bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Monsoon Dynamics and Climate Change
Authors: Zhisheng An , Guoxiong Wu , Jianping Li , Youbin Sun , Yimin Liu , Weijian Zhou , Yanjun Cai , Anmin Duan , Li Li , Jiangyu Mao , Hai Cheng , Zhengguo Shi , Liangcheng Tan , Hong Yan , Hong Ao , Hong Chang , Juan Feng
Published: September 2014

This article provides a comprehensive review of the global monsoon that encompasses findings from studies of both modern monsoons and paleomonsoons. We introduce a definition for the global monsoon that incorporates its three-dimensional distribution and ultimate causes, emphasizing the direct drive of seasonal pressure system changes on monsoon circulation and depicting the intensity in terms of both circulation and precipitation. We explore the global monsoon climate changes across a wide range of timescales from tectonic to intraseasonal. Common features of the global monsoon are global homogeneity, regional diversity, seasonality, quasi-periodicity, irregularity, instability, and asynchroneity. We emphasize the importance of solar insolation, Earth orbital parameters, underlying surface properties, and land-air-sea interactions for global monsoon dynamics. We discuss the primary driving force of monsoon variability on each timescale and the relationships among dynamics on multiple timescales. Natural processes and anthropogenic impacts are of great significance to the understanding of future global monsoon behavior.
Mutualistic Interactions and Biological Invasions
Authors: Traveset Anna , Richardson David M.
Published: September 2014

Mutualisms structure ecosystems and mediate their functioning. They also enhance invasions of many alien species. Invasions disrupt native mutualisms, often leading to population declines, reduced biodiversity, and altered ecosystem functioning. Focusing on three main types of mutualisms (pollination, seed dispersal, and plant-microbial symbioses) and drawing on examples from different ecosystems and from species- and community-level studies, we review the key mechanisms whereby such positive interactions mediate invasions and are in turn influenced by invasions. High interaction generalization is “the norm” in most systems, allowing alien species to infiltrate recipient communities. We identify traits that influence invasiveness (e.g., selfing capacity in plants, animal behavioral traits) or invasibility (e.g., partner choice in mycorrhizas/rhizobia) through mutualistic interactions. Mutualistic disruptions due to invasions are pervasive, and subsequent cascading effects are also widespread. Ecological networks provide a useful framework for predicting tipping points for community collapse in response to invasions and other synergistic drivers of global change.
Consensus and Contention in the Food-Versus-Fuel Debate
Authors: Rosegrant Mark W. , Msangi Siwa
Published: September 2014

This review discusses research on linkages between biofuels, agriculture, and food security. The literature indicates that biofuel expansion affects land use, puts pressure on food and feed markets, and modestly reduces greenhouse gas emissions. Researchers readily identify these outcomes, as well as the multitude of factors besides biofuels that have driven up food prices in recent years. However, precision in quantifying the extent of the impacts and in attributing effects to various drivers is elusive, resulting in a wide range of estimates. Nevertheless, the central tendency is that a food-versus-fuel trade-off is created through biofuel production from food crops, and the continued expansion of biofuel production increases food commodity prices, reduces the availability of calories, and increases malnourishment in developing countries. Higher food prices particularly reduce the poor's access to food, which has possible long-term, irreversible consequences for health, productivity, and well-being.
Implications of Arctic Sea Ice Decline for the Earth System
Authors: Bhatt Uma S. , Walker Donald A. , Walsh John E. , Carmack Eddy C. , Frey Karen E. , Meier Walter N. , Moore Sue E. , Parmentier Frans-Jan W. , Post Eric , Romanovsky Vladimir E. , Simpson William R.
Published: September 2014

Arctic sea ice decline has led to an amplification of surface warming and is projected to continue to decline from anthropogenic forcing, although the exact timing of ice-free summers is uncertain owing to large natural variability. Sea ice reductions affect surface heating patterns and the atmospheric pressure distribution, which may alter midlatitude extreme weather patterns. Increased light penetration and nutrient availability during spring from earlier ice breakup enhances primary production in the Arctic Ocean and its adjacent shelf seas. Ice-obligate marine mammals may be losers, whereas seasonally migrant species may be winners from rapid sea ice decline. Tundra greening is occurring across most of the Arctic, driven primarily by warming temperatures, and is displaying complex spatial patterns that are likely tied to other factors. Sea ice changes are affecting greenhouse gas exchanges as well as halogen chemistry in the Arctic. This review highlights the heterogeneous nature of Arctic change, which is vital for researchers to better understand.
Sports Ballistics
Authors: Clanet Christophe
Published: September 2014

This review describes and classifies the trajectories of sports projectiles that have spherical symmetry, cylindrical symmetry, or (almost) no symmetry. This classification allows us to discuss the large diversity observed in the paths of spherical balls, the flip properties of shuttlecocks, and the optimal position and stability of ski jumpers.
The Clinical Assessment of Intraventricular Flows
Authors: Bermejo Javier , Martínez-Legazpi Pablo , del Álamo Juan C.
Published: September 2014

Recent advances in imaging techniques have allowed physicians to obtain robust measurements of intracardiac flows in the clinical setting. Consequently, the physiological implications of intraventricular fluid dynamics are beginning to be understood. Initial data show that these flows involve complex fluid-structure interactions and mixing phenomena that are modified by disease. Here we critically review the most important aspects of intraventricular fluid mechanics relevant for clinical applications. We discuss current image and numerical methods for assessing intraventricular flows, as well as implemented approaches to analyze their impact on cardiac function. The physiological and clinical insights provided by such techniques are discussed both in health and in disease. The final goal is to encourage research in the application of fluid dynamic foundations to patient-based clinical data. A huge potential is anticipated not only in terms of the basic science of large-scale biological systems, but also in practical terms of improving patient care.
Transcription-Associated Mutagenesis
Authors: Jinks-Robertson Sue , Bhagwat Ashok S.
Published: September 2014

Transcription requires unwinding complementary DNA strands, generating torsional stress, and sensitizing the exposed single strands to chemical reactions and endogenous damaging agents. In addition, transcription can occur concomitantly with the other major DNA metabolic processes (replication, repair, and recombination), creating opportunities for either cooperation or conflict. Genetic modifications associated with transcription are a global issue in the small genomes of microorganisms in which noncoding sequences are rare. Transcription likewise becomes significant when one considers that most of the human genome is transcriptionally active. In this review, we focus specifically on the mutagenic consequences of transcription. Mechanisms of transcription-associated mutagenesis in microorganisms are discussed, as is the role of transcription in somatic instability of the vertebrate immune system.
Centromeric Heterochromatin: The Primordial Segregation Machine
Authors: Bloom Kerry S.
Published: September 2014

Centromeres are specialized domains of heterochromatin that provide the foundation for the kinetochore. Centromeric heterochromatin is characterized by specific histone modifications, a centromere-specific histone H3 variant (CENP-A), and the enrichment of cohesin, condensin, and topoisomerase II. Centromere DNA varies orders of magnitude in size from 125 bp (budding yeast) to several megabases (human). In metaphase, sister kinetochores on the surface of replicated chromosomes face away from each other, where they establish microtubule attachment and bi-orientation. Despite the disparity in centromere size, the distance between separated sister kinetochores is remarkably conserved (approximately 1 μm) throughout phylogeny. The centromere functions as a molecular spring that resists microtubule-based extensional forces in mitosis. This review explores the physical properties of DNA in order to understand how the molecular spring is built and how it contributes to the fidelity of chromosome segregation.
The Structure and Regulation of Flagella inBacillus subtilis
Authors: Mukherjee Sampriti , Kearns Daniel B.
Published: September 2014

Bacterial flagellar motility is among the most extensively studied physiological systems in biology, but most research has been restricted to using the highly similar Gram-negative species Escherichia coli and Salmonella enterica. Here, we review the recent advances in the study of flagellar structure and regulation of the distantly related and genetically tractable Gram-positive bacterium Bacillus subtilis. B. subtilis has a thicker layer of peptidoglycan and lacks the outer membrane of the Gram-negative bacteria; thus, not only phylogenetic separation but also differences in fundamental cell architecture contribute to deviations in flagellar structure and regulation. We speculate that a large number of flagella and the absence of a periplasm make B. subtilis a premier organism for the study of the earliest events in flagellar morphogenesis and the type III secretion system. Furthermore, B. subtilis has been instrumental in the study of heterogeneous gene transcription in subpopulations and of flagellar regulation at the translational and functional level.
Ditransitive Constructions
Authors: Haspelmath Martin
Published: September 2014

Ditransitive constructions are syntactic constructions with three arguments, an agent (A), a theme (T), and a recipient (R), which express an event of possessive transfer (‘give,’ ‘lend,’ etc.) or an event of cognitive transfer (‘tell,’ ‘show,’ etc.). Their cross-linguistic study has revealed three major alignment types: indirective alignment (with the R treated in a special way, distinct from monotransitive P), secundative alignment (with the T treated in a special way), and neutral alignment (or double-object construction). Alignments may be construction specific, that is, different in argument coding and behavioral properties. Languages sometimes exhibit alignment alternations (multiple constructions with roughly the same meaning), and they often exhibit alignment splits (different constructions under different conditions). The splits are always based on the referential prominence of the R and the T, and show more explicit formal coding for less expected scenarios. Constituent order is also typically sensitive to the topic-worthiness of the objects. Object–object primacy is often based on linear order, but may also be determined by topic-worthiness, with the R having primacy over the T. Ditransitive verbs expressing ‘give’ show a stronger tendency for neutral alignment than do others with a more spatial meaning such as ‘bring’ or ‘send.’
The Molecular Ecophysiology of Programmed Cell Death in Marine Phytoplankton
Authors: Bidle Kay D.
Published: September 2014

Planktonic, prokaryotic, and eukaryotic photoautotrophs (phytoplankton) share a diverse and ancient evolutionary history, during which time they have played key roles in regulating marine food webs, biogeochemical cycles, and Earth's climate. Because phytoplankton represent the basis of marine ecosystems, the manner in which they die critically determines the flow and fate of photosynthetically fixed organic matter (and associated elements), ultimately constraining upper-ocean biogeochemistry. Programmed cell death (PCD) and associated pathway genes, which are triggered by a variety of nutrient stressors and are employed by parasitic viruses, play an integral role in determining the cell fate of diverse photoautotrophs in the modern ocean. Indeed, these multifaceted death pathways continue to shape the success and evolutionary trajectory of diverse phytoplankton lineages at sea. Research over the past two decades has employed physiological, biochemical, and genetic techniques to provide a novel, comprehensive, mechanistic understanding of the factors controlling this key process. Here, I discuss the current understanding of the genetics, activation, and regulation of PCD pathways in marine model systems; how PCD evolved in unicellular photoautotrophs; how it mechanistically interfaces with viral infection pathways; how stress signals are sensed and transduced into cellular responses; and how novel molecular and biochemical tools are revealing the impact of PCD genes on the fate of natural phytoplankton assemblages.
Construction and Maintenance of the Ganges-Brahmaputra-Meghna Delta: Linking Process, Morphology, and Stratigraphy
Authors: Wilson Carol A. , Goodbred Steven L.
Published: September 2014

We present a review of the processes, morphology, and stratigraphy of the Ganges-Brahmaputra-Meghna delta (GBMD), including insights gained from detailed elevation data. The review shows that the GBMD is best characterized as a composite system, with different regions having morphologic and stratigraphic attributes of an upland fluvial fan delta; a lowland, backwater-reach delta; a downdrift tidal delta plain; and an offshore subaqueous-delta clinoform. These distinct areas of upland and lowland fluvial reaches and tidal dominance vary in time and space, and we distinguish late-Holocene phases of delta construction, maintenance, and decline similar to delta-lobe cycling in other systems. The overall stability of the GBMD landform, relative to many deltas, reflects the efficient, widespread dispersal of sediment by the large monsoon discharge and high-energy tides that affect this region. However, we do identify portions of the delta that are in decline and losing elevation relative to sea level owing to insufficient sediment delivery. These areas, some of which are well inland of the coast, represent those most at risk to the continued effect of sea-level rise.
Techniques for Quantifying Phytoplankton Biodiversity
Authors: Johnson Zackary I. , Martiny Adam C.
Published: September 2014

The biodiversity of phytoplankton is a core measurement of the state and activity of marine ecosystems. In the context of historical approaches, we review recent major advances in the technologies that have enabled deeper characterization of the biodiversity of phytoplankton. In particular, high-throughput sequencing of single loci/genes, genomes, and communities (metagenomics) has revealed exceptional phylogenetic and genomic diversity whose breadth is not fully constrained. Other molecular tools—such as fingerprinting, quantitative polymerase chain reaction, and fluorescence in situ hybridization—have provided additional insight into the dynamics of this diversity in the context of environmental variability. Techniques for characterizing the functional diversity of community structure through targeted or untargeted approaches based on RNA or protein have also greatly advanced. A wide range of techniques is now available for characterizing phytoplankton communities, and these tools will continue to advance through ongoing improvements in both technology and data interpretation.
Diet of Worms Emended: An Update of Polychaete Feeding Guilds
Authors: Jumars Peter A. , Dorgan Kelly M. , Lindsay Sara M.
Published: September 2014

Polychaetes are common in most marine habitats and dominate many infaunal communities. Functional guild classification based on taxonomic identity and morphology has linked community structure to ecological function. The functional guilds now include osmotrophic siboglinids as well as sipunculans, echiurans, and myzostomes, which molecular genetic analyses have placed within Annelida. Advances in understanding of encounter mechanisms explicitly relate motility to feeding mode. New analyses of burrowing mechanics explain the prevalence of bilateral symmetry and blur the boundary between surface and subsurface feeding. The dichotomy between microphagous deposit and suspension feeders and macrophagous carnivores, herbivores, and omnivores is further supported by divergent digestive strategies. Deposit feeding appears to be limited largely to worms longer than 1 cm, with juveniles and small worms in general restricted to ingesting highly digestible organic material and larger, rich food items, blurring the macrophage-microphage dichotomy that applies well to larger worms.
Intraclass Differences Among Antihypertensive Drugs
Authors: Feldman R.D. , Hussain Y. , Kuyper L.M. , McAlister F.A. , Padwal R.S. , Tobe S.W.
Published: September 2014

The four major classes of antihypertensive drugs—diuretics, β-blockers, calcium channel blockers, and renin-angiotensin system inhibitors (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers)—have significant qualitative and quantitative differences in the adverse effects they cause. Structural and chemical differences have been identified within these classes, especially among the calcium channel blockers and, to a lesser extent, among the thiazide/thiazide-like diuretics. However, it has been more difficult to demonstrate that these differences translate into differential effects with respect to either the surrogate endpoint of blood pressure reduction or, more importantly, hypertension-related cardiovascular complications. Based on a hierarchy-of-evidence approach, differences are apparent between hydrochlorothiazide and chlorthalidone based on evidence of moderate quality. Low-quality evidence suggests atenolol is less effective than other β-blockers. However, no significant intraclass differences have been established among the other classes of antihypertensive drugs.
Emotion and Decision Making
Authors: Lerner Jennifer S. , Li Ye , Valdesolo Piercarlo , Kassam Karim S.
Published: September 2014

A revolution in the science of emotion has emerged in recent decades, with the potential to create a paradigm shift in decision theories. The research reveals that emotions constitute potent, pervasive, predictable, sometimes harmful and sometimes beneficial drivers of decision making. Across different domains, important regularities appear in the mechanisms through which emotions influence judgments and choices. We organize and analyze what has been learned from the past 35 years of work on emotion and decision making. In so doing, we propose the emotion-imbued choice model, which accounts for inputs from traditional rational choice theory and from newer emotion research, synthesizing scientific models.
Polycultural Psychology
Authors: Morris Michael W. , Chiu Chi-yue , Liu Zhi
Published: September 2014

We review limitations of the traditional paradigm for cultural research and propose an alternative framework, polyculturalism. Polyculturalism assumes that individuals' relationships to cultures are not categorical but rather are partial and plural; it also assumes that cultural traditions are not independent, sui generis lineages but rather are interacting systems. Individuals take influences from multiple cultures and thereby become conduits through which cultures can affect each other. Past literatures on the influence of multiple cultural identities and cultural knowledge legacies can be better understood within a polyculturalist rubric. Likewise, the concept elucidates how cultures are changed by contact with other cultures, enabling richer psychological theories of intercultural influence. Different scientific paradigms about culture imply different ideologies and policies; polyculturalism's implied policy of interculturalism provides a valuable complement to the traditional policy frames of multiculturalism and colorblindness.
Motivation and Cognitive Control: From Behavior to Neural Mechanism
Authors: Botvinick Matthew , Braver Todd
Published: September 2014

Research on cognitive control and executive function has long recognized the relevance of motivational factors. Recently, however, the topic has come increasingly to center stage, with a surge of new studies examining the interface of motivation and cognitive control. In the present article we survey research situated at this interface, considering work from cognitive and social psychology and behavioral economics, but with a particular focus on neuroscience research. We organize existing findings into three core areas, considering them in the light of currently vying theoretical perspectives. Based on the accumulated evidence, we advocate for a view of control function that treats it as a domain of reward-based decision making. More broadly, we argue that neuroscientific evidence plays a critical role in understanding the mechanisms by which motivation and cognitive control interact. Opportunities for further cross-fertilization between behavioral and neuroscientific research are highlighted.
Perspectives on Culture and Concepts
Authors: ojalehto bethany l. , Medin Douglas L.
Published: September 2014

The well-respected tradition of research on concepts uses cross-cultural comparisons to explore which aspects of conceptual behavior are universal versus culturally variable. This work continues, but it is being supplemented by intensified efforts to study how conceptual systems and cultural systems interact to modify and support each other. For example, cultural studies within the framework of domain specificity (e.g., folkphysics, folkpsychology, folkbiology) are beginning to query the domains themselves and offer alternative organizing principles (e.g., folksociology, folkecology). Findings highlight the multifaceted nature of both concepts and culture: Individuals adopt distinct conceptual construals in accordance with culturally infused systems such as language and discourse, knowledge and beliefs, and epistemological orientations. This picture complicates questions about cognitive universality or variability, suggesting that researchers may productively adopt a systems-level approach to conceptual organization and cultural epistemologies. Related implications for diversity in cognitive science are discussed.
Action Errors, Error Management, and Learning in Organizations
Authors: Frese Michael , Keith Nina
Published: September 2014

Every organization is confronted with errors. Most errors are corrected easily, but some may lead to negative consequences. Organizations often focus on error prevention as a single strategy for dealing with errors. Our review suggests that error prevention needs to be supplemented by error management—an approach directed at effectively dealing with errors after they have occurred, with the goal of minimizing negative and maximizing positive error consequences (examples of the latter are learning and innovations). After defining errors and related concepts, we review research on error-related processes affected by error management (error detection, damage control). Empirical evidence on positive effects of error management in individuals and organizations is then discussed, along with emotional, motivational, cognitive, and behavioral pathways of these effects. Learning from errors is central, but like other positive consequences, learning occurs under certain circumstances—one being the development of a mind-set of acceptance of human error.
Physical Activity and Cognitive Vitality
Authors: Prakash Ruchika Shaurya , Voss Michelle W. , Erickson Kirk I. , Kramer Arthur F.
Published: September 2014

We examine evidence supporting the associations among physical activity (PA), cognitive vitality, neural functioning, and the moderation of these associations by genetic factors. Prospective epidemiological studies provide evidence for PA to be associated with a modest reduction in relative risk of cognitive decline. An evaluation of the PA-cognition link across the life span provides modest support for the effect of PA on preserving and even enhancing cognitive vitality and the associated neural circuitry in older adults, with the majority of benefits seen for tasks that are supported by the prefrontal cortex and the hippocampus. The literature on children and young adults, however, is in need of well-powered randomized controlled trials. Future directions include a more sophisticated understanding of the dose-response relationship, the integration of genetic and epigenetic approaches, inclusion of multimodal imaging of brain-behavior changes, and finally the design of multimodal interventions that may yield broader improvements in cognitive function.
Physiological effects and therapeutic potential of proinsulin C-peptide
Authors: Yosten Gina L. C. , Maric-Bilkan Christine , Luppi Patrizia , Wahren John
Published: September 2014

Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes.
The SK3 channel promotes placental vascularization by enhancing secretion of angiogenic factors
Authors: Rada Cara C. , Murray Grace , England Sarah K.
Published: September 2014

Proper placental perfusion is essential for fetal exchange of oxygen, nutrients, and waste with the maternal circulation. Impairment of uteroplacental vascular function can lead to pregnancy complications, including preeclampsia and intrauterine growth restriction (IUGR). Potassium channels have been recognized as regulators of vascular proliferation, angiogenesis, and secretion of vasoactive factors, and their dysfunction may underlie pregnancy-related vascular diseases. Overexpression of one channel in particular, the small-conductance calcium-activated potassium channel 3 (SK3), is known to increase vascularization in mice, and mice overexpressing the SK3 channel (SK3T/T mice) have a high rate of fetal demise and IUGR. Here, we show that overexpression of SK3 causes fetal loss through abnormal placental vascularization. We previously reported that, at pregnancy day 14, placentas isolated from SK3T/T mice are smaller than those obtained from wild-type mice. In this study, histological analysis reveals that SK3T/− placentas at this stage have abnormal placental morphology, and microcomputed tomography shows that these placentas have significantly larger and more blood vessels than those from wild-type mice. To identify the mechanism by which these vascularization defects occur, we measured levels of vascular endothelial growth factor (VEGF), placental growth factor, and the soluble form of VEGF receptor 1 (sFlt-1), which must be tightly regulated to ensure proper placental development. Our data reveal that overexpression of SK3 alters systemic and placental ratios of the angiogenic factor VEGF to antiangiogenic factor sFlt-1 throughout pregnancy. Additionally, we observe increased expression of hypoxia-inducing factor 2α in SK3T/− placentas. We conclude that the SK3 channel modulates placental vascular development and fetal health by altering VEGF signaling.
Syndrome-Specific Deficits of Performance and Effects of Practice on Arm Movements with Deafferentation due to Posterior Thalamic Lesion
Authors: Platz Thomas , Mauritz Karl-Heinz
Published: September 2014

Aiming and tapping movements were analysed repeatedly over a three-week period in a patient who was hemideafferented due to an ischaemic posterior thalamic lesion. Contrasting behaviour observed in six healthy subjects, nine hemiparetic patients and one patient with hemianopic stroke, allowed the determination of behavioural deficits related to deafferentation. Finger tapping was not impaired specifically and did not improve with practice in the deafferented patient. When aiming movements were investigated, accuracy of the first, largely preprogrammed, phase of movement and timing of the late homing-in phase were impaired specifically in the deafferented patient. Practice led to a step-like change in preprogramming amplitude of the ballistic movement component, a gradual improvement of temporal efficiency of the early movement phase and a more marked improvement of the homing-in phase. Qualitatively comparable but quantitatively less marked effects of practice were documented for hemiparetic patients. These results demonstrated that deafferentation affects preprogrammed aspects of movement and those influenced by current control and that motor learning is possible with central deafferentation, even for aspects of performance that are impaired specifically. It is postulated that motor learning was mediated by changes in strategy (motor programming) and improved efficiency of intact motor control processes (visuomotor control).
Neuropsychology and Advances in Memory Function
Authors: Gordon B.
Published: September 2014

Recent developments in the functional and neural bases of several aspects of memory are described including long term cortical memory storage, the transition from immediate to permanent memory mediated by medial temporal structures, working memory, memory retrieval, and implicit memory. These are linked to current data on the nature of anterograde and retrograde amnesia in the degenerative diseases, and also to issues in the clinical diagnosis of memory impairments. Understanding the bases of memory can inform the diagnosis of memory impairments in degenerative diseases, and the patterns of impairment seen in the degenerative diseases can help contribute to knowledge of the mechanisms of normal memory.
Memory Training for Individuals with Alzheimer’s Disease Improves Name Recall
Authors: Kesslak J. P. , Nackoul K. , Sandman C. A.
Published: September 2014

Alzheimer’s disease is clinically characterized by a variety of progressive cognitive deficits, most notably an impaired ability to acquire new information, such as name recall. Eleven demented patients and 11 controls participated in a 4 week memory program that included training in name–face recall. Individuals were taught strategies for name–face rehearsal, and administered task specific and standardized tests to assess the intervention efficacy. During the memory training patients improved recall of names and faces (p
Macrophage Derived Platelet Activating Factor Implicated in the Resolution Phase of Gouty Inflammation
Authors: Yagnik Darshna
Published: September 2014

Human blood derivedin vitrodifferentiated monocytes or macrophages are a population of cells which have been investigated over the years to determine the role these cells play in the resolution phase of gout. Macrophages are able to phagocytose monosodium urate monohydrate (MSU) crystals without releasing inflammatory factors. This study analysed macrophage platelet activating factor secretion and its possible role in the pathway of gout resolution. Analysis of sunatants fromin vitrodifferentiated macrophages stimulated with MSU crystals revealed the secretion of platelet activating factor (PAF)  1.54±0.10mean ± SEM; ng/mL per 106cells. This secretion was absent in immature monocytes treated similarly. When these monocytes were pretreated with recombinant human PAF-acetylhydrolase (rhuPAF-AH) and MSU crystals resulted in TNFαsuppression. Addition of WEB2086, a platelet activating factor (PAF) antagonist, to differentiated macrophages with MSU crystals unmasked TNFαsecretion0.7±0.06mean ± SEM; ng/mL per 106cells. This study identifies a role for PAF and the PAF receptor antagonist in the pathway by which macrophages ingest MSU crystals and resolve the concomitant inflammation.
Hermitian Positive Definite Solution of the Matrix Equation X=Q+∑i=1mAi(B+X-1)-1Ai*
Authors: Li Chun-Mei , Peng Jing-Jing
Published: September 2014

We consider the Hermitian positive definite solution of the nonlinear matrix equation X=Q+∑i=1mAi(B+X-1)-1Ai*. Some new sufficient conditions and necessary conditions for the existence of Hermitian positive definite solutions are derived. An iterative method is proposed to compute the Hermitian positive definite solution. In the end, an example is used to illustrate the correctness and application of our results.
New Cultivars Derived from Crosses between Commercial Cultivar and a Wild Population of Papaya Rescued at Its Center of Origin
Authors: Vázquez Calderón Mariela , Zavala León Manuel Jesús , Contreras Martín Fernando Amilcar , Espadas y Gil Francisco , Navarrete Yabur Abelardo , Sánchez Teyer Lorenzo Felipe , Santamaría Jorge M.
Published: September 2014

In order to generate new varieties, this study focused on the rescue and use of landraces and wild Carica papaya L. populations located at southern Yucatan, Mexico, to cross them with a commercial papaya cultivar (Maradol). In the cross L7 × M22, The native parent line L7 was used as the receiver parent while the commercial Maradol (M22) was used as the donor parent, seeking to generate genotypes with improved productivity and reduced plant height. Cluster analysis and principal components analysis grouped the genotypes firstly into those individuals with few fruits and those with many fruits and secondly into individuals with high and low plant height. Selected genotypes H13B, H17B, H19B, H68B, and H71B meet the desirable characteristics, such as reduced plant height (PH) and intermediate number of fruits per plant (NFP). These materials can be used now to produce new crosses to continue with the ongoing breeding program at CICY, seeking new varieties with higher productivity and adequate plant height, and also these genotypes will be preserved and integrated in the germplasm bank in situ and in vitro for further genetic work and possible exchange with other germplasm collections worldwide.
Body Mass Index, Physical Activity, and Serum Markers of Inflammation, Immunity, and Insulin Resistance
Authors: Kitahara Cari M. , Trabert Britton , Katki Hormuzd A. , Chaturvedi Anil K. , Kemp Troy J. , Pinto Ligia A. , Moore Steven C. , Purdue Mark P. , Wentzensen Nicolas , Hildesheim Allan , Shiels Meredith S.
Published: September 2014

Background: Epidemiologic studies examining circulating levels of inflammatory markers in relation to obesity and physical inactivity may aid in our understanding of the role of inflammation in obesity-related cancers. However, previous studies on this topic have focused on a limited set of markers.

Methods: We evaluated associations between body mass index (BMI) and vigorous physical activity level, based on self-report, and serum levels of 78 inflammation-related markers. Markers were measured using a bead-based multiplex method among 1,703 men and women, ages 55–74 years, and with no prior history of cancer at blood draw, and selected for case–control studies nested within the Prostate, Lung, Ovarian, and Colorectal Cancer Screening Trial. Analyses were adjusted for age, sex, smoking, case–control study, physical activity, and BMI.

Results: Twelve markers were positively associated with BMI after FDR correction. ORs and 95% confidence interval (CI) for highest versus lowest levels of CCL2/MCP-1, CXCL5/ENA-78, sTNFRII, CXCL10/IP-10, CXCL6/GCP2, CCL13/MCP-4, amylin, CRP, C-peptide, CCL19/MIP-3b, insulin, and leptin were: 1.50 (1.14–1.98), 1.52 (1.12–2.05), 1.61 (1.17–2.20), 1.69 (1.25–2.28), 1.74 (1.24–2.44), 1.75 (1.22–2.50), 1.91 (1.31–2.78), 2.41 (1.36–4.25), 2.78 (1.83–4.24), 3.30 (2.28–4.78), 4.05 (2.51–6.55), and 50.03 (19.87–125.99) per 5 kg/m2, respectively. Only CXCL12/SDF-1a was associated with physical activity (≥3 vs. <1 h/wk; OR, 3.28; 95% CI, 1.55–6.94) after FDR correction.

Conclusions: BMI was associated with a wide range of circulating markers involved in the inflammatory response.

Impact: This cross-sectional analysis identified serum markers could be considered in future studies aimed at understanding the underlying mechanisms linking inflammation with obesity and obesity-related cancers. Cancer Epidemiol Biomarkers Prev; 23(12); 2840–9. ©2014 AACR.
Intratumor Heterogeneity in Hepatocellular Carcinoma
Authors: Friemel Juliane , Rechsteiner Markus , Frick Lukas , Böhm Friederike , Struckmann Kirsten , Egger Michèle , Moch Holger , Heikenwalder Mathias , Weber Achim
Published: September 2014

Purpose: Morphologic intratumor heterogeneity is well known to exist in hepatocellular carcinoma (HCC), but very few systematic analyses of this phenomenon have been performed. The aim of this study was to comprehensively characterize morphologic intratumor heterogeneity in HCC. Also, taken into account were well-known immunohistochemical markers and molecular changes in liver cells that are considered in proposed classifications of liver cell neoplasms or discussed as molecular therapeutic targets.

Experimental Design: In HCC of 23 patients without medical pretreatment, a total of 120 tumor areas were defined. Analyzed were cell and tissue morphology, expression of the liver cell markers cytokeratin (CK)7, CD44, α-fetoprotein (AFP), epithelial cell adhesion molecule (EpCAM), and glutamine synthetase (GS) along with mutations of TP53 and CTNNB1, assayed by both Sanger and next-generation sequencing.

Results: Overall, intratumor heterogeneity was detectable in the majority of HCC cases (20 of 23, 87%). Heterogeneity solely on the level of morphology was found in 6 of 23 cases (26%), morphologic heterogeneity combined with immunohistochemical heterogeneity in 9 of 23 cases (39%), and heterogeneity with respect to morphologic, immunohistochemical, and mutational status of TP53 and CTNNB1 in 5 of 23 cases (22%).

Conclusions: Our findings demonstrate that intratumor heterogeneity represents a challenge for the establishment of a robust HCC classification and may contribute to treatment failure and drug resistance in many cases of HCC. Clin Cancer Res; 21(8); 1951–61. ©2014 AACR.

See related commentary by Nault and Villanueva, p. 1786
STAT3 Mediates Regorafenib-Induced Apoptosis in Hepatocellular Carcinoma
Authors: Tai Wei-Tien , Chu Pei-Yi , Shiau Chung-Wai , Chen Yao-Li , Li Yong-Shi , Hung Man-Hsin , Chen Li-Ju , Chen Pei-Lung , Su Jung-Chen , Lin Ping-Yi , Yu Hui-Chuan , Chen Kuen-Feng
Published: September 2014

Purpose: Here, we aim to investigate the molecular mechanism of regorafenib and verify the potential druggable target for the treatment of hepatocellular carcinoma (HCC).

Experimental Design: HCC cell lines (PLC5, HepG2, Hep3B, SK-Hep1, and HA59T) were used to investigate the in vitro effect of regorafenib. Phosphatase activity was analyzed in HCC cells and purified SHP-1 proteins. PLC5-bearing mice were used to test the therapeutic efficiency of 20 and 40 mg/kg/d treatment with regorafenib (n \ge 8 mice). The clinical relevance of STAT3 signaling was investigated with 142 tumor samples from different patients with HCC. Descriptive statistical analysis was used to compare the baseline characteristics of patients and the expression of p-STAT3.

Results: Regorafenib inhibited STAT3-related signaling in a dose-dependent manner and was a more potent inhibitor of STAT3 than sorafenib. Regorafenib increased SHP-1 phosphatase activity in purified SHP-1 protein directly. N-SH2 domain deletion and D61A mutants mimicking open-form SHP-1 partially abolished regorafenib-induced STAT3 inhibition and apoptosis. Importantly, a higher level of expression of STAT3 was found in patients with advanced clinical stages (P = 0.009) and poorly differentiated tumors (P = 0.035).

Conclusions: Regorafenib induced significant tumor inhibition by relieving the autoinhibited N-SH2 domain of SHP-1 directly and inhibiting p-STAT3 signals. STAT3 may be suitable as a prognostic marker of HCC development, and may be a druggable target for HCC-targeted therapy using regorafenib. Clin Cancer Res; 20(22); 5768–76. ©2014 AACR.
Pazopanib, a Novel Multitargeted Kinase Inhibitor, Shows PotentIn VitroAntitumor Activity in Gastric Cancer Cell Lines withFGFR2Amplification
Authors: Kim Seung Tae , Jang Hye-Lim , Lee Su Jin , Lee Jeeyun , Choi Yoon-La , Kim Kyoung-Mee , Cho Jeonghee , Park Se Hoon , Park Young Suk , Lim Ho Yeong , Yashiro Masakazu , Kang Won Ki , Park Joon Oh
Published: September 2014

Pazopanib is an orally bioavailable, ATP-competitive, multitargeted tyrosine kinase inhibitor mainly targeting VEGFR2 and PDGFR tyrosine kinases, but the biologic sequences of pazopanib activities beyond antiangiogenesis are poorly defined. We used a panel of 38 gastric cancer cell lines to test the efficacy of pazopanib. In a growth inhibition assay, genomic changes indicated that pazopanib had differential effects on cell growth. Treatment of the KATO-III, OCUM-2M, SNU-16, and HSC-39 gastric cancer cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 to 2.0 μmol/L, whereas the same treatment of those cell lines without FGFR2 amplification had no growth-inhibitory effects. In the ectopic FGFR2-expressing model, treatment with the indicated concentrations of pazopanib significantly inhibited cell growth and colony formation by FGFR2-expressing NIH 3T3 cells with wild-type (WT) FGFR2 and mutant FGFR2 (S252W). Pazopanib also selectively suppressed constitutive FGFR2 signaling and phosphorylation of downstream effectors. In cell-cycle analysis, FGFR2-amplified cells underwent cell-cycle arrest at the G1–S phase after pazopanib treatment, whereas there were no significant effects on cell-cycle progression in cells without FGFR2 amplification treated with pazopanib. In addition, pazopanib increased a substantial fraction of sub-G1 only in FGFR2-amplified cells. These findings show that the activation of FGFR2 signaling by amplification may be a critical mediator of cell proliferation in a small subset of gastric cancer patients and that pazopanib may provide genotype-correlated clinical benefits beyond the setting of highly vascular tumors. Mol Cancer Ther; 13(11); 2527–36. ©2014 AACR.
Eflornithine (DFMO) Prevents Progression of Pancreatic Cancer by Modulating Ornithine Decarboxylase Signaling
Authors: Mohammed Altaf , Janakiram Naveena B. , Madka Venkateshwar , Ritchie Rebekah L. , Brewer Misty , Biddick Laura , Patlolla Jagan Mohan R. , Sadeghi Michael , Lightfoot Stan , Steele Vernon E. , Rao Chinthalapally V.
Published: September 2014

Ornithine decarboxylase (ODC) is the key rate-limiting enzyme in the polyamine synthesis pathway and it is overexpressed in a variety of cancers. We found that polyamine synthesis and modulation of ODC signaling occurs at early stages of pancreatic precursor lesions and increases as the tumor progresses in Kras-activated p48Cre/+-LSL-KrasG12D/+ mice. Interest in use of the ODC inhibitor eflornithine (DFMO) as a cancer chemopreventive agent has increased in recent years since ODC was shown to be transactivated by the c-myc oncogene and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. We tested the effects of DFMO on pancreatic intraepithelial neoplasias (PanIN) and their progression to pancreatic ductal adenocarcinoma (PDAC) in genetically engineered Kras mice. The KrasG12D/+ mice fed DFMO at 0.1% and 0.2% in the diet showed a significant inhibition (P < 0.0001) of PDAC incidence compared with mice fed control diet. Pancreatic tumor weights were decreased by 31% to 43% (P < 0.03–0.001) with both doses of DFMO. DFMO at 0.1% and 0.2% caused a significant suppression (27% and 31%; P < 0.02–0.004) of PanIN 3 lesions (carcinoma in situ). DFMO-treated pancreas exhibited modulated ODC pathway components along with decreased proliferation and increased expression of p21/p27 as compared with pancreatic tissues derived from mice fed control diet. In summary, our preclinical data indicate that DFMO has potential for chemoprevention of pancreatic cancer and should be evaluated in other PDAC models and in combination with other drugs in anticipation of future clinical trials. Cancer Prev Res; 7(12); 1198–209. ©2014 AACR.
The Central Role of Renal Microcirculatory Dysfunction in the Pathogenesis of Acute Kidney Injury
Authors: Ince Can
Published: September 2014

Acute kidney injury (AKI) is a rapidly developing condition often associated with critical illness, with a high degree of morbidity and mortality, whose pathophysiology is ill understood. Recent investigations have identified the dysfunction of the renal microcirculation and its cellular and subcellular constituents as being central to the etiology of AKI. Injury is caused by inflammatory activation involving endothelial leucocyte interactions in combination with dysregulation of the homeostatis between oxygen, nitric oxide, and reactive oxygen species. Effective therapies expected to resolve AKI will have to control inflammation and restore this homeostasis. In order to apply and guide these therapies effectively, diagnostic tools aimed at physiological biomarkers of AKI for monitoring renal microcirculatory function in advance of changes in pharmacological biomarkers associated with structural damage of the kidney will need to be developed.
Intestinal Microbiota-Kidney Cross Talk in Acute Kidney Injury and Chronic Kidney Disease
Authors: Noel Sanjeev , Martina-Lingua Maria N. , Bandapalle Samatha , Pluznick Jennifer , Hamad Abdel Rahim A. , Peterson Daniel A. , Rabb Hamid
Published: September 2014

The pathophysiology of acute kidney injury (AKI) involves multiple and overlapping immunological, biochemical, and hemodynamic mechanisms that modulate the effects of both the initial insult and the subsequent repair. Limited but recent experimental data have revealed that the intestinal microbiota significantly affects outcomes in AKI. Additional evidence shows significant changes in the intestinal microbiota in chronic kidney disease patients and in experimental AKI. In this minireview, we discuss the current status of the effect of intestinal microbiota on kidney diseases, the immunomodulatory effects of intestinal microbiota, and the potential mechanisms by which microbiota can modify kidney diseases and vice versa. We also propose future studies to clarify the role of intestinal microbiota in kidney diseases and to explore how the modification of gut microbiota may be a potential therapeutic tool.