Evaluation of the properties of modified local asphalt binder by using styrene butadiene rubber (SBR) or low-density polyethylene (LDPE)

The influence of styrene butadiene rubber (SBR) or low-density polyethylene (LDPE) polymers on the characteristics of local asphalt binder was analyzed to characterize the rheological properties. The results indicated that the SBR or LDPE increased the softening point. The softening point was enhanced by around 35% when 9% of SBR was used in comparison to the unmodified asphalt, while there was a 15% increment when LDPE was used. The results also indicated that the SBR or LDPE decreased the penetration rate. The penetration decreases by around 36% when 9% of SBR is used compared to the neat asphalt, while a significant increment was 89% when 9% of LDPE is used. Additionally, when 9% SBR was employed, the ductility of the asphalt binder rose by roughly 73%, but 64% less ductility was seen when 9% LDPE was utilized. Finally, the addition of the additive has improved the penetration index, thus reducing the temperature sensitivity. Due to said above, SBR and LDPE are practical and promising modifiers that will be useful in enhancing the performance of the asphalt binder straightforwardly and efficiently

Out-of-Wedlock Pregnancy Among Single Mothers in Khartoum, Sudan: Sociodemographic Characteristics, Causes, and Consequences

Background: Out-of-wedlock childbearing is a global phenomenon that has lifelong consequences on the lives of both mothers and their children. The aim of this study is to identify the sociodemographic characteristics, causes, and consequences of outof- wedlock pregnancy among single mothers in Khartoum, Sudan.Methods: This descriptive, cross-sectional study was conducted at the Mygoma Orphanage Center (MOC) and Shamaa Rehabilitation Center (SRC) using convenience sampling among 200 participants. A validated questionnaire with 25 items was used to collect data. The data were entered into Epi-Data Manager and analyzed using the SPSS. Results: The study found that most of the single mothers in Khartoum who gave birth out of wedlock were young and had just completed their university education. Most of them discovered their pregnancy during the second or third trimester, and nearly half of them did not receive any antenatal care. The majority of the children born to these mothers were preterm and had a low birth weight. Additionally, many mothers reported experiencing social stigma and rejection from their families due to their out-of-wedlock pregnancy. The study also highlighted loneliness, stress, and romantic relations as the main causes of out-of-wedlock pregnancy among single mothers in Khartoum, Sudan.Conclusion: The study provides useful insights into the sociodemographic characteristics, causes, and consequences of out-of-wedlock pregnancy among single mothers in Khartoum, Sudan. Social stigma and lack of support were identified as significant barriers to the reintegration of single mothers and their children into society. Future research should focus on investigating the long-term effects of outof- wedlock pregnancy on mothers and their children

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Development and Evaluation of Content Validity and Acceptance of a Multidomain Intervention Module for Reversal of Cognitive Frailty Among Older Adults

Norhayati Mustafa Khalid,1 Pavapriya Ponvel,1 Azianah Mohamad Ibrahim,1 A’isyah Mohd Safien,1 Nurul Hidayah Md Fadzil,1 Devinder Kaur Ajit Singh,1 Arimi Fitri Mat Ludin,1 Norhayati Ibrahim,1 Ponnusamy Subramaniam,1 Hasnah Haron,1 Roslee Rajikan,1 Divya Vanoh,2 Suzana Shahar1 1Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Dietetics Programme, School of Health Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaCorrespondence: Suzana Shahar, Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Malaysia, Tel +60 392897163, Email [email protected]: There is a limited availability of multidomain interventions that target cognitive frailty. Thus, the aim of the present study was to develop and evaluate the content validity and acceptance of the multidomain intervention module to reverse cognitive frailty among older adults (iAGELESS).Patients and Methods: This study was conducted in two phases: Phase I included the development of the multidomain intervention module iAGELESS and evaluation of content validity, while Phase II consisted of evaluating the acceptance of the module among 18 healthcare and social care providers, 13 older adults with cognitive frailty, and 13 caregivers. Content validity index (CVI) was used to quantify the content validity. Respondents completed a questionnaire which consisted of information on sociodemographic, followed by module acceptance evaluation with respect to content, terminologies, and graphics. The data was then analyzed descriptively.Results: A multidomain intervention module, iAGELESS was developed. The module was found to have appropriate content validity (overall CVI = 0.83). All the caregivers, 92% of older adults with cognitive frailty and 83% of healthcare and social care providers were satisfied with the overall content of the module. More than 50% of those who accepted the module had satisfactory consensus on the ease of the terminologies, length of sentences, pictures, information, color, and font size included in the module.Conclusion: The iAGELESS module demonstrated good content validity and was well accepted, thus warranting its utilization in future studies to determine its effectiveness in reversing cognitive frailty among older adults.Keywords: aging, cognitive frailty, multidomain intervention module, older adults, reversa

Co-Conserved Features Associated with cis Regulation of ErbB Tyrosine Kinases

BACKGROUND: The epidermal growth factor receptor kinases, or ErbB kinases, belong to a large sub-group of receptor tyrosine kinases (RTKs), which share a conserved catalytic core. The catalytic core of ErbB kinases have functionally diverged from other RTKs in that they are activated by a unique allosteric mechanism that involves specific interactions between the kinase core and the flanking Juxtamembrane (JM) and COOH-terminal tail (C-terminal tail). Although extensive studies on ErbB and related tyrosine kinases have provided important insights into the structural basis for ErbB kinase functional divergence, the sequence features that contribute to the unique regulation of ErbB kinases have not been systematically explored. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we use a Bayesian approach to identify the selective sequence constraints that most distinguish ErbB kinases from other receptor tyrosine kinases. We find that strong ErbB kinase-specific constraints are imposed on residues that tether the JM and C-terminal tail to key functional regions of the kinase core. A conserved RIxKExE motif in the JM-kinase linker region and a glutamine in the inter-lobe linker are identified as two of the most distinguishing features of the ErbB family. While the RIxKExE motif tethers the C-terminal tail to the N-lobe of the kinase domain, the glutamine tethers the C-terminal tail to hinge regions critical for inter-lobe movement. Comparison of the active and inactive crystal structures of ErbB kinases indicates that the identified residues are conformationally malleable and can potentially contribute to the cis regulation of the kinase core by the JM and C-terminal tail. ErbB3, and EGFR orthologs in sponges and parasitic worms, diverge from some of the canonical ErbB features, providing insights into sub-family and lineage-specific functional specialization. CONCLUSION/SIGNIFICANCE: Our analysis pinpoints key residues for mutational analysis, and provides new clues to cancer mutations that alter the canonical modes of ErbB kinase regulation

Effect of bilirubin on cytochrome c oxidase activity of mitochondria from mouse brain and liver

<p>Abstract</p> <p>Background</p> <p>The unbound, free concentration (B_f) of unconjugated bilirubin (UCB), and not the total UCB level, has been shown to correlate with bilirubin cytotoxicity, but the key molecular mechanisms accounting for the toxic effects of UCB are largely unknown.</p> <p>Findings</p> <p>Mouse liver mitochondria increase unbound UCB oxidation, consequently increasing the apparent rate constant for unbound UCB oxidation by HRP (Kp), higher than in control and mouse brain mitochondria, emphasizing the importance of determining Kp in complete systems containing the organelles being studied. The <it>in vitro </it>effects of UCB on cytochrome <it>c </it>oxidase activity in mitochondria isolated from mouse brain and liver were studied at B_franging from 22 to 150 nM. The results show that UCB at B_fup to 60 nM did not alter mitochondrial cytochrome <it>c </it>oxidase activity, while the higher concentrations significantly inhibited the enzyme activity by 20% in both liver and brain mitochondria.</p> <p>Conclusions</p> <p>We conclude that it is essential to include the organelles being studied in the medium used in measuring both Kp and B_f. A moderately elevated, pathophysiologically-relevant B_fimpaired the cytochrome <it>c </it>oxidase activity modestly in mitochondria from mouse brain and liver.</p

Isolation and Characterization of Maize PMP3 Genes Involved in Salt Stress Tolerance

Plasma membrane protein 3 (PMP3), a class of small hydrophobic polypeptides with high sequence similarity, is responsible for salt, drought, cold, and abscisic acid. These small hydrophobic ploypeptides play important roles in maintenance of ion homeostasis. In this study, eight ZmPMP3 genes were cloned from maize and responsive to salt, drought, cold and abscisic acid. The eight ZmPMP3s were membrane proteins and their sequences in trans-membrane regions were highly conserved. Phylogenetic analysis showed that they were categorized into three groups. All members of group II were responsive to ABA. Functional complementation showed that with the exception of ZmPMP3-6, all were capable of maintaining membrane potential, which in turn allows for regulation of intracellular ion homeostasis. This process was independent of the presence of Ca2+. Lastly, over-expression of ZmPMP3-1 enhanced growth of transgenic Arabidopsis under salt condition. Through expression analysis of deduced downstream genes in transgenic plants, expression levels of three ion transporter genes and four important antioxidant genes in ROS scavenging system were increased significantly in transgenic plants during salt stress. This tolerance was likely achieved through diminishing oxidative stress due to the possibility of ZmPMP3-1's involvement in regulation of ion homeostasis, and suggests that the modulation of these conserved small hydrophobic polypeptides could be an effective way to improve salt tolerance in plants

Application of the rainbow trout derived intestinal cell line (RTgutGC) for ecotoxicological studies: molecular and cellular responses following exposure to copper.

There is an acknowledged need for in vitro fish intestinal model to help understand dietary exposure to chemicals in the aquatic environment. The presence and use of such models is however largely restrictive due to technical difficulties in the culturing of enterocytes in general and the availability of appropriate established cell lines in particular. In this study, the rainbow trout (Oncorhynchus mykiss) intestinal derived cell line (RTgutGC) was used as a surrogate for the "gut sac" method. To facilitate comparison, RTgutGC cells were grown as monolayers (double-seeded) on permeable Transwell supports leading to a two-compartment intestinal model consisting of polarised epithelium. This two-compartment model divides the system into an upper apical (lumen) and a lower basolateral (portal blood) compartment. In our studies, these cells stained weakly for mucosubstances, expressed the tight junction protein ZO-1 in addition to E-cadherin and revealed the presence of polarised epithelium in addition to microvilli protrusions. The cells also revealed a comparable transepithelial electrical resistance (TEER) to the in vivo situation. Importantly, the cell line tolerated apical saline (1:1 ratio) thus mimicking the intact organ to allow assessment of uptake of compounds across the intestine. Following an exposure over 72 h, our study demonstrated that the RTgutGC cell line under sub-lethal concentrations of copper sulphate (Cu) and modified saline solutions demonstrated uptake of the metal with saturation levels comparable to short term ex situ gut sac preparations. Gene expression analysis revealed no significant influence of pH or time on mRNA expression levels of key stress related genes (i.e. CYP3A, GST, mtA, Pgp and SOD) in the Transwell model. However, significant positive correlations were found between all genes investigated suggesting a co-operative relationship amongst the genes studied. When the outlined characteristics of the cell line are combined with the division of compartments, the RTgutGC double seeded model represents a potential animal replacement model for ecotoxicological studies. Overall, this model could be used to study the effects and predict aquatic gastrointestinal permeability of metals and other environmentally relevant contaminants in a cost effective and high throughput manner