Biology

An alternative mode of epithelial polarity in the <i>Drosophila</i> midgut

PLOS Biology (new articles) - Пт, 2018-10-19 23:00

by Jia Chen, Aram-Christopher Sayadian, Nick Lowe, Holly E. Lovegrove, Daniel St Johnston

Apical–basal polarity is essential for the formation and function of epithelial tissues, whereas loss of polarity is a hallmark of tumours. Studies in Drosophila have identified conserved polarity factors that define the apical (Crumbs, Stardust, Par-6, atypical protein kinase C [aPKC]), junctional (Bazooka [Baz]/Par-3), and basolateral (Scribbled [Scrib], Discs large [Dlg], Lethal [2] giant larvae [Lgl]) domains of epithelial cells. Because these conserved factors mark equivalent domains in diverse types of vertebrate and invertebrate epithelia, it is generally assumed that this system underlies polarity in all epithelia. Here, we show that this is not the case, as none of these canonical factors are required for the polarisation of the endodermal epithelium of the Drosophila adult midgut. Furthermore, like vertebrate epithelia but not other Drosophila epithelia, the midgut epithelium forms occluding junctions above adherens junctions (AJs) and requires the integrin adhesion complex for polarity. Thus, Drosophila contains two types of epithelia that polarise by fundamentally different mechanisms. This diversity of epithelial types may reflect their different developmental origins, junctional arrangement, or whether they polarise in an apical–basal direction or vice versa. Since knock-outs of canonical polarity factors in vertebrates often have little or no effect on epithelial polarity and the Drosophila midgut shares several common features with vertebrate epithelia, this diversity of polarity mechanisms is likely to be conserved in other animals.
Категорії: Biology, Journals

EBP1 nuclear accumulation negatively feeds back on FERONIA-mediated RALF1 signaling

PLOS Biology (new articles) - Пт, 2018-10-19 23:00

by Chiyu Li, Xuanming Liu, Xiaonan Qiang, Xiaoyan Li, Xiushan Li, Sirui Zhu, Long Wang, Yuan Wang, Hongdong Liao, Sheng Luan, Feng Yu

FERONIA (FER), a plasma membrane receptor-like kinase, is a central regulator of cell growth that integrates environmental and endogenous signals. A peptide ligand rapid alkalinization factor 1 (RALF1) binds to FER and triggers a series of downstream events, including inhibition of Arabidopsis H+-ATPase 2 activity at the cell surface and regulation of gene expression in the nucleus. We report here that, upon RALF1 binding, FER first promotes ErbB3-binding protein 1 (EBP1) mRNA translation and then interacts with and phosphorylates the EBP1 protein, leading to EBP1 accumulation in the nucleus. There, EBP1 associates with the promoters of previously identified RALF1-regulated genes, such as CML38, and regulates gene transcription in response to RALF1 signaling. EBP1 appears to inhibit the RALF1 peptide response, thus forming a transcription–translation feedback loop (TTFL) similar to that found in circadian rhythm control. The plant RALF1-FER-EBP1 axis is reminiscent of animal epidermal growth factor receptor (EGFR) signaling, in which EGF peptide induces EGFR to interact with and phosphorylate EBP1, promoting EBP1 nuclear accumulation to control cell growth. Thus, we suggest that in response to peptide signals, plant FER and animal EGFR use the conserved key regulator EBP1 to control cell growth in the nucleus.
Категорії: Biology, Journals

Frontostriatal pathways gate processing of behaviorally relevant reward dimensions

PLOS Biology (new articles) - Пт, 2018-10-19 23:00

by Susanna C. Weber, Thorsten Kahnt, Boris B. Quednow, Philippe N. Tobler

The value of rewards arises from multiple hedonic and motivational dimensions. Reward-encoding brain regions such as the ventral striatum (VS) are known to process these dimensions. However, the mechanism whereby distinct reward dimensions are selected for neural processing and guiding behavior remains unclear. Here, we used functional imaging to investigate how human individuals make either hedonic (liking) or motivational (wanting) evaluations of everyday items. We found that the two types of evaluations were differently modulated depending on whether participants won or lost these items. Neural activity in the VS encoded both hedonic and motivational dimensions of reward, whereas ventromedial prefrontal activity encoded primarily motivational evaluations and central orbitofrontal activity encoded predominantly hedonic evaluations. These distinct prefrontal representations arose regardless of which judgment was currently relevant for behavior. Critically, the VS preferentially processed the reward dimension currently being evaluated and showed judgment-specific functional connectivity with the dimension-specific prefrontal areas. Thus, our data are in keeping with a gating mechanism by which prefrontal cortex (PFC)–VS pathways flexibly encode reward dimensions depending on their behavioral relevance. These findings provide a prototype for a generalized information selection mechanism through content-tailored frontostriatal communication.
Категорії: Biology, Journals

Supercharged geothermal energy could power the planet

Genetics - Пт, 2018-10-19 13:00
The next generation of geothermal plants will unlock more of Earth's bountiful, underground energy and could allow the technology to finally fulfil its promise
Категорії: Biology

7 explanations for why mysterious radio bursts are coming from space

Genetics - Пт, 2018-10-19 12:30
Astronomers are scratching their heads over extremely fast radio bursts. Now they're making a list of all the theories for what - or who - is making them
Категорії: Biology

AI tries to help you protect your children from cyberbullying

Genetics - Пт, 2018-10-19 12:00
Artificial intelligence is being trained to spot cyberbullying on social media so that hurtful posts can be removed before they reach vulnerable teens
Категорії: Biology

Old honeybees make a drumming sound to get young slackers working

Genetics - Пт, 2018-10-19 08:00
The more experienced bees in a colony sometimes run around the honeycomb drumming with their bodies - which seems to energise younger colony members
Категорії: Biology

Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking

PLOS Biology (new articles) - Чт, 2018-10-18 23:00

by Guang-Zhi Jin, Yajuan Zhang, Wen-Ming Cong, Xueyuan Wu, Xiongjun Wang, Siyang Wu, Siyao Wang, Weiping Zhou, Shengxian Yuan, Hong Gao, Guanzhen Yu, Weiwei Yang

Glycogen metabolism commonly altered in cancer is just beginning to be understood. Phosphoglucomutase 1 (PGM1), the first enzyme in glycogenesis that catalyzes the reversible conversion between glucose 1-phosphate (G-1-P) and glucose 6-phosphate (G-6-P), participates in both the breakdown and synthesis of glycogen. Here, we show that PGM1 is down-regulated in hepatocellular carcinoma (HCC), which is associated with the malignancy and poor prognosis of HCC. Decreased PGM1 expression obstructed glycogenesis pathway, which leads to the increased flow of glucose into glycolysis, thereby promoting tumor cell proliferation and HCC development. The loss of forkhead box protein J2 (FOXJ2), at least partly due to low genomic copy number in HCC, releases cellular nucleic acid-binding protein (CNBP), a nucleic acid chaperon, to bind to and promote G-quadruplex formation in PGM1 promoter and therefore decreases PGM1 expression. In addition, integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of HCC. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression.
Категорії: Biology, Journals

Running in the wheel: Defining individual severity levels in mice

PLOS Biology (new articles) - Чт, 2018-10-18 23:00

by Christine Häger, Lydia M. Keubler, Steven R. Talbot, Svenja Biernot, Nora Weegh, Stephanie Buchheister, Manuela Buettner, Silke Glage, André Bleich

The fine-scale grading of the severity experienced by animals used in research constitutes a key element of the 3Rs (replace, reduce, and refine) principles and a legal requirement in the European Union Directive 2010/63/EU. Particularly, the exact assessment of all signs of pain, suffering, and distress experienced by laboratory animals represents a prerequisite to develop refinement strategies. However, minimal and noninvasive methods for an evidence-based severity assessment are scarce. Therefore, we investigated whether voluntary wheel running (VWR) provides an observer-independent behaviour-centred approach to grade severity experienced by C57BL/6J mice undergoing various treatments. In a mouse model of chemically induced acute colitis, VWR behaviour was directly related to colitis severity, whereas clinical scoring did not sensitively reflect severity but rather indicated marginal signs of compromised welfare. Unsupervised k-means algorithm–based cluster analysis of body weight and VWR data enabled the discrimination of cluster borders and distinct levels of severity. The validity of the cluster analysis was affirmed in a mouse model of acute restraint stress. This method was also applicable to uncover and grade the impact of serial blood sampling on the animal’s welfare, underlined by increased histological scores in the colitis model. To reflect the entirety of severity in a multidimensional model, the presented approach may have to be calibrated and validated in other animal models requiring the integration of further parameters. In this experimental set up, however, the automated assessment of an emotional/motivational driven behaviour and subsequent integration of the data into a mathematical model enabled unbiased individual severity grading in laboratory mice, thereby providing an essential contribution to the 3Rs principles.
Категорії: Biology, Journals

Frontal network dynamics reflect neurocomputational mechanisms for reducing maladaptive biases in motivated action

PLOS Biology (new articles) - Чт, 2018-10-18 23:00

by Jennifer C. Swart, Michael J. Frank, Jessica I. Määttä, Ole Jensen, Roshan Cools, Hanneke E. M. den Ouden

Motivation exerts control over behavior by eliciting Pavlovian responses, which can either match or conflict with instrumental action. We can overcome maladaptive motivational influences putatively through frontal cognitive control. However, the neurocomputational mechanisms subserving this control are unclear; does control entail up-regulating instrumental systems, down-regulating Pavlovian systems, or both? We combined electroencephalography (EEG) recordings with a motivational Go/NoGo learning task (N = 34), in which multiple Go options enabled us to disentangle selective action learning from nonselective Pavlovian responses. Midfrontal theta-band (4 Hz–8 Hz) activity covaried with the level of Pavlovian conflict and was associated with reduced Pavlovian biases rather than reduced instrumental learning biases. Motor and lateral prefrontal regions synchronized to the midfrontal cortex, and these network dynamics predicted the reduction of Pavlovian biases over and above local, midfrontal theta activity. This work links midfrontal processing to detecting Pavlovian conflict and highlights the importance of network processing in reducing the impact of maladaptive, Pavlovian biases.
Категорії: Biology, Journals

Preservation of myocardial contractility during acute hypoxia with OMX-CV, a novel oxygen delivery biotherapeutic

PLOS Biology (new articles) - Чт, 2018-10-18 23:00

by Jason Boehme, Natacha Le Moan, Rebecca J. Kameny, Alexandra Loucks, Michael J. Johengen, Amy L. Lesneski, Wenhui Gong, Tina Davis, Kevin Tanaka, Andrew Davis, Youping He, Janel Long-Boyle, Vijay Ivaturi, Jogarao V. S. Gobburu, Jonathan A. Winger, Stephen P. Cary, Sanjeev A. Datar, Jeffrey R. Fineman, Ana Krtolica, Emin Maltepe

The heart exhibits the highest basal oxygen (O2) consumption per tissue mass of any organ in the body and is uniquely dependent on aerobic metabolism to sustain contractile function. During acute hypoxic states, the body responds with a compensatory increase in cardiac output that further increases myocardial O2 demand, predisposing the heart to ischemic stress and myocardial dysfunction. Here, we test the utility of a novel engineered protein derived from the heme-based nitric oxide (NO)/oxygen (H-NOX) family of bacterial proteins as an O2 delivery biotherapeutic (Omniox-cardiovascular [OMX-CV]) for the hypoxic myocardium. Because of their unique binding characteristics, H-NOX–based variants effectively deliver O2 to hypoxic tissues, but not those at physiologic O2 tension. Additionally, H-NOX–based variants exhibit tunable binding that is specific for O2 with subphysiologic reactivity towards NO, circumventing a significant toxicity exhibited by hemoglobin (Hb)-based O2 carriers (HBOCs). Juvenile lambs were sedated, mechanically ventilated, and instrumented to measure cardiovascular parameters. Biventricular admittance catheters were inserted to perform pressure-volume (PV) analyses. Systemic hypoxia was induced by ventilation with 10% O2. Following 15 minutes of hypoxia, the lambs were treated with OMX-CV (200 mg/kg IV) or vehicle. Acute hypoxia induced significant increases in heart rate (HR), pulmonary blood flow (PBF), and pulmonary vascular resistance (PVR) (p < 0.05). At 1 hour, vehicle-treated lambs exhibited severe hypoxia and a significant decrease in biventricular contractile function. However, in OMX-CV–treated animals, myocardial oxygenation was improved without negatively impacting systemic or PVR, and both right ventricle (RV) and left ventricle (LV) contractile function were maintained at pre-hypoxic baseline levels. These data suggest that OMX-CV is a promising and safe O2 delivery biotherapeutic for the preservation of myocardial contractility in the setting of acute hypoxia.
Категорії: Biology, Journals

Banning straws isn’t enough. We must get serious about climate change

Genetics - Чт, 2018-10-18 18:50
To head off climate disaster requires difficult changes to our lifestyles, says Adam Corner, and politicians must not be afraid to say so
Категорії: Biology

Mantis shrimps punch with the force of a bullet – and now we know how

Genetics - Чт, 2018-10-18 17:00
The mantis shrimp has an incredibly fast punch, and it’s because of a structure called a saddle that stores energy and then releases it like an archer's bow
Категорії: Biology

Your brain is like 100 billion mini-computers all working together

Genetics - Чт, 2018-10-18 17:00
Recording the electrical activity of the fine branches of human neurons has revealed that our brain cells are much more sophisticated than those of other animals
Категорії: Biology

Your genes affect which university you go to but that’s no surprise

Genetics - Чт, 2018-10-18 15:00
A study has found links between a person's genes and university. But intelligence and other complex traits are shaped by both genetics and environment
Категорії: Biology

Stephen Hawking, my father: “Harry Potter has magic, we have science”

Genetics - Чт, 2018-10-18 13:20
On the publication of Stephen Hawking's final book, his daughter Lucy Hawking reflects on their shared experiences and coming to terms with his death
Категорії: Biology

Fasting power: Can going without food really make you healthier?

Genetics - Чт, 2018-10-18 12:20
Fasting diets are getting ever more popular, amid promises of weight loss and better health, but does the science stand up? We put the latest one to the test
Категорії: Biology

The BepiColombo spacecraft is about to blast off to Mercury

Genetics - Чт, 2018-10-18 12:15
On 20 October, the BepiColombo spacecraft will begin a 7-year journey to Mercury, where it will orbit and investigate the many mysteries of Mercury
Категорії: Biology

Pregnancy changes how hundreds of genes work in a woman’s body

Genetics - Чт, 2018-10-18 08:00
Genes that alter their expression during healthy pregnancies have been identified for the first time, potentially helping us to predict at-risk pregnancies
Категорії: Biology

Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury

PLOS Biology (new articles) - Ср, 2018-10-17 23:00

by Andrew D. Greenhalgh, Juan G. Zarruk, Luke M. Healy, Sam J. Baskar Jesudasan, Priya Jhelum, Christopher K. Salmon, Albert Formanek, Matthew V. Russo, Jack P. Antel, Dorian B. McGavern, Barry W. McColl, Samuel David

Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate central nervous system (CNS) injury sites. Differential roles for these cell populations after injury are beginning to be uncovered. Here, we show evidence that MDMs and microglia directly communicate with one another and differentially modulate each other’s functions. Importantly, microglia-mediated phagocytosis and inflammation are suppressed by infiltrating macrophages. In the context of spinal cord injury (SCI), preventing such communication increases microglial activation and worsens functional recovery. We suggest that macrophages entering the CNS provide a regulatory mechanism that controls acute and long-term microglia-mediated inflammation, which may drive damage in a variety of CNS conditions.
Категорії: Biology, Journals