Human cytomegalovirus pUL29/28 and pUL38 repression of p53-regulated p21CIP1 and caspase 1 promoters during infection

During infection by human cytomegalovirus (HCMV), the tumor suppressor protein p53, which promotes efficient viral gene expression, is stabilized. However, the expression of numerous p53-responsive cellular genes is not upregulated. The molecular mechanism used to manipulate the transcriptional activity of p53 during infection remains unclear. The HCMV proteins IE1, IE2, pUL44, and pUL84 likely contribute to the regulation of p53. In this study, we used a discovery-based approach to identify the protein targets of the HCMV protein pUL29/28 during infection. Previous studies have demonstrated that pUL29/28 regulates viral gene expression by interacting with the chromatin remodeling complex NuRD. Here, we observed that pUL29/28 also associates with p53, an additional deacetylase complex, and several HCMV proteins, including pUL38. We confirmed the interaction between p53 and pUL29/28 in both the presence and absence of infection. HCMV pUL29/28 with pUL38 altered the activity of the 53-regulatable p21CIP1 promoter. During infection, pUL29/28 and pUL38 contributed to the inhibition of p21CIP1 as well as caspase 1 expression. The expression of several other p53-regulating genes was not altered. Infection using a UL29-deficient virus resulted in increased p53 binding and histone H3 acetylation at the responsive promoters. Furthermore, expression of pUL29/28 and its interacting partner pUL38 contributed to an increase in the steady-state protein levels of p53. This study identified two additional HCMV proteins, pUL29/28 and pUL38, which participate in the complex regulation of p53 transcriptional activity during infection

Guidelines for the assessment of efficacy of clinical hypnosis applications

Research on the efficacy of hypnosis applications continues to grow, but there remain major gaps between the science and clinical practice. One challenge has been a lack of consensus on which applications of hypnosis are efficacious based on research evidence. In 2018, 6 major hypnosis organizations collaborated to form the Task Force for Establishing Efficacy Standards for Clinical Hypnosis. This paper describes a Guideline for the Assessment of Efficacy of Clinical Hypnosis Applications developed by the Task Force, which makes 10 specific recommendations. The guideline is intended to be a tool for those who want to assess the quality of existing evidence on the efficacy of clinical hypnosis for any particular indication. The paper also discusses methodological issues in the interpretation and implementation of these guidelines. Future papers will report on the other products of the Hypnosis Efficacy Task Force, such as best practice recommendations for outcomes research in hypnosis and an international survey of researchers and clinicians on current practice and attitudes about hypnosis

A simple clinical scoring system to improve the sensitivity and standardization of the diagnosis of mycosis fungoides type cutaneous T-cell lymphoma: logistic regression of clinical and laboratory data

Background  The diagnosis of mycosis fungoides (MF) is notoriously difficult to establish because in the early stages, histological features may be nonspecific or merely suggestive. Objectives  To standardize the diagnosis of MF. Methods  We studied 138 patients with suspected MF referred over a 7-year period to a university department of a dermatology-based cutaneous lymphoma clinic. Six diagnostic criteria were evaluated: clinical morphology, clinical distribution, skin biopsy T-cell receptor gene rearrangement (TCR-GR), skin biopsy pan T-cell marker loss ≥ 2, skin biopsy CD4/CD8 ratio ≥ 6, and skin biopsy diffuse epidermal HLA-DR expression. These six clinical and laboratory criteria were compared by logistic regression analysis in patients with histologically diagnosed MF and those with benign disease. Results  Of the 138 patients, 74 had histology of MF, 47 of benign dermatoses and 17 were indeterminate. Close associations were found between a histological diagnosis of MF and TCR-GR (odds ratio 14·4), classical morphology (7·5), classical distribution (2·5) and diffuse epidermal HLA-DR expression (2·8). Logistic regression models were developed depending on the availability of data (either TCR-GR or HLA-DR). Probabilities for correctly diagnosing MF compared with histology as the ‘gold standard’ were derived from these logistic regression models. A scoring system assigning point values based on these probabilities was then created in order to assist the clinician in making the diagnosis. If using TCR-GR data, a positive TCR-GR = 2·5 points, the presence of classical morphology = 2·0 points, and the presence of classical distribution = 1·5 points. A total score of ≥ 3·5 points assigns a high probability (> 85%) of having MF. If using HLA-DR expression, then the presence of classical morphology = 2·5 points, a positive diffuse epidermal HLA-DR expression = 2·0 points, and the presence of classical distribution = 1·5 points. In this case, a total score of ≥ 4·0 points assigns a high probability (> 85%) of MF. Conclusions  The logistic regression models and scoring systems integrate clinical and laboratory assessments, allow rapid probability estimation, and provide a threshold for the diagnosis of MF in an objective, standardized manner.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75520/1/j.1365-2133.2003.05458.x.pd

Translocation as a Population Restoration Technique for Northern Bobwhites: A Review and Synthesis

Northern bobwhite (Colinus virginianus) abundance has declined precipitously for decades across much of the species range, to the point of widespread local, regional, and statewide extirpation. Because of successful translocations of other gallinaceous birds, bobwhite enthusiasts increasingly call for use of the approach. Consequently, the National Bobwhite Technical Committee (NBTC), on behalf of state agencies, requested a review and recommendation by the NBTC Science Subcommittee. Thus, our paper is co-authored by invited experts and includes reviews of peer-reviewed publications, manuscripts in these proceedings, state agency reports, experience by co-authors, and a survey of perspectives on translocations by state wildlife agency members of the NBTC. We discuss the state of science on key aspects of bobwhite conservation, offer best management practices (BMPs) for using translocation as a potential bobwhite restoration technique, and suggest ways to reduce uncertainty about implementation. We note that although conservationists operate on a relatively solid foundation of improving bobwhite abundance via increased quantity, connectivity, and quality of habitat, population restoration success to- date is relatively rare and unpredictable. Similarly, some past translocations have been unreliable with an abundance of failures and inadequate experimental designs. We conclude that because of major uncertainties regarding habitat, population phenomena (e.g., Allee effect) and restoration techniques, outcomes of translocations remain unpredictable; thus, future efforts must be a part of sound and rigorous peer-reviewed research. To improve scientific efforts, we recommend the following BMPs for future translocations: (1) target bobwhite abundance should be \u3e800 post-translocation which will likely necessitate ≥600 ha of suitable and accessible habitat while a larger (e.g., \u3e800 ha) area will be needed in areas with lower carrying capacity and when sites are highly fragmented or isolated, (2) personnel should identify and avoid stressors to bobwhites in all phases of the translocation process (i.e., capture, holding, transportation, and release), (3) source populations should be disease free and from similar environments and latitude; preferably from the nearest suitable source, (4) conspecifics should be present on recipient sites (5) birds should be released just before the breeding season (i.e., March or April), and (6) the translocation should incorporate robust short- and long-term bird (i.e., abundance and/or density) and habitat monitoring efforts (i.e., the Coordinated Implementation Program (CIP) of the National Bobwhite Conservation Initiative (NBCI)). In conclusion, we note that translocation of bobwhites is not a panacea for broad scale restoration of bobwhites; however, the technique should remain at the forefront of bobwhite science, taking into account knowledge of the species’ life history and ecology, so that a practical and reliable solution can be developed. We recognize this paper is just the beginning of vigorous debate, testing of concepts, and on-the ground implementation of successful bobwhite conservation

Emergence of qualia from brain activity or from an interaction of proto-consciousness with the brain: which one is the weirder? Available evidence and a research agenda

This contribution to the science of consciousness aims at comparing how two different theories can explain the emergence of different qualia experiences, meta-awareness, meta-cognition, the placebo effect, out-of-body experiences, cognitive therapy and meditation-induced brain changes, etc. The first theory postulates that qualia experiences derive from specific neural patterns, the second one, that qualia experiences derive from the interaction of a proto-consciousness with the brain\u2019s neural activity. From this comparison it will be possible to judge which one seems to better explain the different qualia experiences and to offer a more promising research agenda

Evolution of Linear Absorption and Nonlinear Optical Properties in V-Shaped Ruthenium(II)-Based Chromophores

In this article, we describe a series of complexes with electron-rich cis-{Ru^(II)(NH_3)_4}^(2+) centers coordinated to two pyridyl ligands bearing N-methyl/arylpyridinium electron-acceptor groups. These V-shaped dipolar species are new, extended members of a class of chromophores first reported by us (Coe, B. J. et al. J. Am. Chem. Soc. 2005, 127, 4845−4859). They have been isolated as their PF_6− salts and characterized by using various techniques including ^1H NMR and electronic absorption spectroscopies and cyclic voltammetry. Reversible Ru^(III/II) waves show that the new complexes are potentially redox-switchable chromophores. Single crystal X-ray structures have been obtained for four complex salts; three of these crystallize noncentrosymmetrically, but with the individual molecular dipoles aligned largely antiparallel. Very large molecular first hyperpolarizabilities β have been determined by using hyper-Rayleigh scattering (HRS) with an 800 nm laser and also via Stark (electroabsorption) spectroscopic studies on the intense, visible d → π^* metal-to-ligand charge-transfer (MLCT) and π → π^* intraligand charge-transfer (ILCT) bands. The latter measurements afford total nonresonant β_0 responses as high as ca. 600 × 10^(−30) esu. These pseudo-C_(2v) chromophores show two substantial components of the β tensor, β_(zzz) and β_(zyy), although the relative significance of these varies with the physical method applied. According to HRS, β_(zzz) dominates in all cases, whereas the Stark analyses indicate that β_(zyy) is dominant in the shorter chromophores, but β_(zzz) and β_(zyy) are similar for the extended species. In contrast, finite field calculations predict that β_(zyy) is always the major component. Time-dependent density functional theory calculations predict increasing ILCT character for the nominally MLCT transitions and accompanying blue-shifts of the visible absorptions, as the ligand π-systems are extended. Such unusual behavior has also been observed with related 1D complexes (Coe, B. J. et al. J. Am. Chem. Soc. 2004, 126, 3880−3891)

Myths and misconceptions about hypnosis and suggestion: Separating fact and fiction

We present 21 prominent myths and misconceptions about hypnosis in order to promulgate accurate information and to highlight questions for future research. We argue that these myths and misconceptions have (a) fostered a skewed and stereotyped view of hypnosis among the lay public, (b) discouraged participant involvement in potentially helpful hypnotic interventions, and (c) impeded the exploration and application of hypnosis in scientific and practitioner communities. Myths reviewed span the view that hypnosis produces a trance or special state of consciousness and allied myths on topics related to hypnotic interventions; hypnotic responsiveness and the modification of hypnotic suggestibility; inducing hypnosis; and hypnosis and memory, awareness, and the experience of nonvolition. By demarcating myth from mystery and fact from fiction, and by highlighting what is known as well as what remains to be discovered, the science and practice of hypnosis can be advanced and grounded on a firmer empirical footing

Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further

Towards a neurocognitive approach to Dance Movement Therapy for mental health: A systematic review

Dance/Movement Therapy (DMT) has become an increasingly recognized and used treatment, though primarily used to target psychological and physical wellbeing in individuals with physical, medical, or neurological illnesses. To contribute to the relative lack of literature within the field of DMT for clinical mental health disorders, using a narrative synthesis, we review the scope of recent, controlled studies of DMT in samples with different psychiatric disorders including depression, schizophrenia, autism, and somatoform disorder. A systematic search of electronic databases (PubMed, Science Direct, World of Science, and Clinicaltrials.gov) was conducted to identify studies examining the effects of DMT in psychiatric populations. 15 studies were eligible for inclusion. After reviewing the principal results of the studies, we highlight strengths and weaknesses of this treatment approach and examine the potential efficacy of using bodily movements as a tool to reduce symptoms. We conclude by placing DMT within the context of contemporary cognitive neuroscience research, drawing out implications of such an orientation for future research, and discussing potential mechanisms by which DMT might reduce psychiatric symptoms. DMT has clear potential as a treatment for a range of conditions and symptoms and thus further research on its utility is warranted

Time perception and the experience of agency in meditation and hypnosis

Mindfulness meditation and hypnosis are related in opposing ways to awareness of intentions. The cold control theory of hypnosis proposes that hypnotic responding involves the experience of involuntariness while performing an actually intentional action. Hypnosis therefore relies upon inaccurate metacognition about intentional actions and experiences. Mindfulness meditation centrally involves awareness of intentions and is associated with improved metacognitive access to intentions. Therefore, mindfulness meditators and highly hypnotizable people may lie at opposite ends of a spectrum with regard to metacognitive access to intention‐related information. Here we review the theoretical background and evidence for differences in the metacognition of intentions in these groups, as revealed by chronometric measures of the awareness of voluntary action: the timing of an intention to move (Libet's “W” judgments) and the compressed perception of time between an intentional action and its outcome (“intentional binding”). We review these measures and critically evaluate their proposed connection to the experience of volition and sense of agency