Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation

Remote Lifestyle Counseling Influences Cardiovascular Health Outcomes in Youth with Overweight or Obesity and Congenital Heart Disease

Background: Children with overweight/obesity and congenital heart disease (CHD) are at increased cardiovascular risk. A lifestyle intervention may help reduce these risks. We sought to determine the feasibility of a smartphone-based lifestyle intervention to improve cardiovascular health outcomes in children with overweight/obesity and CHD. Methods: We examined the effect of bi-weekly nutrition and fitness counseling delivered Results: Statistically significant decreases in waist circumference (WC), body mass index Conclusion: The observed changes in anthropometry were positive with significant improvement to some cardiovascular and metabolic risk indicators. However, this was only observed in the operated group suggesting that other factors, such as perception of condition and self-efficacy, may influence lifestyle behaviors. The results from this pilot study clearly demonstrate the feasibility to perform a larger controlled study on remote lifestyle intervention in children with congenital heart defects and overweight or obesity

Present Day Kinematics of the Eastern California Shear Zone from a Geodetically Constrained Block Model

We use Global Positioning System (GPS) data from 1993–2000 to determine horizontal velocities of 65 stations in eastern California and western Nevada between 35° and 37° N. We relate the geodetic velocities to fault slip rates using a block model that enforces path integral constraints over geologic and geodetic time scales and that includes the effects of elastic strain accumulation on faults locked to a depth of 15 km. The velocity of the Sierra Nevada block with respect to Nevada is 11.1±0.3 mm/yr, with slip partitioned across the Death Valley, (2.8±0.5 mm/yr), Panamint Valley (2.5±0.8 mm/yr), and Airport Lake/Owens Valley (5.3±0.7/4.6±0.5 mm/yr) faults. The western Mojave block rotates at 2.1±0.8°/My clockwise, with 3.7±0.7 mm/yr of left lateral motion across the western Garlock Fault. We infer 11±2 mm/yr of right lateral motion across the Mojave region of the Eastern California Shear Zone

Illinois Homeowners and Wildlife Report

We conducted a mail survey designed to replicate the 2000 study “Attitudes of Homeowners in the Greater Chicago Metropolitan Region (GCMR) Toward Nuisance Wildlife.” The purpose of this study was to determine homeowners’ attitudes toward wildlife around their home, extent and types of wildlife damages experienced,and interactions with and preferences for management actions related to coyotes. A stratified random sample of 5,000 homeowners in the Greater Chicago Metropolitan Region was selected for this study. A total of 1,624 questionnaires (34%) were received. Forty percent of residents responded they fed wildlife on their property during the 12 months prior to the study, and 71% of those respondents were actively feeding wildlife at the time of the survey. Most wildlife feeding was done all year (56%), whereas fewer respondents fed wildlife during winter (22%), spring,summer,and fall (16% for each, respectively) only. Respondents (45%) were not sure if their neighbors were feeding wildlife. Approximately one-third(35%) of homeowners planted flowers, shrubs,provided water or nest boxes on property to specifically benefit wildlife.About 80% of homeowners enjoyed most or all wildlife species around their home, and the same proportion felt wildlife was not a threat or was only as light threat to their home or property. Seeing wildlife on a daily basis was important for 80% of respondents. Problems with wildlife were experienced by 54% of survey respondents, with digging or burrowing being the most frequent problem reported (52%), and45%of respondents had damage to shrubs, yard, or landscaping. Raccoons, skunk, and squirrels were the wildlife species identified to cause the greatest problems to residents.Half (50%) of respondents took action themselves to correct the problem, and a majority (51%) spent less than $50 on the problem during the 12 months prior to this study. Of the residents who hired private professional services (14%), most (65%) rated the services provided as “Good” or “Excellent.” A minority of residents (9%) received information about preventing wildlife damage, or requested information(5%) about wildlife from the Illinois Department of Natural Resources. Of those who did request information from the IDNR, a majority (72%) rated the information provided as “Good” or “Excellent.” Most (69%) survey respondents had not visited the University of Illinois Extension website “Living with Wildlife in Illinois.”A majority(68%)of survey respondents were aware of coyotes in their current community;62% of respondents or their family members observed a coyote in their current community and 55% saw one in a forest preserve. There was no or slight concern for homeowners ’perceived risks of coyotes in their community. When given the options to let the coyote live or to“trap and destroy,” most survey respondents preferred to let coyotes live regardless of frequency or location of coyote situation. Only when a coyote made a den on one’s property did 49% of respondents favor the “trap and destroy” option.unpublishednot peer reviewedOpe

Quantifying regional α -synuclein, amyloid β, and tau accumulation in Lewy body dementia

OBJECTIVE: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid β (Aβ) and tau accumulation, occur in some LBD cases. We sought to quantify α-syn, Aβ, and tau accumulation in neocortical, limbic, and basal ganglia regions. METHODS: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 LBD, seven Alzheimer disease (AD), and six control cases. We measured insoluble α-syn, Aβ, and tau with recently developed sandwich ELISAs. RESULTS: We detected a wide range of insoluble α-syn accumulation in LBD cases. The majority had substantial α-syn accumulation in most regions, and dementia severity correlated with neocortical α-syn. However, three cases had low neocortical levels that were indistinguishable from controls. Eight LBD cases had substantial Aβ accumulation, although the mean Aβ level in LBD was lower than in AD. The presence of Aβ was associated with greater α-syn accumulation. Tau accumulation accompanied Aβ in only one LBD case. INTERPRETATION: LBD is associated with insoluble α-syn accumulation in neocortical regions, but the relatively low neocortical levels in some cases suggest that other changes contribute to impaired function, such as loss of neocortical innervation from subcortical regions. The correlation between Aβ and α-syn accumulation suggests a pathophysiologic relationship between these two processes

Less than 10 percent of star formation in z=0.6 massive galaxies is triggered by major interactions

Both observations and simulations show that major tidal interactions or mergers between gas-rich galaxies can lead to intense bursts of starformation. Yet, the average enhancement in star formation rate (SFR) in major mergers and the contribution of such events to the cosmic SFR are not well estimated. Here we use photometric redshifts, stellar masses and UV SFRs from COMBO-17, 24 micron SFRs from Spitzer and morphologies from two deep HST cosmological survey fields (ECDFS/GEMS and A901/STAGES) to study the enhancement in SFR as a function of projected galaxy separation. We apply two-point projected correlation function techniques, which we augment with morphologically-selected very close pairs (separation <2 arcsec) and merger remnants from the HST imaging. Our analysis confirms that the most intensely star-forming systems are indeed interacting or merging. Yet, for massive (M* > 10^10 Msun) star-forming galaxies at 0.4<z<0.8, we find that the SFRs of galaxies undergoing a major interaction (mass ratios <1:4 and separations < 40 kpc) are only 1.80 +/- 0.30 times higher than the SFRs of non-interacting galaxies when averaged over all interactions and all stages of the interaction, in good agreement with other observational works. We demonstrate that these results imply that <10% of star formation at 0.4 < z < 0.8 is triggered directly by major mergers and interactions; these events are not important factors in the build-up of stellar mass since z=1.Comment: Submitted to ApJ. 41 pages, 11 figure

Interacting Galaxies in the A901/902 Supercluster with STAGES

We present a study of galaxy mergers and the influence of environment in the Abell 901/902 supercluster at z~0.165. We use HST ACS F606W data from the STAGES survey, COMBO-17, Spitzer 24um, and XMM-Newton X-ray data. Our analysis utilizes both a visual classification system, and quantitative CAS parameters to identify systems which show evidence of a recent or ongoing merger of mass ratio >1/10. Our results are: (1) After visual classification and minimizing the contamination from false projection pairs, we find that the merger fraction f_merge is 0.023+/-0.007. The estimated fractions of likely major mergers, likely minor mergers, and ambiguous cases are 0.01+/-0.004, 0.006+/-0.003, and 0.007+/-0.003, respectively. (2) The mergers lie outside the cluster core of radius R < 0.25 Mpc: the lack of mergers in the core is likely due to the large galaxy velocity dispersion in the core. Mergers populate the region (0.25 Mpc < R <= 2 Mpc) between the core and outskirt. In this region, the estimated frequency of mergers is similar to those seen at typical group overdensities. This suggests ongoing growth of the clusters via accretion of group and field galaxies. (3) We compare our observed merger fraction with those reported in other clusters and groups out to z~0.4. Existing data points on the merger fraction for L<= L* galaxies in clusters allow for a range of evolutionary scenarios. (4) The fraction of mergers, which lie on the blue cloud is 80%+/-18% versus 34%+/-7% for non-interacting galaxies, implying that interacting galaxies are preferentially blue. (5) The average SFR, based on UV or UV+IR data, is enhanced by a factor of ~1.5 to 2 in mergers compared to non-interacting galaxies. However, mergers in the clusters contribute only a small fraction (between 10% and 15%) of the total SFR density.(Abridged)Comment: Accepted for publication in ApJ. 34 pages, 16 figures. Version with full resolution figures available at: http://www.as.utexas.edu/~alh/apj/int/ ; updated abridged abstrac

Efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of acute pain after orthopedic trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma and the Orthopedic Trauma Association

OBJECTIVES: Fracture is a common injury after a traumatic event. The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) to treat acute pain related to fractures is not well established. METHODS: Clinically relevant questions were determined regarding NSAID use in the setting of trauma-induced fractures with clearly defined patient populations, interventions, comparisons and appropriately selected outcomes (PICO). These questions centered around efficacy (pain control, reduction in opioid use) and safety (non-union, kidney injury). A systematic review including literature search and meta-analysis was performed, and the quality of evidence was graded per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The working group reached consensus on the final evidence-based recommendations. RESULTS: A total of 19 studies were identified for analysis. Not all outcomes identified as critically important were reported in all studies, and the outcome of pain control was too heterogenous to perform a meta-analysis. Nine studies reported on non-union (three randomized control trials), six of which reported no association with NSAIDs. The overall incidence of non-union in patients receiving NSAIDs compared with patients not receiving NSAIDs was 2.99% and 2.19% (p=0.04), respectively. Of studies reporting on pain control and reduction of opioids, the use of NSAIDs reduced pain and the need for opioids after traumatic fracture. One study reported on the outcome of acute kidney injury and found no association with NSAID use. CONCLUSIONS: In patients with traumatic fractures, NSAIDs appear to reduce post-trauma pain, reduce the need for opioids and have a small effect on non-union. We conditionally recommend the use of NSAIDs in patients suffering from traumatic fractures as the benefit appears to outweigh the small potential risks

Everyone on Radio

This adaptation of Everyman was scheduled for production on the main stage in the Kline Theatre of Gettysburg College. With the onset of COVID-19 and the ensuing advent of distance-learning, that could no longer happen, and originally that was a crushing disappointment. But the show must go on, especially when that show is “Everyman,” an especially apt theatrical choice for a pestilential year. Everyman offers exciting possibilities for audio drama, especially considering the play’s emphasis on the internal struggle of the individual facing death; Everyone on Radio attempts to make the most of these aspects of the play. Never willing to blink in the face of doom, the students in this class rose to the occasion with incredible pluck, optimism, and good humor. In particular, Lauren “Helping” Hand, the peer associate for this year’s course, led the pivot to the podcast platform, and this production is as much hers as anyone’s: She was chief cheerleader, coordinator, and executive producer, in tandem with Joey “Magic Fingers” Maguschak, who acted as senior sound engineer and producer

Investigating Biotic Interactions in Deep Time

Recent renewed interest in using fossil data to understand how biotic interactions have shaped the evolution of life is challenging the widely held assumption that long-term climate changes are the primary drivers of biodiversity change. New approaches go beyond traditional richness and co-occurrence studies to explicitly model biotic interactions using data on fossil and modern biodiversity. Important developments in three primary areas of research include analysis of (i) macroevolutionary rates, (ii) the impacts of and recovery from extinction events, and (iii) how humans (Homo sapiens) affected interactions among non-human species. We present multiple lines of evidence for an important and measurable role of biotic interactions in shaping the evolution of communities and lineages on long timescales.Peer reviewe