bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seasonal dynamics of typhoid and paratyphoid fever
Authors: Saad Neil J. , Lynch Victoria D. , Antillón Marina , Yang Chongguang , Crump John A. , Pitzer Virginia E. 
Published: April 2018

AbstractTyphoid and paratyphoid fever may follow a seasonal pattern, but this pattern is not well characterized. Moreover, the environmental drivers that influence seasonal dynamics are not fully understood, although increasing evidence suggests that rainfall and temperature may play an important role. We compiled a database of typhoid, paratyphoid, or enteric fever and their potential environmental drivers. We assessed the seasonal dynamics by region and latitude, quantifying the mean timing of peak prevalence and seasonal variability. Moreover, we investigated the potential drivers of the seasonal dynamics and compared the seasonal dynamics for typhoid and paratyphoid fever. We observed a distinct seasonal pattern for enteric and typhoid fever by latitude, with seasonal variability more pronounced further from the equator. We also found evidence of a positive association between preceding rainfall and enteric fever among settings 35°–11°N and a more consistent positive association between temperature and enteric fever incidence across most regions of the world. In conclusion, we identified varying seasonal dynamics for enteric or typhoid fever in association with environmental factors. The underlying mechanisms that drive the seasonality of enteric fever are likely dependent on the local context and should be taken into account in future control efforts.
A novel role for ATR/Rad3 in G1 phase
Authors: Bøe Cathrine A. , Håland Tine W. , Boye Erik , Syljuåsen Randi G. , Grallert Beáta 
Published: April 2018

AbstractCheckpoint kinases are important in cellular surveillance pathways that help cells to cope with DNA damage and protect their genomes. In cycling cells, DNA replication is one of the most sensitive processes and therefore all organisms carefully regulate replication initiation and progression. The checkpoint kinase ATR plays important roles both in response to DNA damage and replication stress, and ATR inhibitors are currently in clinical trials for cancer treatment. Therefore, it is important to understand the roles of ATR in detail. Here we show that the fission yeast homologue Rad3 and the human ATR regulate events also in G1 phase in an unperturbed cell cycle. Rad3Δ mutants or human cells exposed to ATR inhibitor in G1 enter S phase prematurely, which results in increased DNA damage. Furthermore, ATR inhibition in a single G1 reduces clonogenic survival, demonstrating that long-term effects of ATR inhibition during G1 are deleterious for the cell. Interestingly, ATR inhibition through G1 and S phase reduces survival in an additive manner, strongly arguing that different functions of ATR are targeted in the different cell-cycle phases. We propose that potential effects of ATR inhibitors in G1 should be considered when designing future treatment protocols with such inhibitors.
A proteomic analysis of an in vitro knock-out of miR-200c
Authors: Ljepoja Bojan , García-Roman Jonathan , Sommer Ann-Katrin , Fröhlich Thomas , Arnold Georg J. , Wagner Ernst , Roidl Andreas 
Published: April 2018

AbstractLoss of miR-200c is correlated to advanced cancer-subtypes due to increased EMT and decreased treatment efficacy by chemotherapeutics. As miRNAs regulate a multitude of targets, the analysis of differentially expressed proteins upon a genomic knock-out (KO) is of interest. In this study, we generated a TALENs KO of miR-200c in MCF7 breast cancer cells, excluded its compensation by family-members and evaluated the impact on the proteome by analyzing three individual KO-clones. We identified 26 key proteins and a variety of enrichments in metabolic and cytoskeletal pathways. In six of these targets (AGR2, FLNA/B, ALDH7A1, SCIN, GSTM3) the differential expression was additionally detected at mRNA level. Together, these alterations in protein abundance accounted for the observed biological phenotypes, i.e. increased migration and chemoresistance and altered metabolism, found in the miR-200c-KO clones. These findings provide novel insights into miR-200c and pave the way for further studies.
FTY720 Decreases Tumorigenesis in Group 3 Medulloblastoma Patient-Derived Xenografts
Authors: Garner Evan F. , Williams Adele P. , Stafman Laura L. , Aye Jamie M. , Mroczek-Musulman Elizabeth , Moore Blake P. , Stewart Jerry E. , Friedman Gregory K. , Beierle Elizabeth A. 
Published: April 2018

AbstractGroup 3 tumors account for 28% of medulloblastomas and have the worst prognosis. FTY720, an immunosuppressant currently approved for treatment of multiple sclerosis, has shown antitumor effects in several human cancer cell lines. We hypothesized that treatment with FTY720 (fingolimod) would decrease tumorigenicity in medulloblastoma patient-derived xenografts (PDXs). Three Group 3 medulloblastoma PDXs (D341, D384 and D425) were utilized. Expression of PP2A and its endogenous inhibitors I2PP2A and CIP2A was detected by immunohistochemistry and immunoblotting. PP2A activation was measured via phosphatase activation kit. Cell viability, proliferation, migration and invasion assays were performed after treatment with FTY720. Cell cycle analysis was completed using flow cytometry. A flank model using D425 human medulloblastoma PDX cells was used to assess the in vivo effects of FTY720. FTY720 activated PP2A and led to decreased medulloblastoma PDX cell viability, proliferation, migration and invasion and G1 cell cycle arrest in all three PDXs. FTY720 treatment of mice bearing D425 medulloblastoma PDX tumors resulted in a significant decrease in tumor growth compared to vehicle treated animals. FTY720 decreased viability, proliferation, and motility in Group 3 medulloblastoma PDX cells and significantly decreased tumor growth in vivo. These results suggest that FTY720 should be investigated further as a potential therapeutic agent for medulloblastoma.
The Role of Intelligence in Social Learning
Authors: Vostroknutov Alexander , Polonio Luca , Coricelli Giorgio 
Published: April 2018

AbstractStudies in cultural evolution have uncovered many types of social learning strategies that are adaptive in certain environments. The efficiency of these strategies also depends on the individual characteristics of both the observer and the demonstrator. We investigate the relationship between intelligence and the ways social and individual information is utilised to make decisions in an uncertain environment. We measure fluid intelligence and study experimentally how individuals learn from observing the choices of a demonstrator in a 2-armed bandit problem with changing probabilities of a reward. Participants observe a demonstrator with high or low fluid intelligence. In some treatments they are aware of the intelligence score of the demonstrator and in others they are not. Low fluid intelligence individuals imitate the demonstrator more when her fluid intelligence is known than when it is not. Conversely, individuals with high fluid intelligence adjust their use of social information, as the observed behaviour changes, independently of the knowledge of the intelligence of the demonstrator. We provide evidence that intelligence determines how social and individual information is integrated in order to make choices in a changing uncertain environment.
Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A
Authors: de Ridder Daniëlle , Marino Silvia , Bishop Ryan T. , Renema Nathalie , Chenu Chantal , Heymann Dominique , Idris Aymen I. 
Published: April 2018

AbstractSemaphorin 3A (Sema3A), a secreted member of the Semaphorin family, increases osteoblast differentiation, stimulates bone formation and enhances fracture healing. Here, we report a previously unknown role of Sema3A in the regulation of ectopic bone formation and osteolysis related to osteosarcoma. Human recombinant (exogenous) Sema3A promoted the expression of osteoblastic phenotype in a panel of human osteosarcoma cell lines and inhibited the ability of these cells to migrate and enhance osteoclastogenesis in vitro. In vivo, administration of exogenous Sema3A in mice after paratibial inoculation of KHOS cells increased bone volume in non-inoculated and tumour-bearing legs. In contrast, Sema3A overexpression reduced the ability of KHOS cells to cause ectopic bone formation in mice and to increase bone nodule formation by engaging DKK1/β-catenin signalling. Thus, Sema3A is of potential therapeutic efficacy in osteosarcoma. However, inhibition of bone formation associated with continuous exposure to Sema3A may limit its long-term usefulness as therapeutic agent.
N-Alkylation of functionalized amines with alcohols using a copper–gold mixed photocatalytic system
Authors: Wang Lyu-Ming , Morioka Yuna , Jenkinson Kellie , Wheatley Andrew E. H. , Saito Susumu , Naka Hiroshi 
Published: April 2018

AbstractDirect functionalization of amino groups in complex organic molecules is one of the most important key technologies in modern organic synthesis, especially in the synthesis of bio-active chemicals and pharmaceuticals. Whereas numerous chemical reactions of amines have been developed to date, a selective, practical method for functionalizing complex amines is still highly demanded. Here we report the first late-stage N-alkylation of pharmaceutically relevant amines with alcohols at ambient temperature. This reaction was achieved by devising a mixed heterogeneous photocatalyst in situ prepared from Cu/TiO2 and Au/TiO2. The mixed photocatalytic system enabled the rapid N-alkylation of pharmaceutically relevant molecules, the selective mono- and di-alkylation of primary amines, and the non-symmetrical dialkylation of primary amines to hetero-substituted tertiary amines.
Modulation of the relationship between spring AO and the subsequent winter ENSO by the preceding November AO
Authors: Chen Shangfeng , Chen Wen , Yu Bin 
Published: April 2018

AbstractPrevious studies indicated that the spring Arctic Oscillation (AO) exerts significant influences on the subsequent winter El Niño-Southern Oscillation (ENSO). This analysis suggests that the spring AO-ENSO linkage is highly modulated by its preceding November AO. When November and the subsequent spring AO indices are in phase, the spring AO has a pronounced influence on ENSO. However, when the November and spring AO indices are out of phase, the spring AO-ENSO connection disappears. Modulation of the November AO on the spring AO-ENSO connection is mainly through the constructive and destructive superposition of the November and spring AO associated sea surface temperature (SST) anomalies in the tropical central-eastern Pacific in spring and summer, as well as the SST anomalies developed further in the tropical Pacific via the positive air-sea feedback.
Quantitation of the cellular content of saliva and buccal swab samples
Authors: Theda Christiane , Hwang Seo Hye , Czajko Anna , Loke Yuk Jing , Leong Pamela , Craig Jeffrey M. 
Published: April 2018

AbstractBuccal swabs and saliva are the two most common oral sampling methods used for medical research. Often, these samples are used interchangeably, despite previous evidence that both contain buccal cells and blood leukocytes in different proportions. For some research, such as epigenetic studies, the cell types contributing to the analysis are highly relevant. We collected such samples from twelve children and twenty adults and, using Papanicolaou staining, measured the proportions of epithelial cells and leukocytes through microscopy. To our knowledge, no studies have compared cellular heterogeneity in buccal swab and saliva samples from adults and children. We confirmed that buccal swabs contained a higher proportion of epithelial cells than saliva and that children have a greater proportion of such cells in saliva compared to adults. At this level of resolution, buccal swabs and saliva contained similar epithelial cell subtypes. Gingivitis in children was associated with a higher proportion of leukocytes in saliva samples but not in buccal swabs. Compared to more detailed and costly methods such as flow cytometry or deconvolution methods used in epigenomic analysis, the procedure described here can serve as a simple and low-cost method to characterize buccal and saliva samples. Microscopy provides a low-cost tool to alert researchers to the presence of oral inflammation which may affect a subset of their samples. This knowledge might be highly relevant to their specific research questions, may assist with sample selection and thus might be crucial information despite the ability of data deconvolution methods to correct for cellular heterogeneity.
Erythrocytes lacking the Langereis blood group protein ABCB6 are resistant to the malaria parasite Plasmodium falciparum
Authors: Egan Elizabeth S. , Weekes Michael P. , Kanjee Usheer , Manzo Jale , Srinivasan Ashwin , Lomas-Francis Christine , Westhoff Connie , Takahashi Junko , Tanaka Mitsunobu , Watanabe Seishi , Brugnara Carlo , Gygi Steven P. , Tani Yoshihiko , Duraisingh Manoj T. 
Published: April 2018

AbstractThe ATP-binding cassette transporterABCB6was recently discovered to encode the Langereis (Lan) blood group antigen. Lan null individuals are asymptomatic, and the function of ABCB6 in mature erythrocytes is not understood. Here, we assessed ABCB6 as a host factor forPlasmodium falciparummalaria parasites during erythrocyte invasion. We show that Lan null erythrocytes are highly resistant to invasion byP. falciparum, in a strain-transcendent manner. Although both Lan null and Jr(a-) erythrocytes harbor excess porphyrin, only Lan null erythrocytes exhibit aP. falciparuminvasion defect. Further, the zoonotic parasiteP. knowlesiinvades Lan null and control cells with similar efficiency, suggesting that ABCB6 may mediateP. falciparuminvasion through species-specific molecular interactions. Using tandem mass tag-based proteomics, we find that the only consistent difference in membrane proteins between Lan null and control cells is absence of ABCB6. Our results demonstrate that a newly identified naturally occurring blood group variant is associated with resistance toPlasmodium falciparum.
MiR-382 functions as tumor suppressor and chemosensitizer in colorectal cancer
Authors: Yao Hui , Xia Dong , Li Zong-lin , Ren Lei , Wang Ming-ming , Chen Wang-sheng , Hu Zheng-chuan , Yi Guo-ping , Xu Liang 
Published: April 2018

Abstract
Increasing evidence suggests that microRNAs (miRNAs) play a critical role in tumorigenesis. Decreased expression of miR-382 has been observed in various types of cancers. However, the biological function of miR-382 in colorectal cancer (CRC) is still largely unknown. Here, we found that miR-382 was down-regulated in human colorectal cancer tissues and cell lines associated with it. MiR-382 inhibited colorectal cancer cell proliferation, migration, invasion, and enhance chemosensitivity. Furthermore, we identified Krüppel-like factor 12 (KLF12) and homeodomain-interacting protein kinase 3 (HIPK3) as the target of miR-382, and miR-382 rescued the promotion effect of KFL12 on migration and enhanced chemosensitivity in colorectal cancer cell lines. Collectively, these findings revealed that miR-382 inhibits migration and enhances chemosensitivity by targeting KLF12 and HIPK3 in colorectal cancer. These findings might serve as a tumor suppressor in CRC.
LRO/LAMP study of the interstellar medium via the HeI 58.4 nm resonance line
Authors: Grava C. , Pryor W. R. , Feldman P. D. , Retherford K. D. , Gladstone G. R. , Greathouse T. K. 
Published: April 2018

Context.Recent measurements by IBEX and detailed modeling have changed our understanding of the flow of the interstellar medium through the solar system. In particular, a time dependence of the direction of the interstellar medium flow has been proposed, and a new population of helium atoms, called the “warm breeze”, has been discovered.Aims.We aim to constrain the structure of the interstellar medium close to the downwind focusing cone using the sensitive LAMP FUV/EUV imaging spectrograph onboard the Lunar Reconnaissance Orbiter.Methods.We measured the brightness of the emission line from interstellar helium atoms resonantly scattering solar photons at 58.4 nm (HeI) and compare it to our “modified cold model” of interstellar HeI sky brightness as a function of ecliptic latitude and longitude. Additionally, we compared LAMP observations to a model with time-dependent inflow direction and a model of the brightness of the “warm breeze”, to see if they can be distinguished by LAMP.Results.We find that the LAMP observations agree within error bars to our “modified cold model”, which in turn is consistent with the latest interstellar helium flow parameters found with IBEX. Our model can therefore be applied to other UV spectroscopic observations of the interstellar helium. However, LAMP observations cannot distinguish between our model and a model with a different inflow direction, since the latter has negligible effect on the 2D brightness of the interstellar HeI emission line. For the same reason, LAMP could not detect the effect of the “warm breeze”. We note a discrepancy between solar irradiances measured by TIMED/SEE and those measured by SDO/EVE. We recommend using values from SDO/EVE. Finally, we derive a value of LAMP sensitivity at the EUV wavelength (58.4 nm) of 0.485 ± 0.014 Hz/Rayleigh.Conclusions.These measurements pave the way to observations of the interstellar wind from lunar orbit.
First hydrodynamics simulations of radiation forces and photoionization feedback in massive star formation
Authors: Kuiper R. , Hosokawa T. 
Published: April 2018

Aims. We present the first simulations of the formation and feedback of massive stars which account for radiation forces as well as photoionization feedback (along with protostellar outflows). In two different accretion scenarios modeled, we determine the relative strength of these feedback components and derive the size of the reservoir from which the forming stars gained their masses.
Methods. We performed direct hydrodynamics simulations of the gravitational collapse of high-density mass reservoirs toward the formation of massive stars including self-gravity, stellar evolution, protostellar outflows, continuum radiation transport, photoionization, and the potential impact of ram pressure from large-scale gravitational infall. For direct comparison, we executed these simulations with and without the individual feedback components.
Results. Protostellar outflows alone limit the stellar mass growth only in an accretion scenario with a finite mass reservoir; when including accretion and ram pressure from large scales (>0.1 pc), protostellar outflows do not limit stellar mass growth at all. Photoionization and HII regions dominate the feedback ladder only at later times, after the star has already contracted down to the zero-age main sequence, and only on large scales. Specifically, photoionization yields a broadening of the bipolar outflow cavities and a reduction of the gravitational infall momentum by about 50%, but does not limit the stellar mass accretion. On the other hand, we find radiation forces restrain the gravitational infall toward the circumstellar disk, impact the gravito-centrifugal equilibrium at the outer edge of the disk, and eventually shut down stellar accretion completely. The most massive star formed in the simulations accreted 95 M⊙ before disk destruction; this mass was drawn-in from an accretion reservoir of ≈240 M⊙ and ≈0.24 pc in radius.
Conclusions. In the regime of very massive stars, the final mass of these stars is controlled by their own radiation force feedback.
Wnt Signaling Pathway in Uterus of Normal and Seminal Vesicle Excised Mated Mice during Pre-implantation Window
Authors: Latifi Zeinab , Fattahi Amir , Hamdi Kobra , Ghasemzadeh Aliye , Karimi Pouran , Nejabati Hamid , Novin Marefat , Roshangar Leila , Nouri Mohammad 
Published: April 2018

Abstract
Introduction The importance of seminal vesicle secretion and uterine Wnt signaling for uterus preparation and embryo implantation has been described.
Materials and Methods In this study, we evaluated the gene expression of Wnt ligands (Wnt4 and Wnt5a) and their corresponding receptors (Fzd2 and Fzd6) using qRT-PCR and active β-catenin protein levels using western blotting in the uterine tissue of female mice mated with intact and seminal vesicle-excised (SVX) males during the pre-implantation window. We evaluated the association between these factors and implantation rates and embryo spacing.
Results mRNA expression of Wnt4 and Wnt5a and active β-catenin protein levels decreased from Day 1 to Day 4, but reached a peak on the fifth day of pregnancy. Fzd2 also reached its highest level on Day 5. Fzd6 expression showed a decreasing trend towards the day of implantation. Lack of seminal vesicle secretion decreased Wnt4 and Wnt5a expression on Days 1 and 5 and β-catenin levels on Day 5. There were almost no significant differences in expression levels of the Fzd2 and Fzd6 receptors between groups. There were positive and negative correlations, respectively, between implantation rates and embryo spacing and Wnt4, Wnt5a and active β-catenin in the control group, but such correlations were not observed in the SVX-mated mice.
Conclusions Significant changes occurred in the expression of several Wnt signaling members and there was a significant association between Wnt signaling and embryo implantation. Seminal vesicle secretion affects Wnt signaling in mice and consequently also affects murine embryo implantation.
Comparison of Nerve Fiber Density between Patients with Uterine Leiomyoma with and without Pain: a Prospective Clinical Study
Authors: Giray Burak , Esim-Buyukbayrak Esra , Hallac-Keser Sevinc , Karageyim-Karsidag Ayse , Turkgeldi Aysegul 
Published: April 2018

Abstract
Introduction We aimed to compare the presence and the amount of nerve fibers in endometrial, myometrial and leiomyoma tissues using protein gene product 9.5 (PGP 9.5) and neurofilament (NF) immunohistochemical staining in uterine leiomyoma patients with and without pain complaint.
Methods Patients undergoing hysterectomy for uterine leiomyoma were prospectively enrolled in the study. Twenty-five uterine leiomyoma patients without pelvic pain complaint (visual analog scale (VAS) < 5) were assigned to Group 1; 23 uterine leiomyoma patients with pelvic pain complaint (VAS ≥ 5) were assigned to Group 2. Endometrial, myometrial and leiomyoma tissues obtained from hysterectomy specimens were stained immunohistochemically using PGP 9.5 and NF dyes. The presence and density of nerve fibers were compared between the two groups.
Results None of the endometrial samples in either groups stained with PGP 9.5 and NF dyes. There was no statistically significant difference in the number of nerve fibers in myometrial and leiomyoma tissues between the two groups with either of the stains (PGP 9.5: p = 0.39 and p = 0.29; NF: p = 0.83 and p = 0.65, respectively). There was agreement between PGP 9.5 and NF immunohistochemical staining for nerve fiber detection in myometrial and leiomyoma tissues (p < 0.05/κ = 0.622 and p < 0.05/κ = 0.388, respectively).
Conclusion This study demonstrates that the quantity and density of nerve fibers in myometrial and leiomyoma tissue in patients with pain were similar to that in patients without pain.