Drosophila immune cells transport oxygen through PPO2 protein phase transition.

Insect respiration has long been thought to be solely dependent on an elaborate tracheal system without assistance from the circulatory system or immune cells1,2. Here we describe that Drosophila crystal cells-myeloid-like immune cells called haemocytes-control respiration by oxygenating Prophenoloxidase 2 (PPO2) proteins. Crystal cells direct the movement of haemocytes between the trachea of the larval body wall and the circulation to collect oxygen. Aided by copper and a neutral pH, oxygen is trapped in the crystalline structures of PPO2 in crystal cells. Conversely, PPO2 crystals can be dissolved when carbonic anhydrase lowers the intracellular pH and then reassembled into crystals in cellulo by adhering to the trachea. Physiologically, larvae lacking crystal cells or PPO2, or those expressing a copper-binding mutant of PPO2, display hypoxic responses under normoxic conditions and are susceptible to hypoxia. These hypoxic phenotypes can be rescued by hyperoxia, expression of arthropod haemocyanin or prevention of larval burrowing activity to expose their respiratory organs. Thus, we propose that insect immune cells collaborate with the tracheal system to reserve and transport oxygen through the phase transition of PPO2 crystals, facilitating internal oxygen homeostasis in a process that is comparable to vertebrate respiration.

S-nitrosylation-triggered unfolded protein response maintains hematopoietic progenitors in Drosophila.

The Drosophila lymph gland houses blood progenitors that give rise to myeloid-like blood cells. Initially, blood progenitors proliferate, but later, they become quiescent to maintain multipotency before differentiation. Despite the identification of various factors involved in multipotency maintenance, the cellular mechanism controlling blood progenitor quiescence remains elusive. Here, we identify the expression of nitric oxide synthase in blood progenitors, generating nitric oxide for post-translational S-nitrosylation of protein cysteine residues. S-nitrosylation activates the Ire1-Xbp1-mediated unfolded protein response, leading to G2 cell-cycle arrest. Specifically, we identify the epidermal growth factor receptor as a target of S-nitrosylation, resulting in its retention within the endoplasmic reticulum and blockade of its receptor function. Overall, our findings highlight developmentally programmed S-nitrosylation as a critical mechanism that induces protein quality control in blood progenitors, maintaining their undifferentiated state by inhibiting cell-cycle progression and rendering them unresponsive to paracrine factors.

Sonographic and computed tomographic features of intestinal mast cell tumors mimicking alimentary lymphoma in 2 dogs.

Two shih tzu dogs were referred to our clinic because of hematochezia and vomiting. Abdominal ultrasonography revealed a focal, asymmetric, exophytic small intestinal mass with loss of wall layering and muscular layer thickening of the adjacent intestine. Computed tomography (CT) in both dogs revealed a focal, asymmetric, homogenously contrast-enhanced exophytic jejunal and duodenal mass with an intact mucosal layer and generalized lymphadenopathy. Metastasis and ulceration were not detected on CT. The initial imaging diagnosis was lymphoma in both dogs; however, histopathological examination revealed the presence of intestinal mast cell tumors (iMCTs). Despite its similarity to alimentary lymphoma, iMCT should be considered a possible diagnosis, based on imaging characteristics, to ensure that proper treatments are selected. This is the first veterinary report describing detailed ultrasonographic and CT characteristics of iMCTs. Key clinical message: This is the first veterinary case report demonstrating sonographic and computed tomographic features of canine iMCT, which can be misdiagnosed as alimentary lymphoma. This report provides another differential diagnosis to consider when determining the appropriate patient treatment direction and histopathological examination.

Caractéristiques échographiques et tomodensitométriques de mastocytomes intestinaux imitant un lymphome alimentaire chez 2 chiens. Deux chiens shih tzu ont été référés à notre clinique en raison d'une hématochézie et de vomissements. L'échographie abdominale a révélé une masse focale, asymétrique et exophytique de l'intestin grêle avec perte de stratification pariétale et épaississement de la couche musculaire de l'intestin adjacent. La tomodensitométrie (TDM) chez les deux chiens a révélé une masse jéjunale et duodénale exophytique focale, asymétrique, homogène et contrastée avec une couche muqueuse intacte et une lymphadénopathie généralisée. Les métastases et les ulcérations n'ont pas été détectées par TDM. Le diagnostic initial d'imagerie était un lymphome chez les deux chiens; cependant, l'examen histopathologique a révélé la présence de mastocytomes intestinaux (iMCT). Malgré sa similitude avec le lymphome alimentaire, l'iMCT doit être considérée comme un diagnostic possible, basé sur les caractéristiques de l'imagerie, afin de garantir la sélection des traitements appropriés. Il s'agit du premier rapport vétérinaire décrivant les caractéristiques échographiques et tomodensitométriques détaillées des iMCT.Message clinique clé :Il s'agit du premier rapport de cas vétérinaire démontrant les caractéristiques échographiques et tomodensitométriques de l'iMCT canin, qui peuvent être diagnostiquées à tort comme un lymphome alimentaire. Ce rapport fournit un autre diagnostic différentiel à prendre en compte lors de la détermination de l'orientation thérapeutique et de l'examen histopathologique appropriés du patient.(Traduit par Dr Serge Messier).

Inter-organ regulation by the brain in Drosophila development and physiology.

The brain plays an essential role in regulating physiological homeostasis by communicating with other organs. Neuronal cells either directly innervate target tissues and transmit signals or secrete systemic factors into the hemolymph to regulate bodily functions, including physiology, development, metabolism, and immunity. In this review, we discuss the systemic functions of inter-organ communication mediated by the brain in four distinct categories: (1) nutrient sensing and feeding, (2) gastrointestinal activity and metabolism, (3) development and metamorphosis, and (4) immunity and hematopoiesis. First, we describe how chemosensory signals are sensed and transmitted to the brain in Drosophila and how the brain stimulates or modifies feeding behavior. Second, we summarize the brain-organ axis that regulates appetite activities and neuroendocrine pathways that maintain metabolic homeostasis. Third, we discuss how overall development in Drosophila is achieved by insulin and how it affects ecdysone signaling to initiate pupariation. Finally, we discuss how the central or peripheral nervous system controls hematopoiesis and innate immunity in Drosophila larvae. Given the functional parallels between Drosophila and humans, homologous pathways are likely to be conserved in human development and disease models, and the fly model system will continue to provide mechanistic insights into understanding complex interactions.

Vanadium Redox Flow Battery Using Activated Carbon Catalyst Produced from Low-Density Polyethylene.

Carbonized and activated low-density polyethylene (LDPE) is suggested as a carbon catalyst for vanadium redox flow battery (VRFB). This carbon catalyst has many surface oxygen functional groups and a large surface area, while such benefits are achieved through activation of carbonized LDPE. According to electrochemical analysis, this carbon catalyst doped graphite felt (GF) enhances the redox reactivity of vanadium ions. More specifically, peak current density and peak potential separation for redox reaction of vanadium ions are 96.0 and 22.1% more improved than those measured by bare GF, while charge transfer resistance for the redox reactions is also improved by use of the catalyst doped GF. When performance of VRFB using this catalyst doped GF is measured, energy efficiency is 39% more improved than that measured without the catalyst. Based on that, this is revealed that new LDPE-based carbon catalyst is effective for performance improvement of VRFB.

A new role for Hif-1α.

A gene normally involved in responding to hypoxia helps to protect insect muscles during migratory flight in a non-oxygen dependent manner.

Morphological and Allometric Changes in Anguilla japonica Larvae.

The freshwater eel Anguilla japonica is rapidly decreasing in number and has not yet been successfully mass produced. This may be at least partially attributable to the unique and long early life history of the eel. Therefore, we investigated its ontogeny of morphometry and growth pattern in larval stages to provide baseline information for understanding the early life history and improving seed rearing technology. This study was conducted for 200 days after hatching (DAH) and analyzed morphometry and allometry for eel larvae. The following cultured eel larval stages were identified: the yolk sac larvae stage (0-6 DAH, 3.23-6.85 mm total length (TL)), the pre-leptocephalus stage (7-30 DAH, 6.85-15.31 mm TL), and the leptocephalus stage (50-200 DAH, 15.31-60.06 mm TL). Cultured and wild eel larvae could be divided into characteristic larval stages at similar sizes. However, compared to wild eels, cultured eels had a slower growth rate and fewer preanal myomeres. Meanwhile, cultured eel larvae rarely had a mixed feeding period as the absorption of endogenous reserves was completed by 7 DAH. The lower jaw of eel larvae was significantly longer than the upper jaw from 50 DAH. In the pre-leptocephalus and leptocephalus stages, eel larvae showed continuous positive allometric growth at trunk height and tail muscle height with change to the willow leaf-like form. These growth characteristics may be the result of adaptation to the migration over long distances and to a diel vertical migration. The inflection point in the body parts growth patterns showed only before 30 DAH, and mass mortality appeared at this period. Therefore, to improve the growth and survival rates of cultured eel seed, it is necessary to focus on improving the feeding and rearing protocol until 30 DAH.

Highly Selective and pH-Stable Reverse Osmosis Membranes Prepared via Layered Interfacial Polymerization.

Ultrathin and smooth polyamide (PA) reverse osmosis (RO) membranes have attracted significant interest due to their potential advantages of high permeance and low fouling propensity. Although a layered interfacial polymerization (LIP) technique aided by the insertion of a polyelectrolyte interlayer has proven effective in fabricating ultrathin and uniform membranes, the RO performance and pH stability of the fabricated LIP membrane remain inadequate. In this study, a poly(piperazineamide) (PIPA) layer prepared via interfacial polymerization (IP) was employed as an interlayer to overcome the limitations of the prototype LIP method. Similar to the control polyelectrolyte-interlayered LIP membrane, the PIPA-interlayered LIP (pLIP) membrane had a much thinner (~20 nm) and smoother selective layer than the membrane fabricated via conventional IP due to the highly surface-confined and uniform LIP reaction. The pLIP membrane also exhibited RO performance exceeding that of the control LIP and conventional IP-assembled membranes, by enabling denser monomer deposition and a more confined interfacial reaction. Importantly, the chemically crosslinked PIPA interlayer endowed the pLIP membrane with higher pH stability than the control polyelectrolyte interlayer. The proposed strategy enables the fabrication of high-performance and pH-stable PA membranes using hydrophilic supports, which can be applied to other separation processes, including osmosis-driven separation and organic solvent filtration.

Metabolic control of cellular immune-competency by odors in Drosophila.

Studies in different animal model systems have revealed the impact of odors on immune cells; however, any understanding on why and how odors control cellular immunity remained unclear. We find that Drosophila employ an olfactory-immune cross-talk to tune a specific cell type, the lamellocytes, from hematopoietic-progenitor cells. We show that neuronally released GABA derived upon olfactory stimulation is utilized by blood-progenitor cells as a metabolite and through its catabolism, these cells stabilize Sima/HIFα protein. Sima capacitates blood-progenitor cells with the ability to initiate lamellocyte differentiation. This systemic axis becomes relevant for larvae dwelling in wasp-infested environments where chances of infection are high. By co-opting the olfactory route, the preconditioned animals elevate their systemic GABA levels leading to the upregulation of blood-progenitor cell Sima expression. This elevates their immune-potential and primes them to respond rapidly when infected with parasitic wasps. The present work highlights the importance of the olfaction in immunity and shows how odor detection during animal development is utilized to establish a long-range axis in the control of blood-progenitor competency and immune-priming.

Effects of Capping Layers with Different Metals on Electrical Performance and Stability of p-Channel SnO Thin-Film Transistors.

In this study, the effects of capping layers with different metals on the electrical performance and stability of p-channel SnO thin-film transistors (TFTs) were examined. Ni- or Pt-capped SnO TFTs exhibit a higher field-effect mobility (µFE), a lower subthreshold swing (SS), a positively shifted threshold voltage (VTH), and an improved negative-gate-bias-stress (NGBS) stability, as compared to pristine TFTs. In contrast, Al-capped SnO TFTs exhibit a lower µFE, higher SS, negatively shifted VTH, and degraded NGBS stability, as compared to pristine TFTs. No significant difference was observed between the electrical performance of the Cr-capped SnO TFT and that of the pristine SnO TFT. The obtained results were primarily explained based on the change in the back-channel potential of the SnO TFT that was caused by the difference in work functions between the SnO and various metals. This study shows that capping layers with different metals can be practically employed to modulate the electrical characteristics of p-channel SnO TFTs.

Single-cell transcriptome maps of myeloid blood cell lineages in Drosophila.

The Drosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and mature hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis and immunity. Three types of mature hemocytes have been characterized in the lymph gland: plasmatocytes, lamellocytes, and crystal cells, which are analogous to vertebrate myeloid cells, yet molecular underpinnings of the lymph gland hemocytes have been less investigated. Here, we use single-cell RNA sequencing to comprehensively analyze heterogeneity of developing hemocytes in the lymph gland, and discover previously undescribed hemocyte types including adipohemocytes, stem-like prohemocytes, and intermediate prohemocytes. Additionally, we identify the developmental trajectory of hemocytes during normal development as well as the emergence of the lamellocyte lineage following active cellular immunity caused by wasp infestation. Finally, we establish similarities and differences between embryonically derived- and larval lymph gland hemocytes. Altogether, our study provides detailed insights into the hemocyte development and cellular immune responses at single-cell resolution.

Floating Ni Capping for High-Mobility p-Channel SnO Thin-Film Transistors.

We utilized Ni as a floating capping layer in p-channel SnO thin-film transistors (TFTs) to improve their electrical performances. By utilizing the Ni as a floating capping layer, the p-channel SnO TFT showed enhanced mobility as high as 10.5 cm2·V-1·s-1. The increase in mobility was more significant as the length of Ni capping layer increased and the thickness of SnO active layer decreased. The observed phenomenon was possibly attributed to the changed vertical electric field distribution and increased hole concentration in the SnO channel by the floating Ni capping layer. Our experimental results demonstrate that incorporating the floating Ni capping layer on the channel layer is an effective method for increasing the field-effect mobility in p-channel SnO TFTs.

Subpopulation of Macrophage-Like Plasmatocytes Attenuates Systemic Growth via JAK/STAT in the Drosophila Fat Body.

Drosophila hemocytes, like those of mammals, are given rise from two distinctive phases during both the embryonic and larval hematopoiesis. Embryonically derived hemocytes, mostly composed of macrophage-like plasmatocytes, are largely identified by genetic markers. However, the cellular diversity and distinct functions of possible subpopulations within plasmatocytes have not been explored in Drosophila larvae. Here, we show that larval plasmatocytes exhibit differential expressions of Hemolectin (Hml) and Peroxidasin (Pxn) during development. Moreover, removal of plasmatocytes by overexpressing pro-apoptotic genes, hid and reaper in Hml-positive plasmatocytes, feeding high sucrose diet, or wasp infestation results in increased circulating hemocytes that are Hml-negative. Interestingly these Hml-negative plasmatocytes retain Pxn expression, and animals expressing Hml-negative and Pxn-positive subtype largely attenuate growth and abrogate metabolism. Furthermore, elevated levels of a cytokine, unpaired 3, are detected when Hml-positive hemocytes are ablated, which in turn activates JAK/STAT activity in several tissues including the fat body. Finally, we observed that insulin signaling is inhibited in this background, which can be recovered by concurrent loss of upd3. Overall, this study highlights heterogeneity in Drosophila plasmatocytes and a functional plasticity of each subtype, which reaffirms extension of their role beyond immunity into metabolic regulation for cooperatively maintaining internal homeostatic balance.

The Role of Lozenge in Drosophila Hematopoiesis.

Drosophila hematopoiesis is comparable to mammalian differentiation of myeloid lineages, and therefore, has been a useful model organism in illustrating the molecular and genetic basis for hematopoiesis. Multiple novel regulators and signals have been uncovered using the tools of Drosophila genetics. A Runt domain protein, lozenge, is one of the first players recognized and closely studied in the hematopoietic lineage specification. Here, we explore the role of lozenge in determination of prohemocytes into a special class of hemocyte, namely the crystal cell, and discuss molecules and signals controlling the lozenge function and its implication in immunity and stress response. Given the highly conserved nature of Runt domain in both invertebrates and vertebrates, studies in Drosophila will enlighten our perspectives on Runx-mediated development and pathologies.

Oxide Thin-Film Transistor-Based Vertically Stacked Complementary Inverter for Logic and Photo-Sensor Operations.

Numerous studies have addressed the utilization of oxide thin-film transistor (TFT)-based complementary logic circuits that are based on two-dimensional (2D) planar structures. However, there are fundamental limits to the 2D planar structured complementary logic circuits, such as a large dimension and a large parasitic resistance. This work demonstrated a vertically stacked three-dimensional complementary inverter composed of a p-channel tin monoxide (SnO) TFT and an n-channel indium-gallium-zinc oxide (IGZO) TFT. A bottom-gate p-channel SnO TFT was formed on the top-gate n-channel IGZO TFT with a shared common gate electrode. The fabricated vertically stacked complementary inverter exhibited full swing characteristics with a voltage gain of ~33.6, a high noise margin of 3.13 V, and a low noise margin of 3.16 V at a supplied voltage of 10 V. The achieved voltage gain of the fabricated complementary inverter was higher than that of the vertically stacked complementary inverters composed of other oxide TFTs in previous works. In addition, we showed that the vertically stacked complementary inverter exhibited excellent visible-light photoresponse. This indicates that the oxide TFT-based vertically stacked complementary inverter can be used as a sensitive photo-sensor operating in the visible spectral range with the voltage read-out scheme.

Iron Homeostasis Controls Myeloid Blood Cell Differentiation in Drosophila.

Iron is an essential divalent ion for aerobic life. Life has evolved to maintain iron homeostasis for normal cellular and physiological functions and therefore imbalances in iron levels exert a wide range of consequences. Responses to iron dysregulation in blood development, however, remain elusive. Here, we found that iron homeostasis is critical for differentiation of Drosophila blood cells in the larval hematopoietic organ, called the lymph gland. Supplementation of an iron chelator, bathophenanthroline disulfate (BPS) results in an excessive differentiation of the crystal cell in the lymph gland. This phenotype is recapitulated by loss of Fer1HCH in the intestine, indicating that reduced levels of systemic iron enhances crystal cell differentiation. Detailed analysis of Fer1HCH-tagged-GFP revealed that Fer1HCH is also expressed in the hematopoietic systems. Lastly, blocking Fer1HCH expression in the mature blood cells showed marked increase in the blood differentiation of both crystal cells and plasmatocytes. Thus, our work suggests a relevance of systemic and local iron homeostasis in blood differentiation, prompting further investigation of molecular mechanisms underlying iron regulation and cell fate determination in the hematopoietic system.

A system dynamics approach for modeling construction workers' safety attitudes and behaviors.

Construction accidents are caused by an unsafe act (i.e., a person's behavior or activity that deviates from normal accepted safe procedure) and/or an unsafe condition (i.e., a hazard or an unsafe mechanical or physical environment). While there has been dramatic improvement in creating safer construction environments, relatively little is known regarding the elimination of construction workers' unsafe acts. To address this deficiency, this paper aims to develop a system dynamics (SD)-based model of construction workers' mental processes that can help analyze the feedback mechanisms and the resultant dynamics regarding the workers' safety attitudes and safe behaviors. The developed model is applied to examine the effectiveness of three safety improvement policies: incentives for safe behaviors, and increased levels of communication and immersion in accidents. Application of the model verifies the strong potential of the developed model to provide a better understanding of how to eliminate unsafe acts, and to function as a robust test-bed to assess the effectiveness of safety programs or training sessions before their implementation.

Eleutherococcus senticosus extract attenuates LPS-induced iNOS expression through the inhibition of Akt and JNK pathways in murine macrophage.

Eleutherococcus senticosus (Araliaceae) is immunological modulator which has been successfully used for anti-inflammatory effectors on anti-rheumatic diseases in oriental medicine. Mitogen-activated protein kinases (MAPKs) and Akt modulate the transcription of many genes involved in the inflammatory process. In this study, we investigated the inhibitory effects of Eleutherococcus senticosus on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharides (LPS)-activated macrophages. Finally, we studied the involvement of MAPKs and Akt signaling in the protective effect of Eleutherococcus senticosus in LPS-activated macrophages. Eleutherococcus senticosus significantly attenuated LPS-induced iNOS expression but not COX-2 expression. In using the standard inhibitors (MAPKs and Akt), our results show that Eleutherococcus senticosus downregulates inflammatory iNOS expression by blocking JNK and Akt activation.