Evidence for Secretion of a Netrin-1-like Protein by Tetrahymena thermophila

Netrin-1 is a pleiotropic signaling molecule with targets in many mammalian cell types. Though first characterized as a chemotactic signal involved in neuronal guidance during development, netrin-1 has since been found to have a regulatory role in angiogenesis, and is also used as a biomarker in certain cancers. Tetrahymena thermophila are free-living protists that rely on chemotactic signals to find food, as well as to escape predators. Chemoattractants cause the cells to swim faster in the forward direction, while chemorepellents cause ciliary reversal, resulting in movement of the cell away from the noxious stimulus. We have previously found that netrin-1 is a chemorepellent in T. thermophila. More recently, we have detected netrin-1 by ELISA in both whole cell extract and secreted protein samples obtained from T. thermophila. In addition, we have immunolocalized netrin-1 staining to the cytosol of T. thermophila using an anti-netrin-1 antibody. We are currently running Western blots to determine the molecular weight of this protein and compare it to its vertebrate counterparts. Further experimentation is needed to determine the physiological role of this protein in T. thermophila

Enhanced cellular infiltration of human adipose-derived stem cells in allograft menisci using a needle-punch method

Abstract Background The meniscus plays a crucial role in knee joint stability, load transmission, and stress distribution. Meniscal tears are the most common reported knee injuries, and the current standard treatment for meniscal deficiency is meniscal allograft transplantation. A major limitation of this approach is that meniscal allografts do not have the capacity to remodel and maintain tissue homeostasis due to a lack of cellular infiltration. The purpose of this study was to provide a new method for enhanced cellular infiltration in meniscal allografts. Methods Twenty medial menisci were collected from cadaveric human sources and split into five experimental groups: (1) control native menisci, (2) decellularized menisci, (3) decellularized menisci seeded with human adipose-derived stem cells (hASC), (4) decellularized needle-punched menisci, and (5) decellularized needle-punched menisci seeded with hASC. All experimental allografts were decellularized using a combined method with trypsin EDTA and peracetic acid. Needle punching (1-mm spacing, 28 G microneedle) was utilized to improve porosity of the allograft. Samples were recellularized with hASC at a density of 250 k/g of tissue. After 28 days of in vitro culture, menisci were analyzed for mechanical, biochemical, and histological characteristics. Results Menisci maintained structural integrity and material properties (compressive equilibrium and dynamic moduli) throughout preparations. Increased DNA content was observed in the needle-punched menisci but not in the samples without needle punching. Histology confirmed these results, showing enhanced cellular infiltration in needle-punched samples. Conclusions The enhanced infiltration achieved in this study could help meniscal allografts better remodel post-surgery. The integration of autologous adipose-derived stem cells could improve long-term efficacy of meniscal transplantation procedures by helping to maintain the meniscus in vivo

Randomized controlled trial of a family cognitive-behavioral preventive intervention for children of depressed parents.

A family cognitive-behavioral preventive intervention for parents with a history of depression and their 9–15-year-old children was compared with a self-study written information condition in a randomized clinical trial (n = 111 families). Outcomes were assessed at postintervention (2 months), after completion of 4 monthly booster sessions (6 months), and at 12-month follow-up. Children were assessed by child reports on depressive symptoms, internalizing problems, and externalizing problems; by parent reports on internalizing and externalizing problems; and by child and parent reports on a standardized diagnostic interview. Parent depressive symptoms and parent episodes of major depression also were assessed. Evidence emerged for significant differences favoring the family group intervention on both child and parent outcomes; strongest effects for child outcomes were found at the 12-month assessment with medium effect sizes on most measures. Implications for the prevention of adverse outcomes in children of depressed parents are highlighted

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions

Ultra-Stable Environment Control for the NEID Spectrometer: Design and Performance Demonstration

Two key areas of emphasis in contemporary experimental exoplanet science are the detailed characterization of transiting terrestrial planets, and the search for Earth analog planets to be targeted by future imaging missions. Both of these pursuits are dependent on an order-of-magnitude improvement in the measurement of stellar radial velocities (RV), setting a requirement on single-measurement instrumental uncertainty of order 10 cm/s. Achieving such extraordinary precision on a high-resolution spectrometer requires thermo-mechanically stabilizing the instrument to unprecedented levels. Here, we describe the Environment Control System (ECS) of the NEID Spectrometer, which will be commissioned on the 3.5 m WIYN Telescope at Kitt Peak National Observatory in 2019, and has a performance specification of on-sky RV precision < 50 cm/s. Because NEID's optical table and mounts are made from aluminum, which has a high coefficient of thermal expansion, sub-milliKelvin temperature control is especially critical. NEID inherits its ECS from that of the Habitable-zone Planet Finder (HPF), but with modifications for improved performance and operation near room temperature. Our full-system stability test shows the NEID system exceeds the already impressive performance of HPF, maintaining vacuum pressures below $10^{-6}$ Torr and an RMS temperature stability better than 0.4 mK over 30 days. Our ECS design is fully open-source; the design of our temperature-controlled vacuum chamber has already been made public, and here we release the electrical schematics for our custom Temperature Monitoring and Control (TMC) system.Comment: Accepted for publication in JATI

Interpretation of Digital Mammograms: Comparison of Speed and Accuracy of Soft-Copy versus Printed-Film Display

PURPOSE: To compare the speed and accuracy of the interpretations of digital mammograms by radiologists by using printed-film versus soft-copy display. MATERIALS AND METHODS: After being trained in interpretation of digital mammograms, eight radiologists interpreted 63 digital mammograms, all with old studies for comparison. All studies were interpreted by all readers in soft-copy and printed-film display, with interpretations of images in the same cases at least 1 month apart. Mammograms were interpreted in cases that included six biopsy-proved cancers and 20 biopsy-proved benign lesions, 20 cases of probably benign findings in patients who underwent 6-month follow-up, and 17 cases without apparent findings. Area under the receiver operating characteristic curve (Az), sensitivity, and specificity were calculated for soft-copy and printed-film display. RESULTS: There was no significant difference in the speed of interpretation, but interpretations with soft-copy display were slightly faster. The differences in Az, sensitivity, and specificity were not significantly different; Az and sensitivity were slightly better for interpretations with printed film, and specificity was slightly better for interpretations with soft copy. CONCLUSION: Interpretation with soft-copy display is likely to be useful with digital mammography and is unlikely to significantly change accuracy or speed