Trans-scale Granular Modelling of Cytoskeleton: a Mini-Review

Living cells are the functional unit of organs that controls reactions to their exterior. However, the mechanics of living cells can be difficult to characterize due to the crypticity of their microscale structures and associated dynamic cellular processes. Fortunately, multiscale modelling provides a powerful simulation tool that can be used to study the mechanical properties of these soft hierarchical, biological systems. This paper reviews recent developments in hierarchical multiscale modeling technique that aimed at understanding cytoskeleton mechanics. Discussions are expanded with respects to cytoskeletal components including: intermediate filaments, microtubules and microfilament networks. The mechanical performance of difference cytoskeleton components are discussed with respect to their structural and material properties. Explicit granular simulation methods are adopted with different coarse-grained strategies for these cytoskeleton components and the simulation details are introduced in this review.     

The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals

Presynaptic terminals are metabolically active and accrue damage through continuous vesicle cycling. How synapses locally regulate protein homeostasis is poorly understood. We show that the presynaptic lipid phosphatase synaptojanin is required for macroautophagy, and this role is inhibited by the Parkinson's disease mutation R258Q. Synaptojanin drives synaptic endocytosis by dephosphorylating PI(4,5)P₂, but this function appears normal in Synaptojanin^RQ knock‐in flies. Instead, R258Q affects the synaptojanin SAC1 domain that dephosphorylates PI(3)P and PI(3,5)P₂, two lipids found in autophagosomal membranes. Using advanced imaging, we show that Synaptojanin^RQ mutants accumulate the PI(3)P/PI(3,5)P₂‐binding protein Atg18a on nascent synaptic autophagosomes, blocking autophagosome maturation at fly synapses and in neurites of human patient induced pluripotent stem cell‐derived neurons. Additionally, we observe neurodegeneration, including dopaminergic neuron loss, in Synaptojanin^RQ flies. Thus, synaptojanin is essential for macroautophagy within presynaptic terminals, coupling protein turnover with synaptic vesicle cycling and linking presynaptic‐specific autophagy defects to Parkinson's disease.     

Cometabolic degradation of polychlorinated biphenyls (PCBs) by axenic cultures of Ralstonia sp. strain SA-5 and Pseudomonas sp. strain SA-6 obtained from Nigerian contaminated soils

Substantial metabolism of 2,3,4,5-tetrachlorobiphenyl (2,3,4,5-tetraCB) and 2,3′,4′,5-tetraCB by axenic cultures of Ralstonia sp. SA-5 and Pseudomonas sp. SA-6 was observed in the presence of biphenyl supplementation, although, the strains were unable to utilize tetrachlorobiphenyls as growth substrate. The former was more amenable to aerobic degradation (∼70% degradation) than the latter (22–45% degradation). Recovery of 2,5-chlorobenzoic acid and chloride from 2,3′,4′,5-tetraCB assay is an indication of initial dioxygenase attack on the 3,4-dichlorophenyl ring. The PCB-degradative ability of both strains was also investigated by GC analysis of individual congeners in Aroclor 1242 (100 ppm) following 12-day incubation with washed benzoate-grown cells. Results revealed two different catabolic properties. Whereas strain SA-6 required biphenyl as inducer of the degradation activity, such induction was not required by strain SA-5. Nearly all the detectable congeners in the mixture were extensively degraded (% reduction in ECD area counts for individual congeners ranged from 50.0 to 100% and 14.2 to 100%, respectively, for SA-5 and SA-6). The two strains exhibited no noticeable specificity for congeners with varying numbers of chlorine substitution and positions. The degradative competence of these isolates most especially SA-5 makes them among the most versatile PCB-metabolizing organisms yet reported.     

Seed Treatment with Trichoderma Species for Control of Damping-off of Cowpea Caused by Macrophomina phaseolina

Cowpea seeds treated with three Trichoderma spp. at four inoculum doses, and at four exposure times in three different formulations were planted in soils amended with Macrophomina phaseolin a, and assessed for stand establishment and post-emergence damping off. The highest percentage plant stands at 21 days after planting were 66% for T. koningii and T. harzianum , and 51% for Trichoderma sp., at 6.8 ×10 7 , 2.0 ×10 10 , and 1.0 ×10 7 colony forming units (CFUs) ml -1 , respectively. Across sampling dates and irrespective of time of exposure to the formulations, the T. harzianum and T. koningii formulations resulted in significantly greater percentage plant stands than the seeds treated with a Trichoderma sp. and the controls. Seed treatment formulations with Trichoderma spp. were derived from propagule suspensions at the most effective inoculum dose in Tween 80, in suspension with cooked cassava starch as an adhesive, or in a slurry with uncooked cassava starch. At 21 days, the suspensions with Tween 80 and cooked starch resulted in significantly higher percentage plant stands than the control, while stands from seeds treated in a slurry formulation and starch solutions were not different. Seed exposure to the different formulations for 10, 20, 30, or 40 min, provided mixed results. Seeds treated with benomyl at 0.5 g a.i/50 g resulted in 95 and 100% stands for the two sets of experiments, respectively.     

Population variation in linkage disequilibrium across the COMT gene considering promoter region and coding region variation

Catechol-O-methyl transferase (COMT) catalyzes the first step in one of the major pathways in the degradation of catecholamines. The COMT gene on chromosome 22 has been considered a candidate gene for many neuropsychiatric disorders, in part because an exon 4 single nucleotide polymorphism (SNP) in COMT causes an amino acid substitution associated with significantly altered enzyme activity. This functional variant, detected as an NlaIII restriction site polymorphism (RSP), is polymorphic in populations from around the world. A four-site haplotype spanning 28 kb effectively encompasses COMT. This haplotype is comprised of two novel polymorphisms [a tetranucleotide short tandem repeat polymorphism (STRP) in intron 1 and a HindIII RSP at the 5' end of COMT], the NlaIII site, and another previously published site - a BglI RSP at the 3' end of the gene. Overall linkage disequilibrium (LD) for this haplotype is strong and significant in 32 population samples from around the world. Conditional probabilities indicate that, in spite of moderate to strong disequilibrium in most non-African populations, the NlaIII site, although often used for prediction, would not always be a reliable predictor of allelic variation at the other sites. Because other functional variation might exist, especially regulatory variation, these findings indicate that haplotypes would be more effective indicators of possible involvement of COMT in disease etiology.     

Cytomorphologic characteristics, differential diagnosis and utility during intraoperative consultation for medulloblastoma

OBJECTIVE: To study the cytologic findings that differentiate LC/A and non-LC/A (NLCA) types. STUDY DESIGN: Cytologic smears, prepared during intraoperative consultation (IOC) of 43 cases of pure histologic type, defined as > 80% of the tumor being composed of 1 of 3 major histologic types--classic, nodular and LC/A--were reviewed and graded semiquantitatively (0-3+) for 14 cytologic features: cellularity, nuclear streaming, endothelial proliferation, necrosis, lymphoglandular bodies, rosette formation, apoptosis, nuclear cannibalism, pleomorphism, macronucleoli, paranuclear inclusions, cytoplasmic vacuoles, mitoses and multinucleation. The grades were compared between the 2 histologic groups, LC/A vs. NLCA, as well as between the preparation methods, squash vs. touch (TP). Values of p < 0.05 were accepted as statistically significant. RESULTS: "Cell wrapping" (cannibalism), pleomorphism, macronucleoli, apoptosis, mitoses and cytoplasmic vacuoles were more significantly observed in LC/A than in NLCA. CONCLUSION: Intraoperative cytologic evaluation of these cytologic parameters allows distinction between LC/A and NLCA, which can be prognostically useful during IOC. Rosette formation, the histologic hallmark of classic medulloblastoma, is not a discriminator. Given the fewer artifacts and sufficient cellularity, TP is the preferred method of cytologic preparation.     

TxtH is a key component of the thaxtomin biosynthetic machinery in the potato common scab pathogen Streptomyces scabies

Streptomyces scabies causes potato common scab disease, which reduces the quality and market value of affected tubers. The predominant pathogenicity determinant produced by S. scabies is the thaxtomin A phytotoxin, which is essential for common scab disease development. Production of thaxtomin A involves the nonribosomal peptide synthetases (NRPSs) TxtA and TxtB, both of which contain an adenylation (A-) domain for selecting and activating the appropriate amino acid during thaxtomin biosynthesis. The genome of S. scabies 87.22 contains three small MbtH-like protein (MLP)-coding genes, one of which (txtH) is present in the thaxtomin biosynthesis gene cluster. MLP family members are typically required for the proper folding of NRPS A-domains and/or stimulating their activities. This study investigated the importance of TxtH during thaxtomin biosynthesis in S. scabies. Biochemical studies showed that TxtH is required for promoting the soluble expression of both the TxtA and TxtB A-domains in Escherichia coli, and amino acid residues essential for this activity were identified. Deletion of txtH in S. scabies significantly reduced thaxtomin A production, and deletion of one of the two additional MLP homologues in S. scabies completely abolished production. Engineered expression of all three S. scabies MLPs could restore thaxtomin A production in a triple MLP-deficient strain, while engineered expression of MLPs from other Streptomyces spp. could not. Furthermore, the constructed MLP mutants were reduced in virulence compared to wild-type S. scabies. The results of our study confirm that TxtH plays a key role in thaxtomin A biosynthesis and plant pathogenicity in S. scabies.     

Seed yield,head characteristics and oil content in sunflower varieties as influenced by seeds from single and multiple headed plants under humid tropical conditions

Field trials were conducted during 2004 and 2005 to determine the effect of sowing seeds from plants with multiple heads and seeds from single headed plants of sunflower on seed yield, head characteristics and oil content of three widely grown open pollinated varieties (Funtua, Record and Isaanka) in the humid forest—savanna transition zone which is outside the current growing areas with a view to improving stability and sunflower productivity in this region. Seeds from multiple headed plants produced plants that flowered and matured 2–3 days later than plants from single headed plants. Apart from days to flowering in 2004, number of days to maturity and plant height were affected independently by variety and seed source factors. However, the seeds from single headed plants produced plants that recorded significantly (P < 0.01) higher head weight, head diameter, achene weight and number per head than plants from seeds of plants with multiple heads. Seed source had little effect on sunflower seed yield and oil content. However, Funtua produced significantly (P < 0.05) high seed yield (1956.0 kg ha^?1 ± 76.06) when seeds from plants with multiple heads were sown, while Isaanka recorded comparatively high seed yield from seeds of plants from either multiple (1221.0 kg ha^?1 ± 165.90) or single heads (1388.0 kg ha^?1 ± 135.84) and Record (1201.0 kg ha^?1 ± 96.97) when seeds from single headed plants were sown. Therefore, it is recommended that prospective sunflower growers who wish to cultivate Isaanka, can sow seeds from either the multiple or single head and preferably the multiple head for Funtua, and single head for Record.     

Enhanced production of succinic acid from methanol–organosolv pretreated Strophanthus preussii by recombinant Escherichia coli

Bioprocess and Biosystems Engineering - A biorefinery process for high yield production of succinic acid from biomass sugars was investigated using recombinant Escherichia coli. The major problem...