ya\u27 between vocative and non-vocative use in Egyptian film language A corpus analysis: pragmatic functions and formal features

This study investigates the functional and formal features of constructions built with the particle ya in the Egyptian Arabic film language of the film eš-šabaḥ (The Ghost) (2007). Studying ya is of interest as it is the most frequent lexical item after the conjunction we (and) in the data. By means of using WordSmith Tools Lexical Analysis Software, a concordance of instances of ya in the data was built. In line with the Speech Act theory by Austin (1975), a quantitative design was employed which enabled the findings to be classified according to their functional and formal properties. Regarding formal features, the results show specific patterns and collocates within each functional category of ya. As regards functional features, 88% of the ya phrases in the data convey vocative use while 12 % indicate non-vocative use. Within the vocative use, ya phrases are found to be mainly identificational, activational, predicational, or unreal. There is a category for contractures with an omitted vocative head. In non-vocative use, ya is found as an exclamation particle. This study has implications for teaching EA, formulating the grammar rules of EA, and translating dialogs from and into EA

Chemistry and NMR studies of Beta-Catenin-TCF4 interaction

Abweichungen im Wnt/Beta-Catenin Signalweg kommen in vielen verschiedenen menschlichen Krebserkrankungen vor. Unter anderem wird dieser Signalweg in Darm- und Eierstockkrebs aktiviert. Aus diesem Grund haben Inhibitoren der TCF4/Beta-Catenin Interaktion großes Potential als Antitumormittel. Mit Hilfe des vor kurzem beschriebenen „Meta-Structure“ Ansatzes haben wir eine Reihe von niedermolekularen Molekülen identifiziert, die an Beta-Catenin binden und als Ausgnagspunkt für zukünftige Entwicklungen dienen könnten. Um diese Interaktionen zu testen, wurden verschiedene Methoden angewandt: 1D 1H-STD, 1D AFP NOESY, 2D NOESY und 19F-NMR. Auch die Fähigkeit der neu identifizierten Liganden mit dem bekannten Bindungspartner TCF4 von Beta-Catenin zu konkurrieren wurde getestet. Zur weiteren Untersuchung der Interaktionen und um weitere neue Liganden synthetisieren und identifizieren zu können, wurde ein sogenannter „Dynamic Combinatorial Library“ Ansatz (Dynamische, kombinierbare Chemikalienbibliothek) adaptiert und mithilfe . Weiters wurden zwei- und dreidimensionale NMR-Experimente durchgeführt, mit welchen die 1N-15H Signale des TCF4 Proteinrückgrats, und zweier separate Teile hiervon, bei pHs von 4,5 und 2,0 zugeordet werden konnten. Ein Vergleich der so bestimmten Frequenzen mit den errechneten Werten eines theoretischen, gänzlich unstrukturierten Proteins gleicher Aminosäuresequenz („Secondary Structure Propensity“) erlaubte es, Aussagen über die Wahrscheinlichkeit von Sekundärstrukturen bei verschiedenen pH-Werten zu machen. Zusätzlich zu der Untersuchung neuer Liganden wurde auch die Struktur des TCF4/Beta-Catenin Komplexes näher untersucht. Hierfür wurden sowohl röntgenkristallographische Experimente verwendet, als auch die selektive Reduzierung von Lysin-Seitenkette mit 13HCHO, welche ein Messen des daraus resultierenden 13C-1H Spektrums erlaubt. Um die Relevanz meiner Untersuchungen zu unterstreichen, werden die sich ergebenden Möglichkeiten für die Entwicklung eines neuen Antitumormittels mit möglichst hohem Sicherheitsprofil erörtert.Aberrant Wnt/Beta-Catenin signaling is observed in a wide spectrum of human malignancies. Activation of this pathway is involved in colon and ovarian cancer. Therefore, inhibitors of the TCF4/Beta-Catenin interaction are of great potential as antitumor agents. We used the recently described protein meta-structure approach to identify novel small molecule compounds as binders for Beta-Catenin. The identified ligands have been tested for binding with the target protein using 1D 1H-STD, 1D AFP NOESY, 2D NOESY and 19F-NMR. The identified binders were demonstrated to compete with the authentic Beta-Catenin binding partner TCF4. In addition, a dynamic combinatorial library has been designed to synthesize new ligands for Beta-Catenin. Moreover, 2D & 3D-NMR experiments were used to assign the backbone signals of full length TCF4 and two different truncations at different pH values. The data obtained from assignment at pH=4.5 and pH=2 were compared with the predicted random coil shifts. Secondary structure propensities were also compared which allowed us to estimate changes in secondary structure propensities upon pH change. Finally, further structural insight into the TCF4/Beta-Catenin complex was provided by a combined X-ray crystallography and NMR study employing selective lysine reductive-methylation reaction. To highlight the importance of our work, the resulting prospects for the development of new powerful anticancer drugs with a high safety profile will also be discussed

Recent Advances

Although often depicted as rigid structures, proteins are highly dynamic systems, whose motions are essential to their functions. Despite this, it is difficult to investigate protein dynamics due to the rapid timescale at which they sample their conformational space, leading most NMR-determined structures to represent only an averaged snapshot of the dynamic picture. While NMR relaxation measurements can help to determine local dynamics, it is difficult to detect translational or concerted motion, and only recently have significant advances been made to make it possible to acquire a more holistic representation of the dynamics and structural landscapes of proteins. Here, we briefly revisit our most recent progress in the theory and use of exact nuclear Overhauser enhancements (eNOEs) for the calculation of structural ensembles that describe their conformational space. New developments are primarily targeted at increasing the number and improving the quality of extracted eNOE distance restraints, such that the multi-state structure calculation can be applied to proteins of higher molecular weights. We then review the implications of the exact NOE to the protein dynamics and function of cyclophilin A and the WW domain of Pin1, and finally discuss our current research and future directions

A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport

All animal cells use the motor cytoplasmic dynein 1 (dynein) to transport diverse cargo toward microtubule minus ends and to organize and position microtubule arrays such as the mitotic spindle. Cargo-specific adaptors engage with dynein to recruit and activate the motor, but the molecular mechanisms remain incompletely understood. Here, we use structural and dynamic nuclear magnetic resonance (NMR) analysis to demonstrate that the C-terminal region of human dynein light intermediate chain 1 (LIC1) is intrinsically disordered and contains two short conserved segments with helical propensity. NMR titration experiments reveal that the first helical segment (helix 1) constitutes the main interaction site for the adaptors Spindly (SPDL1), bicaudal D homolog 2 (BICD2), and Hook homolog 3 (HOOK3). In vitro binding assays show that helix 1, but not helix 2, is essential in both LIC1 and LIC2 for binding to SPDL1, BICD2, HOOK3, RAB-interacting lysosomal protein (RILP), RAB11 family-interacting protein 3 (RAB11FIP3), ninein (NIN), and trafficking kinesin-bind-ing protein 1 (TRAK1). Helix 1 is sufficient to bind RILP, whereas other adaptors require additional segments preceding helix 1 for efficient binding. Point mutations in the C-terminal helix 1 of Caenorhabditis elegans LIC, introduced by genome editing, severely affect development, locomotion, and life span of the animal and disrupt the distribution and transport kinetics of membrane cargo in axons of mechanosensory neurons, identical to what is observed when the entire LIC C-terminal region is deleted. Deletion of the C-terminal helix 2 delays dynein-dependent spindle positioning in the one-cell embryo but overall does not significantly perturb dynein function. We conclude that helix 1 in the intrinsically disordered region of LIC provides a conserved link between dynein and structurally diverse cargo adaptor families that is critical for dynein function in vivo.This work was financed by the Fundo Europeu de Desenvolvimento Regional (FEDER) through the Norte Portugal Regional Operational Programme (NORTE 2020), Portugal 2020 (RG); by the Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project NORTE-01-0145-FEDER-030507 (RG); by FCT fellowships IF/01015/2013/CP1157/CT0006 (RG) and SFRH/ BPD/101898/2014 (DJB); by the European Research Council under the European Union’s Seventh Framework Programme, ERC grant agreement no. ERC-2013-StG-338410-DYNEINOME (RG), and by a start-up package of the University of Colorado (BV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Body of evidence: forensic use of baseline health assessments to convict wildlife poachers

CONTEXT. Given the immense impact of wildlife trade, disease and repatriations on populations, health assessments can" "provide powerful forensic material to help convict wildlife poachers and minimise risks of releasing unhealthy wildlife." AIMS. We aimed to use reference ranges to assess the health of confiscated tortoises, to illustrate forensic application of these ranges, and to advance analyses for future applications." METHODS. We used analyses of variance (ANOVA) and covariance (ANCOVA), and composite indices, to compare wild and confiscate tortoise body condition, haematocrit and haemoglobin concentration of males and females of three tortoise species. Subsequently, we used multivariate statistics (e.g. discriminant analyses) to evaluate the relative importance of species, sex and group (wild or confiscate) on tortoise condition and haematology." KEY RESULTS. Our initial statistical tests demonstrated, at P < 0.05 to P < 0.0005, that confiscate body condition and haematology were compromised compared with that of wild tortoises. Subsequently, discriminant analyses strongly discriminated between most wild and confiscate groups (P < 0.0001), correctly classified individual health as wild or confiscate 80–90% of the time, indicated that species and sex effects were stronger than was the wild-confiscate category, and provided discriminant functions for use on other taxa and studies." CONCLUSIONS. The health assessments discriminated well between wild and confiscate tortoises. The results had considerable forensic value, being relevant, quickly generated using portable field equipment, reliable, accurate, easy to explain and convey in terms of likelihood in a court of law, synergistically consistent among variables and groups, a strong rebuttal to the poachers’ specific statements, and consistent with other types of evidence. Multivariate analyses were consistent with, and more prudent and powerful than, the original statistical analyses. Discriminant functions can be applied in future studies and on other chelonian species, and should be developed for other wildlife species." IMPLICATIONS. Reference ranges provide considerable value for forensics, diagnostics and treatment. Given the disease risks resulting from the massive scale of wildlife trade and release, reference ranges should be developed for more species."Web of Scienc

Manager’s Leadership Is the Main Skill for Ambulatory Health Care Plan Success

To demonstrate effectiveness of ambulatory health care plan implementation among institutions and variables associated with the differences observed. Randomized selection of primary health care (PHC) centers was done. Leadership ability of the plan manager was explored. Univariate/bivariate analyses were performed to observe correlation between variables. Two groups of PHC centers were established according to the efficacy of plan implementation: high and low performance. Differences between groups were observed (592%-1023% more efficacy in controls and practices; P < .001). Leadership was responsible for the main differences observed. Leadership of manager for implementation of the health care plan was the major important variable to reach the best efficacy standards.Facultad de Ciencias Médica

Population ecology of Psammobates oculifer in a semi-arid environment

We studied the ecology of Psammobates oculifer over 13 months near Kimberley, South Africa, to ascertain if the population’s life history traits conform to chelonian patterns in arid environments. Capture rates were highest in spring and lowest in winter when environmental conditions were respectively most and least favourable for tortoise activity. Body condition did not change from autumn to spring, but reached lower values during the summer drought. Capture effort averaged 5 hours/tortoise, which corresponds closely to that of species with low population densities in arid regions. Population size structure was skewed towards adults, indicative of low recruitment and/or low juvenile survivorship. Females were larger and heavier than males, confirming sexual dimorphism in this species. Body size of cohorts scaled to annuli counts, indicating a close correspondence between body size and age. Telemetered adults deposited one or no growth ring in the year of study; consequently, annuli counts could underestimate adult age. Regression analyses showed that male and female growth rates did not differ, but males matured at a smaller size and younger age than females. The smallest male showing reproductive behaviour had 12 annuli and a shell volume of 157 cm3, while similar measures for females were 14 annuli and 185 cm3. The sex ratio of the population did not differ from 1:1 but the bias towards males in spring, and towards females in autumn, indicates that studies limited to particular seasons can misrepresent life history traits of populations. We concluded that the life history of P. oculifer conforms to chelonian patterns in arid regions.Web of Scienc