Ant sperm storage organs do not have phenoloxidase constitutive immune activity

The prophenoloxidase system (proPO-AS) is a primordial constituent of insect innate immunity. Its broad action spectrum, rapid response time, and cytotoxic by-products induced by phenoloxidase (PO) production contribute to the effective clearing of invading pathogens. However, such immune reactions may not be optimal for insect organs that evolved to have mutualistic interactions with non-self-cells. Ant queens are long-lived, but only mate early in adult life and store the sperm in a specialized organ, the spermatheca. They never re-mate so their life-time reproductive success is ultimately sperm-limited, which maintains strong selection for high sperm viability before and after storage. The proPO-AS may therefore be inappropriate for the selective clearing of sexually transmitted infections, as it might also target sperm cells that cannot be replaced.We measured PO enzymatic activity in the sperm storage organs of three ant species before and after mating. Our data show that no PO is produced in the sperm storage organs, relative to other somatic tissues as controls, and that these negative results are not due to non-detection in small volumes as non-immune-relevant catalase activity in single spermatheca fluid samples of both virgin and mated queens was significant. The lack of PO activity in sperm storage organs across three different ant species may represent an evolutionarily conserved adaptation to life-long sperm storage by ant queens. We expect that PO activity will be similarly suppressed in queen spermathecae of other eusocial Hymenoptera (bees and wasps) and, more generally, of insect females that store sperm for long periods.     

The development of lateral line placodes: Taking a broader view

The lateral line system of anamniote vertebrates enables the detection of local water movement and weak bioelectric fields. Ancestrally, it comprises neuromasts – small sense organs containing mechanosensory hair cells – distributed in characteristic lines over the head and trunk, flanked on the head by fields of electroreceptive ampullary organs, innervated by afferent neurons projecting respectively to the medial and dorsal octavolateral nuclei in the hindbrain. Given the independent loss of the electrosensory system in multiple lineages, the development and evolution of the mechanosensory and electrosensory components of the lateral line must be dissociable. Nevertheless, the entire system arises from a series of cranial lateral line placodes, which exhibit two modes of sensory organ formation: elongation to form sensory ridges that fragment (with neuromasts differentiating in the center of the ridge, and ampullary organs on the flanks), or migration as collectives of cells, depositing sense organs in their wake. Intensive study of the migrating posterior lateral line placode in zebrafish has yielded a wealth of information concerning the molecular control of migration and neuromast formation in this migrating placode, in this cypriniform teleost species. However, our mechanistic understanding of neuromast and ampullary organ formation by elongating lateral line placodes, and even of other zebrafish lateral line placodes, is sparse or non-existent. Here, we attempt to highlight the diversity of lateral line development and the limits of the current research focus on the zebrafish posterior lateral line placode. We hope this will stimulate a broader approach to this fascinating sensory system.     

Multicarpellate gynoecia in angiosperms: occurrence,development, organization and architectural constraints

Most angiosperms have gynoecia with two to five carpels. However, more than five carpels (here termed ‘multicarpellate condition’) are present in some representatives of all larger subclades of angiosperms. In such multicarpellate gynoecia, the carpels are in either one or more than one whorl (or series). I focus especially on gynoecia in which the carpels are in a single whorl (or series). In such multicarpellate syncarpous gynoecia, the closure in the centre of the gynoecium is imprecise as a result of slightly irregular development of the carpel flanks. Irregular bumps appear to stuff the remaining holes. In multicarpellate gynoecia, the centre of the remaining floral apex is not involved in carpel morphogenesis, so that this unspent part of the floral apex remains morphologically undifferentiated. It usually becomes enclosed within the gynoecium, but, in some cases, remains exposed and may or may not form simple excrescences. The area within the remaining floral apex is histologically characterized by a parenchyma of simple longitudinal cell rows. In highly multicarpellate gynoecia with the carpels in a whorl, the whorl tends to be deformed into an H‐shaped or star‐shaped structure by differential growth of the floral sectors, so that carpels become aligned in parallel rows, in which they face each other with the ventral sides. In this way, a fractionated compitum may still be functional. Multicarpellate gynoecia (with the carpels in one whorl or series) occur in at least one species in 37 of the 63 angiosperm orders. In contrast, non‐multicarpellate gynoecia are present in at least one species of all 63 orders. The basal condition in angiosperms is more likely non‐multicarpellate. Multicarpellate gynoecia are restricted to flowers that are not highly synorganized. In groups with synorganized androecium and gynoecium and in groups with elaborate monosymmetric flowers, multicarpellate gynoecia are lacking. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2014, 174 , 1–43.     

The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults

Systemic inflammatory illnesses (such as sepsis) are marked by degradation of the endothelial glycocalyx, a layer of glycosaminoglycans (including heparan sulfate, chondroitin sulfate, and hyaluronic acid) lining the vascular lumen. We hypothesized that different pathophysiologic insults would produce characteristic patterns of released glycocalyx fragments. We collected plasma from healthy donors as well as from subjects with respiratory failure due to altered mental status (intoxication, ischemic brain injury), indirect lung injury (non-pulmonary sepsis, pancreatitis), or direct lung injury (aspiration, pneumonia). Mass spectrometry was employed to determine the quantity and sulfation patterns of circulating glycosaminoglycans. We found that circulating heparan sulfate fragments were significantly (23-fold) elevated in patients with indirect lung injury, while circulating hyaluronic acid concentrations were elevated (32-fold) in patients with direct lung injury. N-Sulfation and tri-sulfation of heparan disaccharides were significantly increased in patients with indirect lung injury. Chondroitin disaccharide sulfation was suppressed in all groups with respiratory failure. Plasma heparan sulfate concentrations directly correlated with intensive care unit length of stay. Serial plasma measurements performed in select patients revealed that circulating highly sulfated heparan fragments persisted for greater than 3 days after the onset of respiratory failure. Our findings demonstrate that circulating glycosaminoglycans are elevated in patterns characteristic of the etiology of respiratory failure and may serve as diagnostic and/or prognostic biomarkers of critical illness.     

Decorin Induces Mitophagy in Breast Carcinoma Cells via Peroxisome Proliferator-activated Receptor γ Coactivator-1α (PGC-1α) and Mitostatin

Tumor cell mitochondria are key biosynthetic hubs that provide macromolecules for cancer progression and angiogenesis. Soluble decorin protein core, hereafter referred to as decorin, potently attenuated mitochondrial respiratory complexes and mitochondrial DNA (mtDNA) in MDA-MB-231 breast carcinoma cells. We found a rapid and dynamic interplay between peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and the decorin-induced tumor suppressor gene, mitostatin. This interaction stabilized mitostatin mRNA with concurrent accumulation of mitostatin protein. In contrast, siRNA-mediated abrogation of PGC-1α-blocked decorin-evoked stabilization of mitostatin. Mechanistically, PGC-1α bound MITOSTATIN mRNA to achieve rapid stabilization. These processes were orchestrated by the decorin/Met axis, as blocking the Met-tyrosine kinase or knockdown of Met abrogated these responses. Furthermore, depletion of mitostatin blocked decorin- or rapamycin-evoked mitophagy, increased vascular endothelial growth factor A (VEGFA) production, and compromised decorin-evoked VEGFA suppression. Collectively, our findings underscore the complexity of PGC-1α-mediated mitochondrial homeostasis and establish mitostatin as a key regulator of tumor cell mitophagy and angiostasis.     

Targeting of Splice Variants of Human Cytochrome P450 2C8 (CYP2C8) to Mitochondria and Their Role in Arachidonic Acid Metabolism and Respiratory Dysfunction

In this study, we found that the full-length CYP2C8 (WT CYP2C8) and N-terminal truncated splice variant 3 (∼44-kDa mass) are localized in mitochondria in addition to the endoplasmic reticulum. Analysis of human livers showed that the mitochondrial levels of these two forms varied markedly. Molecular modeling based on the x-ray crystal structure coordinates of CYP2D6 and CYP2C8 showed that despite lacking the N-terminal 102 residues variant 3 possessed nearly complete substrate binding and heme binding pockets. Stable expression of cDNAs in HepG2 cells showed that the WT protein is mostly targeted to the endoplasmic reticulum and at low levels to mitochondria, whereas variant 3 is primarily targeted to mitochondria and at low levels to the endoplasmic reticulum. Enzyme reconstitution experiments showed that both microsomal and mitochondrial WT CYP2C8 efficiently catalyzed paclitaxel 6-hydroxylation. However, mitochondrial variant 3 was unable to catalyze this reaction possibly because of its inability to stabilize the large 854-Da substrate. Conversely, mitochondrial variant 3 catalyzed the metabolism of arachidonic acid into 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid when reconstituted with adrenodoxin and adrenodoxin reductase. HepG2 cells stably expressing variant 3 generated higher levels of reactive oxygen species and showed a higher level of mitochondrial respiratory dysfunction. This study suggests that mitochondrially targeted variant 3 CYP2C8 may contribute to oxidative stress in various tissues.     

Hatching glands in cephalopods – A comparative study

Hatching of embryos from their eggs involves either mechanical and/or chemical support. In particular enzymes are widely used in the animal kingdom to weaken the egg layers and facilitate the embryo's escape. Although numerous morphological and biochemical studies exist on the hatching glands of invertebrates (such as sea urchins, ascidians, insects) and vertebrates (teleosts, amphibians, and mammals), little is known about the morphology of the hatching glands (Hoyle organs) in cephalopod hatchlings.In this study, the internal gland structure and the external appearance of the Hoyle organ are compared among several cephalopod species (Idiosepius pygmaeus; Euprymna scolopes; Sepia officinalis; Loligo gahi; Sepioteuthis lessoniana; Architeuthis sp.; Octopus vulgaris; Tremoctopus gracilis; Argonauta hians). In almost all cases the glandular system is restricted to the posterior part of the dorsal mantle surface. Only Octopus and Argonauta lack a specific glandular structure in this body region and the animals apparently use other mechanisms to penetrate the egg layers.In all decapod species (Idiosepius; Euprymna; Sepia; Loligo; Sepioteuthis; Architeuthis) as well as in Tremoctopus only one specific cell type is present in the Hoyle organ, which synthesizes granular material. The secretory droplets are more or less uniform in electron density in Idiosepius, Euprymna and Tremoctopus but exhibit translucent inclusions in the other decapods. The time of gland development, first synthesis of secretory products and later degeneration after hatching vary between the species.The present study contributes to our knowledge of glandular systems in cephalopods and allows comparison with hatching structures in other invertebrates and vertebrates.     

The impact of respiratory gating on lung dosimetry in stereotactic body radiotherapy for lung cancer

The purpose of this study was to evaluate the impacts of respiratory gating and different gating windows (GWs) on lung dosimetry in stereotactic body radiotherapy (SBRT) for lung cancer.Gated SBRT plans were developed using the four-dimensional computed tomography data from 17 lung cancer patients treated with SBRT. Using amplitude-based end-exhalation gating, we established 2 fixed GWs with approximate duty cycles of 50% (50% GW) and 25% (25% GW), respectively, for this study.For highly mobile tumors (3D mobility > 10 mm), additional benefits in lung-dose reductions were achieved with the 25% GW, as a result of inadequate mobility and planning target volume reductions obtained with the 50% GW. In these tumors, the absolute differences compared to the non-gated and 50% gated plans, were 0.5 Gy and 0.33 Gy for the mean lung dose and 1.11% and 0.71% for the V20, respectively. Dosimetric benefits were achieved with the 50% GW, compared with the non-gated plan, for tumors with both low mobility and small volume (gross tumor volume ≤ 10 cc). Among the identified predictive factors of dosimetric benefits, the lateral distance from midspinal canal and the motion range in anterior–posterior direction might be stronger factors because of their correlations with many of the lung-dose parameters and greater predictive capacity.The results of the present study might facilitate the selection of appropriate patients and the optimal GW according to the tumor characteristics for gated lung SBRT.     

503例儿童急性呼吸道感染常见病毒的检测结果分析

目的通过对503例急性呼吸道感染患儿进行7种常见病毒[流感病毒A、B型（IVA、IVB）,腺病毒（ADV）,副流感病毒1、2、3型（PIV1、PIV2、PIV3）及呼吸道合胞病毒（RSV）]的检测,了解本地区2013年急性呼吸道感染患儿的病毒感染状况。方法应用免疫荧光法对503例急性呼吸道感染患儿的咽拭子进行7种常见病毒的检测。结果 503例患儿中有55例检出病毒阳性,总阳性率为10.93%,均为单一病毒感染。7种常见病毒中,RSV的感染率最高,为76.36%。在各年龄组中,〈1岁组的病毒检出率最高,为29.41%,随着年龄的增长,检出率逐渐降低。从季节分布来看,春季的感染率最高,为23.08%,其次为冬季,感染率10.13%。结论 RSV是2013年本地区儿童急性呼吸道感染的主要病毒,〈1岁组患儿的病毒检出率最高,春季为感染的高发季节。