Spatial Representations in the Human Brain

While extensive research on the neurophysiology of spatial memory has been carried out in rodents, memory research in humans had traditionally focused on more abstract, language-based tasks. Recent studies have begun to address this gap using virtual navigation tasks in combination with electrophysiological recordings in humans. These studies suggest that the human medial temporal lobe (MTL) is equipped with a population of place and grid cells similar to that previously observed in the rodent brain. Furthermore, theta oscillations have been linked to spatial navigation and, more specifically, to the encoding and retrieval of spatial information. While some studies suggest a single navigational theta rhythm which is of lower frequency in humans than rodents, other studies advocate for the existence of two functionally distinct delta–theta frequency bands involved in both spatial and episodic memory. Despite the general consensus between rodent and human electrophysiology, behavioral work in humans does not unequivocally support the use of a metric Euclidean map for navigation. Formal models of navigational behavior, which specifically consider the spatial scale of the environment and complementary learning mechanisms, may help to better understand different navigational strategies and their neurophysiological mechanisms. Finally, the functional overlap of spatial and declarative memory in the MTL calls for a unified theory of MTL function. Such a theory will critically rely upon linking task-related phenomena at multiple temporal and spatial scales. Understanding how single cell responses relate to ongoing theta oscillations during both the encoding and retrieval of spatial and non-spatial associations appears to be key toward developing a more mechanistic understanding of memory processes in the MTL

Activation of the endogenous coagulation system in patients with atrial flutter: Relationship to echocardiographic markers of thromboembolic risk

Background: Atrial thrombus formation in patients with atrial flutter raises concerns of stroke risk. We investigated patients with isthmus-dependent atrial flutter for coagulation abnormalities before and after cardioversion to sinus rhythm by catheter ablation, and evaluated the relationship of the abnormalities to the echocardiographic risk markers of stroke. Methods and results: Plasma samples were drawn prior to insertion of catheters, immediately after the procedure, and 24 hours afterwards. At baseline, coagulation abnormalities were found in 22 out of 25 patients (88%). von Willebrand factor antigen (vWF-Ag) and factor VIII:C were elevated in 17 patients (68%) and 15 patients (60%), respectively. At baseline, mean plasma levels of vWF-Ag (250.1 &#177; 144.4%) and factor VIII:C (215.0 &#177; 77.1%) were increased. Key markers of thrombin generation, thrombin-antithrombin III complex (TAT; 47.8 &#177; 30.9 &#956;g/L vs 14.5 &#177; 13.8 &#956;g/L; p < 0.05) and prothrombin fragments 1.2 (F1.2; 2.5 &#177; 0.5 nmoL/L vs 1.2 &#177; 1.0 nmoL/L) were significantly elevated in the presence of spontaneous echo contrast. Further, both markers of thrombin generation inversely correlated with left atrial appendage emptying velocity (r = -0.42 and -0.63, p < 0.05). Levels of TAT and F1.2 increased after conversion and ablation. Conclusions: Endothelial-dependent coagulation factors were enhanced in most patients with atrial flutter. Spontaneous echo contrast and decreased atrial contractility were associated with increased thrombin generation. After conversion and ablation, an increase in thrombin generation and fibrinolysis suggest a transient pro-thrombotic state. (Cardiol J 2010; 17, 4: 390-396

Transnational policy entrepreneurs and the cultivation of influence : individuals, organizations and their networks

The ‘policy entrepreneur’ concept arises from the Multiple Streams’ theory of agenda setting in Policy Studies. Through conceptual stretching’, the concept is extended to global policy dynamics. Unlike ‘advocacy networks’ and ‘norm entrepreneurs’, the discussion addresses the strategies of ‘insider’ or ‘near-governmental’ non-state actors. The analysis advances the policy entrepreneur concept in three directions. First, the discussion develops the transnational dimensions of this activity through a case study of International Crisis Group. Second, rather than focusing on charismatic individuals, the discussion emphasizes the importance of organizational resources and reputations for policy entrepreneurship and access into international policy communities. Organizations maintain momentum behind policy solutions and pressures for change over the long term when individuals retire or depart for other positions. Third, the discussion outlines four distinct entrepreneur strategies and techniques that both individuals and organizations cultivate and deploy to enhance their power and persuasion in global policy processes and politics

Education for Sustainable Development: Towards the Sustainable University

We  planned  this  conference  in  anticipation  of  the  end  of  the  UN  Decade  of  Education  for  Sustainable   Development  (DESD),  and  the  start  of  the  next  phase  for  those  involved  in  ESD  here  and   internationally.    At  Plymouth  University,  2015  marks  ten  year  anniversary  since  cross-­‐institutional   work  on  sustainability  and  sustainability  education  was  spearheaded  by  the  founding  of  the  Centre  for   Sustainable  Futures  (CSF).    Coincidentally,  2015  also  marks  a  ten  years  since  the  influential  HEFCE   policy  document  ‘Sustainable  Development  in  Higher  Education’  was  released.   Holding  the  conference  in  January  –  named  after  the  Roman  god  of  doorways,  of  endings  and   beginnings  –  we  sought  to  look  at  some  of  what  has  been  achieved  in  sustainability  education  to  date   and  explore  its  prospects  as  we  move  forward.   Following  an  enthusiastic  response  to  the  call  for  abstracts,  the  conference  featured  a  diverse  range   of  research  papers,  posters,  and  roundtable  presentations  from  academics  and  practitioners  across   the  UK  and  beyond.  The  conference  was  arranged  around  three  overarching  themes:     ESD  Pedagogy:  Criticality,  Creativity,  and  Collaboration   What  are  the  teaching  and  learning  processes  that  enable  students  to  develop  their  own  capacity  to   think  critically  and  creatively  in  the  face  of  global  sustainability  challenges  and,  secondly,  to  act   collaboratively  in  ways  that  pursue  more  hopeful  and  sustainable  futures?   Innovative  Learning  Spaces  for  ESD   What  are  the  physical  environments  that  provide  opportunities  for  new  forms  of  sustainability   education  to  flourish?  What  lies  beyond  the  lecture  hall  that  is  conducive  to  student  learning  through   inquiry-­‐based,  active,  participatory,  interdisciplinary  and  experiential  methods?   Towards  the  Sustainable  University   What  are  effective  approaches  for  leading  institutional  change,  organisational  learning,  and  staff  CPD   towards  sustainability?  This  publication  focuses  on  the  last  theme  –  Towards  the  Sustainable  University.    The  previous   PedRIO  Occasional  Paper  8  looks  at  the  first  theme  ESD  Pedagogy:  Criticality,  Creativity,  and   Collaboration

A neural code for egocentric spatial maps in the human medial temporal lobe

Spatial navigation and memory rely on neural systems that encode places, distances, and directions in relation to the external world or relative to the navigating organism. Place, grid, and head-direction cells form key units of world-referenced, allocentric cognitive maps, but the neural basis of self-centered, egocentric representations remains poorly understood. Here, we used human single-neuron recordings during virtual spatial navigation tasks to identify neurons providing a neural code for egocentric spatial maps in the human brain. Consistent with previous observations in rodents, these neurons represented egocentric bearings toward reference points positioned throughout the environment. Egocentric bearing cells were abundant in the parahippocampal cortex and supported vectorial representations of egocentric space by also encoding distances toward reference points. Beyond navigation, the observed neurons showed activity increases during spatial and episodic memory recall, suggesting that egocentric bearing cells are not only relevant for navigation but also play a role in human memory

Pin1-dependent signaling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction

The cell adhesion molecule Neuroligin2 (NL2) is localized selectively at GABAergic synapses, where it interacts with the scaffolding protein gephyrin in the post-synaptic density. However, the role of this interaction for formation and plasticity of GABAergic synapses is unclear. Here, we demonstrate that endogenous NL2 undergoes proline-directed phosphorylation at its unique S714-P consensus site, leading to the recruitment of the peptidyl-prolyl cis-trans isomerase Pin1. This signalling cascade negatively regulates NL2' s ability to interact with gephyrin at GABAergic post-synaptic sites. As a consequence, enhanced accumulation of NL2, gephyrin and GABA A receptors was detected at GABAergic synapses in the hippocampus of Pin1-knockout mice (Pin1\ufffd/\ufffd) associated with an increase in amplitude of spontaneous GABA A -mediated post-synaptic currents. Our results suggest that Pin1-dependent signalling represents a mechanism to modulate GABAergic transmission by regulating NL2/gephyrin interaction. \ufffd 2014 Macmillan Publishers Limited. All rights reserved

Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Chlamydiales and Leishmania

Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde transport that affects syntaxin-5- dependent toxins and pathogens. As a consequence, it has a broad-spectrum activity that has been demonstrated both in vitro and in vivo against ricin, Shiga toxin-producing O104:H4 enterohemorrhagic E. coli and Leishmania sp. and in vitro against Ebola, Marburg and poxviruses and Chlamydiales. An effect is anticipated on other toxins or pathogens that use retrograde trafficking and syntaxin-5. Since Retro-2 targets cell components of the host and not directly the pathogen, no selection of resistant pathogens is expected. These lead compounds need now to be developed as drugs for human use