bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards bedside washing of stored red blood cells: a prototype of a simple apparatus based on microscale sedimentation in normal gravity
Authors: Khanal G. , Huynh R. A. , Torabian K. , Xia H. , Vörös E. , Shevkoplyas S. S.
Published: October 2017

Background and Objectives

Infusion of by‐products of red blood cell (RBC) storage‐induced degradation as well as of the residual plasma proteins and the anticoagulant‐preservative solution contained in units of stored blood serve no therapeutic purpose and may be harmful to some patients. Here, we describe a prototype of a gravity‐driven system for bedside washing of stored RBCs.

Materials and Methods

Stored RBCs were diluted to 10% haematocrit (Hct) with normal saline, matching the conventional washing procedure. The dilute RBC suspensions were passed through a column of coiled tubing to allow RBC sedimentation in normal gravity, thus separating them from the washing solution. Washed RBCs were collected using bifurcations located along the tubing. Washing efficiency was quantified by measuring Hct, morphology, deformability, free haemoglobin and total‐free protein.

Results

The gravity‐driven washing system operating at 0·5 ml/min produced washed RBCs with final Hct of 36·7 ± 3·4% (32·3–41·2%, n = 10) and waste Hct of 3·4 ± 0·7% (2·4–4·3%, n = 10), while removing 80% of free haemoglobin and 90% of total‐free protein. Washing improved the ability of stored RBCs to perfuse an artificial microvascular network by 20%. The efficiency of washing performed using the gravity‐driven system was not significantly different than that of conventional centrifugation.

Conclusions

This proof‐of‐concept study demonstrates the feasibility of washing stored RBCs using a simple, disposable system with efficiency comparable to that of conventional centrifugation, and thus represents a significant first step towards enabling low‐cost washing of stored blood at bedside.
Synthetic liver function is detectable in transgenic porcine livers perfused with human blood
Authors: Cimeno Arielle , French Beth M. , Powell Jessica M. , Phelps Carol , Ayares David , O'Neill Natalie A. , Laird Christopher T. , Pierson Richard N. , Azimzadeh Agnes M. , Barth Rolf N. , LaMattina John C.
Published: October 2017

In addition to immune barriers, molecular incompatibilities between species are predicted to limit pig liver survival in primate xenotransplantation models. Assessment and measurement of synthetic function of genetically modified porcine livers after ex vivo perfusion with human blood have not previously been described. Eight porcine livers from α1,3‐galactosyl transferase knockout and human membrane cofactor (GalTKO.hCD46), six livers from GalTKO.hCD46 and N‐glycolylneuraminic acid knockout (GalTKO.hCD46.Neu5GcKO), and six livers from GalTKO.hCD46 with humanized decay‐accelerating factor (hCD55), endothelial protein C receptor (hEPCR), tissue factor pathway inhibitor (hTFPI), and integrin‐associated protein (hCD47) (GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47) pigs were perfused with human blood under physiologic conditions. Timed blood samples were tested for liver enzymes and for pig‐specific albumin production via Western blot. Porcine albumin levels increased with time in all experiments. By densitometry, GalTKO.hCD46.Neu5GcKO livers had the highest albumin levels, measured both as total produced, and when controlled for perfusion duration, compared to GalTKO.hCD46 (P = .068) and GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47 livers (P = .04). Porcine livers perfused with human blood demonstrated the synthetic ability to produce albumin in all cases. GalTKO.hCD46.Neu5GcKO pig livers demonstrated the most robust albumin production. This suggests that the Neu5GcKO phenotype provides a protective effect on the graft due to decreased human antibody recognition and graft injury.
Generalized synchronization of identical and nonidentical chaotic dynamical systems via master approaches
Authors: Ali-Tahir Shko , Sari Murat , Bouhamidi Abderrahman
Published: October 2017

The main objective of this work is to discuss a generalized synchronization of a coupled chaotic identicaland nonidentical dynamical systems. We propose a method used to study generalized synchronization in masterslavesystems. This method, is based on the classical Lyapunov stability theory, utilizes the master continuous timechaotic system to monitor the synchronized motions. Various numerical simulations are performed to verify theeffectiveness of the proposed approach.
Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community
Authors: Coll Francesc , Harrison Ewan M. , Toleman Michelle S. , Reuter Sandra , Raven Kathy E. , Blane Beth , Palmer Beverley , Kappeler A. Ruth M. , Brown Nicholas M. , Török M. Estée , Parkhill Julian , Peacock Sharon J.
Published: October 2017

Longitudinal genomic and epidemiological surveillance of methicillin-resistant
Staphylococcus aureus
in the UK reveals extensive transmission in hospitals and the community.
The new stars of synaptic regulation
Authors: Dzirasa Kafui
Published: October 2017

Astrocytes regulate synaptic function in amygdala.
Macrophage magic: Why more is better for skin wound healing
Authors: Levi Benjamin
Published: October 2017

Scaffold-seeded macrophage transplantation to a skin wound site accelerates healing.
Gammaherpesvirus is nothing to sneeze at
Authors: Philips Jennifer A.
Published: October 2017

Gammaherpesvirus protects against allergic asthma by inducing the replacement of alveolar macrophages.
Genotype 2 Strains of Porcine Reproductive and Respiratory Syndrome Virus Dysregulate Alveolar Macrophage Cytokine Production via the Unfolded Protein Response
Authors: Chen Wei-Yu , Schniztlein William M. , Calzada-Nova Gabriela , Zuckermann Federico A.
Published: October 2017

Porcine reproductive and respiratory syndrome virus (PRRSV) infects alveolar macrophages (AMϕ), causing dysregulated alpha interferon (IFN-α) and tumor necrosis factor alpha (TNF-α) production through a mechanism(s) yet to be resolved. Here, we show that AMϕ infected with PRRSV secreted a reduced quantity of IFN-α following exposure of the cell to synthetic double-stranded RNA (dsRNA). This reduction did not correlate with reduced IFNA1 gene transcription. Rather, it coincided with two events that occurred late during infection and that were indicative of translational attenuation, specifically, the activation of eukaryotic translation initiation factor 2α (eIF2α) and the appearance of stress granules. Notably, the typical rapid production of TNF-α by AMϕ exposed to lipopolysaccharide (LPS) was suppressed or enhanced by PRRSV, depending on when the LPS exposure occurred after virus infection. If exposure was delayed until 6 h postinfection (hpi) so that the development of the cytokine response coincided with the time in which phosphorylation of eIF2α by the stress sensor PERK (protein kinase RNA [PKR]-like ER kinase) occurred, inhibition of TNF-α production was observed. However, if LPS exposure occurred at 2 hpi, prior to a detectable onset of eIF2α phosphorylation, a synergistic response was observed due to the earlier NF-κB activation via the stress sensor IRE1α (inositol-requiring kinase 1α). These results suggest that the asynchronous actions of two branches of the unfolded protein response (UPR), namely, IRE1α, and PERK, activated by ER stress resulting from the virus infection, are associated with enhancement or suppression of TNF-α production, respectively.

IMPORTANCE
The activation of AMϕ is controlled by the microenvironment to deter excessive proinflammatory cytokine responses to microbes that could impair lung function. However, viral pneumonias frequently become complicated by secondary bacterial infections, triggering severe inflammation, lung dysfunction, and death. Although dysregulated cytokine production is considered an integral component of the exacerbated inflammatory response in viral-bacterial coinfections, the mechanism responsible for this event is unknown. Here, we show that PRRSV replication in porcine AMϕ triggers activation of the IRE1α branch of the UPR, which causes a synergistic TNF-α response to LPS exposure. Thus, the severe pneumonias typically observed in pigs afflicted with PRRSV-bacterial coinfections could result from dysregulated, overly robust TNF-α production in response to opportunistic pathogens that is not commensurate with the typical restrained reaction by uninfected AMϕ. This notion could help in the design of therapies to mitigate the severity of viral and bacterial coinfections.
NS3 from Hepatitis C Virus Strain JFH-1 Is an Unusually Robust Helicase That Is Primed To Bind and Unwind Viral RNA
Authors: Zhou Ting , Ren Xiaoming , Adams Rebecca L. , Pyle Anna Marie
Published: October 2017

Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral replication and assembly (nonstructural protein 3 [NS3]). This helicase has become the focus of extensive basic research on the general helicase mechanism, and it is also of interest as a novel drug target. Despite the importance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV strains that are used to study HCV genetics and mechanism in cell culture (such as JFH-1) is lacking. We therefore set out to determine whether NS3 from the replicatively efficient genotype 2a strain JFH-1 displays novel functional or structural properties. Using biochemical assays for RNA binding and duplex unwinding, we show that JFH-1 NS3 binds RNA much more rapidly than the previously studied NS3 variants from genotype 1b. Unlike NS3 variants from other genotypes, JFH-1 NS3 binds RNA with high affinity in a functionally active form that is capable of immediately unwinding RNA duplexes without undergoing rate-limiting conformational changes that precede activation. Unlike other superfamily 2 (SF2) helicases, JFH-1 NS3 does not require long 3′ overhangs, and it unwinds duplexes that are flanked by only a few nucleotides, as in the folded HCV genome. To understand the physical basis for this, we solved the crystal structure of JFH-1 NS3, revealing a novel conformation that contains an open, positively charged RNA binding cleft that is primed for productive interaction with RNA targets, potentially explaining robust replication by HCV JFH-1.

IMPORTANCE
Genotypes of HCV are as divergent as different types of flavivirus, and yet mechanistic features of HCV variants are presumed to be held in common. One of the most well-studied components of the HCV replication complex is a helicase known as nonstructural protein 3 (NS3). We set out to determine whether this important mechanical component possesses biochemical and structural properties that differ between common strains such as those of genotype 1b and a strain of HCV that replicates with exceptional efficiency (JFH-1, classified as genotype 2a). Indeed, unlike the inefficient genotype 1b NS3, which has been well studied, JFH-1 NS3 is a superhelicase with strong RNA affinity and high unwinding efficiency on a broad range of targets. Crystallographic analysis reveals architectural features that promote enhanced biochemical activity of JFH-1 NS3. These findings show that even within a single family of viruses, drift in sequence can result in the acquisition of radically new functional properties that enhance viral fitness.
Pseudomonas syringae
pv. syringae B728a Regulates Multiple Stages of Plant Colonization via the Bacteriophytochrome BphP1
Authors: McGrane Regina , Beattie Gwyn A.
Published: October 2017

Light may be an important environmental signal for plant-associated bacteria, particularly those that live on leaves. An integrated network of red/far-red- and blue-light-responsive photosensory proteins is known to inhibit swarming motility in the foliar plant pathogen
Pseudomonas syringae
pv. syringae B728a. Here we elucidated factors in the red/far-red-light-sensing bacteriophytochrome BphP1 signal transduction pathway and report evidence for a role of BphP1 in multiple stages of the
P
.
syringae
B728a life cycle. We report that BphP1 signaling involves the downstream regulator Bsi (bacteriophytochrome-regulated swarming inhibitor) and an acyl-homoserine lactone (AHL) signal. Loss of
bphP1
or
bsi
resulted in the early initiation of swarm tendrils during swarming motility, a phenotype that was dependent on red/far-red light and reversed by exogenous AHL, illustrating that the BphP1-Bsi-AHL pathway inhibits the transition from a sessile state to a motile state. Loss of
bphP1
or
bsi
resulted in larger water-soaked lesions induced on bean (
Phaseolus vulgaris
) pods and enhanced movement from soil and buried plant tissues to seeds, demonstrating that BphP1 and Bsi negatively regulate virulence and bacterial movement through soil to seeds. Moreover, BphP1, but not Bsi, contributed to leaf colonization; loss of
bphP1
reduced survival on leaves immediately following inoculation but enhanced the size of the subsequently established populations. Neither Bsi nor Smp, a swarm motility-promoting regulator identified here, affected leaf colonization, indicating that BphP1-mediated contributions to leaf colonization are, at least in part, independent of swarming motility. These results demonstrate that
P
.
syringae
B728a red-light sensing involves a multicomponent, branched regulatory pathway that affects several stages of its life cycle.

IMPORTANCE
Microbes on plants are particularly well positioned to exploit light cues based on the importance of light to plant growth. Photosensory proteins enable organisms to sense light and respond to light, but their roles in the life cycles of plant microbes are poorly understood. This study investigated the cellular components and ecological roles of red/far-red-light sensing in the foliar bacterial pathogen
Pseudomonas syringae
. The study demonstrated that a bacteriophytochrome photosensory protein functions via a multicomponent, branched regulatory pathway that operates primarily through red/far-red-light-mediated inhibition. This pathway negatively regulates the transition from sessile to motile states under conditions conducive to swarming motility. It also negatively regulates virulence on bean pods, movement through soil to seeds, and survival following inoculation on leaves, but it positively contributes to the eventual establishment of leaf-borne populations. These results provide strong evidence that light sensing modulates behaviors at multiple stages in the life cycle of a nonphotosynthetic, plant microbe.
Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity
Authors: Ghulam-Smith Melissa , Olson Alex , White Laura F. , Chasela Charles S. , Ellington Sascha R. , Kourtis Athena P. , Jamieson Denise J. , Tegha Gerald , van der Horst Charles M. , Sagar Manish
Published: October 2017

A significant number of infants acquire HIV-1 through their infected mother’s breast milk, primarily due to limited access to antiretrovirals. Passive immunization with neutralizing antibodies (nAbs) may prevent this transmission. Previous studies, however, have generated conflicting results about the ability of nAbs to halt mother-to-child transmission (MTCT) and their impact on infant outcomes. This study compared plasma neutralizing activity in exposed infants and the infected mothers (n =63) against heterologous HIV-1 variants and the quasispecies present in the mother. HIV-exposed uninfected infants (HEU) (n =42), compared to those that eventually acquired infection (n =21), did not possess higher nAb responses against heterologous envelopes (P= 0.46) or their mothers’ variants (P= 0.45). Transmitting compared to nontransmitting mothers, however, had significantly higher plasma neutralizing activity against heterologous envelopes (P= 0.03), although these two groups did not have significant differences in their ability to neutralize autologous strains (P= 0.39). Furthermore, infants born to mothers with greater neutralizing breadth and potency were significantly more likely to have a serious adverse event (P= 0.03). These results imply that preexisting anti-HIV-1 neutralizing activity does not prevent breast milk transmission. Additionally, high maternal neutralizing breadth and potency may adversely influence both the frequency of breast milk transmission and subsequent infant morbidity.

IMPORTANCEPassive immunization trials are under way to understand if preexisting antibodies can decrease mother-to-child HIV-1 transmission and improve infant outcomes. We examined the influence of preexisting maternal and infant neutralizing activity on transmission and infant morbidity in a breastfeeding mother-infant cohort. Neutralization was examined against both the exposure strains circulating in the infected mothers and a standardized reference panel previously used to estimate breadth. HIV-exposed uninfected infants did not possess a broader and more potent response against both the exposure and heterologous strains compared to infants that acquired infection. Transmitting, compared to nontransmitting, mothers had significantly higher neutralization breadth and potency but similar responses against autologous variants. Infants born to mothers with higher neutralization responses were more likely to have a serious adverse event. Our results suggest that preexisting antibodies do not protect against breast milk HIV-1 acquisition and may have negative consequences for the baby.
Adaptation to Chronic Nutritional Stress Leads to Reduced Dependence on Microbiota in
Drosophila melanogaster
Authors: Erkosar Berra , Kolly Sylvain , van der Meer Jan R. , Kawecki Tadeusz J.
Published: October 2017

Numerous studies have shown that animal nutrition is tightly linked to gut microbiota, especially under nutritional stress. In
Drosophila melanogaster
, microbiota are known to promote juvenile growth, development, and survival on poor diets, mainly through enhanced digestion leading to changes in hormonal signaling. Here, we show that this reliance on microbiota is greatly reduced in replicated
Drosophila
populations that became genetically adapted to a poor larval diet in the course of over 170 generations of experimental evolution. Protein and polysaccharide digestion in these poor-diet-adapted populations became much less dependent on colonization with microbiota. This was accompanied by changes in expression levels of dFOXO transcription factor, a key regulator of cell growth and survival, and many of its targets. These evolutionary changes in the expression of dFOXO targets to a large degree mimic the response of the same genes to microbiota, suggesting that the evolutionary adaptation to poor diet acted on mechanisms that normally mediate the response to microbiota. Our study suggests that some metazoans have retained the evolutionary potential to adapt their physiology such that association with microbiota may become optional rather than essential.

IMPORTANCE
Animals depend on gut microbiota for various metabolic tasks, particularly under conditions of nutritional stress, a relationship usually regarded as an inherent aspect of animal physiology. Here, we use experimental evolution in fly populations to show that the degree of host dependence on microbiota can substantially and rapidly change as the host population evolves in response to poor diet. Our results suggest that, although microbiota may initially greatly facilitate coping with suboptimal diets, chronic nutritional stress experienced over multiple generations leads to evolutionary adaptation in physiology and gut digestive properties that reduces dependence on the microbiota for growth and survival. Thus, despite its ancient evolutionary history, the reliance of animal hosts on their microbial partners can be surprisingly flexible and may be relaxed by short-term evolution.
Treatment of hemorrhagic head and neck lesions by direct puncture and nBCA embolization
Authors: Deib Gerard , El Mekabaty Amgad , Gailloud Philippe , Pearl Monica Smith
Published: October 2017

Life-threatening bleeding in the head and neck region requires urgent management. These hemorrhagic lesions, for example, a ruptured pseudoaneurysm, are often treated by transarterial embolization (TAE), but prior intervention or surgery, inflammation, anatomic variants, and vessel tortuosity may render an endovascular approach challenging, time-consuming, and sometimes impossible. We report two cases of severe head and neck hemorrhages successfully embolized withn-butyl cyanoacrylate via direct puncture, and propose this approach as a fast, safe, and effective alternative to TAE.
Dieulafoy’s lesion of the colon and rectum: a case series and literature review
Authors: Inayat Faisal , Ullah Waqas , Hussain Qulsoom , Abdullah Hafez Mohammad Ammar
Published: October 2017

Dieulafoy’s lesion is a dilated, aberrant, submucosal vessel that erodes the overlying epithelium without obvious ulceration. It is most commonly located in the lesser curvature of the stomach but rare occurrences in extragastric sites have also been reported. Herein, we describe a case series of three patients who presented with lower gastrointestinal bleeding. Colonoscopy revealed a caliber-persistent tortuous submucosal artery protruding into the lumen of the colon or rectum. The patients were diagnosed with Dieulafoy’s lesion and primary haemostasis was achieved with the endoscopic haemoclip application. The purpose of this review is to summarise the available data on the pathophysiology, epidemiology, clinical presentation, diagnosis and management of patients with Dieulafoy’s lesion of the colon and rectum.
Atypical hydrocephalus in an Angus herd in Missouri, USA
Authors: Melendez Pedro , Volkmann Dietrich , Pithua Patrick
Published: October 2017

An atypical hydrocephalus case from a 24‐month‐old Angus heifer was diagnosed after a caesarean section was performed. The cow was euthanased after she fell twice during the surgery before having the opportunity to exteriorise the uterus. The fetus was removed from the dam post euthanasia. This teratogenic abnormality resembled a new genetic condition diagnosed in 2009 in the Angus breed called neuropathic hydrocephalus (recessive gene). The calf and dam were not sampled, but the bull, coming from a commercial Angus farm, tested positive for this gene. This case reinforces the importance of a consistent diagnostic methodology when genetic diseases are suspected.
Long-term decline of sugar maple following forest harvest, Hubbard Brook Experimental Forest, New Hampshire
Authors: Cleavitt Natalie L. , Battles John J. , Johnson Chris E. , Fahey Timothy J.
Published: October 2017

Forest harvesting can impact site quality by removing essential nutrients, exacerbating the effects of historic base cation losses associated with acid deposition. We studied the 30-year trajectory of forest recovery from clearcutting (whole-tree harvest (WTH)) in a forest originally dominated by sugar maple (Acer saccharum Marsh.). At both the watershed scale (21.9 ha) and the “detailed” plot scale (1 m2), a dramatic decline of sugar maple was observed, along with maintenance of American beech (Fagus grandifolia Ehrh.) and an increase in birch, mainly yellow birch (Betula alleghaniensis Britt.). Many of the “detailed” plots where sugar maple failed to recruit became unoccupied rather than being “won” by another species. The decline of sugar maple was most severe in the upper elevation zones of the watershed, where low base status (especially Ca) of the soils was a likely driver. The results support previous studies indicating that regeneration by sugar maple is severely compromised on base cation depleted soils. Lower survival of seedlings for sugar maple emphasized the importance of maintaining advance regeneration to favor desired species such as sugar maple. Foresters should consider that sites with low base saturation and exchangeable Ca are likely to exhibit regeneration failure for sugar maple in the long term, even those with initial dominance by this species.
Cell adhesion molecule-1 shedding induces apoptosis of renal epithelial cells and exacerbates human nephropathies
Authors: Kato Takashi , Hagiyama Man , Takashima Yasutoshi , Yoneshige Azusa , Ito Akihiko
Published: October 2017

Chronic kidney disease (CKD) is an important problem throughout the world, associated with the increase of blood urea nitrogen (BUN) and serum creatinine (sCre) and with renal tubular injuries. It is crucial to elucidate the molecular mechanisms of renal injuries to identify the new therapeutics and early diagnostic methods. We focused on cell adhesion molecule-1 (CADM1) protein. CADM1, its isoform SP4, is expressed in the epithelial cells of various tissues, including renal distal tubules, localized on the lateral cell membrane, mediates cell-cell adhesion via trans-homophilic binding, and interacts with various proteins. We previously reported that its expression was downregulated by post-proteolytic cleavage (α- and β-shedding) in pulmonary diseases. To investigate whether CADM1 α-shedding occurs in human nephropathies, we performed Western blotting and immunohistochemical analysis of specimens with arterionephrosclerosis (AS) and diabetic nephropathy (DN) from autopsied kidneys. CADM1 α-shedding was induced in AS and DN kidneys and derived from the decrease in full-length CADM1 (FL-CADM1) and increase of the COOH-terminal fragment (α-CTF). In particular, the reduced FL-CADM1 level was correlated with tubular and tubulointerstitial injuries and the increases in BUN and sCre levels. Apoptosis of renal tubular epithelial cells (TECs) was promoted in both nephropathies, and it was significantly correlated with the decrease in the FL-CADM1. Furthermore, FL-CADM1 knockdown by small interfering RNA downregulated anti-apoptotic Bcl-2 protein and promoted apoptosis of cultured renal TECs. The present study suggests that the reduction of FL-CADM1 leads to renal TEC apoptosis and could exacerbate renal tubular and tubulointerstitial injuries, which contribute to the development of CKD.
Momentary level of slow default mode network activity is associated with distinct propagation and connectivity patterns in the anesthetized mouse cortex
Authors: Kang Minseok , Lee Young-Beom , Gohel Bakul , Yoo Kwangsun , Lee Peter , Chung Jinyong , Jeong Yong
Published: October 2017

Complex spatiotemporal changes of slow spontaneous activity occur in the form of propagating waves in the cortex, leading to the transient formation of a specific activation topography, followed by a transition in the topography. The topographies resemble the stimulation-induced activation patterns and the underlying structural projections, suggesting that they contain motifs of task-related activation. However, little is known about how propagation-mediated transitions between topographies are structured in terms of functional connectivity. Therefore, we investigated whether specific topographies or regions are associated with transitions involving long-range connections and hub modulation. We hypothesized that the activity level of the default mode network (DMN) at a given topography would affect the pattern of upcoming transitions, since high activity levels of the DMN are a distinct feature of the brain at rest. Using mesoscale voltage-sensitive dye imaging in the cortex of lightly anesthetized mice, we revealed that momentary levels of DMN activity are associated with distinct patterns of activity propagation and functional connectivity. High levels of DMN activity led to activity propagation across secondary and association cortices, increasing the centrality of a main hub region, whereas low-level activity led to global, diffuse, yet efficient changes in functional connectivity. Furthermore, low levels of activity resulted in increased long-range connectivity between frontal and posterior regions of the cortex. Our results indicate that DMN activity is associated with functional connectivity and wave propagation patterns, raising the possibility that the DMN may be involved in the modulation of long-range information processing associated with upcoming transitions.

NEW & NOTEWORTHY Using voltage-sensitive dye imaging with high spatiotemporal resolution, we have revealed that increased DMN activity is associated with activity propagation to secondary/association cortices, whereas decreased activity is associated with stronger long-range frontal-posterior connections in the mouse cortex. Hub metric and global functional connectivity parameters were accompanied by activity level changes. These results indicate that the DMN may aid in modulating the structure of transitions.
Object maintenance beyond their visible parts in working memory
Authors: Chen Siyi , Töllner Thomas , Müller Hermann J. , Conci Markus
Published: October 2017

Completion of a partially occluded object requires that a representation of the whole is constructed based on the information provided by the physically specified parts of the stimulus. Such processes of amodal completion rely on the generation and maintenance of a mental image that renders the completed object in visual working memory (VWM). The present study examined this relationship between VWM storage and processes of object completion. We recorded event-related potentials to track VWM maintenance by means of the contralateral delay activity (CDA) during a change detection task in which composite objects (notched shapes abutting an occluding shape) to be memorized were primed to induce either a globally completed object or a noncompleted, mosaic representation. The results revealed an effect of completion in VWM despite physically identical visual input: change detection was more accurate for completed compared with mosaic representations when observers were required to memorize two objects, and these differences were reduced with four memorized items. At the electrophysiological level, globally completed (vs. mosaic) objects gave rise to a corresponding increase in CDA amplitudes. These results indicate that although incorporating the occluded portions of the presented shapes requires mnemonic resources, the complete object representations thus formed in VWM improve change detection performance by providing a more simple, regular shape. Overall, these findings demonstrate that mechanisms of object completion modulate VWM, with the memory load being determined by the structured representations of the memorized stimuli.

NEW & NOTEWORTHY This study shows that completion of partially occluded objects requires visual working memory (VWM) resources. In the experiment reported, we induced observers to memorize a given visual input either as completed or as noncompleted objects. The results revealed both a behavioral performance advantage for completed vs. noncompleted objects despite physically identical input, and an associated modulation of an electrophysiological component that reflects VWM object retention, thus indicating that constructing an integrated object consumes mnemonic resources.
Bulk Heterojunction Organic Solar Cell Area-Dependent Parameter Fluctuation
Authors: Trindade A. J. , Pereira L.
Published: October 2017

Organic solar cell efficiency is known to be active area dependent and is usually a problem in the upscale factor for market applications. In this work, a detailed study of organic photovoltaic devices with active layer based on poly(3-hexylthiophene) (P3HT) and 1-(3-methoxycarbonyl)-propyl-1-phenyl-(6,6)C61 (PCBM) is made, evaluating the effect of the change on the active area from 10−2 to 4 cm4. The device structure was kept simple in order to allow the understanding of the physical effects involved. Device figures of merit were extracted from the equivalent circuit using a genetic-based algorithm, and their relationship with the active area was compared. It is observed that the efficiency drops significantly with the active area increase (as the fill factor) while the parallel and series resistance, adjusted to the active area, seems to be relatively constant and increases linearly, respectively. The short circuit current and the generated photocurrent also drop significantly with the active area increase. The open circuit voltage does not show major changes. These results are discussed considering the main influences for the observed efficiency data. Particularly, as the basic circuit model seems to fail to explain the macroscopic results, the behavior can be related with the enlargement of defect interaction.
Functional Characterization of Preadipocytes Derived from Human Periaortic Adipose Tissue
Authors: Vargas Diana , Camacho Jaime , Duque Juan , Carreño Marisol , Acero Edward , Pérez Máximo , Ramirez Sergio , Umaña Juan , Obando Carlos , Guerrero Albert , Sandoval Néstor , Rodríguez Gina , Lizcano Fernando
Published: October 2017

Adipose tissue can affect the metabolic control of the cardiovascular system, and its anatomic location can affect the vascular function differently. In this study, biochemical and phenotypical characteristics of adipose tissue from periaortic fat were evaluated. Periaortic and subcutaneous adipose tissues were obtained from areas surrounding the ascending aorta and sternotomy incision, respectively. Adipose tissues were collected from patients undergoing myocardial revascularization or mitral valve replacement surgery. Morphological studies with hematoxylin/eosin and immunohistochemical assay were performed in situ to quantify adipokine expression. To analyze adipogenic capacity, adipokine expression, and the levels of thermogenic proteins, adipocyte precursor cells were isolated from periaortic and subcutaneous adipose tissues and induced to differentiation. The precursors of adipocytes from the periaortic tissue accumulated less triglycerides than those from the subcutaneous tissue after differentiation and were smaller than those from subcutaneous adipose tissue. The levels of proteins involved in thermogenesis and energy expenditure increased significantly in periaortic adipose tissue. Additionally, the expression levels of adipokines that affect carbohydrate metabolism, such as FGF21, increased significantly in mature adipocytes induced from periaortic adipose tissue. These results demonstrate that precursors of periaortic adipose tissue in humans may affect cardiovascular events and might serve as a target for preventing vascular diseases.
Disclosure of Parental HIV Status to Children: Experiences of Adults Receiving Antiretroviral Treatment at an Urban Clinic in Kampala, Uganda
Authors: Osingada Charles Peter , Okuga Monica , Nabirye Rose Chalo , Sewankambo Nelson Kaulukusi , Nakanjako Damalie
Published: October 2017

Limited data are available on the experiences of parental HIV disclosure to children in Uganda. We conducted a qualitative study comprising sixteen in-depth interviews and four focus group discussions with parents receiving highly active antiretroviral therapy. Analysis was done using Atlas.ti qualitative research software. Back-and-forth triangulation was done between transcripts of the in-depth interviews and focus group discussions, and themes and subthemes were developed. Barriers to parents’ disclosure included perceptions that children are too young to understand what HIV infection means and fears of secondary disclosure by the children. Immediate outcomes of disclosure included children getting scared and crying, although such instances often gave way to more enduring positive experiences for the parents, such as support in adherence to medical care, help in household chores, and a decrease in financial demands from the children. Country-specific interventions are needed to improve the process of parental HIV disclosure to children and this should encompass preparation on how to deal with the immediate psychological challenges associated with the parent’s disclosure.
An Analysis of the Mechanical Characteristics and Constitutive Relation of Cemented Mercury Slag
Authors: Li Xinwei , Zhang Sui , Yan E-chuan , Shu Duoyou , Cao Yangbing , Li Hui , Wang Siyang , He You
Published: October 2017

This study focuses on mercury slag in the Tongren area of Guizhou Province, China. Computed tomography (CT) is used with uniaxial and triaxial compression tests to examine the mechanical changes in cemented mercury slag and its formation. The CT results for the uniaxial compression test reveal the overall failure process of the mercury slag structure. Based on the coarse-grained soil triaxial test, a modified Duncan-Chang model is compared with the actual monitoring results and is found to be suitable for the analysis of the slag constitutive model.
An Evaluation of Hand-Force Prediction Using Artificial Neural-Network Regression Models of Surface EMG Signals for Handwear Devices
Authors: Yokoyama Masayuki , Koyama Ryohei , Yanagisawa Masao
Published: October 2017

Hand-force prediction is an important technology for hand-oriented user interface systems. Specifically, surface electromyography (sEMG) is a promising technique for hand-force prediction, which requires a sensor with a small design space and low hardware costs. In this study, we applied several artificial neural-network (ANN) regression models with different numbers of neurons and hidden layers and evaluated handgrip forces by using a dynamometer. A handwear with dry electrodes on the dorsal interosseous muscles was used for our evaluation. Eleven healthy subjects participated in our experiments. sEMG signals with six different levels of forces from 0 N to 200 N and maximum voluntary contraction (MVC) are measured to train and test our ANN regression models. We evaluated three different methods (intrasession, intrasubject, and intersubject evaluation), and our experimental results show a high correlation (0.840, 0.770, and 0.789 each) between the predicted forces and observed forces, which are normalized by the MVC for each subject. Our results also reveal that ANNs with deeper layers of up to four hidden layers show fewer errors in intrasession and intrasubject evaluations.
Astragaloside IV Ameliorates Airway Inflammation in an Established Murine Model of Asthma by Inhibiting the mTORC1 Signaling Pathway
Authors: Jin Hualiang , Wang Limin , Li Bei , Cai Cui , Ye Jian , Xia Junbo , Ma Shenglin
Published: October 2017

Astragaloside IV (AS‐IV), a main active constituent of Astragalus membranaceus, has been confirmed to have antiasthmatic effects. However, it remained unclear whether the beneficial effects of AS‐IV on asthma were attributed to the mTOR inhibition; this issue was the focus of the present work. BALB/c mice were sensitized and challenged with ovalbumin followed with 3 weeks of rest/recovery and then reexposure to ovalbumin. AS‐IV was administrated during the time of rest and reexposure. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokines (IL‐4, IL‐5, IL‐13, IL‐17, and INF‐γ), and CD4+CD25+Foxp3+Treg cells in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling were examined. AS‐IV markedly suppressed airway hyperresponsiveness and reduced IL‐4, IL‐5, and IL‐17 levels and increased INF‐γ levels in the BALF. Histological studies showed that AS‐IV markedly decreased inflammatory infiltration in the lung tissues. Notably, AS‐IV inhibited mTORC1 activity, whereas it had limited effects on mTORC2, as assessed by phosphorylation of mTORC1 and mTORC2 substrates S6 ribosomal protein, p70 S6 Kinase, and Akt, respectively. CD4+CD25+Foxp3+Treg cells in BALF were not significantly changed by AS‐IV. Together, these results suggest that the antiasthmatic effects of AS‐IV were at least partially from inhibiting the mTORC1 signaling pathway.
The Aroma Composition of Baby Ginger Paocai
Authors: Luo Songming , Li Qiang , Chen Anjun , Liu Xingyan , Pu Biao
Published: October 2017

The purpose of this study was to analyze the volatile compounds in baby ginger paocai and the fresh baby ginger and identify the key aroma components that contribute to the flavor of baby ginger paocai. A total of 86 volatile compounds from the two baby ginger samples were quantified; these compounds were extracted by headspace solid-phase microextraction (HS-SPME) and analyzed by gas chromatography–mass spectrometry (GC-MS). The aroma composition of baby ginger paocai was different from that of fresh baby ginger. Baby ginger paocai was characterized by the presence of aroma-active compounds which varied in concentration from 0.03 to 28.14%. Geranyl acetate was the aroma component with the highest relative content in baby ginger paocai.β-myrcene, eucalyptol, trans-β-ocimene, Z-ocimene, linalool, decanal, cis-citral, geraniol, geranyl acetate, curcumene, andβ-bisabolene contributed to the overall aroma of the product of baby ginger paocai which had gone through a moderate fermentation process.
Ecosystem Drought Response Timescales from Thermal Emission versus Shortwave Remote Sensing
Authors: Andujar Erika , Krakauer Nir Y. , Yi Chuixiang , Kogan Felix
Published: October 2017

Remote sensing is used for monitoring the impacts of meteorological drought on ecosystems, but few large-scale comparisons of the response timescale to drought of different vegetation remote sensing products are available. We correlated vegetation health products derived from polar-orbiting radiometer observations with a meteorological drought indicator available at different aggregation timescales, the Standardized Precipitation Evapotranspiration Index (SPEI), to evaluate responses averaged globally and over latitude and biome. The remote sensing products are Vegetation Condition Index (VCI), which uses normalized difference vegetation index (NDVI) to identify plant stress, Temperature Condition Index (TCI), based on thermal emission as a measure of surface temperature, and Vegetation Health Index (VHI), the average of VCI and TCI. Globally, TCI correlated best with 2-month timescale SPEI, VCI correlated best with longer timescale droughts (peak mean correlation at 13 months), and VHI correlated best at an intermediate timescale of 4 months. Our results suggest that thermal emission (TCI) may better detect incipient drought than vegetation color (VCI). VHI had the highest correlations with SPEI at aggregation times greater than 3 months and hence may be the most suitable product for monitoring the effects of long droughts.
Proposing Development and Utility of a Mobility Composite Measure in Patients with a Neurologic Disorder
Authors: Swank Chad , Almutairi Sattam , Medley Ann
Published: October 2017

Background. Outcome measures typically assess single domains making holistic assessment difficult. Our purpose was to develop a mobility composite measure (MCM) based on four commonly used outcome measures and compare this composite score to the individual measures in patients with neurologic disorders.Methods. We retrospectively reviewed 148 medical records for inclusion of primary neurologic diagnosis and scoring for 5 times sit-to-stand test (5TSST), 10-meter walk test (10MWT), 2-minute walk test (2MWT), and activities-specific balance confidence (ABC) scale.Results. After establishing that a single concept was being assessed with interitem correlations, raw scores were converted to percentage of normal and combined into the MCM for analysis from admission to discharge. Scores on each measure significantly improved after intervention (5TSST,p<.001; 10MWT,p<.001; 2MWT,p<.001; ABC,p=.02). Mean MCM (n=93) admission scores were67.55±31.88% and discharge scores were74.81±34.39% (p=.002). On average, patients improved 7.26% on the MCM exceeding the threshold of expected error (MDC95= 3.59%).Conclusions. MCM detected change in patient outcomes statistically and clinically and appears to capture a holistic picture of functional status. We recommend a prospective study to further investigate a “composite measure” incorporating measures from several functional domains.
A Subpopulation of Stromal Cells Controls Cancer Cell Homing to the Bone Marrow
Authors: Rossnagl Stephanie , Ghura Hiba , Groth Christopher , Altrock Eva , Jakob Franz , Schott Sarah , Wimberger Pauline , Link Theresa , Kuhlmann Jan Dominik , Stenzl Arnulf , Hennenlotter Jörg , Todenhöfer Tilmann , Rojewski Markus , Bieback Karen , Nakchbandi Inaam A.
Published: October 2017

Breast and prostate cancer cells home to the bone marrow, where they presumably hijack the hematopoietic stem cell niche. We characterize here the elusive premetastatic niche by examining the role of mesenchymal stromal cells (MSC) in cancer cell homing. Decreasing the number of MSC pharmacologically enhanced cancer cell homing to the bone marrow in mice. In contrast, increasing the number of these MSCs by various interventions including G-CSF administration diminished cancer cell homing. The MSC subpopulation that correlated best with cancer cells expressed stem, endothelial, and pericytic cell markers, suggesting these cells represent an undifferentiated component of the niche with vascular commitment. In humans, a MSC subpopulation carrying markers for endothelial and pericytic cells was lower in the presence of cytokeratin+ cells in bone marrow. Taken together, our data show that a subpopulation of MSC with both endothelial and pericytic cell surface markers suppresses the homing of cancer cells to the bone marrow. Similar to the presence of cytokeratin+ cells in the bone marrow, this MSC subpopulation could prove useful in determining the risk of metastatic disease, and its manipulation might offer a new possibility for diminishing bone metastasis formation.

Significance: These findings establish an inverse relationship between a subpopulation of mesenchymal stromal cells and cancer cells in the bone marrow. Cancer Res; 78(1); 129–42. ©2017 AACR.
CBX8 Exhibits Oncogenic Activity via AKT/β-Catenin Activation in Hepatocellular Carcinoma
Authors: Zhang Chris Zhiyi , Chen Shi-Lu , Wang Chun-Hua , He Yang-Fan , Yang Xia , Xie Dan , Yun Jing-Ping
Published: October 2017

Deregulation of polycomb proteins influences the development and progression of hepatocellular carcinoma. Here we show that chromobox 8 (CBX8) expression is increased in hepatocellular carcinoma and correlates with poor outcome in two independent cohorts containing a total of 879 cases. Ectopic expression of CBX8 facilitated tumor growth and metastasis, whereas CBX8 silencing suppressed these effects. CBX8 efficiently activated AKT/β-catenin signaling via upregulation of the transcription factor EGR1 and miR-365-3p in a noncanonical manner: CBX8 directly bound the EGR1 promoter to enhance its activity. In the nucleus, CBX8 also interacted with EGR1 to prevent its degradation. Furthermore, CBX8 increased the transcription of miR-365a-3p, which promoted the nuclear localization of β-catenin by targeting the 3′-UTR ZNRF1. Inhibiting either EGR1 or miR-365a-3p partially rescued CBX8-mediated malignant phenotypes. In clinical samples, CBX8 expression closely correlated with EGR1, miR-365a-3p, and nuclear β-catenin. Collectively, our results show that CBX8 functions as an oncogene to upregulate EGR1 and miR-365-3p to stimulate the AKT/β-catenin pathway. This newly identified signaling axis may suggest new therapeutic strategies against hepatocellular carcinoma.

Significance: Elucidation of a key new element of the β-catenin signaling pathway in liver cancer may suggest new therapeutic targets. Cancer Res; 78(1); 51–63. ©2017 AACR.