GSK3 and lamellipodin balance lamellipodial protrusions and focal adhesion maturation in mouse neural crest migration.

Neural crest cells are multipotent cells that delaminate from the neuroepithelium, migrating throughout the embryo. Aberrant migration causes developmental defects. Animal models are improving our understanding of neural crest anomalies, but in vivo migration behaviors are poorly understood. Here, we demonstrate that murine neural crest cells display actin-based lamellipodia and filopodia in vivo. Using neural crest-specific knockouts or inhibitors, we show that the serine-threonine kinase glycogen synthase kinase-3 (GSK3) and the cytoskeletal regulator lamellipodin (Lpd) are required for lamellipodia formation while preventing focal adhesion maturation. Lpd is a substrate of GSK3, and phosphorylation of Lpd favors interactions with the Scar/WAVE complex (lamellipodia formation) at the expense of VASP and Mena interactions (adhesion maturation and filopodia formation). This improved understanding of cytoskeletal regulation in mammalian neural crest migration has general implications for neural crest anomalies and cancer.

Unravelling the Novel Effects of Three Volatile Compounds in Preventing Fibril Formation of Disease Related Tau and α-Synuclein Proteins- Towards Identifying Candidate Aromatic Substances for Treating Neurodegenerative Diseases.

Background: The aggregation of tau and α-synuclein into fibrillary assemblies in nerve cells is the molecular hallmark of Alzheimer's and Parkinson's diseases, respectively. In our previous studies, we investigated the anti-amyloidogenic effects of three different aroma-producing (volatile) compounds including cinnamaldehyde, phenyl ethyl alcohol, and TEMED on the fibrillation process of HEWL, as a model protein. Our previous results showed that while TEMED was able to completely stop the process of fibril formation, cinnamaldehyde and phenyl ethyl alcohol gave rise to oligomeric/protofibrillar forms and were involved in the entrapment of intermediate species of HEWL. In this study, we investigated the anti-amyloidogenic effect of the same three volatile compounds on recombinantly produced tau and α-synuclein proteins. Methods: The thioflavin T fluorescence assay, circular dichroism, SDS-PAGE/native-PAGE, dynamic light scattering, and atomic force microscopy were used, where necessary, to further our understanding of the inhibitory effects of the three volatile compounds on the fibril formation of tau and α-synuclein proteins and allow for a comparison with previous data obtained for HEWL. Results: Our results revealed that contrary to the results obtained for HEWL (a globular protein), the volatile compound TEMED was no longer able to prevent fibril formation in either of the natively unstructured tau or α-synuclein proteins, and instead, cinnamaldehye and phenyl ethyl alcohol, in particular, had the role of preventing fibril formation of tau or α-synuclein. Conclusion: The results of this study further emphasized the exclusion of HEWL as a model protein for fibrillation studies and highlighted the importance of studying brain-related proteins such as tau or α-synuclein and the need to assess the effects of volatile compounds such as cinnamaldehye and phenyl ethyl alcohol as potential substances in the treatment of neurodegenerative diseases.

Perception of Smile Aesthetics of Patients with Anterior Malocclusions and Lips Influence: A Comparison of Dental Professionals', Dental Students,' and Laypersons' Opinions.

OBJECTIVES: The aim of the study was to evaluate the perception of smile aesthetics in patients with varying degrees of anterior crowding and spacing among dental specialists, dentists, dental students, and laypersons and to assess the effect of the lips position. MATERIALS AND METHODS: Clinical photos of cases of anterior crowding (mild, moderate, and severe) and spacing (mild, moderate, and severe) with and without the associated lips were used. The images were evaluated by 250 persons including dental specialists, dentists, dental students, and laypersons using the rating scale method, (extremely unaesthetic to extremely aesthetic, 1 to 5, respectively). Nonparametric tests were used to analyse the data on SPSS version 24. RESULTS: According to the 250 responses, the aesthetic perception of all severities of anterior crowding and mild and moderate spacing was found to be more aesthetic when displayed with the lips (p < 0.05). Additionally, the higher the level of dental education, the lower the aesthetic perception with and without the lips (p < 0.05). CONCLUSIONS: The lips play a significant role in improving the aesthetics of crowded anterior teeth and spaced anterior teeth. Dental educational level influences the aesthetic perception of anterior crowding and spacing. This may have an impact on treatment planning and need for orthodontic intervention.

Rethinking Assessment Concepts in Dental Education.

INTRODUCTION: Dental education involves teaching and assessing the acquisition of verifiable domains that require superior psychomotor, communication, and cognitive skills. Evolving technologies and methods of assessment could enhance student's learning environment and improve tutor assessment experience. The aim of this study was to review the current body of research and evaluate the effectiveness of various methods of assessments in improving learning and performance in preclinical and clinical dental practice. MATERIALS AND METHODS: A search strategy was implemented using electronic search in major databases. The following key terms, clinical skills, preclinical, dental students, and assessment, were included in the search. Two reviewers independently screened all the articles retrieved following very specific inclusion criteria. RESULTS: The initial search generated 5371 articles and 24 articles were selected for review and data extraction. Cohen's kappa coefficient was used to measure interrater agreement and a score of 94.7% was obtained. CONCLUSION: Preclinical assessment is an effective tool for promoting skills transfer to clinical phase. Early psychomotor skills assessment is valuable. It allows early intervention in the learning process and assists in effective utilization of learning resources. Technology-enhanced assessment systems allow better patient simulation, enhance learning and self-assessment experiences, and improve performance evaluation. However, these systems serve as an adjunct to conventional assessment methods. Further research should aim at calibrating and integrating these systems to optimize students learning and performance.

Depression, anxiety and associated factors among housemaids working in Addis Ababa Ethiopia.

BACKGROUND: Housemaids are part of women with low socioeconomic status and most of them are migrant from rural to central part of Ethiopia, less educated, either with poor, separated, single or divorced family and/or dead parents. Housemaid may experience problems like depression and anxiety more than other groups of women. Therefore, the aim of this study was to assess the magnitude and determinants of those problems among housemaids. OBJECTIVE: To assess the magnitude and determinants of depression & anxiety among housemaids in Addis Ababa; Ethiopia; 2018. METHODS: Community based cross-sectional study was conducted from May 1 to August 30, 2018 among housemaids working in Addis Ababa, Ethiopia. Multistage sampling technique was applied with a total of 826 samples. Quantitative data was employed by using structured questionnaires. The collected data was coded, entered in to Epi-Info version 7 and analyzed by using SPSS version 20. Descriptive, analytical statistical procedures; bivariate and multivariate binary logistic regressions with odds ratios and 95% confidence interval was employed. The statistical significance was declared at p value < 0.05. RESULTS: This study enrolled 862 participants with response rate 99.5%, 99.5% refers to the number of people who actually completed the interview. The result showed prevalence of depression and anxiety among housemaids 27.5% and 32.3% respectively. Among all participants 44.6% (95% CI= 41.0 - 47.9) have mild, 18.5% (95% CI= 15.7 - 21.2) have moderate and 6.1% (95% CI= 4.5 - 7.8) have severe form of comorbid anxiety with depression. Depression (44.9%) and anxiety (41.9%) found more prevalent among the age group 16 to 20. In this study history of parental divorce, participant's divorce, physical violence and sexual violence are positively associated. Other factors; being less educated and living with relatives; were associated negatively. CONCLUSION: The prevalence of Depression and Anxiety is found high among housemaid; its prevalence is more among age group 16 to 20 than other age groups. Violence, participant's divorce, history of parental divorce and contraceptive use has positively associated with depression and anxiety.

The aroma of TEMED as an activation and stabilizing signal for the antibacterial enzyme HEWL.

The unpleasant smell released from dead bodies, may serve as an alarm for avoiding certain behaviour or as feeding or oviposition attractants for animals. However, little is known about their effect on the structure and function of proteins. Previously, we reported that using the aroma form of TEMED (a diamine), representative of the "smell of death", could completely inhibit the fibril formation of HEWL, as an antibacterial enzyme, and a model protein for fibrillation studies. To take this further, in this study we investigated the kinetics of TEMED using a number of techniques and in particular X-ray crystallography to identify the binding site(s) of TEMED and search for hotspot(s) necessary to inhibit fibril formation of HEWL. Structural data, coupled with other experimental data reported in this study, revealed that TEMED completely inhibited fibril formation and stabilized the structure of HEWL through enhancement of the CH-Π interaction and binding to an inhibitor hotspot comprised of residues Lys33, Phe34, Glu35 and Asn37 of HEWL. Additionally, results from this study showed that the binding of TEMED increased the activity and thermal stability of HEWL, helping to improve the function of this antibacterial enzyme. In conclusion, the role of the "smell of death", as an important signal molecule affecting the activity and stability of HEWL was greatly highlighted, suggesting that aroma producing small molecules can be signals for structural and functional changes in proteins.

Ultra-compact ultra-fast 1-bit comparator based on a two-dimensional nonlinear photonic crystal structure.

In this paper, a compact optical high-speed 1-bit comparator is proposed based on photonic crystals. In this structure, the nonlinear rods are used at the cross-connecting point of two optical waveguides. The optical transmission and reflection from these rods depend on the amount of the optical intensity. In response to the different states of the input ports, different values of the optical power reach these rods and the interference patterns make the correct function of the output ports. The refractive index and the Kerr coefficient of nonlinear rods are 1.4m2/W and 10-14m2/W, respectively. The footprint of the structure is 55µm2, which is much smaller than the previous works. Besides, the lower delay time is the other advantage of this work compared with the previous works. Based on the simulation results, the proposed structure can be used in integrated optical circuits.

The role of Cinnamaldehyde and Phenyl ethyl alcohol as two types of precipitants affecting protein hydration levels.

Release of water is the main force which drives proteins towards crystallisation (giving rise to protein crystals for crystallography) and aggregation (main cause of neurodegenerative diseases), and as such it is possible to make changes in the crystallisation/aggregation process by using compounds which are able to reduce the amount of water molecules around proteins. Cinnamaldehyde and Phenyl ethyl alcohol are the active constituents of cinnamon and rose flower, respectively. Traditional Iranian Medicine (TIM) suggests the use of cinnamon and rose flower for the reduction of excess coldness and wetness from the brain of patients suffering from Dementia. Using crystallisation as a model system and X-ray crystallography, we tested whether Cinnamaldehyde or Phenyl ethyl alcohol can mimic the role of precipitants resulting in the formation of crystals of HEWL (as a model protein) by releasing water from the surrounding protein environment. Results have revealed that both Cinnamaldehyde and Phenyl ethyl alcohol, in particular, were capable to adequately act as 'precipitants' but in the presence of NaCl (as a salt), resulting in better crystals of HEWL by changing the amount of charge and/or making water molecules unavailable in the symmetry related position, in line with the role suggested for these compounds by TIM.

Cinnamaldehyde and Phenyl Ethyl Alcohol promote the entrapment of intermediate species of HEWL, as revealed by structural, kinetics and thermal stability studies.

Numerous efforts have been directed towards investigating the different stages leading to the fibrillation process in neurodegenerative diseases and finding the factors modulating it. In this study, using a wide range of molecular techniques as well as fibrillation kinetics coupled with differential scanning fluorimetry (DSF) and crystal structure determination of HEWL treated with cinnamaldehyde (Cin) and Phenyl ethyl alcohol (PEA) in their aroma form during fibrillation, we were able to identify the binding positions of Cin and PEA in HEWL. Additionally, crystal structures were used to suggest residues Thr43, Asn44, Arg45 and Arg68 as a plausible 'hotspot' promoting entrapment of intermediate species in the process of fibril formation in HEWL. We were also able to use DSF to show that Cin can significantly decrease the thermal stability of HEWL, promoting the formation of partially unfolded intermediate species. In conclusion, our data led us to emphasize that compounds in their 'aroma form' can influence the structure and stability of protein molecules and suggest reconsideration of HEWL as a model protein for fibrillation studies related to neurodegenerative diseases based on the initial structure of the proteins, whether globular (HEWL) or intrinsically disordered.

Voluntary exercise and estradiol reverse ovariectomy-induced spatial learning and memory deficits and reduction in hippocampal brain-derived neurotrophic factor in rats.

Ample evidences have demonstrated the beneficial effects of physical exercise on cognitive functions such as learning and memory. It is well established that female sex hormones have an important role in regulating learning and memory. This study was designed to investigate the effects of voluntary exercise and estrogen replacement on learning and memory deficits and reduction in hippocampal brain derived neurotrophic factor (BDNF) levels induced by ovariectomy. Ovariectomized rats were given daily vehicle or 17 ß-estradiol (20 µg/kg) and allowed to freely exercise in a running wheel over the course of 2 weeks. After this period, they were trained and tested on a water-maze spatial task for 5 consecutive days, followed by a probe test one day later. At the end of the behavioral tests, all animals were decapitated and their hippocampal levels of BDNF were measured. Ovariectomy impaired spatial learning and memory and reduced hippocampal BDNF levels. Exercise significantly improved performance during both training and the retention of the water-maze task and increased hippocampal BDNF. Exercise, 17 ß-estradiol and their combination recovered the impairing effects of ovariectomy on learning and memory performance. The combined treatment did not produce stronger effect than either exercise or 17 ß-estradiol alone. Our findings provide an important evidence about positive influences of regular exercise and estrogen treatment against cognitive and BDNF deficits induced in ovariectomized rats, an experimental model of menopause.

Concha bullosa, nasal septal deviation, and their impacts on maxillary sinus volume among Emirati people: A cone-beam computed tomography study.

PURPOSE: To determine the prevalence of concha bullosa (CB) and nasal septal deviation (NSD) and their impact on maxillary sinus volume (MSV). MATERIALS AND METHODS: Cone-beam computed tomographic (CBCT) images of 106 Emirati people were used in this study. The direction and angle of septal deviation were calculated. The presence of CB, which could be unilateral, contralateral, or bilateral in relation to the direction of NSD, was also recorded. MSV was measured using reconstructed Digital Imaging and Communication in Medicine images on Dolphin 3D imaging software version 11.8 premium (Dolphin Imaging, Chatsworth, CA, USA). P values <0.05 were considered to indicate statistical significance. RESULTS: CB was detected in 37.7% of the sample; 20.7% of the sample showed single unilateral CB and 16.6% had single bilateral CB. NSD was seen in 74.5% of the sample. In the participants with CB, 45.5% showed mild deviation, 34.4% showed moderate deviation, and only 12.5% showed severe septal deviation. CB, but not NSD, was associated with significantly higher MSV on the affected side (P=0.001). CONCLUSION: Although NSD was observed in more than two-thirds of the sample and CB was present in more than one-third of the sample, only CB had a significant impact on MSV.

Novel X-ray sequences and crystal structures of Persian and Starry sturgeon methemoglobins: Highlighting the role of heme pocket waters in causing autoxidation.

Although there is a high sequence similarity between mammalian and fish hemoglobin (Hb), the oxidation and heme loss rates can vary greatly between them such that fish Hbs oxidise much more rapidly than mammalian Hbs. There is to date no sequence or structural data for any sturgeon Hb to reveal the level of autoxidation in these fish. In this study, novel high resolution X-ray sequences and crystal structures of methemoglobin (Met-Hb) from two sturgeon fish including Persian sturgeon (Acipenser percisus) and Starry sturgeon (Acipenser stellatus) belonging to the Caspian sea has been determined. A comprehensive sequence and structure comparison between these sturgeon Met-Hbs and a number of non-sturgeon and normal and sickle cell anaemia human Hb in varying heme states has been carried out highlighting (i) the structural variability in the heme propionate groups; (ii) the existence of certain residues or their displacement and shift in the heme pocket allowing entry of water molecules into the heme pocket; (iii) the importance of the number of water molecules in the heme pocket; (iv) the hydrogen bonding between oxygens of A and D propionate groups and that of waters in the heme pocket; and (v) the role of heme binding waters causing oxidative stress and heme autoxidation.

Root Dimensions in Patients with Mild Hypodontia and a Control Group.

OBJECTIVES: The aim of this study was to compare root dimensions (length and mesiodistal widths) between subjects with mild hypodontia and an age- and sex-matched control group. MATERIALS AND METHODS: Root dimension measurements of all permanent teeth excluding third molars were made on standardly taken orthopantomograms of 50 individuals (25 hypodontia and 25 controls) attending the University of Sharjah Dental Hospital. The length and two mesiodistal widths were measured for each fully formed root. The length of the root was measured digitally by drawing a line from the midpoint and bisecting the mesiodistal cemento-enamel junction (CEJ) of the tooth and extended to its apex. The mesiodistal widths of each root were measured at the cervical region and at half way of and perpendicular to the length of the root. STATISTICAL ANALYSIS: Two sample t-tests were used to compare root dimension measurements between the hypodontia and control groups. RESULTS: There were no significant differences between genders with regard to root length or widths measurements, and therefore genders were combined for further analysis. Patients with hypodontia have significantly shorter root lengths than controls for the upper central incisors, upper canines, first premolars, and lower first molars (p < 0.05). Similarly, root width at the midpoint of the root was found to be less in hypodontia group than that in controls for the upper central incisors, lower first premolars, upper first molars, and all second premolars (p < 0.05). Similar pattern of differences was found with regard to the root width at the cervical region (p < 0.05). CONCLUSIONS: Patients with hypodontia have shorter and narrower roots of the whole permanent dentition except the upper lateral incisors, lower incisors, lower canines, and all second molars when compared with controls. In effect, this may affect the orthodontic treatment planning and implant placement.

Molecular insights into the effect of ozone on human hemoglobin in autohemotherapy: Highlighting the importance of the presence of blood antioxidants during ozonation.

Ozone has been known for several decades, with its antiseptic and therapeutic effects determined by the hormesis theory. It is shown that the therapeutic efficacy of ozone therapy may be partly due to the controlled and moderate oxidative stress produced by the reaction of ozone with several biological components. In this study, the effect of ozone on healthy human hemoglobin (Hb) in the whole blood environment (in the presence of antioxidants) and in the purified form (in the absence of antioxidants) is investigated using a number of different techniques including intrinsic fluorescence, circular dichroism and UV-VIS absorption spectroscopy as well as SDS- and Native-PAGE and dynamic light scattering. The results show that the presence of antioxidants prevents damage to Hb while its absence means that as the exposure to ozone is increased, Hb is increasingly damaged. These results highlight the importance for the use of appropriate doses of ozone, for patients with different diseases and hence antioxidant levels, in autohemotherapy.

Unraveling the novel effects of aroma from small molecules in preventing hen egg white lysozyme amyloid fibril formation.

This study investigated for the first time the molecular effectiveness of 'aroma' from three small molecules including a phenol (phenyl ethyl alcohol; PEA) and an aldehyde (cinnamaldehyde; Cin) both containing an aromatic ring, and a diamine (N,N,N,N'- Tetramethylethylenediamine; TEMED) at two different amounts (small; S and large; L) in preventing hen egg white lysozyme (HEWL) amyloid fibril formation using Thioflavin T and Nile red fluorescence assays, circular dichroism spectroscopy, SDS-polyacrylamide gel electrophoresis, atomic force microscopy, dynamic light scattering and HEWL activity test. Interestingly, the results revealed that (1) the aroma of PEA, identified as an active constituent of Rosa damascena, prevented fibril formation since PEA-L was able to trap the oligomeric form of HEWL in contrast to PEA-S where protofibrils but not mature fibrils were formed; (2) Cin, previously shown to prevent fibril formation in the liquid form, was also shown to do so in the aroma form by producing protofibrils and not mature fibrils in both Cin- L and Cin-S aroma forms and (3) the aroma of TEMED-L was able to retain HEWL's native structure completely and prevented both aggregation and fibril formation, while TEMED-S prevented HEWL fibril formation and instead directed the pathway towards amorphous aggregate formation. Furthermore, the ability to trap oligomeric species (by PEA-L aroma) is of great importance for further research as it provides routes for preventing the formation of toxic oligomeric intermediates along the fibrillation pathway. Last but not least, the novelty of this in vitro study on the effect of aroma at the molecular level with a unique experimental set-up using HEWL as a model protein in assessing amyloid fibril formation paves the way for more and detailed studies on the importance of aroma producing molecules and their effects.

Controlled release of an endostatin peptide using chitosan nanoparticles.

Whereas several anticancer peptides are in different stages of clinical development, their administration is limited by the fast elimination from the systemic circulation. Peptide loading on nano-carriers can pave the way for their future application. We have recently indicated that a disulfide loop rather than a Zn-binding loop improves the anti-angiogenic and antitumor activities of the N-terminal fragment of endostatin. In this study, chitosan nanoparticles (CS NPs) are used for the controlled release of the engineered peptide. Loading of the peptide into CS NPs using the ionic gelation method was confirmed by FTIR and resulted in final particle size, poly-dispersity index and surface charge of 186.5 ± 24.0 nm, 0.26 ± 0.02 and 20.1 ± 0.4 mV respectively. The SEM morphological analysis revealed spherical particles with an average size of 80 ± 5 nm. Peptide loading studies revealed that CS NPs are able to adsorb the peptide as ~70%. The release measurements indicated an initial burst release by 49% after 2 hr and complete release after 80 hr. According to in vitro studies, the loaded peptide was much more toxic for endothelial cells than different cancer cell lines. These results underscore the promise of CS NPs as therapeutics nanosystems and open a perspective for improving the clinical applications of peptide drugs.

The Effect of Number of Teeth and Chewing Ability on Cognitive Function of Elderly in UAE: A Pilot Study.

Cognitive decline is one of the major causes of disability among the aging population. The aim of this study was to explore the relationship between oral health parameters (number of teeth, chewing ability, and presence of a denture) and cognitive function in the elderly across the UAE. Fifty persons (age ≥ 60; 71.26 ± 10.23) were enrolled in the study. Cognitive status was assessed using the standardized mini-mental state examination (SMMSE) and accordingly, cognitively normal subjects scoring ≥24 were considered as the control group and cognitively impaired individuals scoring ≤23 were considered as the low scoring group. Chewing ability was examined, number of teeth was noted, and demographical data was collected. The results of this pilot study showed that individuals with low SMMSE scores were significantly less educated (P < 0.01) and had fewer number of remaining teeth (P < 0.05) and impaired chewing ability (P < 0.05). These results demonstrate a significant link between the number of teeth, chewing ability, and cognitive function. However, this pilot study had its limitations and was the first of its kind in the UAE and Gulf region; therefore, future research addressing the limitations is needed to further explore this association.