bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Risk and Resilience of Terrestrial Ecosystem Productivity under the Influence of Extreme Climatic Conditions over India
Authors: Jha Srinidhi , Das Jew , Goyal Manish Kumar
Published: December 2019

Analysing the link between terrestrial ecosystem productivity (i.e., Net Primary Productivity: NPP) and extreme climate conditions is vital in the context of increasing threats due to climate change. To reveal the impact of changing extreme conditions on NPP, a copula-based probabilistic model was developed, and the study was carried out over 25 river basins and 10 vegetation types of India. Further, the resiliency of the terrestrial ecosystems to sustain the extreme disturbances was evaluated at annual scale, monsoon, and non-monsoon seasons. The results showed, 15 out of 25 river basins were at high risks, and terrestrial ecosystems in only 5 river basins were resilient to extreme climatic conditions. Moreover, at least 50% area under 4 out of 10 vegetation cover types was found to be facing high chances of a drastic reduction in NPP, and 8 out of 10 vegetation cover types were non-resilient with the changing extreme climate conditions.
Palm Kernel Shell as an effective adsorbent for the treatment of heavy metal contaminated water
Authors: Baby Rabia , Saifullah Bullo , Hussein Mohd Zobir
Published: December 2019

Heavy metal contamination in water causes severe adverse effects on human health. Millions of tons of kernel shell are produced as waste from oil palm plantation every year. In this study, palm oil kernel shell (PKS), an agricultural waste is utilized as effective adsorbent for the removal of heavy metals, namely; Cr6+, Pb2+, Cd2+ and Zn2+ from water. Different parameters of adsorptions; solution pH, adsorbent dosage, metal ions concentration and contact time were optimized. The PKS was found to be effective in the adsorption of heavy metal ions Cr6+, Pb2+, Cd2+ and Zn2+ from water with percentage removal of 98.92%, 99.01%, 84.23% and 83.45%, respectively. The adsorption capacities for Cr6+, Pb2+, Cd2+ and Zn2+ were found to be 49.65 mg/g, 43.12 mg/g, 49.62 mg/g and 41.72 mg/g respectively. Kinetics of adsorption process were determined for each metal ion using different kinetic models like the pseudo-first order, pseudo-second order and parabolic diffusion models. For each metal ion the pseudo-second order model fitted well with correlation coefficient, R2 = 0.999. Different isotherm models, namely Freundlich and Langmuir were applied for the determination of adsorption interaction between metal ions and PKS. Adsorption capacity was also determined for each of the metal ions. PKS was found to be very effective adsorbent for the treatment of heavy metal contaminated water and short time of two hours is required for maximum adsorption. This is a comprehensive study almost all the parameters of adsorptions were studied in detail. This is a cost effective and greener approach to utilize the agricultural waste without any chemical treatment, making it user friendly adsorbent.
Identification of trace metals and potential anthropogenic influences on the historic New York African Burial Ground population: A pXRF technology approach
Authors: Clinton Carter K. , Duncan Candice M. , Shaw Richard K. , Jackson Latifa , Jackson Fatimah L. C.
Published: December 2019

The New York African Burial Ground (NYABG) is the country’s oldest and largest burial site of free and enslaved Africans. Re-discovered in 1991, this site provided evidence of the biological and cultural existence of a 17th and 18th Century historic population viewing their skeletal remains. However, the skeletal remains were reburied in October 2003 and are unavailable for further investigation. The analysis of grave soil samples with modern technology allows for the assessment of trace metal presence. Portable X-ray fluorescence (pXRF) spectrometry provides a semi-quantitative and non-destructive method to identify trace metals of this population and in the surrounding environment. Sixty-five NYABG soil samples were analyzed on a handheld Bruker Tracer III- SD XRF with 40 kV of voltage and a 30μA current. Presence of As, Cu, and Zn can potentially decipher the influence of the local 18th Century pottery factories. Elevated levels of Sr validate the assumed heavy vegetative diets of poor and enslaved Africans of the time. Decreased levels of Ca may be due in part to the proximity of the Collect Pond, the existing water table until the early 19th Century, and Manhattan’s rising sea level causing an elevated water table washing away the leached Ca from human remains. These data help us reconstruct the lives of these early Americans in what became New York City.
SureSelect targeted enrichment, a new cost effective method for the whole genome sequencing of Candidatus Liberibacter asiaticus
Authors: Cai Weili , Nunziata Schyler , Rascoe John , Stulberg Michael J.
Published: December 2019

Huanglongbing (HLB) is a worldwide deadly citrus disease caused by the phloem-limited bacteria ‘Candidatus Liberibacter asiaticus’ (CLas) vectored by Asian citrus psyllids. In order to effectively manage this disease, it is crucial to understand the relationship among the bacterial isolates from different geographical locations. Whole genome sequencing approaches will provide more precise molecular characterization of the diversity among populations. Due to the lack of in vitro culture, obtaining the whole genome sequence of CLas is still a challenge, especially for medium to low titer samples. Hundreds of millions of sequencing reads are needed to get good coverage of CLas from an HLB positive citrus sample. In order to overcome this limitation, we present here a new method, Agilent SureSelect XT HS target enrichment, which can specifically enrich CLas from a metagenomic sample while greatly reducing cost and increasing whole genome coverage of the pathogen. In this study, the CLas genome was successfully sequenced with 99.3% genome coverage and over 72X sequencing coverage from low titer tissue samples (equivalent to 28.52 Cq using Li 16 S qPCR). More importantly, this method also effectively captures regions of diversity in the CLas genome, which provides precise molecular characterization of different strains.
Finding mesopelagic prey in a changing Southern Ocean
Authors: McMahon Clive R. , Hindell Mark A. , Charrassin Jean-Benoit , Corney Stuart , Guinet Christophe , Harcourt Robert , Jonsen Ian , Trebilco Rowan , Williams Guy , Bestley Sophie
Published: December 2019

Mesopelagic fish and squid occupy ocean depths extending below the photic zone and their vertical migrations represent a massive pathway moving energy and carbon through the water column. Their spatio-temporal distribution is however, difficult to map across remote regions particularly the vast Southern Ocean. This represents a key gap in understanding biogeochemical processes, marine ecosystem structure, and how changing ocean conditions will affect marine predators, which depend upon mesopelagic prey. We infer mesopelagic prey vertical distribution and relative abundance in the Indian sector of the Southern Ocean (20° to 130°E) with a novel approach using predator-derived indices. Fourteen years of southern elephant seal tracking and dive data, from the open ocean between the Antarctic Polar Front and the southern Antarctic Circumpolar Current front, clearly show that the vertical distribution of mesopelagic prey is influenced by the physical hydrographic processes that structure their habitat. Mesopelagic prey have a more restricted vertical migration and higher relative abundance closer to the surface where Circumpolar Deep Water rises to shallower depths. Combining these observations with a future projection of Southern Ocean conditions we show that changes in the coupling of surface and deep waters will potentially redistribute mesopelagic prey. These changes are small overall, but show important spatial variability: prey will increase in relative abundance to the east of the Kerguelen Plateau but decrease to the west. The consequences for deep-diving specialists such as elephant seals and whales over this time scale will likely be minor, but the changes in mesoscale vertical energy flow have implications for predators that forage within the mesopelagic zone as well as the broader pelagic ecosystem.
Analysis of circulating microRNAs aberrantly expressed in alcohol-induced osteonecrosis of femoral head
Authors: Hong Guoju , Han Xiaorui , He Wei , Xu Jiake , Sun Ping , Shen Yingshan , Wei Qiushi , Chen Zhenqiu
Published: December 2019

Serum miRNAs are potential biomarkers for predicting the progress of bone diseases, but little is known about miRNAs in alcohol-induced osteonecrosis of femoral head (AIONFH). This study evaluated disease-prevention value of specific serum miRNA expression profiles in AIONFH. MiRNA PCR Panel was taken to explore specific miRNAs in serum of AIONFH cases. The top differentially miRNAs were further validated by RT-qPCR assay in serum and bone tissues of two independent cohorts. Their biofunction and target genes were predicted by bioinformatics databases. Target genes related with angiogenesis and osteogenesis were quantified by RT-qPCR in necrotic bone tissue. Our findings demonstrated that multiple miRNAs were evaluated to be differentially expressed with high dignostic values. MiR-127-3p, miR-628-3p, and miR-1 were downregulated, whereas miR-885-5p, miR-483-3p, and miR-483-5p were upregulated in serum and bone samples from the AIONFH patients compared to those from the normal control individuals (p < 0.01). The predicted target genes of the indicated miRNAs quantified by qRT-PCR, including IGF2, PDGFA, RUNX2, PTEN, and VEGF, were presumed to be altered in necrotic bone tissue of AIONFH patients. The presence of five altered miRNAs in AIONFH patients may serve as non-invasive biomarkers and potential therapeutic targets for the early diagnosis of AIONFH.
In Vivo Mapping of the Choriocapillaris in High myopia: a Widefield Swept Source Optical Coherence Tomography Angiography
Authors: Mastropasqua Rodolfo , Viggiano Pasquale , Borrelli Enrico , Evangelista Federica , Libertini Daniele , Di Antonio Luca , Toto Lisa
Published: December 2019

To report variation of choriocapillaris (CC) flow in widefield in high in myopic subjects compared with an age-matched normal control group using ultra widefield optical coherence tomography angiography (UW-OCTA). This is a Prospective, cross-sectional study. Thirty high myopia subjects and fifty healthy subjects were enrolled. Healthy and high myopia subjects were imaged with the SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). For each eye, five 12 × 12-mm OCTA volume scans were acquired. The en face CC images were then exported to imageJ and a semi-automated algorithm was used for subsequent quantitative analysis. The main outcome was a quantitative analysis of the CC. This analysis was performed in three different regions: (i) peripapillary, (ii) macular, and (iii) periphery. In addition, CC variables were further investigated in distinct fields within these three different regions. Thirty myopic eyes (32 subjects; myopic group) and fifty eyes (50 subjects; control group) without elevated myopia were included in the analysis. Mean ± SD age was 26.9 ± 2.9 years [median: 27 years; range: 20.0–40.0 years]. Mean ± SD axial length was 26.6 ± 0.6 mm [median: 26.2 mm; range: 26.1 to 28.0 mm]. Mean ± SD axial length was 26.6 ± 0.6 mm [median: 26.2 mm; range: 26.1 to 28.0 mm] in the myopic group and 23.9 ± 1.1 mm [median: 23.9 mm; range: 21.8 to 25.9 mm] in the control group. The total signal void area was significantly greater in myopic eyes compared with control group. The peripapillary region exhibited the greatest total signal void area (p < 0.0001 vs macular region, p < 0.0001 vs peripheral region). Within the macular region, the foveal area exhibited a greater total signal void area in comparison with both the parafoveal area (p < 0.0001) and the perifoveal area (p < 0.0001). In conclusion we report quantitative mapping of the choriocapillaris in myopic eyes compared with an age-matched normal control group. The CC perfusion appears to have a wide topographical variation.
A cellular defense memory imprinted by early life toxic stress
Authors: Gecse Eszter , Gilányi Beatrix , Csaba Márton , Hajdú Gábor , Sőti Csaba
Published: December 2019

Stress exposure early in life is implicated in various behavioural and somatic diseases. Experiences during the critical perinatal period form permanent, imprinted memories promoting adult survival. Although imprinting is widely recognized to dictate behaviour, whether it actuates specific transcriptional responses at the cellular level is unknown. Here we report that in response to early life stresses, Caenorhabditis elegans nematodes form an imprinted cellular defense memory. We show that exposing newly-born worms to toxic antimycin A and paraquat, respectively, stimulates the expression of toxin-specific cytoprotective reporters. Toxin exposure also induces avoidance of the toxin-containing bacterial lawn. In contrast, adult worms do not exhibit aversive behaviour towards stress-associated bacterial sensory cues. However, the mere re-encounter with the same cues reactivates the previously induced cytoprotective reporters. Learned adult defenses require memory formation during the L1 larval stage and do not appear to confer increased protection against the toxin. Thus, exposure of C. elegans to toxic stresses in the critical period elicits adaptive behavioural and cytoprotective responses, which do not form imprinted aversive behaviour, but imprint a cytoprotective memory. Our findings identify a novel form of imprinting and suggest that imprinted molecular defenses might underlie various pathophysiological alterations related to early life stress.
Metasurface-based ultra-lightweight high-gain off-axis flat parabolic reflectarray for microwave beam collimation/focusing
Authors: Silva Sinhara R. , Rahman Abdur , de Melo Kort-Kamp Wilton , Rushton Jeremiah J. , Singleton John , Taylor Antoinette J. , Dalvit Diego A. R. , Chen Hou-Tong , Azad Abul K.
Published: December 2019

Ultra-lightweight deployable antennas with high-gain are pivotal communication components for small satellites, which are intrinsically constrained in size, weight, and power. In this work, we design and demonstrate metasurface-based ultra-lightweight flat off-axis reflectarrays for microwave beam collimation and focusing, similar to a parabolic dish-antenna. Our ultra-thin reflectarrays employ resonators of variable sizes to cover the full 2π phase range, and are arranged on the metasurface to realize a two-dimensional parabolic focusing phase distribution. We demonstrate a 30° off-axis focusing reflector that exhibits a measured gain of 27.5 dB at the central operating frequency of 11.8 GHz and a 3 dB directionality <$$\pm $$±1.6°. Furthermore, we carry out full-wave simulations of the reflectarray, showing high gain of the beam focusing/collimation functionality, in good agreement with measurements. The demonstrated reflectarrays will enable low-cost, lightweight, and high-gain deployable transceivers for small-satellite platforms.
The effects of ship wakes in the Venice Lagoon and implications for the sustainability of shipping in coastal waters
Authors: Scarpa Gian Marco , Zaggia Luca , Manfè Giorgia , Lorenzetti Giuliano , Parnell Kevin , Soomere Tarmo , Rapaglia John , Molinaroli Emanuela
Published: December 2019

We analyse the impact of ship traffic in the vicinity of navigation channels in a wide shallow waterbody. The crucial hydrodynamic driver in this situation is the depression (Bernoulli) wake that may be transferred into a long-living solitary wave of depression over the shoals. The analysis considers navigation channels in the Venice Lagoon using a new large dataset of approximately 600 measured wake events associated to specific ships whose data are provided by the AIS system. Since the development of the modern industrial port and the opening of the Malamocco–Marghera channel in the late 1960s, growing pressure on the lagoon caused by ship traffic has raised concerns about its physical integrity and habitat survival. The transit of large vessels has been shown to have serious impacts on the shallow water areas adjacent to waterways. Depression wakes created by such vessels can reach significant dimensions (water level dropdown of up to 2.45 m at the channel margin), causing unusually large retreat rates of several sections of the shoreline and which may adversely affect the lagoon morphology. The wakes are analysed in relation to ship and morphological parameters. A formulation is proposed to predict wake amplitude on the basis of ship characteristics and motion.
A modular cGAN classification framework: Application to colorectal tumor detection
Authors: Tavolara Thomas E. , Niazi M. Khalid Khan , Arole Vidya , Chen Wei , Frankel Wendy , Gurcan Metin N.
Published: December 2019

Automatic identification of tissue structures in the analysis of digital tissue biopsies remains an ongoing problem in digital pathology. Common barriers include lack of reliable ground truth due to inter- and intra- reader variability, class imbalances, and inflexibility of discriminative models. To overcome these barriers, we are developing a framework that benefits from a reliable immunohistochemistry ground truth during labeling, overcomes class imbalances through single task learning, and accommodates any number of classes through a minimally supervised, modular model-per-class paradigm. This study explores an initial application of this framework, based on conditional generative adversarial networks, to automatically identify tumor from non-tumor regions in colorectal H&E slides. The average precision, sensitivity, and F1 score during validation was 95.13 ± 4.44%, 93.05 ± 3.46%, and 94.02 ± 3.23% and for an external test dataset was 98.75 ± 2.43%, 88.53 ± 5.39%, and 93.31 ± 3.07%, respectively. With accurate identification of tumor regions, we plan to further develop our framework to establish a tumor front, from which tumor buds can be detected in a restricted region. This model will be integrated into a larger system which will quantitatively determine the prognostic significance of tumor budding.
Growth Hormone Effects on Bone Loss-Induced by Mild Traumatic Brain Injury and/or Hind Limb Unloading
Authors: Kesavan Chandrasekhar , Bajwa Nikita M. , Watt Heather , Mohan Subburaman
Published: December 2019

Growth hormone (GH) deficiency and loss of physical activity are common features in traumatic brain injury (TBI) patients that may contribute to bone loss. Therefore, we tested the hypothesis that GH treatment will rescue the hind limb unloading (UL)-induced skeletal deficit in TBI mice. Mild TBI was induced once per day for four consecutive days. UL (right hind limb) and treatment (3 mg/day GH or vehicle) began two weeks after the first TBI episode and lasted for four weeks. GH treatment increased femur BMD and lean body mass but decreased the % fat measured by DXA in the Control group. Micro-CT analysis revealed that the TBI, UL and TBI-UL groups showed reduced tibia trabecular (Tb) bone mass by 15%, 70%, and 75%, respectively compared to Control mice and that GH treatment significantly increased Tb. bone mass in all four groups. Vertebra also showed reduced Tb. bone mass in TBI, UL and TBI-UL groups. GH treatment increased vertebral Tb. bone mass in Control and UL groups but not in the TBI or TBI-UL group. GH treatment increased serum IGF-I levels similarly in TBI, UL and TBI-UL groups at day 14, suggesting the GH effect on liver IGF-I production was unaffected by skeletal UL. In contrast, GH effect on expression of ALP, IGFBP5 and axin2 in bone were compromised by UL. In conclusion, skeletal UL caused a greater Tb. bone deficit than mild TBI alone and that GH anabolic effects in the TBI and UL groups vary depending on the skeletal site.
High polymorphism detected by massively parallel sequencing of autosomal STRs using old blood samples from a Chinese Han population
Authors: Dai Wenshen , Pan Yajiao , Sun Xiaochen , Wu Riga , Li Luo , Yang Dongming
Published: December 2019

The development of massively parallel sequencing (MPS) has quickly changed forensic short tandem repeat (STR) genotyping. By providing detailed sequence information, MPS technology may be used as an alternative or additional method to overcome the limitations of capillary electrophoresis-based STR profiling. Most current NGS processes are labour-intensive with regard to library preparation and require high-quality DNA template. In this study, a 16-plex STR typing system (SeqType®R16) was used to achieve direct library preparation without DNA extraction and adaptor ligation. The efficiency of this system was tested in 601 individuals, including 593 old blood samples from the Chinese Han population and eight positive controls. It took approximately 4 hours for library preparation, including blood direct multiplex PCR (1.5 hours), mixing of the product (15 minutes), single tube purification (2 hours) and quantification (15 minutes). The results showed that MPS presented a broader allele range and higher discrimination power. Except for FGA and D19S433, the allele number almost doubled or more than doubled at all complex STR loci and simple STR loci, including D13S317, D16S539, D5S818, and D7S820. The range of discrimination power increased from 0.8008–0.9572 to 0.8401–0.9753, and the culminated matching probability decreased from 1.7 × 10−15 to 1.1 × 10−17.
One-step artificial antigen presenting cell-based vaccines induce potent effector CD8 T cell responses
Authors: Su Qingtai , Igyártó Botond Z.
Published: December 2019

The production and wide use of artificial antigen presenting cells (aAPCs) in the clinic as cancer immunotherapeutics are hindered by the need of identifying immunogenic cancer antigens and production of recombinant patient-specific major histocompatibility complexes (MHC) loaded with these peptides. To overcome these limitations, in this study, we tested the idea of whether peptide-MHCs can directly be captured from cell lysates, including cancer cells using affinity beads, and used to initiate T cell responses. In theory, these affinity beads covered with the unknown peptide-MHC repertoire captured from the cancer cells could interact with a wide range of antigen-specific T cells and promote anti-cancer responses. Indeed, we found that we can successfully pull-down peptide-MHCs from cell lysates and the aAPCs generated using this technique were able to induce antigen-specific cytotoxic effector T cell responses that led to in vitro and in vivo tumor cell killing. In summary, we present here a novel technique to generate patient-specific aAPCs, that might have the potential to revolutionize the field of cancer vaccines, and provide patients with a vaccine in matters of days at minimal costs.
WNT gene polymorphisms and predisposition to apical periodontitis
Authors: de Souza Letícia Chaves , Cavalla Franco , Maili Lorena , Garlet Gustavo P. , Vieira Alexandre R. , Silva Renato M. , Letra Ariadne
Published: December 2019

Single nucleotide polymorphisms (SNPs) in WNT genes may impact gene/protein function and contribute to individual predisposition to apical periodontitis (AP). Here, we investigated the association of SNPs in/nearby WNT3, WNT3A, WNT5A, WNT8A, WNT9B and WNT11 genes with AP using a case-control dataset. Cases were defined as individuals with deep caries and AP (n = 188); controls had deep caries and no AP (n = 230). Genotyping was performed using Taqman chemistry in real time PCR. Data analyses was performed using Fisher Exact tests assuming a Bonferroni correction threshold value of 0.005. Single-SNP association analysis revealed a trend for association with WNT3 rs9890413 genotypes (P = 0.009) under a dominant model and allelic association for WNT3A rs1745420 (P = 0.009). Haplotypes involving WNT3-WNT9B-WNT3A alleles were also significantly associated with AP (P ≤ 0.003). Luciferase reporter assays showed higher transcriptional activity (1.4-fold) with the alternate G allele in rs1745420. Expression of WNT3, WNT3A and WNT5A in AP tissues was significantly higher than in control tissues, and inversely correlated with the expression of SERPINB1, COL1A1 and TIMP1 (P < 0.05). Our results suggest that WNT genes have a role in modulating AP and polymorphisms in these genes may increase susceptibility to AP.
Structural properties of [2Fe-2S] ISCA2-IBA57: a complex of the mitochondrial iron-sulfur cluster assembly machinery
Authors: Nasta Veronica , Da Vela Stefano , Gourdoupis Spyridon , Ciofi-Baffoni Simone , Svergun Dmitri I. , Banci Lucia
Published: December 2019

In mitochondria, a complex protein machinery is devoted to the maturation of iron-sulfur cluster proteins. Structural information on the last steps of the machinery, which involve ISCA1, ISCA2 and IBA57 proteins, needs to be acquired in order to define how these proteins cooperate each other. We report here the use of an integrative approach, utilizing information from small-angle X-ray scattering (SAXS) and bioinformatics-driven docking prediction, to determine a low-resolution structural model of the human mitochondrial [2Fe-2S]2+ISCA2-IBA57 complex. In the applied experimental conditions, all the data converge to a structural organization of dimer of dimers for the [2Fe-2S]2+ISCA2-IBA57 complex with ISCA2 providing the homodimerization core interface. The [2Fe-2S] cluster is out of the ISCA2 core while being shared with IBA57 in the dimer. The specific interaction pattern identified from the dimeric [2Fe-2S]2+ISCA2-IBA57 structural model allowed us to define the molecular grounds of the pathogenic Arg146Trp mutation of IBA57. This finding suggests that the dimeric [2Fe-2S] ISCA2-IBA57 hetero-complex is a physiologically relevant species playing a role in mitochondrial [4Fe-4S] protein biogenesis.
The unique structural features of carbonmonoxy hemoglobin from the sub-Antarctic fish Eleginops maclovinus
Authors: Balasco Nicole , Vitagliano Luigi , Merlino Antonello , Verde Cinzia , Mazzarella Lelio , Vergara Alessandro
Published: December 2019

Tetrameric hemoglobins (Hbs) are prototypical systems for the investigations of fundamental properties of proteins. Although the structure of these proteins has been known for nearly sixty years, there are many aspects related to their function/structure that are still obscure. Here, we report the crystal structure of a carbonmonoxy form of the Hb isolated from the sub-Antarctic notothenioid fish Eleginops maclovinus characterised by either rare or unique features. In particular, the distal site of the α chain results to be very unusual since the distal His is displaced from its canonical position. This displacement is coupled with a shortening of the highly conserved E helix and the formation of novel interactions at tertiary structure level. Interestingly, the quaternary structure is closer to the T-deoxy state of Hbs than to the R-state despite the full coordination of all chains. Notably, these peculiar structural features provide a rationale for some spectroscopic properties exhibited by the protein in solution. Finally, this unexpected structural plasticity of the heme distal side has been associated with specific sequence signatures of various Hbs.
Course of depressive symptoms in men and women: differential effects of social, psychological, behavioral and somatic predictors
Authors: Tibubos Ana N. , Brähler Elmar , Ernst Mareike , Baumgarten Carlotta , Wiltink Joerg , Burghardt Juliane , Michal Matthias , Ghaemi Kerahrodi Jasmin , Schulz Andreas , Wild Philipp S. , Münzel Thomas , Schmidtmann Irene , Lackner Karl J. , Pfeiffer Norbert , Borta Andreas , Beutel Manfred E.
Published: December 2019

In this study, we aimed to identify the most important and sex-specific social, psychological, behavioral and somatic predictors of recurrent depressive symptoms. Data was obtained at two measurement points within five years by the Gutenberg Health Study (GHS). Out of N = 12,061 individuals, a sample of 877 (age 52.3 ± 9.9) who reported clinically relevant depressive symptoms at baseline was analyzed. Univariate analyses and multiple logistic regression analyses were conducted. Almost half of participants depressed at baseline also reported depressive symptoms five years later. Sex-stratified multivariate analyses revealed that solely social support remained a significant protective predictor against recurrence of depression in men (OR = 0.93; CI95% = 0.87–0.99), whereas in women smoking (OR = 1.97; CI95% = 1.23–3.22), and Type D personality (OR = 1.65; CI95% = 1.10–2.49) were significant risk factors. However, when analyzing the entire sample, no interaction effect between sex and each predictor turned out to be significant. Only social support was retained as an overall predictive factor. As depressive symptoms recur, depressive vulnerability is established involving personality, health behavior and social factors. Although no significant sex-specific interactions were observed, sex-stratified analyses point out different patterns for relevant predictors of recurrent depressive symptoms in men and women.
3β, 6β-dichloro-5-hydroxy-5α-cholestane facilitates neuronal development through modulating TrkA signaling regulated proteins in primary hippocampal neuron
Authors: Hannan Md. Abdul , Haque Md. Nazmul , Dash Raju , Alam Mahboob , Moon Il Soo
Published: December 2019

Potentiating neuritogenesis through pharmacological intervention might hold therapeutic promise in neurodegenerative disorders and acute brain injury. Here, we investigated the novel neuritogenic potentials of a steroidal chlorohydrin, 3β, 6β-dichloro-5-hydroxy-5α-cholestane (hereafter, SCH) and the change in cellular proteome to gain insight into the underlying mechanism of its neurotrophic activity in hippocampal neurons. Morphometric analysis showed that SCH promoted early neuronal differentiation, dendritic arborization and axonal maturation. Proteomic and bioinformatic analysis revealed that SCH induced upregulation of several proteins, including those associated with neuronal differentiation and development. Immunocytochemical data further indicates that SCH-treated neurons showed upregulation of Hnrnpa2b1 and Map1b, validating their proteomic profiles. In addition, a protein-protein interaction network analysis identified TrkA as a potential target connecting most of the upregulated proteins. The neurite outgrowth effect of SCH was suppressed by TrkA inhibitor, GW441756, verifying TrkA-dependent activity of SCH, which further supports the connection of TrkA with the upregulated proteins. Also, the computational analysis revealed that SCH interacts with the NGF-binding domain of TrkA through Phe327 and Asn355. Collectively, our findings provide evidence that SCH promotes neuronal development via upregulating TrkA-signaling proteins and suggest that SCH could be a promising therapeutic agent in the prevention and treatment of neurodegenerative disorders.
Identification of a Phenylthiazole Small Molecule with Dual Antifungal and Antibiofilm Activity Against Candida albicans and Candida auris
Authors: Mohammad Haroon , Eldesouky Hassan E. , Hazbun Tony , Mayhoub Abdelrahman S. , Seleem Mohamed N.
Published: December 2019

Candida species are a leading source of healthcare infections globally. The limited number of antifungal drugs combined with the isolation of Candida species, namely C. albicans and C. auris, exhibiting resistance to current antifungals necessitates the development of new therapeutics. The present study tested 85 synthetic phenylthiazole small molecules for antifungal activity against drug-resistant C. albicans. Compound 1 emerged as the most potent molecule, inhibiting growth of C. albicans and C. auris strains at concentrations ranging from 0.25–2 µg/mL. Additionally, compound 1 inhibited growth of other clinically-relevant yeast (Cryptococcus) and molds (Aspergillus) at a concentration as low as 0.50 µg/mL. Compound 1 exhibited rapid fungicidal activity, reducing the burden of C. albicans and C. auris below the limit of detection within 30 minutes. Compound 1 exhibited potent antibiofilm activity, similar to amphotericin B, reducing the metabolic activity of adherent C. albicans and C. auris biofilms by more than 66% and 50%, respectively. Furthermore, compound 1 prolonged survival of Caenorhabditis elegans infected with strains of C. albicans and C. auris, relative to the untreated control. The present study highlights phenylthiazole small molecules, such as compound 1, warrant further investigation as novel antifungal agents for drug-resistant Candida infections.
Epigenetic deregulation of GATA3 in neuroblastoma is associated with increased GATA3 protein expression and with poor outcomes
Authors: Almutairi Bader , Charlet Jessica , Dallosso Anthony R. , Szemes Marianna , Etchevers Heather C. , Malik Karim T. A. , Brown Keith W.
Published: December 2019

To discover epigenetic changes that may underly neuroblastoma pathogenesis, we identified differentially methylated genes in neuroblastoma cells compared to neural crest cells, the presumptive precursors cells for neuroblastoma, by using genome-wide DNA methylation analysis. We previously described genes that were hypermethylated in neuroblastoma; in this paper we report on 67 hypomethylated genes, which were filtered to select genes that showed transcriptional over-expression and an association with poor prognosis in neuroblastoma, highlighting GATA3 for detailed studies. Specific methylation assays confirmed the hypomethylation of GATA3 in neuroblastoma, which correlated with high expression at both the RNA and protein level. Demethylation with azacytidine in cultured sympathetic ganglia cells led to increased GATA3 expression, suggesting a mechanistic link between GATA3 expression and DNA methylation. Neuroblastomas that had completely absent GATA3 methylation and/or very high levels of protein expression, were associated with poor prognosis. Knock-down of GATA3 in neuroblastoma cells lines inhibited cell proliferation and increased apoptosis but had no effect on cellular differentiation. These results identify GATA3 as an epigenetically regulated component of the neuroblastoma transcriptional control network, that is essential for neuroblastoma proliferation. This suggests that the GATA3 transcriptional network is a promising target for novel neuroblastoma therapies.
Evolutionary conservation of the intrinsic disorder-based Radical-Induced Cell Death1 hub interactome
Authors: Christensen Lise Friis , Staby Lasse , Bugge Katrine , O’Shea Charlotte , Kragelund Birthe B. , Skriver Karen
Published: December 2019

Radical-Induced Cell Death1 (RCD1) functions as a cellular hub interacting with intrinsically disordered transcription factor regions, which lack a well-defined three-dimensional structure, to regulate plant stress. Here, we address the molecular evolution of the RCD1-interactome. Using bioinformatics, its history was traced back more than 480 million years to the emergence of land plants with the RCD1-binding short linear motif (SLiM) identified from mosses to flowering plants. SLiM variants were biophysically verified to be functional and to depend on the same RCD1 residues as the DREB2A transcription factor. Based on this, numerous additional members may be assigned to the RCD1-interactome. Conservation was further strengthened by similar intrinsic disorder profiles of the transcription factor homologs. The unique structural plasticity of the RCD1-interactome, with RCD1-binding induced α-helix formation in DREB2A, but not detectable in ANAC046 or ANAC013, is apparently conserved. Thermodynamic analysis also indicated conservation with interchangeability between Arabidopsis and soybean RCD1 and DREB2A, although with fine-tuned co-evolved binding interfaces. Interruption of conservation was observed, as moss DREB2 lacked the SLiM, likely reflecting differences in plant stress responses. This whole-interactome study uncovers principles of the evolution of SLiM:hub-interactions, such as conservation of α-helix propensities, which may be paradigmatic for disorder-based interactomes in eukaryotes.
Ultrasound-induced Cavitation enhances the efficacy of Chemotherapy in a 3D Model of Pancreatic Ductal Adenocarcinoma with its microenvironment
Authors: Leenhardt R. , Camus M. , Mestas J. L. , Jeljeli M. , Abou Ali E. , Chouzenoux S. , Bordacahar B. , Nicco C. , Batteux F. , Lafon C. , Prat F.
Published: December 2019

Pancreatic ductal adenocarcinoma (PDAC) is supported by a complex microenvironment whose physical contribution to chemoresistance could be overcome by ultrasound (US) therapy. This study aims to investigate the ability of US-induced inertial cavitation in association with chemotherapy to alter tumor cell viability via microenvironment disruption. For this purpose, we used a 3D-coculture PDAC model partially mimicking the tumor and its microenvironment. Coculture spheroids combining DT66066 cells isolated from KPC-transgenic mice and murine embryonic fibroblasts (iMEF) were obtained by using a magnetic nanoshuttle method. Spheroids were exposed to US with incremental inertial cavitation indexes. Conditions studied included control, gemcitabine, US-cavitation and US-cavitation + gemcitabine. Spheroid viability was assessed by the reduction of resazurin and flow cytometry. The 3D-coculture spheroid model incorporated activated fibroblasts and produced type 1-collagen, thus providing a partial miniature representation of tumors with their microenvironment. Main findings were: (a) Gemcitabine (5 μM) was significantly less cytotoxic in the presence of KPC/iMEFs spheroids compared with KPC (fibroblast-free) spheroids; (b) US-induced inertial cavitation combined with Gemcitabine significantly decreased spheroid viability compared to Gemcitabine alone; (c) both cavitation and chemotherapy affected KPC cell viability but not that of fibroblasts, confirming the protective role of the latter vis-à-vis tumor cells. Gemcitabine toxicity is enhanced when cocultured spheroids of KPC and iMEF are exposed to US-cavitation. Although the model used is only a partial representation of PDAC, this experience supports the hypothesis that US-inertial cavitation can enhance drug penetration and cytotoxicity by disrupting PDAC microenvironment.
Damages caused by hurricane Irma in the human-degraded mangroves of Saint Martin (Caribbean)
Authors: Walcker R. , Laplanche C. , Herteman M. , Lambs L. , Fromard F.
Published: December 2019

In early September 2017, Irma was the most powerful hurricane that struck the northern Caribbean over the last 100 years. In the 21st century, the stronger types of tropical cyclones will likely increase in frequency due to the climate change and internal climate variability. Lessons to anticipate the response of mangroves to this intensification can be learned from this extreme event. Here, we analysed damages caused in mangrove forests of the Saint Martin Island. Mangroves of this island were previously degraded due to historic human pressures and recent over-urbanisation. Forest inventories and time series of very high resolution satellite images revealed that approximately 80% of the mangrove area was damaged by the hurricane. Results highlighted distinct rates of forest recovery. Early and rapid recoveries were largely observed in most study sites. However, some mangroves were still unable to recover fourteen months after the disturbance. The human-induced degradation of the ecosystem prior to the hurricane is hypothesised to be the main factor controlling the absence of forest recovery. We suggest that human-degraded mangroves will be weakened in the face of such extreme events. We advocate to preserve and restore mangroves in order to guarantee all the valuable ecosystem services they provided.
Egg parasitoid exploitation of plant volatiles induced by single or concurrent attack of a zoophytophagous predator and an invasive phytophagous pest
Authors: Martorana Letizia , Brodeur Jacques , Foti Maria Cristina , Agrò Alfonso , Colazza Stefano , Peri Ezio
Published: December 2019

Zoophytophagous insect predators can induce physiological responses in plants by activating defence signalling pathways, but whether plants can respond to facultative phytophagy by recruiting natural enemies remains to be investigated. In Y-tube olfactometer bioassays, using a system including a Vicia faba plant, the zoophytophagous predator Podisus maculiventris and the egg parasitoid Telenomus podisi, we first demonstrated that T. podisi females are attracted by broad bean plants damaged by feeding activity of P. maculiventris and on which host egg masses had been laid, while they are not attracted by undamaged plants or plants damaged by feeding activity alone. In a second experiment, we evaluated the impact of the invasive phytophagous pest Halyomorpha halys on this plant volatile-mediated tritrophic communication. Results showed that the invasive herbivorous adults do not induce plants to recruit the native egg parasitoid, but they can disrupt the local infochemical network. In fact, T. podisi females are not attracted by volatiles emitted by plants damaged by H. halys feeding alone or combined with oviposition activity, nor are they attracted by plants concurrently infested by P. maculiventris and H. halys, indicating the specificity in the parasitoid response and the ability of the invasive herbivore in interrupting the semiochemical communication between plants and native egg parasitoids. To the best of our knowledge, this is the first study showing that zoophytophagous predator attacks induce indirect plant defences similarly to those defence strategies adopted by plants as a consequence of single or concurrent infestations of herbivorous insects.
Optimized Biodiesel Production from Waste Cooking Oil (WCO) using Calcium Oxide (CaO) Nano-catalyst
Authors: Degfie Tadesse Anbessie , Mamo Tadios Tesfaye , Mekonnen Yedilfana Setarge
Published: December 2019

Biodiesel production from waste cooking oil (WCO) provides an alternative energy means of producing liquid fuels from biomass for various uses. Biodiesel production by recycling WCO and methanol in the presence of calcium oxide (CaO) nano-catalyst offers several benefits such as economic, environmental and waste management. A nano-catalyst of CaO was synthesized by thermal-decomposition method and calcinated at 500 °C followed by characterization using x-ray diffraction (XRD) and scanning electron microscope (SEM) techniques. The XRD results revealed nano-scale crystal sizes at high purity, with a mean particle size of ~29 nm. The SEM images exhibited morphology of irregular shapes and porous structure of the synthesized nanocatalysts. The highest conversion of WCO to biodiesel was estimated to be 96%, at optimized experimental conditions i.e., 50 °C, 1:8 WCO oil to methanol ratio, 1% by weight of catalyst loading rate and 90 minutes reaction time, which is among few highest conversions reported so far. Biodiesel properties were tested according to the American (ASTM D6571) fuel standards. All reactions are carried-out under atmospheric pressure and 1500 rpm of agitation.
Tensin1 expression and function in chronic obstructive pulmonary disease
Authors: Stylianou Panayiota , Clark Katherine , Gooptu Bibek , Smallwood Dawn , Brightling Christopher E. , Amrani Yassine , Roach Katy M. , Bradding Peter
Published: December 2019

Chronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. Genome wide association studies have shown significant associations between airflow obstruction or COPD with a non-synonymous SNP in the TNS1 gene, which encodes tensin1. However, the expression, cellular distribution and function of tensin1 in human airway tissue and cells are unknown. We therefore examined these characteristics in tissue and cells from controls and people with COPD or asthma. Airway tissue was immunostained for tensin1. Tensin1 expression in cultured human airway smooth muscle cells (HASMCs) was evaluated using qRT-PCR, western blotting and immunofluorescent staining. siRNAs were used to downregulate tensin1 expression. Tensin1 expression was increased in the airway smooth muscle and lamina propria in COPD tissue, but not asthma, when compared to controls. Tensin1 was expressed in HASMCs and upregulated by TGFβ1. TGFβ1 and fibronectin increased the localisation of tensin1 to fibrillar adhesions. Tensin1 and α-smooth muscle actin (αSMA) were strongly co-localised, and tensin1 depletion in HASMCs attenuated both αSMA expression and contraction of collagen gels. In summary, tensin1 expression is increased in COPD airways, and may promote airway obstruction by enhancing the expression of contractile proteins and their localisation to stress fibres in HASMCs.
Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives
Authors: Lo Cascio Filippa , Puangmalai Nicha , Ellsworth Anna , Bucchieri Fabio , Pace Andrea , Palumbo Piccionello Antonio , Kayed Rakez
Published: December 2019

The pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers.
Generation of ECG signals from a reaction-diffusion model spatially discretized
Authors: Quiroz-Juárez M. A. , Jiménez-Ramírez O. , Vázquez-Medina R. , Breña-Medina V. , Aragón J. L. , Barrio R. A.
Published: December 2019

We propose a model to generate electrocardiogram signals based on a discretized reaction-diffusion system to produce a set of three nonlinear oscillators that simulate the main pacemakers in the heart. The model reproduces electrocardiograms from healthy hearts and from patients suffering various well-known rhythm disorders. In particular, it is shown that under ventricular fibrillation, the electrocardiogram signal is chaotic and the transition from sinus rhythm to chaos is consistent with the Ruelle-Takens-Newhouse route to chaos, as experimental studies indicate. The proposed model constitutes a useful tool for research, medical education, and clinical testing purposes. An electronic device based on the model was built for these purposes