bluuebunny/crossref_metadata_2025 huggingface dataset:
On Two Novel Parameters for Validation of Predictive QSAR Models
Authors: Pratim Roy Partha , Paul Somnath , Mitra Indrani , Roy Kunal
Published: April 2009

Validation is a crucial aspect of quantitative structure–activity relationship (QSAR) modeling. The present paper shows that traditionally used validation parameters (leave-one-out Q2 for internal validation and predictive R2 for external validation) may be supplemented with two novel parameters rm2 and Rp2 for a stricter test of validation. The parameter rm2(overall) penalizes a model for large differences between observed and predicted values of the compounds of the whole set (considering both training and test sets) while the parameter Rp2 penalizes model R2 for large differences between determination coefficient of nonrandom model and square of mean correlation coefficient of random models in case of a randomization test. Two other variants of rm2 parameter, rm2(LOO) and rm2(test), penalize a model more strictly than Q2 and R2pred respectively. Three different data sets of moderate to large size have been used to develop multiple models in order to indicate the suitability of the novel parameters in QSAR studies. The results show that in many cases the developed models could satisfy the requirements of conventional parameters (Q2 and R2pred) but fail to achieve the required values for the novel parameters rm2 and Rp2. Moreover, these parameters also help in identifying the best models from among a set of comparable models. Thus, a test for these two parameters is suggested to be a more stringent requirement than the traditional validation parameters to decide acceptability of a predictive QSAR model, especially when a regulatory decision is involved.
Chemical Compositions and Antibacterial Activities of the Essential Oils from Aerial Parts and Corollas of Origanum acutidens (Hand.-Mazz.) Ietswaart, an Endemic Species to Turkey
Authors: Cosge Belgin , Turker Arzu , Ipek Arif , Gurbuz Bilal
Published: April 2009

Essential oils extracted by hydrodistillation from the aerial parts and corollas of Origanum acutidens (Hand.-Mazz.) Ietswaart, an endemic Turkish flora species, were analyzed by GC-MS. The amounts of essential oil obtained from the aerial parts and the corollas were 0.73% and 0.93%, respectively. Twenty-five components in both the aerial parts oil and the corolla oil, representing 95.11% and 93.88%, respectively, were identified. The aerial parts and corolla oils were characterized by the predominance of two components: p-cymene (9.43% and 17.51%) and carvacrol (67.51% and 52.33%), respectively. The essential oils were also evaluated for their antimicrobial activity against ten bacteria by the disc diffusion assay. Our findings showed the following order in the sensitivity to the essential oils, as indicated by the corresponding inhibition zones: Proteus vulgaris > Salmonella typhimurium > Enterobacter cloacae > Klebsiella pneumonia > Escherichia coli > Serratia marcescens > Pseudomonas aeruginosa for the aerial parts essential oil, and Salmonella typhimurium > Proteus vulgaris > Enterobacter cloacae > Escherichia coli > Klebsiella pneumoniae > Serratia marcescens > Pseudomonas aeruginosa for the corolla essential oil. The studied essential oils thus exhibited a broad-spectrum of activity against both Gram-positive and Gram-negative bacteria, whereas the tested Gram-positive bacteria were more susceptible to the essential oil samples.
A Combination Vaccine for Allergy and Rhinovirus Infections Based on Rhinovirus-Derived Surface Protein VP1 and a Nonallergenic Peptide of the Major Timothy Grass Pollen Allergen Phl p 1
Authors: Edlmayr Johanna , Niespodziana Katarzyna , Linhart Birgit , Focke-Tejkl Margarete , Westritschnig Kerstin , Scheiblhofer Sandra , Stoecklinger Angelika , Kneidinger Michael , Valent Peter , Campana Raffaela , Thalhamer Josef , Popow-Kraupp Theresia , Valenta Rudolf
Published: May 2009

Allergens and rhinovirus infections are among the most common elicitors of respiratory diseases. We report the construction of a recombinant combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived VP1, the surface protein which is critically involved in infection of respiratory cells, and a nonallergenic peptide of the major grass pollen allergen Phl p 1. Recombinant hybrid molecules consisting of VP1 and a Phl p 1-derived peptide of 31 aa were expressed in Escherichia coli. The hybrid molecules did not react with IgE Abs from grass pollen allergic patients and lacked allergenic activity when exposed to basophils from allergic patients. Upon immunization of mice and rabbits, the hybrids did not sensitize against Phl p 1 but induced protective IgG Abs that cross-reacted with group 1 allergens from different grass species and blocked allergic patients’ IgE reactivity to Phl p 1 as well as Phl p 1-induced basophil degranulation. Moreover, hybrid-induced IgG Abs inhibited rhinovirus infection of cultured human epithelial cells. The principle of fusing nonallergenic allergen-derived peptides onto viral carrier proteins may be used for the engineering of safe allergy vaccines which also protect against viral infections.
Expression Hierarchy of T Cell Epitopes from Melanoma Differentiation Antigens: Unexpected High Level Presentation of Tyrosinase-HLA-A2 Complexes Revealed by Peptide-Specific, MHC-Restricted, TCR-Like Antibodies
Authors: Michaeli Yael , Denkberg Galit , Sinik Keren , Lantzy Liz , Chih-Sheng Chiang , Beauverd Celine , Ziv Tamar , Romero Pedro , Reiter Yoram
Published: May 2009

Peptide Ags presented by class I MHC molecules on human melanomas and that are recognized by CD8+ T cells are the subjects of many studies of antitumor immunity and represent attractive candidates for therapeutic approaches. However, no direct quantitative measurements exist to reveal their expression hierarchy on the cell surface. Using novel recombinant Abs which bind these Ags with a peptide-specific, MHC-restricted manner, we demonstrate a defined pattern of expression hierarchy of peptide-HLA-A2 complexes derived from three major differentiation Ags: gp100, Melan-A/Mart-1, and tyrosinase. Studying melanoma cell lines derived from multiple patients, we reveal a surprisingly high level of presentation of tyrosinase-derived complexes and moderate to very low expression of complexes derived from other Ags. No correlation between Ag presentation and mRNA expression was found; however, protein stability may play a major role. These results provide new insights into the characteristics of Ag presentation and are particularly important when such targets are being considered for immunotherapy. These results may shed new light on relationships between Ag presentation and immune response to cancer Ags.
Hematopoietic Progenitor Kinase 1 Is a Negative Regulator of Dendritic Cell Activation
Authors: Alzabin Saba , Bhardwaj Nina , Kiefer Friedemann , Sawasdikosol Sansana , Burakoff Steven
Published: May 2009

Hematopoietic progenitor kinase 1 (HPK1) is a hematopoietic cell-restricted member of the Ste20 kinases that acts as a negative regulator of T cell functions through the AP-1, NFAT, and NFκB pathways. Using HPK1-deficient (HPK1−/−) mice, we report in this study a novel role for HPK1 in dendritic cells (DCs). Specifically, we observed that matured HPK1−/− bone marrow-derived DCs (BMDCs) are superior to their wild-type (WT) counterpart in stimulating T cell proliferation in vivo and in vitro. Several characteristics of HPK1−/− BMDCs may account for this enhanced activity: Matured HPK1−/− BMDCs express higher levels of costimulatory molecules CD80, CD86, and I-Ab as well as produce more proinflammatory cytokines IL-12, IL-1β, TNF-α, and IL-6 than their WT littermates. The role of HPK1 as a proapoptotic molecule was assessed post activation with LPS, and results indicated that HPK1−/− BMDCs are significantly resistant to LPS-induced apoptosis. Our results led us to investigate the role of HPK1−/− BMDCs in tumor immunotherapy. Using a s.c. murine model of Lewis Lung Carcinoma, we found that HPK1−/− BMDCs eliminate established s.c. Lewis Lung Carcinoma more efficiently than their WT counterpart. Our data reveal a novel role for HPK1 as a negative regulator of DC functions, identifying its potential as a molecular target for DC-based immunotherapy against cancers.
A Major Lipid Raft Protein Raftlin Modulates T Cell Receptor Signaling and Enhances Th17-Mediated Autoimmune Responses
Authors: Saeki Kazuko , Fukuyama Satoru , Ayada Toranoshin , Nakaya Mako , Aki Daisuke , Takaesu Giichi , Hanada Toshikatsu , Matsumura Yumiko , Kobayashi Takashi , Nakagawa Ryusuke , Yoshimura Akihiko
Published: May 2009

The membrane microdomains known as lipid rafts have been shown to act as platforms for the initiation of various receptor signals. Through proteomic analysis, we have identified a novel protein termed Raftlin (raft-linking protein) as a major protein in lipid rafts. To determine the physiological and immunological functions of Raftlin in mammals, we generated Raftlin-deficient mice, as well as Raftlin-transgenic (Tg) mice. Although Raftlin was originally identified in B cells, we observe no severe abnormalities in the B cells of these mice, presumably due to a high expression of Raftlin-homologue (Raftlin-2). T cells, in contrast, expressed a substantial amount of Raftlin but no Raftlin-2. In Raftlin-deficient mice, T cell-dependent Ab production was reduced, and experimental autoimmune encephalomyelitis, a Th17-dependent autoimmune disease model, was ameliorated. In Raftlin-Tg mice, in contrast, Ab production was enhanced and experimental autoimmune encephalomyelitis was more severe. Cytokine production, especially that of IL-17, was reduced in Raftlin-deficient T cells, while it was enhanced in Raftlin-Tg T cells. We found that these changes were associated with the strength of the TCR-mediated signals. Importantly, localization of Lck protein in the lipid rafts was enhanced by Raftlin overexpression and reduced by Raftlin deficiency. These data indicate that Raftlin modulates TCR signals and is necessary for the fine-tuning of T cell-mediated immune responses.
Cutting Edge: Natalizumab Blocks Adhesion but Not Initial Contact of Human T Cells to the Blood-Brain Barrier In Vivo in an Animal Model of Multiple Sclerosis
Authors: Coisne Caroline , Mao Wenxian , Engelhardt Britta
Published: May 2009

The humanized anti-α4 integrin Ab Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis. Natalizumab is thought to exert its therapeutic efficacy by blocking the α4 integrin-mediated binding of circulating immune cells to the blood-brain barrier (BBB). As α4 integrins control other immunological processes, natalizumab may, however, execute its beneficial effects elsewhere. By means of intravital microscopy we demonstrate that natalizumab specifically inhibits the firm adhesion but not the rolling or capture of human T cells on the inflamed BBB in mice with acute experimental autoimmune encephalomyelitis (EAE). The efficiency of natalizumab to block T cell adhesion to the inflamed BBB was found to be more effective in EAE than in acute systemic TNF-α-induced inflammation. Our data demonstrate that α4 integrin-mediated adhesion of human T cells to the inflamed BBB during EAE is efficiently blocked by natalizumab and thus provide the first direct in vivo proof of concept of this therapy in multiple sclerosis.
Critical Roles of NK and CD8+ T Cells in Central Nervous System Listeriosis
Authors: Hayashi Toshiyuki , Nagai Shigenori , Fujii Hideki , Baba Yukiko , Ikeda Eiji , Kawase Takeshi , Koyasu Shigeo
Published: May 2009

Listeria monocytogenes (LM) causes a life-threatening infectious disease affecting the brain of humans and domestic animals. Unfortunately, no adequate murine models for CNS listeriosis exist. Using intraparenchymal injection, we have established a new murine model for CNS listeriosis. Injection of a small volume of bacterial suspension limits the bacteria to the brain parenchyma with no leakage into the ventricular system. This new method enabled us to investigate the progression of and recovery from listerial brain infection, revealing roles for both innate and adaptive immune cells in CNS listeriosis. In the early phase of CNS listeriosis, NK cell-derived IFN-γ is a critical cytokine in the limitation of bacterial growth by the host defense. During the later phase, CD8+ but not CD4+ T cells play a critical role and LM-specific CD8+ T cells kill LM-infected microglia. Thus, innate and adaptive immune responses combine to successfully eliminate bacteria from the brain.
IL4Rα+ Myeloid-Derived Suppressor Cell Expansion in Cancer Patients
Authors: Mandruzzato Susanna , Solito Samantha , Falisi Erika , Francescato Samuela , Chiarion-Sileni Vanna , Mocellin Simone , Zanon Antonio , Rossi Carlo R. , Nitti Donato , Bronte Vincenzo , Zanovello Paola
Published: May 2009

Myeloid-derived suppressor cells (MDSC) contribute to immune dysfunctions induced by tumors both in experimental models and patients. In mice, MDSC are phenotypically heterogeneous cells that vary in their surface markers, likely depending on soluble factors produced by different tumors. We recently described a subset of inflammatory monocytes with immunosuppressive properties that can be found within the tumor mass, blood, and lymphoid organs of tumor-bearing mice. These cells expressed the α-chain of the receptor for IL-4 (IL4Rα) that was critical for their negative activity on CD8+ T cells. In cancer patients, the nature of MDSC is still poorly defined because evidence exists for both monocytic and granulocytic features. We show in this study that myeloid cells with immunosuppressive properties accumulate both in mononuclear and polymorphonuclear fractions of circulating blood leukocytes of patients with colon cancer and melanoma, thus unveiling a generalized alteration in the homeostasis of the myeloid compartment. Similarly to mouse MDSC, IL4Rα is up-regulated in both myeloid populations but its presence correlates with an immunosuppressive phenotype only when mononuclear cells, but not granulocytes, of tumor-bearing patients are considered.
Follicular and Marginal Zone B Cells Fail to Cross-Present MHC Class I-Restricted Epitopes Derived from Viral Particles
Authors: Keller Susanne A. , von Allmen Caroline E. , Hinton Heather J. , Bauer Monika , Muntwiler Simone , Dietmeier Klaus , Saudan Philippe , Bachmann Martin F.
Published: May 2009

Viruses and virus-like particles (VLPs) are known to be potent inducers of B cell as well as Th cell and CTL responses. It is well established that professional APCs such as dendritic cells (DCs) and macrophages efficiently process viral particles for both MHC class I- and MHC class II-associated presentation, which is essential for induction of CTL and Th cell responses, respectively. Less is known, however, about the ability of B cells to present epitopes derived from viral particles to T cells. Using two different VLPs, in this study we show in vitro as well as in vivo that DCs present VLP-derived peptides in association with MHC class I as well as class II. In contrast, although B cells were able to capture VLPs similarly as DCs and although they efficiently processed VLPs for presentation in association with MHC class II, they failed to process exogenous VLPs for presentation in association with MHC class I. Thus, in contrast to DCs, B cells are not involved in the process of cross-priming. This finding is of physiological importance because B cells with the ability to cross-present Ag to specific CD8+ T cells may be killed by these cells, preventing the generation of neutralizing Ab responses.
IgM Antibodies to Apoptosis-Associated Determinants Recruit C1q and Enhance Dendritic Cell Phagocytosis of Apoptotic Cells
Authors: Chen Yifang , Park Yong-Beom , Patel Ekta , Silverman Gregg J.
Published: May 2009

Natural Abs, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis, but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neoantigenic determinants on apoptotic thymocytes is dominated by Abs to oxidation-associated Ags, phosphorylcholine (PC), a head group that becomes exposed during programmed cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive oxidation species. While natural Abs to apoptotic cells in naive adult mice were dominated by PC and MDA specificities, the amounts of these Abs were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA Abs was affected by VH gene inheritance. Ab interactions with apoptotic cells also mediated the recruitment of C1q, which enhanced apoptotic cell phagocytosis by immature dendritic cells. Significantly, IgM Abs to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural Abs that recognize neoantigens on apoptotic cells, in naive mice and those induced by immune exposure to apoptotic cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells.
Targeted Disruption of the Gene Encoding the Murine Small Subunit of Carboxypeptidase N (CPN1) Causes Susceptibility to C5a Anaphylatoxin-Mediated Shock
Authors: Mueller-Ortiz Stacey L. , Wang Dachun , Morales John E. , Li Li , Chang Jui-Yoa , Wetsel Rick A.
Published: May 2009

Carboxypeptidase N (CPN) is a plasma zinc metalloprotease, which consists of two enzymatically active small subunits (CPN1) and two large subunits (CPN2) that protect the protein from degradation. Historically, CPN has been implicated as a major regulator of inflammation by its enzymatic cleavage of functionally important arginine and lysine amino acids from potent phlogistic molecules, such as the complement anaphylatoxins C3a and C5a. Because of no known complete CPN deficiencies, the biological impact of CPN in vivo has been difficult to evaluate. Here, we report the generation of a mouse with complete CPN deficiency by targeted disruption of the CPN1 gene. CPN1−/− mice were hypersensitive to lethal anaphylactic shock due to acute complement activation by cobra venom factor. This hypersensitivity was completely resolved in CPN1−/−/C5aR−/− but not in CPN1−/−/C3aR−/− mice. Moreover, CPN1−/− mice given C5a i.v., but not C3a, experienced 100% mortality. This C5a-induced mortality was reduced to 20% when CPN1−/− mice were treated with an antihistamine before C5a challenge. These studies describe for the first time a complete deficiency of CPN and demonstrate 1) that CPN plays a requisite role in regulating the lethal effects of anaphylatoxin-mediated shock, 2) that these lethal effects are mediated predominantly by C5a-induced histamine release, and 3) that C3a does not contribute significantly to shock following acute complement activation.
Proximal Glycans Outside of the Epitopes Regulate the Presentation of HIV-1 Envelope gp120 Helper Epitopes
Authors: Li Hualin , Xu Chong-Feng , Blais Steven , Wan Qi , Zhang Hui-Tang , Landry Samuel J. , Hioe Catarina E.
Published: May 2009

Glycosylation of HIV-1 envelope gp120 determines not only the proper structure, but also the immune responses against this Ag. Although glycans may be part of specific epitopes or shield other epitopes from T cells and Abs, this study provides evidence for a different immunomodulatory function of glycans associated with gp120 residues N230 and N448. These glycans are required for efficient MHC class II-restricted presentation of nearby CD4 T cell epitopes, even though they are not part of the epitopes. The glycans do not affect CD4 T cell recognition of more distant epitopes and are not essential for the proper folding and function of gp120. Data on CD4 T cell recognition of N448 mutants combined with proteolysis analyses and surface electrostatic potential calculation around residue N448 support the notion that N448 glycan near the epitope’s C terminus renders the site to be surface accessible and allows its efficient processing. In contrast, the N230 glycan contributes to the nearby epitope presentation at a step other than the proteolytic processing of the epitope. Hence, N-glycans can determine CD4 T cell recognition of nearby gp120 epitopes by regulating the different steps in the MHC class II processing and presentation pathway after APCs acquire the intact gp120 Ag exogenously. Modifications of amino acids bearing glycans at the C termini of gp120 helper epitopes may prove to be a useful strategy for enhancing the immunogenicity of HIV-1 envelope gp120.
Cutting Edge: Negative Regulation of Dendritic Cells through Acetylation of the Nonhistone Protein STAT-3
Authors: Sun Yaping , Chin Y. Eugene , Weisiger Elizabeth , Malter Chelsea , Tawara Isao , Toubai Tomomi , Gatza Erin , Mascagni Paolo , Dinarello Charles A. , Reddy Pavan
Published: May 2009

Histone deacetylase (HDAC) inhibition modulates dendritic cell (DC) functions and regulates experimental graft-vs-host disease and other immune-mediated diseases. The mechanisms by which HDAC inhibition modulates immune responses remain largely unknown. STAT-3 is a transcription factor shown to negatively regulate DC functions. In this study we report that HDAC inhibition acetylates and activates STAT-3, which regulates DCs by promoting the transcription of IDO. These findings demonstrate a novel functional role for posttranslational modification of STAT-3 through acetylation and provide mechanistic insights into HDAC inhibition-mediated immunoregulation by induction of IDO.
Cutting Edge: Unusual NK Cell Responses to HIV-1 Peptides Are Associated with Protection against Maternal-Infant Transmission of HIV-1
Authors: Tiemessen Caroline T. , Shalekoff Sharon , Meddows-Taylor Stephen , Schramm Diana B. , Papathanasopoulos Maria A. , Gray Glenda E. , Sherman Gayle G. , Coovadia Ashraf H. , Kuhn Louise
Published: May 2009

Most infants exposed to HIV-1 in utero and at delivery do not acquire infection. We show that mothers and infants who have CD3-negative cells that respond to HIV-1 peptides are substantially less likely to transmit and acquire infection, respectively. The CD3-negative cells, shown to be NK cells, respond with remarkable specificity and high magnitude to HIV-1 peptides from Env (envelope) and Reg (regulatory) protein regions, as measured by a whole blood intracellular cytokine assay only in the context of HIV-1 infection or exposure. These findings identify an important new measure of protective immunity to HIV-1 that highlights the importance of innate immunity in preventing the establishment of HIV-1 infection.
Copper‐Catalyzed N‐Arylation/Hydroamin(d)ation Domino Synthesis of Indoles and its Application to the Preparation of a Chek1/KDR Kinase Inhibitor Pharmacophore
Authors: Ackermann Lutz , Barfüßer Sebastian , Potukuchi Harish K.
Published: April 2009

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Inexpensive copper catalysts allow for efficient syntheses of N‐aryl‐, N‐acyl‐, or N‐H‐(aza)indoles starting from ortho‐alkynylbromoarenes. The broad scope of this domino N‐arylation/hydroamin(d)ation process is highlighted by the synthesis of highly functionalized indoles, as well as of a Chek1/KDR inhibitor pharmacophore.
Phosphinidene Addition to Conjugated Allenes
Authors: Bertini Federica , Wit Jan B. M. , Ünal Murat , de Kanter Franciscus J. J. , Schakel Marius , Slootweg J. Chris , Ehlers Andreas W. , Nijbacker Tom , Komen Corine M. D. , Lutz Martin , Spek Anthony L. , Lammertsma Koop
Published: April 2009

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Generating the transient electrophilic tungsten pentacarbonyl‐phenylphosphinidene complex PhPW(CO)5 in the presence of 2,7‐dimethylocta‐2,3,5,6‐tetraene leads to the formation of a 3,4‐disubstituted phosphole or a complexed phospholene, depending on the reaction conditions. The formation of the phospholene results from the reaction of PhPW(CO)5 with the diallene, while the formation of the phosphole arises from reaction with 3,4‐diisopropylidene‐cyclobutene, which is formed in situ from the isomerization of the conjugated allene.
Mimicking biological delivery through feedback‐controlled drug release systems based on molecular imprinting
Authors: Kryscio David R. , Peppas Nicholas A.
Published: April 2009

Intelligent drug delivery systems (DDS) are able to rapidly detect a biological event and respond appropriately by releasing a therapeutic agent; thus, they are advantageous over their conventional counterparts. Molecular imprinting is a promising area that generates a polymeric network which can selectively recognize a desired analyte. This field has been studied for a variety of applications over a long period of time, but only recently has it been investigated for biomedical and pharmaceutical applications. Recent work in the area of molecularly imprinted polymers in drug delivery highlights the potential of these recognitive networks as environmentally responsive DDS that can ultimately lead to feedback controlled recognitive release systems. © 2009 American Institute of Chemical Engineers AIChE J, 2009.
The gestational timing of pregnancy loss: Adaptive strategy?
Authors: Baird Donna Day
Published: April 2009

This commentary links early pregnancy milestones (rescue of the corpus luteum, the luteal‐placental shift, and blocking of the spiral arteries) with the pattern of gestation‐specific pregnancy loss in humans. The objective is to describe the pattern and present an adaptive hypothesis: that high first trimester pregnancy loss results from selection to reduce the risk of maternal morbidity and mortality associated with human delivery. Specific questions within the broad framework of this hypothesis can be addressed with research in comparative physiology and endocrinology. Am. J. Hum. Biol., 2009. Published 2009 Wiley‐Liss, Inc.
Testing three evolutionary models of the demographic transition: Patterns of fertility and age at marriage in urban South India
Authors: Shenk Mary K.
Published: April 2009

Over the last three decades many authors have addressed the demographic transition from the perspective of evolutionary theory. Some authors have emphasized parental investment factors such as the costs of raising children, others have emphasized the effects of mortality and other forms of risk, and others have emphasized the biased transmission of cultural norms from people of high status. Yet the literature says little about the relative strengths of each of these types of motivations or about which ones are more likely to serve as the primary impetus for large‐scale demographic change. In this paper, I examine how each of these factors has influenced the demographic transition in urban South India during the course of the 20th century using two measures of fertility transition: number of surviving children and age at marriage. I find that investment‐related, risk‐related, and cultural transmission predictors all have significant individual effects on the outcome variables, which persist when they are entered in combination. When the three types of predictors are compared, however, investment‐related models appear to provide more robust explanations for patterns in both fertility and age of marriage. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.
TRPM7 is not associated with amyotrophic lateral sclerosis‐parkinsonism dementia complex in the Kii peninsula of Japan
Authors: Hara Kenju , Kokubo Yasumasa , Ishiura Hiroyuki , Fukuda Yuko , Miyashita Akinori , Kuwano Ryozo , Sasaki Ryogen , Goto Jun , Nishizawa Masatoyo , Kuzuhara Shigeki , Tsuji Shoji
Published: April 2009

Amyotrophic lateral sclerosis‐parkinsonism dementia complex (ALS/PDC) is a distinct neurodegenerative disorder characterized by ALS pathology with neurofibrillary tangles (NFTs) in the spinal cord and brain. Recent clinical studies have revealed a high incidence and a high familial occurrence of ALS/PDC in both Guam and the Kii peninsula of Japan, suggesting a strong genetic predisposition to this disorder. The T1482I variant (rs8042919) of TRPM7 gene which is suggested to play roles in regulating the cellular homeostasis of Ca2+, Mg2+, and trace metals, has recently been reported to be associated with Guamanian patients with ALS/PDC. To investigate whether TRPM7 is associated with Kii ALS/PDC, we conducted parametric linkage analyses of the TRPM7 locus in a large extended family with ALS/PDC. Linkage analysis did not reveal any evidence supporting the linkage to the TRPM7 locus. Resequencing of the entire coding region of TRPM7 did not reveal any pathogenic mutations in an affected individual in this family. The allele frequencies of the T1482I in affected individuals in this family or in those from other families are not significantly different from those in regional controls or those in HapMap‐JPT samples. These results indicate that TRPM7 is not associated with ALS/PDC in the Kii peninsula of Japan. © 2009 Wiley‐Liss, Inc.
Distribution and abundance of sacred monkeys in Igboland, southern Nigeria
Authors: Baker Lynne R. , Tanimola Adebowale A. , Olubode Oluseun S. , Garshelis David L.
Published: April 2009

Although primates are hunted on a global scale, some species are protected against harassment and killing by taboos or religious doctrines. Sites where the killing of sacred monkeys or the destruction of sacred groves is forbidden may be integral to the conservation of certain species. In 2004, as part of a distribution survey of Sclater's guenon (Cercopithecus sclateri) in southern Nigeria, we investigated reports of sacred monkeys in the Igbo‐speaking region of Nigeria. We confirmed nine new sites where primates are protected as sacred: four with tantalus monkeys (Chlorocebus tantalus) and five with mona monkeys (Cercopithecus mona). During 2004–2006, we visited two communities (Akpugoeze and Lagwa) previously known to harbor sacred populations of Ce. sclateri to estimate population abundance and trends. We directly counted all groups and compared our estimates with previous counts when available. We also estimated the size of sacred groves and compared these with grove sizes reported in the literature. The mean size of the sacred groves in Akpugoeze (2.06 ha, n=10) was similar to others in Africa south of the Sahel, but larger than the average grove in Lagwa (0.49 ha, n=15). We estimated a total population of 124 Sclater's monkeys in 15 groups in Lagwa and 193 monkeys in 20 groups in Akpugoeze. The Akpugoeze population was relatively stable over two decades, although the proportion of infants declined, and the number of groups increased. As Sclater's monkey does not occur in any official protected areas, sacred populations are important to the species' long‐term conservation. Despite the monkeys' destruction of human crops, most local people still adhere to the custom of not killing monkeys. These sites represent ideal locations in which to study the ecology of Sclater's monkey and human–wildlife interactions. Am. J. Primatol. 71:574–586, 2009. © 2009 Wiley‐Liss, Inc.
An Efficient Method Based on the Photothermal Effect for the Release of Molecules from Metal Nanoparticle Surfaces
Authors: Bakhtiari Amir Bahman Samsam , Hsiao Dennis , Jin Guoxia , Gates Byron D. , Branda Neil R.
Published: April 2009

Bei der Lichtabsorption heizen sich Metallnanopartikel auf. Dadurch erhöht sich auch die Temperatur in ihrer Umgebung. Dieses Phänomen lässt sich nutzen, um in einem molekularen System, das an der Nanopartikeloberfläche verankert ist, selektiv Bindungsbrüche herbeizuführen (siehe Bild). Der Prozess könnte zu einer allgemeinen Methode der lokalisierten Wirkstoff‐Freisetzung ausgearbeitet werden, die schwere Gewebsschäden vermeidet.

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All‐in‐One Target‐Cell‐Specific Magnetic Nanoparticles for Simultaneous Molecular Imaging and siRNA Delivery
Authors: Lee Jae‐Hyun , Lee Kyuri , Moon Seung Ho , Lee Yuhan , Park Tae Gwan , Cheon Jinwoo
Published: April 2009

Eine gezielte Genstummschaltung in Krebszellen gelang mit magnetischen Eisenoxid‐Nanopartikeln (MEIO), an denen ein Fluoreszenzfarbstoff, siRNA sowie ein RGD‐Peptid zur Erkennung von Krebszellen angebracht waren (siehe Bild). Die verschiedenen funktionellen Einheiten ermöglichen eine kombinierte makroskopische (Kernspin‐) und mikroskopische (Fluoreszenz‐)Tomographie der Zielzellen. Dieses System könnte sich für die parallele diagnostische und therapeutische Anwendung eignen.

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Total Synthesis and Stereochemical Assignment of Micrococcin P1
Authors: Lefranc David , Ciufolini Marco A.
Published: April 2009

Was lange währt …︁ Fünfzig Jahre nach Entdeckung des Thiopeptid‐Antibiotikums Micrococcin P1 ist es nun gelungen, die konstitutionellen und stereochemischen Ungewissheiten in Bezug auf seine Struktur durch eine Totalsynthese und die Zuordnung der absoluten Konfiguration zu beseitigen (siehe Bild).

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Understanding Covalent Mechanochemistry
Authors: Ribas‐Arino Jordi , Shiga Motoyuki , Marx Dominik
Published: April 2009

Die Zeit ist reif: Eine allgemeingültige theoretische Beschreibung auf der Grundlage von krafttransformierten Potentialflächen erklärt die Resultate aktueller Experimente im aufstrebenden Feld der kovalenten Mechanochemie.

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Spontaneous Formation of Giant Unilamellar Vesicles from Microdroplets of a Polyion Complex by Thermally Induced Phase Separation
Authors: Oana Hidehiro , Kishimura Akihiro , Yonehara Kei , Yamasaki Yuichi , Washizu Masao , Kataoka Kazunori
Published: April 2009

Wasserpumpe: Vesikel aus polyionischen Komplexen (PICs) entstehen spontan aus PIC‐Mikrotröpfchen, die beim Vermischen kationischer und anionischer Polymere gebildet werden (siehe Bild). Der Bildungsprozess kann durch lokales Erhitzen mit einem fokussierten IR‐Laser, der die Trennung der Mikrophasen mit anschließendem Wassereinfluss auslöst, reversibel kontrolliert werden. Die ursprüngliche Größe der PIC‐Tröpfchen bestimmt die Größe der unilamellaren Vesikel.

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Enantioselective Robinson‐Type Annulation Reaction Catalyzed by Chiral Phosphoric Acids
Authors: Akiyama Takahiko , Katoh Takuya , Mori Keiji
Published: April 2009

Durch zwei Phosphorsäuren werden eine enantioselektive Michael‐Addition und eine nachfolgende intramolekulare Aldolreaktion katalysiert, die Cyclohexenonderivate mit hervorragenden Enantioselektivitäten liefern. Bei der zweiten Reaktion wird eine ausgeprägte kinetische Racematspaltung beobachtet. Ar=Aryl; X=H, Halogen; Y=H, Me, Halogen.

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An Efficient Method Based on the Photothermal Effect for the Release of Molecules from Metal Nanoparticle Surfaces
Authors: Bakhtiari Amir Bahman Samsam , Hsiao Dennis , Jin Guoxia , Gates Byron D. , Branda Neil R.
Published: April 2009

Please release me: The heat generated when metal nanoparticles absorb light results in a significant increase in the temperature of the environment around the particles and is used to selectively break bonds within a molecular system anchored to the nanoparticle surface (see picture). This process represents an advantageous and more universal method to deliver chemicals locally, while avoiding excessive tissue damage.

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All‐in‐One Target‐Cell‐Specific Magnetic Nanoparticles for Simultaneous Molecular Imaging and siRNA Delivery
Authors: Lee Jae‐Hyun , Lee Kyuri , Moon Seung Ho , Lee Yuhan , Park Tae Gwan , Cheon Jinwoo
Published: April 2009

Cancer‐cell‐targeted gene silencing was observed with a magnetic‐nanoparticle platform (MEIO, magnetism‐engineered iron oxide) on which a fluorescent dye, siRNA, and a RGD‐peptide targeting moiety were attached (see picture). The different functionalities enable the macroscopic (magnetic resonance) and microscopic (fluorescence) imaging of target cells. This system may be suitable for concurrent diagnostic and therapeutic applications.

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A Xenon‐129 Biosensor for Monitoring MHC–Peptide Interactions
Authors: Schlundt Andreas , Kilian Wolfgang , Beyermann Michael , Sticht Jana , Günther Sebastian , Höpner Sabine , Falk Kirsten , Roetzschke Olaf , Mitschang Lorenz , Freund Christian
Published: April 2009

Caged in: The formation of a complex between a peptide ligand and a major histocompatibility complex (MHC) class II protein is detected by a 129Xe biosensor. Cryptophane molecules that trap Xe atoms are modified with a hemagglutinin (HA) peptide, which binds to the MHC protein. The interaction can be monitored by an NMR chemical shift change of cage–HA bound 129Xe.

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Development of a Fluorescent Pb2+ Sensor
Authors: Marbella Lauren , Serli‐Mitasev Barbara , Basu Partha
Published: April 2009

A real turn‐on: The emission intensity of heterocycle 1 increases upon binding to Pb2+. Thus, 1 acts as a small‐molecule “turn‐on” fluorescent sensor for lead. The sensor is highly selective and is functional over a wide range of pH values.

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Understanding Covalent Mechanochemistry
Authors: Ribas‐Arino Jordi , Shiga Motoyuki , Marx Dominik
Published: April 2009

The time is ripe: A general theoretical framework based on force‐transformed potential energy surfaces rationalizes the intriguing results of recent experiments in the emerging field of covalent mechanochemistry.

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Developmental expression of odorant‐binding proteins and chemosensory proteins in the embryos of Locusta migratoria
Authors: Yu Yanxue , Zhang Shangan , Zhang Long , Zhao Xingbo
Published: April 2009

We have investigated the development of chemosensilla and the secretion of odorant‐binding proteins (OBPs) and chemosensory proteins (CSPs) in the embryo of Locusta migratoria manilensis. We first report the changes of each sensillum in embryo just preceding hatch in detail and show that different sensilla have different developmental processes. Trichogen cells are first involved in forming the structure of pegs, and then, after retraction, they start secreting OBPs and CSPs in the sensillar lymph. The synthesis of LmigOBP1 starts during the embryogenesis about 0.5 h preceding hatching, specifically in sensilla trichodea and basiconica of the antenna. LmigOBP2, instead, was only found in the outer sensillum lymph (oSl) of sensilla chaetica of the antenna, while we could not detect LmigOBP3 in any type of sensilla of the antenna. The ontogenesis of CSPs in the embryos is similar to that of OBPs. Expression of CSPI homolog in Locusta migratoria is detected using the antiserum raised against SgreCSPI. CSPI is specifically expressed in the outer sensillum lymph of sensilla chaetica of the antenna, and anti‐LmigCSPII dose not label any sensilla of the embryos. These data indicate that in locusts, OBPs and CSPs follow different temporal expression patterns, and also that OBPs are expressed in different types of sensilla. © 2009 Wiley Periodicals, Inc.
Cognitive impairment and employment status in systemic lupus erythematosus: A prospective longitudinal study
Authors: Appenzeller Simone , Cendes Fernando , Costallat Lilian T. L.
Published: April 2009

Objective

To determine the relationship between cognitive impairment and employment in patients with systemic lupus erythematosus (SLE).

Methods

A total of 167 consecutive patients with SLE were prospectively evaluated, and underwent standardized neuropsychological tests. Multivariate logistic regression was used to determine the likelihood of being unemployed, adjusting for sociodemographic characteristics, employment status at study entry, disease activity, disease duration, damage scores, and depression.

Results

At study entry, 118 (70.7%) of 167 patients were employed. In the multivariate analysis, after adjusting for confounders, unemployment was predicted by the number of cognitive domains impaired (odds ratio [OR] 1.76, 95% confidence interval [95% CI] 1.58–6.72), depression (OR 1.3, 95% CI 1.1–3.1), fewer years of education (OR 0.12, 95% CI 0.02–0.34), and the presence of anticardiolipin antibodies (OR 1.43, 95% CI 1.2–6.1). Complex attention (OR 1.7, 95% CI 1.2–3.6), memory (OR 3.1, 95% CI 1.5–6.2), and executive functions (OR 2.4, 95% CI 1.9–6.1) were predictors of unemployment at study entry. After 3 years, 61 (51.7%) of 118 patients were employed (OR 2.25, 95% CI 1.38–3.68; P = 0.001). The likelihood of being unemployed after 3 years was predicted by the number of cognitive domains impaired (OR 3.8, 95% CI 2.5–7.71), depression (OR 2.31, 95% CI 1.01–5.21), fewer years of education (OR 0.09, 95% CI 0.01–0.42), and the presence of anticardiolipin antibodies (OR 2.1, 95% CI 1.2–4.9). Complex attention (OR 2.2, 95% CI 1.1–3.8), memory (OR 3.6, 95% CI 2.1–6.4), executive functions (OR 1.8, 95% CI 1.2–7.3), and reasoning/problem solving (OR 1.9, 95% CI 1.4–7.2) were associated with unemployment after 3 years.

Conclusion

The number of cognitive spheres, and especially attention, memory, and executive functions, are important factors associated with unemployment in patients with SLE.
Do acute‐phase reactants predict response to glucocorticoid therapy in retroperitoneal fibrosis?
Authors: Magrey Marina N. , Husni M. Elaine , Kushner Irving , Calabrese Leonard H.
Published: April 2009

Objective

To determine the value of the erythrocyte sedimentation rate (ESR) and the C‐reactive protein (CRP) level at the time of diagnosis for predicting radiographic response to glucocorticoid therapy in patients with retroperitoneal fibrosis (RFP).

Methods

Data were collected retrospectively for 37 patients with an established diagnosis of RFP (the diagnosis was proven by biopsy in 31 patients), all of whom met the following inclusion criteria: 1) availability of a recorded baseline ESR and/or CRP level and results of computed tomography or magnetic resonance imaging, 2) availability of followup CRP level and/or ESR with radiographic imaging 12–24 weeks after initiation of therapy, and 3) treatment with prednisone monotherapy at a starting dosage of 40–60 mg daily. Patients were divided into 2 therapeutic response groups: group 1 showed radiographic regression, and group 2 showed no change or radiographic progression. Any progression or regression was determined by an estimated change of ≥25%.

Results

The median baseline CRP levels were 2.2 mg/dl (interquartile range [IQR] 1.4–8.0) in group 1 and 1.2 mg/dl (IQR 0.8–4.1) in group 2 (P = 0.35). The median baseline ESR in group 1 was 57.5 mm/hour (IQR 39.2–102.5), which was not statistically different from the median ESR in group 2 (58 mm/hour [IQR 33–66]). The mean CRP level and ESR tended to be higher in patients with radiographic regression, but these differences failed to reach statistical significance. Spearman's correlation coefficient revealed no correlation between the baseline CRP level (r = −0.11, P = 0.51) or ESR (r = −0.06, P = 0.71) and the radiographic response.

Conclusion

The ESR and CRP level at baseline are poor predictors of a therapeutic response to glucocorticoid therapy in patients with RPF.
Medial opening wedge high tibial osteotomy: A prospective cohort study of gait, radiographic, and patient‐reported outcomes
Authors: Birmingham Trevor B. , Giffin J. Robert , Chesworth Bert M. , Bryant Dianne M. , Litchfield Robert B. , Willits Kevin , Jenkyn Thomas R. , Fowler Peter J.
Published: April 2009

Objective

To evaluate the effect of medial opening wedge high tibial osteotomy on gait, radiographic, and patient‐reported outcomes over a 2‐year postoperative period in patients with varus alignment and medial compartment knee osteoarthritis, and to identify significant predictors of outcome.

Methods

We used an observational cohort study design and prospectively administered 3‐dimensional quantitative gait analysis, hip to ankle weight‐bearing radiographs, and patient‐reported outcomes preoperatively and 6, 12, 18, and 24 months postoperatively. Observed changes with 95% confidence intervals (95% CIs) were calculated. Multivariate linear regression and cluster analysis were used to evaluate associations between patient characteristics and 2‐year outcomes in dynamic knee joint load (external knee adduction moment during gait) and Knee Injury and Osteoarthritis Outcome Scores (KOOS).

Results

A total of 126 patients (mean age 47.48 years) were included in the study. Mean changes suggested clinically important improvements in malalignment (change in mechanical axis angle 8.04° [95% CI 7.16°, 8.93°]), medial compartment load during gait (change in knee adduction moment −1.38 [95% CI −1.53, −1.22] percentage body weight × height), and all KOOS domain scores (change in pain 23.19 [95% CI 19.49, 26.89] KOOS points). A small (13%) increase in knee adduction moment was observed from 6 to 24 months postoperatively. Few preoperative clinical and/or gait characteristics assessed at baseline were significantly associated with 2‐year outcomes.

Conclusion

A medial opening wedge high tibial osteotomy with correction to approximately neutral alignment produces substantial and clinically important changes in dynamic knee joint load and patient‐reported measures of pain, function, and quality of life 2 years postoperatively. Changes in knee adduction moment observed in the first 2 years postoperatively should be explored as potential predictors of longer‐term success and subgroups of patients with poor outcomes.
The PRL –1149 G/T polymorphism and rheumatoid arthritis susceptibility
Authors: Lee Yvonne C. , Raychaudhuri Soumya , Cui Jing , de Vivo Immaculata , Ding Bo , Alfredsson Lars , Padyukov Leonid , Costenbader Karen H. , Seielstad Mark , Graham Robert R. , Klareskog Lars , Gregersen Peter K. , Plenge Robert M. , Karlson Elizabeth W.
Published: April 2009

Objective

Previous studies have demonstrated that the PRL −1149 T (minor) allele decreases prolactin expression and may be associated with autoimmune disease. The aim of this study was to determine the role of the PRL −1149 G/T polymorphism (rs1341239) in rheumatoid arthritis (RA) susceptibility.

Methods

We examined the association between PRL −1149 G/T and RA risk in 4 separate study populations, consisting of a total of 3,405 RA cases and 4,111 controls of self‐reported white European ancestry. Samples were genotyped using 1 of 3 genotyping platforms, and strict quality control metrics were applied. We tested for association using a 2‐tailed Cochran‐Mantel‐Haenszel additive, fixed‐effects model.

Results

In the individual populations, odds ratios (ORs) for an association between PRL −1149 T and RA risk ranged from 0.80 to 0.97. In a joint meta‐analysis across all 4 populations, the OR for an association between PRL −1149 T and RA risk was 0.90 (95% confidence interval 0.84–0.96, P = 0.001).

Conclusion

Our findings indicate a possible association between the PRL −1149 T allele and decreased RA risk. The effect size is small but similar to ORs for other genetic polymorphisms associated with complex traits, including RA.