The complete mitochondrial genome of Pauropus longiramus (Myriapoda: Pauropoda): implications on early diversification of the myriapods revealed from comparative analysis

Myriapods are among the earliest arthropods and may have evolved to become part of the terrestrial biota more than 400 million years ago. A noticeable lack of mitochondrial genome data from Pauropoda hampers phylogenetic and evolutionary studies within the subphylum Myriapoda. We sequenced the first complete mitochondrial genome of a microscopic pauropod, Pauropus longiramus (Arthropoda: Myriapoda), and conducted comprehensive mitogenomic analyses across the Myriapoda. The pauropod mitochondrial genome is a circular molecule of 14,487 bp long and contains the entire set of thirty-seven genes. Frequent intergenic overlaps occurred between adjacent tRNAs, and between tRNA and protein-coding genes. This is the first example of a mitochondrial genome with multiple intergenic overlaps and reveals a strategy for arthropods to effectively compact the mitochondrial genome by overlapping and truncating tRNA genes with neighbor genes, instead of only truncating tRNAs. Phylogenetic analyses based on protein-coding genes provide strong evidence that the sister group of Pauropoda is Symphyla. Additionally, approximately unbiased (AU) tests strongly support the Progoneata and confirm the basal position of Chilopoda in Myriapoda. This study provides an estimation of myriapod origins around 555 Ma (95% CI: 444-704 Ma) and this date is comparable with that of the Cambrian explosion and candidate myriapod-like fossils. A new time-scale suggests that deep radiations during early myriapod diversification occurred at least three times, not once as previously proposed. A Carboniferous origin of pauropods is congruent with the idea that these taxa are derived, rather than basal, progoneatans.     

Candesartan antagonizes pressure overload-evoked cardiac remodeling through Smad7 gene-dependent MMP-9 suppression

The present study was designed to investigate the underlying molecular mechanism for Angiotensin II type 1 receptor blockers (ARBs) mediated cardio-protection against pressure overload-induced cardiac remodeling with a focus on Smad7. ROCK-1, Smad3 and fibronectin expressions were increased in male C57BL/6 mice underwent transverse aortic constriction (TAC) for 2weeks. Treatment with Candesartan (2mg/kg per day) could effectively downregulate Smad3 and fibronectin accompanied by upregulating of Smad7. Further data showed that Candesartan inhibited TGF-β1 signal-induced epithelial-to-mesenchymal transition (EMT) through attenuating matrix metalloproteinases (MMP-9), such effect was abolished by knocking-down Smad7. Moreover, TAC for 2weeks caused increased collagen deposition, thickness of left ventricular anterior and posterior wall at end-diastole (LVAWD and LVPWD) and LVEF% reduction, which were reversed by treatment with Candesartan, but failed after knocking-down Smad7. In addition, LV dP/dt(max) and dP/dt(min) were increased by TAC for 2weeks, and treatment with Candesartan or Nifedipine effectively depressed the high levels of dP/dt(min) induced by TAC. However, only Candesartan-mediated protective role in improving cardiac function was suppressed by tail-vein injection of Smad7 siRNA. This study uncovered a novel role for ARBs in preventing pressure overload-induced cardiac remodeling via Smad7 upregulation, which suppressed MMP-9 expression and TGF-β1 signal-mediated EMT progress.     

Inference for Proportions in a 2 × 2 Contingency Table: HPD or not HPD?

Summary Highest posterior density intervals are common in Bayesian inference, but as noted by Agresti and Min (2005, Biometrics 61, 515–523) they are not invariant under transformations. Agresti and Min suggested central or “tail” intervals as preferable in the context of the relative risk and odds ratio. A modification to this is proposed for extreme outcomes, as invariance is maintained when replacing central intervals by one‐sided intervals. Bayes–Laplace priors for the binomial parameters appear preferable here, compared to Jeffreys priors, contrary to Agresti and Min's suggestion based on frequentist coverage.     

Pax7 shows higher satellite cell frequencies and concentrations within intrafusal fibers of muscle spindles

Intrafusal fibers within muscle spindles make up a small subpopulation of muscle fibers. These proprioceptive fibers differ from most extrafusal fibers because, even in maturity, their diameters remain small, and they retain expression of developmental myosins. Although both extrafusal and intrafusal fibers contain satellite cells (SCs), comparatively little is known about intrafusal SCs. Analyzing chicken fast-phasic posterior (PLD) and slow-tonic anterior (ALD) latissimus dorsi muscles, we show that SCs of both intrafusal and extrafusal fibers express Pax7. We further test the hypotheses that intrafusal fibers display parameters reflective of extrafusal immaturity. These hypotheses are that intrafusal fibers contain (a) higher SC frequencies (number of SC nuclei/all nuclei within basal lamina) and concentrations (closer together) and (b) smaller myonuclear domains than do adjacent extrafusal fibers. IHC techniques were applied to PLD and ALD muscles excised at 30 and 138 days posthatch. The hypotheses were validated, suggesting that intrafusal fibers have greater capacities for growth, regeneration, and repair than do adjacent extrafusal fibers. During maturation, extrafusal and intrafusal fibers show similar trends of decreasing SC frequencies and concentrations and increases in myonuclear domains. Thus, extrafusal and intrafusal fibers alike should exhibit reduced capacities for growth, regeneration, and repair during maturation.     

Evolution and functional divergence of monocarboxylate transporter genes in vertebrates

Monocarboxylate transporters (MCTs) form a gene family with an ancient past. The identification of MCTs (MCHs) from bacteria, protozoa, fungi, invertebrates, as well as vertebrates, but not from plants and virus, allowed illuminating the phylogenetic and evolutionary history of this gene family. The significant expansion of vertebrate MCT genes should have primarily occurred after the divergence of vertebrates and invertebrates, but before the divergence time between ray-finned fish and mammals. The divergence of insect MCTs should have at least occurred in the common ancestor of fruit fly, beetle, and honeybee. Fungi monocarboxylate transporter homologues (MCHs) might evolve independently from an ancient ancestor. The results of functional divergence analysis provided statistical evidences for shifted evolutionary rate and/or changes of amino acid property after gene duplication. The sliding window analysis of the d(N)/d(S) ratio values showed that strong functional constraints must impose on the N- and C-terminal domains of vertebrate MCTs. These corresponding regions may play crucial roles for functionality of MCT proteins.     

颈前路“杂交式”与颈后路治疗多节段脊髓型颈椎病的临床比较

目的:比较颈前路"杂交式"减压融合与颈后路全椎板减压侧块内固定术治疗多节段脊髓型颈椎病的临床特点。方法:选择36例行"杂交式"颈前路治疗及33例行颈后路全椎板减压侧块内固定术治疗的多节段脊髓型颈椎病患者,观察两组患者手术前后一般资料、出血量、手术时间、颈椎生理曲度、JOA评分及并发症的发生情况。结果:两组患者术前的一般资料包括年龄(颈前路组:56.23±7.64岁,颈后路组:55.76±8.18岁)、性别(颈前路组:22男/14女,颈后路组:20男/13女)、颈椎生理曲度D值(颈前路组:7.41±3.14,颈后路组:8.19±2.74)、JOA评分(颈前路组:9.08±1.09分,颈后路组:8.82±1.26分)、病程(颈前路组:17.24±7.36月,颈后路组:15.75±5.78月)和受累节段(颈前路组:3.11±0.26个,颈后路组:3.24±0.39个)比较差异均无统计学意义(P0.05)。与颈后路相比,颈前路的术中出血量(颈前路组:221.79±178.02 mL,颈后路组:483.07±434.25 mL)更少,差异有统计学意义(P0.05),手术时间(颈前路组:196.54±51.88 min,颈后路组:175.12±54.93 min)更长,但差异无统计学意义(P0.05)。随着时间的延长,颈前路组患者颈椎生理曲度和JOA评分逐渐增大,而颈后路组患者椎生理曲度减少,JOA评分逐渐增大,差异有统计学意义(P0.05)。颈前路组出现植骨未融合、声音嘶哑和脑脊漏液,颈后路组发生轴性疼痛和C5神经根麻痹,但两组患者并发症的发生率比较差异无统计学意义(颈前路组:13.89%,颈后路组:12.12%)(P0.05)。结论:颈前路"杂交式"减压融合与颈后路全椎板减压侧块内固定术在治疗多节段脊髓型颈椎病上各有优点,临床根据患者的情况而采取合适的治疗方式。     

Drosophila Chitinase 2 is expressed in chitin producing organs for cuticle formation

The architecture of the outer body wall cuticle is fundamental to protect arthropods against invading pathogens and numerous other harmful stresses. Such robust cuticles are formed by parallel running chitin microfibrils. Molting and also local wounding leads to dynamic assembly and disassembly of the chitin-matrix throughout development. However, the underlying molecular mechanisms that organize proper chitin-matrix formation are poorly known. Recently we identified a key region for cuticle thickening at the apical cell surface, the cuticle assembly zone, where Obstructor-A (Obst-A) coordinates the formation of the chitin-matrix. Obst-A binds chitin and the deacetylase Serpentine (Serp) in a core complex, which is required for chitin-matrix maturation and preservation. Here we present evidence that Chitinase 2 (Cht2) could be essential for this molecular machinery. We show that Cht2 is expressed in the chitin-matrix of epidermis, trachea, and the digestive system. There, Cht2 is enriched at the apical cell surface and the dense chitin-matrix. We further show that in Cht2 knockdown larvae the assembly zone is rudimentary, preventing normal cuticle formation and pore canal organization. As sequence similarities of Cht2 and the core complex proteins indicate evolutionarily conserved molecular mechanisms, our findings suggest that Cht2 is involved in chitin formation also in other insects.     

Limb Patterning: From Signaling Gradients to Molecular Oscillations

The developing forelimb is patterned along the proximal–distal and anterior–posterior axes by opposing gradients of retinoic acid and fibroblast growth factors and by graded sonic hedgehog signaling, respectively. However, how coordinated patterning along both axes is accomplished with temporal precision remains unknown. The limb molecular oscillator hairy2 was recently shown to be a direct readout of the combined signaling activities of retinoic acid, fibroblast growth factor and sonic hedgehog in the limb mesenchyme. Herein, an integrated time-space model is presented to conciliate the progress zone and two-signal models for limb patterning. We propose that the limb clock may allow temporal information to be decoded into positional information when the distance between opposing signaling gradients is no longer sufficient to provide distinct cell fate specification.