Interactive association between RhoA transcriptional signaling inhibitor,CCG1423 and human serum albumin: Biophysical and in silico studies

Multiple spectroscopic techniques, such as fluorescence, absorption, and circular dichroism along with in silico studies were used to characterize the binding of a potent inhibitor molecule, CCG1423 to the major transport protein, human serum albumin (HSA). Fluorescence and absorption spectroscopic results confirmed CCG1423–HSA complex formation. A strong binding affinity stabilized the CCG1423–HSA complex, as evident from the values of the binding constant (K_a = 1.35 × 10⁶–5.43 × 10⁵ M^?1). The K_SV values for CCG1423–HSA system were inversely correlated with temperature, suggesting the involvement of static quenching mechanism. Thermodynamic data anticipated that CCG1423–HSA complexation was mainly driven by hydrophobic and van der Waals forces as well as hydrogen bonds. In silico analysis also supported these results. Three-dimensional fluorescence and circular dichroism spectral analysis suggested microenvironmental perturbations around protein fluorophores and structural (secondary and tertiary) changes in the protein upon CCG1423 binding. CCG1423 binding to HSA also showed some protection against thermal denaturation. Site-specific marker-induced displacement results revealed CCG1423 binding to Sudlow’s site I of HSA, which was also confirmed by the computational results. A few common ions were also found to interfere with the CCG1423–HSA interaction.     

Somatic embryogenesis and plant regeneration in Anthurium scherzerianum

The effects of xylooligosaccharides isolated from the cell walls of Betula platyphylla var. japonica on cells and protoplasts of Pinus radiata were examined. The addition of a semi-purified mixture of xylooligosaccharides at a concentration of 5μg.ml⁻¹ promoted elongation of cultured cells, whereas the neutral fraction of this mixture had no effect; a similar effect was seen in the presence of conditioned medium. The unfractionated mixture of xylooligosaccharides was also found to enhance the viability of protoplasts prepared from cell cultures of Pinus radiata in a concentration dependent manner, highly similar to the effect provided by addition of medium conditioned by pine cells. Such effects are considered to be due to the addition of components that play a structural role in the cell wall of pines. It is inferred that the acidic components of the xylooligosaccharide mixture derived from t Betula are responsible for this effect in the distant pine species. It is speculated that acidic xylooligosaccharides operate either by replacing, or mimicking, the natural cell wall components required for growth and development of pine cultured cells. This revised version was published online in June 2006 with corrections to the Cover Date.     

Stopping azithromycin mass drug administration for trachoma: A systematic review

The World Health Organization (WHO) recommends continuing azithromycin mass drug administration (MDA) for trachoma until endemic regions drop below 5% prevalence of active trachoma in children aged 1–9 years. Azithromycin targets the ocular strains of Chlamydia trachomatis that cause trachoma. Regions with low prevalence of active trachoma may have little if any ocular chlamydia, and, thus, may not benefit from azithromycin treatment. Understanding what happens to active trachoma and ocular chlamydia prevalence after stopping azithromycin MDA may improve future treatment decisions. We systematically reviewed published evidence for community prevalence of both active trachoma and ocular chlamydia after cessation of azithromycin distribution. We searched electronic databases for all peer-reviewed studies published before May 2020 that included at least 2 post-MDA surveillance surveys of ocular chlamydia and/or the active trachoma marker, trachomatous inflammation–follicular (TF) prevalence. We assessed trends in the prevalence of both indicators over time after stopping azithromycin MDA. Of 140 identified studies, 21 met inclusion criteria and were used for qualitative synthesis. Post-MDA, we found a gradual increase in ocular chlamydia infection prevalence over time, while TF prevalence generally gradually declined. Ocular chlamydia infection may be a better measurement tool compared to TF for detecting trachoma recrudescence in communities after stopping azithromycin MDA. These findings may guide future trachoma treatment and surveillance efforts.     

HybridFlood: minimizing the effects of redundant messages and maximizing search efficiency of unstructured peer-to-peer networks

Peer-to-peer systems are important Internet applications. A major portion of Internet traffic belongs to such applications. Flooding search is a basic search scheme for unstructured peer-to-peer networks, where a node must send a query message to all its neighbors when seeking a file (in a file sharing situation). Flooding has no knowledge about network topology and files distribution, thus it offers an attractive method for file discovery in dynamic and evolving networks. Although pure flooding can achieve high coverage but it produces exponentially redundant messages in each hop. Consequently, the growth of redundant messages limits system scalability and causes unnecessary traffic in networks. Besides, flooding has no opportunity to get an advantage of node diversity of participating in unstructured P2P networks. To improve this searching scheme and reduce redundant messages, this paper proposes a novel algorithm named HybridFlood. This algorithm is divided into two steps. The first step follows the flooding with a limited number of hops. In the second step, nosey nodes are selected in each searching horizon. The nosey nodes are nodes which have the most links to other nodes. These nodes maintain the data index of all client nodes. We provided analytical studies for flooding and HybridFlood. The analytical results provided the best threshold point of hop for optimum coverage growth rate and redundant messages in flooding. It also proved in HybridFlood broadcasting messages are cut down at least an order of magnitude. Thus, the proposed algorithm extends the search efficiency by reducing redundant messages in each hop. The simulation experiments validated analytical results.     

In Vitro Antifungal Susceptibility of <Emphasis Type="Italic">Neoscytalidium dimidiatum</Emphasis> Clinical Isolates from Malaysia

Neoscytalidium dimidiatum is an opportunistic fungus causing cutaneous infections mostly, which are difficult to treat due to antifungal resistance. In Malaysia, N. dimidiatum is associated with skin and nail infections, especially in the elderly. These infections may be mistaken for dermatophyte infections due to similar clinical appearance. In this study, Neoscytalidium isolates from cutaneous specimens, identified using morphological and molecular methods (28 Neoscytalidium dimidiatum and 1 Neoscytalidium sp.), were evaluated for susceptibility towards antifungal agents using the CLSI broth microdilution (M38-A2) and Etest methods. Amphotericin B, voriconazole, miconazole and clotrimazole showed high in vitro activity against all isolates with MIC ranging from 0.0313 to 1 µg/mL. Susceptibility towards fluconazole and itraconazole was noted in up to 10% of isolates, while ketoconazole was inactive against all isolates. Clinical breakpoints for antifungal drugs are not yet available for most filamentous fungi, including Neoscytalidium species. However, the results indicate that clinical isolates of N. dimidiatum in Malaysia were sensitive towards miconazole, clotrimazole, voriconazole and amphotericin B, in vitro.     

Conservation of some rare and endangered plants from Peninsular Malaysia

Malaysia has approximately 15,000 species of vascular plants. Its flora is distributed between two major geographical regions; Peninsular Malaysia on mainland Asia and the states of Sabah and Sarawak on the island of Borneo. Peninsular Malaysia has over 8,300 plant species and Sabah and Sarawak in a recent estimate have about 12,000 species. Total species endemism for Peninsular Malaysia is about 30%; its tree endemism is 26.3%. For Sabah and Sarawak, the endemism level is higher, recently revised figures gave a tree species endemism of 42.1%. Malaysia has recently published its national strategy for plant conservation, which now forms the basis of conservation activities for the country. Since 2004, we have been running a project entitled “Conservation Monitoring of Rare and Threatened Plants of Peninsular Malaysia”, in which conservation status assessment is scored for a number of families. Results of the assessment of 458 taxa included 46.1% in some threat category. Detailed conservation studies are in progress for 33 species of threatened plants. Initial work on these species include spatial distribution studies at regional level based on herbarium records, and at a more local level, population studies to determine demography of populations. Regular phenological observations were also made for many of the species.     

<Emphasis Type="Italic">Amycolatopsis vastitatis</Emphasis> sp. nov., an isolate from a high altitude subsurface soil on Cerro Chajnantor,northern Chile

The taxonomic position of a novel Amycolatopsis strain isolated from a high altitude Atacama Desert subsurface soil was established using a polyphasic approach. The strain, isolate H5^T, was shown to have chemical properties typical of members of the genus Amycolatopsis such as meso-diaminopimelic acid as the diamino acid in the cell wall peptidoglycan, arabinose and galactose as diagnostic sugars and MK-9(H₄) as the predominant isoprenologue. It also has cultural and morphological properties consistent with its classification in the genus, notably the formation of branching substrate hyphae which fragment into rod-like elements. 16S rRNA gene sequence analyses showed that the strain is closely related to the type strain of Amycolatopsis mediterranei but could be distinguished from this and other related Amycolatopsis strains using a broad range of phenotypic properties. It was separated readily from the type strain of Amycolatopsis balhymycina, its near phylogenetic neighbour, based on multi-locus sequence data, by low average nucleotide identity (92.9%) and in silico DNA/DNA relatedness values (51.3%) calculated from draft genome assemblies. Consequently, the strain is considered to represent a novel species of Amycolatopsis for which the name Amycolatopsis vastitatis sp. nov. is proposed. The type strain is H5^T (= NCIMB 14970^T = NRRL B-65279^T).     

Determinants of Default from Tuberculosis Treatment among Patients with Drug-Susceptible Tuberculosis in Karachi,Pakistan: A Mixed Methods Study

Purpose

Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy.

Methods

In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013.

Results

Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04–1.71), being 35–59 years of age (OR: 1.54, 95% CI: 1.14–2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17–2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35–59 years of age (aOR: 1.49, 95% CI: 1.10–2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12–2.77) were associated with default.

Conclusions

In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment.