bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complementary Methodologies To Investigate Human Gut Microbiota in Host Health, Working towards Integrative Systems Biology
Authors: Méndez-García Celia , Barbas Coral , Ferrer Manuel , Rojo David 
Published: September 2017

ABSTRACTIn 1680, Antonie van Leeuwenhoek noted compositional differences in his oral and fecal microbiota, pioneering the study of the diversity of the human microbiome. From Leeuwenhoek's time to successful modern attempts at changing the gut microbial landscape to cure disease, there has been an exponential increase in the recognition of our resident microbes as part of ourselves. Thus, the human host and microbiome have evolved in parallel to configure a balanced system in which microbes survive in homeostasis with our innate and acquired immune systems, unless disease occurs. A growing number of studies have demonstrated a correlation between the presence/absence of microbial taxa and some of their functional molecules (i.e., genes, proteins, and metabolites) with health and disease states. Nevertheless, misleading experimental design on human subjects and the cost and lack of standardized animal models pose challenges to answering the question of whether changes in microbiome composition are cause or consequence of a certain biological state. In this review, we evaluate the state of the art of methodologies that enable the study of the gut microbiome, encouraging a change in broadly used analytic strategies by choosing effector molecules (proteins and metabolites) in combination with coding nucleic acids. We further explore microbial and effector microbial product imbalances that relate to disease and health.
Fibrinogen Activates the Capture of Human Plasminogen by Staphylococcal Fibronectin-Binding Proteins
Authors: Herman-Bausier Philippe , Pietrocola Giampiero , Foster Timothy J. , Speziale Pietro , Dufrêne Yves F. 
Published: September 2017

ABSTRACT

Invasive bacterial pathogens can capture host plasminogen (Plg) and allow it to form plasmin. This process is of medical importance as surface-bound plasmin promotes bacterial spread by cleaving tissue components and favors immune evasion by degrading opsonins. In
Staphylococcus aureus
, Plg binding is in part mediated by cell surface fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here, we use single-cell and single-molecule techniques to demonstrate that FnBPs capture Plg by a sophisticated activation mechanism involving fibrinogen (Fg), another ligand found in the blood. We show that while FnBPs bind to Plg through weak (∼200-pN) molecular bonds, direct interaction of the adhesins with Fg through the high-affinity dock, lock, and latch mechanism dramatically increases the strength of the FnBP-Plg bond (up to ∼2,000 pN). Our results point to a new model in which the binding of Fg triggers major conformational changes in the FnBP protein, resulting in the buried Plg-binding domains being projected and exposed away from the cell surface, thereby promoting strong interactions with Plg. This study demonstrated a previously unidentified role for a ligand-binding interaction by a staphylococcal cell surface protein, i.e., changing the protein orientation to activate a cryptic biological function.

IMPORTANCE
Staphylococcus aureus
captures human plasminogen (Plg) via cell wall fibronectin-binding proteins (FnBPs), but the underlying molecular mechanism is not known. Here we show that the forces involved in the interaction between Plg and FnBPs on the
S. aureus
surface are weak. However, we discovered that binding of fibrinogen to FnBPs dramatically strengthens the FnBP-Plg bond, therefore revealing an unanticipated role for Fg in the capture of Plg by
S. aureus
. These experiments favor a model where Fg-induced conformational changes in FnBPs promote their interaction with Plg. This work uncovers a previously undescribed activation mechanism for a staphylococcal surface protein, whereby ligand-binding elicits a cryptic biological function.
Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in
Archaea
Authors: Fu Xian , Adams Zachary , Liu Rui , Hepowit Nathaniel L. , Wu Yifei , Bowmann Connor F. , Moskovitz Jackob , Maupin-Furlow Julie A. 
Published: September 2017

ABSTRACT

Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme found in all domains of life that catalyzes the reduction of methionine-
S
-sulfoxide (MSO) to methionine in proteins and free amino acids. We demonstrate that archaeal MsrA has a ubiquitin-like (Ubl) protein modification activity that is distinct from its stereospecific reduction of MSO residues. MsrA catalyzes this Ubl modification activity, with the Ubl-activating E1 UbaA, in the presence of the mild oxidant dimethyl sulfoxide (DMSO) and in the absence of reductant. In contrast, the MSO reductase activity of MsrA is inhibited by DMSO and requires reductant. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis reveals that MsrA-dependent Ubl conjugates are associated with DNA replication, protein remodeling, and oxidative stress and include the Ubl-modified MsrA, Orc3 (Orc1/Cdc6), and Cdc48d (Cdc48/p97 AAA+ ATPase). Overall, we found archaeal MsrA to have opposing MSO reductase and Ubl modifying activities that are associated with oxidative stress responses and controlled by exposure to mild oxidant.

IMPORTANCE
Proteins that are damaged by oxidative stress are often targeted for proteolysis by the ubiquitin-proteasome system (UPS). The mechanisms that control this response are poorly understood, especially under conditions of mild oxidative stress when protein damage is modest. Here, we discovered a novel function of archaeal MsrA in guiding the Ubl modification of target proteins in the presence of mild oxidant. This newly reported activity of MsrA is distinct from its stereospecific reduction of methionine-
S
-sulfoxide to methionine residues. Our results are significant steps forward, first, in elucidating a protein factor that guides Ubl modification in archaea, and second, in providing an insight into oxidative stress responses that can trigger Ubl modification in a cell.
Broad-Host-Range Expression Reveals Native and Host Regulatory Elements That Influence Heterologous Antibiotic Production in Gram-Negative Bacteria
Authors: Zhang Jia Jia , Tang Xiaoyu , Zhang Michelle , Nguyen Darlene , Moore Bradley S. 
Published: September 2017

ABSTRACT

Heterologous expression has become a powerful tool for studying microbial biosynthetic gene clusters (BGCs). Here, we extend the transformation-associated recombination cloning and heterologous expression platform for microbial BGCs to include Gram-negative proteobacterial expression hosts. Using a broad-host-range expression platform, we test the implicit assumption that biosynthetic pathways are more successfully expressed in more closely related heterologous hosts. Cloning and expression of the violacein BGC from
Pseudoalteromonas luteoviolacea
2ta16 revealed robust production in two proteobacterial hosts,
Pseudomonas putida
KT2440 and
Agrobacterium tumefaciens
LBA4404, but very little production of the antibiotic in various laboratory strains of
Escherichia coli
, despite their closer phylogenetic relationship. We identified a nonclustered LuxR-type quorum-sensing receptor from
P. luteoviolacea
2ta16, PviR, that increases pathway transcription and violacein production in
E. coli
by ∼60-fold independently of acyl-homoserine lactone autoinducers. Although
E. coli
harbors the most similar homolog of PviR identified from all of the hosts tested, overexpression of various
E. coli
transcription factors did not result in a statistically significant increase in violacein production, while overexpression of two
A. tumefaciens
PviR homologs significantly increased production. Thus, this work not only introduces a new genetic platform for the heterologous expression of microbial BGCs, it also challenges the assumption that host phylogeny is an accurate predictor of host compatibility.

IMPORTANCE
Although Gram-positive heterologous hosts such as
Streptomyces
have been developed and optimized to support diverse secondary metabolic reactions, there has been comparatively less work on Gram-negative hosts, some of which grow faster and are easier to work with. This work presents a new genetic platform for direct cloning and broad-host-range heterologous expression of BGCs in Gram-negative proteobacterial expression hosts, and we leverage this platform to uncover regulatory elements that influence violacein expression from
Pseudoalteromonas
. Although it is often assumed that BGCs will be more successfully expressed in more closely related hosts, our work suggests that this may not be a general rule of thumb, as heterologous production of natural products can be influenced by specific host regulatory and/or biosynthetic elements, and the identity and effectiveness of those elements are difficult to predict. We argue for the use of a diverse set of heterologous hosts, which may also provide insights into the BGC biosynthetic mechanism and the biological function of BGCs.
A Radiomics Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer
Authors: Wu Shaoxu , Zheng Junjiong , Li Yong , Yu Hao , Shi Siya , Xie Weibin , Liu Hao , Su Yangfan , Huang Jian , Lin Tianxin 
Published: September 2017

AbstractPurpose: To develop and validate a radiomics nomogram for the preoperative prediction of lymph node (LN) metastasis in bladder cancer.Experimental Design: A total of 118 eligible bladder cancer patients were divided into a training set (n = 80) and a validation set (n = 38). Radiomics features were extracted from arterial-phase CT images of each patient. A radiomics signature was then constructed with the least absolute shrinkage and selection operator algorithm in the training set. Combined with independent risk factors, a radiomics nomogram was built with a multivariate logistic regression model. Nomogram performance was assessed in the training set and validated in the validation set. Finally, decision curve analysis was performed with the combined training and validation set to estimate the clinical usefulness of the nomogram.Results: The radiomics signature, consisting of nine LN status–related features, achieved favorable prediction efficacy. The radiomics nomogram, which incorporated the radiomics signature and CT-reported LN status, also showed good calibration and discrimination in the training set [AUC, 0.9262; 95% confidence interval (CI), 0.8657–0.9868] and the validation set (AUC, 0.8986; 95% CI, 0.7613–0.9901). The decision curve indicated the clinical usefulness of our nomogram. Encouragingly, the nomogram also showed favorable discriminatory ability in the CT-reported LN-negative (cN0) subgroup (AUC, 0.8810; 95% CI, 0.8021–0.9598).Conclusions: The presented radiomics nomogram, a noninvasive preoperative prediction tool that incorporates the radiomics signature and CT-reported LN status, shows favorable predictive accuracy for LN metastasis in patients with bladder cancer. Multicenter validation is needed to acquire high-level evidence for its clinical application. Clin Cancer Res; 23(22); 6904–11. ©2017 AACR.
Intercultural Ritual Transgression as a Catalyst for Early Christian Theological Reflection — A Consideration of 1 Corinthians 8
Authors: Smit Peter-Ben 
Published: September 2017

Abstract
What led to the issues that Paul addresses in 1 Corinthians 8? This paper argues that the missionary expansion of the early community led to a renegotiation of its ritual boundaries, in particular concerning question of ritual participation. Theory concerning ‘ritual failure’ is used in order to analyse the dynamics involved.
Resistance to Anglican Missionary (umca) Activities in Southern Malawi in 1861
Authors: Mbaya Henry 
Published: September 2017

Abstract
This paper recounts the encounter that occurred between the Anglican missionaries of the Universities Mission to Central Africa (umca) and the local Mang’anja people at Magomero, in Southern Malawi in 1861. It situates the encounter in the context of slave trade and local conflicts, and war between the Mang’anja and the Yao people in which the missionaries themselves were embroiled. The paper argues that, centred on the differences in perceptions, interpretations of issues that related to land, culture and religious worldviews, the encounter entailed some acts of resistance by the local Mang’anja people.
Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar
Authors: Landier Jordi , Kajeechiwa Ladda , Thwin May Myo , Parker Daniel M. , Chaumeau Victor , Wiladphaingern Jacher , Imwong Mallika , Miotto Olivo , Patumrat Krittaya , Duanguppama Jureeporn , Cerqueira Dominique , Malleret Benoit , Rénia Laurent , Nosten Suphak , von Seidlein Lorenz , Ling Clare , Proux Stéphane , Corbel Vincent , Simpson Julie A. , Dondorp Arjen M. , White Nicholas J. , Nosten François H. 
Published: September 2017

Background: Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers. This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar. Methods: Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored. Results: MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic P. falciparum carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable. Conclusions: This MDA was safe and feasible, and, could accelerate elimination of P. falciparum in addition to EDT and LLINs when community participation was sufficient.
Pengendalian penyakit hawar (lateblight) pada Kentang (Solanum tuberosum L.) melalui penerapan solarisasi tanah dan aplikasi agen hayati Trichoderma harzianum
Authors: Brugman Eirene , Purbajanti Endang Dwi , Fuskhah Eny 
Published: September 2017

The purpose of the research was to assess the effectiveness of soil solarization and biological agent Trichoderma harzianum application in controlling lateblight disease caused by Phytophthora infestans on potato. The experiment was assigned in a split plot design with soil solarization as main plot and the density of Trichoderma harzianum as sub-plot. Soil solarization treatment consisted of solarization (A1) and non-solarization (B1). Density of Trichoderma harzianum used is B1(control)= 0g, B2 = 10g (107 cfu/l), B3 = 20g (2 x 108 cfu/l), B4 = 30g (3 x 108 cfu/l) and B5 = 40 g (4 x 108 cfu/l). Soil solarization treatment is carried out by using transparent polyethylene sheets with a thickness of 45 µm. Parameters measured were soil temperature, intensity level of pathogen attack, the rate of infection and total yield. Data were subjected to ANOVA and followed by LSD test. Soil solarization for 4 weeks increase the soil temperature by 7,6oC and significantly increase the production of potato by 14.28%. Application of biological agent Trichoderma harzianum on level B4 30g (3 x 108 cfu /L) gives the best results in reducing the the intensity level of pathogen attack by 69.13% and the rate of disease infection into 1,012 unit/day. The results of this research may provide benefical information in the future for plant protection activities. Keywords : P.infestans, Trichoderma harzianum, soil solarization, potato
BAG S53P4 putty as bone graft substitute – a rabbit model
Authors: Saarenpää Ilkka , Stoor Patricia , Frantzén Janek 
Published: September 2017

AbstractBioactive glass (BAG) S53P4 granules represent a bone augmentation biomaterial for the surgical treatment of bony defects, even in challenging conditions such as osteomyelitis. The aim of this eight-week rabbit implantation study was to evaluate the biocompatibility and bone regeneration performance of a BAG S53P4 putty formulation following its implantation into the proximal tibia bone of twenty-eight New Zealand white rabbits. BAG S53P4 putty was compared to BAG S53P4 granules (0.5-0.8 mm) to evaluate whether the synthetic putty binder influences the bone regeneration of the osteostimulative granules. The putty formulation facilitates clinical use because of its mouldability, injectability and ease of mixing with autograft. Implantation of putty and granules into proximal tibia defects resulted in good osseointegration of the two groups. Both biomaterials were biocompatible, showed high new bone formation, high vascularization and periosteal growth. No signs of disturbed bone formation were observed due to the PEG-glycerol binder in the BAG S53P4 putty. Instead, intramedullary ossification and stromal cell reaction were more advanced in the putty group compared to the control group (p = 0.001 and p < 0.001). In conclusion, the novel mouldable BAG S53P4 putty showed reliable bone regeneration in bony defects without adverse tissue or cell reactions.
A rare case of a neonatal hepatic tumor presenting as hydrops fetalis
Authors: Shukla Samarth , Cheung Sandy , Boyar Vitaliya 
Published: September 2017

Abstract
Hepatic hemangioendothelioma is a rare and benign vascular tumor, usually asymptomatic at birth. However, it can present with severe cardio-respiratory symptoms and consumptive coagulopathy. Here we present a severe case of hepatic hemangioendothelioma presenting as hydrops fetalis, suggesting that it can have significant prenatal and postnatal morbidity.
Exact distributions of order statistics from ln,p-symmetric sample distributions
Authors: Müller K. , Richter W.-D. 
Published: September 2017

Abstract
We derive the exact distributions of order statistics from a finite number of, in general, dependent random variables following a joint ln,p-symmetric distribution. To this end,we first review the special cases of order statistics fromspherical aswell as from p-generalized Gaussian sample distributions from the literature. To study the case of general ln,p-dependence, we use both single-out and cone decompositions of the events in the sample space that correspond to the cumulative distribution function of the kth order statistic if they are measured by the ln,p-symmetric probability measure.We show that in each case distributions of the order statistics from ln,p-symmetric sample distribution can be represented as mixtures of skewed ln−ν,p-symmetric distributions, ν ∈ {1, . . . , n − 1}.
Hängen die Ergebnisse der zweiten juristischen Prüfung vom Examensort ab?
Authors: Kähler Lorenz , Engel Uwe , Ritter Franziska 
Published: September 2017

Zusammenfassung
Die Examensergebnisse sind für Juristen von so zentraler Bedeutung, dass sich die Frage aufdrängt, ob und wie stark die Prüfungen in den einzelnen Bundesländern miteinander vergleichbar sind. Das ist bisher nicht systematisch untersucht worden. Statistische Anhaltspunkte für diesen Vergleich ergeben sich aber durch einen Vergleich derjenigen, die das Bundesland nach der ersten juristischen Prüfung wechseln, mit denjenigen, die dort beide Prüfungen ablegen. Der folgende Beitrag stellt die Ergebnisse einer empirischen Studie vor, nach der sich ein Wechsel des Bundeslandes auf die zu erwartende Note auswirken kann.
Hypothalamic Tuberomammillary Nucleus Neurons: Electrophysiological Diversity and Essential Role in Arousal Stability
Authors: Fujita Akie , Bonnavion Patricia , Wilson Miryam H. , Mickelsen Laura E. , Bloit Julien , de Lecea Luis , Jackson Alexander C. 
Published: September 2017

Histaminergic (HA) neurons, found in the posterior hypothalamic tuberomammillary nucleus (TMN), extend fibers throughout the brain and exert modulatory influence over numerous physiological systems. Multiple lines of evidence suggest that the activity of HA neurons is important in the regulation of vigilance despite the lack of direct, causal evidence demonstrating its requirement for the maintenance of arousal during wakefulness. Given the strong correlation between HA neuron excitability and behavioral arousal, we investigated both the electrophysiological diversity of HA neurons in brain slices and the effect of their acute silencingin vivoin male mice. For this purpose, we first validated a transgenic mouse line expressing cre recombinase in histidine decarboxylase-expressing neurons (Hdc-Cre) followed by a systematic census of the membrane properties of both HA and non-HA neurons in the ventral TMN (TMNv) region. Through unsupervised hierarchical cluster analysis, we found electrophysiological diversity both between TMNv HA and non-HA neurons, and among HA neurons. To directly determine the impact of acute cessation of HA neuron activity on sleep–wake states in awake and behaving mice, we examined the effects of optogenetic silencing of TMNv HA neuronsin vivo. We found that acute silencing of HA neurons during wakefulness promotes slow-wave sleep, but not rapid eye movement sleep, during a period of low sleep pressure. Together, these data suggest that the tonic firing of HA neurons is necessary for the maintenance of wakefulness, and their silencing not only impairs arousal but is sufficient to rapidly and selectively induce slow-wave sleep.SIGNIFICANCE STATEMENTThe function of monoaminergic systems and circuits that regulate sleep and wakefulness is often disrupted as part of the pathophysiology of many neuropsychiatric disorders. One such circuit is the posterior hypothalamic histamine (HA) system, implicated in supporting wakefulness and higher brain function, but has been difficult to selectively manipulate owing to cellular heterogeneity in this region. Here we use a transgenic mouse to interrogate both the characteristic firing properties of HA neurons and their specific role in maintaining wakefulness. Our results demonstrate that the acute, cell type-specific silencing of HA neurons during wakefulness is sufficient to not only impair arousal but to rapidly and selectively induce slow-wave sleep. This work furthers our understanding of HA-mediated mechanisms that regulate behavioral arousal.