Comprehensive network map of interferon gamma signaling

Interferon gamma (IFN-γ), is a cytokine, which is an important regulator of host defense system by mediating both innate and adaptive immune responses. IFN-γ signaling is primarily associated with inflammation and cell-mediated immune responses. IFN-γ is also represented as antitumor cytokine which facilitates immunosurveillance in tumor cells. In addition, IFN-γ mediated signaling also elicits pro-tumorigenic transformations and promotes tumor progression. Impact of IFN-γ signaling in mammalian cells has been widely studied which indicate that IFN-γ orchestrates distinct cellular functions including immunomodulation, leukocyte trafficking, apoptosis, anti-microbial, and both anti- and pro-tumorigenic role. However, a detailed network of IFN-γ signaling pathway is currently lacking. Therefore, we systematically curated the literature information pertaining to IFN-γ signaling and develop a comprehensive signaling network to facilitate better understanding of IFN-γ mediated signaling. A total of 124 proteins were catalogued that were experimentally proven to be involved in IFN-γ signaling cascade. These 124 proteins were found to participate in 81 protein-protein interactions, 94 post-translational modifications, 20 translocation events, 54 activation/inhibiton reactions. Further, 236 differential expressed genes were also documented in IFN-γ mediated signaling. IFN-γ signaling pathway is made freely available to scientific audience through NetPath at (http://www.netpath.org/pathways?path_id=NetPath_32). We believe that documentation of reactions pertaining to IFN-γ signaling and development of pathway map will facilitate further research in IFN-γ associated human diseases including cancer.     

An overview of the oxytocin-oxytocin receptor signaling network

Oxytocin, a nine amino acid long neuropeptide hormone, is synthesized in the hypothalamus and stored and released from the neural lobe of the pituitary gland. Although commonly known for its central role in the regulation of parturition and lactation, oxytocin signaling also plays a key role in modulating social behavior, evoking contentment, initiating maternal behavior, inducing trust, generosity and bonding in humans and animals. Oxytocin signaling can prove to be of great importance in therapeutics and drug targeting because of its diverse range of actions. However, a well annotated map of oxytocin signaling pathway is currently lacking in the publicly available pathway resources. Therefore, we systematically curated the available signaling information of oxytocin from published literature and collated the data to develop a more complete map. We cataloged 66 molecules belonging to oxytocin signaling pathway, which included 9 protein-protein interactions, 39 post-translational modifications, 14 protein translocation events and 22 activation/inhibition events. Further, Oxytocin signaling network data is made freely available to academic fraternity by integrating this into NetPath (http://www.netpath.org/), a freely available human signaling pathway resource developed previously by our group.     

Larval host records of butterflies in Japan

Using Japanese literature, we created a consolidated list of host records of butterflies in Japan. The list used the host records described in eight major illustrated reference books, two checklists, and 14 other pieces of literature. The presence of larvae on plants, the observation of larvae eating plants or insects in the field were considered as host records. We collected all species recorded in Japan. Scientific, family, and Japanese names of butterflies were consolidated using the BINRAN database (http://binran.lepimages.jp/). Scientific and Japanese names of host plants were based on the YList database (http://ylist.info/). If scientific names of host plants were not found in YList, we used scientific names based on The Plant List (http://www.theplantlist.org/). Family names of host plants were based on the Catalogue of Life database (http://www.catalogueoflife.org/). Scientific, family, and Japanese names of host insects were based on the MOKUROKU database (http://konchudb.agr.agr.kyushu-u.ac.jp/mokuroku/) for Hymenoptera and the catalogue of the Paraneoptera of Japan published by the Entomological Society of Japan for Hemiptera. We also provided the references of each host record and the original names described in the referred literature. Two datasets, HostDB and ReferenceDB, were created to include 3600 records of butterfly larval hosts in Japan, along with scientific and Japanese names of each species and a literature list. These datasets will be useful for basic and applied biological studies of butterflies. Data files are stored in the Ecological Research Data Archives (http://db.cger.nies.go.jp/JaLTER/ER_DataPapers/) and available from http://hostbj.lepumus.net/. These datasets are published under the Creative Commons License Attribution-ShareAlike 4.0 (CC BY-SA, https://creativecommons.org/licenses/by-sa/4.0/).     

An integrated signal transduction network of macrophage migration inhibitory factor

Macrophage migration inhibitory factor (MIF) is a glycosylated multi-functional protein that acts as an enzyme as well as a cytokine. MIF mediates its actions through a cell surface class II major histocompatibility chaperone, CD74 and co-receptors such as CD44, CXCR2, CXCR4 or CXCR7. MIF has been implicated in the pathogenesis of several acute and chronic inflammatory diseases. Although MIF is a molecule of biomedical importance, a public resource of MIF signaling pathway is currently lacking. In view of this, we carried out detailed data mining and documentation of the signaling events pertaining to MIF from published literature and developed an integrated reaction map of MIF signaling. This resulted in the cataloguing of 68 molecules belonging to MIF signaling pathway, which includes 24 protein-protein interactions, 44 post-translational modifications, 11 protein translocation events and 8 activation/inhibition events. In addition, 65 gene regulation events at the mRNA levels induced by MIF signaling have also been catalogued. This signaling pathway has been integrated into NetPath (http://www.netpath.org), a freely available human signaling pathway resource developed previously by our group. The MIF pathway data is freely available online in various community standard data exchange formats. We expect that data on signaling events and a detailed signaling map of MIF will provide the scientific community with an improved platform to facilitate further molecular as well as biomedical investigations on MIF.     

Paternal care behaviors of Japanese giant salamander <Emphasis Type="Italic">Andrias japonicus</Emphasis> in natural populations

Parental care among salamanders is typically provided by females. A rare case of parental care by male salamanders appears to occur in Cryptobranchidae. Yet, paternal behaviors have rarely been reported from natural populations of any Cryptobranchid salamanders, and their adaptive significance is poorly understood. The present study aimed to examine paternal care behaviors in a fully aquatic Japanese giant salamander (Andrias japonicus) in situ. At the beginning of the summer breeding season, large males, called den-masters, occupy burrows along stream banks for breeding and nesting. We videotaped post-breeding behaviors of two den-masters that stayed with the eggs, one in a natural and the other in an artificial nest in natural streams. We identified three behaviors, tail fanning, agitating and egg eating, to be parental care. Tail fanning provides oxygenated water for the eggs. We found that the den-master in the artificial nest, where dissolved oxygen level was lower, displayed tail fanning more frequently. Agitating the eggs with its head and body likely prevents yolk adhesions. The den-masters selectively ate whiter eggs that appeared to be dead or infected with water mold. This behavior, which we termed hygienic filial cannibalism, likely prevents water mold from spreading over healthy eggs. Digital video images relating to this article are available at http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj01a, http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj02a, http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj03a and http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj04a.     

The scent of your enemy is my friend? The acquisition of large carnivore scent by a smaller carnivore

Scent marking is critical to intraspecific communication in many mammal species, but little is known regarding its role in communication among different species. We used 4 years of motion-triggered video to document the use of scent marking areas—termed “community scrapes”—by pumas (Puma concolor) (http://www.momo-p.com/showdetail-e.php?movieid=momo160812pc01a) and other carnivore species. We found that gray foxes (Urocyon cinereoargenteus) routinely rubbed their cheeks on puma scrapes (http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc01a), and tested a series of hypotheses to determine its function. We found that gray foxes selected puma scrapes over other objects, and cheek rubbing by foxes was also correlated with how recently a puma had visited the scrape, suggesting that foxes were intent upon accumulating fresh puma scent. Cheek rubbing by foxes was not correlated with their breeding season or with how recently another fox had visited the site. Finally we found a cascading pattern in the occurrence of pumas, coyotes (Canis latrans) and gray foxes at community scrapes, suggesting that gray foxes may use puma scent to deter predation. This is the first published study to find evidence of a subordinate species using the scent of a dominant species to communicate with heterospecifics. The behavioral cascade we found in scent marking patterns also suggests that scent marking could be a mechanism that impacts the distribution and abundance of species. Additional videos pertaining to this article include http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc02a, and http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc03a.     

The FOCUS,AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis

Background

Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients’ functional outcome.

Methods/Design

The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2–15 days after stroke onset. Patients are randomised centrally via each trials’ web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances; the Stroke Impact Scale; EuroQol (EQ5D-5 L); the vitality subscale of the 36-Item Short Form Health Survey (SF36); diagnosis of depression; adherence to medication; serious adverse events including death and recurrent stroke; and resource use at six and 12 months and the mRS at 12 months.

Discussion

Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the individual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020.

Trial registration

FOCUS: ISRCTN, ISRCTN83290762. Registered on 23 May 2012. EudraCT, 2011-005616-29. Registered on 3 February 2012.AFFINITY: Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Registered on 22 July 2011.EFFECTS: ISRCTN, ISRCTN13020412. Registered on 19 December 2014. Clinicaltrials.gov, NCT02683213. Registered on 2 February 2016. EudraCT, 2011-006130-16. Registered on 8 August 2014.

     

Accessing data from the International Mouse Phenotyping Consortium: state of the art and future plans

The International Mouse Phenotyping Consortium (IMPC) (http://www.mousephenotype.org) will reveal the pleiotropic functions of every gene in the mouse genome and uncover the wider role of genetic loci within diverse biological systems. Comprehensive informatics solutions are vital to ensuring that this vast array of data is captured in a standardised manner and made accessible to the scientific community for interrogation and analysis. Here we review the existing EuroPhenome and WTSI phenotype informatics systems and the IKMC portal, and present plans for extending these systems and lessons learned to the development of a robust IMPC informatics infrastructure.     

Optimization and control in bacterial Lag phase

The lag phase of bacterial growth is important from a medical and food safety perspective, but difficult to study due to the low density and metabolic rate of cells. A new study by Alon and colleagues reveals that the gene expression program during early lag phase prioritizes carbon source utilization enzymes over genes responsible for biomass accumulation. This cellular strategy ultimately maximizes growth, making the best long-term use of the new nutrient-rich environment.See research article: http://www.biomedcentral.com/1752-0509/7/136     

The Year of the Wisent

Delving into European prehistory, two recent studies analyze ancient DNA from bison species depicted by our ancestors on the walls of their caves. The DNA tells a story of migrations driven by climate change but leaves some mystery clouding the genetic descent and climate preference of the still-extant wisent, otherwise known as the European bison.See research articles: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0317-7 http://www.nature.com/articles/ncomms13158     

Ethological description of a fixed action pattern in a kissing bug (Triatominae): vision,gustation, proboscis extension and drinking of water and guava

Triatomines (Heteroptera, Reduviidae) are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease in America. These true bugs have traditionally been considered to be blood suckers, although some species have been catalogued as being entomophagous. By using their highly specialized mouthparts, these insects have evolved a stereotyped habit which includes lifting up the proboscis, piercing and sucking, when the occasion arises. Most triatomines bite their sleeping and unaware vertebrate or invertebrate hosts, but they can also search for other targets, guided, in part, by visual and chemical stimuli. In this study, we observed that triatomines apparently visually identify a drop of water in the distance, then taste it with their legs, upon which proboscis extension and sucking ensues. This invariant behavior or fixed action pattern, observed in several triatomine species (Rhodnius prolixus, Triatoma infestans and Panstrongylus geniculatus), was also elicited by a dummy drop of water and guava fruit. We discuss evolutionary and ethological aspects of this innate behavior. Digital video images related to this article are available at http://www.momo-p.com/showdetail-e.php?movieid=momo180314rp01a and http://www.momo-p.com/showdetail-e.php?movieid=momo180314rp03a.     

Opening a can of centipedes: new insights into mechanisms of body segmentation

The search for a common developmental genetic mechanism of body segmentation appears to become more difficult, and more interesting, as new segmented organisms are added to the roster. Recent work in this journal by Brena and Akam on segmentation of the geophilomorph centipede Strigamia maritima, an arthropod distantly related to the standard insect models, contains developmental and evolutionary surprises that highlight the importance of a wider sampling of phyla.See research article: http://www.biomedcentral.com/1741-7007/11/112     

Proteasome inhibition,the pursuit of new cancer therapeutics,and the adaptor molecule p130Cas

Current interest in proteasome inhibitors for cancer therapy has stimulated considerable research efforts to identify the molecular pathway to their cytotoxicity with a view to identifying the mechanisms of sensitivity and resistance as well as informing the development of new drugs. Zhao and Vuori describe this month in BMC Biology experiments indicating a novel role of the adaptor protein p130Cas in sensitivity to apoptosis induced not only by proteasome inhibitors but also by the unrelated drug doxorubicin.See research article: http://www.biomedcentral.com/1741-7007/9/73     

Interspecific responses of wild African carnivores to odour of 3-mercapto-3-methylbutanol,a component of wildcat and leopard urine

The scent of 3-mercapto-3-methylbutanol (3-M-3-MB), a volatile component of leopard (Panthera pardus) and domestic cat (Felis silvestris catus) urine, released at about 10 ng/s from slow-release dispensers, elicited scent-marking from African civet (Civettictis civetta), small-spotted genet (Genetta genetta) and slender mongoose (Galerella sanguinea), as well as African wildcat (F. s. cafra). A female leopard was apparently repelled by the scent. The scent-marking and scent-rubbing by species other than African wildcats and leopards were unexpected and have important implications for the design of studies to investigate chemical communication between wild mammals and the use of camera traps to estimate animal numbers. Videos showing the behaviours referred to in this article are available at; http://www.momo-p.com/showdetail-e.php?movieid=momo161223fs01a; http://www.momo-p.com/showdetail-e.php?movieid=momo161223gs01a; http://www.momo-p.com/showdetail-e.php?movieid=momo161223gg01a.     

Advances in transgenic animal models and techniques

On May 11th and 12th 2017 was held in Nantes, France, the international meeting “Advances in transgenic animal models and techniques” (http://www.trm.univ-nantes.fr/). This biennial meeting is the fifth one of its kind to be organized by the Transgenic Rats ImmunoPhenomic (TRIP) Nantes facility (http://www.tgr.nantes.inserm.fr/). The meeting was supported by private companies (SONIDEL, Scionics computer innovation, New England Biolabs, MERCK, genOway, Journal Disease Models and Mechanisms) and by public institutions (International Society for Transgenic Technology, University of Nantes, INSERM UMR 1064, SFR François Bonamy, CNRS, Région Pays de la Loire, Biogenouest, TEFOR infrastructure, ITUN, IHU-CESTI and DHU-Oncogeffe and Labex IGO). Around 100 participants, from France but also from different European countries, Japan and USA, attended the meeting.     

Web-based design and analysis tools for CRISPR base editing

Background

As a result of its simplicity and high efficiency, the CRISPR-Cas system has been widely used as a genome editing tool. Recently, CRISPR base editors, which consist of deactivated Cas9 (dCas9) or Cas9 nickase (nCas9) linked with a cytidine or a guanine deaminase, have been developed. Base editing tools will be very useful for gene correction because they can produce highly specific DNA substitutions without the introduction of any donor DNA, but dedicated web-based tools to facilitate the use of such tools have not yet been developed.

Results

We present two web tools for base editors, named BE-Designer and BE-Analyzer. BE-Designer provides all possible base editor target sequences in a given input DNA sequence with useful information including potential off-target sites. BE-Analyzer, a tool for assessing base editing outcomes from next generation sequencing (NGS) data, provides information about mutations in a table and interactive graphs. Furthermore, because the tool runs client-side, large amounts of targeted deep sequencing data (<?1?GB) do not need to be uploaded to a server, substantially reducing running time and increasing data security. BE-Designer and BE-Analyzer can be freely accessed at http://www.rgenome.net/be-designer/ and http://www.rgenome.net/be-analyzer/, respectively.

Conclusion

We develop two useful web tools to design target sequence (BE-Designer) and to analyze NGS data from experimental results (BE-Analyzer) for CRISPR base editors.

     

The current status of ethnobiological research in Latin America: gaps and perspectives

Background

Recent reviews have demonstrated an increase in the number of papers on ethnobiology in Latin America. Among factors that have influenced this increase are the biological and cultural diversity of these countries and the general scientific situation in some countries. This study aims to assess the panorama of ethnobiological research in Latin America by analyzing its evolution, trends, and future prospects.

Methods

To conduct this study, we searched for papers in the Scopus (http://www.scopus.com) and Web of Science (http://www.isiknowledge.com) databases. The search was performed using combinations of keywords and the name of each Latin American country. The following countries were included in this study: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Guatemala, Haiti, Honduras, Mexico, Panama, Paraguay, Peru, Venezuela, and Uruguay.

Results and conclusions

According to our inclusion criteria, 679 ethnobiological studies conducted in Latin America were found for the period between 1963 and 2012. Of these studies, 289 (41%) were conducted in Brazil, 153 in Mexico (22%), 61 in Peru (9%), 58 in Argentina (8%), 45 in Bolivia (6%), and 97 (14%) in other Latin American countries. The increased number of publications related to this area of knowledge in recent years demonstrates the remarkable growth of ethnobiology as a science. Ethnobiological research may be stimulated by an increase in the number of scientific events and journals for study dissemination and by the creation of undergraduate courses and graduate programs to train ethnoscientists who will produce high-quality studies, especially in certain countries.

     

Mating and aggressive behaviour of <Emphasis Type="Italic">Brachyrhaphis olomina</Emphasis> (Cyprinodontiformes: Poeciliidae)

Despite the increasing interest in the use of intromittent male genitalia and coercive mating behaviour in poeciliids, detailed studies of the mating behaviour of most species in this family are lacking. We describe here the mating and aggressive behaviours of Brachyrhaphis olomina, and correlate them with the condition of the female’s ovum and embryos (immature, mature and pregnant). B. olomina performed a wide range of aggressive (sidle spread, tail beating, coordinate) and mating behaviours (approximation, touch, lateral display, touch-lateral display). Some behaviours (e.g. tail beating) are shared with other poeciliids, but two sexual behaviours (touch and lateral display) and one aggressive (coordinate) behaviour may be unique to B. olomina and were not reported in a previous study. Differences in male behaviour when paired with a female with mature ovum (more mating displays, no agonistic movements) suggest that males detect the female’s reproductive condition from some distance. The distinctive nature of mating behaviour in B. olomina highlights the importance of studying different species to have a better understanding of the evolution of mating and aggressive behaviours in poeciliids. Digital video images related to the article are available at http://www.momo-p.com/showdetail-e.php?movieid=momo170720bo01a, http://www.momo-p.com/showdetail-e.php?movieid=momo170720bo02a and http://www.momo-p.com/showdetail-e.php?movieid=momo170720bo03a.