bluuebunny/crossref_metadata_2025 huggingface dataset:
Single incision laparoscopic surgery using conventional laparoscopic instruments versus two-port laparoscopic surgery for adnexal lesions
Authors: Huang Kuan-Ju , Lin Kuan-Ting , Wu Chin-Jui , Li Ying-Xuan , Chang Wen-Chun , Sheu Bor-Ching
Published: February 2021

Single incision laparoscopic surgery (SILS) has emerged as least invasive interventions for gynecologic disease. However, SILS is slow to gain in popularity due to difficulties in triangulation and instrument crowding. Besides, the costly instruments may influence patients’ will to have this procedure, and limit other medical expense as well. To optimize outcome and reduce cost, the objective of this study is to evaluate the feasibility and safety for patients undergoing adnexal surgeries using conventional laparoscopic instruments with SILS (SILS-C), and to compare with those of patients subject to TP using conventional laparoscopic instruments (TP-C). This is a retrospective case–control study. The data dated from April 2011 to April 2018. Patients who received concomitant multiple surgeries, were diagnosed with suspected advanced stage ovarian malignancy, or required frozen sections for intraoperative pathologic diagnosis were excluded. Demographic data, including the age, body weight, height, previous abdominal surgery were obtained. The surgical outcomes were compared using conventional statistical methods. 259 patients received SILS-C. The operating time was 63.83 ± 25.31 min. Blood loss was 2.38 ± 6.09 c.c. 58 patients (24.38%) needed addition of port to complete surgery. 384 patients received TP-C. Compared with SILS-C, the operating time was shorter (57.32 ± 26.38 min, OR = 0.984, CI = 0.975–0.992). The patients were further divided into unilateral or bilateral adnexectomy, and unilateral or bilateral cystectomy. Other than the operating time in unilateral cystectomy (66.12 ± 19.5 vs. 58.27 ± 23.92 min, p = .002), no statistical differences were observed in the subgroup analysis. Single incision laparoscopic surgery using conventional laparoscopic instruments is feasible and safe as initial approach to adnexal lesions. In complex setting as unilateral cystectomy or pelvic adhesions, two-port access may be considered.
Decision theory for precision therapy of breast cancer
Authors: Kenn Michael , Cacsire Castillo-Tong Dan , Singer Christian F. , Karch Rudolf , Cibena Michael , Koelbl Heinz , Schreiner Wolfgang
Published: February 2021

Correctly estimating the hormone receptor status for estrogen (ER) and progesterone (PGR) is crucial for precision therapy of breast cancer. It is known that conventional diagnostics (immunohistochemistry, IHC) yields a significant rate of wrongly diagnosed receptor status. Here we demonstrate how Dempster Shafer decision Theory (DST) enhances diagnostic precision by adding information from gene expression. We downloaded data of 3753 breast cancer patients from Gene Expression Omnibus. Information from IHC and gene expression was fused according to DST, and the clinical criterion for receptor positivity was re-modelled along DST. Receptor status predicted according to DST was compared with conventional assessment via IHC and gene-expression, and deviations were flagged as questionable. The survival of questionable cases turned out significantly worse (Kaplan Meier p < 1%) than for patients with receptor status confirmed by DST, indicating a substantial enhancement of diagnostic precision via DST. This study is not only relevant for precision medicine but also paves the way for introducing decision theory into OMICS data science.
The role of oxidised self-lipids and alveolar macrophage CD1b expression in COPD
Authors: Ween Miranda P. , White Jake B. , Tran Hai B. , Mukaro Violet , Jones Charles , Macowan Matthew , Hodge Gregory , Trim Paul J. , Snel Marten F. , Hodge Sandra J.
Published: February 2021

In chronic obstructive pulmonary disease (COPD) apoptotic bronchial epithelial cells are increased, and their phagocytosis by alveolar macrophages (AM) is decreased alongside bacterial phagocytosis. Epithelial cellular lipids, including those exposed on uncleared apoptotic bodies, can become oxidized, and may be recognized and presented as non-self by antigen presenting cells. CD1b is a lipid-presenting protein, previously only described in dendritic cells. We investigated whether CD1b is upregulated in COPD AM, and whether lipid oxidation products are found in the airways of cigarette smoke (CS) exposed mice. We also characterise CD1b for the first time in a range of macrophages and assess CD1b expression and phagocytic function in response to oxidised lipid. Bronchoalveolar lavage and exhaled breath condensate were collected from never-smoker, current-smoker, and COPD patients and AM CD1b expression and airway 8-isoprostane levels assessed. Malondialdehyde was measured in CS-exposed mouse airways by confocal/immunofluorescence. Oxidation of lipids produced from CS-exposed 16HBE14o- (HBE) bronchial epithelial cells was assessed by spectrophotometry and changes in lipid classes assessed by mass spectrometry. 16HBE cell toxicity was measured by flow cytometry as was phagocytosis, CD1b expression, HLA class I/II, and mannose receptor (MR) in monocyte derived macrophages (MDM). AM CD1b was significantly increased in COPD smokers (4.5 fold), COPD ex-smokers (4.3 fold), and smokers (3.9 fold), and AM CD1b significantly correlated with disease severity (FEV1) and smoking pack years. Airway 8-isoprostane also increased in smokers and COPD smokers and ex-smokers. Malondialdehyde was significantly increased in the bronchial epithelium of CS-exposed mice (MFI of 18.18 vs 23.50 for control). Oxidised lipid was produced from CS-exposed bronchial epithelial cells (9.8-fold of control) and showed a different overall lipid makeup to that of control total cellular lipid. This oxidised epithelial lipid significantly upregulated MDM CD1b, caused bronchial epithelial cell toxicity, and reduced MDM phagocytic capacity and MR in a dose dependent manner. Increased levels of oxidised lipids in the airways of COPD patients may be responsible for reduced phagocytosis and may become a self-antigen to be presented by CD1b on macrophages to perpetuate disease progression despite smoking cessation.
Resolving whether inhalation of depleted uranium contributed to Gulf War Illness using high-sensitivity mass spectrometry
Authors: Parrish Randall R. , Haley Robert W.
Published: February 2021

Of the hypothesized causes of Gulf War Illness (GWI), a chronic multi-symptom illness afflicting approximately 25% of military personnel deployed to the 1991 Gulf War, exposure to depleted uranium (DU) munitions has attracted international concern. Past research has not tested the potential association of GWI with inhaled DU nor used isotope mass spectrometry of sufficient sensitivity to rigorously assess prior DU exposure. We applied a standard biokinetic model to predict the urinary concentration and uranium isotopic ratios for a range of inhalation exposures. We then applied sensitive mass spectrometry capable of detecting the predicted urinary DU to 154 individuals of a population-representative sample of U.S. veterans in whom GWI had been determined by standard case definitions and DU inhalation exposures obtained by medical history. We found no difference in the 238U/235U ratio in veterans meeting the standard case definitions of GWI versus control veterans, no differences by levels of DU inhalation exposure, and no 236U associated with DU was detected. These findings show that even the highest likely levels of DU inhalation played no role in the development of GWI, leaving exposure to aerosolized organophosphate compounds (pesticides and sarin nerve agent) as the most likely cause(s) of GWI.
System design for inferring colony-level pollination activity through miniature bee-mounted sensors
Authors: Abdel-Raziq Haron M. , Palmer Daniel M. , Koenig Phoebe A. , Molnar Alyosha C. , Petersen Kirstin H.
Published: February 2021

In digital agriculture, large-scale data acquisition and analysis can improve farm management by allowing growers to constantly monitor the state of a field. Deploying large autonomous robot teams to navigate and monitor cluttered environments, however, is difficult and costly. Here, we present methods that would allow us to leverage managed colonies of honey bees equipped with miniature flight recorders to monitor orchard pollination activity. Tracking honey bee flights can inform estimates of crop pollination, allowing growers to improve yield and resource allocation. Honey bees are adept at maneuvering complex environments and collectively pool information about nectar and pollen sources through thousands of daily flights. Additionally, colonies are present in orchards before and during bloom for many crops, as growers often rent hives to ensure successful pollination. We characterize existing Angle-Sensitive Pixels (ASPs) for use in flight recorders and calculate memory and resolution trade-offs. We further integrate ASP data into a colony foraging simulator and show how large numbers of flights refine system accuracy, using methods from robotic mapping literature. Our results indicate promising potential for such agricultural monitoring, where we leverage the superiority of social insects to sense the physical world, while providing data acquisition on par with explicitly engineered systems.
Plasma microRNA signature associated with retinopathy in patients with type 2 diabetes
Authors: Santovito Donato , Toto Lisa , De Nardis Velia , Marcantonio Pamela , D’Aloisio Rossella , Mastropasqua Alessandra , De Cesare Domenico , Bucci Marco , Paganelli Camilla , Natarelli Lucia , Weber Christian , Consoli Agostino , Mastropasqua Rodolfo , Cipollone Francesco
Published: February 2021

Diabetic retinopathy (DR) is a leading cause of vision loss and disability. Effective management of DR depends on prompt treatment and would benefit from biomarkers for screening and pre-symptomatic detection of retinopathy in diabetic patients. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which are released in the bloodstream and may serve as biomarkers. Little is known on circulating miRNAs in patients with type 2 diabetes (T2DM) and DR. Here we show that DR is associated with higher circulating miR-25-3p (P = 0.004) and miR-320b (P = 0.011) and lower levels of miR-495-3p (P < 0.001) in a cohort of patients with T2DM with DR (n = 20), compared with diabetic subjects without DR (n = 10) and healthy individuals (n = 10). These associations persisted significant after adjustment for age, gender, and HbA1c. The circulating levels of these miRNAs correlated with severity of the disease and their concomitant evaluation showed high accuracy for identifying DR (AUROC = 0.93; P < 0.001). Gene ontology analysis of validated targets revealed enrichment in pathways such as regulation of metabolic process (P = 1.5 × 10–20), of cell response to stress (P = 1.9 × 10–14), and development of blood vessels (P = 2.7 × 10–14). Pending external validation, we anticipate that these miRNAs may serve as putative disease biomarkers and highlight novel molecular targets for improving care of patients with diabetic retinopathy.
Peripheral BDNF and psycho-behavioral aspects are positively modulated by high-intensity intermittent exercise and fitness in healthy women
Authors: de Poli Rodrigo Araujo Bonetti , Lopes Vithor Hugo Fialho , Lira Fábio Santos , Zagatto Alessandro Moura , Jimenez-Maldonado Alberto , Antunes Barbara Moura
Published: February 2021

Acute high-intensity intermittent exercise (HIIE) induces the myokine secretion associated with neurogenesis, as well brain-derived neurotrophic factor (BDNF); however, it remains unknown how the menstrual phase influences this secretion after an acute exercise session. The current study aimed to investigate the effects of HIIE performed in luteal and follicular menstrual phases on BDNF, cognitive function, mood, and exercise enjoyment. Fourteen healthy women completed four experimental sessions, randomly. One graded exercise test (GXT) and one HIIE session (10 × 1-min runs 90% peak GXT velocity [1-min recovery]) were performed for each menstrual phase. Blood samples were collected at rest and immediately after efforts, and the profile of mood states questionnaire (POMS) and Stroop-task test were applied. During the HIIE, subjective scales were applied (feeling, felt arousal, rate of perceived exertion, and physical activity enjoyment). The main results showed that the serum BDNF presented no difference between menstrual phases (p = 0.870); however, HIIE increased BDNF concentration in both menstrual phases (p = 0.030). In addition, the magnitude of circulating BDNF variation (Δ%BDNF) and $$\dot{\text{V}}{{\text{O}}}_{\text{2max}}$$

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demonstrated an inverse relationship in the follicular phase (r =  − 0.539, p = 0.046), whereas in the luteal phase, Δ%BDNF was negatively correlated with time test (r =  − 0.684, p = 0.007) and RPE (r =  − 0.726, p = 0.004) in GXT. No differences between menstrual phases were observed for POMS (p ≥ 0.05); however, HIIE attenuated tension (p < 0.01), depression (p < 0.01), and anger moods (p < 0.01), independently of menstrual phases. The subjective scales and Stroop-task test did not show differences. In conclusion, menstrual cycle phase does not affect serum BDNF levels, cognitive function, mood, and exercise enjoyment. Contrary, HIIE increases peripheral BDNF and attenuates tension, depression, and anger independently of menstrual phase. In addition, Δ%BDNF was correlated with physical fitness in the follicular phase, exhibiting higher changes in women with lower physical fitness status.
An elongated COI fragment to discriminate botryllid species and as an improved ascidian DNA barcode
Authors: Salonna Marika , Gasparini Fabio , Huchon Dorothée , Montesanto Federica , Haddas-Sasson Michal , Ekins Merrick , McNamara Marissa , Mastrototaro Francesco , Gissi Carmela
Published: February 2021

Botryllids are colonial ascidians widely studied for their potential invasiveness and as model organisms, however the morphological description and discrimination of these species is very problematic, leading to frequent specimen misidentifications. To facilitate species discrimination and detection of cryptic/new species, we developed new barcoding primers for the amplification of a COI fragment of about 860 bp (860-COI), which is an extension of the common Folmer's barcode region. Our 860-COI was successfully amplified in 177 worldwide-sampled botryllid colonies. Combined with morphological analyses, 860-COI allowed not only discriminating known species, but also identifying undescribed and cryptic species, resurrecting old species currently in synonymy, and proposing the assignment of clade D of the model organismBotryllus schlosseritoBotryllus renierii. Importantly, within clade A ofB. schlosseri, 860-COI recognized at least two candidate species against only one recognized by the Folmer's fragment, underlining the need of further genetic investigations on this clade. This result also suggests that the 860-COI could have a greater ability to diagnose cryptic/new species than the Folmer's fragment at very short evolutionary distances, such as those observed within clade A. Finally, our new primers simplify the amplification of 860-COI even in non-botryllid ascidians, suggesting their wider usefulness in ascidians.
Kar9 symmetry breaking alone is insufficient to ensure spindle alignment
Authors: Meziane Miram , Genthial Rachel , Vogel Jackie
Published: February 2021

Spindle positioning must be tightly regulated to ensure asymmetric cell divisions are successful. In budding yeast, spindle positioning is mediated by the asymmetric localization of microtubule + end tracking protein Kar9. Kar9 asymmetry is believed to be essential for spindle alignment. However, the temporal correlation between symmetry breaking and spindle alignment has not been measured. Here, we establish a method of quantifying Kar9 symmetry breaking and find that Kar9 asymmetry is not well coupled with stable spindle alignment. We report the spindles are not aligned in the majority of asymmetric cells. Rather, stable alignment is correlated with Kar9 residence in the bud, regardless of symmetry state. Our findings suggest that Kar9 asymmetry alone is insufficient for stable alignment and reveal a possible role for Swe1 in regulating Kar9 residence in the bud.
The first observation of 4D tomography measurement of plasma structures and fluctuations
Authors: Moon Chanho , Yamasaki Kotaro , Nagashima Yoshihiko , Inagaki Shigeru , Ido Takeshi , Yamada Takuma , Kasuya Naohiro , Kosuga Yusuke , Sasaki Makoto , Kawachi Yuichi , Nishimura Daiki , Kobayashi Taiki , Fujisawa Akihide
Published: February 2021

A tomography system is installed as one of the diagnostics of new age to examine the three-dimensional characteristics of structure and dynamics including fluctuations of a linear magnetized helicon plasma. The system is composed of three sets of tomography components located at different axial positions. Each tomography component can measure the two-dimensional emission profile over the entire cross-section of plasma at different axial positions in a sufficient temporal scale to detect the fluctuations. The four-dimensional measurement including time and space successfully obtains the following three results that have never been found without three-dimensional measurement: (1) in the production phase, the plasma front propagates from the antenna toward the end plate with an ion acoustic velocity. (2) In the steady state, the plasma emission profile is inhomogeneous, and decreases along the axial direction in the presence of the azimuthal asymmetry. Furthermore, (3) in the steady state, the fluctuations should originate from a particular axial position located downward from the helicon antenna.
Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells
Authors: Amoroso Francesca , Glass Kimberley , Singh Reema , Liberal Francisco , Steele Rebecca E. , Maguire Sarah , Tarapore Rohinton , Allen Joshua E. , Van Schaeybroeck Sandra , Butterworth Karl T. , Prise Kevin , O’Sullivan Joe M. , Jain Suneil , Waugh David J. , Mills Ian G.
Published: February 2021

Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. The unfolded protein response (UPR) can be cytoprotective but when acutely activated can lead to cell death. In this study, we sought to enhance the acute activation of the UPR using radiation and ONC201, an UPR activator. Treating PCa cells with ONC201 quickly increased the expression of all the key regulators of the UPR and reduced the oxidative phosphorylation, with cell death occurring 72 h later. We exploited this time lag to sensitize prostate cancer cells to radiation through short-term treatment with ONC201. To understand how priming occurred, we performed RNA-Seq analysis and found that ONC201 suppressed the expression of cell cycle and DNA repair factors. In conclusion, we have shown that ONC201 can prime enhanced radiation response.
A nationwide cohort study for comparative vascular safety of long-acting insulin analogue versus intermediate-acting human insulin in type 2 diabetes
Authors: Yang Chun-Ting , Li Kuan-Ying , Yang Chen-Yi , Ou Huang-Tz , Kuo Shihchen
Published: February 2021

Little is known about the comparative vascular safety of basal insulins (intermediate-acting human insulin [IAHI] or long-acting insulin analogue [LAIA]) in type 2 diabetes (T2D). This study sought to examine the vascular and hypoglycemic effects associated with IAHI versus LAIA in real-world patients with T2D. We utilized Taiwan’s National Health Insurance Research Database to identify T2D patients who stably used IAHI (N = 11,521) or LAIA (N = 37,651) in the period 2004–2012. A rigorous three-step matching algorithm that considered the initiation date of basal insulin, previous exposure of antidiabetic treatments, comorbidities, diabetes severity and complications, and concomitant medications was applied to achieve the between-group comparability. Study outcomes, including cardiovascular diseases (CVDs), microvascular diseases (MVDs), and hypoglycemia, were assessed up to the end of 2013. Compared with LAIA, the use of IAHI was associated with greater risks of composite CVDs (adjusted hazard ratio [aHR]: 1.79; 95% confidence interval [CI] 1.20–2.67) and hospitalized hypoglycemia (aHR: 1.82; 95% CI 1.51–2.20), but a lower risk of composite MVDs (aHR: 0.88; 95% CI 0.84–0.91). Subgroup and sensitivity analyses showed a consistent trend of results with that in the primary analyses. In summary, although the use of IAHI versus LAIA among T2D patients in usual practice may be associated with a lower risk of MVDs, strategies should be optimized for minimizing the risks of hypoglycemia and CVDs in this population.
Effect of palmitoylation on the dimer formation of the human dopamine transporter
Authors: Zeppelin Talia , Pedersen Kasper B. , Berglund Nils A. , Periole Xavier , Schiøtt Birgit
Published: February 2021

The human dopamine transporter (hDAT) is one in three members of the monoamine transporter family (MAT). hDAT is essential for regulating the dopamine concentration in the synaptic cleft through dopamine reuptake into the presynaptic neuron; thereby controlling hDAT dopamine signaling. Dysfunction of the transporter is linked to several psychiatric disorders. hDAT and the other MATs have been shown to form oligomers in the plasma membrane, but only limited data exists on which dimeric and higher order oligomeric states are accessible and energetically favorable. In this work, we present several probable dimer conformations using computational coarse-grained self-assembly simulations and assess the relative stability of the different dimer conformations using umbrella sampling replica exchange molecular dynamics. Overall, the dimer conformations primarily involve TM9 and/or TM11 and/or TM12 at the interface. Furthermore, we show that a palmitoyl group (palm) attached to hDAT on TM12 modifies the free energy of separation for interfaces involving TM12, suggesting that S-palmitoylation may change the relative abundance of dimers involving TM12 in a biological context. Finally, a comparison of the identified interfaces of hDAT and palmitoylated hDAT to the human serotonin transporter interfaces and the leucine transporter interface, suggests similar dimer conformations across these protein family.
Competing effects of spreading rate, crystal fractionation and source variability on Fe isotope systematics in mid-ocean ridge lavas
Authors: Richter Marianne , Nebel Oliver , Schwindinger Martin , Nebel-Jacobsen Yona , Dick Henry J. B.
Published: February 2021

Two-thirds of the Earth is covered by mid-ocean ridge basalts, which form along a network of divergent plate margins. Basalts along these margins display a chemical diversity, which is consequent to a complex interplay of partial mantle melting in the upper mantle and magmatic differentiation processes in lower crustal levels. Igneous differentiation (crystal fractionation, partial melting) and source heterogeneity, in general, are key drivers creating variable chemistry in mid-ocean ridge basalts. This variability is reflected in iron isotope systematics (expressed as δ57Fe), showing a total range of 0.2 ‰ from δ57Fe =  + 0.05 to + 0.25 ‰. Respective contributions of source heterogeneity and magma differentiation leading to this diversity, however, remain elusive. This study investigates the iron isotope systematics in basalts from the ultraslow spreading Gakkel Ridge in the Arctic Ocean and compares them to existing data from the fast spreading East Pacific Rise ridge. Results indicate that Gakkel lavas are driven to heavier iron isotope compositions through partial melting processes, whereas effects of igneous differentiation are minor. This is in stark contrast to fast spreading ridges showing reversed effects of near negligible partial melting effects followed by large isotope fractionation along the liquid line of descent. Gakkel lavas further reveal mantle heterogeneity that is superimposed on the igneous differentiation effects, showing that upper mantle Fe isotope heterogeneity can be transmitted into erupting basalts in the absence of homogenisation processes in sub-oceanic magma chambers.
Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
Authors: Lee Junguee , Park Ki Cheol , Sul Hae Joung , Hong Hyun Jung , Kim Kun-Ho , Kero Jukka , Shong Minho
Published: February 2021

The primary cilium is well-preserved in human differentiated thyroid cancers such as papillary and follicular carcinoma. Specific thyroid cancers such as Hürthle cell carcinoma, oncocytic variant of papillary thyroid carcinoma (PTC), and PTC with Hashimoto’s thyroiditis show reduced biogenesis of primary cilia; these cancers are often associated the abnormalities in mitochondrial function. Here, we examined the association between primary cilia and the mitochondria-dependent apoptosis pathway. Tg-Cre;Ift88flox/flox mice (in which thyroid follicles lacked primary cilia) showed irregularly dilated follicles and increased apoptosis of thyrocytes. Defective ciliogenesis caused by deleting the IFT88 and KIF3A genes from thyroid cancer cell lines increased VDAC1 oligomerization following VDAC1 overexpression, thereby facilitating upregulation of mitochondria-dependent apoptosis. Furthermore, VDAC1 localized with the basal bodies of primary cilia in thyroid cancer cells. These results demonstrate that loss-of-function of primary cilia results in apoptogenic stimuli, which are responsible for mitochondrial-dependent apoptotic cell death in differentiated thyroid cancers. Therefore, regulating primary ciliogenesis might be a therapeutic approach to targeting differentiated thyroid cancers.
Mining Google and Apple mobility data: temporal anatomy for COVID-19 social distancing
Authors: Cot Corentin , Cacciapaglia Giacomo , Sannino Francesco
Published: February 2021

We employ the Google and Apple mobility data to identify, quantify and classify different degrees of social distancing and characterise their imprint on the first wave of the COVID-19 pandemic in Europe and in the United States. We identify the period of enacted social distancing via Google and Apple data, independently from the political decisions. Our analysis allows us to classify different shades of social distancing measures for the first wave of the pandemic. We observe a strong decrease in the infection rate occurring two to five weeks after the onset of mobility reduction. A universal time scale emerges, after which social distancing shows its impact. We further provide an actual measure of the impact of social distancing for each region, showing that the effect amounts to a reduction by 20–40% in the infection rate in Europe and 30–70% in the US.
Enrichment analyses of diseases and pathways associated with precocious puberty using PrecocityDB
Authors: Sharma Mridula , Kundu Indra , Barai Ram Shankar , Bhaye Sameeksha , Desai Karishma , Pokar Khushal , Idicula-Thomas Susan
Published: February 2021

Precocious puberty (PP) is an important endocrine disorder affecting children globally. Several genes, SNPs and comorbidities are reported to be associated with PP; however, this data is scattered across scientific literature and has not been systematically collated and analysed. In this study, we present PrecocityDB as the first manually curated online database on genes and their ontology terms, SNPs, and pathways associated with PP. A tool for visualizing SNP coordinates and allelic variation on each chromosome, for genes associated with PP is also incorporated in PrecocityDB. Pathway enrichment analysis of PP-associated genes revealed that endocrine and cancer-related pathways are highly enriched. Disease enrichment analysis indicated that individuals with PP seem to be highly likely to suffer from reproductive and metabolic disorders such as PCOS, hypogonadism, and insulin resistance. PrecocityDB is a useful resource for identification of comorbid conditions and disease risks due to shared genes in PP. PrecocityDB is freely accessible at http://www.precocity.bicnirrh.res.in. The database source code and content can be downloaded through GitHub (https://github.com/bic-nirrh/precocity).
Enhancing learning in a perceptual-cognitive training paradigm using EEG-neurofeedback
Authors: Parsons Brendan , Faubert Jocelyn
Published: February 2021

This paper provides the framework and supporting evidence for a highly efficient closed-loop paradigm that modifies a classic learning scenario using real-time brain activity in order to improve learning performance in a perceptual-cognitive training paradigm known as 3-dimensional multiple object tracking, or 3D-MOT. Results demonstrate that, over 10 sessions, when manipulating this novel task by using real-time brain signals, speed and degree of learning can be substantially improved compared with a classic learning system or an active sham-control group. Superior performance persists even once the feedback signal is removed, which suggests that the effects of enhanced training are consolidated and do not rely on continued feedback. This type of learning paradigm could contribute to overcoming one of the fundamental limitations of neurofeedback and other cognitive enhancement techniques, a lack of observable transfer effects, by utilizing a method that can be directly integrated into the context in which improved performance is sought.
Performance of high resolution (400 m) PM2.5 forecast over Delhi
Authors: Jena Chinmay , Ghude Sachin D. , Kumar Rajesh , Debnath Sreyashi , Govardhan Gaurav , Soni Vijay K. , Kulkarni Santosh H. , Beig G. , Nanjundiah Ravi S. , Rajeevan M.
Published: February 2021

This study reports a very high-resolution (400 m grid-spacing) operational air quality forecasting system developed to alert residents of Delhi and the National Capital Region (NCR) about forthcoming acute air pollution episodes. Such a high-resolution system has been developed for the first time and is evaluated during October 2019-February 2020. The system assimilates near real-time aerosol observations from in situ and space-borne platform in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to produce a 72-h forecast daily in a dynamical downscaling framework. The assimilation of aerosol optical depth and surface PM2.5 observations improves the initial condition for surface PM2.5 by about 45 µg/m3 (about 50%).The accuracy of the forecast degrades slightly with lead time as mean bias increase from + 2.5 µg/m3 on the first day to − 17 µg/m3 on the third day of forecast. Our forecast is found to be very skillful both for PM2.5 concentration and unhealthy/ very unhealthy air quality index categories, and has been helping the decision-makers in Delhi make informed decisions.
Plasma lipocalin-2/NGAL is stable over 12 weeks and is not modulated by exercise or dieting
Authors: Nakai Michael E. , Denham Joshua , Prestes Priscilla R. , Eikelis Nina , Lambert Elisabeth A. , Straznicky Nora E. , Schlaich Markus P. , Esler Murray D. , O’Brien Brendan J. , Charchar Fadi J. , Lambert Gavin W. , Marques Francine Z.
Published: February 2021

Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18–55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise.
Feeding efficiency gains can increase the greenhouse gas mitigation potential of the Tanzanian dairy sector
Authors: Hawkins James , Yesuf Gabriel , Zijlstra Mink , Schoneveld George C. , Rufino Mariana C.
Published: February 2021

We use an attributional life cycle assessment (LCA) and simulation modelling to assess the effect of improved feeding practices and increased yields of feed crops on milk productivity and GHG emissions from the dairy sector of Tanzania’s southern highlands region. We calculated direct non-CO2 emissions from dairy production and the CO2 emissions resulting from the demand for croplands and grasslands using a land footprint indicator. Baseline GHG emissions intensities ranged between 19.8 and 27.8 and 5.8–5.9 kg CO2eq kg−1 fat and protein corrected milk for the Traditional (local cattle) and Modern (improved cattle) sectors. Land use change contributed 45.8–65.8% of the total carbon footprint of dairy. Better feeding increased milk yields by up to 60.1% and reduced emissions intensities by up to 52.4 and 38.0% for the Traditional and Modern sectors, respectively. Avoided land use change was the predominant cause of reductions in GHG emissions under all the scenarios. Reducing yield gaps of concentrate feed crops lowered emissions further by 11.4–34.9% despite increasing N2O and CO2 emissions from soils management and input use. This study demonstrates that feed intensification has potential to increase LUC emissions from dairy production, but that fertilizer-dependent yield gains can offset this increase in emissions through avoided emissions from land use change.
An in vitro study on factors affecting endotoxin neutralization in human plasma using the Limulus amebocyte lysate test
Authors: Harm Stephan , Schildböck Claudia , Strobl Karin , Hartmann Jens
Published: February 2021

Endotoxin neutralization, caused by plasma components, makes it difficult to detect endotoxins in human blood. In this study, we investigated which factors influence the recovery of endotoxins using limulus ameobocyte lysate (LAL)-based assays. The individual factors that were examined in more detail were lipoprotein content, type of blood anticoagulation, kinetics and serum levels of divalent cations. Furthermore, it was investigated whether there is a direct correlation between LAL activity and monocyte activation. We could show that polyanionic heparin increases endotoxin recovery in blood, while citrate anticoagulation promotes endotoxin neutralization. Furthermore, we could show that the endotoxin activity in human plasma and serum decreases strongly over time. Time-dependent endotoxin neutralization reaches its maximum after 4–6 h incubation. By means of filtration tests we could determine that endotoxins in the plasma bind to lipoproteins but do not influence their activity. Comparative measurements have shown that high LAL activity of endotoxins in plasma simultaneously possesses high monocyte activating properties in whole blood. For the maximum recovery of endotoxins in human blood the physiological calcium and magnesium concentrations are sufficient. In this study, it was shown that the endotoxin neutralizing plasma components have a molecular weight similar to β2-microglobulin (11.7 kDa). For the exact identification of the endotoxin neutralizing plasma components, which caused a modulation of the immunostimulating endotoxin activity, further investigations have to be carried out in the future.
Cellular correlates of gray matter volume changes in magnetic resonance morphometry identified by two-photon microscopy
Authors: Asan Livia , Falfán-Melgoza Claudia , Beretta Carlo A. , Sack Markus , Zheng Lei , Weber-Fahr Wolfgang , Kuner Thomas , Knabbe Johannes
Published: February 2021

Magnetic resonance imaging (MRI) of the brain combined with voxel-based morphometry (VBM) revealed changes in gray matter volume (GMV) in various disorders. However, the cellular basis of GMV changes has remained largely unclear. We correlated changes in GMV with cellular metrics by imaging mice with MRI and two-photon in vivo microscopy at three time points within 12 weeks, taking advantage of age-dependent changes in brain structure. Imaging fluorescent cell nuclei allowed inferences on (i) physical tissue volume as determined from reference spaces outlined by nuclei, (ii) cell density, (iii) the extent of cell clustering, and (iv) the volume of cell nuclei. Our data indicate that physical tissue volume alterations only account for 13.0% of the variance in GMV change. However, when including comprehensive measurements of nucleus volume and cell density, 35.6% of the GMV variance could be explained, highlighting the influence of distinct cellular mechanisms on VBM results.
Radon degassing triggered by tidal loading before an earthquake
Authors: Omori Yasutaka , Nagahama Hiroyuki , Yasuoka Yumi , Muto Jun
Published: February 2021

The presence of anomalous geochemical changes related to earthquakes has been controversial despite widespread, long time challenges for earthquake prediction. Establishing a quantitative relationship among geochemical changes and geodetical and seismological changes can clarify their hidden connection. Here we determined the response of atmospheric radon (222Rn) to diurnal tidal (K1 constituent) loading in the reported 11-year-long variation in the atmospheric radon concentration, including its anomalous evolution for 2 months before the devastating 1995 Kobe earthquake in Japan. The response to the tidal loading had been identified for 5 years before the occurrence of the earthquake. Comparison between these radon responses relative to crustal strain revealed that the response efficiency for the diurnal K1 tide was larger than that for the earthquake by a factor of 21–33, implying the involvement of crustal fluid movement. The radon responses occurred when compressional crustal stress decreased or changed to extension. These findings suggest that changes in radon exhaled from the ground were induced by ascent flow of soil gas acting as a radon carrier and degassed from mantle-derived crustal fluid upwelling due to modulation of the crustal stress regime.
Effect of temperature, CO2 and O2 on motility and mobility of Anisakidae larvae
Authors: Guan Aiyan , Van Damme Inge , Devlieghere Frank , Gabriël Sarah
Published: February 2021

Anisakidae, marine nematodes, are underrecognized fish-borne zoonotic parasites. Studies on factors that could trigger parasites to actively migrate out of the fish are very limited. The objective of this study was to assess the impact of different environmental conditions (temperature, CO2 and O2) on larval motility (in situ movement) and mobility (migration) in vitro. Larvae were collected by candling or enzymatic digestion from infected fish, identified morphologically and confirmed molecularly. Individual larvae were transferred to a semi-solid Phosphate Buffered Saline agar, and subjected to different temperatures (6 ℃, 12 ℃, 22 ℃, 37 ℃) at air conditions. Moreover, different combinations of CO2 and O2 with N2 as filler were tested, at both 6 °C and 12 °C. Video recordings of larvae were translated into scores for larval motility and mobility. Results showed that temperature had significant influence on larval movements, with the highest motility and mobility observed at 22 ℃ for Anisakis spp. larvae and 37 ℃ for Pseudoterranova spp. larvae. During the first 10 min, the median migration of Anisakis spp. larvae was 10 cm at 22 ℃, and the median migration of Pseudoterranova spp. larvae was 3 cm at 37 ℃. Larval mobility was not significantly different under the different CO2 or O2 conditions at 6 °C and 12 ℃. It was concluded that temperature significantly facilitated larval movement with the optimum temperature being different for Anisakis spp. and Pseudoterranova spp., while CO2 and O2 did not on the short term. This should be further validated in parasite-infected/spiked fish fillets.
Insights into long non-coding RNA regulation of anthocyanin carrot root pigmentation
Authors: Chialva Constanza , Blein Thomas , Crespi Martin , Lijavetzky Diego
Published: February 2021

Carrot (Daucus carota L.) is one of the most cultivated vegetable in the world and of great importance in the human diet. Its storage organs can accumulate large quantities of anthocyanins, metabolites that confer the purple pigmentation to carrot tissues and whose biosynthesis is well characterized. Long non-coding RNAs (lncRNAs) play critical roles in regulating gene expression of various biological processes in plants. In this study, we used a high throughput stranded RNA-seq to identify and analyze the expression profiles of lncRNAs in phloem and xylem root samples using two genotypes with a strong difference in anthocyanin production. We discovered and annotated 8484 new genes, including 2095 new protein-coding and 6373 non-coding transcripts. Moreover, we identified 639 differentially expressed lncRNAs between the phenotypically contrasted genotypes, including certain only detected in a particular tissue. We then established correlations between lncRNAs and anthocyanin biosynthesis genes in order to identify a molecular framework for the differential expression of the pathway between genotypes. A specific natural antisense transcript linked to the DcMYB7 key anthocyanin biosynthetic transcription factor suggested how the regulation of this pathway may have evolved between genotypes.
Elevated inflammatory responses and targeted therapeutic intervention in a preclinical mouse model of ataxia-telangiectasia lung disease
Authors: Saunders Rudel A. , Michniacki Thomas F. , Hames Courtney , Moale Hilary A. , Wilke Carol , Kuo Molly E. , Nguyen Johnathan , Hartlerode Andrea J. , Moore Bethany B. , Sekiguchi JoAnn M.
Published: February 2021

Ataxia-telangiectasia (A-T) is an autosomal recessive, multisystem disorder characterized by cerebellar degeneration, cancer predisposition, and immune system defects. A major cause of mortality in A-T patients is severe pulmonary disease; however, the underlying causes of the lung complications are poorly understood, and there are currently no curative therapeutic interventions. In this study, we examined the lung phenotypes caused by ATM-deficient immune cells using a mouse model of A-T pulmonary disease. In response to acute lung injury, ATM-deficiency causes decreased survival, reduced blood oxygen saturation, elevated neutrophil recruitment, exaggerated and prolonged inflammatory responses and excessive lung injury compared to controls. We found thatATMnull bone marrow adoptively transferred to WT recipients induces similar phenotypes that culminate in impaired lung function. Moreover, we demonstrated that activated ATM-deficient macrophages exhibit significantly elevated production of harmful reactive oxygen and nitrogen species and pro-inflammatory cytokines. These findings indicate that ATM-deficient immune cells play major roles in causing the lung pathologies in A-T. Based on these results, we examined the impact of inhibiting the aberrant inflammatory responses caused by ATM-deficiency with reparixin, a CXCR1/CXCR2 chemokine receptor antagonist. We demonstrated that reparixin treatment reduces neutrophil recruitment, edema and tissue damage inATMmutant lungs. Thus, our findings indicate that targeted inhibition of CXCR1/CXCR2 attenuates pulmonary phenotypes caused by ATM-deficiency and suggest that this treatment approach represents a viable therapeutic strategy for A-T lung disease.
Environmental stressors, complex interactions and marine benthic communities’ responses
Authors: Carrier-Belleau Charlotte , Drolet David , McKindsey Christopher W. , Archambault Philippe
Published: February 2021

The increasing number and diversity of anthropogenic stressors in marine habitats have multiple negative impacts on biological systems, biodiversity and ecosystem functions. Methods to assess cumulative effects include experimental manipulations, which may identify non-linear responses (i.e. synergies, antagonisms). However, experiments designed to test these ideas are uncommon, generally focusing on single biological responses. We conducted a manipulative experiment to investigate the isolated and combined effects of warming (+ 6 °C), salinity variation (freshwater pulses or presses), and nutrient enrichment (natural or enriched) following one and three month’s exposure, on responses measured at multiple levels of biological complexity in a simple bivalve assemblage. More specifically, we determined effects on bivalve mortality, growth, shell mineralization, and energy content, as well as microphytobenthos biomass. Salinity variation and nutrient enrichment, individually and combined, caused strong impacts on some of the measured variables and their effect varied through time. In contrast, warming had no effect. Our work highlights the prevalence of antagonistic interactions, the importance of examining effects of single and multiple stressors through time, and of considering multiple responses to understand the complexity behind stressor interactions.
Interaction study of monoisoamyl dimercaptosuccinic acid with bovine serum albumin using biophysical and molecular docking approaches
Authors: Thakur Ashima , Patwa Jayant , Pant Suyash , Sharma Abha , Flora S. J. S.
Published: February 2021

Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a lipophilic chelator has been evaluated for its potential use as an antidote in arsenic poisoning. The pharmacokinetics and pharmacodynamics properties of a drug could be understood via study its mechanism of interaction with bovine serum albumin protein (BSA). Therefore, the interaction between MiADMSA with BSA was investigated using various spectroscopic techniques and computational methods. Linear quenching of BSA intrinsic fluorescence intensity with the increasing concentration of MiADMSA was observed in the fluorescence study. Furthermore, synchronous results revealed that MiADMSA slightly changed the conformation of BSA. The binding constant value of the BSA-MiADMSA complex was found 1.60 × 104 M−1 at 298 K. The value of thermodynamic parameters ΔG, ΔH, and ΔS described that the process is spontaneous, endothermic, and hydrophobic forces are involved in the interaction of MiADMSA with BSA. Competitive site marker experiments showed that MiADMSA binds to site-II of BSA. Conformational changes of BSA with the interaction of MiADMSA were apparent by CD, UV–Visible, FT-IR, and 3D fluorescence spectroscopy. To strengthen the experimental findings we have also performed a theoretical study on the BSA-MiADMSA complex. Two sites were identified with docking score of − 6.642 kcal/mol at site IIa and − 3.80 kcal/mol for site IIb via molecular docking study. Molecular dynamics simulation study inferred the stability of the BSA-MiADMSA complex which was analyzed in a long simulation run. The experimental and computational studies have shown the effective binding of MiADMSA with BSA which is essential for the transportation and elimination of a drug from the body.