Circadian rhythms are regular oscillations of an organism's physiology with a period of approximately 24 h. In the model plant Arabidopsis thaliana, circadian rhythms regulate a suite of ...physiological processes, including transcription, photosynthesis, growth, and flowering. The circadian clock and external rhythmic factors have extensive control of the underlying biochemistry and physiology. Therefore, it is critical to consider the time of day when performing gravitropism experiments, even if the circadian clock is not a focus of study. We describe the critical factors and methods to be considered and methods to investigate the possible circadian regulation of gravitropic responses.
For long-term space missions, it is necessary to understand how organisms respond to changes in gravity. Plant roots are positively gravitropic; the primary root grows parallel to gravity's pull even ...after being turned away from the direction of gravity. We examined if this gravitropic response varies depending on the time of day reorientation occurs. When plants were reoriented in relation to the gravity vector or placed in simulated microgravity, the magnitude of the root gravitropic response varied depending on the time of day the initial change in gravity occurred. The response was greatest when plants were reoriented at dusk, just before a period of rapid growth, and were minimal just before dawn as the plants entered a period of reduced root growth. We found that this variation in the magnitude of the gravitropic response persisted in constant light (CL) suggesting the variation is circadian-regulated. Gravitropic responses were disrupted in plants with disrupted circadian clocks, including plants overexpressing Circadian-clock Associated 1 (CCA1) and
-2, in the reorientation assay and on a 2D clinostat. These findings indicate that circadian-regulated pathways modulate the gravitropic responses, thus, highlighting the importance of considering and recording the time of day gravitropic experiments are performed.
Objective
To conduct an exploratory examination of dietary patterns and quality during pregnancy in African-American women who were class I, II, or III obese, and those women with normal ...pre-pregnancy body mass index (pBMI), as well to identify dietary factors associated with GWG, and changes in the distal gut microbiome. African American women represent the largest group affected by pre-pregnancy obesity, a risk factor for several adverse birth outcomes.
Methods
This prospective study investigated the association between diet, distal gut microbiome, and GWG among African-American women (n = 21) with obesity (n = 15) compared to women with a normal pre-pregnancy body mass index (pBMI) (n = 6) at two time points, 27–29 and 37–39 weeks gestation. Dietary patterns associated with obesity severity and GWG gain were assessed using Welch’s T-test and Mann–Whitney U. The association between the gut microbiome and dietary patterns was assessed using a regression-based kernel association test and the adaptive microbiome-based sum of powered score test.
Results
In early pregnancy, dietary intake of Total Fruits and Greens and Beans was significantly different between pBMI and GWG groups; significance was 0.022 and 0.028 respectively. Women with Class II/III obesity and those with GWG above guidelines had Healthy Eating Index (HEI) scores below 50, meeting less than 75% of dietary guidelines, and did not meet recommendations for fruit and vegetable or fiber intake. We found no significant associations between the microbiome composition and diet (HEI Scores).
Conclusions for Practice
Overall, the results indicate that women with pBMI obesity are not meeting minimum dietary guidelines for nutrient intakes during pregnancy, specifically fruits, vegetables, and fiber, regardless of GWG. Interventions for African-American women with pre-pregnancy obesity, with a focus on increasing consumption of fruits and vegetables, would be beneficial to control GWG and improve birth outcomes.
Abstract Purpose We describe a novel algorithm for identifying transgender people and determining their male-to-female (MTF) or female-to-male (FTM) identity in electronic medical records of an ...integrated health system. Methods A computer program scanned Kaiser Permanente Georgia electronic medical records from January 2006 through December 2014 for relevant diagnostic codes, and presence of specific keywords (e.g., “transgender” or “transsexual”) in clinical notes. Eligibility was verified by review of de-identified text strings containing targeted keywords, and if needed, by an additional in-depth review of records. Once transgender status was confirmed, FTM or MTF identity was assessed using a second program and another round of text string reviews. Results Of 813,737 members, 271 were identified as possibly transgender: 137 through keywords only, 25 through diagnostic codes only, and 109 through both codes and keywords. Of these individuals, 185 (68%, 95% confidence interval CI: 62%–74%) were confirmed as definitely transgender. The proportions (95% CIs) of definite transgender status among persons identified via keywords, diagnostic codes, and both were 45% (37%–54%), 56% (35%–75%), and 100% (96%–100%). Of the 185 definitely transgender people, 99 (54%, 95% CI: 46%–61%) were MTF, 84 (45%, 95% CI: 38%–53%) were FTM. For two persons, gender identity remained unknown. Prevalence of transgender people (per 100,000 members) was 4.4 (95% CI: 2.6–7.4) in 2006 and 38.7 (95% CI: 32.4–46.2) in 2014. Conclusions The proposed method of identifying candidates for transgender health studies is low cost and relatively efficient. It can be applied in other similar health care systems.
ABSTRACT
A mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model was used for preclinical to clinical translation of inotuzumab ozogamicin, a CD22-targeting antibody-drug conjugate (ADC) for ...B cell malignancies including non-Hodgkin’s lymphoma (NHL) and acute lymphocytic leukemia (ALL). Preclinical data was integrated in a PK/PD model which included (1) a plasma PK model characterizing disposition and clearance of inotuzumab ozogamicin and its released payload
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-Ac-γ-calicheamicin DMH, (2) a tumor disposition model describing ADC diffusion into the tumor extracellular environment, (3) a cellular model describing inotuzumab ozogamicin binding to CD22, internalization, intracellular
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-Ac-γ-calicheamicin DMH release, binding to DNA, or efflux from the tumor cell, and (4) tumor growth and inhibition in mouse xenograft models. The preclinical model was translated to the clinic by incorporating human PK for inotuzumab ozogamicin and clinically relevant tumor volumes, tumor growth rates, and values for CD22 expression in the relevant patient populations. The resulting stochastic models predicted progression-free survival (PFS) rates for inotuzumab ozogamicin in patients comparable to the observed clinical results. The model suggested that a fractionated dosing regimen is superior to a conventional dosing regimen for ALL but not for NHL. Simulations indicated that tumor growth is a highly sensitive parameter and predictive of successful outcome. Inotuzumab ozogamicin PK and
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-Ac-γ-calicheamicin DMH efflux are also sensitive parameters and would be considered more useful predictors of outcome than CD22 receptor expression. In summary, a multiscale, mechanism-based model has been developed for inotuzumab ozogamicin, which can integrate preclinical biomeasures and PK/PD data to predict clinical response.
Circadian rhythms are regular oscillations of an organism’s physiology with a period of approximately 24 hours. Across genera, circadian clocks act as regulators to maintain robust oscillations, ...incorporate environmental cues, and “fine-tune” an organism for its environment. In Arabidopsis, the circadian clock regulates photosynthesis, flowering, hormone production, and growth. Despite its pervasive role in regulation, little work had been done to study the effects of the circadian clock on the gravitropic response.Gravitropism is one process by which plants orient themselves in physical space. Generally, root tissue is positively gravitropic and shoot tissue is negatively gravitropic so that roots grow downward while shoots grow upward. Gravity sensing in the root occurs in a specialized group of columella cells located in the root cap. Starch-filled plastids called amyloplasts sediment within these cells, triggering a signaling cascade which initiates the formation of a lateral auxin gradient, and eventually a growth response. By evaluating the Arabidopsis gravitropic response throughout a time-course experiment, we determined that the circadian clock regulates the gravitropic response.Additionally, we developed a growth system for use with the random positioning machine (RPM), a microgravity simulator, to evaluate the response to microgravity over a time-course. Plant growth in microgravity is of considerable interest to space agencies developing plans for long-term, deep space missions. Evidence from non-plant species has hinted that gravity may feedback into the circadian clock, potentially acting as a zeitgeber. The development and optimization of growth protocols using this system enabled a time-course experiment to study the circadian clock and will enable new experimental designs in simulated microgravity.
Anthropogenically induced arrested succession is a global problem in forest ecosystems. In northern Michigan (U.S.A.), oil development has arrested succession in forest landscapes since the 1970s and ...oil well pads have not reforested up to 30 years after being vacated. To explore pathways for reforestation, we evaluated survivorship and growth of northern red oak (Quercus rubra), white oak (Q. alba), jack pine (Pinus banksiana), and red pine (P. resinosa) at monthly intervals during growing seasons from 2015 to 2019 on pads, which had been vacated 9–34 years prior to the initiation of our study. We planted trees in four soil surface treatments—experimental control (planting only, no treatment), disking, fertilization, and disking with fertilization. While monitoring survivorship and growth of planted trees, we concurrently examined natural reforestation in untreated control areas on each pad and differences between soil characteristics of pads and surrounding forests. Pinus resinosa displayed highest overall survivorship regardless of treatment, but maximum survivorship in disked soils and experimental control areas. Other species had highest survivorship in disked soils. There was no significant reforestation in untreated control areas during the 5‐year study period. Pads had higher levels of Bray P, Ca, and Mg, but lower levels of Fe, organic matter, and moisture than forest soils. Concentrations of toxic chemicals associated with drilling activities were not different between pad and forest soils or, if different, within acceptable levels for plant growth. In reforesting well pads, restorationists should plant P. resinosa in disked soil to achieve highest tree survivorship and density.
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