bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hallucinations in Neurodegenerative Diseases
Authors: Burghaus Lothar , Eggers Carsten , Timmermann Lars , Fink Gereon R. , Diederich Nico J. 
Published: February 2011

SUMMARYPatients with neurodegenerative disease frequently experience hallucinations and illusionary perceptions. As early symptoms, hallucinations may even have diagnostic relevance (i.e., for the diagnosis of Lewy Body Dementia). In the later course of the disease, hallucinations may appear as characteristic symptoms and often constitute a particular challenge for therapeutic endeavors. Here, the distinction of disease‐inherent hallucinations from medication‐associated perceptual disturbances is particularly relevant. Synucleinopathies and tauopathies have different risk profiles for hallucinations. In synucleinopathies hallucinations are much more frequent and phenomenology is characterized by visual, short‐lived hallucinations, with insight preserved for a long time. A “double hit” theory proposes that dysfunctionality of both associative visual areas and changes of limbic areas or the ventral striatum are required. In contrast, in tauopathies the hallucinations are more rare and mostly embedded in confusional states with agitation and with poorly defined or rapidly changing paranoia. The occurrence of hallucinations has even been proposed as an exclusion criterion for tauopathies with Parkinsonian features such as progressive supranuclear palsy. To date, treatment remains largely empirical, except the use of clozapine and cholinesterase inhibitors in synucleinopathies, which is evidence‐based. The risk of increased neuroleptic sensitivity further restricts the treatment options in patients with Lewy Body Dementia. Coping Strategies and improvement of visual acuity and sleep quality may be useful therapeutic complements.
Anticholinergics for Overactive Bladder Therapy: Central Nervous System Effects
Authors: Chancellor Michael , Boone Timothy 
Published: February 2011

SUMMARYThe mainstay of pharmacological treatment of overactive bladder (OAB) is anticholinergic therapy using muscarinic receptor antagonists (tertiary or quaternary amines). Muscarinic receptors in the brain play an important role in cognitive function, and there is growing awareness that antimuscarinic OAB drugs may have adverse central nervous system (CNS) effects, ranging from headache to cognitive impairment and episodes of psychosis. This review discusses the physicochemical and pharmacokinetic properties of OAB antimuscarinics that affect their propensity to cause adverse CNS effects, as observed in phase III clinical trials and in specific investigations on cognitive function and sleep architecture. PubMed/MEDLINE was searched for “OAB” plus “muscarinic antagonists” or “anticholinergic drug.” Additional relevant literature was identified by examining the reference lists of papers identified through the search. Preclinical and clinical trials in adults were assessed, focusing on the OAB antimuscarinics approved in the United States. The blood–brain barrier (BBB) plays a key role in protecting the CNS, but it is penetrable. The lipophilic tertiary amines, particularly oxybutynin, are more likely to cross the BBB than the hydrophilic quaternary amine trospium chloride, for which there are very few reports of adverse CNS effects. In fact, in 2008 the US product labels for oral oxybutynin were modified to include the potential for anticholinergic CNS events and a warning to monitor patients for adverse CNS effects. Even modest cognitive impairment in the elderly may negatively affect independence; therefore, selection of an antimuscarinic OAB drug with reduced potential for CNS effects is advisable.
53Mn‐53Cr ages of Kaidun carbonates
Authors: PETITAT M. , MARROCCHI Y. , McKEEGAN K. D. , MOSTEFAOUI S. , MEIBOM A. , ZOLENSKY M. E. , GOUNELLE M. 
Published: February 2011

Abstract– We report the 53Mn‐53Cr systematics of three dolomite grains from two different CI1 clasts contained within the Kaidun meteorite breccia. Three internal isochrones result in initial 53Mn/55Mn ratios of (4.2 ± 0.4) × 10−6, (4.6 ± 1.3) × 10−6, and (5.2 ± 1.1) × 10−6. These initial values are consistent with those measured for dolomite in the Orgueil CI1 chondrite (Hoppe et al. 2007; Petitat et al. 2009) but significantly lower than the initial ratio determined by Hutcheon et al. (1999) from a combination of different carbonate types within various lithologies of the Kaidun meteorite. We construct an accretion scenario for the Kaidun breccia by comparing the mineralogy and formation time scales of carbonates in the Kaidun CI1 lithologies to the analogous ones of the CI1 chondrite Orgueil. In Orgueil, dolomite precipitation precedes the formation of the first bruennerite grains by a few million years (Hoppe et al. 2007; Petitat et al. 2009). As the CI1 clasts in Kaidun lack breunnerite grains, and considering that aqueous alteration occurred prior to reaccretion of the various clasts onto the Kaidun parent body (e.g., MacPherson et al. 2009), we hypothesize that after rapid accretion and early aqueous alteration occurring within the first approximately 4 Myr after solar system formation, impact disruption of several asteroids and their reassembly into the Kaidun parent asteroid was complete within an additional approximately 2 Myr. This confirms that aqueous alteration, impact, and reaccretion of material in the asteroid belt were early processes that began contemporaneously with chondrule formation.
Opportunity and Means: Horizontal Gene Transfer from the Human Host to a Bacterial Pathogen
Authors: Anderson Mark T. , Seifert H. Steven 
Published: February 2011

ABSTRACT

The acquisition and incorporation of genetic material between nonmating species, or horizontal gene transfer (HGT), has been frequently described for phylogenetically related organisms, but far less evidence exists for HGT between highly divergent organisms. Here we report the identification and characterization of a horizontally transferred fragment of the human long interspersed nuclear element L1 to the genome of the strictly human pathogen
Neisseria gonorrhoeae
. A 685-bp sequence exhibiting 98 to 100% identity to copies of the human L1 element was identified adjacent to the
irg4
gene in some
N. gonorrhoeae
genomes. The L1 fragment was observed in ~11% of the
N. gonorrhoeae
population sampled but was not detected in
Neisseria meningitidis
or commensal
Neisseria
isolates. In addition,
N. gonorrhoeae
transcripts containing the L1 sequence were detected by reverse transcription-PCR, indicating that an L1-derived gene product may be produced. The high degree of identity between human and gonococcal L1 sequences, together with the absence of L1 sequences from related
Neisseria
species, indicates that this HGT event occurred relatively recently in evolutionary history. The identification of L1 sequences in
N. gonorrhoeae
demonstrates that HGT can occur between a mammalian host and a resident bacterium, which has important implications for the coevolution of both humans and their associated microorganisms.

IMPORTANCE
The interactions between microbes and their hosts are relevant to several aspects of biology, including evolution, development, immunity, and disease.
Neisseria gonorrhoeae
serves as a particularly informative model for this interaction because it has exclusively coevolved with humans and is not known to be found in any other environment. In addition, investigation of the evolutionary relationship between
N. gonorrhoeae
and humans has practical implications, since gonorrhea is a prevalent sexually transmitted infection worldwide. This study was undertaken to characterize the horizontal transfer of genetic information from humans to
N. gonorrhoeae
, an event that has been scarcely recognized between any mammalian host and bacterial pathogen. Here we provide evidence that this genetic exchange was the result of a recent evolutionary event that has been propagated within the gonococcal population.
Enhanced Mucosal Immune Responses to HIV Virus-Like Particles Containing a Membrane-Anchored Adjuvant
Authors: Vassilieva Elena V. , Wang Bao-Zhong , Vzorov Andrei N. , Wang Li , Wang Ying-Chun , Bozja Jadranka , Xu Rui , Compans Richard W. 
Published: February 2011

ABSTRACT
Previously, a modified HIV Env protein with a heterologous membrane anchor was found to be incorporated into HIV virus-like particles (VLPs) at 10-fold-higher levels than those of unmodified Env. To further improve the immunogenicity of such VLPs, membrane-anchored forms of bacterial flagellin (FliC) or a flagellin with a truncated variable region (tFliC) were constructed to be incorporated into the VLPs as adjuvants. HIV-specific immune responses induced by the resulting VLPs were determined in a guinea pig model. The VLPs induce enhanced systemic antibody responses by either systemic or mucosal vaccination and enhanced mucosal immunity by a mucosal immunization route, as demonstrated by high levels of HIV-specific serum IgG and mucosal IgG and IgA. The quality of the antibody responses was also improved, as shown by enhanced neutralization capacity. VLPs incorporating FliC were more effective in inducing systemic responses, while VLPs containing tFliC were more effective in inducing mucosal IgA responses. The IgG titers in sera were found to last for at least 5 months without a significant drop. These results indicate that HIV VLPs incorporating high levels of Env and a molecular adjuvant have excellent potential for further development as a prophylactic HIV vaccine.

IMPORTANCE
A prophylactic vaccine is urgently needed to control the spread of HIV/AIDS. Antigens inducing strong systemic and mucosal immune responses are promising as vaccines for this mucosally transmitted disease. We found that novel HIV virus-like particles (VLPs) presenting a high level of Env in its native membrane-bound form and coincorporating an innate immune-signaling adjuvant in the same particles were effective in inducing enhanced systemic and mucosal immunity. As new HIV vaccine candidates, these VLPs bridge the gaps of the innate and adaptive, as well as systemic and mucosal, immune responses, providing a new approach for HIV vaccine development.
Streptolysin O Inhibits Clathrin-Dependent Internalization of Group A
Streptococcus
Authors: Logsdon Lauren K. , Håkansson Anders P. , Cortés Guadalupe , Wessels Michael R. 
Published: February 2011

ABSTRACT

Group A
Streptococcus
(GAS) can be internalized by epithelial cells, including keratinocytes from human skin or pharyngeal epithelium. Internalization of GAS by epithelial cells has been postulated both to play a role in host defense and to provide a sanctuary site for GAS survival. The cholesterol-binding cytolysin streptolysin O (SLO) appears to enhance virulence in part by inhibiting GAS internalization by human keratinocytes and by disrupting the lysosomal degradation of internalized GAS. We now report that low-level production of SLO by an inducible expression system reduced GAS internalization by keratinocytes. Induced SLO expression also prevented lysosomal colocalization with intracellular bacteria and acidification of GAS-containing vacuoles. Exogenous recombinant SLO mimicked the inhibitory effect of SLO secretion on GAS entry but not that on colocalization with the lysosomal marker LAMP-1, implying that disruption of lysosomal degradation requires intracellular secretion of SLO. The internalization of SLO-negative GAS was blocked by the depletion of host cell cholesterol and by the inhibition or knocking down of the expression of clathrin or dynamin. SLO also inhibited the cellular uptake of other cargos that are internalized by clathrin-mediated uptake or by macropinocytosis. We conclude that SLO interferes with the internalization of GAS through local perturbation of the keratinocyte cell membrane and disruption of a clathrin-dependent uptake pathway.

IMPORTANCE
Streptolysin O (SLO) is a member of a family of pore-forming toxins, the cholesterol-dependent cytolysins, that are produced by many Gram-positive bacterial pathogens. While SLO can lyse host cells at high doses, much smaller amounts appear to contribute to pathogenesis by inhibiting the internalization of group A
Streptococcus
(GAS) by pharyngeal keratinocytes and by preventing efficient intracellular killing by lysosomal fusion. This study provides evidence that SLO blocks a clathrin-dependent pathway for the internalization of GAS through effects on the cell surface, whereas inhibition of lysosomal fusion depends on the intracellular production of SLO. These observations may have broader implications for understanding the pathogenesis of multiple bacterial species that produce cholesterol-dependent cytolysins.
The role of geoarchaeology in extending our perspective
Authors: Wilson Lucy 
Published: February 2011

Abstract
Specialists and the general public alike are very aware of human impacts on our environment. Climate change, deforestation, desertification, soil erosion and other topics are currently much in the news, but human influence on the environment is not a new phenomenon. Geoarchaeologists study the traces of human interactions with the geosphere dating back to ancient times, as well as up to and in the present. Geoarchaeological investigations provide the key to recognizing landscape and environmental change within a region, as well as reconstructing ancient landscapes and palaeoclimatic regimes. Such an interdisciplinary approach makes it possible to interpret the ways that humans affect the geosphere, through such things as subsistence and resource exploitation activities, settlement location, and local and regional land-use patterns. This approach also allows us to determine the effects of environmental change on human societies. For millennia, humans have been coping with, or provoking, environmental change. We have exploited, extracted, over-used but also in many cases nurtured the resources that the geosphere offers. In the geoarchaeological perspective, human life has never been separate from nature. Geoarchaeology can thus provide a more inclusive and longer-term view of human–geosphere interactions, and serve as a valuable aid to those who try to determine sustainable policies for the future.
Reconstruction of the fire history in the
Siedlungskammer
Burgweinting (Bavaria, Germany) in relation to settlement and environmental history
Authors: Raab A. , Brützke W. , Christophel D. , Völkel J. , Raab T. 
Published: February 2011

Abstract

Palaeoenvironmental investigations were carried out in the
Siedlungskammer
(prehistoric settlement area) Burgweinting (Regensburg, Bavaria, Germany) to reveal past settlement conditions and human impact on the environment. Two sequences were obtained from the Islinger Mühlbach Fen, in close proximity to the archaeological excavation site in Burgweinting, which documents an almost continuous settlement history since the Neolithic Period. The analyses of the sequences comprise stratigraphic, geochemical and microscopic charcoal analyses. For chronological information, radiocarbon dating was conducted on a total of 10 samples. Thus, the first long-term fire record was reconstructed for the investigation area, and the results were correlated, based on radiocarbon dating, with the available environmental information and settlement history in the
Siedlungskammer
Burgweinting. The fire record reveals an almost continuous, but alternating fire history. Furthermore, it shows that fire played an important role in the
Siedlungskammer
Burgweinting and that most probably as early as the Mesolithic hunterer–gatherers deliberately used fire.
Holocene land use in western Sicily: a geoarchaeological perspective
Authors: Heinzel Chad , Kolb Michael 
Published: February 2011

Abstract
Geoarchaeological research within Sicily continues to characterize the effects of anthropogenic and geological processes upon the island's Holocene alluvial landscape developments. Interdisciplinary approaches have been used including geomorphological mapping, archaeological survey and excavations to characterize land-use practices though the mid- to late Holocene. Landscape development changes are recorded in the alluvial sediments as a consequence of land use by the indigenous and Roman settlers of Sicilian valleys in the Nebrodi and Polizzo Mountains. A marked change in erosion has been identified during the late Roman occupation of Sicily, probably as a product of intensive pastoralism and land clearing. Sedimentation during indigenous hilltop occupation of north–central and western Sicily was dominated by coarse-grained (cobble or boulder) deposits attributed to flash-flooding. Sedimentation that temporally coincided with the Greek and later Roman occupation of the adjacent valleys is marked by fine-grained deposits. These data continue to support the geological and archaeological interpretations of human–landscape interactions in Sicily. Furthermore, such geoarchaeological data may be used in models to strengthen our present and future landscape conservation methods.
Alluvial stratigraphy and geoarchaeology in the Big Fork River Valley, Minnesota: human response to Late Holocene environmental change
Authors: Hill Christopher L. , Rapp George , Jing Zhichun 
Published: February 2011

Abstract

The Late Quaternary geomorphology and stratigraphy of the Big Fork River valley, within the Rainy River basin of northern Minnesota, reveals evidence of prehistoric human interaction with late Holocene riverine environments. By 11 000
14
C BP, deglaciation made the region inhabitable by human groups using Clovis artefacts. Human habitation would also have been possible during the Moorhead low-water stage of glacial Lake Agassiz, starting at 10 500
14
C BP. Near its confluence with the Rainy River, the valley floor of the Big Fork valley consists of a floodplain complex and two terraces. The multi-component stratified Hannaford site is situated within the active floodplain. Overbank deposits contain artefacts in primary context, whereas artefacts within the point bar deposits are in secondary archaeological context; these deposits are associated with changing alluvial settings as the river moved eastward. Aggradation of the valley fill beneath the lowest surface (T
0
, floodplain complex) began by 3000 years ago and is associated with human activities focused on seasonal fishing and the use of riparian resources from 1300 to 650
14
C BP.
Convergence of Paths for Perturbed Maximal Monotone Mappings in Hilbert Spaces
Authors: Qing Yuan , Qin Xiaolong , Zhou Haiyun , Kang ShinMin 
Published: February 2011

AbstractLet "Equation missing" be a Hilbert space and "Equation missing" a nonempty closed convex subset of "Equation missing". Let "Equation missing" be a maximal monotone mapping and "Equation missing" a bounded demicontinuous strong pseudocontraction. Let "Equation missing" be the unique solution to the equation "Equation missing". Then"Equation missing" is bounded if and only if "Equation missing" converges strongly to a zero point of A as "Equation missing" which is the unique solution in "Equation missing", where "Equation missing" denotes the zero set of "Equation missing", to the following variational inequality "Equation missing", for all "Equation missing".
Cooperation between Pik3ca and p53 Mutations in Mouse Mammary Tumor Formation
Authors: Adams Jessica R. , Xu Keli , Liu Jeff C. , Agamez Natalia M. Ruiz , Loch Amanda J. , Wong Ruth G. , Wang Wei , Wright Katherine L. , Lane Timothy F. , Zacksenhaus Eldad , Egan Sean E. 
Published: February 2011

Abstract
PIK3CA, which codes for the p110α catalytic subunit of phosphatidylinositol 3-kinase, is one of the most frequently mutated genes in human breast cancer. Here, we describe a mouse model for PIK3CA-induced breast cancer by using the ROSA26 (R26) knock-in system, in which targeted Pik3ca alleles can be activated through transgenic expression of Cre recombinase. We mated Pik3caH1047R and Pik3cawt knock-in lines with MMTV-Cre transgenics, which express Cre in mammary epithelium. Starting at approximately 5 months of age, female R26-Pik3caH1047R;MMTV-Cre mice, but not control R26-Pik3cawt;MMTV-Cre mice, developed mammary tumors, as well as lymphoid and skin malignancies. R26-Pik3caH1047R;MMTV-Cre mammary tumors were typically either adenosquamous carcinoma or adenomyoepithelioma. As p53 is the most commonly mutated gene in breast cancer, we tested for genetic interaction between Pik3caH1047R and p53 loss-of-function mutations in R26-Pik3caH1047R;p53loxP/+;MMTV-Cre mice. This led to decreased survival of double-mutant animals, which developed lymphoma and mammary tumors with rapid kinetics. Mammary tumors that formed in p53loxP/+;MMTV-Cre conditional mutants were either poorly differentiated adenocarcinoma or spindle cell/EMT, whereas R26-Pik3caH1047R;p53loxP/+;MMTV-Cre mammary tumors were mostly adenosquamous carcinoma or spindle cell/EMT indicating that double-mutant mice develop a distinct spectrum of mammary tumors. Thus, an oncogenic variant of PIK3CA implicated in multiple human breast cancer subtypes can induce a very diverse spectrum of mammary tumors in mice. Furthermore, Pik3caH1047R shows cooperation with p53, which altered the specific tumors that formed. Thus, the two most frequently mutated genes in human breast cancer show cooperation in mammary tumor formation. Cancer Res; 71(7); 2706–17. ©2011 AACR.
ICER Evokes Dusp1-p38 Pathway Enhancing Chemotherapy Sensitivity in Myeloid Leukemia
Authors: Pigazzi Martina , Manara Elena , Beghin Alessandra , Baron Emma , Tregnago Claudia , Basso Giuseppe 
Published: February 2011

Abstract
Purpose: The inducible cyclic adenosine monophosphate (cAMP) early repressor (ICER) is found downregulated in acute myeloid leukemia (AML), failing to control cAMP response element binding protein (CREB) transcriptional activity, recently demonstrated to mediate AML progression. We aimed to characterize ICER's role in drug sensitivity by treating myeloid cell lines and primary AML with chemotherapics.
Experimental design: The effects on CREB target genes induced by ICER restoration and drug treatment were studied by quantitative real-time PCR (qRT-PCR) and western blot. Cell cycle and apoptosis analysis were performed. Possible ICER-evoked pathways were investigated in vitro. The mechanism involved in enhanced drug sensitivity was described in primary AML cultures by silencing ICER main target genes.
Results: AML cell lines reduced cell growth and enhanced apoptotic behavior after chemotherapy treatment if ICER was expressed. A significantly lowered expression of CREB target genes involved in cell cycle control (CyA1, B1, D1), and in the mitogen-activated protein kinase signaling pathway (ERK, AKT, DUSP1/4), was found after Etoposide treatment. The dual-specificity phosphatases DUSP1 and DUSP4, directly repressed by ICER, activated the p38 pathway, which triggered enhanced caspase-dependent apoptosis. The silencing of DUSP1/4 in HL60 confirmed the same enhanced drug sensitivity induced by ICER. Primary AML cultures, silenced for DUSP1 as well as restored of ICER expression, showed DUSP1 downregulation and p38 activation.
Conclusion: ICER mediates chemotherapy anticancer activity through DUSP1-p38 pathway activation and drives the cell program from survival to apoptosis. ICER restoration or DUSP1 inhibition might be possible strategies to sensitize AML cancer cells to conventional chemotherapy and to inhibit tumor growth. Clin Cancer Res; 17(4); 742–52. ©2011 AACR.