bluuebunny/crossref_metadata_2025 huggingface dataset:
The long-term associations between parental behaviors, cognitive function and brain activation in adolescence
Authors: Dandash Orwa , Cherbuin Nicolas , Schwartz Orli , Allen Nicholas B. , Whittle Sarah
Published: May 2021

Parenting behavior has a vital role in the development of the brain and cognitive abilities of offspring throughout childhood and adolescence. While positive and aggressive parenting behavior have been suggested to impact neurobiology in the form of abnormal brain activation in adolescents, little work has investigated the links between parenting behavior and the neurobiological correlates of cognitive performance during this age period. In the current longitudinal fMRI study, associations between parenting behaviors and cognitive performance and brain activation across mid- and late-adolescence were assessed. Observed measures of maternal aggressive and positive behavior were recorded in early adolescence (12 years) and correlated with fMRI activation and in-scanner behavioral scores on the multi-source interference task (MSIT) during mid- (16 years; 95 participants) and late-adolescence (19 years; 75 participants). There was a significant reduction in inhibitory-control-related brain activation in posterior parietal and cingulate cortices as participants transitioned from mid- to late-adolescence. Positive maternal behavior in early-adolescence was associated with lower activation in the left parietal and DLPFC during the MSIT in mid-adolescence, whereas maternal aggressive behavior was associated with longer reaction time to incongruent trials in late-adolescence. The study supports the notion that maternal behavior may influence subsequent neurocognitive development during adolescence.
Kinematic changes in goal-directed movements in a fear-conditioning paradigm
Authors: Nishi Yuki , Osumi Michihiro , Sumitani Masahiko , Yozu Arito , Morioka Shu
Published: May 2021

In individuals with a musculoskeletal disorder, goal-directed reaching movements of the hand are distorted. Here, we investigated a pain-related fear-conditioning effect on motor control. Twenty healthy participants (11 women and 9 men, 21.7 ± 2.7 years) performed a hand-reaching movement task. In the acquisition phase, a painful electrocutaneous stimulus was applied on the reaching hand simultaneous with the completion of reaching. In the subsequent extinction phase, the task context was the same but the painful stimulus was omitted. We divided the kinematic data of the hand-reaching movements into acceleration and deceleration periods based on the movement-velocity characteristics, and the duration of each period indicated the degree of impairment in the feedforward and feedback motor controls. We assessed the wavelet coherence between electromyograms of the triceps and biceps brachii muscles. In the acquisition phase, the durations of painful movements were significantly longer in both the acceleration and deceleration periods. In the extinction phase, painful movements were longer only in the acceleration period and higher pain expectation and fear were maintained. Similarly, the wavelet coherence of muscles in both periods were decreased in both the acquisition and extinction phases. These results indicate that negative emotional modulations might explain the altered motor functions observed in pain patients.
Longitudinal recordings of single units in the basal amygdala during fear conditioning and extinction
Authors: Lee Junghwa , An Bobae , Choi Sukwoo
Published: May 2021

The balance between activities of fear neurons and extinction neurons in the basolateral nucleus of the basal amygdala (BAL) has been hypothesized to encode fear states after extinction. However, it remains unclear whether these neurons are solely responsible for encoding fear states. In this study, we stably recorded single-unit activities in the BAL during fear conditioning and extinction for 3 days, providing a comprehensive view on how different BAL neurons respond during fear learning. We found BAL neurons that showed excitatory responses to the conditioned stimulus (CS) after fear conditioning (‘conditioning-potentiated neurons’) and another population that showed excitatory responses to the CS after extinction (‘extinction-potentiated neurons’). Interestingly, we also found BAL neurons that developed inhibitory responses to the CS after fear conditioning (‘conditioning-inhibited neurons’) or after extinction (‘extinction-inhibited neurons’). BAL neurons that showed excitatory responses to the CS displayed various functional connectivity with each other, whereas less connectivity was observed among neurons with inhibitory responses to the CS. Intriguingly, we found correlative neuronal activities between conditioning-potentiated neurons and neurons with inhibitory responses to the CS. Our findings suggest that distinct BAL neurons, which are responsive to the CS with excitation or inhibition, encode various facets of fear conditioning and extinction.
Human low-threshold mechanoafferent responses to pure changes in friction controlled using an ultrasonic haptic device
Authors: Dione Mariama , Watkins Roger Holmes , Vezzoli Eric , Lemaire-Semail Betty , Wessberg Johan
Published: May 2021

The forces that are developed when manipulating objects generate sensory cues that inform the central nervous system about the qualities of the object’s surface and the status of the hand/object interaction. Afferent responses to frictional transients or slips have been studied in the context of lifting/holding tasks. Here, we used microneurography and an innovative tactile stimulator, the Stimtac, to modulate both the friction level of a surface, without changing the surface or adding a lubricant, and, to generate the frictional transients in a pure and net fashion. In three protocols, we manipulated: the frictional transients, the friction levels, the rise times, the alternation of phases of decrease or increase in friction to emulate grating-like stimuli. Afferent responses were recorded in 2 FAIs, 1 FAII, 2 SAIs and 3 SAIIs from the median nerve of human participants. Independently of the unit type, we observed that: single spikes were generated time-locked to the frictional transients, and that reducing the friction level reduced the number of spikes during the stable phase of the stimulation. Our results suggest that those frictional cues are encoded in all the unit types and emphasize the possibility to use the Stimtac device to control mechanoreceptor firing with high temporal precision.
Magnetic properties of (Bi1−xLax)(Fe,Co)O3 films fabricated by a pulsed DC reactive sputtering and demonstration of magnetization reversal by electric field
Authors: Kuppan Munusamy , Yamamoto Daichi , Egawa Genta , Kalainathan Sivaperuman , Yoshimura Satoru
Published: May 2021

(Bi1−xLax)(Fe,Co)O3 multiferroic magnetic film were fabricated using pulsed DC (direct current) sputtering technique and demonstrated magnetization reversal by applied electric field. The fabricated (Bi0.41La0.59)(Fe0.75Co0.25)O3 films exhibited hysteresis curves of both ferromagnetic and ferroelectric behavior. The saturated magnetization (Ms) of the multiferroic film was about 70 emu/cm3. The squareness (S) (= remanent magnetization (Mr)/Ms) and coercivity (Hc) of perpendicular to film plane are 0.64 and 4.2 kOe which are larger compared with films in parallel to film plane of 0.5 and 2.5 kOe. The electric and magnetic domain structures of the (Bi0.41La0.59)(Fe0.75Co0.25)O3 film analyzed by electric force microscopy (EFM) and magnetic force microscopy (MFM) were clearly induced with submicron scale by applying a local electric field. This magnetization reversal indicates the future realization of high performance magnetic device with low power consumption.
Heat-activated nanomedicine formulation improves the anticancer potential of the HSP90 inhibitor luminespib in vitro
Authors: Epp-Ducharme Brittany , Dunne Michael , Fan Linyu , Evans James C. , Ahmed Lubabah , Bannigan Pauric , Allen Christine
Published: May 2021

The heat shock protein 90 inhibitor, luminespib, has demonstrated potent preclinical activity against numerous cancers. However, clinical translation has been impeded by dose-limiting toxicities that have necessitated dosing schedules which have reduced therapeutic efficacy. As such, luminespib is a prime candidate for reformulation using advanced drug delivery strategies that improve tumor delivery efficiency and limit off-target side effects. Specifically, thermosensitive liposomes are proposed as a drug delivery strategy capable of delivering high concentrations of drug to the tumor in combination with other chemotherapeutic molecules. Indeed, this work establishes that luminespib exhibits synergistic activity in lung cancer in combination with standard of care drugs such as cisplatin and vinorelbine. While our research team has previously developed thermosensitive liposomes containing cisplatin or vinorelbine, this work presents the first liposomal formulation of luminespib. The physico-chemical properties and heat-triggered release of the formulation were characterized. Cytotoxicity assays were used to determine the optimal drug ratios for treatment of luminespib in combination with cisplatin or vinorelbine in non-small cell lung cancer cells. The formulation and drug combination work presented in this paper offer the potential for resuscitation of the clinical prospects of a promising anticancer agent.
Robust real-time 3D imaging of moving scenes through atmospheric obscurant using single-photon LiDAR
Authors: Tobin Rachael , Halimi Abderrahim , McCarthy Aongus , Soan Philip J. , Buller Gerald S.
Published: May 2021

Recently, time-of-flight LiDAR using the single-photon detection approach has emerged as a potential solution for three-dimensional imaging in challenging measurement scenarios, such as over distances of many kilometres. The high sensitivity and picosecond timing resolution afforded by single-photon detection offers high-resolution depth profiling of remote, complex scenes while maintaining low power optical illumination. These properties are ideal for imaging in highly scattering environments such as through atmospheric obscurants, for example fog and smoke. In this paper we present the reconstruction of depth profiles of moving objects through high levels of obscurant equivalent to five attenuation lengths between transceiver and target at stand-off distances up to 150 m. We used a robust statistically based processing algorithm designed for the real time reconstruction of single-photon data obtained in the presence of atmospheric obscurant, including providing uncertainty estimates in the depth reconstruction. This demonstration of real-time 3D reconstruction of moving scenes points a way forward for high-resolution imaging from mobile platforms in degraded visual environments.
An in vivo confocal microscopy study of corneal changes in patients with systemic sclerosis
Authors: Szalai Eszter , Szucs Gabriella , Szamosi Szilvia , Aszalos Zsuzsa , Afra Ildiko , Kemeny-Beke Adam
Published: May 2021

To investigate corneal microstructure of systemic sclerosis (SSc) patients using in vivo confocal microscopy (IVCM). 33 patients with SSc and 30 age-matched healthy subjects were recruited. All participants underwent comprehensive ophthalmic examination including IVCM (Heidelberg Retina Tomograph III, Heidelberg Engineering GmbH, Heidelberg, Germany) and ocular surface evaluation. Subbasal nerve plexus morphology was investigated using automated software analysis (ACCMetrics V3; University of Manchester, Manchester, UK). Keratocyte cell densities in the anterior stroma were significantly lower in patients with SSc compared to controls (P < 0.0001). In 7 SSc patients no keratocyte nuclei were identified in the anterior stroma and in most patients scattered hyperreflective punctate material were observed in the anterior stroma. Significantly lower subbasal nerve fiber parameters were found in patients with SSc compared to healthy subjects (P < 0.05). There were no significant correlations between the duration of SSc and any of the corneal cell density values. Tear break-up time values (4.82 ± 3.15 s) and Ocular Surface Disease Index scores (33.27 ± 30.11) were abnormal, Schirmer values (6.78 ± 5.82 mm) were borderline in SSc patients. In SSc, corneal morphological changes and accumulation of punctate material in the stroma was detected with confocal microscopy. Severe ocular surface disease was observed in SSc patients with significant impairment in subbasal nerve plexus morphology resembling peripheral neuropathy.
Hydrochemistry of sediment pore water in the Bratsk reservoir (Baikal region, Russia)
Authors: Poletaeva V. I. , Tirskikh E. N. , Pastukhov M. V.
Published: May 2021

This study aimed to identify the factors responsible for the major ion composition of pore water from the bottom sediments of the Bratsk water reservoir, which is part of the largest freshwater Baikal-Angara water system. In the Bratsk reservoir, the overlying water was characterized as HCO3–Ca–Mg type with the mineralization ranging between 101.2 and 127.7 mg L−1 and pore water was characterized as HCO3–SO4–Ca, SO4–Cl–Ca–Mg and mixed water types, which had mineralization varying from 165.9 to 4608.1 mg L−1. The ionic composition of pore waters varied both along the sediment depth profile and across the water area. In pore water, the difference between the highest and lowest values was remarkably large: 5.1 times for K+, 13 times for Mg2+, 16 times for HCO3−, 20 times for Ca2+, 23 times for Na+, 80 times for SO42−, 105 times for Cl−. Such variability at different sites of the reservoir was due to the interrelation between major ion concentrations in the pore water and environmental parameters. The major factor responsible for pore water chemistry was the dissolution of sediment-forming material coming from various geochemical provinces. In the south part of the reservoir, Cl−, Na+ and SO42− concentrations may significantly increase in pore water due to the effect of subaqueous flow of highly mineralized groundwater.
Glial cells modulate retinal cell survival in rotenone-induced neural degeneration
Authors: Tawarayama Hiroshi , Inoue-Yanagimachi Maki , Himori Noriko , Nakazawa Toru
Published: May 2021

Administration of the mitochondrial complex I inhibitor rotenone provides an excellent model to study the pathomechanism of oxidative stress-related neural degeneration diseases. In this study, we examined the glial roles in retinal cell survival and degeneration under the rotenone-induced oxidative stress condition. Mouse-derived Müller, microglial (BV-2), and dissociated retinal cells were used for in vitro experiments. Gene expression levels and cell viability were determined using quantitative reverse transcription-polymerase chain reaction and the alamarBlue assay, respectively. Conditioned media were prepared by stimulating glial cells with rotenone. Retinal ganglion cells (RGCs) and inner nuclear layer (INL) were visualized on rat retinal sections by immunohistochemistry and eosin/hematoxylin, respectively. Rotenone dose-dependently induced glial cell death. Treatment with rotenone or rotenone-stimulated glial cell-conditioned media altered gene expression of growth factors and inflammatory cytokines in glial cells. The viability of dissociated retinal cells significantly increased upon culturing in media conditioned with rotenone-stimulated or Müller cell-conditioned media-stimulated BV-2 cells. Furthermore, intravitreal neurotrophin-5 administration prevented the rotenone-induced reduction of RGC number and INL thickness in rats. Thus, glial cells exerted both positive and negative effects on retinal cell survival in rotenone-induced neural degeneration via altered expression of growth factors, especially upregulation of microglia-derived Ntf5, and proinflammatory cytokines.
White-tailed deer S96 prion protein does not support stable in vitro propagation of most common CWD strains
Authors: Otero Alicia , Duque Velásquez Camilo , Aiken Judd , McKenzie Debbie
Published: May 2021

PrPC variation at residue 96 (G/S) plays an important role in the epidemiology of chronic wasting disease (CWD) in exposed white-tailed deer populations. In vivo studies have demonstrated the protective effect of serine at codon 96, which hinders the propagation of common CWD strains when expressed in homozygosis and increases the survival period of S96/wt heterozygous deer after challenge with CWD. Previous in vitro studies of the transmission barrier suggested that following a single amplification step, wt and S96 PrPC were equally susceptible to misfolding when seeded with various CWD prions. When we performed serial prion amplification in vitro using S96-PrPC, we observed a reduction in the efficiency of propagation with the Wisc-1 or CWD2 strains, suggesting these strains cannot stably template their conformations on this PrPC once the primary sequence has changed after the first round of replication. Our data shows the S96-PrPC polymorphism is detrimental to prion conversion of some CWD strains. These data suggests that deer homozygous for S96-PrPC may not sustain prion transmission as compared to a deer expressing G96-PrPC.
Urine biomarkers for the prediction of mortality in COVID-19 hospitalized patients
Authors: Morell-Garcia Daniel , Ramos-Chavarino David , Bauça Josep M. , Argente del Castillo Paula , Ballesteros-Vizoso Maria Antonieta , García de Guadiana-Romualdo Luis , Gómez-Cobo Cristina , Pou J. Albert , Amezaga-Menéndez Rocío , Alonso-Fernández Alberto , Llompart Isabel , García-Raja Ana
Published: May 2021

Risk factors associated with severity and mortality attributable to COVID-19 have been reported in different cohorts, highlighting the occurrence of acute kidney injury (AKI) in 25% of them. Among other, SARS-CoV-2 targets renal tubular cells and can cause acute renal damage. The aim of the present study was to evaluate the usefulness of urinary parameters in predicting intensive care unit (ICU) admission, mortality and development of AKI in hospitalized patients with COVID-19. Retrospective observational study, in a tertiary care hospital, between March 1st and April 19th, 2020. We recruited adult patients admitted consecutively and positive for SARS-CoV-2. Urinary and serum biomarkers were correlated with clinical outcomes (AKI, ICU admission, hospital discharge and in-hospital mortality) and evaluated using a logistic regression model and ROC curves. A total of 199 COVID-19 hospitalized patients were included. In AKI, the logistic regression model with a highest area under the curve (AUC) was reached by the combination of urine blood and previous chronic kidney disease, with an AUC of 0.676 (95%CI 0.512–0.840; p = 0.023); urine specific weight, sodium and albumin in serum, with an AUC of 0.837 (95% CI 0.766–0.909; p < 0.001) for ICU admission; and age, urine blood and lactate dehydrogenase levels in serum, with an AUC of 0.923 (95%CI 0.866–0.979; p < 0.001) for mortality prediction. For hospitalized patients with COVID-19, renal involvement and early alterations of urinary and serum parameters are useful as prognostic factors of AKI, the need for ICU admission and death.
Potential local adaptation of corals at acidified and warmed Nikko Bay, Palau
Authors: Kurihara Haruko , Watanabe Atsushi , Tsugi Asami , Mimura Izumi , Hongo Chuki , Kawai Takashi , Reimer James Davis , Kimoto Katsunori , Gouezo Marine , Golbuu Yimnang
Published: May 2021

Ocean warming and acidification caused by increases of atmospheric carbon dioxide are now thought to be major threats to coral reefs on a global scale. Here we evaluated the environmental conditions and benthic community structures in semi-closed Nikko Bay at the inner reef area in Palau, which has high pCO2 and seawater temperature conditions with high zooxanthellate coral coverage. Nikko Bay is a highly sheltered system with organisms showing low connectivity with surrounding environments, making this bay a unique site for evaluating adaptation and acclimatization responses of organisms to warmed and acidified environments. Seawater pCO2/Ωarag showed strong gradation ranging from 380 to 982 µatm (Ωarag: 1.79–3.66), and benthic coverage, including soft corals and turf algae, changed along with Ωarag while hard coral coverage did not change. In contrast to previous studies, net calcification was maintained in Nikko Bay even under very low mean Ωarag (2.44). Reciprocal transplantation of the dominant coral Porites cylindrica showed that the calcification rate of corals from Nikko Bay did not change when transplanted to a reference site, while calcification of reference site corals decreased when transplanted to Nikko Bay. Corals transplanted out of their origin sites also showed the highest interactive respiration (R) and lower gross photosynthesis (Pg) to respiration (Pg:R), indicating higher energy acquirement of corals at their origin site. The results of this study give important insights about the potential local acclimatization and adaptation capacity of corals to different environmental conditions including pCO2 and temperature.
Effect of 4-week physical exercises on tryptophan, kynurenine and kynurenic acid content in human sweat
Authors: Saran Tomasz , Turska Monika , Kocki Tomasz , Zawadka Magdalena , Zieliński Grzegorz , Turski Waldemar A. , Gawda Piotr
Published: May 2021

The aim of the study was the detection of TRP, kynurenine (KYN), and kynurenic acid (KYNA) in human sweat, and determining whether physical activity affects their content in this secrete. Two different methods were used simultaneously—collection of sweat by means of an absorption pad from the inter scapular region, and collection of a drop of sweat from the region of the forehead. Quantitative determinations of TRP, KYN and KYNA were performed using high performance liquid chromatography with ultraviolet and fluorescence detection. Determinations of sodium was carried out by the method of inductively coupled plasma collision/reaction cell ionization mass spectrophotometry. It was found that physical exercises evoked a decrease in the amount of KYN, and an increase in the amount of KYNA in sweat recorded on day 14, but not on day 28 of training. It appears that physical exercises result in a long-term increase in the kynurenine transaminase activity responsible for the formation of KYNA from KYN. Based on this results, it can be suggested that measurement of TRP, KYN and KYNA in sweat may have diagnostic potential and may help to establish an exercise regime appropriate for the age, gender and health status of rehabilitation patients.
Change in rheotactic behavior patterns of dinoflagellates in response to different microfluidic environments
Authors: Li Si-Wei , Lin Po-Hsu , Ho Tung-Yuan , Hsieh Chih-hao , Sun Chen-li
Published: May 2021

Plankton live in dynamic fluid environments. Their ability to change in response to different hydrodynamic cues is critical to their energy allocation and resource uptake. This study used a microfluidic device to evaluate the rheotactic behaviors of a model dinoflagellate species, Karlodinium veneficum, in different flow conditions. Although dinoflagellates experienced forced alignment in strong shear (i.e. “trapping”), fluid straining did not play a decisive role in their rheotactic movements. Moderate hydrodynamic magnitude (20 < |uf| < 40 µm s−1) was found to induce an orientation heading towards an oncoming current (positive rheotaxis), as dinoflagellates switched to cross-flow swimming when flow speed exceeded 50 µm s−1. Near the sidewalls of the main channel, the steric mechanism enabled dinoflagellates to adapt upstream orientation through vertical migration. Under oscillatory flow, however, positive rheotaxis dominated with occasional diversion. The varying flow facilitated upstream exploration with directional controlling, through which dinoflagellates exhibited avoidance of both large-amplitude perturbance and very stagnant zones. In the mixed layer where water is not steady, these rheotactic responses could lead to spatial heterogeneity of dinoflagellates. The outcome of this study helps clarify the interaction between swimming behaviors of dinoflagellates and the hydrodynamic environment they reside in.
Expression of the myeloid inhibitory receptor CLEC12A correlates with disease activity and cytokines in early rheumatoid arthritis
Authors: Vaillancourt Myriam , Desaulniers Philippe , Paré Guillaume , Pagé Nathalie , Lachhab Asmaa , Kerever Anthony , Julien Anne-Sophie , Amiable Nathalie , Pelletier Martin , Tessier Philippe A. , Bessette Louis , Michou Laëtitia , Fortin Paul R. , Fernandes Maria J.
Published: May 2021

The myeloid inhibitory receptor CLEC12A negatively regulates inflammation. Reduced CLEC12A expression enhances inflammation in CLEC12A knock-out mice with collagen antibody-induced arthritis. Moreover, CLEC12A internalisation augments human neutrophil activation. We thus postulated that CLEC12A expression on circulating myeloid cells of rheumatoid arthritis patients is associated with disease manifestations. Cell-surface, CLEC12A receptor expression was determined on circulating neutrophils and monocytes of eRA patients and of healthy donors. Generalized estimating equations model, Student’s t-test and Spearman’s correlations were performed to compare CLEC12A expression between groups and test its association with disease activity and clinical parameters. Plasma cytokines were measured by multiplex immunoassay. Patients with reduced neutrophil or monocyte CLEC12A expression at baseline and at 3 months have an increased simple disease activity index. Low baseline CLEC12A expression also correlates with a higher SDAI at 6 months. In contrast, positive correlations were observed between baseline CLEC12A expression and several cytokines. Moreover, neutrophil and monocyte CLEC12A expression is significantly higher in early rheumatoid arthritis patients at baseline than healthy controls. Circulating neutrophil and monocyte CLEC12A expression correlates with disease activity at baseline and is predictive of SDAI at later stages of the disease indicative of a regulatory role for CLEC12A in RA.
Calcification in free-living coralline algae is strongly influenced by morphology: Implications for susceptibility to ocean acidification
Authors: Schubert Nadine , Hofmann Laurie C. , Almeida Saá Antonella C. , Moreira Anderson Camargo , Arenhart Rafael Güntzel , Fernandes Celso Peres , de Beer Dirk , Horta Paulo A. , Silva João
Published: May 2021

Rhodolith beds built by free-living coralline algae are important ecosystems for marine biodiversity and carbonate production. Yet, our mechanistic understanding regarding rhodolith physiology and its drivers is still limited. Using three rhodolith species with different branching morphologies, we investigated the role of morphology in species’ physiology and the implications for their susceptibility to ocean acidification (OA). For this, we determined the effects of thallus topography on diffusive boundary layer (DBL) thickness, the associated microscale oxygen and pH dynamics and their relationship with species’ metabolic and light and dark calcification rates, as well as species’ responses to short-term OA exposure. Our results show that rhodolith branching creates low-flow microenvironments that exhibit increasing DBL thickness with increasing branch length. This, together with species’ metabolic rates, determined the light-dependent pH dynamics at the algal surface, which in turn dictated species’ calcification rates. While these differences did not translate in species-specific responses to short-term OA exposure, the differences in the magnitude of diurnal pH fluctuations (~ 0.1–1.2 pH units) between species suggest potential differences in phenotypic plasticity to OA that may result in different susceptibilities to long-term OA exposure, supporting the general view that species’ ecomechanical characteristics must be considered for predicting OA responses.
5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis
Authors: Choi Jong Min , Baek Seung Eun , Kim Ji On , Jeon Eun Yeong , Jang Eun Jeong , Kim Chi Dae
Published: May 2021

Monocyte chemoattractant protein-1 (MCP-1) plays an important role in initiating vascular inflammation; however, its cellular source in the injured vasculatures is unclear. Given the importance of high mobility group box 1 (HMGB1) in tissue injury, we investigated the role of vascular smooth muscle cells (VSMCs) in MCP-1 production in response to HMGB1. In primary cultured rat aortic VSMCs stimulated with HMGB1, the expression of MCP-1 and 5-lipoxygenase (LO) was increased. The increased MCP-1 expression in HMGB1 (30 ng/ml)-stimulated cells was significantly attenuated in 5-LO-deficient cells as well as in cells treated with zileuton, a 5-LO inhibitor. Likewise, MCP-1 expression and production were also increased in cells stimulated with exogenous leukotriene B4 (LTB4), but not exogenous LTC4. LTB4-induced MCP-1 expression was attenuated in cells treated with U75302, a LTB4 receptor 1 (BLTR1) inhibitor as well as in BLTR1-deficient cells, but not in 5-LO-deficient cells. Moreover, HMGB1-induced MCP-1 expression was attenuated in BLTR1-deficient cells or by treatment with a BLTR1 inhibitor, but not other leukotriene receptor inhibitors. In contrast to MCP-1 expression in response to LTB4, the increased MCP-1 production in HMGB1-stimulated VSMC was markedly attenuated in 5-LO-deficient cells, indicating a pivotal role of LTB4-BLTR1 signaling in MCP-1 expression in VSMCs. Taken together, 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via BLTR1 signaling, suggesting the LTB4-BLTR1 signaling axis as a potential therapeutic target for vascular inflammation in the injured vasculatures.
Totipotency of mouse zygotes extends to single blastomeres of embryos at the four-cell stage
Authors: Maemura Marino , Taketsuru Hiroaki , Nakajima Yuki , Shao Ruiqi , Kakihara Ayaka , Nogami Jumpei , Ohkawa Yasuyuki , Tsukada Yu-ichi
Published: May 2021

In multicellular organisms, oocytes and sperm undergo fusion during fertilization and the resulting zygote gives rise to a new individual. The ability of zygotes to produce a fully formed individual from a single cell when placed in a supportive environment is known as totipotency. Given that totipotent cells are the source of all multicellular organisms, a better understanding of totipotency may have a wide-ranging impact on biology. The precise delineation of totipotent cells in mammals has remained elusive, however, although zygotes and single blastomeres of embryos at the two-cell stage have been thought to be the only totipotent cells in mice. We now show that a single blastomere of two- or four-cell mouse embryos can give rise to a fertile adult when placed in a uterus, even though blastomere isolation disturbs the transcriptome of derived embryos. Single blastomeres isolated from embryos at the eight-cell or morula stages and cultured in vitro manifested pronounced defects in the formation of epiblast and primitive endoderm by the inner cell mass and in the development of blastocysts, respectively. Our results thus indicate that totipotency of mouse zygotes extends to single blastomeres of embryos at the four-cell stage.
Mobile sonouroflowmetry using voiding sound and volume
Authors: El Helou Elie , Naba Joy , Youssef Karim , Mjaess Georges , Sleilaty Ghassan , Helou Samar
Published: May 2021

Uroflowmetry (UF) is a common clinic-based non-invasive test to diagnose Lower Urinary Tract Dysfunction (LUTD). Accurate home-based uroflowmetry methods are needed to conveniently conduct repeated uroflowmetries when patients are physiologically ready to urinate. To this end, we propose and evaluate a novel mobile sonouroflowmetry (SUF) method that estimates the urinary flow rate from a sound signal recorded using a mobile phone. By linearly mapping the total sound energy to the total voided volume, the sound energy curve is transformed to a flow rate curve allowing the estimation of the flow rate over time. An evaluation using data from 44 healthy young men showed high similarity between the UF and SUF flow rates with a mixed-effects model correlation coefficient of 0.993 and a mean root mean square error of 2.37 ml/s. Maximum flow rates were estimated with an average absolute error of 2.41 ml/s. Future work on mobile uroflowmetry can use these results as an initial benchmark for flow rate estimation accuracy.
Genetic contributions to the expression of acquired causes of cardiac hypertrophy in non-ischemic sudden cardiac death victims
Authors: Holmström Lauri , Pylkäs Katri , Tervasmäki Anna , Vähätalo Juha , Porvari Katja , Pakanen Lasse , Kaikkonen Kari S. , Perkiömäki Juha S. , Kiviniemi Antti M. , Kerkelä Risto , Ukkola Olavi , Myerburg Robert J. , Huikuri Heikki V. , Junttila Juhani
Published: May 2021

The contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to SCD.
NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis
Authors: Wang Xuan , Cai Jun , Zhao Lei , Zhang Dejun , Xu Guojie , Hu Jianli , Zhang Tao , Jin Min
Published: May 2021

Experimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent studies have also implicated NUMB as a PCa suppressor and an inhibitor of PCa stem cells (PCSCs); however, exactly how NUMB functions in these contexts remains unclear. Here, by employing bioinformatics analysis and luciferase assays and by conducting rescue experiments, we first show that NUMB is directly targeted by microRNA-9-5p (miR-9-5p), an oncogenic miR associated with poor prognosis in many malignancies. We further show that miR-9-5p levels are inversely correlated with NUMB expression in CD44+ PCSCs. miR-9-5p reduced NUMB expression and inhibited numerous PCSC properties including proliferation, migration, invasion as well as self-renewal. Strikingly, overexpression of NUMB in CD44+ PCSCs overcame all of the above PCSC properties enforced by miR-9-5p. Taken together, our results suggest that inhibiting the expression of the oncomiR miR-9-5p and overexpressing NUMB may represent novel therapeutic strategies to target PCSCs and PCa metastasis.
A validation study comparing existing prediction models of acute kidney injury in patients with acute heart failure
Authors: Lee Tao Han , Fan Pei-Chun , Chen Jia-Jin , Wu Victor Chien‐Chia , Lee Cheng-Chia , Yen Chieh-Li , Kuo George , Hsu Hsiang-Hao , Tian Ya-Chung , Chang Chih-Hsiang
Published: May 2021

Acute kidney injury (AKI) is a common complication in acute heart failure (AHF) and is associated with prolonged hospitalization and increased mortality. The aim of this study was to externally validate existing prediction models of AKI in patients with AHF. Data for 10,364 patients hospitalized for acute heart failure between 2008 and 2018 were extracted from the Chang Gung Research Database and analysed. The primary outcome of interest was AKI, defined according to the KDIGO definition. The area under the receiver operating characteristic (AUC) curve was used to assess the discrimination performance of each prediction model. Five existing prediction models were externally validated, and the Forman risk score and the prediction model reported by Wang et al. showed the most favourable discrimination and calibration performance. The Forman risk score had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.696, 0.829, and 0.817, respectively. The Wang et al. model had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.73, 0.858, and 0.845, respectively. The Forman risk score and the Wang et al. prediction model are simple and accurate tools for predicting AKI in patients with AHF.
Expression and purification of functional recombinant CUL2•RBX1 from E. coli
Authors: Diaz Stephanie , Li Lihong , Wang Kankan , Liu Xing
Published: May 2021

Cullin-2 (CUL2) based cullin-RING ligases (CRL2s) comprise a family of ubiquitin E3 ligases that exist only in multi-cellular organisms and are crucial for cellular processes such as embryogenesis and viral pathogenesis. CUL2 is the scaffold protein that binds one of the interchangeable substrate receptor modules, which consists of adaptor proteins and the substrate receptor protein. The VHL protein is a substrate receptor known to target hypoxia-inducible factor α (HIF1α) for ubiquitination and degradation. Because of its critical role in the ubiquitination of important cellular factors such as HIF1α, CRL2s have been investigated for their biological functions and the development of novel therapeutics against diseases. Given the importance of CRL2s in biological and biomedical research, methods that efficiently produce functional CUL2 proteins will greatly facilitate studies on the mechanism and regulation of CRL2s. Here, we report two cost-effective systems for the expression and purification of recombinant human CUL2 from E. coli cells. The purified CUL2 proteins were ~ 95% pure, could bind their substrate receptor modules, and were enzymatically active in transferring ubiquitin or ubiquitin-like protein to the corresponding substrate in in vitro assays. The presented methodological advancements will help advance research in CRL2 function and regulation.
Temporal variation in scattering and intrinsic attenuation due to earthquakes in East Asia
Authors: Iqbal Muhammad Zafar , Chung Tae Woong , Nam Myung Jin , Yoshimoto Kazuo
Published: May 2021

Separated attenuation values have not been used in post-seismic variation research, although the scattering attenuation (Qs−1) parameter that can be used to estimate crustal inhomogeneity due to cracks. In this study, three earthquakes that occurred in Kumamoto (M7.3), Tottori (M6.6), and Gyeongju (M5.8) in 2016 were investigated by applying a multiple lapse time window analysis to seismograms recorded before and after the events. At a low frequency, significantly greater variation of theQs−1value was observed than the intrinsic attenuation (Qi−1) for the Kumamoto earthquake, whereas similarly large variation was observed for the Gyeongju earthquake. For the surrounding Kumamoto earthquake area of increased attenuation, even higher decreases inQs–1andQi–1were also observed. The increases occurred within a two year-period after mainshock. The large increases in attenuation, corresponding to regions with high peak ground acceleration, were limited to the basin area with an elevation below 500 m. Furthermore, post-seismic increases in attenuation values were found to correlate with the magnitude and length of the quiet periods of the earthquakes. From this study,Qs–1andQi–1were shown as new parameters that can quantitatively measure the post-seismic deformation due to crustal earthquake.
First theoretical determination of relative biological effectiveness of very high energy electrons
Authors: Delorme Rachel , Masilela Thongchai A. M. , Etoh Camille , Smekens François , Prezado Yolanda
Published: May 2021

Very high energy electrons (VHEEs, E > 70 MeV) present promising clinical advantages over conventional beams due to their increased range, improved penumbra and relative insensitivity to tissue heterogeneities. They have recently garnered additional interest in their application to spatially fractionated radiotherapy or ultra-high dose rate (FLASH) therapy. However, the lack of radiobiological data limits their rapid development. This study aims to provide numerical biologically-relevant information by characterizing VHEE beams (100 and 300 MeV) against better-known beams (clinical energy electrons, photons, protons, carbon and neon ions). Their macro- and microdosimetric properties were compared, using the dose-averaged linear energy transfer ($$\overline{{L_{d} }}$$

L
d

¯

) as the macroscopic metric, and the dose-mean lineal energy $$\overline{{y_{d} }}$$

y
d

¯

and the dose-weighted lineal energy distribution, yd(y), as microscopic metrics. Finally, the modified microdosimetric kinetic model was used to calculate the respective cell survival curves and the theoretical RBE. From the macrodosimetric point of view, VHEEs presented a potential improved biological efficacy over clinical photon/electron beams due to their increased $$\overline{{L_{d} }}$$

L
d

¯

. The microdosimetric data, however, suggests no increased biological efficacy of VHEEs over clinical electron beams, resulting in RBE values of approximately 1, giving confidence to their clinical implementation. This study represents a first step to complement further radiobiological experiments.
Epidemiology of keratitis/scleritis-related endophthalmitis in a university hospital in Thailand
Authors: Dhirachaikulpanich Dhanach , Soraprajum Kunravitch , Boonsopon Sutasinee , Pinitpuwadol Warinyupa , Lourthai Preeyachan , Punyayingyong Noppakhun , Tesavibul Nattaporn , Choopong Pitipol
Published: May 2021

To demonstrate the demographics, associated factors, clinical presentations, microbiology, management, visual outcome and complications of keratitis/scleritis-related endophthalmitis (KSE). A retrospective chart of all endophthalmitis patients diagnosed between September 2001 and August 2011 was reviewed. Only endophthalmitis cases with previous corneal or scleral infection were included in the study. The patients were followed until losing vision or eyeball, becoming phthisis, or the end of 2018. Eighty-seven patients with KSE were identified, all unilateral. The mean age was 56.4 ± 21.4 years. There was a slight male predilection (55 patients, 63.2%). The mean follow-up time was 50 ± 149 weeks. The causative pathogens were identified in 35 patients (40.2%), with the highest frequency being bacteria. The most common bacterium was Pseudomonas aeruginosa (n = 13), and the most common fungus was Aspergillus sp. (n = 5). Fifteen patients achieved (17.2%) final visual acuity (VA) of hand motion or better after treatment. Eyeball removal was performed in 61 (70.1%) patients. From multivariate analysis, the only prognostic factor for poor final VA (worse than hand motion, HM) was poor VA (worse than HM) at the initial visit (relative risk 1.97, 95% confidence interval 1.15–3.36, p = 0.013). KSE is uncommon but has a devastating outcome. We found that the patient’s initial VA was the only predictor for their final vision. P. aeruginosa was the most common identifiable organism in this study. However, several fungal infections were recognised. These findings should raise awareness for treatment of KSE in the tropics.
Artificial neural network analysis of microbial diversity in the central and southern Adriatic Sea
Authors: Šantić Danijela , Piwosz Kasia , Matić Frano , Vrdoljak Tomaš Ana , Arapov Jasna , Dean Jason Lawrence , Šolić Mladen , Koblížek Michal , Kušpilić Grozdan , Šestanović Stefanija
Published: May 2021

Bacteria are an active and diverse component of pelagic communities. The identification of main factors governing microbial diversity and spatial distribution requires advanced mathematical analyses. Here, the bacterial community composition was analysed, along with a depth profile, in the open Adriatic Sea using amplicon sequencing of bacterial 16S rRNA and the Neural gas algorithm. The performed analysis classified the sample into four best matching units representing heterogenic patterns of the bacterial community composition. The observed parameters were more differentiated by depth than by area, with temperature and identified salinity as important environmental variables. The highest diversity was observed at the deep chlorophyll maximum, while bacterial abundance and production peaked in the upper layers. The most of the identified genera belonged to Proteobacteria, with uncultured AEGEAN-169 and SAR116 lineages being dominant Alphaproteobacteria, and OM60 (NOR5) and SAR86 being dominant Gammaproteobacteria. Marine Synechococcus and Cyanobium-related species were predominant in the shallow layer, while Prochlorococcus MIT 9313 formed a higher portion below 50 m depth. Bacteroidota were represented mostly by uncultured lineages (NS4, NS5 and NS9 marine lineages). In contrast, Actinobacteriota were dominated by a candidatus genus Ca. Actinomarina. A large contribution of Nitrospinae was evident at the deepest investigated layer. Our results document that neural network analysis of environmental data may provide a novel insight into factors affecting picoplankton in the open sea environment.
Optical fibre based real-time measurements during an LDR prostate brachytherapy implant simulation: using a 3D printed anthropomorphic phantom
Authors: Woulfe P. , Sullivan F. J. , Byrne L. , Doyle A. J. , Kam W. , Martyn M. , O’Keeffe S.
Published: May 2021

An optical fibre sensor based on radioluminescence, using the scintillation material terbium doped gadolinium oxysulphide (Gd2O2S:Tb) is evaluated, using a 3D printed anthropomorphic phantom for applications in low dose-rate (LDR) prostate brachytherapy. The scintillation material is embedded in a 700 µm diameter cavity within a 1 mm plastic optical fibre that is fixed within a brachytherapy needle. The high spatial resolution dosimeter is used to measure the dose contribution from Iodine-125 (I-125) seeds. Initially, the effects of sterilisation on the sensors (1) repeatability, (2) response as a function of angle, and (3) response as a function of distance, are evaluated in a custom polymethyl methacrylate phantom. Results obtained in this study demonstrate that the output response of the sensor, pre- and post-sterilisation are within the acceptable measurement uncertainty ranging from a maximum standard deviation of 4.7% pre and 5.5% post respectively, indicating that the low temperature sterilisation process does not damage the sensor or reduce performance. Subsequently, an LDR brachytherapy plan reconstructed using the VariSeed treatment planning system, in an anthropomorphic 3D printed training phantom, was used to assess the suitability of the sensor for applications in LDR brachytherapy. This phantom was printed based on patient anatomy, with the volume and dimensions of the prostate designed to represent that of the patient. I-125 brachytherapy seeds, with an average activity of 0.410 mCi, were implanted into the prostate phantom under trans-rectal ultrasound guidance; following the same techniques as employed in clinical practice by an experienced radiation oncologist. This work has demonstrated that this sensor is capable of accurately identifying when radioactive I-125 sources are introduced into the prostate via a brachytherapy needle.