A novel mitochondrial genome architecture in thrips (Insecta: Thysanoptera): extreme size asymmetry among chromosomes and possible recent control region duplication

Background

Multipartite mitochondrial genomes are very rare in animals but have been found previously in two insect orders with highly rearranged genomes, the Phthiraptera (parasitic lice), and the Psocoptera (booklice/barklice).

Results

We provide the first report of a multipartite mitochondrial genome architecture in a third order with highly rearranged genomes: Thysanoptera (thrips). We sequenced the complete mitochondrial genomes of two divergent members of the Scirtothrips dorsalis cryptic species complex. The East Asia 1 species has the single circular chromosome common to animals while the South Asia 1 species has a genome consisting of two circular chromosomes. The fragmented South Asia 1 genome exhibits extreme chromosome size asymmetry with the majority of genes on the large, 14.28 kb, chromosome and only nad6 and trnC on the 0.92 kb mini-circle chromosome. This genome also features paralogous control regions with high similarity suggesting a very recent origin of the nad6 mini-circle chromosome in the South Asia 1 cryptic species.

Conclusions

Thysanoptera, along with the other minor paraenopteran insect orders should be considered models for rapid mitochondrial genome evolution, including fragmentation. Continued use of these models will facilitate a greater understanding of recombination and other mitochondrial genome evolutionary processes across eukaryotes.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1672-4) contains supplementary material, which is available to authorized users.     

Anti-type II collagen immune complex-induced granulocyte reactivity is associated with joint erosions in RA patients with anti-collagen antibodies

IntroductionRheumatoid arthritis (RA) patients with autoantibodies against collagen type II (CII) are characterized by acute RA onset with elevated inflammatory measures and early joint erosions as well as increased production of tumor necrosis factor-α (ΤΝF-α) by peripheral blood mononuclear cells (PBMC) stimulated by anti-CII immune complexes (IC) in vitro. Polymorphonuclear granulocytes (PMN) are abundant in RA synovial fluids, where they might interact directly with anti-CII IC in the articular cartilage, but no studies have investigated PMN responses towards anti-CII IC. The aim was to investigate whether PMN react towards anti-CII IC, and to what extent such reactivity might relate to the clinical acute onset RA phenotype associated with elevated levels of anti-CII.MethodsPMN and PBMC isolated from healthy donors were stimulated with IC made with a set of 72 baseline patient sera (24 anti-CII positive, 48 anti-CII negative) chosen from a clinically well-characterized RA cohort with two-year radiological follow-up with Larsen scoring. PMN expression of cluster of differentiation (CD)11b, CD66b, CD16 and CD32 was measured by flow cytometry, whereas PMN production of myeloperoxidase (MPO) and interleukin (IL)-17, and PBMC production of ΤΝF-α was measured with enzyme linked immunosorbent assay.ResultsPMN expression of CD11b, CD66b and MPO, and PBMC production of ΤΝF-α were upregulated whereas PMN expression of CD16 and CD32 were downregulated by anti-CII IC. CD16, CD66b, and MPO production correlated to serum anti-CII levels (Spearman’s ρ = 0.315, 0.675 and 0.253, respectively). CD16 was associated with early joint erosions (P = 0.024, 0.034, 0.046 at baseline, one and two years) and CD66b was associated with changes in joint erosions (P = 0.017 and 0.016, at one and two years compared to baseline, respectively). CD66b was associated with baseline C-reactive protein and PBMC production of ΤΝF-α was associated with baseline erythrocyte sedimentation rate, in accordance with our earlier findings. No clinical associations were observed for MPO or IL-17.ConclusionPMN responses against anti-CII IC are more closely associated with early joint erosions than are PBMC cytokine responses. PMN reactivity against anti-CII IC may contribute to joint destruction in newly diagnosed RA patients with high levels of anti-CII.     

Synthesis, biological evaluation and molecular docking studies of stellatin derivatives as cyclooxygenase (COX-1, COX-2) inhibitors and anti-inflammatory agents

Stellatin (4), isolated from Dysophylla stellata is a cyclooxygenase (COX) inhibitor. The present study reports the synthesis and biological evaluation of new stellatin derivatives for COX-1, COX-2 inhibitory and anti-inflammatory activities. Eight derivatives showed more pronounced COX-2 inhibition than stellatin and, 17 and 21 exhibited the highest COX-2 inhibition. They also exhibited the significant anti-inflammatory activity in TPA-induced mouse ear edema assay and their anti-inflammatory effects were more than that of stellatin and indomethacin at 0.5 mg/ear. The derivatives were further evaluated for antioxidant activity wherein 16 and 17 showed potent free radical scavenging activity against DPPH and ABTS radicals. Molecular docking study revealed the binding orientations of stellatin and its derivatives into the active sites of COX-1 and COX-2 and thereby helps to design the potent inhibitors.     

Advanced glycation end product recognition by the receptor for AGEs

Nonenzymatic protein glycation results in the formation of advanced glycation end products (AGEs) that are implicated in the pathology of diabetes, chronic inflammation, Alzheimer's disease, and cancer. AGEs mediate their effects primarily through a receptor-dependent pathway in which AGEs bind to a specific cell surface associated receptor, the Receptor for AGEs (RAGE). N(?)-carboxy-methyl-lysine (CML) and N(?)-carboxy-ethyl-lysine (CEL), constitute two of the major AGE structures found in tissue and blood plasma, and are physiological ligands of RAGE. The solution structure of a CEL-containing peptide-RAGE V domain complex reveals that the carboxyethyl moiety fits inside a positively charged cavity of the V domain. Peptide backbone atoms make specific contacts with the V domain. The geometry of the bound CEL peptide is compatible with many CML (CEL)-modified sites found in plasma proteins. The structure explains how such patterned ligands as CML (CEL)-proteins bind to RAGE and contribute to RAGE signaling.     

Spontaneous demonstration of counterclockwise right atrial activation following successful isthmus ablation

We describe an uncommon case of typical flutter with symptomatic sinus node dysfunction, in which a permanent junctional rhythm developed following ablation of the cavo-tricuspid isthmus. This rhythm activated the right atrium in counter clockwise manner thus providing spontaneous proof of unidirectional isthmus block, a phenomenon that is usually demonstrated by proximal coronary sinus pacing.     

Identification of hotspot regions of MurB oxidoreductase enzyme using homology modeling,molecular dynamics and molecular docking techniques

Despite the availability of effective chemotherapy and a moderately protective vaccine, new anti-tuberculosis agents are urgently needed to decrease the global incidence of tuberculosis (TB) disease. The MurB gene belongs to the bacterial cell wall biosynthesis pathway and is an essential drug target in Mycobacterium tuberculosis (Mtb) that has no mammalian counterparts. Here, we present an integrated approach involving homology modeling, molecular dynamics and molecular docking studies on Mtb-MurB oxidoreductase enzyme. A homology model of Mtb-MurB enzyme was built for the first time in order to carry out structure-based inhibitor design. The accuracy of the model was validated using different techniques. The molecular docking study on this enzyme was undertaken using different classes of well known MurB inhibitors. Estimation of binding free energy by docking analysis indicated the importance of Tyr155, Arg156, Ser237, Asn241 and His304 residues within the Mtb-MurB binding pocket. Our computational analysis is in good agreement with experimental results of site-directed mutagenesis. The present study should therefore play a guiding role in the experimental design of Mtb-MurB inhibitors for in vitro/in vivo analysis.     

Toward rational design of bacterial genomes

The advent of genetic engineering-the ability to edit and insert DNA into living organisms-in the latter half of the 20th century created visions of a new era of synthetic biology, where novel biological functions could be designed and implemented for useful purposes. We are witnessing an exciting revolution of scale, wherein technical progresses allow for the manipulation of genetic material at the whole genome level. This will enable the manufacture of increasingly complex genetic designs to solve pressing challenges in health, energy and the environment-if and when such designs can be specified. We argue that the organized development of key common application organisms, engineered for engineerability, and attendant libraries of parts, pathways and standardized manufacturing are necessary for this genome-scale technology to realize its promise.     

Neuropathic pain and psychological morbidity in patients with treated leprosy: a cross-sectional prevalence study in Mumbai

Background

Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated.

Methodology/Principal Findings

Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity.

Conclusions/Significance

One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity.     

A comparison of clinical and epidemiological characteristics of fatal human infections with H5N1 and human influenza viruses in Thailand, 2004-2006

Background

The National Avian Influenza Surveillance (NAIS) system detected human H5N1 cases in Thailand from 2004–2006. Using NAIS data, we identified risk factors for death among H5N1 cases and described differences between H5N1 and human (seasonal) influenza cases.

Methods and Findings

NAIS identified 11,641 suspect H5N1 cases (e.g. persons with fever and respiratory symptoms or pneumonia, and exposure to sick or dead poultry). All suspect H5N1 cases were tested with polymerase chain reaction (PCR) assays for influenza A(H5N1) and human influenza viruses. NAIS detected 25 H5N1 and 2074 human influenza cases; 17 (68%) and 22 (1%) were fatal, respectively. We collected detailed information from medical records on all H5N1 cases, all fatal human influenza cases, and a sampled subset of 230 hospitalized non-fatal human influenza cases drawn from provinces with ≥1 H5N1 case or human influenza fatality.Fatal versus non-fatal H5N1 cases were more likely to present with low white blood cell (p = 0.05), lymphocyte (p<0.02), and platelet counts (p<0.01); have elevated liver enzymes (p = 0.05); and progress to circulatory (p<0.001) and respiratory failure (p<0.001). There were no differences in age, medical conditions, or antiviral treatment between fatal and non-fatal H5N1 cases. Compared to a sample of human influenza cases, all H5N1 cases had direct exposure to sick or dead birds (60% vs. 100%, p<0.05). Fatal H5N1 and fatal human influenza cases were similar clinically except that fatal H5N1 cases more commonly: had fever (p<0.001), vomiting (p<0.01), low white blood cell counts (p<0.01), received oseltamivir (71% vs. 23%, p<.001), but less often had ≥1 chronic medical conditions (p<0.001).

Conclusions

In the absence of diagnostic testing during an influenza A(H5N1) epizootic, a few epidemiologic, clinical, and laboratory findings might provide clues to help target H5N1 control efforts. Severe human influenza and H5N1 cases were clinically similar, and both would benefit from early antiviral treatment.