Assessing the origin of Neotropical mountain dung beetle assemblages (Scarabaeidae: Scarabaeinae): the comparative influence of vertical and horizontal colonization

Aims The fauna of mountains and their surrounding regions are likely to be influenced principally by two biological processes: horizontal colonization along similar altitudinal levels by elements originating from lineages inhabiting higher latitudes; and vertical colonization by lineages from the same latitude, but at lower altitudes. We examine whether the expected patterns derived from the latter process can be observed in mountain dung beetle assemblages. Specifically, we study the variation in species composition and richness with altitude in five regions spanning elevation gradients, analysing whether the altitudinal rates of change in the number of species and genera differ, and whether beta‐diversity scores for adjacent sites in each altitudinal gradient are different for species and genera. Location Eastern Cordillera of the Colombian Andes. Methods Field work was carried out in 1997–99 at 27 sites in five regions with elevation gradients, with 10–32 pitfall traps placed in each site. For each altitudinal level the numbers of species and genera were analysed with respect to altitude, and the slope of the linear regression between these variables was calculated. The slope of the curve of the altitude against the cumulative number of species and genera was also calculated for each altitudinal gradient to describe the compositional change between adjacent sites (beta diversity). Species and generic slopes were compared using analysis of covariance. The turnover of species along each altitudinal gradient was measured using presence/absence data and Cody's beta‐diversity index between adjacent pairs of sites. A cluster analysis was used to detect faunistically homogeneous groups of localities. Results Species richness always decreased with altitude, although the slopes did not differ significantly from zero. The number of genera also decreased with increasing altitude, but generally at a significantly slower rate than for species. Variation in the species beta‐diversity scores between altitudinal levels did not follow a homogeneous pattern in the different regions. Two main altitudinal groups of sites with a boundary c. 1500–1750 m a.s.l. can be detected with respect to faunistic similarity. Low‐ and mid‐altitude sites are inhabited by all of the genera (19) and 80% of all species collected. Eight genera and 61 species (c. 60% of the total) are unable to inhabit high‐altitude sites, and only 20 species appear to be exclusive to these high‐altitude environments (> 2000 m a.s.l.). Main conclusions The dominant processes explaining dung beetle composition in the high north‐eastern Andean mountains are probably those of vertical colonization. The limited role of horizontal colonization processes, or colonization from northern or southern lineages, could be a consequence of the isolation and recent geological origin of these mountains.     

Prediction of the articular eminence shape in a patient with unilateral hypoplasia of the right mandibular ramus before and after distraction osteogenesis—A simulation study

The aim of this work was to predict the shape of the articular eminence in a patient with unilateral hypoplasia of the right mandibular ramus before and after distraction osteogenesis (DO). Using a patient-specific musculoskeletal model of the mandible the hypothesis that the observed differences in this patient in the left and right articular eminence inclinations were consistent with minimisation of joint loads was tested. Moreover, a prediction was made of the final shape of the articular eminence after DO when the expected remodelling has reached a steady state. The individual muscle forces and the average TMJ loading were computed for each combination of articular eminence angles both before and after DO. This exhaustive parameter study provides a full overview of average TMJ loading depending on the angles of the articular eminences. Before DO the parameter study resulted in different articular eminence inclinations between left and right sides consistent with patient data obtained from CT scans, indicating that in this patient the articular eminence shapes result from minimisation of joint loads. The simulation model predicts development of almost equal articular eminence shapes after DO. The same tendency was observed in cone beam CT scans (NewTom) of the patient taken 6.5 years after surgery.     

Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase

Oncogenic mutation of the RET receptor tyrosine kinase is observed in several human malignancies. Here, we describe three novel type II RET tyrosine kinase inhibitors (TKI), ALW-II-41-27, XMD15-44 and HG-6-63-01, that inhibit the cellular activity of oncogenic RET mutants at two digit nanomolar concentration. These three compounds shared a 3-trifluoromethyl-4-methylpiperazinephenyl pharmacophore that stabilizes the ‘DFG-out’ inactive conformation of RET activation loop. They blocked RET-mediated signaling and proliferation with an IC50 in the nM range in fibroblasts transformed by the RET/C634R and RET/M918T oncogenes. They also inhibited autophosphorylation of several additional oncogenic RET-derived point mutants and chimeric oncogenes. At a concentration of 10 nM, ALW-II-41-27, XMD15-44 and HG-6-63-01 inhibited RET kinase and signaling in human thyroid cancer cell lines carrying oncogenic RET alleles; they also inhibited proliferation of cancer, but not non-tumoral Nthy-ori-3-1, thyroid cells, with an IC50 in the nM range. The three compounds were capable of inhibiting the ‘gatekeeper’ V804M mutant which confers substantial resistance to established RET inhibitors. In conclusion, we have identified a type II TKI scaffold, shared by ALW-II-41-27, XMD15-44 and HG-6-63-01, that may be used as novel lead for the development of novel agents for the treatment of cancers harboring oncogenic activation of RET.     

Improved Framework for Tractography Reconstruction of the Optic Radiation

The optic radiation (OR) is one of the major components of the visual system and a key structure at risk in white matter diseases such as multiple sclerosis (MS). However, it is challenging to perform track reconstruction of the OR using diffusion MRI due to a sharp change of direction in the Meyer’s loop and the presence of kissing and crossing fibers along the pathway. As such, we aimed to provide a highly precise and reproducible framework for tracking the OR from thalamic and visual cortex masks. The framework combined the generation of probabilistic streamlines by high order fiber orientation distributions estimated with constrained spherical deconvolution and an automatic post-processing based on anatomical exclusion criteria (AEC) to compensate for the presence of anatomically implausible streamlines. Specifically, those ending in the contralateral hemisphere, cerebrospinal fluid or grey matter outside the visual cortex were automatically excluded. We applied the framework to two distinct high angular resolution diffusion-weighted imaging (HARDI) acquisition protocols on one cohort, comprised of ten healthy volunteers and five MS patients. The OR was successfully delineated in both HARDI acquisitions in the healthy volunteers and MS patients. Quantitative evaluation of the OR position was done by comparing the results with histological reference data. Compared with histological mask, the OR reconstruction into a template (OR-TCT) was highly precise (percentage of voxels within the OR-TCT correctly defined as OR), ranging from 0.71 to 0.83. The sensitivity (percentage of voxels in histological reference mask correctly defined as OR in OR-TCT) ranged from 0.65 to 0.81 and the accuracy (measured by F1 score) was 0.73 to 0.77 in healthy volunteers. When AEC was not applied the precision and accuracy decreased. The absolute agreement between both HARDI datasets measured by the intraclass correlation coefficient was 0.73. This improved framework allowed us to reconstruct the OR with high reliability and accuracy independently of the acquisition parameters. Moreover, the reconstruction was possible even in the presence of tissue damage due to MS. This framework could also be applied to other tracts with complex configuration.     

Dysregulation of the Descending Pain System in Temporomandibular Disorders Revealed by Low-Frequency Sensory Transcutaneous Electrical Nerve Stimulation: A Pupillometric Study

Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS) is dysregulated in patients suffering from temporomandibular disorders (TMDs), suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG) is involved in the descending modulation of defensive behavior and pain through μ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS) has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of μ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation) and long after (recovery period) sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired modulation of the descending pain system may be involved in TMD.     

Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

Background

Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques.

Methods

A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK.

Results

A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort).

Conclusion

The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.