT 4-hydroxytamoxifen; rDNA ribosomal DNA; ROS reactive oxygen species; SQSTM1/p62 sequestosome 1; TET tet methylcytosine dioxygenase; TFAM transcription factor A, mitochondrial; TOMM20 translocase of outer mitochondrial membrane 20; VDAC voltage dependent anion channel.Hybrid Assistive Limb (HAL) is a wearable human assistant cyborg-type robot that helps lower-leg movement based on bioelectrical signals detected from the voluntary movement of the person wearing it. In this study, we developed a novel staged HAL treatment protocol for patients with acute stroke. The Regain Program for Gait with HAL (RPG-HAL) was formulated in four steps, based on the severity of limb paralysis. Twenty-one patients with acute stroke received a combination treatment of RPG-HAL and conventional rehabilitation. The feasibility and safety of RPG-HAL were evaluated based on changes in physical function and activities of daily living (ADL). RPG-HAL yielded improvement in gait speed, cadence, step length, and functional ambulation category (FAC). The effect size was >0.8 in all measurements. FAC (1.90) and Barthel Index (BI) (1.92) exhibited the highest scores. Twelve out of 14 patients with FAC 0 before RPG-HAL reached the upper FAC. Thus, earlier intervention using RPG-HAL as improving physical function, ADL, and gait ability in patients with stroke.Human-induced pluripotent stem cell (hiPSC) and stem cell (hSC) derived cardiomyocytes (CM) are gaining popularity as in vitro model for cardiology and pharmacology studies. A remaining flaw of these cells, as shown by single-cell electrophysiological characterization, is a more depolarized resting membrane potential (RMP) compared to native CM. Most reports attribute this to a lower expression of the Kir2.1 potassium channel that generates the IK1 current. However, most RMP recordings are obtained from isolated hSC/hiPSC-CMs whereas in a more native setting these cells are interconnected with neighboring cells by connexin-based gap junctions, forming a syncytium. Hereby, these cells are electrically connected and the total pool of IK1 increases. Therefore, the input resistance (Ri) of interconnected cells is lower than that of isolated cells. During patch clamp experiments pipettes need to be well attached or sealed to the cell, which is reflected in the seal resistance (Rs), because a nonspecific ionic current can leak through this pipette-cell contact or seal and balance out small currents within the cell such as IK1. By recording the action potential of isolated hSC-CMs and that of hSC-CMs cultured in small monolayers, we show that the RMP of hSC-CMs in monolayer is approximately -20 mV more hyperpolarized compared to isolated cells. Accordingly, adding carbenoxolone, a connexin channel blocker, isolates the cell that is patch clamped from its neighboring cells of the monolayer and depolarizes the RMP. The presented data show that the recorded RMP of hSC-CMs in a syncytium is more negative than that determined from isolated hSC/hiPSC-CMs, most likely because the active pool of Kir2.1 channels increased.Non-negligible nighttime transpiration rates (TRN) have been identified in grasses such as wheat and barley. Evidence from the last 30 years indicate that in drought-prone environments with high evaporative demand, TRN could amount to 8-55% of daytime TR, leading several investigators to hypothesize that reducing TRN might represent a viable water-saving strategy that minimizes seemingly ‘wasteful’ water loss that is not traded for CO2 fixation. More recently however, evidence suggests that actual increases in TRN during pre-dawn hours, which are presumably controlled by the circadian clock, mediate drought tolerance – not through water conservation – but by enabling maximized gas exchange early in the morning before midday depression sets in. Finally, new findings point to a previously undocumented role for leaf sheaths as substantial contributors (up to 45%) of canopy TRN, although the extent of their involvement in these two strategies remains unknown. In this paper, we synthesize and reconcile key results from experimental and simulation-based modeling efforts conducted at scales ranging from the leaf tissue to the field plot on wheat and barley to show that both strategies could in fact concomitantly enable yield gains under limited water supply.