Frontal theta activation during motor synchronization in autism

Autism is characterized by two primary characteristics: deficits in social interaction and repetitive behavioral patterns. Because interpersonal communication is extremely complicated, its underlying brain mechanisms remain unclear. Here we showed that both characteristics can be explained by a unifying underlying mechanism related to difficulties with irregularities. To address the issues, we measured electroencephalographm during a cooperative tapping task, which required participants to tap a key alternately and synchronously with constant rhythmic a PC program, a variable rhythmic PC program, or a human partner. We found that people with autism had great difficulty synchronizing tapping behavior with others, and exhibited greater than normal theta-wave (6 Hz) activity in the frontal cortex during the task, especially when their partner behaved somewhat irregularly (i.e. a variable rhythmic PC program or a human partner). Importantly, the higher theta-wave activity was related to the severity of autism, not the performance on the task. This indicates that people with autism need to use intense cognition when trying to adapt to irregular behavior and can easily become overtaxed. Difficulty adapting to irregular behavior in others is likely related to their own tendencies for repetitive and regular behaviors. Thus, while the two characteristics of autism have been comprehended separately, our unifying theory makes understanding the condition and developing therapeutic strategies more tractable

Thyroid Hormone Sensitizes the Imprinting-Associated Induction of Biological Motion Preference in Domestic Chicks

Filial imprinting is associated with induction of predisposed preference to animations that bear visual features of Johansson's biological motion (BM), and the induction is limited to a few days after hatching. As thyroid hormone (3,5,3′-triiodothyronine, T3) plays a critical role in determining the sensitive period of imprinting, we examined if exogenously applied T3 (or iopanoic acid, IOP; a selective inhibitor for converting enzymes) could also sensitize (or desensitize) the BM induction. Chicks were trained by using a non-BM stimulus (rotating red toy) according to a conventional imprinting procedure. Trained chicks were tested for preference to a point-light BM animation (walking chick) over a non-BM animation (linear motion), and for the preference for the familiarized stimulus (red toy) over an unfamiliar one (yellow toy). In 1-day chicks, those injected with IOP showed significantly lower scores than controls on both BM and imprinting tests. In 4-days chicks, those injected with T3 showed higher scores than control, but the difference in BM score was not significant. Imprinting and the accompanying T3 surge may be necessary for the predisposed BM preference to appear in 1-day chicks. Even after the conventional sensitive period is over, exogenous T3 can partly re-sensitize the BM preference as it does imprinting

GABA-A and GABA-B Receptors in Filial Imprinting Linked With Opening and Closing of the Sensitive Period in Domestic Chicks (Gallus gallus domesticus)

Filial imprinting of domestic chicks has a well-defined sensitive (critical) period lasting in the laboratory from hatching to day 3. It is a typical model to investigate the molecular mechanisms underlying memory formation in early learning. We recently found that thyroid hormone 3,5,3′-triiodothyronine (T3) is a determinant of the sensitive period. Rapid increases in cerebral T3 levels are induced by imprinting training, rendering chicks imprintable. Furthermore, the administration of exogenous T3 makes chicks imprintable on days 4 or 6 even after the sensitive period has ended. However, how T3 affects neural transmission to enable imprinting remains mostly unknown. In this study, we demonstrate opposing roles for gamma-aminobutyric acid (GABA)-A and GABA-B receptors in imprinting downstream of T3. Quantitative reverse transcription polymerase chain reaction and immunoblotting showed that the GABA-A receptor expression increases gradually from days 1 to 5, whereas the GABA-B receptor expression gradually decreases. We examined whether neurons in the intermediate medial mesopallium (IMM), the brain region responsible for imprinting, express both types of GABA receptors. Immunostaining showed that morphologically identified putative projection neurons express both GABA-A and GABA-B receptors, suggesting that those GABA receptors interact with each other in these cells to modulate the IMM outputs. The roles of GABA-A and GABA-B receptors were investigated using various agonists and antagonists. Our results show that GABA-B receptor antagonists suppressed imprinting on day 1, while its agonists made day 4 chicks imprintable without administration of exogenous T3. By contrast, GABA-A receptor agonists suppressed imprinting on day 1, while its antagonists induced imprintability on day 4 without exogenous T3. Furthermore, both GABA-A receptor agonists and GABA-B receptor antagonists suppressed T3-induced imprintability on day 4 after the sensitive period has ended. Our data from these pharmacological experiments indicate that GABA-B receptors facilitate imprinting downstream of T3 by initiating the sensitive period, while the GABA-A receptor contributes to the termination of the sensitive period. In conclusion, we propose that opposing roles of GABA-A and GABA-B receptors in the brain during development determine the induction and termination of the sensitive period

A STUDY ON POSTOPERATIVE MORTALITY AND MORBIDITY AFTER PANCREATODUODENECTOMY

The early postoperative results of pancreatoduodenectomy performed in our institute during the last 20 years were reviewed, dividing the cases into two groups, from 1970 to 1979 and from 1980 to 1989. Among a total of 136 pancreatoduodenctomies, 52 were performed in the earlier decade and 84 in the latter decade. Patients were significantly older in the latter than in the earlier decade. In the earlier decade, postoperative complications developed in 28.8% of the patients with a 19.2% overall mortality rate. In the latter decade, the complications occurred in 27.4% with a 6.0% mortality rate. There was a significant decrease in overall mortality rate between the two decades. The most common complication was the dehiscence of pancreatojejunostmy, but life-threatening major leakage was decreased. It was considered that recent improvements in surgical techniques and intraoperative and perioperative management contributed to the improvement of the results of this procedure. However, continuing efforts are needed to reduce the morbidity rate, which remains high

Comparison of Count Normalization Methods for Statistical Parametric Mapping Analysis Using a Digital Brain Phantom Obtained from Fluorodeoxyglucose-positron Emission Tomography

Objective(s): Alternative normalization methods were proposed to solve the biased information of SPM in the study of neurodegenerative disease. The objective of this study was to determine the most suitable count normalization method for SPM analysis of a neurodegenerative disease based on the results of different count normalization methods applied on a prepared digital phantom similar to one obtained using fluorodeoxyglucose-positron emission tomography (FDG-PET) data of a brain with a known neurodegenerative condition.Methods: Digital brain phantoms, mimicking mild and intermediate neurodegenerative disease conditions, were prepared from the FDG-PET data of 11 healthy subjects. SPM analysis was performed on these simulations using different count normalization methods. Results: In the slight-decrease phantom simulation, the Yakushev method correctly visualized wider areas of slightly decreased metabolism with the smallest artifacts of increased metabolism. Other count normalization methods were unable to identify this slightly decreases and produced more artifacts. The intermediate-decreased areas were well visualized by all methods. The areas surrounding the grey matter with the slight decreases were not visualized withthe GM and VOI count normalization methods but with the Andersson. The Yakushev method well visualized these areas. Artifacts were present in all methods. When the number of reference area extraction was increased, the Andersson method better-captured the areas with decreased metabolism and reduced the artifacts of increased metabolism. In the Yakushev method, increasing the threshold for the reference area extraction reduced such artifacts.Conclusion: The Yakushev method is the most suitable count normalization method for the SPM analysis of neurodegenerative disease

Cancer of the Pancreas in 125 Patients

In this report, we did a retrospective study of 125 patients with cancer of the pancreas. Seventeen (36.2%) of the 47 patients with cancer of the pancreatic head underwent resection; 11.2% died within 30 days of surgery, 33.3 survived the first year, and 13.3 survived the first three years. The longest survival was for five years. Nine (23%) of the 39 patients with cancer of the pancreatic body and tail underwent resection; 11.1% died within 30 days, 37.5% survived the first year, and none survived more than three years. The longest survival was for 35 months. Important factors affecting the prognosis were invasion by the cancer of veins or lymph vessels in the surrounding tissues, and metastasis to regional lymph nodes. Lymphatic drainage of small cancers of the pancreatic head were established early. Invasion to the retroperitoneal tissue in cancer of the pancreatic body and tail was more common than in cancer of the pancreatic head. For the patient of early cancer of the pancreas, we strongly recommend total pancreatectomy over WHIPPLE\u27s pancreatoduodenectomy, based on results of our analysis of the outcome in our patients following these two operations. Key words: Cancer of the pancreas, Total pancreatectomy, WHIPPLE\u27s pancreatoduodenectom

ROTUNDIFOLIA4 Regulates Cell Proliferation Along the Body Axis in Arabidopsis Shoot

Molecular genetics has been successful in identifying leaf- size regulators such as transcription factors, phytohormones, and signal molecules. Among them, a ROTUNDIFOLIA4-LIKE/DEVIL (RTFL/DVL) family of Arabidopsis, genes encoding peptides with no secretion-signal sequence, is unique in that their overexpressors have a reduced number of leaf cells specifically along the proximodistal axis. However, because the RTFL/DVL lack any obvious homology with functionally identified domains, and because of genetic redundancy among RTFL/DVL, their molecular and developmental roles are unclear. In this study we focused on one member in the family, ROTUNDIFOLIA4 (ROT4), and identified the core functional region within it and we found no proteolytic processing in planta. Developmental analysis of leaf primordia revealed that ROT4 overexpression reduces the meristematic zone size within the leaf blade. Moreover, induced local overexpression demonstrated that ROT4 acts as a regulator of the leaf shape via a change in positional cue along the longitudinal axis. Similarly, ROT4 overexpression results in a protrusion of the main inflorescence stem, again indicating a change in positional cue along the longitudinal axis. These results suggest that ROT4 affects the positional cue and cell proliferation along the body axis

Double differential cross section for light mass fragment production on tens of MeV proton, deuteron, helium and carbon induced reactions

Double differential cross sections (DDXs) of light mass fragment (LMFs - Li,Be,B,C,N and O) productions were measured for tens of MeV proton, deuteron helium and carbon induced reactions on Be, C, Al, Ti and Cu targets. The incident energies for the measurements were chosen to allow us to compare DDXs with same incident energy but different projectiles on various targets. Systematic data were obtained to see the differences between projectile energies, particles, targets and emitted particles. From the comparison, reaction processes of not only evaporation from complete fusion nucleus, but also scattering, pickup, stripping and projectile fragmentation were observed

A radioprotective agonist for p53 transactivation

Inhibiting p53-dependent apoptosis by inhibitors of p53 is an effective strategy for preventing radiation-induced damage in hematopoietic lineages, while p53 and p21 also play radioprotective roles in the gastrointestinal epithelium. We previously identified some zinc(II) chelators, including 8-quinolinol derivatives that suppress apoptosis in attempts to discover compounds that target the zinc-binding site in p53. We found that 5-chloro-8-quinolinol (5CHQ) has a unique p53-modulating activity that shifts its transactivation from proapoptotic to protective responses including enhancing p21 induction and suppressing PUMA induction. This p53-modulating activity also influenced p53 and p53-target gene expression in unirradiated cells without inducing DNA damage. The specificity of 5CHQ for p53 and p21 was demonstrated by silencing the expression of each protein. These effects seems to be attributable to the sequence-specific alteration of p53 DNA-binding, as evaluated by chromatin immunoprecipitation and electrophoretic mobility shift assays. In addition, 5-chloro-8-methoxyquinoline itself had no antiapoptotic activity, indicating that the hydroxyl group at the 8-position is required for its antiapoptotic activity. We applied this remarkable agonistic activity to protecting the hematopoietic and gastrointestinal system in mouse irradiation models. The dose-reduction factors of 5CHQ in total-body and abdominally irradiated mice were about 1.2 and 1.3, respectively. 5CHQ effectively protected mouse epithelial stem cells from a lethal dose of abdominal irradiation. Furthermore, the specificity of 5CHQ for p53 in reducing the lethality induced by abdominal irradiation was revealed in Trp53-KO mice. These results indicate that the pharmacological upregulation of radioprotective p53-target genes is an effective strategy for addressing the gastrointestinal syndrome