bluuebunny/crossref_metadata_2025 huggingface dataset:
Exhumation and deformation history of the lower crustal section of the Valstrona di Omegna in the Ivrea Zone, southern Alps
Authors: Siegesmund S. , Layer P. , Dunkl I. , Vollbrecht A. , Steenken A. , Wemmer K. , Ahrendt H.
Published: July 2008

The Ivrea Zone (southern Alps) is one of the key regions interpreted as exposing a section of the lower continental crust and was the subject of several review-type articles. The Ivrea–Verbano Zone was rotated into an upright position along the Insubric mylonite belt. In the southeast, this unit is in contact with the Strona Ceneri Zone, which is interpreted as upper continental crust crossing the Permian Cossato–Mergozzo–Brissagio Line (CMB Line). The CMB mylonites are locally overprinted by the mylonites and cataclasites of the Pogallo Line, which was active during the Jurassic. In addition, the sinistral, steeply inclined Rosarolo shear zone was active over a long time span from the ductile into the brittle field, i.e. from the Early Permian (high-temperature ultra-mylonites) to the Neo-Alpine basic dykes and pseudotachylites. The high-temperature mylonites accommodated crustal extension and may be related to normal faults generated by magmatic underplating. The reactivation at different crustal levels during exhumation and tilting is documented by strain increments at decreasing P/T conditions. Its present subvertical orientation was attained during the Neo-Alpine deformation. Constraints on its exhumation history are based on new
40
Ar/
39
Ar hornblende ages, K–Ar biotite ages and zircon fission-track data along the NE–SW trending Valstrona section. A re-interpretation of existing U–Pb monazite ages is included, based on a higher closure temperature for monazite. The oldest monazite ages are observed in proximity to the Pogallo Line (
c
. 292 Ma). Heat input by mafic intrusions was sufficient to reset the U–Pb monazite system, as is evidenced by the youngest ages in the vicinity of the Insubric Line. The re-interpretation favours the hypothesis that the oldest monazite ages are the result of complete resetting by a Permian thermal event. The
40
Ar/
39
Ar hornblende ages and K–Ar biotite ages document the cooling after Permian heating. Roughly parallel age progressions decrease from the Pogallo Line (hornblende: 271 Ma vs. biotite: 227 Ma) towards the Insubric Line (hornblende: 201 Ma vs. biotite: 156 Ma). Zircon fission-track ages run parallel to the biotite ages in the upper part of the profile, whereas towards the Insubric Line a significant deviation from the biotite age progression is attributed to tilting of the basement during the Oligocene. Zircon fission-track ages around 38 Ma are found close to the Insubric Line. No age offset, neither at the CMB nor at the Pogallo Line, is observed. This confirms the hypothesis that the Pogallo Line is an oblique normal fault, and that the CMB Line has accommodated only minor vertical displacement. The capture of the different cooling ages confirms the tilting of the Ivrea–Verbano Zone during the Neo-Alpine deformation and contradicts the tilting of the Ivrea–Verbano Zone during the Permian.
Post-Variscan to Early Alpine sedimentary basins in the Tauern Window (eastern Alps)
Authors: Veselá P. , Lammerer B. , Wetzel A. , Söllner F. , Gerdes A.
Published: July 2008

The crystalline basement of the Tauern Window is locally covered by Palaeozoic to Mesozoic sediments that experienced Alpine tectonometamorphism. The sedimentary cover has been subdivided into mappable lithological units. The correlation of these units, the use of some dated marker intervals and independent palinspastic restoration provide evidence that the depositional area was differentiated into basins and swells. At the end of the Variscan orogeny, during the Carboniferous and Permian, intermontane basins formed in basement rocks and mainly continental clastics accumulated in elongate troughs. Later, probably during the Triassic, there was levelling of the previous relief and subsidence of the basins, but continental sedimentation still prevailed although interrupted by some marine transgressions. Thereafter, probably during the Jurassic, the area was progressively flooded and the sedimentation became increasingly calcareous. The Upper Jurassic carbonates document complete submergence. In some areas, the Upper Jurassic carbonates directly rest on crystalline basement indicating renewed tectonic stretching. The sedimentary cover shows striking similarities with coeval deposits within the Germanic Basin and the study area is therefore considered to have been part of the southern European continental margin of the Tethys (the so-called Vindelician Land).
The Meliata suture in the Carpathians: regional significance and implications for the evolution of high-pressure wedges within collisional orogens
Authors: Dallmeyer R. David , Neubauer Franz , Fritz Harald
Published: July 2008

The Meliata nappe of the Western Carpathian orogen is comprised of Triassic deep-sea metasedimentary rocks and fragments of blueschist-bearing ophiolite. These were structurally emplaced onto Permian/Triassic shelf sequences and its Variscan basement. The nappe records a succession of deformational events which formed under decreasing pressure conditions. Subduction-related burial and resulting blueschist metamorphism is dated by
40
Ar/
39
Ar plateau ages recorded by four phengitic muscovite concentrates (160–150 Ma). These crystallized during ductile deformation characterized by predominantly coaxial NW–SE stretching. The structures were overprinted by semiductile, nonpenetrative fabric elements which formed under greenschist facies conditions and contemporaneously with fabrics which developed in footwall tectonic units. Kinematic indicators record top north to NW shear during Middle Cretaceous loading of the Meliata unit onto the Inner Carpathian nappe complex recorded by a
40
Ar/
39
Ar whole rock phyllite age of 105.8±1.5 Ma. A subsequent southeastern sense of shear is interpreted to have resulted from extension during Late Cretaceous uplift along hinterland margins of the tectonic wedge. The Meliata unit is part of a major Late Jurassic/Early Cretaceous suture which initially extended from the Alps to the Hellenides. It has been subsequently disrupted as a result of later strike-slip faulting following Tertiary collision of the Cretaceous orogen, and was transported onto extra-Alpine European units.
Subduction-related metamorphism in the Alps: review of isotopic ages based on petrology and their geodynamic consequences
Authors: Berger Alfons , Bousquet Romain
Published: July 2008

We summarize ages of the high‐pressure/low‐temperature (HP/LT) metamorphic evolution of the central and the western Alps. The individual isotopic mineral ages are interpreted to represent either: (1) early growth of metamorphic minerals on the prograde path; (2) timing close to peak metamorphism; or (3) retrograde resetting of the chronometers at still‐elevated pressures. Therefore, each individual age cannot easily be transferred to a geodynamic setting at a certain time. These different data indicate a subduction‐related metamorphism between 62 and 35 Ma in different units (e.g. Voltri Massif, Schistes Lustrés of the western Alps, Tauern Window). Oceanic and continental basement units show isotope ages related to eclogitic or blueschist facies metamorphism between 75 and 40 Ma. Most of these ages may record equilibration along the retrograde path, except of some Lu/Hf garnet ages and some zircon SHRIMP ages, which provide information on the prograde path. These different isotope ages are interpreted as different steps along pressure–time paths and so may provide some information on the geodynamic evolution. The data record a continuous subduction, which is ongoing for several tens of millions years. In a large‐scale picture, we have to assume fragmentation of the downgoing plate in order to explain the available P–T and t data. This interpretation questions the ongoing driving force for subduction during the disappearance of the Alpine Tethys.
Linguistic Diversity in the Caucasus
Authors: Comrie Bernard
Published: July 2008

The Caucasus is characterized by a relatively high level of linguistic diversity, whether measured in terms of number of languages, number of language families, or structural properties. This is in stark contrast to low levels of linguistic diversity in neighboring areas (Europe, the Middle East), although the Caucasus does not reach such high levels of linguistic diversity as are found in New Guinea. There is even a variation between greater diversity in the North Caucasus and less diversity in the South Caucasus. Illustrative structural properties show not only idiosyncratic properties of individual languages and families but also features that have spread across the boundaries separating languages and families, sometimes with variation across languages with regard to finer points of detail, although few features characterize the Caucasus as a single linguistic area. Social factors have probably played at least as important a role as has geography in the development of linguistic diversity in the Caucasus.
The Anthropology of Crime and Criminalization
Authors: Schneider Jane , Schneider Peter
Published: July 2008

The ambiguity of the concept of crime is evident in the two strands of anthropological research covered in this review. One strand, the anthropology of criminalization, explores how state authorities, media, and citizen discourse define particular groups and practices as criminal, with prejudicial consequences. Examples are drawn from research on peasant rebellion, colonialism, youth, and racially or ethnically marked urban poor. The other strand traces ethnographic work on more or less organized illegal and predatory activity: banditry, rustling, trafficking, street gangs, and mafias. Although a criminalizing perspective tends to conflate these diverse forms of “organized” crime, in particular erasing the boundary between street gangs and drug trafficking, the forms have discrete histories and motivations. Their particularities, as well as their historical interactions, illuminate everyday responses to crime and suggest ways to put in perspective the “crime talk” of today, which borders on apocalyptic.
Linguistic Anthropology of Education
Authors: Wortham Stanton
Published: July 2008

Linguistic anthropological theories and methods have enriched our understanding of education. Almost all education is mediated by language, and linguistic anthropologists use both precise linguistic analyses and powerful anthropological theories to describe how educational language use establishes important social relations. Because educational institutions influence processes of concern to anthropologists—including the production of differentially valued identities, the circulation and transformation of cultural models, and nation states’ establishment of official peoples—linguistic anthropological research on education also contributes to cultural and linguistic anthropology more generally. This article defines linguistic anthropology through its focus on language form, use, ideology, and domain, and it reviews linguistic anthropological research that focuses on these four aspects of educational language use.
A Historical Appraisal of Clicks: A Linguistic and Genetic Population Perspective
Authors: Güldemann Tom , Stoneking Mark
Published: July 2008

Clicks are often considered an exotic feature of languages, and the fact that certain African “Khoisan” groups share the use of clicks as consonants and exhibit deep genetic divergences has been argued to indicate that clicks trace back to an early common ancestral language ( Knight et al. 2003 ). Here, we review the linguistic evidence concerning the use of click sounds in languages and the genetic evidence concerning the relationships of African click-speaking groups. The linguistic evidence suggests that genealogical inheritance and contact-induced transmission are equally relevant for the distribution of clicks in African languages. The genetic evidence indicates that there has been substantial genetic drift in some groups, obscuring their genetic relationships. Overall, the presence of clicks in human languages may in fact not trace back to the dawn of human language, but instead reflect a much later episode in the diversification of human speech.
The Archaeology of Childhood
Authors: Baxter Jane Eva
Published: July 2008

The archaeology of childhood has grown over the past decade and a half as a vibrant field of specialized interest within archaeology as a whole. A thematic treatment of the literature highlights a variety of approaches to how and why archaeologists should study children using the archaeological record. These themes are organized chronologically and begin with critiques of archaeological approaches that do not include children and an exploration of the relationship between childhood studies and studies of gender, identity, and agency in the archaeological record. Theoretical and methodological developments that draw attention to new ways of looking at the archaeological record to identify cultural constructions of childhood and lived experiences of children are presented. Finally, current tensions and pluralities in the literature are explored as the archaeology of childhood reaches a new stage in its own maturity as a field of inquiry.
Demographic Transitions and Modernity
Authors: Johnson-Hanks Jennifer
Published: July 2008

Much contemporary anthropology is concerned with the origin, character, and consequences of late modernity. Surprisingly absent in this literature is the importance of population size, structure, and process. In particular, the demographic transition—or historical change from a high to a low equilibrium of birth and death rates—is an important component of modernity that deserves greater anthropological engagement. This review outlines demographic transition and transition theory, then discusses two ways in which transition intersects with literatures on modernity: through individual rationality and governmentality. Confronting both the material of population and the theories about it has the potential to significantly reconfigure anthropologies of the present.
Detecting the Genetic Signature of Natural Selection in Human Populations: Models, Methods, and Data
Authors: Hancock Angela M. , Di Rienzo Anna
Published: July 2008

Patterns of DNA sequence variation in the genome contain a record of past selective events. The ability to collect increasingly large data sets of polymorphisms has allowed investigators to perform hypothesis-driven studies of candidate genes as well as genome-wide scans for signatures of adaptations. This genetic approach to the study of natural selection has identified many signals consistent with predictions from anthropological studies. Selective pressures related to variation in climate, diet, and pathogen exposure have left strong marks on patterns of human variation. Additional signals of adaptations are observed in genes involved in chemosensory perception and reproduction. Several ongoing projects aim to sequence the complete genome of 1000 individuals from different human populations. These large-scale projects will provide data for more complete genome scans of selection, but more focused studies aimed at testing specific hypotheses will continue to hold an important place in elucidating the history of adaptations in humans.
Evolutionary Linguistics
Authors: Croft William
Published: July 2008

Both qualitative concepts and quantitative methods from evolutionary biology have been applied to linguistics. Many linguists have noted the similarity between biological evolution and language change, but usually have employed only selective analogies or metaphors. The development of generalized theories of evolutionary change (Dawkins and Hull) has spawned models of language change on the basis of such generalized theories. These models have led to the positing of new mechanisms of language change and new types of selection that may not have biological parallels. Quantitative methods have been applied to questions of language phylogeny in the past decade. Research has focused on widely accepted families with cognates already established by the comparative method (Indo-European, Bantu, Austronesian). Increasingly sophisticated phylogeny reconstruction models have been applied to these families to resolve questions of subgrouping, contact, and migration. Little progress has been made so far in analyzing sound correspondences in the cognates themselves.
From Resilience to Resistance: Political Ecological Lessons from Antibiotic and Pesticide Resistance
Authors: Orzech Kathryn M. , Nichter Mark
Published: July 2008

This article investigates the interplay of natural and human systems with reference to the growing global problem of antibiotic resistance. Among the diverse causes of antibiotic resistance, we focus broadly on three related causes: pharmaceutical practice and the liberal consumption of antibiotics, the use of antibiotic-containing products in the home, and the use of antibiotics in commercial animal husbandry and agriculture. We draw a parallel between pesticide and antibiotic resistance and examine whether lessons learned from one case may be applicable to the other. Although our main focus is a microecological analysis examining how humans are changing their environments, our conclusion addresses larger implications of this problem for global health. Through the theoretical lens of political ecology, we ask how we may address the “tragedy of the antibiotic commons” through public education and consumer activism as well as global health governance.
The Human Brain Evolving: A Personal Retrospective
Authors: Holloway Ralph L.
Published: July 2008

Minor controversies notwithstanding, the evolution of the human brain has been an intermingled composite of allometric and nonallometric increases of brain volume and reorganizational events such as the reduction of primary visual cortex and a relative increase in both posterior association and (most probably) prefrontal cortex, as well as increased cerebral asymmetries, including Broca's and Wernicke's regions, with some of these changes already occurring in australopithecine times. As outlined in Holloway (1967), positive feedback (amplification-deviation) has been a major mechanism in size increases. Exactly how this mélange of organs evolved will require many more paleontological discoveries with relatively intact crania, an unraveling of the genetic bases for both brain structures and their relationship to behaviors, and a far more complete picture of how the brain varies between male and female and among different populations throughout the world. After all, the human brain is still evolving, but for how long is quite uncertain.
Post-Post-Transition Theories: Walking on Multiple Paths
Authors: Buyandelgeriyn Manduhai
Published: July 2008

This article reviews recent ethnographic works on the former Soviet Union, Eastern and Central Europe, and Mongolia that explore the experiences of people enduring drastic transformations following the collapse of socialism in 1990 and the consequent implementation of a neoliberal “shock therapy.” The anthropologists working on postsocialist societies have shown that transition theories are inherently faulty and their implementation often had damaging results. The current condition is not a period of transition or “bridge” between socialism and capitalism. Instead individuals’ activities, memory, social networks, and culturally specific values lead to uncertainty as a state of dynamic being. This article argues that uncertainty is a complex conceptual space that offers further opportunities to step away from the evolutionary mode of thinking and to develop theories of multiple ways of being.
The Effects of Kin on Primate Life Histories
Authors: Strier Karen B.
Published: July 2008

Advances in our understanding of primate life histories and dispersal patterns provide insights into the ways in which facultative responses to local ecological and demographic conditions are mediated by phylogenetic constraints. The long life spans characteristic of primates provide the necessary conditions for overlapping generations of related individuals to maintain extended kin bonds. Dispersal regimes dictate the opportunities for biological kin to interact with one another and define the range of potential reproductive and social partners within and beyond their natal groups. Dispersal patterns also affect variation in components of life histories such as female age at first reproduction, reproductive rates, and trade-offs between investment in current vs. future offspring and extended kin. Understanding these dynamics has important implications for assessing the viability of small populations and the ability of different primates to adapt.
Reproduction and Preservation of Linguistic Knowledge: Linguistics’ Response to Language Endangerment
Authors: Himmelmann Nikolaus P.
Published: July 2008

In responding to the globally accelerating rate at which linguistic varieties are disappearing, structural linguistics is confronted with a number of challenges for which it is ill-equipped because of limitations in its basic conceptualization of linguistic knowledge. In addition to providing a brief history of the recent promotion of language endangerment to a major concern of the discipline as a whole, this article discusses three such challenges: (a) new demands on linguistic fieldwork practices, (b) rhetorical tensions arising from the need to address a multiplicity of audiences; (c) the limits of the traditional descriptive trilogy and its replacement by the concept of language documentation. On a theoretical level, these challenges are all linked to the problem that the structuralist conception of linguistic structures lacks adequate grounding in the social realities of the speech community, a problem that has accompanied linguistic structuralism since its inception.
The Archaeological Evidence for Social Evolution
Authors: Marcus Joyce
Published: July 2008

Social evolution can be defined as the appearance of new forms of social or sociopolitical organization. In the case of the prehistoric record, such changes are perhaps most successfully studied when archaeologists collaborate with ethnologists or ethnohistorians. Although ethnologists can provide unequaled detail on agents and institutions, many evolutionary transitions took longer than any ethnologist's lifetime. The archaeological record therefore provides an important proving ground for evolutionary theory. In this review, I synthesize some of the evidence supporting social evolution from both Old World and New World archaeology. I also argue that for the study of social evolution to advance, the field of anthropology must be willing to generalize; to compare and contrast cultures from different parts of the world; and to search for common patterns in the ways human societies responded to similar challenges.
Replicative Aging in Yeast: The Means to the End
Authors: Steinkraus K.A. , Kaeberlein M. , Kennedy B.K.
Published: July 2008

Progress in aging research is now rapid, and surprisingly, studies in a single-celled eukaryote are a driving force. The genetic modulators of replicative life span in yeast are being identified, the molecular events that accompany aging are being discovered, and the extent to which longevity pathways are conserved between yeast and multicellular eukaryotes is being tested. In this review, we provide a brief retrospective view on the development of yeast as a model for aging and then turn to recent discoveries that have pushed aging research into novel directions and also linked aging in yeast to well-developed hypotheses in mammals. Although the question of what causes aging still cannot be answered definitively, that day may be rapidly approaching.
Communication Between the Synapse and the Nucleus in Neuronal Development, Plasticity, and Disease
Authors: Cohen Sonia , Greenberg Michael E.
Published: July 2008

Sensory experience is critical for the proper development and plasticity of the brain throughout life. Successful adaptation to the environment is necessary for the survival of an organism, and this process requires the translation of specific sensory stimuli into changes in the structure and function of relevant neural circuits. Sensory-evoked activity drives synaptic input onto neurons within these behavioral circuits, initiating membrane depolarization and calcium influx into the cytoplasm. Calcium signaling triggers the molecular mechanisms underlying neuronal adaptation, including the activity-dependent transcriptional programs that drive the synthesis of the effector molecules required for long-term changes in neuronal function. Insight into the signaling pathways between the synapse and the nucleus that translate specific stimuli into altered patterns of connectivity within a circuit provides clues as to how activity-dependent programs of gene expression are coordinated and how disruptions in this process may contribute to disorders of cognitive function.
The Renaissance of Field Experimentation in Evaluating Interventions
Authors: Shadish William R. , Cook Thomas D.
Published: July 2008

Most experiments are done in laboratories. However, there is also a theory and practice of field experimentation. It has had its successes and failures over the past four decades but is now increasingly used for answering causal questions. This is true for both randomized and—perhaps more surprisingly—nonrandomized experiments. In this article, we review the history of the use of field experiments, discuss some of the reasons for their current renaissance, and focus the bulk of the article on the particular technical developments that have made this renaissance possible across four kinds of widely used experimental and quasi-experimental designs—randomized experiments, regression discontinuity designs in which those units above a cutoff get one treatment and those below get another, short interrupted time series, and nonrandomized experiments using a nonequivalent comparison group. We focus this review on some of the key technical developments addressing problems that previously stymied accurate effect estimation, the solution of which opens the way for accurate estimation of effects under the often difficult conditions of field implementation—the estimation of treatment effects under partial treatment implementation, the prevention and analysis of attrition, analysis of nested designs, new analytic developments for both regression discontinuity designs and short interrupted time series, and propensity score analysis. We also cover the key empirical evidence showing the conditions under which some nonrandomized experiments may be able to approximate results from randomized experiments.
Hypothermia increases the gain of excitation-contraction coupling in guinea pig ventricular myocytes
Authors: Shutt Robin H. , Howlett Susan E.
Published: July 2008

Components of excitation-contraction (EC)-coupling were compared at 37°C and 22°C to determine whether hypothermia altered the gain of EC coupling in guinea pig ventricular myocytes. Ca2+concentration (fura-2) and cell shortening (edge detector) were measured simultaneously. Hypothermia increased fractional shortening (8.3 ± 1.7 vs. 2.6 ± 0.3% at 37°C), Ca2+transients (157 ± 33 vs. 35 ± 5 nM at 37°C), and diastolic Ca2+(100 ± 9 vs. 60 ± 6 nM at 37°C) in field-stimulated myocytes (2 Hz). In experiments with high-resistance microelectrodes, the increase in contractions and Ca2+transients was accompanied by a twofold increase in action potential duration (APD). When voltage-clamp steps eliminated changes in APD, cooling still increased contractions and Ca2+transients. Hypothermia increased sarcoplasmic reticulum (SR) Ca2+stores (83 ± 17 at 37°C to 212 ± 50 nM, assessed with caffeine) and increased fractional SR Ca2+release twofold. In contrast, peak Ca2+current was much smaller at 22°C than at 37°C (1.3 ± 0.4 and 3.5 ± 0.7 pA/pF, respectively). In cells dialyzed with sodium-free pipette solutions to inhibit Ca2+influx via reverse-mode Na+/Ca2+exchange, hypothermia still increased contractions, Ca2+transients, SR stores, and fractional release but decreased the amplitude of Ca2+current. The rate of SR Ca2+release per unit Ca2+current, a measure of EC-coupling gain, was increased sixfold by hypothermia. This increase in gain occurred regardless of whether cells were dialyzed with sodium-free solutions. Thus an increase in EC-coupling gain contributes importantly to positive inotropic effects of hypothermia in the heart.
Kv1.3 channels in postganglionic sympathetic neurons: expression, function, and modulation
Authors: Doczi Megan A. , Morielli Anthony D. , Damon Deborah H.
Published: July 2008

Kv1.3 channels are known to modulate many aspects of neuronal function. We tested the hypothesis that Kv1.3 modulates the function of postganglionic sympathetic neurons. RT-PCR, immunoblot, and immunohistochemical analyses indicated that Kv1.3 channels were expressed in these neurons. Immunohistochemical analyses indicated that Kv1.3 protein was localized to neuronal cell bodies, processes, and nerve fibers at sympathetic neurovascular junctions. Margatoxin (MgTX), a specific inhibitor of Kv1.3, was used to assess the function of the channel. Electrophysiological analyses indicated that MgTX significantly reduced outward currents [ P < 0.05; n = 18 (control) and 15 (MgTX)], depolarized resting membrane potential, and decreased the latency to action potential firing [ P < 0.05; n = 11 (control) and 13 (MgTX)]. The primary physiological input to postganglionic sympathetic neurons is ACh, which activates nicotinic and muscarinic ACh receptors. MgTX modulated nicotinic ACh receptor agonist-induced norepinephrine release ( P < 0.05; n ≥ 6), and MgTX-sensitive current was suppressed upon activation of muscarinic ACh receptors with bethanechol ( P < 0.05; n = 12). These data indicate that Kv1.3 affects the function of postganglionic sympathetic neurons, which suggests that Kv1.3 influences sympathetic control of cardiovascular function. Our data also indicate that modulation of Kv1.3 is likely to affect sympathetic control of cardiovascular function.
Astrocyte responses to injury: VEGF simultaneously modulates cell death and proliferation
Authors: Schmid-Brunclik Nicole , Bürgi-Taboada Carole , Antoniou Xanthi , Gassmann Max , Ogunshola Omolara O.
Published: July 2008

Hypoxia is linked to changes in blood-brain barrier (BBB) permeability, and loss of BBB integrity is characteristic of many pathological brain diseases including stroke. In particular, astrocytes play a central role in brain homeostasis and BBB function. We investigated how hypoxia affects astrocyte survival and assessed whether VEGF release through hypoxia-inducible factor-1α (HIF-1α) induction plays a role in tolerance of these cells to insult. Thus primary astrocytes were subjected to normoxic (21% O2), hypoxic (1% O2), or near-anoxic (<0.1% O2) conditions in the presence or absence of glucose. Cell death was significantly initiated after combined oxygen glucose deprivation, and, surprisingly, astrocyte proliferation increased concomitantly. Near anoxic, but not hypoxic, conditions stabilized HIF-1α protein and provoked DNA binding activity, whereas oxygen and glucose deprivation accelerated HIF-1α accumulation. Unexpectedly, Hif-1α knockdown studies showed that elevated VEGF levels following increased insult was only partially due to HIF-1α induction, suggesting alternative mechanisms of VEGF regulation. Notably, endogenous VEGF signaling during insult was essential for cell fate since VEGF inhibition appreciably augmented cell death and reduced proliferation. These data suggest Hif-1 only partially contributes to VEGF-mediated astrocyte responses during chronic injury (as occurs in clinical hypoxic/ischemic insults) that may ultimately be responsible for disrupting BBB integrity.
Nicotinic acetylcholine receptor expression and regulation in the rat kidney after ischemia-reperfusion injury
Authors: Yeboah Michael M. , Xue Xiangying , Javdan Mohammad , Susin Myron , Metz Christine N.
Published: July 2008

The cholinergic anti-inflammatory pathway is a mechanism whereby local inflammation is modulated by the brain via the vagus nerve and nicotinic acetylcholine receptors (nAChRs). The nAChR family are ligand-gated ion channels that consist of many different subtypes formed by the specific assembly of five polypeptide subunits including α1–10, β1–4, γ, δ, and ε. The α7 receptor (α7nAChR) mediates the anti-inflammatory effects of cholinergic stimulation. We recently demonstrated that cholinergic agonists attenuate renal ischemia-reperfusion (I/R) injury in rats. We also showed that tubular epithelial cells express functional nAChRs in vitro. The current studies report the expression, localization, and regulation of the α7nAChR in the rat kidney after I/R injury. We also examined, in this model, potential interactions between cholinergic stimulation and the STAT3 pathway, a key signaling cascade that has been linked to α7nAChR activation. RT-PCR and immunohistochemistry showed constitutive expression of many nAChR subunits. Immunohistochemistry localized basal α7nAChR expression to the endothelium of cortical peritubular capillaries, and its distribution was upregulated after I/R injury. Western blotting also showed an increase in α7nAChR subunit protein after renal I/R injury. Interestingly, pretreatment with nicotine, which improves the outcome after renal I/R injury, reduced the α7nAChR protein after I/R injury. Finally, we found that I/R injury stimulated the STAT3 pathway, whereas pretreatment with nicotine downregulated its activation. These results suggest that the α7nAChR plays an important role in the pathophysiology of renal I/R injury.
Reduction of chronic allograft nephropathy by inhibition of extracellular signal-regulated kinase 1 and 2 signaling
Authors: Wang Shuang , Jiang Jifu , Guan Qiunong , Wang Hao , Nguan Christopher Y. C. , Jevnikar Anthony M. , Du Caigan
Published: July 2008

Chronic allograft nephropathy (CAN), the most common cause of late kidney allograft failure, is not effectively prevented by immunosuppressive regimens. Activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) via MEK mediates actions of various growth factors, including transforming growth factor (TGF)-β1, which plays a key role in CAN. Hence, we tested the therapeutic potential of MEK-ERK1/2 signaling disruption to prevent CAN. Kidneys from C57BL/6J (H-2b) mice were transplanted to bilaterally nephrectomized BALB/c (H-2d) mice. At 14 days after transplantation, the recipients were subjected to 28 days of treatment with the MEK inhibitor CI-1040. All six CI-1040-treated allografts survived, while two of seven grafts in the vehicle-treated group were lost. At the end of the experiment, the function and structure of grafts in the CI-1040-treated group were significantly preserved, as indicated by lower levels of serum creatinine or blood urea nitrogen than in the vehicle-treated group [30 ± 6 vs. 94 ± 39 μM creatinine ( P = 0.0015) and 22 ± 8 vs. 56 ± 25 mM BUN ( P = 0.0054)] and reduced CAN in the CI-1040-treated group compared with vehicle controls (CAN score = 4.2 vs. 10.3, P = 0.0119). The beneficial effects induced by CI-1040 were associated with reduction of ERK1/2 phosphorylation and TGFβ1 levels in grafts. Also, CI-1040 potently suppressed not only TGFβ biosynthesis in kidney cell cultures but also antiallograft immune responses in vitro and in vivo. Our data suggest that interference of MEK-ERK1/2 signaling with a pharmacological agent (e.g., CI-1040) has therapeutic potential to prevent CAN in kidney transplantation.
Separate and combined effects of exercise training and weight loss on exercise efficiency and substrate oxidation
Authors: Amati Francesca , Dubé John J. , Shay Chris , Goodpaster Bret H.
Published: July 2008

Perturbations in body weight have been shown to affect energy expenditure and efficiency during physical activity. The separate effects of weight loss and exercise training on exercise efficiency or the proportion of energy derived from fat oxidation during physical activity, however, are not known. The purpose of this study was to determine the separate and combined effects of exercise training and weight loss on metabolic efficiency, economy (EC), and fat oxidation during steady-state moderate submaximal exercise. Sixty-four sedentary older (67 ± 0.5 yr) overweight to obese (30.7 ± 0.4 kg/m2) volunteers completed 4 mo of either diet-induced weight loss (WL; n = 11), exercise training (EX; n = 36), or the combination of both interventions (WLEX; n = 17). Energy expenditure, gross efficiency (GE), EC, and proportion of energy expended from fat (EF) were determined during a 1-h submaximal (50% of peak aerobic capacity) cycle ergometry exercise before the intervention and at the same absolute work rate after the intervention. We found that EX increased GE by 4.7 ± 2.2%. EC was similarly increased by 4.2 ± 2.1% by EX. The addition of concomitant WL to EX (WLEX) resulted in greater increases in GE (9.0 ± 3.3%) compared with WL alone but not compared with EX alone. These effects remained after adjusting for changes in lean body mass. The proportion of energy derived from fat during the bout of moderate exercise increased with EX and WLEX but not with WL. From these findings, we conclude that exercise training, either alone or in combination with weight loss, increases both exercise efficiency and the utilization of fat during moderate physical activity in previously sedentary, obese older adults. Weight loss alone, however, significantly improves neither efficiency nor utilization of fat during exercise.
Detecting Neural-State Transitions Using Hidden Markov Models for Motor Cortical Prostheses
Authors: Kemere Caleb , Santhanam Gopal , Yu Byron M. , Afshar Afsheen , Ryu Stephen I. , Meng Teresa H. , Shenoy Krishna V.
Published: July 2008

Neural prosthetic interfaces use neural activity related to the planning and perimovement epochs of arm reaching to afford brain-directed control of external devices. Previous research has primarily centered on accurately decoding movement intention from either plan or perimovement activity, but has assumed that temporal boundaries between these epochs are known to the decoding system. In this work, we develop a technique to automatically differentiate between baseline, plan, and perimovement epochs of neural activity. Specifically, we use a generative model of neural activity to capture how neural activity varies between these three epochs. Our approach is based on a hidden Markov model (HMM), in which the latent variable (state) corresponds to the epoch of neural activity, coupled with a state-dependent Poisson firing model. Using an HMM, we demonstrate that the time of transition from baseline to plan epochs, a transition in neural activity that is not accompanied by any external behavior changes, can be detected using a threshold on the a posteriori HMM state probabilities. Following detection of the plan epoch, we show that the intended target of a center-out movement can be detected about as accurately as that by a maximum-likelihood estimator using a window of known plan activity. In addition, we demonstrate that our HMM can detect transitions in neural activity corresponding to targets not found in training data. Thus the HMM technique for automatically detecting transitions between epochs of neural activity enables prosthetic interfaces that can operate autonomously.
Locomotor and Reflex Adaptation After Partial Denervation of Ankle Extensors in Chronic Spinal Cats
Authors: Frigon Alain , Rossignol Serge
Published: July 2008

This work investigates the capacity of the spinal cord to generate locomotion after a complete spinal section and its ability to adapt its locomotor pattern after a peripheral nerve lesion. To study this intrinsic adaptive capacity, the left lateral gastrocnemius-soleus (LGS) nerve was sectioned in three cats that expressed a stable locomotion following a complete spinal transection. The electromyograph (EMG) of multiple hindlimb muscles and reflexes, evoked by stimulating the left tibial (Tib) nerve at the ankle, were recorded before and after denervation during treadmill locomotion. Following denervation, the mean amplitude of EMG bursts of multiple hindlimb muscles increased during locomotion, similar to what is found after an identical denervation in otherwise intact cats. Reflex changes were noted in ipsilateral flexors, such as semitendinosus and tibialis anterior, but not in the ipsilateral knee extensor vastus lateralis following denervation. The present results demonstrate that the spinal cord possesses the circuitry necessary to mediate increased EMG activity in multiple hindlimb muscles and also to produce changes in reflex pathways after a muscle denervation. The similarity of changes following LGS denervation in cats with an intact and transected spinal cord suggests that spinal mechanisms play a major role in the locomotor adaptation.
Low-Fat Dietary Pattern and Risk of Benign Proliferative Breast Disease: A Randomized, Controlled Dietary Modification Trial
Authors: Rohan Thomas E. , Negassa Abdissa , Caan Bette , Chlebowski Rowan T. , Curb J. David , Ginsberg Mindy , Lane Dorothy S. , Neuhouser Marian L. , Shikany James M. , Wassertheil-Smoller Sylvia , Page David L.
Published: July 2008

Modifiable factors, including diet, might alter breast cancer risk. We used the Women's Health Initiative Dietary Modification trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of, and considered to be on the pathway to, invasive breast cancer. The Women's Health Initiative Dietary Modification trial was a randomized, controlled, primary prevention trial conducted in 40 U.S. clinical centers from 1993 to 2005. A total of 48,835 postmenopausal women, ages 50 to 79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the dietary modification intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to ≥5 servings/d and intake of grain products to ≥6 servings/d, but resulted in smaller, albeit significant, changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between dietary modification and benign proliferative breast disease was 1.09 (95% confidence interval, 0.98-1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake do not alter the risk of benign proliferative breast disease.
Amelanotic Esophageal Malignant Melanoma: Case Report and Short Review of the Literature
Authors: Kranzfelder Michael , Seidl Stefan , Dobritz Martin , Brücher Björn L.D.M.
Published: July 2008

Malignant melanoma in the esophagus is a rare condition which has been described only occasionally in case reports or in larger series of patients with esophageal disease. We describe here the very rare case of a patient who presented initially with a 2-month history of dysphagia and weight loss which led to the endoscopic diagnosis of an unclear lesion in the distal esophagus. Biopsies were taken revealing positive immunohistochemical staining against HMB-45. As there were no signs of skin melanoma and there was an absence of pigmentation, a diagnosis of primary amelanotic malignant melanoma was made. Primary staging of the lesion was completed with computed tomography (CT), which revealed a locally advanced tumor with lymph node metastases at the lesser curvature of the stomach and celiac trunk. As there is still a lack of potential protocols for multimodal neoadjuvant treatment for this rare tumor entity, a palliative abdominothoracic esophagectomy with systemic lymphadenectomy and intrathoracic anastomosis was carried out. Due to an intraoperative R2 situation, clip marking was performed to allow postoperative radiotherapy. Two months postoperatively, the planning CT scan for radiotherapy revealed progression of the retroperitoneal tumor mass, which was enclosing the celiac trunk, renal vein, and superior mesenteric artery. Multiple new liver and lung metastases were also found. During the following weeks, the patient developed acute renal failure and was admitted for dialysis, and the planned radiotherapy was deferred. At the end of May 2007, 4 months after the primary diagnosis, the patient died due to acute renal failure.
A Pancreatic Polypeptide-Producing Pancreatic Tumor Causing WDHA Syndrome
Authors: Amrilleva Vera , Slater Emily P. , Waldmann Jens , Bonorden Dorothee , Fendrich Volker
Published: July 2008

We report the case of a 46-year-old female patient with WDHA (watery diarrhea/hypokalemia/achlorhydria) syndrome caused by a pancreatic polypeptide-producing tumor in the head of the pancreas. Whereas VIP and other pancreatic endocrine hormones were in the normal range, only serum levels of pancreatic polypeptide were elevated. Imaging studies identified a pancreatic tumor in the head of the gland. After laparotomy, the tumor of 3 cm in size was enucleated. Final pathology documented a pancreatic endocrine tumor with immunohistochemical staining demonstrating the presence of pancreatic polypeptide. The patient remained cured after a follow-up of more than three years. The present case illustrates that, although rare, WDHA syndrome may be associated with a pancreatic polypeptide-secreting endocrine tumor of the pancreas.
Mortality and Reinfarction among Patients Using Different Beta-Blockers for Secondary Prevention after a Myocardial Infarction
Authors: Andersen Søren Skøtt , Hansen Morten Lock , Gislason Gunnar H. , Folke Fredrik , Schramm Tina Ken , Fosbøl Emil , Sørensen Rikke , Rasmussen Søren , Abildstrøm Steen Z. , Madsen Mette , Køber Lars , Torp-Pedersen Christian
Published: July 2008

Objectives: To study differences in the clinical efficacy of various brands of β-blocker in secondary prevention after a myocardial infarction (MI). Methods: All patients hospitalized with a first MI between 1995 and 2002 who were still alive 30 days after discharge and had had at least one prescription for a β-blocker filled were identified by individual-level linkage of nationwide registries of hospitalizations and drugs dispensed from pharmacies. A total of 32,259 MI patients were included in the study. Multivariable Cox proportional hazard models were used to analyze the risks of death and recurrent MI related to treatment with different β-blockers. Results: The risks for death and recurrent MI were similar in patients using different β-blockers, except that mortality from all causes among patients with a prescription for sotalol was higher. Subgroup analyses of high-risk patients with diabetes or congestive heart failure and of patients using comparable dosages of β-blockers did not show effects on the risk of death or recurrent MI. Conclusion: Except for sotalol, the different types of β-blocker had similar clinical efficacy in reducing mortality and the recurrence of MI. The equivalent efficacy remained when high-risk patients were analyzed separately.