In Vivo Observation of Structural Changes in Neocortical Catecholaminergic Projections in Response to Drugs of Abuse

Catecholaminergic (dopamine and norepinephrine) projections to the cortex play an important role in cognitive functions and dysfunctions including learning, addiction, and mental disorders. While dynamics of glutamatergic synapses have been well studied in such contexts, little is known regarding catecholaminergic projections, owing to lack of robust methods. Here we report a system to monitor catecholaminergic projections in vivo over the timeframes that such events occur. Green fluorescent protein (GFP) expression driven by tyrosine hydroxylase promoter in a transgenic mouse line enabled us to perform two-photon imaging of cortical catecholaminergic projections through a cranial window. Repetitive imaging of the same axons over 24 h revealed the highly dynamic nature of catecholaminergic boutons. Surprisingly, administration of single high dose methamphetamine (MAP) induced a transient increase in bouton volumes. This new method opens avenues for longitudinal in vivo evaluation of structural changes at single release sites of catecholamines in association with physiology and pathology of cortical functions

Enhancing genomics-based outbreak detection of endemic Salmonella enterica serovar Typhimurium using dynamic thresholds.

Salmonella enterica serovar Typhimurium is the leading cause of salmonellosis in Australia, and the ability to identify outbreaks and their sources is vital to public health. Here, we examined the utility of whole-genome sequencing (WGS), including complete genome sequencing with Oxford Nanopore technologies, in examining 105 isolates from an endemic multi-locus variable number tandem repeat analysis (MLVA) type over 5 years. The MLVA type was very homogeneous, with 90 % of the isolates falling into groups with a five SNP cut-off. We developed a new two-step approach for outbreak detection using WGS. The first clustering at a zero single nucleotide polymorphism (SNP) cut-off was used to detect outbreak clusters that each occurred within a 4 week window and then a second clustering with dynamically increased SNP cut-offs were used to generate outbreak investigation clusters capable of identifying all outbreak cases. This approach offered optimal specificity and sensitivity for outbreak detection and investigation, in particular of those caused by endemic MLVA types or clones with low genetic diversity. We further showed that inclusion of complete genome sequences detected no additional mutational events for genomic outbreak surveillance. Phylogenetic analysis found that the MLVA type was likely to have been derived recently from a single source that persisted over 5 years, and seeded numerous sporadic infections and outbreaks. Our findings suggest that SNP cut-offs for outbreak cluster detection and public-health surveillance should be based on the local diversity of the relevant strains over time. These findings have general applicability to outbreak detection of bacterial pathogens

Tycho Brahe's 1572 supernova as a standard type Ia explosion revealed from its light echo spectrum

Type Ia supernovae (SNe Ia) are thermonuclear explosions of white dwarf stars in close binary systems. They play an important role as cosmological distance indicators and have led to the discovery of the accelerated expansion of the Universe. Among the most important unsolved questions are how the explosion actually proceeds and whether accretion occurs from a companion or via the merging of two white dwarfs. Tycho Brahe's supernova of 1572 (SN 1572) is thought to be one of the best candidates for a SN Ia in the Milky Way. The proximity of the SN 1572 remnant has allowed detailed studies, such as the possible identification of the binary companion, and provides a unique opportunity to test theories of the explosion mechanism and the nature of the progenitor. The determination of the yet unknown exact spectroscopic type of SN 1572 is crucial to relate these results to the diverse population of SNe Ia. Here we report an optical spectrum of Tycho Brahe's supernova near maximum brightness, obtained from a scattered-light echo more than four centuries after the direct light of the explosion swept past Earth. We find that SN 1572 belongs to the majority class of normal SNe Ia. The presence of a strong Ca II IR feature at velocities exceeding 20,000 km/s, which is similar to the previously observed polarized features in other SNe Ia, suggests asphericity in SN 1572.Comment: 15 pages, 3 figures - accepted for publication in Natur

Soft tissue window of CT scans in the initial stage of ONJ: A case report

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A Model-Based Bayesian Estimation of the Rate of Evolution of VNTR Loci in Mycobacterium tuberculosis

Variable numbers of tandem repeats (VNTR) typing is widely used for studying the bacterial cause of tuberculosis. Knowledge of the rate of mutation of VNTR loci facilitates the study of the evolution and epidemiology of Mycobacterium tuberculosis. Previous studies have applied population genetic models to estimate the mutation rate, leading to estimates varying widely from around to per locus per year. Resolving this issue using more detailed models and statistical methods would lead to improved inference in the molecular epidemiology of tuberculosis. Here, we use a model-based approach that incorporates two alternative forms of a stepwise mutation process for VNTR evolution within an epidemiological model of disease transmission. Using this model in a Bayesian framework we estimate the mutation rate of VNTR in M. tuberculosis from four published data sets of VNTR profiles from Albania, Iran, Morocco and Venezuela. In the first variant, the mutation rate increases linearly with respect to repeat numbers (linear model); in the second, the mutation rate is constant across repeat numbers (constant model). We find that under the constant model, the mean mutation rate per locus is (95% CI: ,)and under the linear model, the mean mutation rate per locus per repeat unit is (95% CI: ,). These new estimates represent a high rate of mutation at VNTR loci compared to previous estimates. To compare the two models we use posterior predictive checks to ascertain which of the two models is better able to reproduce the observed data. From this procedure we find that the linear model performs better than the constant model. The general framework we use allows the possibility of extending the analysis to more complex models in the future

An evaluation of indices for quantifying tuberculosis transmission using genotypes of pathogen isolates

BACKGROUND: Infectious diseases are often studied by characterising the population structure of the pathogen using genetic markers. An unresolved problem is the effective quantification of the extent of transmission using genetic variation data from such pathogen isolates. METHODS: It is important that transmission indices reflect the growth of the infectious population as well as account for the mutation rate of the marker and the effects of sampling. That is, while responding to this growth rate, indices should be unresponsive to the sample size and the mutation rate. We use simulation methods taking into account both the mutation and sampling processes to evaluate indices designed to quantify transmission of tuberculosis. RESULTS: Previously proposed indices generally perform inadequately according to the above criteria, with the partial exception of the recently proposed Transmission-Mutation Index. CONCLUSION: Any transmission index needs to take into account mutation of the marker and the effects of sampling. Simple indices are unlikely to capture the full complexity of the underlying processes

Tumours and tumour-like lesions of the lower face at Korle Bu Teaching Hospital, Ghana – an eight year study

<p>Abstract</p> <p>Background</p> <p>The oro-facial region including the jawbones, the maxilla and mandible and related tissues can be the site of a multitude of neoplastic conditions. These tumours have a predilection for the entire facial region; however, odontogenic tumours tend to affect the mandible more than the maxilla, especially, in West African children. We report results from a retrospective study spanning eight years on the frequency, clinical presentation, sites and character of lower face tumours seen in the main referral hospital in Ghana.</p> <p>Patients and methods</p> <p>Records of consecutive patients of all age and sex seen by the first author's team at the Department of Oral and Maxillofacial Surgery, Korle-Bu Teaching Hospital with tumours affecting the lower part of the face from January 1996 to December 2003 were retrieved, coded and entered into a database. The data were then analyzed by age, sex, presenting signs and symptoms, site of lesion, and their histology.</p> <p>Results</p> <p>A total of 394 patients with oro-facial swellings were retrieved from the registry out of which 210 had lower face tumour and tumour-like lesions. The complete data set was obtained for 171 patients, comprising 99 (58%) males and 72 (42%) females. The most common clinical presenting features were mandibular facial swelling (63%), intra-oral swelling (55%), pain (41%) and ulceration (29%). The tumours were predominantly found in the right (43%), anterior (19%) and left (18%) aspects of the lower face. The remainder making up 20% were found in the floor of the mouth, tongue and lips. Seventy eight (45.6%) of the patients presented with lesions that were classified as malignant of which 54 (62%) were diagnosed as squamous cell carcinoma (SCC). Sixty-two (36.3%) had benign odontogenic tumours and thirty-one (18.1%) had non-odontogenic tumour-like lesions. Fifty-four (62%) of malignant tumours were squamous cell carcinoma; 58 (93.6%) of the benign odontogenic tumours were classified as ameloblastoma. The mean age at presentation of all lesions was 40.4 years with over 50% of benign lesions in patients aged between 11 and 30 years. Malignant tumours were more commonly detected in patients between 41 and 70 years (63%).</p> <p>Conclusion</p> <p>Tumours and tumour-like lesions of the lower face comprising the mandible, tongue and adjacent structures are a diverse group of neoplasm and are seen commonly in practice of Maxillofacial surgery. Both malignant and benign tumours are seen in the Ghanaian population. In the present study, SCC and ameloblastoma were the commonest malignant and benign odontogenic tumours seen respectively; the two representing more than 65% of all tumours.</p

Malignant melanoma of the mandibular gingiva

Oral malignant melanoma is an infrequent neoplasia making up less than 1% of all melanomas, which exhibits much more aggressive behavior than those found on the skin. We present an aggressive case of oral malignant melanoma located on the mandibular gingiva in a 24-year-old male patient, who developed metastases to not only the regional lymph nodes but also the lungs and liver. The advanced stage of the disease contraindicated any surgical intervention and palliative chemotherapy was planned

An asymmetric explosion as the origin of spectral evolution diversity in type Ia supernovae

Type Ia Supernovae (SNe Ia) form an observationally uniform class of stellar explosions, in that more luminous objects have smaller decline-rates. This one-parameter behavior allows SNe Ia to be calibrated as cosmological `standard candles', and led to the discovery of an accelerating Universe. Recent investigations, however, have revealed that the true nature of SNe Ia is more complicated. Theoretically, it has been suggested that the initial thermonuclear sparks are ignited at an offset from the centre of the white-dwarf (WD) progenitor, possibly as a result of convection before the explosion. Observationally, the diversity seen in the spectral evolution of SNe Ia beyond the luminosity decline-rate relation is an unresolved issue. Here we report that the spectral diversity is a consequence of random directions from which an asymmetric explosion is viewed. Our findings suggest that the spectral evolution diversity is no longer a concern in using SNe Ia as cosmological standard candles. Furthermore, this indicates that ignition at an offset from the centre of is a generic feature of SNe Ia.Comment: To appear in Nature, 1st July 2010 issue. 36 pages including supplementary materials. 4 figures, 3 supplementary figures, 1 supplementary tabl

Examining a staging model for anorexia nervosa: empirical exploration of a four stage model of severity.

Background: An illness staging model for anorexia nervosa (AN) has received increasing attention, but assessing the merits of this concept is dependent on empirically examining a model in clinical samples. Building on preliminary findings regarding the reliability and validity of the Clinician Administered Staging Instrument for Anorexia Nervosa (CASIAN), the current study explores operationalising CASIAN severity scores into stages and assesses their relationship with other clinical features. Method: In women with DSM-IV-R AN and sub-threshold AN (all met AN criteria using DSM 5), receiver operating curve (ROC) analysis (n = 67) assessed the relationship between the sensitivity and specificity of each stage of the CASIAN. Thereafter chi-square and post-hoc adjusted residual analysis provided a preliminary assessment of the validity of the stages comparing the relationship between stage and treatment intensity and AN sub-types, and explored movement between stages after six months (Time 3) in a larger cohort (n = 171). Results: The CASIAN significantly distinguished between milder stages of illness (Stage 1 and 2) versus more severe stages of illness (Stages 3 and 4), and approached statistical significance in distinguishing each of the four stages from one other. CASIAN Stages were significantly associated with treatment modality and primary diagnosis, and CASIAN Stage at Time 1 was significantly associated with Stage at 6 month follow-up. Conclusions: Provisional support is provided for a staging model in AN. Larger studies with longer follow-up of cases are now needed to replicate and extend these findings and evaluate the overall utility of staging as well as optimal staging models