bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders
Authors: Crouse Bethany , Robinson Christine , Huseby Kelcher April , Laudenbach Megan , Abrahante Juan E. , Pravetoni Marco
Published: October 2020

Opioid use disorders (OUD) affect over 27 million people worldwide. Anti-opioid vaccines offer a promising strategy to treat OUD and prevent overdose. Using immunomodulation of cytokine signaling to increase vaccine efficacy, this study found that blocking IL-4 improved the efficacy of vaccines targeting oxycodone and fentanyl in male and female mice. Genetic deletion of the IL-4 receptor, STAT6, or antibody-based depletion of IL-13, did not increase vaccine efficacy against opioids, suggesting the involvement of type I IL-4 receptors. Enhancement of vaccine efficacy with blockade of IL-4 was associated with improved germinal center formation in secondary lymphoid organs and selective transcriptome signatures in the activated CD4+T cell population subset. These data suggest that IL-4 is both a pharmacological target and a potential biomarker of vaccine efficacy against OUD.
Long-term surveys of age structure in 13 ungulate and one ostrich species in the Serengeti, 1926–2018
Authors: Rogy Pierre , Sinclair Anthony R. E.
Published: October 2020

The Serengeti ecosystem spans an extensive network of protected areas in Tanzania, eastern Africa, and a UNESCO Wold Heritage Site. It is home to some of the largest animal migrations on the planet. Here, we describe a dataset consisting of the sample counts of three age classes (infant, juvenile and adult) of 13 ungulate and one ostrich species. Sample counts were tallied visually from the ground, or, in some instances, aerial photographs, during a period extending from 1926 to 2018. Observed animals were assigned to age classes based on specific criteria for each species. For nine of the 14 species of this dataset, the number of sampling years is over 30. This resulted in a total of 533 different records of count across age classes. By computing age-class ratios, these data can be used to measure long-term recruitment success at different ages of the tallied species. In particular, the temporal extent of these data allows comparison of patterns to other long-term processes, such as the El Niño-Southern Oscillation (ENSO).
Lower leg muscle–tendon unit characteristics are related to marathon running performance
Authors: Kovács Bálint , Kóbor István , Gyimes Zsolt , Sebestyén Örs , Tihanyi József
Published: October 2020

The human ankle joint and plantar flexor muscle–tendon unit play an important role in endurance running. It has been assumed that muscle and tendon interactions and their biomechanical behaviours depend on their morphological and architectural characteristics. We aimed to study how plantar flexor muscle characteristics influence marathon running performance and to determine whether there is any difference in the role of the soleus and gastrocnemii. The right lower leg of ten male distance runners was scanned with magnetic resonance imagining. The cross-sectional areas of the Achilles tendon, soleus, and lateral and medial gastrocnemius were measured, and the muscle volumes were calculated. Additional ultrasound scanning was used to estimate the fascicle length of each muscle to calculate the physiological cross-sectional area. Correlations were found between marathon running performance and soleus volume (r = 0.55, p = 0.048), soleus cross-sectional area (r = 0.57, p = 0.04), soleus physiological cross-sectional area (PCSA-IAAF r = 0.77, p < 0.01, CI± 0.28 to 0.94), Achilles tendon thickness (r = 0.65, p < 0.01), and soleus muscle-to-tendon ratio (r = 0.68, p = 0.03). None of the gastrocnemius characteristics were associated with marathon performance. We concluded that a larger soleus muscle with a thicker Achilles tendon is associated with better marathon performance. Based on these results, it can be concluded the morphological characteristics of the lower leg muscle–tendon unit correlate with running performance.
A comparison of the prognostic value of composite ratios and cumulative scores in patients with operable rectal cancer
Authors: Dolan Ross D. , Alwahid Muhammed , McSorley Stephen T. , Park James H. , Stevenson Richard P. , Roxburgh Campbell S. , Horgan Paul G. , McMillan Donald C.
Published: October 2020

The aim of this study was to directly compare the prognostic value of cumulative scores and composite ratios in patients with operable rectal cancer. Within a single surgical unit preoperative differential blood cell results including neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, as well as CRP (C) and albumin (A) levels were recorded. These results were used to construct a series of composite ratios (NLR, PLR, LMR, CAR) and cumulative scores (NLS, PLS, LMS, NPS, mGPS). The relationship between composite ratios and the cumulative scores and clinicopathological characteristics, cancer specific survival (CSS) and overall survival (OS) were examined. A total of 413 patients were included. When adjusted for TNM stage, surgical approach, time of surgery and margin involvement mGPS (p < 0.05) was associated with CSS. In addition, most composite ratios/scores showed correlations with neoadjuvant therapy (p < 0.001). When a direct comparison between NPS (myeloid) and mGPS (liver) was carried out they showed similar associations with both CSS and OS. Therefore, both composite ratios and cumulative scores have been shown to be prognostic in patients with operable rectal cancer.
Bacteria incorporated with calcium lactate pentahydrate to improve the mortar properties and self-healing occurrence
Authors: Chaerun Siti Khodijah , Syarif Ridwan , Wattimena Ridho Kresna
Published: October 2020

Concrete can be harmful to the environment due to its high energy consumption and CO2 emission and also has a potential crack formation, which can promote a drop in its strength. Therefore, concrete is considered as a non-sustainable material. The mechanisms by which bacterial oxidation of organic carbon can precipitate calcite that may fill the voids and cracks on cement-based materials have been extensively investigated to prevent and heal the micro-cracks formation. Hence, this study focused on utilizing a new alkaliphilic bacterial strain indigenous to an Indonesian site, Lysinibacillus sphaericus strain SKC/VA-1, incorporated with calcium lactate pentahydrate, as a low-cost calcium source, with various bacterial inoculum concentrations. The bacterium was employed in this study due to its ability to adapt to basic pH, thus improving the physical properties and rejuvenating the micro-cracks. Experimentally, the addition of calcium lactate pentahydrate slightly affected the mortar properties. Likewise, bacteria-incorporated mortar exhibited an enhancement in the physical properties of mortar. The highest improvement of mechanical properties (an increase of 45% and 36% for compressive and indirect tensile strength, respectively) was achieved by the addition of calcium lactate pentahydrate incorporated with 10% v/v bacterial inoculum [about 7 × 107 CFU/ml (colony-forming unit/ml)]. The self-healing took place more rapidly on bacterial mortar supplemented with calcium lactate pentahydrate than on the control specimen. XRD analysis demonstrated that the mineralogical composition of self-healing precipitates was primarily dominated by calcite (CaCO3), indicating the capacity of L. sphaericus strain SKC/VA-1 to precipitate calcite through organic carbon oxidation for self-healing the artificial crack on the mortar. To our knowledge, this is the first report on the potential utilization of the bacterium L. sphaericus incorporated with calcium lactate pentahydrate to increase the mortar properties, including its self-healing ability. However, further study with the water-cement ratio variation is required to investigate the possibility of using L. sphaericus and calcium lactate pentahydrate as an alternative method rather than reducing the water-cement ratio to enhance the mortar properties.
A combined fMRI and EMG study of emotional contagion following partial sleep deprivation in young and older humans
Authors: Tamm Sandra , Schwarz Johanna , Thuné Hanna , Kecklund Göran , Petrovic Predrag , Åkerstedt Torbjörn , Fischer Håkan , Lekander Mats , Nilsonne Gustav
Published: October 2020

Sleep deprivation is proposed to inhibit top-down-control in emotion processing, but it is unclear whether sleep deprivation affects emotional mimicry and contagion. Here, we aimed to investigate effects of partial sleep deprivation on emotional contagion and mimicry in young and older humans. Participants underwent partial sleep deprivation (3 h sleep opportunity at the end of night), crossed-over with a full sleep condition in a balanced order, followed by a functional magnetic resonance imaging and electromyography (EMG) experiment with viewing of emotional and neutral faces and ratings of emotional responses. The final sample for main analyses was n = 69 (n = 36 aged 20–30 years, n = 33 aged 65–75 years). Partial sleep deprivation caused decreased activation in fusiform gyri for angry faces and decreased ratings of happiness for all stimuli, but no significant effect on the amygdala. Older participants reported more anger compared to younger participants, but no age differences were seen in brain responses to emotional faces or sensitivity to partial sleep deprivation. No effect of the sleep manipulation was seen on EMG. In conclusion, emotional contagion, but not mimicry, was affected by sleep deprivation. Our results are consistent with the previously reported increased negativity bias after insufficient sleep.

The Stockholm sleepy brain study: effects of sleep deprivation on cognitive and emotional processing in young and old.https://clinicaltrials.gov/ct2/show/NCT02000076.
Validation of a method to quantify microfibres present in aquatic surface microlayers
Authors: Birkenhead Joshua , Radford Freya , Stead Jessica L. , Cundy Andrew B. , Hudson Malcolm D.
Published: October 2020

Many of the methods for microplastics quantification in the environment are criticised creating problems with data validity. Quantification of microplastics in the surface microlayer of aquatic environments using glass plate dipping holds promise as a simple field method, but its efficiency has yet to be validated. We tested a standard glass plate dipping method to assess recovery of four common polymer microfibres and two common natural fibres, under three different salinities (freshwater, brackish water, saltwater). Overall recovery rates were low (26.8 ± 1.54%) but higher recoveries were observed under saltwater treatments (36.5 ± 3.01%) than brackish water (24.5 ± 1.92%) or freshwater (19.3 ± 1.92%). The fibre types showed different recovery rates, with acrylic yielding significantly higher recovery rates (37.0 ± 2.71%) than other fibres across treatments. No clear relationship between the density of the fibres and the recovery efficiency was seen. We suggest that, where this method is used for monitoring microplastics, the results will typically underestimate the total amount present, but that recovery is sufficiently consistent to allow comparison of differences between sampling locations. When comparing data across river-estuarine or similar transects salinity should be monitored to account for salinity-induced differences in sampling recovery.
Pre-treatment with the angiotensin receptor 1 blocker losartan protects renal blood flow and oxygen delivery after propofol-induced hypotension in pigs
Authors: Franzén Stephanie , Frithiof Robert
Published: October 2020

Hypotensive events are strongly correlated to the occurrence of perioperative acute kidney injury, but the underlying mechanisms for this are not completely elucidated. We hypothesised that anaesthesia-induced hypotension causes renal vasoconstriction and decreased oxygen delivery via angiotensin II-mediated renal vasoconstriction. Pigs were anaesthetised, surgically prepared and randomised to vehicle/losartan treatment (0.15 mg*kg−1). A deliberate reduction in arterial blood pressure was caused by infusion of propofol (30 mg*kg−1) for 10 min. Renal function and haemodynamics were recorded 60 min before and after hypotension. Propofol induced hypotension in all animals (p < 0.001). Renal blood flow (RBF) and renal oxygen delivery (RDO2) decreased significantly regardless of treatment but more so in vehicle-treated compared to losartan-treated (p = 0.001, p = 0.02, respectively). During recovery RBF and RDO2 improved to a greater extent in the losartan-treated compared to vehicle-treated (+ 28 ml*min−1, 95%CI 8–50 ml*min−1, p = 0.01 and + 3.1 ml*min−1, 95%CI 0.3–5.8 ml*min−1, p = 0.03, respectively). Sixty minutes after hypotension RBF and RDO2 remained depressed in vehicle-treated, as renal vascular resistance was still increased (p < 0.001). In losartan-treated animals RBF and RDO2 had normalised. Pre-treatment with losartan improved recovery of renal blood flow and renal oxygen delivery after propofol-induced hypotension, suggesting pronounced angiotensin II-mediated renal vasoconstriction during blood pressure reductions caused by anaesthesia.
TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes
Authors: Hook Sharon C. , Chadt Alexandra , Heesom Kate J. , Kishida Shosei , Al-Hasani Hadi , Tavaré Jeremy M. , Thomas Elaine C.
Published: October 2020

Proteins involved in the spaciotemporal regulation of GLUT4 trafficking represent potential therapeutic targets for the treatment of insulin resistance and type 2 diabetes. A key regulator of insulin- and exercise-stimulated glucose uptake and GLUT4 trafficking is TBC1D1. This study aimed to identify proteins that regulate GLUT4 trafficking and homeostasis via TBC1D1. Using an unbiased quantitative proteomics approach, we identified proteins that interact with TBC1D1 in C2C12 myotubes including VPS13A and VPS13C, the Rab binding proteins EHBP1L1 and MICAL1, and the calcium pump SERCA1. These proteins associate with TBC1D1 via its phosphotyrosine binding (PTB) domains and their interactions with TBC1D1 were unaffected by AMPK activation, distinguishing them from the AMPK regulated interaction between TBC1D1 and AMPKα1 complexes. Depletion of VPS13A or VPS13C caused a post-transcriptional increase in cellular GLUT4 protein and enhanced cell surface GLUT4 levels in response to AMPK activation. The phenomenon was specific to GLUT4 because other recycling proteins were unaffected. Our results provide further support for a role of the TBC1D1 PTB domains as a scaffold for a range of Rab regulators, and also the VPS13 family of proteins which have been previously linked to fasting glycaemic traits and insulin resistance in genome wide association studies.
Marital status and survival of patients with colorectal signet ring cell carcinoma: a population-based study
Authors: Feng Li , Yang Yong-jing , Du Juan , Yu Yong-jiang , Diao Jian-dong
Published: October 2020

The prognostic role of marital status on colorectal signet ring cell carcinoma (SRCC) has not been studied. In this study, the correlation of marital status with prognosis of colorectal SRCC was analyzed. Eligible subjects were extracted from the Surveillance, Epidemiology, and End Results (SEER) dataset from 2004 to 2015, followed by comparison of cancer-specific survival (CSS) and overall survival (OS) between married and unmarried group. 3152 patients were identified including 1777 married patients (56.38%). Married populations tended to be more patients aged < 65, male, receiving chemotherapy, and less black race and large tumor size compared to unmarried group (all P < 0.05).Moreover, 5-year CSS (30.04% vs. 28.19%, P = 0.0013) and OS rates (26.68% vs. 22.94%, P < 0.0001) were superior in married population. Multivariate analysis revealed that marital status was an independent favorable prognostic indicator, and married population had better CSS (HR: 0.898; 95% CI: 0.822–0.980; P = 0.016) and OS (HR: 0.898; 95%CI: 0.827–0.975; P = 0.011).In addition, CSS as well as OS were superior in married populations than unmarried ones in most subgroups. Marital status was an independent prognostic factor for survival in patients with colorectal SRCC. Additionally, married patients obtained better survival advantages.
The effect of proteolytic enzymes and pH on GII.4 norovirus, during both interactions and non-interaction with Histo-Blood Group Antigens
Authors: Chassaing Manon , Robin Maëlle , Loutreul Julie , Majou Didier , Belliot Gaël , de Rougemont Alexis , Boudaud Nicolas , Gantzer Christophe
Published: October 2020

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Histo-Blood Groups Antigens (HBGAs) have been described as attachment factors, promoting HuNoV infection. However, their role has not yet been elucidated. This study aims to evaluate the ability of HBGAs to protect HuNoVs against various factors naturally found in the human digestive system. The effects of acid pH and proteolytic enzymes (pepsin, trypsin, and chymotrypsin) on GII.4 virus-like particles (VLPs) and GII.4 HuNoVs were studied, both during interactions and non-interaction with HBGAs. The results showed that GII.4 VLPs and GII.4 HuNoVs behaved differently following the treatments. GII.4 VLPs were disrupted at a pH of less than 2.0 and in the presence of proteolytic enzymes (1,500 units/mL pepsin, 100 mg/mL trypsin, and 100 mg/mL chymotrypsin). VLPs were also partially damaged by lower concentrations of trypsin and chymotrypsin (0.1 mg/mL). Conversely, the capsids of GII.4 HuNoVs were not compromised by such treatments, since their genomes were not accessible to RNase. HBGAs were found to offer GII.4 VLPs no protection against an acid pH or proteolytic enzymes.
Tetraspanins are involved in Burkholderia pseudomallei-induced cell-to-cell fusion of phagocytic and non-phagocytic cells
Authors: Sangsri Tanes , Saiprom Natnaree , Tubsuwan Alisa , Monk Peter , Partridge Lynda J. , Chantratita Narisara
Published: October 2020

Tetraspanins are four-span transmembrane proteins of host cells that facilitate infections by many pathogens.Burkholderia pseudomalleiis an intracellular bacterium and the causative agent of melioidosis, a severe disease in tropical regions. This study investigated the role of tetraspanins inB. pseudomalleiinfection. We used flow cytometry to determine tetraspanins CD9, CD63, and CD81 expression on A549 and J774A.1 cells. Their roles inB. pseudomalleiinfection were investigated in vitro using monoclonal antibodies (MAbs) and recombinant large extracellular loop (EC2) proteins to pretreat cells before infection. Knockout of CD9 and CD81 in cells was performed using CRISPR Cas9 to confirm the role of tetraspanins. Pretreatment of A549 cells with MAb against CD9 and CD9-EC2 significantly enhancedB. pseudomalleiinternalization, but MAb against CD81 and CD81-EC2 inhibited MNGC formation. Reduction of MNGC formation was consistently observed in J774.A1 cells pretreated with MAbs specific to CD9 and CD81 and with CD9-EC2 and CD81-EC2. Data from knockout experiments confirmed that CD9 enhanced bacterial internalization and that CD81 inhibited MNGC formation. Our data indicate that tetraspanins are host cellular factors that mediated internalization and membrane fusion duringB. pseudomalleiinfection. Tetraspanins may be the potential therapeutic targets for melioidosis.
Individual differences in working memory capacity moderate effects of post-learning activity on memory consolidation over the long term
Authors: Martini Markus , Marhenke Robert , Martini Caroline , Rossi Sonja , Sachse Pierre
Published: October 2020

Similar to sleeping after learning, a brief period of wakeful resting after encoding new information supports memory retention in contrast to task-related cognition. Recent evidence suggests that working memory capacity (WMC) is related to sleep-dependent declarative memory consolidation. We tested whether WMC moderates the effect of a brief period of wakeful resting compared to performing a distractor task subsequent to encoding a word list. Participants encoded and immediately recalled a word list followed by either an 8 min wakeful resting period (eyes closed, relaxed) or by performing an adapted version of the d2 test of attention for 8 min. At the end of the experimental session (after 12–24 min) and again, after 7 days, participants were required to complete a surprise free recall test of both word lists. Our results show that interindividual differences in WMC are a central moderating factor for the effect of post-learning activity on memory retention. The difference in word retention between a brief period of wakeful resting versus performing a selective attention task subsequent to encoding increased in higher WMC individuals over a retention interval of 12–24 min, as well as over 7 days. This effect was reversed in lower WMC individuals. Our results extend findings showing that WMC seems not only to moderate sleep-related but also wakeful resting-related memory consolidation.
Crustal deformation rates in Kashmir valley and adjoining regions from continuous GPS measurements from 2008 to 2019
Authors: Jade Sridevi , Mir Ramees R. , Vivek Chiranjeevi G. , Shrungeshwara T. S. , Parvez I. A. , Chandra Rakesh , Babu D. Suri , Gupta S. Vishal , Ankit  , Rajana Siva Sai Kumar , Gaur V. K.
Published: October 2020

We present GPS velocities in Kashmir valley and adjoining regions from continuous Global Positioning System (cGPS) network during 2008 to 2019. Results indicate total arc normal shortening rates of ~ 14 mm/year across this transect of Himalaya that is comparable to the rates of ~ 10 to 20 mm/year reported else-where in the 2500 km Himalaya Arc. For the first time in Himalayas, arc-parallel extension rate of ~ 7 mm/year was recorded in the Kashmir valley, pointing to oblique deformation. Inverse modeling of the contemporary deformation rates in Kashmir valley indicate oblique slip of ~ 16 mm/year along the decollement with locking depth of ~ 15 km and width of ~ 145 km. This result is consistent with the recorded micro-seismicity and low velocity layer at a depth of 12 to 16 km beneath the Kashmir valley obtained from collocated broadband seismic network. Geodetic strain rates are consistent with the dislocation model and micro-seismic activity, with high strain accumulation (~ 7e−08 maximum compression) to the north of Kashmir valley and south of Zanskar ranges. Assuming the stored energy was fully released during 1555 earthquake, high geodetic strain rate since then and observed micro-seismicity point to probable future large earthquakes of Mw ~ 7.7 in Kashmir seismic gap.
Chasing coevolutionary signals in intrinsically disordered proteins complexes
Authors: Iserte Javier A. , Lazar Tamas , Tosatto Silvio C. E. , Tompa Peter , Marino-Buslje Cristina
Published: October 2020

Intrinsically disordered proteins/regions (IDPs/IDRs) are crucial components of the cell, they are highly abundant and participate ubiquitously in a wide range of biological functions, such as regulatory processes and cell signaling. Many of their important functions rely on protein interactions, by which they trigger or modulate different pathways. Sequence covariation, a powerful tool for protein contact prediction, has been applied successfully to predict protein structure and to identify protein–protein interactions mostly of globular proteins. IDPs/IDRs also mediate a plethora of protein–protein interactions, highlighting the importance of addressing sequence covariation-based inter-protein contact prediction of this class of proteins. Despite their importance, a systematic approach to analyze the covariation phenomena of intrinsically disordered proteins and their complexes is still missing. Here we carry out a comprehensive critical assessment of coevolution-based contact prediction in IDP/IDR complexes and detail the challenges and possible limitations that emerge from their analysis. We found that the coevolutionary signal is faint in most of the complexes of disordered proteins but positively correlates with the interface size and binding affinity between partners. In addition, we discuss the state-of-art methodology by biological interpretation of the results, formulate evaluation guidelines and suggest future directions of development to the field.
Technical considerations when designing a gene expression panel for renal transplant diagnosis
Authors: Toulza F. , Dominy K. , Cook T. , Galliford J. , Beadle J. , McLean A. , Roufosse C.
Published: October 2020

Gene expression analysis is emerging as a new diagnostic tool in transplant pathology, in particular for the diagnosis of antibody-mediated rejection. Diagnostic gene expression panels are defined on the basis of their pathophysiological relevance, but also need to be tested for their robustness across different preservatives and analysis platforms. The aim of this study is the investigate the effect of tissue sampling and preservation on candidate genes included in a renal transplant diagnostic panel. Using the NanoString platform, we compared the expression of 219 genes in 51 samples, split for formalin-fixation and paraffin-embedding (FFPE) and RNAlater preservation (RNAlater). We found that overall, gene expression significantly correlated between FFPE and RNAlater samples. However, at the individual gene level, 46 of the 219 genes did not correlate across the 51 matched FFPE and RNAlater samples. Comparing gene expression results using NanoString and qRT-PCR for 18 genes in the same pool of RNA (RNAlater), we found a significant correlation in 17/18 genes. Our study indicates that, in samples from the same routine diagnostic renal transplant biopsy procedure split for FFPE and RNAlater, 21% of 219 genes of potential biological significance do not correlate in expression. Whether this is due to fixatives or tissue sampling, selection of gene panels for routine diagnosis should take this information into consideration.
Potent inhibition of tumour cell proliferation and immunoregulatory function by mitochondria-targeted atovaquone
Authors: Cheng Gang , Hardy Micael , Topchyan Paytsar , Zander Ryan , Volberding Peter , Cui Weiguo , Kalyanaraman Balaraman
Published: October 2020

The FDA-approved prophylactic antimalarial drug atovaquone (ATO) recently was repurposed as an antitumor drug. Studies show that ATO exerts a profound antiproliferative effect in several cancer cells, including breast, ovarian, and glioma. Analogous to the mechanism of action proposed in parasites, ATO inhibits mitochondrial complex III and cell respiration. To enhance the chemotherapeutic efficacy and oxidative phosphorylation inhibition, we developed a mitochondria-targeted triphenylphosphonium-conjugated ATO with varying alkyl side chains (Mito4-ATO, Mito10-ATO, Mito12-ATO, and Mito16-ATO). Results show, for the first time, that triphenylphosphonium-conjugated ATO potently enhanced the antiproliferative effect of ATO in cancer cells and, depending upon the alkyl chain length, the molecular target of inhibition changes from mitochondrial complex III to complex I. Mito4-ATO and Mito10-ATO inhibit both pyruvate/malate-dependent complex I and duroquinol-dependent complex III-induced oxygen consumption whereas Mito12-ATO and Mito16-ATO inhibit only complex I-induced oxygen consumption. Mitochondrial target shifting may have immunoregulatory implications.
Perception of vibrotactile distance on the back
Authors: Plaisier Myrthe A. , Sap Lotte I. N. , Kappers Astrid M. L.
Published: October 2020

Vibrotactile displays worn on the back can be used as sensory substitution device. Often vibrotactile stimulation is chosen because vibration motors are easy to incorporate and relatively cheap. When designing such displays knowledge about vibrotactile perception on the back is crucial. In the current study we investigated distance perception. Biases in distance perception can explain spatial distortions that occur when, for instance, tracing a shape using vibration. We investigated the effect of orientation (horizontal vs vertical), the effect of positioning with respect to the spine and the effect of switching vibration motors on sequentially versus simultaneously. Our study includes four conditions. The condition which had a horizontal orientation with both vibration motors switching on sequentially on the same side of the spine was chosen is the baseline condition. The other three conditions were compared to this baseline condition. We found that distances felt longer in the vertical direction than in the horizontal direction. Furthermore, distances were perceived to be longer when vibration motors were distributed on both sides of the spine compared to when they were on the same side. Finally, distances felt shorter when vibration motors were switched on simultaneously compared to sequentially. In the simultaneous case a distance of 4 cm was not clearly perceived differently than a distance of 12 cm. When designing vibrotactile displays these anisotropies in perceived distance need to be taken into account because otherwise the intended shape will not match the perceived shape. Also, dynamically presented distances are more clearly perceived than static distances. This finding supports recommendations made in previous studies that dynamic patterns are easier to perceive than static patterns.
Identification of drivers of breast cancer invasion by secretome analysis: insight into CTGF signaling
Authors: Hellinger Johanna W. , Schömel Franziska , Buse Judith V. , Lenz Christof , Bauerschmitz Gerd , Emons Günter , Gründker Carsten
Published: October 2020

An altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion. Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of breast cancer.
High plasma salivary α-amylase, but not high AMY1 copy number, associated with low obesity rate in Qatari adults: cross-sectional study
Authors: Al-Akl Neyla , Thompson Richard I. , Arredouani Abdelilah
Published: October 2020

The relationship between salivary α-amylase activity (psAAa) or AMY1 copy number and the risk of obesity remains controversial. We aimed to assess this relationship in a cohort from Qatar, where obesity affects 43% of adults. The relationship was investigated cross-sectionally in 923 Qatari adults from the Qatar biobank cohort. AMY1 CN was estimated form whole genome sequencing data. The associations with obesity prevalence were assessed by linear and logistic regressions. We found no difference in AMY1 CN between obese and normal-weight individuals. However, the psAAa was significantly lower in obese individuals. Significant inverse correlations were found between adiposity markers and psAAa in both sexes, but were marginally stronger in men. A significant effect of high psAAa, but not AMY1 CN, on reduced obesity rates was identified in men (OR per psAAa unit 0.957 [95% CI 0.937–0.977], p < 0.001, with psAAa ranging between 5 to 66 U/L). A significantly higher prevalence of obesity was observed in the lowest quartile of psAAa in men (75% (Q1) vs. 36% (Q4), p < 0.001) and women (74% (Q1) vs 56% (Q4), p = 0.009). Our findings suggest that high psAAa, but not AMY1 CN, has a potential positive benefit against obesity in the Qatari population.
Cold weather increases the risk of scrotal torsion events: results of an ecological study of acute scrotal pain in Scotland over 25 years
Authors: Molokwu Chidi N. , Ndoumbe Judith K. , Goodman Chris M.
Published: October 2020

The role of ambient temperature in the aetiology of acute scrotal pain (ASP) remains uncertain. The most common causes of ASP are torsion of the testis (TT) or its appendages (TA) and epidymo-orchitis (EO). We undertook an ecological study of ASP in Scotland to determine whether a seasonal variation could be observed. Episode reports for TT, TA and EO in Scotland over 25 years were collated monthly. Statistical analyses were performed to determine whether changes in ambient temperature during the year could explain variations in monthly frequency. 7882 episodes of TT and TA (Group A), and 25,973 episodes of EO (Group B) were reported. There was significant variance in the frequency of Group A (p < 0.0001) and B (p = 0.0031) episodes by month, higher frequency of Group A episodes in the colder half of the year (p < 0.0001), and an inverse correlation between the frequency of Group A episodes and ambient temperature (Spearman r = − 0.8757, 95% CI − 0.9661 to − 0.5941, p = 0.0004). Ambient temperature is likely to be playing a role in the aetiology of TT and TA in Scotland but not EO. Further study is warranted to explain underlying mechanisms.
Pharmacologic profiling of patient-derived xenograft models of primary treatment-naïve triple-negative breast cancer
Authors: Powell Reid T. , Redwood Abena , Liu Xuan , Guo Lei , Cai Shirong , Zhou Xinhui , Tu Yizheng , Zhang Xiaomei , Qi Yuan , Jiang Yan , Echeverria Gloria , Feng Ningping , Ma XiaoYan , Giuliani Virginia , Marszalek Joseph R. , Heffernan Timothy P. , Vellano Christopher P. , White Jason B. , Stephan Clifford , Davies Peter J. , Moulder Stacy , Symmans W. Fraser , Chang Jeffrey T. , Piwnica-Worms Helen
Published: October 2020

Triple-negative breast cancer (TNBC) accounts for 15–20% of breast cancer cases in the United States, lacks targeted therapeutic options, and is associated with a 40–80% risk of recurrence. Thus, identifying actionable targets in treatment-naïve and chemoresistant TNBC is a critical unmet medical need. To address this need, we performed high-throughput drug viability screens on human tumor cells isolated from 16 patient-derived xenograft models of treatment-naïve primary TNBC. The models span a range of TNBC subtypes and exhibit a diverse set of putative driver mutations, thus providing a unique patient-derived, molecularly annotated pharmacologic resource that is reflective of TNBC. We identified therapeutically actionable targets including kinesin spindle protein (KSP). The KSP inhibitor targets the mitotic spindle through mechanisms independent of microtubule stability and showed efficacy in models that were resistant to microtubule inhibitors used as part of the current standard of care for TNBC. We also observed subtype selectivity of Prima-1Met, which showed higher levels of efficacy in the mesenchymal subtype. Coupling pharmacologic data with genomic and transcriptomic information, we showed that Prima-1Met activity was independent of its canonical target, mutant p53, and was better associated with glutathione metabolism, providing an alternate molecularly defined biomarker for this drug.
Direct measurement of the thermoelectric properties of electrochemically deposited Bi2Te3 thin films
Authors: Recatala-Gomez Jose , Kumar Pawan , Suwardi Ady , Abutaha Anas , Nandhakumar Iris , Hippalgaonkar Kedar
Published: October 2020

The best known thermoelectric material for near room temperature heat-to-electricity conversion is bismuth telluride. Amongst the possible fabrication techniques, electrodeposition has attracted attention due to its simplicity and low cost. However, the measurement of the thermoelectric properties of electrodeposited films is challenging because of the conducting seed layer underneath the film. Here, we develop a method to directly measure the thermoelectric properties of electrodeposited bismuth telluride thin films, grown on indium tin oxide. Using this technique, the temperature dependent thermoelectric properties (Seebeck coefficient and electrical conductivity) of electrodeposited thin films have been measured down to 100 K. A parallel resistor model is employed to discern the signal of the film from the signal of the seed layer and the data are carefully analysed and contextualized with literature. Our analysis demonstrates that the thermoelectric properties of electrodeposited films can be accurately evaluated without inflicting any damage to the films.
Multi-strain volatile profiling of pathogenic and commensal cutaneous bacteria
Authors: Fitzgerald Shane , Duffy Emer , Holland Linda , Morrin Aoife
Published: October 2020

The detection of volatile organic compounds (VOC) emitted by pathogenic bacteria has been proposed as a potential non-invasive approach for characterising various infectious diseases as well as wound infections. Studying microbial VOC profiles in vitro allows the mechanisms governing VOC production and the cellular origin of VOCs to be deduced. However, inter-study comparisons of microbial VOC data remains a challenge due to the variation in instrumental and growth parameters across studies. In this work, multiple strains of pathogenic and commensal cutaneous bacteria were analysed using headspace solid phase micro-extraction coupled with gas chromatography–mass spectrometry. A kinetic study was also carried out to assess the relationship between bacterial VOC profiles and the growth phase of cells. Comprehensive bacterial VOC profiles were successfully discriminated at the species-level, while strain-level variation was only observed in specific species and to a small degree. Temporal emission kinetics showed that the emission of particular compound groups were proportional to the respective growth phase for individual S. aureus and P. aeruginosa samples. Standardised experimental workflows are needed to improve comparability across studies and ultimately elevate the field of microbial VOC profiling. Our results build on and support previous literature and demonstrate that comprehensive discriminative results can be achieved using simple experimental and data analysis workflows.
Superior survival in right-sided versus left-sided colon signet ring cell carcinoma
Authors: Zhao Zhuang , Wang Dun-wei , Yan Na , Pan Shu , Li Zhi-wen
Published: October 2020

This study aimed to explore the association of tumor sidedness with the prognosis of patients with colon signet ring cell carcinoma (SRCC). Eligible patients were retrieved from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Cancer-specific survival (CSS) and overall survival (OS) were compared between patients with left-sided colon SRCC and those with right-sided lesions. A total of 2660 patients were included, among them, 1983 (74.5%) had right-sided colon SRCC. Compared to patients with left-sided colon SRCC, those who had the right-sided colon SRCC showed higher proportion of white race, female, aged ≥ 65 years, receiving total colectomy and ≥ 4 regional lymph node dissection; while had lower proportion of advanced AJCC stage. Besides, right-sided patients exhibited superior 5-year CSS (32.74% vs. 25.89%, P = 0.001) and OS (27.38% vs. 23.02%, P = 0.024) rates compared with left-sided ones. Multivariate analysis revealed that tumor sidedness was an independent prognostic factor. To be specific, patients with right-sided colon SRCC showed better CSS (HR: 0.873; 95% CI 0.777–0.981; P = 0.023) and OS (HR: 0.838; 95% CI 0.753–0.965; P = 0.002). Moreover, subgroup analysis demonstrated superior CSS and OS for right-sided patients in most subgroups. Tumor sidedness was an independent prognostic indicator for colon SRCC. Besides, patients with right-sided colon SRCC have superior prognosis than those with left-sided lesions.
Value of liver iron concentration in healthy volunteers assessed by MRI
Authors: Obrzut Marzanna , Atamaniuk Vitaliy , Glaser Kevin J. , Chen Jun , Ehman Richard L. , Obrzut Bogdan , Cholewa Marian , Gutkowski Krzysztof
Published: October 2020

Iron overload is a relatively common clinical condition resulting from disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, and myelodysplasia that can lead to progressive fibrosis and eventually cirrhosis of the liver. Therefore, it is essential to recognize the disease process at the earliest stage. Liver biopsy is the reference test for the assessment of liver fibrosis. It also allows for quantifying liver iron concentration (LIC) in patients. However, this is an invasive method with significant limitations and possible risks. Magnetic resonance imaging (MRI) and evaluation of the R2* relaxation rate can be an alternative to biopsy for assessing LIC. However, it causes a need for accurate R2* data corresponding to standard value for further comparison with examined patients. This study aimed to assess the normative values of liver R2* in healthy individuals. A total of 100 volunteers that met established criteria were enrolled in the study: 36 (36%) men and 64 (64%) women. The mean age was 22.9 years (range 20 to 32 years). R2* was estimated by an MRI exam with a 1.5 T clinical magnetic resonance scanner. Images for measuring the LIC and liver fat concentration were obtained using the IDEAL-IQ technique for liver imaging. The Mean (SD) liver R2* was 28.34 (2.25) s−1 (95% CI, 27.78–28.90, range 23.67–33.00 s−1) in females, 29.57 (3.20) s−1 (95% CI, 28.49–30.66, range 23.93–37.77 s−1) in males, and 28.72 (2.69) s−1 (range 23.67–37.77 s−1) in the whole group. R2* value in this particular population with a high proportion of young women did not exceed 38 s−1. In the absence of fibrosis or steatosis, liver stiffness and fat fraction did not show any relationship with R2*.
Author Correction: Reconstructed Skin Models Revealed Unexpected Differences in Epidermal African and Caucasian Skin
Authors: Girardeau-Hubert Sarah , Deneuville Céline , Pageon Hervé , Abed Kahina , Tacheau Charlotte , Cavusoglu Nükhet , Donovan Mark , Bernard Dominique , Asselineau Daniel
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Mass distribution of magnetized quark-nugget dark matter and comparison with requirements and observations
Authors: VanDevender J. Pace , Shoemaker Ian M. , Sloan T. , VanDevender Aaron P. , Ulmen Benjamin A.
Published: October 2020

Quark nuggets are a candidate for dark matter consistent with the Standard Model. Previous models of quark nuggets have investigated properties arising from their being composed of strange, up, and down quarks and have not included any effects caused by their self-magnetic field. However, Tatsumi found that the core of a magnetar star may be a quark nugget in a ferromagnetic state with core magnetic field Bsurface = 1012±1 T. We apply Tatsumi’s result to quark-nugget dark-matter and report results on aggregation of magnetized quark nuggets (MQNs) after formation from the quark-gluon plasma until expansion of the universe freezes out the mass distribution to ~ 10−24 kg to ~ 1014 kg. Aggregation overcomes weak-interaction decay. Computed mass distributions show MQNs are consistent with requirements for dark matter and indicate that geologic detectors (craters in peat bogs) and space-based detectors (satellites measuring radio-frequency emissions after passage through normal matter) should be able to detect MQN dark matter. Null and positive observations narrow the range of a key parameter Bo ~ Bsurface to 1 × 1011 T < Bo ≤ 3 × 1012 T.
Individual dietary specialization reduces intraspecific competition, rather than feeding activity, in black amur bream (Megalobrama terminalis)
Authors: Xia Yuguo , Li Yuefei , Zhu Shuli , Li Jie , Li Shanghao , Li Xinhui
Published: October 2020

Individual specialization and high plasticity in feeding activity are common in natural populations. However, the role of these two in intraspecific competition is unclear. In this study, the rhythm of feeding activity, dietary composition, niche width, niche overlap, and individual specialization was explored in four different size groups of black amur bream (Megalobrama terminalis), using microscopic identification of foregut contents and stable isotope analysis (δ13C and δ15N) of dorsal muscle. Both methods observed ontogenetic shifts in dietary preference and individual specializations, and revealed that the total niche width of large individuals was greater than small individuals. Mixed linear models indicated that feeding activity was significantly influenced by time (p < 0.0001), and no significant changes among size groups was evident (p = 0.244). Niche overlaps revealed that there was intensive diet competition between different size groups of black amur bream. Individual specialization in small juveniles was likely to be stronger than sub-adult and adult groups. Pearson’s correlation analysis revealed that the individual specialization was positively correlated with mean diet similarity within a group. The results indicated that intraspecific competition is reduced mainly by individual dietary specialization, rather than shift in feeding activity.
Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A
Authors: Mahesh Guruswamy , Rivas Gustavo B. S. , Caster Courtney , Ost Evan B. , Amunugama Ravi , Jones Richard , Allen David L. , Hardin Paul E.
Published: October 2020

Circadian clocks keep time via ~ 24 h transcriptional feedback loops. In Drosophila, CLOCK-CYCLE (CLK-CYC) activators and PERIOD-TIMELESS (PER-TIM) repressors are feedback loop components whose transcriptional status varies over a circadian cycle. Although changes in the state of activators and repressors has been characterized, how their status is translated to transcriptional activity is not understood. We used mass spectrometry to identify proteins that interact with GFP-tagged CLK (GFP-CLK) in fly heads at different times of day. Many expected and novel interacting proteins were detected, of which several interacted rhythmically and were potential regulators of protein levels, activity or transcriptional output. Genes encoding these proteins were tested to determine if they altered circadian behavior via RNAi knockdown in clock cells. The NIPPED-A protein, a scaffold for the SAGA and Tip60 histone modifying complexes, interacts with GFP-CLK as transcription is activated, and reducing Nipped-A expression lengthens circadian period. RNAi analysis of other SAGA complex components shows that the SAGA histone deubiquitination (DUB) module lengthened period similarly to Nipped-A RNAi knockdown and weakened rhythmicity, whereas reducing Tip60 HAT expression drastically weakened rhythmicity. These results suggest that CLK-CYC binds NIPPED-A early in the day to promote transcription through SAGA DUB and Tip60 HAT activity.