bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold molecules: Progress in quantum engineering of chemistry and quantum matter
Authors: Bohn John L. , Rey Ana Maria , Ye Jun
Published: September 2017

Cooling atoms to ultralow temperatures has produced a wealth of opportunities in fundamental physics, precision metrology, and quantum science. The more recent application of sophisticated cooling techniques to molecules, which has been more challenging to implement owing to the complexity of molecular structures, has now opened the door to the longstanding goal of precisely controlling molecular internal and external degrees of freedom and the resulting interaction processes. This line of research can leverage fundamental insights into how molecules interact and evolve to enable the control of reaction chemistry and the design and realization of a range of advanced quantum materials.
Synthetic oligosaccharides can replace animal-sourced low–molecular weight heparins
Authors: Xu Yongmei , Chandarajoti Kasemsiri , Zhang Xing , Pagadala Vijayakanth , Dou Wenfang , Hoppensteadt Debra Moorman , Sparkenbaugh Erica M. , Cooley Brian , Daily Sharon , Key Nigel S. , Severynse-Stevens Diana , Fareed Jawed , Linhardt Robert J. , Pawlinski Rafal , Liu Jian
Published: September 2017

A synthetic homogeneous low–molecular weight heparin provides a safe and effective therapeutic alternative.
ILC
regs
: The new kid in class
Authors: Scharschmidt Tiffany C.
Published: September 2017

ILC
regs
are a population of innate lymphoid cells that control innate intestinal inflammation through IL-10.
Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients
Authors: Dumas Eric K. , Gross Timothy , Larabee Jason , Pate Lance , Cuthbertson Hannah , Charlton Sue , Hallis Bassam , Engler Renata J. M. , Collins Limone C. , Spooner Christina E. , Chen Hua , Ballard Jimmy , James Judith A. , Farris A. Darise
Published: September 2017

Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of
Bacillus anthracis
that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with
Bacillus anthracis
spores or ET. This study compared humoral responses to ET in recipients of AVP (
n
= 33) versus anthrax vaccine adsorbed (AVA;
n
= 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 ± 58.6) of EF antibodies than AVA (4.2% and 7.8 ± 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines.
Protective Vaccine Efficacy of the Complete Form of PPE39 Protein from Mycobacterium tuberculosis Beijing/K Strain in Mice
Authors: Kim Ahreum , Hur Yun-Gyoung , Gu Sunwha , Cho Sang-Nae
Published: September 2017

The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of
Mycobacterium tuberculosis
in South Korea. Mice were immunized with MTKB_24820,
M. bovis
Bacilli Calmette-Guérin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the
M. tuberculosis
-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses (
P
< 0.05) and recalled gamma interferon (IFN-γ), interleukin-2 (IL-2), IL-6, and IL-17 responses (
P
< 0.05 or
P
< 0.01) to MTBK_24820. After challenge with the Beijing/K strain, an approximately 0.5 to 1.0 log
10
reduction in CFU in lungs and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared to those for control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4
+
T cells producing protective cytokines, such as IFN-γ and IL-17, in lungs and spleens (
P
< 0.01) and CD4
+
multifunctional T cells producing IFN-γ, tumor necrosis factor alpha (TNF-α), and/or IL-17 (
P
< 0.01) than in control mice, suggesting protection comparable to that of BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN-γ production were at the N terminus (amino acids 85 to 102 and 217 to 234). Its vaccine potential, along with protective immune responses
in vivo
, may be informative for vaccine development, particularly in regions where the
M. tuberculosis
Beijing/K-strain is frequently isolated from TB patients.
Filling Knowledge Gaps for Mimivirus Entry, Uncoating, and Morphogenesis
Authors: Andrade Ana Cláudia dos Santos Pereira , Rodrigues Rodrigo Araújo Lima , Oliveira Graziele Pereira , Andrade Kétyllen Reis , Bonjardim Cláudio Antônio , La Scola Bernard , Kroon Erna Geessien , Abrahão Jônatas Santos
Published: September 2017

Since the discovery of mimivirus, its unusual structural and genomic features have raised great interest in the study of its biology; however, many aspects concerning its replication cycle remain uncertain. In this study, extensive analyses of electron microscope images, as well as biological assay results, shed light on unclear points concerning the mimivirus replication cycle. We found that treatment with cytochalasin, a phagocytosis inhibitor, negatively impacted the incorporation of mimivirus particles by
Acanthamoeba castellanii
, causing a negative effect on viral growth in amoeba monolayers. Treatment of amoebas with bafilomicin significantly impacted mimivirus uncoating and replication. In conjunction with microscopic analyses, these data suggest that mimiviruses indeed depend on phagocytosis for entry into amoebas, and particle uncoating (and stargate opening) appears to be dependent on phagosome acidification. In-depth analyses of particle morphogenesis suggest that the mimivirus capsids are assembled from growing lamellar structures. Despite proposals from previous studies that genome acquisition occurs before the acquisition of fibrils, our results clearly demonstrate that the genome and fibrils can be acquired simultaneously. Our data suggest the existence of a specific area surrounding the core of the viral factory where particles acquire the surface fibrils. Furthermore, we reinforce the concept that defective particles can be formed even in the absence of virophages. Our work provides new information about unexplored steps in the life cycle of mimivirus.

IMPORTANCE
Investigating the viral life cycle is essential to a better understanding of virus biology. The combination of biological assays and microscopic images allows a clear view of the biological features of viruses. Since the discovery of mimivirus, many studies have been conducted to characterize its replication cycle, but many knowledge gaps remain to be filled. In this study, we conducted a new examination of the replication cycle of mimivirus and provide new evidence concerning some stages of the cycle which were previously unclear, mainly entry, uncoating, and morphogenesis. Furthermore, we demonstrate that atypical virion morphologies can occur even in the absence of virophages. Our results, along with previous data, allow us to present an ultimate model for the mimivirus replication cycle.
Characterization of a Replicating Mammalian Orthoreovirus with Tetracysteine-Tagged μNS for Live-Cell Visualization of Viral Factories
Authors: Bussiere Luke D. , Choudhury Promisree , Bellaire Bryan , Miller Cathy L.
Published: September 2017

Within infected host cells, mammalian orthoreovirus (MRV) forms viral factories (VFs), which are sites of viral transcription, translation, assembly, and replication. The MRV nonstructural protein μNS comprises the structural matrix of VFs and is involved in recruiting other viral proteins to VF structures. Previous attempts have been made to visualize VF dynamics in live cells, but due to current limitations in recovery of replicating reoviruses carrying large fluorescent protein tags, researchers have been unable to directly assess VF dynamics from virus-produced μNS. We set out to develop a method to overcome this obstacle by utilizing the 6-amino-acid (CCPGCC) tetracysteine (TC) tag and FlAsH-EDT2 reagent. The TC tag was introduced into eight sites throughout μNS, and the capacity of the TC-μNS fusion proteins to form virus factory-like (VFL) structures and colocalize with virus proteins was characterized. Insertion of the TC tag interfered with recombinant virus rescue in six of the eight mutants, likely as a result of loss of VF formation or important virus protein interactions. However, two recombinant (r)TC-μNS viruses were rescued and VF formation, colocalization with associating virus proteins, and characterization of virus replication were subsequently examined. Furthermore, the rTC-μNS viruses were utilized to infect cells and examine VF dynamics using live-cell microscopy. These experiments demonstrate active VF movement with fusion events as well as transient interactions between individual VFs and demonstrate the importance of microtubule stability for VF fusion during MRV infection. This work provides important groundwork for future in-depth studies of VF dynamics and host cell interactions.

IMPORTANCEMRV has historically been used as a model to study the double-stranded RNA (dsRNA)Reoviridaefamily, the members of which infect and cause disease in humans, animals, and plants. During infection, MRV forms VFs that play a critical role in virus infection but remain to be fully characterized. To study VFs, researchers have focused on visualizing the nonstructural protein μNS, which forms the VF matrix. This work provides the first evidence of recovery of replicating reoviruses in which VFs can be labeled in live cells via introduction of a TC tag into the μNS open reading frame. Characterization of each recombinant reovirus sheds light on μNS interactions with viral proteins. Moreover, utilizing the TC-labeling FlAsH-EDT2 biarsenical reagent to visualize VFs, evidence is provided of dynamic VF movement and interactions at least partially dependent on intact microtubules.
Livedoid eruption in a patient affected by T-γδ large granular lymphocyte leukaemia
Authors: Biolo Giulia , Sacco Giorgia , Russo Irene , Alaibac Mauro
Published: September 2017

Livedo is an ischaemic dermopathy characterised by a reddish-blue to violaceous mottling of the skin with a net-like reticular appearance. Livedo has been described in association with several medical conditions including lymphoproliferative disorders. Here, we describe the case of a 60-year-old woman who was presented with asymptomatic and persistent livedoid eruption on her trunk, lower and upper extremities as manifestation of an indolent form of T-γδ large granular lymphocyte leukaemia. To the best of our knowledge, this is the first report describing the association between livedo reticularis and T-γδ large granular lymphocyte leukaemia. It is plausible that a pathogenetic role of the neoplastic process is based on a cytotoxic antiendothelial activity.
Bilateral tarsal tunnel syndrome attributed to bilateral fibrous tarsal coalition and symmetrical hypertrophy of the sustentaculum tali
Authors: Bhat Anil K , Madi Sandesh , Mane Prajwal Prabhudev , Acharya Ashwath
Published: September 2017

Tarsal tunnel syndrome (TTS) is one of the frequently encountered entrapment neuropathies of the lower limb. Most often the aetiology is considered to be idiopathic. However, it has to be thoroughly investigated to rule out diverse extrinsic and intrinsic causes. The sustentaculum tali (ST) forms the superior part of the distal tarsal tunnel, and any increase in its size may result in irritation of the tibial nerve or its branches, the medial and lateral plantar nerves or decrease the overall volume of the tarsal tunnel culminating to clinical features of TTS. A hypertrophied ST is an extremely rare cause for TTS, and we report perhaps a first case of bilateral TTS in a young adult due to bilateral symmetrical hypertrophied ST which in turn was a result of bilateral fibrous tarsal coalition. Staged bilateral surgical excision of the hypertrophied part of ST and the underlying fibrous tarsal coalition ensured prompt symptomatic relief.
Granulomatous hepatitis in a patient with Crohn's disease and cholestasis
Authors: Patedakis Litvinov Bogdan Ioannis , Pathak Amit P
Published: September 2017

We describe a case of a 23-year-old woman with a history of Crohn's disease (CD), who initially presented with sepsis-like symptoms, subsequently developed severe cholestasis and following extensive inpatient workup was found to have non-caseating granulomas on her liver biopsy. Infectious aetiologies were excluded and the patient was treated with oral corticosteroids, which ameliorated but did not completely reverse the cholestasis. We review the differential diagnosis of hepatic granulomas and discuss the potential difficulties in establishing their exact aetiology in patients with CD.
Analysing voice quality and pitch in interactions of emergency care simulation
Authors: Coffey Frank , Tsuchiya Keiko , Timmons Stephen , Baxendale Bryn , Adolphs Svenja , Atkins Sarah
Published: September 2017

Background/aims

In emergency care, healthcare professionals (HCPs) interact with both a patient and their colleagues at the same time. How HCPs regulate the two distinct interactions is our central interest. Focusing on HCPs’ use of their voice quality and pitch, a multimodal analysis of the interaction in a simulation training session was conducted. Our aims are (1) to compare the use of HCPs’ voice quality and pitch in HCP–patient and HCP–HCP interactions, (2) to examine how different voice quality and pitch function in interaction, and (3) to develop the research methodology so as to integrate multimodal features in emergency care interaction for analysis.

Methods

Three HCPs performed a scripted acute care scenario (chest pain) at the simulation centre. The multimodal corpus-based approach was applied to analyse the varying voice pitch and quality of the HCPs, in interactions with a simulated patient (SP) and with two other HCPs, in emergency care training.

Results

The HCPs tended to use a clear voice when they talk to an SP and a ‘shattered’ voice to colleagues in the team. The pitch was raised to talk to an SP, by Helen (a nurse) and Mike (a doctor).

Conclusion

This indicates that the HCPs strategically change their voice quality and pitch according to the addressees, regulating the interaction.
Cardiorespiratory demand of acute voluntary cycling with functional electrical stimulation in individuals with multiple sclerosis with severe mobility impairment
Authors: Edwards Thomas , Motl Robert W. , Pilutti Lara A.
Published: September 2017

Exercise training is one strategy for improving cardiorespiratory fitness (CRF) in multiple sclerosis (MS); however, few modalities are accessible for those with severe mobility impairment. Functional electrical stimulation (FES) cycling is an adapted exercise modality with the potential for improving CRF in people with severe MS. The objective of this study was to characterize the cardiorespiratory response of acute voluntary cycling with FES in people with MS with severe mobility impairment, and to compare this response to passive leg cycling. Eleven participants with MS that required assistance for ambulation completed a single bout of voluntary cycling with FES or passive leg cycling. Oxygen consumption, heart rate (HR), work rate (WR), and ratings of perceived exertion (RPE) were recorded throughout the session. For the FES group, mean exercising oxygen consumption was 8.7 ± 1.8 mL/(kg·min)−1, or 63.5% of peak oxygen consumption. Mean HR was 102 ± 9.7 bpm, approximately 76.4% of peak HR. Mean WR was 27.0 ± 9.2 W, or 57.3% of peak WR, and median RPE was 13.5 (interquartile range = 5.5). Active cycling with FES was significantly (p < 0.05) more intense than passive leg cycling based on oxygen consumption, HR, WR, and RPE during exercise. In conclusion, voluntary cycling with FES elicited an acute response that corresponded with moderate-to vigorous-intensity activity, suggesting that active cycling with FES can elicit a sufficient stimulus for improving CRF.
On the precision of predicting fishing location using data from the vessel monitoring system (VMS)
Authors: Muench Angela , DePiper Geret Sean , Demarest Chad
Published: September 2017

Defining fishing grounds based on data from vessel monitoring systems (VMS) has been a widely researched topic in recent years. Much of the research has focused on filtering algorithms for identifying fishing locations from VMS point data, most often supplemented with either imputed or reported vessel speed information. This study compared the precision of categorizing fishing locations from VMS data either by the most wide-spread “speed rule” approach or by a probability model. Using data from Northeast U.S. Fisheries for fishing years 2010–2014, we showed that the traditional representation of fishing activities as derived by speed rules leads to a severe misrepresentation of fishing grounds for gears other than bottom otter trawl. Predictions based on probability models outperformed gear-specific speed rules in classifying VMS polls for sink gillnet and scallop dredge trips, without adding substantial computational effort. The probability models thus provide the largest improvements in gears with complicated fishing patterns, while controlling for issues such as fleet dynamics that historically have not been dealt with in the static speed rules but which can have significant impacts on the quality of predictions.
Cosmogenic activation of materials
Authors: Cebrián Susana
Published: September 2017

Experiments looking for rare events like the direct detection of dark matter particles, neutrino interactions or the nuclear double beta decay are operated deep underground to suppress the effect of cosmic rays. But, the production of radioactive isotopes in materials due to previous exposure to cosmic rays is a hazard when ultra-low background conditions are required. In this context, the generation of long-lived products by cosmic nucleons has been studied for many detector media and for other materials commonly used. Here, the main results obtained on the quantification of activation yields on the Earth’s surface will be summarized, considering both measurements and calculations following different approaches. The isotope production cross-sections and the cosmic ray spectrum are the two main ingredients when calculating this cosmogenic activation; the different alternatives for implementing them will be discussed. Activation that can take place deep underground mainly due to cosmic muons will be briefly commented too. Presently, the experimental results for the cosmogenic production of radioisotopes are scarce and discrepancies between different calculations are important in many cases, but the increasing interest on this background source which is becoming more and more relevant can help to change this situation.
Circular geodesics in tidal-charged black hole
Authors: Pradhan Parthapratim
Published: September 2017

We study the existence and stability criteria for circular geodesics of spherically symmetric tidal-charged black hole (BH). We investigate in details the equatorial causal geodesics of the tidal-charged BH in comparison with spherically symmetric Reissner–Nordström BH spacetime. We particularly focused on both the null circular geodesics and time-like circular geodesics. Using the effective potential diagram, we have compared the geodesic structure between two spacetimes. We have derived the ISCO (innermost stable circular orbit), MBCO (marginally bound circular orbit) and CPO (circular photon orbit) for both the spacetimes. Moreover, we have derived the quasi-normal modes[Formula: see text]QNMs[Formula: see text] frequency in the eikonal limit for both the spacetimes via Lyapunov exponent. In the appendix section, we have shown that a spherically symmetric tidal-charged BH can act as particle accelerators with ultra-high center-of-mass (CM) energy in the limiting case of maximal BH tidal-charge[Formula: see text] and it is possible when two neutral particles are colliding near the horizon.
Transport maps for β-matrix models in the multi-cut regime
Authors: Bekerman Florent
Published: September 2017

We use the transport methods develop in [F. Bekerman, A. Figalli and A. Guionnet, Transport maps for [Formula: see text]-matrix models and universality, Commun. Math. Phys. 338(2) (2013) 589–619] to obtain universality results for local statistics of eigenvalues in the bulk and at the edge for [Formula: see text]-matrix models in the multi-cut regime. We construct an approximate transport map inbetween two probability measures from the fixed filling fraction model discussed in [G. Borot, A. Guionnet and K. K. Kozlowski, Large-N asymptotic expansion for mean field models with coulomb gas interaction, Int. Math. Res. Not. (2015)] and deduce from it universality in the initial model.
Interplay of mid-Carboniferous sediment sources on the northern margin of the Wales-Brabant High
Authors: Hallsworth C. R. , Chisholm J. I.
Published: September 2017

Heavy mineral analysis and garnet geochemistry of late Visean and Namurian sandstones in the southernmost part of the Pennine Basin show clear distinctions between sediment transported from a distant northern source and sediment derived from local sources to the south on the Wales-Brabant High. Monazite is common in northern sandstones, whereas it is rare in southern sandstones. Southern sandstones may also contain chrome spinel: variations in its abundance identify spatial and temporal variations in the southern supply. There is evidence in some sandstones that material from the two sources has become mixed. Feldspar content has been used historically as an indicator of provenance in the study area, but the new data show that it might not always be reliable. Detailed stratigraphical analysis across the region has allowed the identification of the interplay of different southern and northern sediment supplies through time. The integration of heavy mineral analysis with palaeocurrent data has enabled the approximate geographical distribution of lobes of northern and southern sediment to be mapped out for successive intervals of late Visean and Namurian time. The southern sediment was carried into the basin throughout the late Visean and Namurian by small river systems, several of which can be recognized within the study area. The northern sediment entered via two lobes; it first entered the region in mid-Namurian (late Kinderscoutian) times and continued through the later Namurian into the Westphalian.
A Requirements Analysis Framework for Development of Service Oriented Systems
Authors: Banerjee Shreya , Sarkar Anirban
Published: September 2017

In Service Oriented Systems (SOS), implementation of business processes is accomplished through services in distributed, loosely coupled manner based on business process requirements of the users. Consequently, importance of businessprocess requirements analysis for development of SOS is strongly highlighted in both academia and industry. Usually, traditional requirements engineering is competent enough to specify and analysis business requirements for development of software systems efficiently. However, Service Oriented Requirement Engineering (SORE) emerging for SOS development is differed from traditional requirement engineering due to complex nature of services. Yet, a serious gap is still exist between early and detailed specification of business process requirements in SORE and further mapping towards design of SOS from set of business processes. To address this issue, in this paper, a requirements analysis framework is proposed for development of SOS systems. The contribution of the proposed work is formal representation of business process requirements for SOS based on business scenario and Cause-Effect-Dependency (CED) graph in dimensions of six aspects of services -- What, Why, How, Who, When and Where (5W1H). Both early and detailed level requirements analysis in the context of SORE is facilitated by the proposed approach. Beside, traceability of proposed approach towards design of business processes for development of SOS is also exhibited in this paper. Moreover, the practical utility of the proposed approach is demonstrated using a suitable case study.
Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated Ca2+, cGMP, and lysophosphatidic acid
Authors: Avula Leela Rani , Chen Tiane , Kovbasnjuk Olga , Donowitz Mark
Published: September 2017

The intestinal epithelial brush border Na+/H+ exchanger NHE3 accounts for a large component of intestinal Na absorption. NHE3 is regulated during digestion by signaling complexes on its COOH terminus that include the four multi-PDZ domain-containing NHERF family proteins. All bind to NHE3 and take part in different aspects of NHE3 regulation. Because the roles of each NHERF appear to vary on the basis of the cell model or intestinal segment studied and because of our recent finding that a NHERF3-NHERF2 heterodimer appears important for NHE3 regulation in Caco-2 cells, we examined the role of NHERF3 and NHERF2 in C57BL/6 mouse jejunum using homozygous NHERF2 and NHERF3 knockout mice. NHE3 activity was determined with two-photon microscopy and the dual-emission pH-sensitive dye SNARF-4F. The jejunal apical membrane of NHERF3-null mice appeared similar to wild-type (WT) mice in surface area, microvillus number, and height, which is similar to results previously reported for jejunum of NHERF2-null mice. NHE3 basal activity was not different from WT in either NHERF2- or NHERF3-null jejunum, while d-glucose-stimulated NHE3 activity was reduced in NHERF2, but similar to WT in NHERF3 KO. LPA stimulation and UTP (elevated Ca2+) and cGMP inhibition of NHE3 were markedly reduced in both NHERF2- and NHERF3-null jejunum. Forskolin inhibited NHE3 in NHERF3-null jejunum, but the extent of inhibition was reduced compared with WT. The forskolin inhibition of NHE3 in NHERF2-null mice was too inconsistent to determine whether there was an effect and whether it was altered compared with the WT response. These results demonstrate similar requirement for NHERF2 and NHERF3 in mouse jejunal NHE3 regulation by LPA, Ca2+, and cGMP. The explanation for the similarity is not known but is consistent with involvement of a brush-border NHERF3-NHERF2 heterodimer or sequential NHERF-dependent effects in these aspects of NHE3 regulation.

NEW & NOTEWORTHY NHERF2 and NHERF3 are apical membrane multi-PDZ domain-containing proteins that are involved in regulation of intestinal NHE3. This study demonstrates that NHERF2 and NHERF3 have overlapping roles in NHE3 stimulation by LPA and inhibition by elevated Ca2+ and cGMP. These results are consistent with their role being as a NHERF3-NHERF2 heterodimer or via sequential NHERF-dependent signaling steps, and they begin to clarify a role for multiple NHERF proteins in NHE3 regulation.
Hepatocyte nuclear factor 4α regulates the expression of intestinal epithelial Na+/H+ exchanger isoform 3
Authors: Muthusamy Saminathan , Jeong Jong Jin , Cheng Ming , Bonzo Jessica A. , Kumar Anoop , Gonzalez Frank J. , Borthakur Alip , Dudeja Pradeep K. , Saksena Seema , Malakooti Jaleh
Published: September 2017

Na+/H+ exchanger isoform 3 (NHE3) plays a key role in coupled electroneutral NaCl absorption in the mammalian intestine. Reduced NHE3 expression or function has been implicated in the pathogenesis of diarrhea associated with inflammatory bowel disease (IBD) or enteric infections. Our previous studies revealed transcriptional regulation of NHE3 by various agents such as TNF-α, IFN-γ, and butyrate involving transcription factors Sp1 and Sp3. In silico analysis revealed that the NHE3 core promoter also contains a hepatocyte nuclear factor 4α (HNF-4α) binding site that is evolutionarily conserved in several species suggesting that HNF-4α has a role in NHE3 regulation. Nhe3 mRNA levels were reduced in intestine-specific Hnf4α-null mice. However, detailed mechanisms of NHE3 regulation by HNF-4α are not known. We investigated the regulation of NHE3 gene expression by HNF-4α in vitro in the human intestinal epithelial cell line C2BBe1 and in vivo in intestine-specific Hnf4α-null ( Hnf4αΔIEpC) and control ( Hnf4αfl/fl) mice. HNF-4α knockdown by short interfering RNA in C2BBe1 cells significantly decreased NHE3 mRNA and NHE3 protein levels. Gel mobility shift and chromatin immunoprecipitation assays revealed that HNF-4α directly interacts with the HNF-4α motif in the NHE3 core promoter. Site-specific mutagenesis on the HNF-4α motif decreased, whereas ectopic overexpression of HNF-4α increased, NHE3 promoter activity. Furthermore, loss of HNF-4α in Hnf4αΔIEpC mice decreased colonic Nhe3 mRNA and NHE3 protein levels. Our results demonstrate a novel role for HNF-4α in basal regulation of NHE3 expression. These studies represent an important and novel target for therapeutic intervention in IBD-associated diarrhea.

NEW & NOTEWORTHY Our studies for the first time show that hepatocyte nuclear factor 4α directly regulates NHE3 promoter activity and its basal expression in the intestine.
Hemoglobin polymerization via disulfide bond formation in the hypoxia-tolerant turtleTrachemys scripta: implications for antioxidant defense and O2transport
Authors: Petersen Asbjørn G. , Petersen Steen V. , Frische Sebastian , Drakulic Srdja , Golas Monika M. , Sander Bjoern , Fago Angela
Published: September 2017

The ability of many reptilian hemoglobins (Hbs) to form high-molecular weight polymers, albeit known for decades, has not been investigated in detail. Given that turtle Hbs often contain a high number of cysteine (Cys), potentially contributing to the red blood cell defense against reactive oxygen species, we have examined whether polymerization of Hb could occur via intermolecular disulfide bonds in red blood cells of freshwater turtle Trachemys scripta, a species that is highly tolerant of hypoxia and oxidative stress. We find that one of the two Hb isoforms of the hemolysate HbA is prone to polymerization in vitro into linear flexible chains of different size that are visible by electron microscopy but not the HbD isoform. Polymerization of purified HbA is favored by hydrogen peroxide, a main cellular reactive oxygen species and a thiol oxidant, and inhibited by thiol reduction and alkylation, indicating that HbA polymerization is due to disulfide bonds. By using mass spectrometry, we identify Cys5 of the αA-subunit of HbA as specifically responsible for forming disulfide bonds between adjacent HbA tetramers. Polymerization of HbA does not affect oxygen affinity, cooperativity, and sensitivity to the allosteric cofactor ATP, indicating that HbA is still fully functional. Polymers also form in T. scripta blood after exposure to anoxia but not normoxia, indicating that they are of physiological relevance. Taken together, these results show that HbA polymers may form during oxidative stress and that Cys5αAof HbA is a key element of the antioxidant capacity of turtle red blood cells.
Comparative NMR and NIRS analysis of oxygen-dependent metabolism in exercising finger flexor muscles
Authors: Bendahan David , Chatel Benjamin , Jue Thomas
Published: September 2017

Muscle contraction requires the physiology to adapt rapidly to meet the surge in energy demand. To investigate the shift in metabolic control, especially between oxygen and metabolism, researchers often depend on near-infrared spectroscopy (NIRS) to measure noninvasively the tissue O2. Because NIRS detects the overlapping myoglobin (Mb) and hemoglobin (Hb) signals in muscle, interpreting the data as an index of cellular or vascular O2requires deconvoluting the relative contribution. Currently, many in the NIRS field ascribe the signal to Hb. In contrast,1H NMR has only detected the Mb signal in contracting muscle, and comparative NIRS and NMR experiments indicate a predominant Mb contribution. The present study has examined the question of the NIRS signal origin by measuring simultaneously the1H NMR,31P NMR, and NIRS signals in finger flexor muscles during the transition from rest to contraction, recovery, ischemia, and reperfusion. The experiment results confirm a predominant Mb contribution to the NIRS signal from muscle. Given the NMR and NIRS corroborated changes in the intracellular O2, the analysis shows that at the onset of muscle contraction, O2declines immediately and reaches new steady states as contraction intensity rises. Moreover, lactate formation increases even under quite aerobic condition.
Regulatory T cells in acute and chronic kidney diseases
Authors: Sharma Rahul , Kinsey Gilbert R.
Published: September 2017

Foxp3-expressing CD4+regulatory T cells (Tregs) make up one subset of the helper T cells (Th) and are one of the major mechanisms of peripheral tolerance. Tregs prevent abnormal activation of the immune system throughout the lifespan, thus protecting from autoimmune and inflammatory diseases. Recent studies have elucidated the role of Tregs beyond autoimmunity. Tregs play important functions in controlling not only innate and adaptive immune cell activation, but also regulate nonimmune cell function during insults and injury. Inflammation contributes to a multitude of acute and chronic diseases affecting the kidneys. This review examines the role of Tregs in pathogenesis of renal inflammatory diseases and explores the approaches for enhancing Tregs for prevention and therapy of renal inflammation.
Intrinsic exercise capacity in rats influences dopamine neuroplasticity induced by physical training
Authors: Rabelo Patrícia C. R. , Horta Nayara A. C. , Cordeiro Letícia M. S. , Poletini Maristela O. , Coimbra Cândido C. , Szawka Raphael E. , Soares Danusa D.
Published: September 2017

The study evaluates whether the intrinsic capacity for physical exercise influences dopamine neuroplasticity induced by physical training. Male rats were submitted to three progressive tests until fatigue. Based on the maximal time of exercise (TE), rats were considered as low performance (LP), standard performance (SP) or high performance (HP) to exercise. Eight animals from each group (LP, SP, and HP) were randomly subdivided in sedentary (SED) or trained (TR). Physical training was performed for 6 wk. After that, concentrations of dopamine (DA), serotonin (5-HT), and their metabolites and mRNA levels of D1 receptor ( Drd1), D2 receptor ( Drd2), dopamine transporter ( Dat), tyrosine hydroxylase ( Th), glia cell line neurotrophic factor ( Gdnf), and brain-derived neurotrophic factor ( Bdnf) were determined in the caudate-putamen (CPu). TE was increased with training in all performance groups. However, the relative increase was markedly higher in LP rats, and this was associated with a training-induced increase in dopaminergic activity in the CPu, which was determined by the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio. An opposite monoamine response was found in HP-TR rats, in which physical training decreased the DOPAC/DA ratio in the CPu. Moreover, LP-SED rats displayed higher levels of Drd2 in the CPu compared with the other SED groups, and this higher expression was decreased by physical training. Physical training also decreased Dat and increased Gdnf in the CPu of LP rats. Physical training decreased Bdnf in the CPu only in HP rats. Thus, we provide evidence that the intrinsic capacity to exercise affects the neuroplasticity of the dopaminergic system in response to physical training.

NEW & NOTEWORTHY The findings reported reveal that dopaminergic neuroplasticity in caudate-putamen induced by physical training is influenced by the intrinsic capacity to exercise in rats. To evaluate the dopaminergic neuroplasticity, we analyzed mRNA levels of D1 receptor, D2 receptor, dopamine transporter, tyrosine hydroxylase, glia cell line neurotrophic factor, and brain-derived neurotrophic factor as well as concentrations of dopamine, serotonin, and their metabolites. These results expand our knowledge about the interrelationship between genetic background, physical training, and dopaminergic neuroplasticity.
The effect of prior knowledge and intelligibility on the cortical entrainment response to speech
Authors: Baltzell Lucas S. , Srinivasan Ramesh , Richards Virginia M.
Published: September 2017

It has been suggested that cortical entrainment plays an important role in speech perception by helping to parse the acoustic stimulus into discrete linguistic units. However, the question of whether the entrainment response to speech depends on the intelligibility of the stimulus remains open. Studies addressing this question of intelligibility have, for the most part, significantly distorted the acoustic properties of the stimulus to degrade the intelligibility of the speech stimulus, making it difficult to compare across “intelligible” and “unintelligible” conditions. To avoid these acoustic confounds, we used priming to manipulate the intelligibility of vocoded speech. We used EEG to measure the entrainment response to vocoded target sentences that are preceded by natural speech (nonvocoded) prime sentences that are either valid (match the target) or invalid (do not match the target). For unintelligible speech, valid primes have the effect of restoring intelligibility. We compared the effect of priming on the entrainment response for both 3-channel (unintelligible) and 16-channel (intelligible) speech. We observed a main effect of priming, suggesting that the entrainment response depends on prior knowledge, but not a main effect of vocoding (16 channels vs. 3 channels). Furthermore, we found no difference in the effect of priming on the entrainment response to 3-channel and 16-channel vocoded speech, suggesting that for vocoded speech, entrainment response does not depend on intelligibility.

NEW & NOTEWORTHY Neural oscillations have been implicated in the parsing of speech into discrete, hierarchically organized units. Our data suggest that these oscillations track the acoustic envelope rather than more abstract linguistic properties of the speech stimulus. Our data also suggest that prior experience with the stimulus allows these oscillations to better track the stimulus envelope.
Tests of the sorption and olfactory “fovea” hypotheses in the mouse
Authors: Coppola David M. , Ritchie Brittaney E. , Craven Brent A.
Published: September 2017

The spatial distribution of receptors within sensory epithelia (e.g., retina and skin) is often markedly nonuniform to gain efficiency in information capture and neural processing. By contrast, odors, unlike visual and tactile stimuli, have no obvious spatial dimension. What need then could there be for either nearest-neighbor relationships or nonuniform distributions of receptor cells in the olfactory epithelium (OE)? Adrian (Adrian ED. J Physiol 100: 459–473, 1942; Adrian ED. Br Med Bull 6: 330–332, 1950) provided the only widely debated answer to this question when he posited that the physical properties of odors, such as volatility and water solubility, determine a spatial pattern of stimulation across the OE that could aid odor discrimination. Unfortunately, despite its longevity, few critical tests of the “sorption hypothesis” exist. Here we test the predictions of this hypothesis by mapping mouse OE responses using the electroolfactogram (EOG) and comparing these response “maps” to computational fluid dynamics (CFD) simulations of airflow and odorant sorption patterns in the nasal cavity. CFD simulations were performed for airflow rates corresponding to quiet breathing and sniffing. Consistent with predictions of the sorption hypothesis, water-soluble odorants tended to evoke larger EOG responses in the central portion of the OE than the peripheral portion. However, sorption simulation patterns along individual nasal turbinates for particular odorants did not correlate with their EOG response gradients. Indeed, the most consistent finding was a rostral-greater to caudal-lesser response gradient for all the odorants tested that is unexplained by sorption patterns. The viability of the sorption and related olfactory “fovea” hypotheses are discussed in light of these findings.

NEW & NOTEWORTHY Two classical ideas concerning olfaction’s receptor-surface two-dimensional organization—the sorption and olfactory fovea hypotheses—were found wanting in this study that afforded unprecedented comparisons between electrophysiological recordings in the mouse olfactory epithelium and computational fluid dynamic simulations of nasal airflow. Alternatively, it is proposed that the olfactory receptor layouts in macrosmatic mammals may be an evolutionary contingent state devoid of the functional significance found in other sensory epithelia like the cochlea and retina.
Roles of Interferons in Pregnant Women with Dengue Infection: Protective or Dangerous Factors
Authors: Zhang Hao , He Zhiyi , Zeng Wenting , Peng Hong-Juan
Published: September 2017

Dengue infection is a serious public health problem in tropical and subtropical areas. With the recent outbreaks of Zika disease and its reported correlation with microcephaly, the large number of pregnancies with dengue infection has become a serious concern. This review describes the epidemiological characteristics of pregnancy with dengue and the initial immune response to dengue infection, especially in IFNs production in this group of patients. Dengue is much more prevalent in pregnant women compared with other populations. The severity of dengue is correlated with the level of IFNs, while the serum IFN level must be sufficiently high to maintain the pregnancy and to inhibit virus replication.
Dietary Flaxseed Oil Prevents Western‐Type Diet‐Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein‐E Knockout Mice
Authors: Han Hao , Qiu Fubin , Zhao Haifeng , Tang Haiying , Li Xiuhua , Shi Dongxing
Published: September 2017

The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Intake of n‐3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n‐3) and docosahexaenoic acid (DHA, C22:6n‐3), is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α‐linolenic acid (ALA, C18:3n‐3), a plant‐derived n‐3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein‐E knockout (apoE‐KO) mice were given a normal chow diet, a western‐type high‐fat and high‐cholesterol diet (WTD), or a WTD diet containing 10% flaxseed oil (WTD + FO) for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD‐induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP‐1c, ACC), triacylglycerol catabolism (PPARα, CPT1A, and ACOX1), inflammation (NF‐κB, IL‐6, TNF‐α, and MCP‐1), and oxidative stress (ROS, MDA, GSH, and SOD).
Pancreatic Tuberculosis with Vascular Involvement and Peritoneal Dissemination in a Young Man
Authors: Zhu Meng , Zhang Ning , Tao Wei , Wang Zhitao , He Shuixiang
Published: September 2017

Pancreatic tuberculosis (TB) is an extremely rare form of extrapulmonary tuberculosis even in endemic areas that masquerades as a mass or inflammation because of lack of typical clinical manifestations and radiologic features and therefore usually misdiagnosed as a pancreatic malignancy or pancreatitis. Here we present a 23-year-old young man with pancreatic tuberculosis mimicking pancreatic head carcinoma A man who suffered from upper abdominal pain and nausea for half a month was admitted to our hospital. Narrow band imaging (NBI) and gastroscopic imaging, together with endoscopic ultrasonography (EUS), revealed a duodenal bulb mucous prominences lesion. Computed tomography (CT) and magnetic resonance imaging (MRI) both suggested a pancreatic mass which resembled a pancreatic head tumor that had a higher risk of malignancy. The patient therefore accepted an exploratory laparotomy and pancreatoduodenectomy, Whipple operation. Biopsies of pancreas, duodenum, lymph nodes, omentum, and adipose tissues were all performed, revealing tuberculosis infection in pancreas, hepatic portal vein infiltration, and peritoneal dissemination. The patient was treated successfully after operation and recovered with standard anti-TB drugs for 6 months. Timely reporting of this rare case can help physicians improve their ability to identify several specific illnesses and diseases that share confusing signs or symptoms clinically and radiographically.
Gibberellic Acid Production by Different Fermentation Systems Using Citric Pulp as Substrate/Support
Authors: de Oliveira Juliana , Rodrigues Cristine , Vandenberghe Luciana P. S. , Câmara Marcela C. , Libardi Nelson , Soccol Carlos R.
Published: September 2017

Gibberellic acid (GA3) is an important phytohormone, a member of gibberellins family, which acts as a promoter and regulator of plant growth. This study aimed to evaluate GA3 production by Fusarium moniliforme LPB03 and Gibberella fujikuroi LPB06 using different techniques of fermentation, solid state fermentation (SSF), submerged fermentation (SmF), and semisolid state fermentation (SSSF), and different types of bioreactors. In all techniques, citric pulp (CP), a subproduct obtained from the extraction of orange juice, was employed as the substrate/support. GA3 production by SSF reached 7.60 g kg−1 and 7.34 g kg−1 in Erlenmeyer flasks and column bioreactors, respectively. For SmF, the highest concentration of GA3 obtained was 236.00 mg L−1 in Erlenmeyer flasks, 273.00 mg L−1 in a 10 L stirred tank reactor (STR), and 203.00 mg L−1 in a 1.5 L bubble column reactor (BCR). SSSF was conducted with a CP suspension. In this case, GA3 concentration reached 331.00 mg L−1 in Erlenmeyer flasks and 208 mg L−1 in a BCR. The choice of the fermentation technique is undoubtedly linked to the characteristics and productivity of each process. The methods studied are inexpensive and were found to produce good proportions of GA3, making them suitable for several applications.