A new Early Cretaceous lizard in Myanmar amber with exceptionally preserved integument

We here report on a well-preserved juvenile lizard specimen in Albian amber (ca. 110 mya) from the Hkamti site (Myanmar). This new taxon is represented by an articulated skull and the anterior portion of the trunk, including the pectoral girdle and forelimbs. The scleral ossicles and eyelid are also visible, and the specimen exhibits pristine detail of the integument (of both head and body). In a combined molecular and morphological analysis, it was consistently recovered as a scincoid lizard (Scinciformata), as sister to Tepexisaurus + Xantusiidae. However, the phylogenetic position of the new taxon should be interpreted with caution as the holotype is an immature individual. We explored the possibility of miscoding ontogenetically variable characters by running alternative analyses in which these characters were scored as missing data for our taxon. With the exception of one tree, in which it was sister to Amphisbaenia, the specimen was recovered as a Pan-xantusiid. Moreover, we cannot rule out the possibility that it represents a separate lineage of uncertain phylogenetic position, as it is the case for many Jurassic and Cretaceous taxa. Nonetheless, this fossil offers a rare opportunity to glimpse the external appearance of one group of lizards during the Early Cretaceous

Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis

Introduction Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compared the concentrations of cerebrospinal fluid (CSF) and serum proteins between children who had TBM-related stroke and children with TBM without stroke. Methods We collected CSF and serum from 47 children consecutively admitted to the Tygerberg Academic Hospital in Cape Town, South Africa between November 2016, and November 2017, on suspicion of having TBM. A multiplex platform was used to measure the concentrations of 69 host proteins in CSF and serum from all study participants. Results After classification of study participants, 23 (48.9%) out of the 47 study participants were diagnosed with TBM, of which 14 (60.9%) demonstrated radiological arterial ischemic infarction. The levels of lipocalin-2, sRAGE, IP-10/ CXCL10, sVCAM-1, MMP-1, and PDGF-AA in CSF samples and the levels of D-dimer, ADAMTS13, SAA, ferritin, MCP-1/ CCL2, GDF-15 and IL-13 in serum samples were statistically different between children who had TBM-related stroke and children with TBM without stroke. After correcting for multiple testing, only the levels of sVCAM-1, MMP-1, sRAGE, and IP-10/ CXCL10 in CSF were statistically different between the two groups. CSF and serum protein biosignatures indicated stroke in children diagnosed with TBM with up to 100% sensitivity and 88.9% specificity. Conclusion Serum and CSF proteins may serve as biomarkers for identifying individuals with stroke amongst children diagnosed with TBM at admission and may guide us to understand the biology of stroke in TBM. This was a pilot study, and thus further investigations in larger studies are needed

Potential of Host Markers Produced by Infection Phase-Dependent Antigen-Stimulated Cells for the Diagnosis of Tuberculosis in a Highly Endemic Area

CITATION: Chegou, N. N. et al. 2012. Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area. PLoS ONE, 7(6): e38501, doi:10.1371/journal.pone.0038501.The original publication is available at http://journals.plos.org/plosoneBackground: Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions: Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays. © 2012 Chegou et al.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038501Publisher's versio

Similarities and Differences in Chinese and Caucasian Adults' Use of Facial Cues for Trustworthiness Judgments

All cultural groups in the world place paramount value on interpersonal trust. Existing research suggests that although accurate judgments of another's trustworthiness require extensive interactions with the person, we often make trustworthiness judgments based on facial cues on the first encounter. However, little is known about what facial cues are used for such judgments and what the bases are on which individuals make their trustworthiness judgments.In the present study, we tested the hypothesis that individuals may use facial attractiveness cues as a “shortcut” for judging another's trustworthiness due to the lack of other more informative and in-depth information about trustworthiness. Using data-driven statistical models of 3D Caucasian faces, we compared facial cues used for judging the trustworthiness of Caucasian faces by Caucasian participants who were highly experienced with Caucasian faces, and the facial cues used by Chinese participants who were unfamiliar with Caucasian faces. We found that Chinese and Caucasian participants used similar facial cues to judge trustworthiness. Also, both Chinese and Caucasian participants used almost identical facial cues for judging trustworthiness and attractiveness.The results suggest that without opportunities to interact with another person extensively, we use the less racially specific and more universal attractiveness cues as a “shortcut” for trustworthiness judgments

Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting

<p>Abstract</p> <p>Background</p> <p>Confirming tuberculosis (TB) disease in suspects in resource limited settings is challenging and calls for the development of more suitable diagnostic tools. Different <it>Mycobacterium tuberculosis (M.tb) </it>infection phase-dependent antigens may be differentially recognized in infected and diseased individuals and therefore useful as diagnostic tools for differentiating between <it>M.tb </it>infection states. In this study, we assessed the diagnostic potential of 118 different <it>M.tb </it>infection phase-dependent antigens in TB patients and household contacts (HHCs) in a high-burden setting.</p> <p>Methods</p> <p>Antigens were evaluated using the 7-day whole blood culture technique in 23 pulmonary TB patients and in 19 to 21 HHCs (total n = 101), who were recruited from a high-TB incidence community in Cape Town, South Africa. Interferon-gamma (IFN-γ) levels in culture supernatants were determined by ELISA.</p> <p>Results</p> <p>Eight classical TB vaccine candidate antigens, 51 DosR regulon encoded antigens, 23 TB reactivation antigens, 5 TB resuscitation promoting factors (rpfs), 6 starvation and 24 other stress response-associated TB antigens were evaluated in the study. The most promising antigens for ascertaining active TB were the rpfs (Rv0867c, Rv2389c, Rv2450c, Rv1009 and Rv1884c), with Areas under the receiver operating characteristics curves (AUCs) between 0.72 and 0.80. A combination of <it>M.tb </it>specific ESAT-6/CFP-10 fusion protein, Rv2624c and Rv0867c accurately predicted 73% of the TB patients and 80% of the non-TB cases after cross validation.</p> <p>Conclusions</p> <p>IFN-γ responses to TB rpfs show promise as TB diagnostic candidates and should be evaluated further for discrimination between <it>M.tb </it>infection states.</p

The UNC-45 Chaperone Is Critical for Establishing Myosin-Based Myofibrillar Organization and Cardiac Contractility in the Drosophila Heart Model

UNC-45 is a UCS (UNC-45/CRO1/She4P) class chaperone necessary for myosin folding and/or accumulation, but its requirement for maintaining cardiac contractility has not been explored. Given the prevalence of myosin mutations in eliciting cardiomyopathy, chaperones like UNC-45 are likely to be equally critical in provoking or modulating myosin-associated cardiomyopathy. Here, we used the Drosophila heart model to examine its role in cardiac physiology, in conjunction with RNAi-mediated gene silencing specifically in the heart in vivo. Analysis of cardiac physiology was carried out using high-speed video recording in conjunction with movement analysis algorithms. unc-45 knockdown resulted in severely compromised cardiac function in adults as evidenced by prolonged diastolic and systolic intervals, and increased incidence of arrhythmias and extreme dilation; the latter was accompanied by a significant reduction in muscle contractility. Structural analysis showed reduced myofibrils, myofibrillar disarray, and greatly decreased cardiac myosin accumulation. Cardiac unc-45 silencing also dramatically reduced life-span. In contrast, third instar larval and young pupal hearts showed mild cardiac abnormalities, as severe cardiac defects only developed during metamorphosis. Furthermore, cardiac unc-45 silencing in the adult heart (after metamorphosis) led to less severe phenotypes. This suggests that UNC-45 is mostly required for myosin accumulation/folding during remodeling of the forming adult heart. The cardiac defects, myosin deficit and decreased life-span in flies upon heart-specific unc-45 knockdown were significantly rescued by UNC-45 over-expression. Our results are the first to demonstrate a cardiac-specific requirement of a chaperone in Drosophila, suggestive of a critical role of UNC-45 in cardiomyopathies, including those associated with unfolded proteins in the failing human heart. The dilated cardiomyopathy phenotype associated with UNC-45 deficiency is mimicked by myosin knockdown suggesting that UNC-45 plays a crucial role in stabilizing myosin and possibly preventing human cardiomyopathies associated with functional deficiencies of myosin

The serum zinc concentration as a potential biological marker in patients with major depressive disorder

Despite many clinical trials assessing the role of zinc in major depressive disorder (MDD), the conclusions still remain ambiguous. The aim of the present clinical study was to determine and comparison the zinc concentration in the blood of MDD patients (active stage or remission) and healthy volunteers (controls), as well as to discuss its potential clinical usefulness as a biomarker of the disease. In this study 69 patients with current depressive episode, 45 patients in remission and 50 controls were enrolled. The zinc concentration was measured by electrothermal atomic absorption spectrometry (ET AAS). The obtained results revealed, that the zinc concentration in depressed phase were statistically lower than in the healthy volunteers [0.89 vs. 1.06 mg/L, respectively], while the zinc level in patients achieve remission was not significantly different from the controls [1.07 vs. 1.06 mg/L, respectively]. Additionally, among the patients achieve remission a significant differences in zinc concentration between group with and without presence of drug-resistance in the previous episode of depression were observed. Also, patients in remission demonstrated correlation between zinc level and the average number of depressive episodes in the last year. Serum zinc concentration was not dependent on atypical features of depression, presence of psychotic symptoms or melancholic syndrome, age, age of onset or duration of disease, number of episodes in the life time, duration of the episode/remission and severity of depression measured by the Hamilton Rating Scale for Depression (HDRS), and the Montgomery-Asberg Depression Rating Scale (MADRS). Concluding, our findings confirm the correlation between zinc deficit present in the depressive episode, and are consistent with the majority of previous studies. These results may also indicate that serum zinc concentration might be considered as a potential biological marker of MDD

Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins

The cell envelope of mycobacteria, a group of Gram positive bacteria, is composed of a plasma membrane and a Gram-negative-like outer membrane containing mycolic acids. In addition, the surface of the mycobacteria is coated with an ill-characterized layer of extractable, non-covalently linked glycans, lipids and proteins, collectively known as the capsule, whose occurrence is a matter of debate. By using plunge freezing cryo-electron microscopy technique, we were able to show that pathogenic mycobacteria produce a thick capsule, only present when the cells were grown under unperturbed conditions and easily removed by mild detergents. This detergent-labile capsule layer contains arabinomannan, α-glucan and oligomannosyl-capped glycolipids. Further immunogenic and proteomic analyses revealed that Mycobacterium marinum capsule contains high amounts of proteins that are secreted via the ESX-1 pathway. Finally, cell infection experiments demonstrated the importance of the capsule for binding to cells and dampening of pro-inflammatory cytokine response. Together, these results show a direct visualization of the mycobacterial capsular layer as a labile structure that contains ESX-1-secreted proteins

A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway

Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-XL overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD) expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria

Focus on Function – a randomized controlled trial comparing two rehabilitation interventions for young children with cerebral palsy

<p>Abstract</p> <p>Background</p> <p>Children with cerebral palsy receive a variety of long-term physical and occupational therapy interventions to facilitate development and to enhance functional independence in movement, self-care, play, school activities and leisure. Considerable human and financial resources are directed at the "intervention" of the problems of cerebral palsy, although the available evidence supporting current interventions is inconclusive. A considerable degree of uncertainty remains about the appropriate therapeutic approaches to manage the habilitation of children with cerebral palsy. The primary objective of this project is to conduct a multi-site randomized clinical trial to evaluate the efficacy of a task/context-focused approach compared to a child-focused remediation approach in improving performance of functional tasks and mobility, increasing participation in everyday activities, and improving quality of life in children 12 months to 5 years of age who have cerebral palsy.</p> <p>Method/Design</p> <p>A multi-centred randomized controlled trial research design will be used. Children will be recruited from a representative sample of children attending publicly-funded regional children's rehabilitation centers serving children with disabilities in Ontario and Alberta in Canada. Target sample size is 220 children with cerebral palsy aged 12 months to 5 years at recruitment date. Therapists are randomly assigned to deliver either a context-focused approach or a child-focused approach. Children follow their therapist into their treatment arm. Outcomes will be evaluated at baseline, after 6 months of treatment and at a 3-month follow-up period. Outcomes represent the components of the International Classification of Functioning, Disability and Health, including body function and structure (range of motion), activities (performance of functional tasks, motor function), participation (involvement in formal and informal activities), and environment (parent perceptions of care, parental empowerment).</p> <p>Discussion</p> <p>This paper presents the background information, design and protocol for a randomized controlled trial comparing a task/context-focused approach to a child-focused remediation approach in improving functional outcomes for young children with cerebral palsy.</p> <p>Trial registration</p> <p>[clinical trial registration #: NCT00469872]</p