Identifying essential genes in bacterial metabolic networks with machine learning methods

Background  

Identifying essential genes in bacteria supports to identify potential drug targets and an understanding of minimal requirements for a synthetic cell. However, experimentally assaying the essentiality of their coding genes is resource intensive and not feasible for all bacterial organisms, in particular if they are infective.     

Trees on networks: resolving statistical patterns of phylogenetic similarities among interacting proteins

Background  

Phylogenies capture the evolutionary ancestry linking extant species. Correlations and similarities among a set of species are mediated by and need to be understood in terms of the phylogenic tree. In a similar way it has been argued that biological networks also induce correlations among sets of interacting genes or their protein products.     

The activity of jaw elevator muscles during peanut chewing in patients with temporomandibular joint and muscle pain dysfunction syndrome

A synchronized system of EMG and jaw motion tracking device was used to observe some chewing parameters of jaw elevator muscles in 15 patients with temporomandibular joint and muscle pain dysfunction syndrome (TMJ) and 15 normal subjects. Duration of tooth contact (DTC), duration of muscle contraction before tooth contact (DMC), total duration of muscle contraction (DTM) and velocity of jaw movement during peanut chewing were observed. Symptoms of the TMJ patients included pain and tenderness at joints and muscles, and limitation and clicking at joints during jaw movements. It was found that the TMJ patients needed more numerous breaking off strokes before trituration at the occlusal level. There was a longer DMC in the earlier trituration period and TMJ patients had longer DMC than in normals. No difference was found between right and left side chewing or between temporalis and masseter muscles. DTM in the TMJ group was only slightly longer than in normals and the difference between early and late chewing periods was statistically not significant. DTC was only slightly shorter in the TMJ group while the difference between early and late chewing periods in both groups was significant. The average and maximum closing velocities were significantly lower in the TMJ group in both right and left chewing. The difference in the opening phase was not as significant. It was concluded that DMC and jaw closing velocity are more sensitive parameters than DTM and DTC on the diagnosis of TMJ dysfunction with or without occlusal interference. DTM and DTC are parameters more closely related to the influence of occlusal factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Computational and Experimental Investigation of the Antimicrobial Peptide Cecropin XJ and its Ligands as the Impact Factors of Antibacterial Activity

Cecropin XJ, as a heat stable antimicrobial peptide (AMP), displayed broad bacteriostatic activities, effectively inhibited proliferation of cancer cells and induced cell apoptosis in vitro. However, it exhibited little hemolytic activity and very low cytotoxicity to erythrocytes and normal cells. Although exerts multiple remarkable bioactivities, the refined molecular conformation of native Cecropin XJ remains unsolved. The aim of the present study is to comprehensively investigate the physicochemical characteristics and structure-function relationship of this antimicrobial peptide by using a series of bioinformatics and experimental approaches. In this study, we revealed that the mature Cecropin XJ consists of 41 amino acids, containing two α-helical structures from Lys⁷ to Lys²⁵ and from Ala²⁹ to Ile³⁹. The phylogenetic tree indicated that Cecropin XJ belongs to the Class I AMPs of cecropin family. Hydrophobic analysis showed Cecropin XJ is a typical amphiphilic molecule. The surface of Cecropin XJ was found to have a much wide range of electrostatic potential from ?83.243 to +83.243. The amphipathicity and surface potential of Cecropin XJ partially supported the AMP pore-forming hypothesis. Scanning electron microscopy experimentally confirmed the damages of Cecropin XJ to microbial membrane. Four predicted docking sites respectively for magnesium ion (Mg²⁺), adenosine diphosphate (ADP), bacteriopheophytin (BPH), and guanosine triphosphate (GTP) were found on the surface of Cecropin XJ. Thereinto, Mg²⁺ was experimentally proved to suppress the antibacterial activity of Cecropin XJ; both GTP and ADP enhanced the bactericidal activities to varying degrees. The present study provides a foundation for further investigation of molecular evolution, structural modification, and functional mechanisms of Cecropin XJ.     

Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein

The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent ¹⁵N and ¹³C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide ¹H nuclei, and quantitative measurements of site-specific ¹⁵N–¹⁵N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 3₁₀-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant.     

Characterization of newly established colorectal cancer cell lines: correlation between cytogenetic abnormalities and allelic deletions associated with multistep tumorigenesis

We have established a series of 20 colorectal cancer cell lines and performed cytogenetic and RFLP analyses to show that the recurrent genetic abnormalities of chromosomes 1, 5, 17 and 18 associated with multistep tumorigenesis in colorectal cancer, and frequently detected as recurrent abnormalities in primary tumours, are also retained in long-term established cell lines. Earlier studies by us and other investigators showed that allelic losses of chromosomes 1 and 17 in primary colorectal cancers predicted poorer survival for the patients (P = 0.03). We utilized the cell lines to identify specific chromosomal sites or gene(s) on chromosomes 1 and 17 which confer more aggressive phenotype. Cytogenetic deletions of chromosome 1p were detected in 14 out of the 20 (70%) cell lines, whereas allelic deletions for 1p using polymorphic markers were detected in 13 out of 18 (72%) informative cell lines for at least one polymorphic marker. We have performed Northern blotting, immunohistochemical staining (p53 mRNA, protein) and RFLP analysis using several probes including p53 and nm23. RFLP analysis using a total of seven polymorphic markers located on 17p and 17q arms showed allelic losses aroundthe p53 locus in 16 out of the 20 cell lines (80%), four of which were losses of thep53 locus itself. In addition, seven cell lines (out of nine informative cases) also showed losses of thenm23 gene, four with concurrent losses of thep53 locus, while the remaining three were homozygous. In addition, five out of seven cell lines withnm23 deletions were derived from hepatic metastatic tumours, and one cell line was obtained from recurrent tumour. A comparison between allelic deletions of 1p and functional loss ofnm23 gene revealed a close association between these two events in cell lines derived from hepatic metastasis. Following immunohistochemical staining, nine out of the twenty cell lines showed high levels (25–80%) of mutant p53, four showed intermediate levels (>20%), and seven had undetectable levels of the protein. Of these seven, four showed complete absence of mRNA. Of the remaining three cell lines one showed aberrant mRNA due to germline rearrangement of thep53 gene, whereas in two cell lines normal levels of mRNA were present. Nineteen of the 20 cell lines had normal germline configurations for thep53 gene, while one showed a rearrangement. These data suggest that functional loss ofp53 andnm23 genes accomplished by a variety of mechanisms may be associated with poor prognosis and survival. In addition, concurrent deletions of chromosome regions 17p, 17q and 1p were closely associated with high-stage hepatic metastatic disease. These cell lines with well-characterized genetic alterations and known clinical history provide an invaluable source of material for various biological and clinical studies relating to multistep colorectal tumorigenesis.