Franklin M. Wright to Professor Silver, 15 November 1960

Professional correspondenc

Observation of an action with a congruent contextual background facilitates corticospinal excitability: A combined TMS and eye-tracking experiment

Action observation produces activity in similar regions of the brain to those involved in action execution and can offer an effective intervention for motor (re)learning, although optimal viewing conditions for such interventions remain to be established. In this experiment, single-pulse transcranial magnetic stimulation (TMS) and eye-tracking were used simultaneously to investigate the effect of manipulating background context on both corticospinal excitability and visual attention during action observation. Twenty-four participants observed four different videos: (i) a static hand holding a sponge (control condition); and an index finger-thumb pinch of a sponge against (ii) a plain black background; (iii) a background containing objects that were incongruent with the observed action; and (iv) a background containing objects that were congruent with the observed action. TMS was delivered to the hand representation of the left primary motor cortex and motor evoked potentials were recorded from the first dorsal interosseous and abductor digiti minimi muscles of the right hand. Eye movements were recorded throughout the experiment. Results indicated that corticospinal excitability was facilitated during the congruent context condition compared to both the static hand and plain black background conditions. In addition, the number of fixations and percentage of time participants spent fixating on the background scene were significantly greater during the incongruent and congruent conditions compared to the static hand and plain black background conditions. These results indicate that the provision of additional visual information that is congruent with the observed movement contributes to a facilitation of corticospinal excitability by providing the observer with information regarding the goal and intention of the observed action. Providing congruent contextual information may enhance the efficacy of action observation interventions for motor (re)learning

New experimental tests of sum rules for charmed baryon masses

New experimental measurements are used to test model independent sum rules for charmed baryon masses. Sum rules for medium-strong mass differences are found to be reasonably well satisfied with increasing accuracy, and the new measurements permit an improved prediction of $2778\pm 9$ MeV for the mass of the $\Omega_c^{*0}$. But an isospin breaking sum rule for the $\Sigma_c$ mass splittings is still in significant disagreement posing a serious problem for the quark model of charmed baryons. Individual $\Sigma_c$ mass splittings are investigated, using the new CLEO measurement of the $\Xi_c^\prime$ mass splitting, but the accuracy is not yet sufficient for a good test.Comment: 6 pages, latex, no figure

Conserved YKL-40 changes in mice and humans after postoperative delirium

Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%–50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to characterize systemic and central nervous system (CNS) inflammatory changes following surgery in mice and humans. Matched plasma and cerebrospinal fluid (CSF) samples from the “Investigating Neuroinflammation Underlying Postoperative Brain Connectivity Changes, Postoperative Cognitive Dysfunction, Delirium in Older Adults” (INTUIT; NCT03273335) study were compared to murine endpoints. Delirium-like behavior was evaluated in aged mice using the 5-Choice Serial Reaction Time Test (5-CSRTT). Using a well established orthopedic surgical model in the FosTRAP reporter mouse we detected neuronal changes in the prefrontal cortex, an area implicated in attention, but notably not in the hippocampus. In aged mice, plasma interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40), and neurofilament light chain (NfL) levels increased after orthopedic surgery, but hippocampal YKL-40 expression was decreased. Given the growing evidence for a YKL-40 role in delirium and other neurodegenerative conditions, we assayed human plasma and CSF samples. Plasma YKL-40 levels were similarly increased after surgery, with a trend toward a greater postoperative plasma YKL-40 increase in patients with delirium. However, YKL-40 levels in CSF decreased following surgery, which paralleled the findings in the mouse brain. Finally, we confirmed changes in the blood-brain barrier (BBB) as early as 9 h after surgery in mice, which warrants more detailed and acute evaluations of BBB integrity following surgery in humans. Together, these results provide a nuanced understanding of neuroimmune interactions underlying postoperative delirium in mice and humans, and highlight translational biomarkers to test potential cellular targets and mechanisms

Statistical Genetics and Evolution of Quantitative Traits

The distribution and heritability of many traits depends on numerous loci in the genome. In general, the astronomical number of possible genotypes makes the system with large numbers of loci difficult to describe. Multilocus evolution, however, greatly simplifies in the limit of weak selection and frequent recombination. In this limit, populations rapidly reach Quasi-Linkage Equilibrium (QLE) in which the dynamics of the full genotype distribution, including correlations between alleles at different loci, can be parameterized by the allele frequencies. This review provides a simplified exposition of the concept and mathematics of QLE which is central to the statistical description of genotypes in sexual populations. We show how key results of Quantitative Genetics such as the generalized Fisher's "Fundamental Theorem", along with Wright's Adaptive Landscape, emerge within QLE from the dynamics of the genotype distribution. We then discuss under what circumstances QLE is applicable, and what the breakdown of QLE implies for the population structure and the dynamics of selection. Understanding of the fundamental aspects of multilocus evolution obtained through simplified models may be helpful in providing conceptual and computational tools to address the challenges arising in the studies of complex quantitative phenotypes of practical interest.Comment: to appear in Rev.Mod.Phy

An international survey of speciality training in oral and maxillofacial pathology

BACKGROUND: Speciality training in oral and maxillofacial pathology (OMFP) across the world would be aided by guidance on a generic curriculum and training programme that all countries could use as a template. In order to facilitate this, we require an understanding of the various forms which OMFP training takes across the world. METHODS: We sent a questionnaire to OMF pathologists in the 42 countries represented in the IAOP membership, via their Regional Councillor. The questionnaire included detailed demographics, entry requirements, specialty training program and facilities/ resources. RESULTS: Replies were received from 22/42 countries (52%). OMFP is a dental/dental and medical speciality in 72%, and in 92% of those, this is recognised by a licensing board. Training was undertaken in an academic environment in 85% (with many offering a further academic qualification) and the median length of training was 4 years. General/anatomical pathology training is mandated in 85% of programs and a common core of general sub-specialities was identified. An end of training assessment was conducted in 80% of programs with most including written, practical and oral elements. Training program directors and educational supervisors were in place in 12/16 programs and, in most, Quality Assurance of training was externally monitored. In only one country was the number of trainees linked to workforce planning. CONCLUSIONS: Training in OMFP varies across the world. However, we feel there is sufficient commonality for the development of an agreed indicative framework on education and training in Oral and Maxillofacial Pathology, perhaps under the auspices of the IAOP.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-0714hb201

A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma

A prior screening programme carried out using MTT assay by our group identified a series of novel benzimidazole derivatives, among which Methyl 2-(5-fluoro-2- hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) showed highest anticancer efficacy compared to that of chemotherapeutic agent, cisplatin. In the present study, we found that MBIC inhibited cell viability in different hepatocellular carcinoma (HCC) cell lines without exerting significant cytotoxic effects on normal liver cells. Annexin V-FITC/PI flow cytometry analysis and Western blotting results indicated that MBIC can induce apoptosis in HCC cells, which was found to be mediated through mitochondria associated proteins ultimately leading to the activation of caspase-3. The exposure to MBIC also resulted in remarkable impairment of HCC cell migration and invasion. In addition, treatment with MBIC led to a rapid generation of reactive oxygen species (ROS) and substantial activation of c-Jun-N-terminal kinase (JNK). The depletion of ROS by N-Acetyl cysteine (NAC) partially blocked MBIC-induced apoptosis and JNK activation in HCC cells. Finally, MBIC significantly inhibited tumor growth at a dose of 25 mg/kg in an orthotopic HCC mouse model. Taken together, these results demonstrate that MBIC may inhibit cell proliferation via ROS-mediated activation of the JNK signaling cascade in HCC cells

Panoramic SETI: on-sky results from prototype telescopes and instrumental design

The Panoramic SETI (Search for Extraterrestrial Intelligence) experiment (PANOSETI) aims to detect and quantify optical transients from nanosecond to second precision over a large field-of-view (∼4,450 square-degrees). To meet these challenging timing and wide-field requirements, the PANOSETI experiment will use two assemblies of ∼45 telescopes to reject spurious signals by coincidence detection, each one comprising custom-made fast photon-counting hardware combined with (f/1.32) focusing optics. Preliminary on-sky results from pairs of PANOSETI prototype telescopes (100 sq.deg.) are presented in terms of instrument performance and false alarm rates. We found that a separation of >1 km between telescopes surveying the same field-of-view significantly reduces the number of false positives due to nearby sources (e.g., Cherenkov showers) in comparison to a side- by-side configuration of telescopes. Design considerations on the all-sky PANOSETI instrument and expected field-of-views are reported

Herschel observations of extra-ordinary sources: Detection of Hydrogen Fluoride in absorption towards Orion~KL

We report a detection of the fundamental rotational transition of hydrogen fluoride in absorption towards Orion KL using Herschel/HIFI. After the removal of contaminating features associated with common molecules ("weeds"), the HF spectrum shows a P-Cygni profile, with weak redshifted emission and strong blue-shifted absorption, associated with the low-velocity molecular outflow. We derive an estimate of 2.9 x 10^13 cm^-2 for the HF column density responsible for the broad absorption component. Using our best estimate of the H2 column density within the low-velocity molecular outflow, we obtain a lower limit of ~1.6 x 10^-10 for the HF abundance relative to hydrogen nuclei, corresponding to 0.6% of the solar abundance of fluorine. This value is close to that inferred from previous ISO observations of HF J=2--1 absorption towards Sgr B2, but is in sharp contrast to the lower limit of 6 x 10^-9 derived by Neufeld et al. (2010) for cold, foreground clouds on the line of sight towards G10.6-0.4.Comment: 5 pages, 3 figures, paper to be published in the Herschel special issue of A&A letter