Improving outcome after stroke: overcoming the translational roadblock

Stroke poses a massive burden of disease, yet we have few effective therapies. The paucity of therapeutic options stands contrary to intensive research efforts. The failure of these past investments demands a thorough re-examination of the pathophysiology of ischaemic brain injury. Several critical areas hold the key to overcoming the translational roadblock: (1) vascular occlusion: current recanalization strategies have limited effectiveness and may have serious side effects; (2) complexity of stroke pathobiology: therapy must acknowledge the 'Janus-faced' nature of many stroke targets and must identify endogenous neuroprotective and repair mechanisms; (3) inflammation and brain-immune-system interaction: inflammation contributes to lesion expansion, but is also instrumental in lesion containment and repair; stroke outcome is modulated by the interaction of the injured brain with the immune system; (4) regeneration: the potential of the brain for reorganization, plasticity and repair after injury is much greater than previously thought; (5) confounding factors, long-term outcome and predictive modelling. These 5 areas are linked on all levels and therefore need to be tackled by an integrative approach and innovative therapeutic strategies.

Long-term cellular and regional specificity of the photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina

This study investigated the anatomical consequences of a photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina. Retinae were examined 2 weeks, 1, 3, and 6 months after systemic IAA injection. The retinae were processed using standard histological methods to assess the gross morphology and topographical distribution of damage, and by immunohistochemistry to examine specific cell populations in the retina. Degeneration was restricted to the photoreceptors and was most common in the ventral retina and visual streak. In damaged regions, the outer nuclear layer was reduced in thickness or eliminated entirely, with a concomitant loss of immunoreactivity for rhodopsin. However, the magnitude of the effect varied between animals with the same IAA dose and survival time, suggesting individual differences in the bioavailability of the toxin. In all eyes, the inner retina remained intact, as judged by the thickness of the inner nuclear layer, and by the pattern of immunoreactivity for protein kinase C-alpha (rod bipolar cells) and calbindin D-28 (horizontal cells). Müller cell stalks became immunoreactive for glial fibrillary acidic protein (GFAP) even in IAA-treated retinae that had no signs of cell loss, indicating a response of the retina to the toxin. However, no marked hypertrophy or proliferation of Müller cells was observed with either GFAP or vimentin immunohistochemistry. Thus the selective, long lasting damage to the photoreceptors produced by this toxin did not lead to a reorganization of the surviving cells, at least with survival as long as 6 months, in contrast to the remodeling of the inner retina that is observed in inherited retinal degenerations such as retinitis pigmentosa and retinal injuries such as retinal detachment.

Governor Forrest Anderson’s Leadership & Political Acumen -- Alec Hansen “In the Crucible of Change”

Montana Governor Forrest Anderson was perhaps the most experienced and qualified person ever to be elected as Governor of Montana. Having previously served as a county attorney, a member of the legislature, a Supreme Court Justice, and twelve years as Attorney General, Anderson roared to a large victory in 1968 over the Incumbent GOP Governor Tim Babcock. Though the progressive change period in Montana began a few years earlier, Anderson’s 1968 win catapulted progressive policy-making into the mainstream of Montana political and governmental affairs. He used his unique skills and leadership to craftily architect the reorganization of the executive branch which had been kept weak since statehood so that the peoples’ government would not be able to challenge corporations who so dominated Montana. Anderson, whose “Pay More, What For?” campaign slogan strongly separated him from Tim Babcock and the GOP on the sales tax issue, not only beat back the regressive sales tax in the 1968 election, but oversaw its demise at the polls in 1971, shaping politics in Montana for decades to come. Anderson also was a strong proponent of the concept of a new Montana Constitution and contributed strategically to its calling and passage. Anderson served only one term as Governor for health reasons, but made those four years a launch pad for progressive politics and government in Montana. In this film, Alec Hansen, Special Assistant to Governor Anderson, provides an insider’s perspective as he reflects on the unique way in which Governor Anderson got things done at this critical period “In the Crucible of Change.” Alec Hansen is best known in Montana political and governmental circles as the long-time chief of the Montana League of Cities and Towns, but he cut his teeth in public service with Governor Forrest Anderson. Alec was born in Butte in 1941, attended local schools graduating from Butte High in 1959. After several years working as a miner and warehouseman for the Anaconda Company in Butte, he attended UM and graduated in History and Political Science in 1966. He joined the U.S. Navy and served with amphibious forces in Vietnam. After discharge from the Navy in 1968, he worked as a news and sports reporter for The Montana Standard in Butte until in September of 1969 he joined Governor Anderson as a Special Assistant focused on press, communications and speech-writing. Alec has noted that drafts were turned into pure Forrest Anderson remarks by the man himself. He learned at the knee of “The Fox” for the rest of Anderson’s term and continued with Governor Tom Judge for two years before returning to Butte to work for the Anaconda Company as the Director of Communications for Montana operations. In 1978, after Anaconda was acquired by the Atlantic Richfield Company, Alec went to work in February for U.S. Senator Paul Hatfield in Washington D.C., leaving after Hatfield’s primary election loss in June 1978. He went back to work for Gov. Judge, remaining until the end of 1980. In 1981 Alec worked as a contract lobbyist and news and sports reporter for the Associated Press in Helena. In 1982, the Montana League of Cities and Towns hired him as Executive Director, a position he held until retirement in 2014. Alec and his wife Colleen, are the parents of two grown children, with one grandson.

Governor Tom Judge: Early Years - The Path to Becoming Montana's 18th Governor -- Sidney Armstrong, Larry Pettit & Kent Kleinkopf “In the Crucible of Change”

The dramatic period of progressive change in Montana that is documented "In the Crucible of Change" series really exploded with the election of Governors Forrest Anderson and Tom Judge. Anderson's single term saw the dispatching of the sales tax as an issue for a long period, the reorganization of the executive branch of state government and the revision of Montana's Constitution. As a former legislator, county attorney, Supreme Court justice, and Attorney General, Anderson brought unmatched experience to the governorship when elected. Tom Judge, although much younger (elected MT’s youngest governor at age 38 immediately following Anderson), also brought serious experience to the governorship: six years as a MT State Representative, two years as a MT State Senator, four years is Lieutenant Governor and significant business experience. The campaign and election of John F. Kennedy in 1960 spurred other young Americans to service, including Tom Judge. First elected in 1960, he rose rapidly through MT’s political-governmental hierarchy until he took over the governorship in time to implement many of the changes started in Governor Anderson’s term. But as a strong progressive leader in his own right, Governor Judge sponsored and implemented significant advancements of his own for Montana. Those accomplishments, however, are the subject of other films in this series. This film deals with Tom Judge’s early years – his rise to the governorship from when he returned home after college at Notre Dame and newspaper experience in Kentucky to his actual election in November 1972. That story is discussed in this episode by three major players in the effort, all directly involved in Tom Judge’s early years and path to the governorship: Sidney Armstrong, Larry Pettit and Kent Kleinkopf. Their recollections of the early Tom Judge and the period of his advancement to the governorship provide an insider’s perspective of the growth of this significant leader of the important period of progressive change documented “In the Crucible of Change.” Sidney Armstrong, President of Sidney Armstrong Consulting, serves on the board and as the Executive Director of the Greater Montana Foundation. Formerly Executive Director of the Montana Community Foundation (MCF), she has served on national committees and participated in national foundation initiatives. While at MCF, she worked extensively with MT Governors Racicot and Martz on the state charitable endowment tax credit and other endowed philanthropy issues. A member of MT Governor Thomas L. Judge’s staff in the 1970s, she was also part of Governor Brian Schweitzer’s 2004 Transition Team, continuing to serve as a volunteer advisor during his term. In the 1980s, Sidney also worked for the MT State AFL-CIO and the MT Democratic Party as well as working two sessions with the MT Senate as Assistant Secretary of the Senate and aide to the President. A Helena native, and great granddaughter of pioneer Montanans, Sidney has served on numerous nonprofit boards, and is currently a board member for the Montana History Foundation. Recently she served on the board of the Holter Museum of Art and was a Governor’s appointee to the Humanities Montana board. She is a graduate of the International School of Geneva, Switzerland and the University of Montana. Armstrong's Irish maternal immigrant great-grandparents, Thomas and Maria Cahill Cooney, came to Virginia City, MT in a covered wagon in 1865, looking for gold. Eventually, they settled on the banks of the Missouri River outside Helena as ranchers. She also has roots in Butte, MT, where her journalist father's family, both of whom were newspaper people, lived. Her father, Richard K. O’Malley, is also the author of a well-known book about Butte, Mile High, Mile Deep, recently re-published by Russell Chatham. She is the mother of four and the grandmother of eight. Dr. Lawrence K. Pettit (Larry Pettit) (b. 5/2/1937) has had a dual career in politics and higher education. In addition to being Montana’s first Commissioner of Higher Education (the subject of another film in this series); Pettit, of Lewistown, served as legislative assistant to U.S. Senators James E. Murray and Lee Metcalf, campaign manager, head of transition team and assistant to Montana Governor Thomas L. Judge; taught political science at The Pennsylvania State University (main campus), was chair of political science at Montana State University, Deputy Commissioner for Academic Programs at the Texas Higher Education Coordinating Board, Chancellor of the University System of South Texas (since merged with Texas A&M University), President of Southern Illinois University, and President of Indiana University of Pennsylvania from where he retired in 2003. He has served as chair of the Commission on Leadership for the American Council on Education, president of the National Association of (University) System Heads, and on many national and state boards and commissions in higher education. Pettit is author of “If You Live by the Sword: Politics in the Making and Unmaking of a University President.” More about Pettit is found at http://www.lawrencekpettit.com… Kent Kleinkopf of Missoula is co-founder of a firm with a national scope of business that specializes in litigation consultation, expert vocational testimony, and employee assistance programs. His partner (and wife of 45 years) Kathy, is an expert witness in the 27 year old business. Kent received a BA in History/Education from the University of Idaho and an MA in Economics from the University of Utah. The Kleinkopfs moved to Helena, MT in 1971 where he was Assistant to the Commissioner of State Lands (later Governor) Ted Schwinden. In early 1972 Kent volunteered full time in Lt. Governor Tom Judge’s campaign for Governor, driving the Lt. Governor extensively throughout Montana. After Judge was elected governor, Kent briefly joined the staff of Governor Forrest Anderson, then in 1973 transitioned to Judge’s Governor’s Office staff, where he became Montana’s first “Citizens’ Advocate.” In that capacity he fielded requests for assistance from citizens with concerns and information regarding State Agencies. While on the Governor’s staff, Kent continued as a travel aide with the governor both in Montana and nationally. In 1977 Kent was appointed Director of the MT Department of Business Regulation. That role included responsibility as Superintendent of Banking and Chairman of the State Banking Board, where Kent presided over the chartering of many banks, savings and loans, and credit unions. In 1981 the Kleinkopfs moved to Missoula and went into the business they run today. Kent was appointed by Governor Brian Schweitzer to the Board of the Montana Historical Society in 2006, was reappointed and continues to serve. Kathy and Kent have a daughter and son-in-law in Missoula.

Flotillins interact with PSGL-1 in neutrophils and, upon stimulation, rapidly organize into membrane domains subsequently accumulating in the uropod

BACKGROUND: Neutrophils polarize and migrate in response to chemokines. Different types of membrane microdomains (rafts) have been postulated to be present in rear and front of polarized leukocytes and disruption of rafts by cholesterol sequestration prevents leukocyte polarization. Reggie/flotillin-1 and -2 are two highly homologous proteins that are ubiquitously enriched in detergent resistant membranes and are thought to shape membrane microdomains by forming homo- and hetero-oligomers. It was the goal of this study to investigate dynamic membrane microdomain reorganization during neutrophil activation. METHODOLOGY/PRINCIPAL FINDINGS: We show now, using immunofluorescence staining and co-immunoprecipitation, that endogenous flotillin-1 and -2 colocalize and associate in resting spherical and polarized primary neutrophils. Flotillins redistribute very early after chemoattractant stimulation, and form distinct caps in more than 90% of the neutrophils. At later time points flotillins accumulate in the uropod of polarized cells. Chemotactic peptide-induced redistribution and capping of flotillins requires integrity and dynamics of the actin cytoskeleton, but does not involve Rho-kinase dependent signaling related to formation of the uropod. Both flotillin isoforms are involved in the formation of this membrane domain, as uropod location of exogenously expressed flotillins is dramatically enhanced by co-overexpression of tagged flotillin-1 and -2 in differentiated HL-60 cells as compared to cells expressing only one tagged isoform. Flotillin-1 and -2 associate with P-selectin glycoprotein ligand 1 (PSGL-1) in resting and in stimulated neutrophils as shown by colocalization and co-immunoprecipitation. Neutrophils isolated from PSGL-1-deficient mice exhibit flotillin caps to the same extent as cells isolated from wild type animals, implying that PSGL-1 is not required for the formation of the flotillin caps. Finally we show that stimulus-dependent redistribution of other uropod-located proteins, CD43 and ezrin/radixin/moesin, occurs much slower than that of flotillins and PSGL-1. CONCLUSIONS/SIGNIFICANCE: These results suggest that flotillin-rich actin-dependent membrane microdomains are importantly involved in neutrophil uropod formation and/or stabilization and organize uropod localization of PSGL-1.

A 700-year paleoecological record of boreal ecosystem responses to climatic variation from Alaska

Recent observations and model simulations have highlighted the sensitivity of the forest - tundra ecotone to climatic forcing. In contrast, paleoecological studies have not provided evidence of tree-line fluctuations in response to Holocene climatic changes in Alaska, suggesting that the forest - tundra boundary in certain areas may be relatively stable at multicentennial to millennial time scales. We conducted a multiproxy study of sediment cores from an Alaskan lake near the altitudinal limits of key boreal-forest species. Paleoecological data were compared with independent climatic reconstructions to assess ecosystem responses of the forest - tundra boundary to Little Ice Age (LIA) climatic. uctuations. Pollen, diatom, charcoal, macrofossil, and magnetic analyses provide the first continuous record of vegetation -. re - climate interactions at decadal to centennial time scales during the past 700 years from southern Alaska. Boreal-forest diebacks characterized by declines of Picea mariana, P. glauca, and tree Betula occurred during the LIA ( AD 1500 - 1800), whereas shrubs ( Alnus viridis, Betula glandulosa/nana) and herbaceous taxa (Epilobium, Aconitum) expanded. Marked increases in charcoal abundance and changes in magnetic properties suggest increases in. re importance and soil erosion during the same period. In addition, the conspicuous reduction or disappearance of certain aquatic ( e. g., Isoetes, Nuphar, Pediastrum) and wetland ( Sphagnum) plants and major shifts in diatom assemblages suggest pronounced lake-level. uctuations and rapid ecosystem reorganization in response to LIA climatic deterioration. Our results imply that temperature shifts of 1 - 2 degrees C, when accompanied by major changes in moisture balance, can greatly alter high-altitudinal terrestrial, wetland, and aquatic ecosystems, including conversion between boreal-forest tree line and tundra. The climatic and ecosystem variations in our study area appear to be coherent with changes in solar irradiance, suggesting that changes in solar activity contributed to the environmental instability of the past 700 years.

Cross-modal plasticity in the human thalamus: evidence from intraoperative macrostimulations

During stereotactic functional neurosurgery, stimulation procedure to control for proper target localization provides a unique opportunity to investigate pathophysiological phenomena that cannot be addressed in experimental setups. Here we report on the distribution of response modalities to 487 intraoperative thalamic stimulations performed in 24 neurogenic pain (NP), 17 parkinsonian (PD) and 10 neuropsychiatric (Npsy) patients. Threshold responses were subdivided into somatosensory, motor and affective, and compared between medial (central lateral nucleus) and lateral (ventral anterior, ventral lateral and ventral medial) thalamic nuclei and between patients groups. Major findings were as follows: in the medial thalamus, evoked responses were for a large majority (95%) somatosensory in NP patients, 47% were motor in PD patients, and 54% affective in Npsy patients. In the lateral thalamus, a much higher proportion of somatosensory (83%) than motor responses (5%) was evoked in NP patients, while the proportion was reversed in PD patients (69% motor vs. 21% somatosensory). These results provide the first evidence for functional cross-modal changes in lateral and medial thalamic nuclei in response to intraoperative stimulations in different functional disorders. This extensive functional reorganization sheds new light on wide-range plasticity in the adult human thalamocortical system.

Cell shape-dependent early responses of fibroblasts to cyclic strain

Randomly spread fibroblasts on fibronectin-coated elastomeric membranes respond to cyclic strain by a varying degree of focal adhesion assembly and actin reorganization. We speculated that the individual shape of the cells, which is linked to cytoskeletal structure and pre-stress, might tune these integrin-dependent mechanotransduction events. To this aim, fibronectin circles, squares and rectangles of identical surface area (2000μm(2)) were micro-contact printed onto elastomeric substrates. Fibroblasts plated on these patterns occupied the corresponding shapes. Cyclic 10% equibiaxial strain was applied to patterned cells for 30min, and changes in cytoskeleton and cell-matrix adhesions were quantified after fluorescence staining. After strain, megakaryocytic leukemia-1 protein translocated to the nucleus in most cells, indicating efficient RhoA activation independently of cell shape. However, circular and square cells (with radial symmetry) showed a significantly greater increase in the number of actin stress fibers and vinculin-positive focal adhesions after cyclic strain than rectangular (bipolar) cells of identical size. Conversely, cyclic strain induced larger changes in pY397-FAK positive focal complexes and zyxin relocation from focal adhesions to stress fibers in bipolar compared to symmetric cells. Thus, radially symmetric cells responded to cyclic strain with a larger increase in assembly, whereas bipolar cells reacted with more pronounced reorganization of actin stress fibers and matrix contacts. We conclude that integrin-mediated responses to external mechanical strain are differentially modulated in cells that have the same spreading area but different geometries, and do not only depend on mere cell size.

RNA-dependent genome processing during nuclear differentiation: the model systems of stichotrichous ciliates

We introduce ciliated protozoa, and more specifically the stichotrichous ciliates Oxytricha and Stylonychia, as biological model systems for the analysis of programmed DNA-reorganization processes during nuclear differentiation. These include DNA excision, DNA elimination, reordering of gene segments and specific gene amplification. We show that small nuclear RNAs specify DNA sequences to be excised or retained, but also discuss the need for a RNA template molecule derived from the parental nucleus for these processes. This RNA template guides reordering of gene segments to become functional genes and determines gene copy number in the differentiated nucleus. Since the template is derived from the parental macronucleus, gene reordering and DNA amplification are inherited in a non-Mendelian epigenetic manner.

Microscopic analysis of chromatin localization and dynamics in C. elegans

During development, the genome undergoes drastic reorganization within the nuclear space. To determine tridimensional genome folding, genome-wide techniques (damID/Hi-C) can be applied using cell populations, but these have to be calibrated using microscopy and single-cell analysis of gene positioning. Moreover, the dynamic behavior of chromatin has to be assessed on living samples. Combining fast stereotypic development with easy genetics and microscopy, the nematode C. elegans has become a model of choice in recent years to study changes in nuclear organization during cell fate acquisition. Here we present two complementary techniques to evaluate nuclear positioning of genes either by fluorescence in situ hybridization in fixed samples or in living worm embryos using the GFP-lacI/lacO chromatin-tagging system.

BRAIN ACTIVATION AND CONNECTIVITY IN NON-DISABLED MULTIPLE SCLEROSIS PATIENTS

Multiple sclerosis (MS) is the most common demyelinating disease affecting the central nervous system. There is no cure for MS and current therapies have limited efficacy. While the majority of individuals with MS develop significant clinical disability, a subset experiences a disease course with minimal impairment even in the presence of significant apparent tissue damage on magnetic resonance imaging (MRI). The current studies combined functional MRI and diffusion tensor imaging (DTI) to elucidate brain mechanisms associated with lack of clinical disability in patients with MS. Recent evidence has implicated cortical reorganization as a mechanism to limit the clinical manifestation of the disease. Functional MRI was used to test the hypothesis that non-disabled MS patients (Expanded Disability Status Scale ≤ 1.5) show increased recruitment of cognitive control regions (dorsolateral prefrontal and anterior cingulate cortex) while performing sensory, motor and cognitive tasks. Compared to matched healthy controls, patients increased activation of cognitive control brain regions when performing non-dominant hand movements and the 2-back working memory task. Using dynamic causal modeling, we tested whether increased cognitive control recruitment is associated with alterations in connectivity in the working memory functional network. Patients exhibited similar network connectivity to that of control subjects when performing working memory tasks. We subsequently investigated the integrity of major white matter tracts to assess structural connectivity and its relation to activation and functional integration of the cognitive control system. Patients showed substantial alterations in callosal, inferior and posterior white matter tracts and less pronounced involvement of the corticospinal tracts and superior longitudinal fasciculi (SLF). Decreased structural integrity within the right SLF in patients was associated with decreased performance, and decreased activation and connectivity of the cognitive control system when performing working memory tasks. These studies suggest that patient with MS without clinical disability increase cognitive control system recruitment across functional domains and rely on preserved functional and structural connectivity of brain regions associated with this network. Moreover, the current studies show the usefulness of combining brain activation data from functional MRI and structural connectivity data from DTI to improve our understanding of brain adaptation mechanisms to neurological disease.

Glutamate and nitric oxide as regulatory transmitters in developing rabbit retina

Glutamate is the major excitatory neurotransmitter in the retina and serves as the synaptic messenger for the three classes of neurons which constitute the vertical pathway--the photoreceptors, bipolar cells and ganglion cells. In addition, the glutamate system has been localized morphologically, pharmacologically as well as molecularly during the first postnatal week of development before synaptogenesis occurs. The role which glutamate plays in the maturing visual system is complex but ranges from mediating developmental neurotoxicity to inducing neurite outgrowth.^ Nitric oxide/cGMP is a novel intercellular messenger which is thought to act in concert with the glutamate system in regulating a variety of cellular processes in the brain as well as retina, most notably neurotoxicity. Several developmental activities including programmed cell death, synapse elimination and synaptic reorganization are possible functions of cellular regulation modulated by nitric oxide as well as glutamate.^ The purpose of this thesis is to (1) biochemically characterize the endogenous pools of glutamate and determine what fraction exists extracellularly; (2) examine the morphological expression of NO producing cells in developing retina; (3) test the functional coupling of the NMDA subtype of glutamate receptor to the NO system by examining neurotoxicity which has roles in both the maturing and adult retina.^ Biochemical sampling of perfusates collected from the photoreceptor surface of ex vivo retina demonstrated that although the total pool of glutamate present at birth is relatively modest, a high percentage resides in extracellular pools. As a result, immature neurons without significant synaptic connections survive and develop in a highly glutamatergic environment which has been shown to be toxic in the adult retina.^ The interaction of the glutamate system with the NO system has been postulated to regulate neuronal survival. We therefore examined the developmental expression of the enzyme responsible for producing NO, nitric oxide synthase (NOS), using an antibody to the constitutive form of NOS found in the brain. The neurons thought to produce the majority of NO in the adult retina, a subpopulation of widefield amacrine cells, were not immunoreactive until the end of the second postnatal week. However, a unique developmental expression was observed in the ganglion cell layer and developing outer nuclear layer of the retina during the first postnatal week. We postulate NO producing neurons may not be present in a mature configuration therefore permitting neuronal survival in a highly glutamatergic microenvironment and allowing NO to play a development-specific role at this time.^ The next set of experiments constituted a functional test of the hypothesis that the absence of the prototypic NO producing cells in developing retina protects immature neurons against glutamate toxicity. An explant culture system developed in order to examine cellular responses of immature and adult neurons to glutamate toxicity showed that immature neurons were affected by NMDA but were less responsive to NMDA and NO mediated toxicity. In contrast, adult explants exhibited significant NMDA toxicity which was attenuated by NMDA antagonists, 2-amino-5-phosphonovaleric acid (APV), dextromethorphan (Dex) and N$\rm\sp{G}$-D-methyl arginine (metARG). These results indicated that pan-retinal neurotoxicity via the NMDA receptor and/or NO activation occurred in the adult retina but was not significant in the neonate. (Abstract shortened by UMI.) ^

The effect of abrupt climatic warming on biogeochemical cycling and N2O emissions in a terrestrial ecosystem

The large, rapid increase in atmospheric N2O concentrations that occurred concurrent with the abrupt warming at the end of the Last Glacial period might have been the result of a reorganization in global biogeochemical cycles. To explore the sensitivity of nitrogen cycling in terrestrial ecosystems to abrupt warming, we combined a scenario of climate and vegetation composition change based on multiproxy data for the Oldest Dryas–Bølling abrupt warming event at Gerzensee, Switzerland, with a biogeochemical model that simulates terrestrial N uptake and release, including N2O emissions. As for many central European sites, the pollen record at the Gerzensee is remarkable for the abundant presence of the symbiotic nitrogen fixer Hippophaë rhamnoides (L.) during the abrupt warming that also marks the beginning of primary succession on immature glacial soils. Here we show that without additional nitrogen fixation, climate change results in a significant increase of N2O emissions of approximately factor 3.4 (from 6.4 ± 1.9 to 21.6 ± 5.9 mg N2O–N m− 2 yr− 1). Each additional 1000 mg m− 2 yr− 1 of nitrogen added to the ecosystem through N-fixation results in additional N2O emissions of 1.6 mg N2O–N m− 2 yr− 1 for the time with maximum H. rhamnoides coverage. Our results suggest that local reactions of emissions to abrupt climate change could have been considerably faster than the overall atmospheric concentration changes observed in polar ice. Nitrogen enrichment of soils due to the presence of symbiotic N-fixers during early primary succession not only facilitates the establishment of vegetation on soils in their initial stage of development, but can also have considerable influence on biogeochemical cycles and the release of reactive nitrogen trace gases to the atmosphere.

State of the Antarctic and Southern Ocean Climate System

This paper reviews developments in our understanding of the state of the Antarctic and Southern Ocean climate and its relation to the global climate system over the last few millennia. Climate over this and earlier periods has not been stable, as evidenced by the occurrence of abrupt changes in atmospheric circulation and temperature recorded in Antarctic ice core proxies for past climate. Two of the most prominent abrupt climate change events are characterized by intensification of the circumpolar westerlies (also known as the Southern Annular Mode) between similar to 6000 and 5000 years ago and since 1200-1000 years ago. Following the last of these is a period of major trans-Antarctic reorganization of atmospheric circulation and temperature between A. D. 1700 and 1850. The two earlier Antarctic abrupt climate change events appear linked to but predate by several centuries even more abrupt climate change in the North Atlantic, and the end of the more recent event is coincident with reorganization of atmospheric circulation in the North Pacific. Improved understanding of such events and of the associations between abrupt climate change events recorded in both hemispheres is critical to predicting the impact and timing of future abrupt climate change events potentially forced by anthropogenic changes in greenhouse gases and aerosols. Special attention is given to the climate of the past 200 years, which was recorded by a network of recently available shallow firn cores, and to that of the past 50 years, which was monitored by the continuous instrumental record. Significant regional climate changes have taken place in the Antarctic during the past 50 years. Atmospheric temperatures have increased markedly over the Antarctic Peninsula, linked to nearby ocean warming and intensification of the circumpolar westerlies. Glaciers are retreating on the peninsula, in Patagonia, on the sub-Antarctic islands, and in West Antarctica adjacent to the peninsula. The penetration of marine air masses has become more pronounced over parts of West Antarctica. Above the surface, the Antarctic troposphere has warmed during winter while the stratosphere has cooled year-round. The upper kilometer of the circumpolar Southern Ocean has warmed, Antarctic Bottom Water across a wide sector off East Antarctica has freshened, and the densest bottom water in the Weddell Sea has warmed. In contrast to these regional climate changes, over most of Antarctica, near-surface temperature and snowfall have not increased significantly during at least the past 50 years, and proxy data suggest that the atmospheric circulation over the interior has remained in a similar state for at least the past 200 years. Furthermore, the total sea ice cover around Antarctica has exhibited no significant overall change since reliable satellite monitoring began in the late 1970s, despite large but compensating regional changes. The inhomogeneity of Antarctic climate in space and time implies that recent Antarctic climate changes are due on the one hand to a combination of strong multidecadal variability and anthropogenic effects and, as demonstrated by the paleoclimate record, on the other hand to multidecadal to millennial scale and longer natural variability forced through changes in orbital insolation, greenhouse gases, solar variability, ice dynamics, and aerosols. Model projections suggest that over the 21st century the Antarctic interior will warm by 3.4 degrees +/- 1 degrees C, and sea ice extent will decrease by similar to 30%. Ice sheet models are not yet adequate enough to answer pressing questins about the effect of projected warming on mass balance and sea level. Considering the potentially major impacts of a warming climate on Antarctica, vigorous efforts are needed to better understand all aspects of the highly coupled Antarctic climate system as well as its influence on the Earth's climate and oceans.

Reduction in Northward Incursions of the South Asian Monsoon Since ~1400 AD Inferred from a Mt. Everest Ice Core

A highly resolved Mt. Everest ice core reveals a decrease in marine and increase in continental air masses related to relatively high summer surface pressure over Mongolia, and reduction in northward incursions of the summer South Asian monsoon since similar to 1400 AD. Previously published proxy records from lower sites south of the Himalayas indicate strengthening of the monsoon since this time. These regional differences are consistent with a south north seesaw in convective activity in the Asian monsoon region, and reflect a southward shift in the mean summer position of the monsoon trough since similar to 1400 AD. The change in monsoonal circulation at 1400 AD is synchronous with a reduction in solar irradiance and the onset of the LIA. This demonstrates a hemispheric scale circulation reorganization at this time, and the potential for future large shifts in monsoonal circulation.