Distribution of melanopsin positive neurons in pigmented and albino mice: evidence for melanopsin interneurons in the mouse retina.

Here we have studied the population of intrinsically photosensitive retinal ganglion cells (ipRGCs) in adult pigmented and albino mice. Our data show that although pigmented (C57Bl/6) and albino (Swiss) mice have a similar total number of ipRGCs, their distribution is slightly different: while in pigmented mice ipRGCs are more abundant in the temporal retina, in albinos the ipRGCs are more abundant in superior retina. In both strains, ipRGCs are located in the retinal periphery, in the areas of lower Brn3a(+)RGC density. Both strains also contain displaced ipRGCs (d-ipRGCs) in the inner nuclear layer (INL) that account for 14% of total ipRGCs in pigmented mice and 5% in albinos. Tracing from both superior colliculli shows that 98% (pigmented) and 97% (albino) of the total ipRGCs, become retrogradely labeled, while double immunodetection of melanopsin and Brn3a confirms that few ipRGCs express this transcription factor in mice. Rather surprisingly, application of a retrograde tracer to the optic nerve (ON) labels all ipRGCs, except for a sub-population of the d-ipRGCs (14% in pigmented and 28% in albino, respectively) and melanopsin positive cells residing in the ciliary marginal zone (CMZ) of the retina. In the CMZ, between 20% (pigmented) and 24% (albino) of the melanopsin positive cells are unlabeled by the tracer and we suggest that this may be because they fail to send an axon into the ON. As such, this study provides the first evidence for a population of melanopsin interneurons in the mammalian retina

Elucidating sources and roles of Granzymes A and B during bacterial infection and sepsis

During bacterial sepsis, proinflammatory cytokines contribute to multiorgan failure and death in a pro- cess regulated in part by cytolytic cell granzymes. When challenged with a sublethal dose of the identi- fied mouse pathogen Brucella microti, wild-type (WT) and granzyme A (gzmA)/ mice eliminate the organism from liver and spleen in 2 or 3 weeks, whereas the bacteria persist in mice lacking perforin or granzyme B as well as in mice depleted of Tc cells. In comparison, after a fatal challenge, only gzmA/ mice exhibit increased survival, which correlated with reduced proinflammatory cytokines. Depletion of natural killer (NK) cells protects WT mice from sepsis without influencing bacterial clearance and the transfer of WT, but not gzmA/ NK, cells into gzmA/ recipients restores the susceptibility to sepsis. Therefore, infection-related pathology, but not bacterial clearance, appears to require gzmA, suggesting the protease may be a therapeutic target for the prevention of bacterial sepsis without affecting immune control of the pathogen

Extra-uterine (abdominal) full term foetus in a 15-day pregnant rabbit

[EN] Background: While ectopic pregnancies account for 1-2% of all pregnancies, abdominal pregnancy is extremely rare, accounting for approximately 1% of ectopic pregnancies. Extrauterine abdominal pregnancy is defined as the implantation and development of an embryo in the peritoneal cavity. The present report is the first of an incidental case of abdominal pregnancy within four full-term foetus simultaneously with 2 weeks of physiological gestation in a healthy doe rabbit. Case presentation: The doe was born on November 3, 2014 and the first partum took place on May 18, 2015. The doe had previously delivered and weaned an average of 12.0 +/- 1.41 live kits at birth (no stillbirths were recorded) during 5 consecutive pregnancies. The last mating was on December 18, 2015 and the detection of pregnancy failure post breeding (by abdominal palpation) on December 31, 2015. Then, the doe was artificially inseminated on January 27, 2016, diagnosed pregnant on February 11, 2016 and subsequently euthanized to recover the foetus. A ventral midline incision revealed a reproductive tract with 12 implantation sites with 15 days old foetus and 4 term foetus in abdominal cavity. There were two foetus floating on either side of the abdominal cavity and two suspended near the greater curvature of the stomach. They were attached to internal organs by means of one or 2 thread-like blood vessels that linked them to the abdominal surfaces. Conclusions: In our opinion a systematic monitoring of rabbit breeding should be included to fully understand and enhance current knowledge of this phenomenon of abdominal pregnancy.This work was supported by Spanish Research Project AGL2014-53405-C2-1-P (Interministerial Commission on Science and Technology).Marco-Jiménez, F.; Garcia-Dominguez, X.; Valdes-Hernández, J.; Vicente Antón, JS. (2017). Extra-uterine (abdominal) full term foetus in a 15-day pregnant rabbit. BMC Veterinary Research. 13:1-4. https://doi.org/10.1186/s12917-017-1229-7S1413Petracci M, Bianchi M, Cavani C. Development of rabbit meat products fortified with n-3 polyunsaturated fatty acids. Nutrients. 2009;1:111–8.FAOSTAT (Food and Agriculture Organization of the United Nations, authors). Available online: http://faostat.fao.org/site/569/DesktopDefault.aspx?PageID=569#ancor . Accessed Sept 2012.Segura Gil P, Peris Palau B, Martínez Martínez J, Ortega Porcel J, Corpa Arenas JM. Abdominal pregnancies in farm rabbits. Theriogenology. 2004;62:642–51.Rosell JM, de la Fuente LF. Culling and mortality in breeding rabbits. Prev Vet Med. 2009;88:120–7.Tena-Betancourt E, Tena-Betancourt CA, Zúniga-Muñoz AM, Hernández-Godínez B, Ibáñez-Contreras A, Graullera-Rivera V. Multiple extrauterine pregnancy with early and near full-term mummified foetuses in a New Zealand white rabbit (Oryctolagus Cuniculus). J Am Assoc Lab Anim Sci. 2014;53:204–7.Sánchez JP, Theilgaard P, Mínguez C, Baselga M. Constitution and evaluation of a long-lived productive rabbit line. J Anim Sci. 2008;86:515–25.Savietto D, Friggens NC, Pascual JJ. Reproductive robustness differs between generalist and specialist maternal rabbit lines: the role of acquisition and allocation of resources. Genet Sel Evol. 2015;47:2.Viudes-de-Castro MP, Vicente JS. Effect of sperm count on the fertility and prolificity rates of meat rabbits. Anim Reprod Sci. 1997;46:313–9.Marco-Jiménez F, Garcia-Dominguez X, Jimenez-Trigos E, Vera-Donoso CD, Vicente JS. Vitrification of kidney precursors as a new source for organ transplantation. Cryobiology. 2015;70:278–82.Garcia-Dominguez X, Vera-Donoso CD, Jimenez-Trigos E, Vicente JS, Marco-Jimenez. First steps towards organ banks: vitrification of renal primordial. Cryo Letters. 2016;37:47–52.Arvidsson A. Extra-uterine pregnancy in a rabbit. Vet Rec. 1998;142:176.Glišić A, Radunović N, Atanacković J. Methotrexate and fallopian tubes in ectopic pregnancy. Acta veterinaria. 2006;56:375–82.Nwobodo EI. Abdominal pregnancy. A case report. Ann Afr Med. 2004;3:195–6.Nassali MN, Benti TM, Bandani-Ntsabele M, Musinguzi E. A case report of an asymptomatic late term abdominal pregnancy with a live birth at 41 weeks of gestation. BMC Res Notes. 2016;9:31.Baffoe P, Fofie C, Gandau BN. Term abdominal pregnancy with healthy new-born: a case report. Ghana Med J. 2011;45:81–3.Eleje GU, Adewae O, Osuagwu IK, Obianika CE. Post-date extra-uterine abdominal pregnancy in a rhesus negative Nullipara with successful outcome: a case report. J Women's Health. 2013;6:2.Hong CC, Armstrong ML. Ectopic pregnancy in 2 guinea-pigs. Lab Anim. 1978;12:243–4.Peters LJ. Abdominal pregnancy in a golden hamster (Mesocricetus Auratus). Lab Anim Sci. 1982;32:392–3.Xiccato G, Trocino A, Boiti C, Brecchia G. Reproductive rhythm and litter weaning age as they affect rabbit doe performance and body energy balance. Anim Sci. 2005;81:289–96.Fortun-Lamothe L, De Rochambeau H, Lebas F, Tudela F. Influence of the number of suckling young on reproductive performance in intensively reared rabbits does. In: Blasco A, editor. Proceedings of the 7th world rabbit congress; 2002. p. 125–32

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

Argumentation in school science : Breaking the tradition of authoritative exposition through a pedagogy that promotes discussion and reasoning

The value of argumentation in science education has become internationally recognised and has been the subject of many research studies in recent years. Successful introduction of argumentation activities in learning contexts involves extending teaching goals beyond the understanding of facts and concepts, to include an emphasis on cognitive and metacognitive processes, epistemic criteria and reasoning. The authors focus on the difficulties inherent in shifting a tradition of teaching from one dominated by authoritative exposition to one that is more dialogic, involving small-group discussion based on tasks that stimulate argumentation. The paper builds on previous research on enhancing the quality of argument in school science, to focus on how argumentation activities have been designed, with appropriate strategies, resources and modelling, for pedagogical purposes. The paper analyses design frameworks, their contexts and lesson plans, to evaluate their potential for enhancing reasoning through foregrounding the processes of argumentation. Examples of classroom dialogue where teachers adopt the frameworks/plans are analysed to show how argumentation processes are scaffolded. The analysis shows that several layers of interpretation are needed and these layers need to be aligned for successful implementation. The analysis serves to highlight the potential and limitations of the design frameworks

Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation

Several psychiatric, neurologic and neurodegenerative disorders present increased brain ventricles volume, being hydrocephalus the disease with the major manifestation of ventriculomegaly caused by the accumulation of high amounts of cerebrospinal fluid (CSF). The molecules and pathomechanisms underlying cerebral ventricular enlargement are widely unknown. Kinase D interacting substrate of 220 kDa (KIDINS220) gene has been recently associated with schizophrenia and with a novel syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity (SINO syndrome), diseases frequently occurring with ventriculomegaly. Here we show that Kidins220, a transmembrane protein effector of various key neuronal signalling pathways, is a critical regulator of CSF homeostasis. We observe that both KIDINS220 and the water channel aquaporin-4 (AQP4) are markedly downregulated at the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. We also find that Kidins220 deficient mice develop ventriculomegaly accompanied by water dyshomeostasis and loss of AQP4 in the brain ventricular ependymal layer and astrocytes. Kidins220 is a known cargo of the SNX27-retromer, a complex that redirects endocytosed plasma membrane proteins (cargos) back to the cell surface, thus avoiding their targeting to lysosomes for degradation. Mechanistically, we show that AQP4 is a novel cargo of the SNX27-retromer and that Kidins220 deficiency promotes a striking and unexpected downregulation of the SNX27-retromer that results in AQP4 lysosomal degradation. Accordingly, SNX27 silencing decreases AQP4 levels in wild-type astrocytes whereas SNX27 overexpression restores AQP4 content in Kidins220 deficient astrocytes. Together our data suggest that the KIDINS220-SNX27-retromer-AQP4 pathway is involved in human ventriculomegaly and open novel therapeutic perspectives

Cerebellar astrocytes co-express several ADP receptors. Presence of functional P2Y13-like receptors

Astrocytes exhibit a form of excitability based on variations of intracellular Ca2+ concentration in response to various stimuli, including ADP, ATP, UTP and dinucleotides. Here, we investigate the presence of the recently cloned ADP-sensitive receptors, P2Y12 and P2Y13 subtypes, which are negatively coupled to adenylate cyclase, in cerebellar astrocytes. We checked the effect of specific agonists, 2-methylthioadenosine diphosphate (2MeSADP) and ADP, on adenylate cyclase stimulation induced by isoproterenol. Both agonists significantly reduced the cAMP accumulation induced by isoproterenol. The inhibitory effect was concentration-dependent with IC50 values of 46 ± 13 and 23 ± 14 nM for 2MeSADP and ADP, respectively. The experiments were carried out in the presence of MRS-2179, a specific antagonist of P2Y1 receptor, to avoid any contribution of this receptor. Using fura-2 microfluorimetry we also proved that astrocytes responded to 2MeSADP stimulations with calcium responses in the absence and also in the presence of MRS-2179. Both effects, inhibition of adenylate cyclase and intracellular calcium mobilization, were not modified by 2MeSAMP, an antagonist of P2Y12 receptor, suggesting that were mediated by P2Y13-like receptors

Updating known distribution models for forecasting climate change impact on endangered species

To plan endangered species conservation and to design adequate management programmes, it is necessary to predict their distributional response to climate change, especially under the current situation of rapid change. However, these predictions are customarily done by relating de novo the distribution of the species with climatic conditions with no regard of previously available knowledge about the factors affecting the species distribution. We propose to take advantage of known species distribution models, but proceeding to update them with the variables yielded by climatic models before projecting them to the future. To exemplify our proposal, the availability of suitable habitat across Spain for the endangered Bonelli’s Eagle (Aquila fasciata) was modelled by updating a pre-existing model based on current climate and topography to a combination of different general circulation models and Special Report on Emissions Scenarios. Our results suggested that the main threat for this endangered species would not be climate change, since all forecasting models show that its distribution will be maintained and increased in mainland Spain for all the XXI century. We remark on the importance of linking conservation biology with distribution modelling by updating existing models, frequently available for endangered species, considering all the known factors conditioning the species’ distribution, instead of building new models that are based on climate change variables only.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS