bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural killer cells modulate motor neuron-immune cell cross talk in models of Amyotrophic Lateral Sclerosis
Authors: Garofalo Stefano , Cocozza Germana , Porzia Alessandra , Inghilleri Maurizio , Raspa Marcello , Scavizzi Ferdinando , Aronica Eleonora , Bernardini Giovanni , Peng Ling , Ransohoff Richard M. , Santoni Angela , Limatola Cristina
Published: April 2020

In amyotrophic lateral sclerosis (ALS), immune cells and glia contribute to motor neuron (MN) degeneration. We report the presence of NK cells in post-mortem ALS motor cortex and spinal cord tissues, and the expression of NKG2D ligands on MNs. Using a mouse model of familial-ALS, hSOD1G93A, we demonstrate NK cell accumulation in the motor cortex and spinal cord, with an early CCL2-dependent peak. NK cell depletion reduces the pace of MN degeneration, delays motor impairment and increases survival. This is confirmed in another ALS mouse model, TDP43A315T. NK cells are neurotoxic to hSOD1G93AMNs which express NKG2D ligands, while IFNγ produced by NK cells instructs microglia toward an inflammatory phenotype, and impairs FOXP3+/Treg cell infiltration in the spinal cord of hSOD1G93Amice. Together, these data suggest a role of NK cells in determining the onset and progression of MN degeneration in ALS, and in modulating Treg recruitment and microglia phenotype.
Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones
Authors: Tsukada Kento , Shinki Shono , Kaneko Akiho , Murakami Kazuma , Irie Kazuhiro , Murai Masatoshi , Miyoshi Hideto , Dan Shingo , Kawaji Kumi , Hayashi Hironori , Kodama Eiichi N. , Hori Aki , Salim Emil , Kuraishi Takayuki , Hirata Naoya , Kanda Yasunari , Asai Teigo
Published: April 2020

A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera. In addition, we design extended DDP pathways by combinatorial biosynthesis. In total, ten DDP pathways, including five native pathways, four extended pathways and one shunt pathway, are heterologously reconstituted in a genetically tractable heterologous host, Aspergillus oryzae, resulting in the production of 22 DDPs, including 15 new analogues. We also demonstrate the advantage of expanding the diversity of DDPs to probe various bioactive molecules through a wide range of biological evaluations.
Sex-associated molecular differences for cancer immunotherapy
Authors: Ye Youqiong , Jing Ying , Li Liang , Mills Gordon B. , Diao Lixia , Liu Hong , Han Leng
Published: April 2020

Immune checkpoint blockade therapies have extended patient survival across multiple cancer lineages, but there is a heated debate on whether cancer immunotherapy efficacy is different between male and female patients. We summarize the existing meta-analysis to show inconsistent conclusions for whether gender is associated with the immunotherapy response. We analyze molecular profiling from ICB-treated patients to identify molecular differences for immunotherapy responsiveness. We perform comprehensive analyses for patients from The Cancer Genome Atlas (TCGA) and reveal divergent patterns for sex bias in immune features across multiple cancer types. We further validate our observations in multiple independent data sets. Considering that the majority of clinical trials are in melanoma and lung cancer, meta-analyses that pool multiple cancer types have limitations to discern whether cancer immunotherapy efficacy is different between male and female patients. Future studies should include omics profiling to investigate sex-associated molecular differences in immunotherapy.
Turning charge-density waves into Cooper pairs
Authors: Chikina Alla , Fedorov Alexander , Bhoi Dilipkumar , Voroshnin Vladimir , Haubold Erik , Kushnirenko Yevhen , Kim Kee Hoon , Borisenko Sergey
Published: April 2020

The relationship between charge-density waves (CDWs) and superconductivity is a long-standing debate. Often observed as neighbors in phase diagrams, it is still unclear whether they cooperate, compete, or simply coexist. Using angle-resolved photoemission spectroscopy, we demonstrate here that by tuning the energy position of the van Hove singularity in Pd-doped 2H-TaSe2, one is able to suppress CDW and enhance superconductivity by more than an order of magnitude. We argue that it is particular fermiology of the material that is responsible for each phenomenon, thus explaining their persistent proximity as phases.
Rapid dose-dependent Natural Killer (NK) cell modulation and cytokine responses following human rVSV-ZEBOV Ebolavirus vaccination
Authors: Pejoski David , de Rham Casimir , Martinez-Murillo Paola , Santoro Francesco , Auderset Floriane , Medaglini Donata , Pozzi Gianni , Vono Maria , Lambert Paul-Henri , Huttner Angela , Haks Mariëlle C. , Ottenhoff Tom H. M. , Villard Jean , Siegrist Claire-Anne ,   the VEBCON Consortium, Addo Marylyn M. , Agnandji Selidji Todagbe , Becker Stephan , Bejon Philip , Brosnahan Jessica S. , Fast Patricia , Huttner Angela , Krähling Verena , Kieny Marie-Paule , Kremsner Peter G. , Krishna Sanjeev , Lapujade Olivier , Moorthy Vasee , Njuguna Patricia , Savarese Barbara , Siegrist Claire-Anne ,   VSV-EBOVAC Consortium, Agnandji Selidji Todagbe , Ahmed Rafi , Anderson Jenna , Auderset Floriane , Bejon Philip , Borgianni Luisa , Brosnahan Jessica S. , Ciabattini Annalisa , Engler Olivier , Haks Mariëlle C. , Harandi Ali M. , Heppner Donald Gray , Gerlini Alice , Huttner Angela , Kremsner Peter G. , Martinez-Murillo Paola , Medaglini Donata , Monath Thomas , Ndungu Francis , Njuguna Patricia , Ottenhoff Tom H. M. , Page Mark , Pejoski David , Pozzi Gianni , Santoro Francesco , Siegrist Claire-Anne ,   VSV-EBOPLUS Consortium, Agnandji Selidji Todagbe , Anderson Jenna , Auderset Floriane , Borgianni Luisa , Ciabattini Annalisa , Dubey Sheri , Engler Olivier , Fernandes José F. , Haks Mariëlle C. , Harandi Ali M. , Gerlini Alice , Huttner Angela , Kremsner Peter G. , Martinez-Murillo Paola , Medaglini Donata , Monath Thomas , Nakaya Helder , O’Rourke Fiona , Ottenhoff Tom H. M. , Pejoski David , Pozzi Gianni , Rothenberger Sylvia , Santoro Francesco , Siegrist Claire-Anne
Published: April 2020

The rVSV-ZEBOV Ebolavirus vaccine confers protection within days after immunization, suggesting the contribution of innate immune responses. We report modulation of rVSV-ZEBOV vaccinee blood CD56+ NK cell numbers, NKG2D or NKp30 surface receptor expression, Killer Immunoglobulin-like Receptor (KIR)+ cell percentages and NK-cell-related genes on day 1 post immunization. Inverse correlations existed between the concentration of several plasma cytokines and inhibitory KIR+ CD56dim or cytokine-responsive CD56bright NK cells. Thus, NK cells may contribute to the early protective efficacy of rVSV-ZEBOV in humans.
A fine-tuned global distribution dataset of marine forests
Authors: Assis Jorge , Fragkopoulou Eliza , Frade Duarte , Neiva João , Oliveira André , Abecasis David , Faugeron Sylvain , Serrão Ester A.
Published: April 2020

Species distribution records are a prerequisite to follow climate-induced range shifts across space and time. However, synthesizing information from various sources such as peer-reviewed literature, herbaria, digital repositories and citizen science initiatives is not only costly and time consuming, but also challenging, as data may contain thematic and taxonomic errors and generally lack standardized formats. We address this gap for important marine ecosystem-structuring species of large brown algae and seagrasses. We gathered distribution records from various sources and provide a fine-tuned dataset with ~2.8 million dereplicated records, taxonomically standardized for 682 species, and considering important physiological and biogeographical traits. Specifically, a flagging system was implemented to signal potentially incorrect records reported on land, in regions with limiting light conditions for photosynthesis, and outside the known distribution of species, as inferred from the most recent published literature. We document the procedure and provide a dataset in tabular format based on Darwin Core Standard (DwC), alongside with a set of functions in R language for data management and visualization.
A dataset of multi-functional ecological traits of Brazilian bees
Authors: Borges Rafael Cabral , Padovani Kleber , Imperatriz-Fonseca Vera Lucia , Giannini Tereza Cristina
Published: April 2020

Worldwide, bees are the most important group of animal pollinators. The ecosystem service they provide is vital in natural areas and croplands, and the taxonomic and functional diversity associated with bees is vital in understanding ecosystem functioning ensuring biodiversity conservation, food security and human livelihoods. A dataset of bees from mountainous areas of Carajás National Forest (eastern Amazon) and Nova Lima (Atlantic Forest) is presented here. It is a compilation of sampling efforts from 1983 to 2018 through the accession of data stored in museum collections. In total, 222 and 144 bee species were recorded in Carajás and Nova Lima, respectively. This represents the most robust dataset of Brazilian bees including species traits (body size, flight range, distribution, crop pollination, sociality and nesting) of 328 species. This dataset contributes to advances in the knowledge of the functional trait ecology of wild bees and can benefit further studies that analyze the response of wild bees to land use and climate changes, and its effects on the provision of crop pollination services.
Author Correction: Proteinaceous secretion of bioadhesive produced during crawling and settlement of Crassostrea gigas larvae
Authors: Foulon Valentin , Artigaud Sébastien , Buscaglia Manon , Bernay Benoit , Fabioux Caroline , Petton Bruno , Elies Philippe , Boukerma Kada , Hellio Claire , Guérard Fabienne , Boudry Pierre
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Elicitation of integrated immunity in mice by a novel pneumococcal polysaccharide vaccine conjugated with HBV surface antigen
Authors: Qian Wen , Huang Zhen , Chen Yuqiu , Yang Jinling , Wang Lili , Wu Kai , Chen Min , Chen Nanping , Duan Yongzhong , Shi Jing , Zhang Ying , Li Qihan
Published: April 2020

The conjugation of polysaccharides with an effective carrier protein is critical for the development of effective bacterial polysaccharide vaccines. Therefore, the identification and optimization of carrier proteins to induce an effective immune response is necessary for developing a combined vaccine. In the current study, we utilized hepatitis B virus surface antigen (HBsAg) as a novel carrier protein combined with a capsular polysaccharide molecule to develop a new pneumococcal conjugated vaccine. The specific antibodies and T cell immune response against the capsular polysaccharide and HBsAg in the mice immunized with this conjugated vaccine were evaluated. In addition, the unique gene profiles of immune cells induced by this conjugated vaccine in the immunized mice were analyzed. Our results demonstrated that the vaccine consisting of pneumonia type 33 F capsular polysaccharide (Pn33Fps) conjugated with HBsAg can induce strong specific immune responses against both antigens in vivo in immunized mice. Furthermore, the conjugated vaccine induced higher expression of genes related to the activation of immunity and higher antibody titers against Pn33Fps and HBsAg in mice than those obtained via vaccination with a single antigen. Analyses of the dynamic expression changes in immunity-related genes in mice immunized with Pn33Fps_HBs, Pn33Fps, or HBsAg indicated the potent immunogenicity of the conjugated vaccine. In addition, a pathological evaluation of the organs from immunized mice further suggested that the conjugated vaccine is safe. Together, these results indicate that a conjugated vaccine consisting of Pn33Fps with HBsAg is a novel and effective vaccine.
Fabrication of Perfusable Vascular Channels and Capillaries in 3D Liver-like Tissue
Authors: Mori Nobuhito , Akagi Yuka , Imai Yukiko , Takayama Yuzo , Kida Yasuyuki S.
Published: April 2020

Although various production methods for 3D vascularised tissues have been developed, constructing capillary-like structures branching from perfusable large channels remains difficult. This study describes a method to fabricate tube-shaped 3D liver-like tissue (tubular liver tissue) with large channels and capillary-like structures using a perfusion device. The perfusion device functions as an interface between the tissue and an external pump, as it has connectors equipped with anchors that hold the tissue in response to its shrinkage, which is accompanied by the self-organisation of capillary-like structures. Histological analysis revealed that perfusion via the large channel induced capillary formation around the channel and maintained proper tissue functions. Accompanied by structural examinations, global gene expression analysis supported this finding; specifically, genes involved in angiogenesis were enriched in the perfused condition. Furthermore, we confirmed the penetrability of the capillary-like structures by infusing India ink, as well as substance exchange by measuring the amounts of secreted albumin. These lines of evidence indicate that our method can be used to construct 3D tissues, which is useful for fields of in vitro tissue regeneration for drug development and regenerative medicine.
Colloidal Silicon Dioxide in Tablet form (Carbowhite) Efficacy in Patients with Acute Diarrhea: Results of Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study
Authors: Tieroshyn Vadim , Moroz Larisa , Prishliak Oleksandra , Shostakovich-Koretska Lyudmila , Kruglova Oksana , Gordienko Lyudmila
Published: April 2020

The acute diarrhea is a wide-spread disease. The prescription of enterosorbents is appropriate as a primary measure for the treatment of the acute diarrhea for effective prevention of the fluid and electrolyte loss, as well as method for symptom relief of the attack of the disease. Aim of the study - the antidiarrheal efficacy and safety study of high-dispersion silicon dioxide enterosorbent in tablet dosage form in patients with acute diarrhea. This was randomized, double-blind, placebo-controlled, 4-center study. Acute diarrhea was defined as three and more episodes of watery stool per day either during 48 hours or less before study entry in the patients having normal stool recently. It has been postulated that symptoms and signs of acute diarrhea have to be caused by direct infection of the gastrointestinal tract and did not associated with moderate-to-severe systemic states. 144 patients with established acute diarrhea were randomized into treatment group (enterosorbent “Carbowhite”, n = 120) or placebo group. Date collection including severity diarrhea, systemic symptoms was performed at baseline and daily during 7 days. Stool examination and serological assay were performed at baseline. The primary end points were declared as time to complete recovery from acute diarrhea. It has been found that the use of the siliceous enterosorbent (“Carbowhite”) allowed to reduce (p < 0.001) the treatment period averagely for 0.9 days (95% confidence interval 0.5–1.2 days) in comparison with placebo. Data of safety monitoring has revealed that both patient groups had negative stool culture, while initiation of antibiotic treatment was run more frequently in placebo group (8.3%) compared to investigational product group (4.1%, P = 0.044). The siliceous enterosorbent “Carbowhite” was well tolerated and reduced the recovery time of the acute episode of the diarrhea in the clinically significant form.
Urbanisation alters ecological interactions: Ant mutualists increase and specialist insect predators decrease on an urban gradient
Authors: Rocha Elise A. , Fellowes Mark D. E.
Published: April 2020

The modification of habitats in urban areas is thought to alter patterns of species interactions, by filtering specialist species and those at higher trophic levels. However, empirical studies addressing these hypotheses remain limited in scope and number. This work investigates (1) how main urban land uses affect predator-prey and mutualistic interactions, and (2) how specialist and generalist predators respond to size and availability of urban green spaces. In a large town in the UK, experimental colonies of ant-attended Black bean aphid Aphis fabae and non-ant-attended Pea aphid Acyrthosiphon pisum were monitored over two years. Ants were more frequently found in highly urbanised sites; however mutualistic ants were also more often encountered when the habitat was more plant diverse. Aphids were not affected by urban land uses, but A. fabae numbers were positively related to the presence of mutualists, and so indirectly affected by urbanisation. Predators were the only group negatively affected by increased urbanisation, and specialist species were positively related to increased proportion of urban green areas within the habitats. While this work supports the hypothesis that specialist predators are negatively affected by urbanisation, we also show that a fundamental ecological interaction, mutualism, is affected by urbanisation.
HgCdTe mid-Infrared photo response enhanced by monolithically integrated meta-lenses
Authors: Li Fangzhe , Deng Jie , Zhou Jing , Chu Zeshi , Yu Yu , Dai Xu , Guo Huijun , Chen Lu , Guo Shangkun , Lan Mengke , Chen Xiaoshuang
Published: April 2020

Polarization-independent dielectric meta-lens is proposed to monolithically integrate with a HgCdTe infrared photodetector to concentrate power flux into a reduced photosensitive area for performance enhancement. Although a reduction in photosensitive area could suppress the dark current, the more seriously reduced light absorptance would degrade the specific detectivity D*. The integration of the meta-lens could reverse the situation by improving the absorptance of the photosensitive region. The meta-lens composed of an array of nano-pillars with varying diameters is formed by carving the CdZnTe substrate of the HgCdTe detector so that the integration could be accomplished in situ. The meta-lens focuses the incident light through the CdZnTe medium and at the HgCdTe photosensitive region. The focal spot is about the wavelength size and the focusing efficiency is above 63%. Concerning a HgCdTe detector with a pitch size of 40 μm × 40 μm, when the photosensitive area is reduced to 5 μm × 5 μm, the meta-lens could still keep the light absorptance above 50%, which is 49 times higher than that of the device without the meta-lens. The dark current reduces with the decreasing photosensitive area in a linear manner. When the photosensitive area shrinks from 40 μm × 40 μm to 10 μm × 10 μm or 5 μm × 5 μm, the dark current reduces by 16 or even 64 times. Compared to the pristine device, the employment of the meta-lens together with the reduction in photosensitive area could enhance D* by 5.5 times for the photosensitive area as 5 μm × 5 μm. Further, the meta-lens exhibits a good dispersion tolerance over the wavelength range from 3.3 μm to 5 μm. The averaged detectivity enhancement over this spectrum range is around 3 times for the photosensitive area as 5 μm × 5 μm. The angular response of the meta-lens integrated detector depends on the focal length. For a focal length of 73 µm or 38 µm, the angle of view for a 5 μm × 5 μm photosensitive area is 4.0° or 7.7°. For the inter-pillar distance to be 2 µm in our design, the influence of the coupling effect between the nano-pillars on the performance of the meta-lens is little.
Serum biomarkers from cell-based assays for AhRL and MIS strongly predicted the future development of diabetes in a large community-based prospective study in Korea
Authors: Lee Hong Kyu , Park Wook Ha , Kang Young Cheol , Kang Sora , Im Suyeol , Park Sol , Kim Jin Taek , Lee Minhyeok , Seok Junhee , Oh Man-Suk , Choi Hoon Sung , Pak Youngmi Kim
Published: April 2020

Exposure to environment-polluting chemicals (EPC) is associated with the development of diabetes. Many EPCs exert toxic effects via aryl hydrocarbon receptor (AhR) and/or mitochondrial inhibition. Here we investigated if the levels of human exposure to a mixture of EPC and/or mitochondrial inhibitors could predict the development of diabetes in a prospective study, the Korean Genome and Epidemiological Study (KoGES). We analysed AhR ligands (AhRL) and mitochondria-inhibiting substances (MIS) in serum samples (n = 1,537), collected during the 2008 Ansung KoGES survey with a 4-year-follow-up. Serum AhRL, determined by the AhR-dependent luciferase reporter assay, represents the contamination level of AhR ligand mixture in serum. Serum levels of MIS, analysed indirectly by MIS-ATP or MIS-ROS, are the serum MIS-induced mitochondria inhibiting effects on ATP content or reactive oxygen species (ROS) production in the cultured cells. Among 919 normal subjects at baseline, 7.1% developed impaired glucose tolerance (IGT) and 1.6% diabetes after 4 years. At the baseline, diabetic and IGT sera displayed higher AhRL and MIS than normal sera, which correlated with indices of insulin resistance. When the subjects were classified according to ROC cut-off values, fully adjusted relative risks of diabetes development within 4 years were 7.60 (95% CI, 4.23–13.64), 4.27 (95% CI, 2.38–7.64), and 21.11 (95% CI, 8.46–52.67) for AhRL ≥ 2.70 pM, MIS-ATP ≤ 88.1%, and both, respectively. Gender analysis revealed that male subjects with AhRL ≥ 2.70 pM or MIS-ATP ≤ 88.1% showed higher risk than female subjects. High serum levels of AhRL and/or MIS strongly predict the future development of diabetes, suggesting that the accumulation of AhR ligands and/or mitochondrial inhibitors in body may play an important role in the pathogenesis of diabetes.
Sulfur-enriched leonardite and humic acid soil amendments enhance tolerance to drought and phosphorus deficiency stress in maize (Zea mays L.)
Authors: Kaya Cengiz , Şenbayram Mehmet , Akram Nudrat Aisha , Ashraf Muhammed , Alyemeni Mohammed Nasser , Ahmad Parvaiz
Published: April 2020

Soil amendments are known to promote several plant growth parameters. In many agro-ecosystems, water scarcity and drought induced phosphorus deficiency limits crop yield significantly. Considering the climate change scenario, drought and related stress factors will be even more severe endangering the global food security. Therefore, two parallel field trials were conducted to examine at what extent soil amendment of leonardite and humic acid would affect drought and phosphorus tolerance of maize. The treatments were: control (C: 100% A pan and 125 kg P ha−1), P deficiency (phosphorus stress (PS): 62.5 kg P ha−1), water deficit stress (water stress (WS): 67% A pan), and PS + WS (67% A pan and 62.5 kg P ha−1). Three organic amendments were (i) no amendment, (ii) 625 kg S + 750 kg leonardite ha−1 and (iii) 1250 kg S + 37.5 kg humic acid ha−1) tested on stress treatments. Drought and P deficiency reduced plant biomass, grain yield, chlorophyll content, Fv/Fm, RWC and antioxidant activity (superoxide dismutase, peroxidase, and catalase), but increased electrolyte leakage and leaf H2O2 in maize plants. The combined stress of drought and P deficiency decreased further related plant traits. Humic acid and leonardite enhanced leaf P and yield in maize plants under PS. A significant increase in related parameters was observed with humic acid and leonardite under WS. The largest increase in yield and plant traits in relation to humic acid and leonardite application was observed under combined stress situation. The use of sulfur-enriched amendments can be used effectively to maintain yield of maize crop in water limited calcareous soils.
Apoptosis characterization in mononuclear blood leukocytes of HIV patients during dengue acute disease
Authors: Torrentes-Carvalho Amanda , Sánchez-Arcila Juan Camilo , Azamor Tamiris , Barbosa Luciana Santos , Hottz Eugênio Damaceno , Gandini Mariana , Bozza Fernando Augusto , da Cunha Rivaldo Venâncio , de Oliveira Pinto Luzia Maria , Damasco Paulo Vieira , de Azeredo Elzinandes Leal
Published: April 2020

Dengue virus (DENV) co-circulation in Brazil represents a challenge for treatment and vaccine development. Despite public health impact, the occurrence of coinfections with other viruses is a common event. Increased T cell activation and altered inflammatory response are found during DENV coinfection with Human Immunodeficiency Virus (HIV) impacting HIV-pathogenesis. Even with Antiretroviral therapy (ART), HIV- treated patients had chronic immune activation and lymphocyte apoptosis. However, apoptotic mechanisms have not been investigated during coinfection with DENV. Our attention was attracted to apoptotic cell markers expressions in PBMCs from DENV and DENV/HIV coinfected patients. We found CD4/CD8 ratio inversion in most coinfected patients. CD4 T and CD8 T-cell subsets from DENV and DENV/HIV groups expressed low levels of anti-apoptotic protein Bcl-2. Furthermore, CD8 CD95 double positive cells frequency expressing low levels of Bcl-2 were significantly higher in these patients. Additionally, the density of Bcl-2 on classical monocytes (CD14++CD16−) was significantly lower during DENV infection. Upregulation of pro-apoptotic proteins and anti-apoptotic proteins were found in DENV and DENV/HIV, while catalase, an antioxidant protein, was upregulated mainly in DENV/HIV coinfection. These findings provide evidence of apoptosis triggering during DENV/HIV coinfection, which may contribute to knowledge of immunological response during DENV acute infection in HIV-patients treated with ART.
Development of novel Ti-Mo-Mn alloys for biomedical applications
Authors: Lourenço Mariana Luna , Cardoso Giovana Collombaro , Sousa Karolyne dos Santos Jorge , Donato Tatiani Ayako Goto , Pontes Fenelon Martinho Lima , Grandini Carlos Roberto
Published: April 2020

Due to excellent biocompatibility and corrosion resistance, the application of titanium alloys in orthopedic and dental implants has been increasing since the 1970s. However, the elasticity of these alloys as measured by their Young’s modulus is still about two to four times higher than that of human cortical bone. The most widely used titanium alloy for biomedical applications is Ti-6Al-4V, however, previous studies have shown that the vanadium used in this alloy causes allergic reactions in human tissue and aluminum, also used in the alloy, has been associated with neurological disorders. To solve this problem, new titanium alloys without the presence of these elements and with the addition of different elements, usually beta-stabilizers, are being developed. Manganese is a strong candidate as an alloying element for the development of new beta-type titanium alloys, due to its abundance and low cytotoxicity. In this study, Ti-10Mo-5Mn, Ti-15Mo-2.5Mn and Ti-15Mo-5Mn alloys were prepared in an arc furnace, which resulted in an alloy structure clearly showing the predominance of the beta phase with a body-centered cubic crystalline structure. The observed microstructure confirmed the results on the structural characterization of alloys. Measurement of the indirect cytotoxicity of the alloys showed that the extracts of the studied alloys are not cytotoxic for fibroblastic cells.
Generating homogenous cortical preplate and deep-layer neurons using a combination of 2D and 3D differentiation cultures
Authors: Alsanie Walaa F. , Bahri Ola A. , Habeeballah Hamza H. , Alhomrani Majid , Almehmadi Mazen M. , Alsharif Khalaf , Felemban Ebaa M. , Althobaiti Yusuf S. , Almalki Atiah H. , Alsaab Hashem O. , Gaber Ahmed , Hassan Mohamed M. , Hardy Ana Maria Gregio , Alhadidi Qasim
Published: April 2020

Embryonic stem cells (ESCs) can be used to derive different neural subtypes. Current differentiation protocols generate heterogeneous neural subtypes rather than a specific neuronal population. Here, we present a protocol to derive separate two-deep layer cortical neurons from mouse ESCs (mESCs). mESCs were differentiated into mature Tbr1 or Ctip2-positive neurons using a monolayer-based culture for neural induction and neurosphere-based culture for neural proliferation and expansion. The differentiation protocol relies on SMAD inhibition for neural induction and the use of FGF2 and EGF for proliferation and it is relatively short as mature neurons are generated between differentiation days 12–16. Compared with the monolayer-based differentiation method, mESCs can be directed to generate specific deep-layer cortical neurons rather than heterogeneous cortical neurons that are generated using the monolayer differentiation culture. The early analysis of progenitors using flow cytometry, immunocytochemistry, and qRT-PCR showed high neuralization efficiency. The immunocytochemistry and flow cytometry analyses on differentiation days 12 and 16 showed cultures enriched in Tbr1- and Ctip2-positive neurons, respectively. Conversely, the monolayer differentiation culture derived a mixture of Tbr1 and Ctip2 mature neurons. Our findings suggested that implementing a neurosphere-based culture enabled directing neural progenitors to adopt a specific cortical identity. The generated progenitors and neurons can be used for neural-development investigation, drug testing, disease modelling, and examining novel cellular replacement therapy strategies.
Suppressed humoral immunity is associated with dengue nonstructural protein NS1-elicited anti-death receptor antibody fractions in mice
Authors: Tsai Chung-Lin , Sun Der-Shan , Su Mei-Tzu , Lien Te-Sheng , Chen Yen-Hsu , Lin Chun-Yu , Huang Chung-Hao , King Chwan-Chuen , Li Chen-Ru , Chen Tai-Hung , Chiu Yu-Hsiang , Lu Chun-Chi , Chang Hsin-Hou
Published: April 2020

Dengue virus (DENV) infections may cause life-threatening dengue hemorrhagic fever (DHF). Suppressed protective immunity was shown in these patients. Although several hypotheses have been formulated, the mechanism of DENV-induced immunosuppression remains unclear. Previously, we found that cross-reactive antibodies against tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 1 (death receptor 4 [DR4]) were elicited in DHF patients, and that anti-DR4 autoantibody fractions were elicited by nonstructural protein 1 (NS1) immunizations in experimental mice. In this study, we found that anti-DR4 antibodies could suppress B lymphocyte function in vitro and in vivo. Treatment with the anti-DR4 immunoglobulin (Ig) induced caspase-dependent cell death in immortalized B lymphocyte Raji cells in vitro. Anti-DR4 Igs elicited by NS1 and DR4 immunizations markedly suppressed mouse spleen transitional T2 B (IgM+IgD+), bone marrow pre-pro-B (B220+CD43+), pre-B (B220+CD43−), and mature B cell (B220+IgD+) subsets in mice. Furthermore, functional analysis revealed that the pre-elicitation of anti-NS1 and anti-DR4 Ig titers suppressed subsequently neutralizing antibody production by immunization with DENV envelop protein. Our data suggest that the elicitation of anti-DR4 titers through DENV NS1 immunization plays a suppressive role in humoral immunity in mice.
On the stoichiometry of zirconium carbide
Authors: Gasparrini Claudia , Rana Dhan-sham , Le Brun Niccolò , Horlait Denis , Markides Christos N. , Farnan Ian , Lee William E.
Published: April 2020

The dependencies of the enhanced thermomechanical properties of zirconium carbide (ZrCx) with sample purity and stoichiometry are still not understood due to discrepancies in the literature. Multiple researchers have recently reported a linear relation between the carbon to zirconium atomic ratio (C/Zr) and the lattice parameter, in contrast with a more established relationship that suggests that the lattice parameter value attains a maximum value at a C/Zr ~ 0.83. In this study, the relationship between C/Zr atomic ratio and the lattice parameter is critically assessed: it is found that recent studies reporting the thermophysical properties of ZrCxhave unintentionally produced and characterised samples containing zirconium oxycarbide. To avoid such erroneous characterization of ZrCxthermophysical properties in the future, we propose a method for the accurate measurement of the stoichiometry of ZrCxusing three independent experimental techniques, namely: elemental analysis, thermogravimetric analysis and nuclear magnetic resonance spectroscopy. Although a large scatter in the results (ΔC/Zr = 0.07) from these different techniques was found when used independently, when combining the techniques together consistent values ofxin ZrCxwere obtained.
Correlation of circulating ANGPTL5 levels with obesity, high sensitivity C-reactive protein and oxidized low-density lipoprotein in adolescents
Authors: Hammad Maha M. , Abu-Farha Mohamed , Al-Taiar Abdullah , Alam-Eldin Nada , Al-Sabah Reem , Shaban Lemia , Al-Mulla Fahd , Abubaker Jehad , Rahman Abdur
Published: April 2020

Angiopoietin-like proteins (ANGPTL) is a family of eight members known to play an important role in metabolic diseases. Of these, ANGPTL5 is suggested to regulate triglyceride metabolism and is increased in obesity and diabetes. However, its role in metabolic diseases in adolescents is not well-studied. In this study, we tested the hypothesis of a positive association between plasma ANGPTL5, and obesity, high sensitivity C-reactive protein (HsCRP) and oxidized low-density lipoprotein (Ox-LDL) in adolescents. Adolescents (N = 431; age 11–14 years) were randomly selected from middle schools in Kuwait. Obesity was classified by the BMI-for-age based on the WHO growth charts. Plasma ANGPTL5, HsCRP, and Ox-LDL were measured using ELISA. The prevalence of overweight and obesity was 20.65% and 33.18%, respectively. Mean (SD) plasma ANGPTL5 levels were significantly higher in obese, compared with overweight and normal-weight adolescents (23.05 (8.79) vs 18.39 (7.08) ng/mL, and 18.26 (6.95) ng/ml, respectively). ANGPTL5 was positively associated with both HsCRP (ρ=0.27, p < 0.001) and Ox-LDL (ρ = 0.24, p < 0.001). In Conclusion, ANGPTL5 levels are elevated in obese adolescents and are associated with cardiovascular disease risk factors, HsCRP and Ox-LDL. The use of ANGPTL5 as a powerful diagnostic and prognostic tool in obesity and metabolic diseases needs to be further evaluated.
Effect of UVC Irradiation on the Oxidation of Histidine in Monoclonal Antibodies
Authors: Miyahara Yuya , Shintani Koya , Hayashihara-Kakuhou Kayoko , Zukawa Takehiro , Morita Yukihiro , Nakazawa Takashi , Yoshida Takuya , Ohkubo Tadayasu , Uchiyama Susumu
Published: April 2020

We oxidized histidine residues in monoclonal antibody drugs of immunoglobulin gamma 1 (IgG1) using ultraviolet C irradiation (UVC: 200–280 nm), which is known to be potent for sterilization or disinfection. Among the reaction products, we identified asparagine and aspartic acid by mass spectrometry. In the photo-induced oxidation of histidine in angiotensin II, 18O atoms from H218O in the solvent were incorporated only into aspartic acid but not into asparagine. This suggests that UVC irradiation generates singlet oxygen and induces [2 + 2] cycloaddition to form a dioxetane involving the imidazole Cγ − Cδ2 bond of histidine, followed by ring-opening in the manner of further photo-induced retro [2 + 2] cycloaddition. This yields an equilibrium mixture of two keto-imines, which can be the precursors to aspartic acid and asparagine. The photo-oxidation appears to occur preferentially for histidine residues with lower pKa values in IgG1. We thus conclude that the damage due to UVC photo-oxidation of histidine residues can be avoided in acidic conditions where the imidazole ring is protonated.
Sustainable and recyclable heterogenous palladium catalysts from rice husk-derived biosilicates for Suzuki-Miyaura cross-couplings, aerobic oxidations and stereoselective cascade carbocyclizations
Authors: Afewerki Samson , Franco Ana , Balu Alina M. , Tai Cheuk-Wai , Luque Rafael , Córdova Armando
Published: April 2020

A new eco-friendly approach for the preparation of sustainable heterogeneous palladium catalysts from rice husk-derived biogenic silica (RHP-Si and RHU-Si). The designed heterogeneously supported palladium species (RHP-Si-NH2-Pd and RHU-Si-NH2-Pd) were fully characterized and successfully employed as catalysts for various chemical transformations (C–C bond-forming reactions, aerobic oxidations and carbocyclizations). Suzuki-Miyaura transformations were highly efficient in a green solvent system (H2O:EtOH (1:1) with excellent recyclability, providing the cross-coupling products with a wide range of functionalities in high isolated yields (up to 99%). Palladium species (Pd(0)-nanoparticles or Pd(II)) were also efficient catalysts in the green aerobic oxidation of an allylic alcohol and a co-catalytic stereoselective cascade carbocyclization transformation. In the latter case, a quaternary stereocenter was formed with excellent stereoselectivity (up to 27:1 dr).
A preliminary analysis on the effect of copper on Anopheles coluzzii insecticide resistance in vegetable farms in Benin
Authors: Talom Armand Defo , Essoung Michele Agnes , Gbankoto Adam , Tchigossou Genevieve , Akoton Romaric , Sahabi Bio Bangana A. , Atoyebi Seun Michael , Fotso Kuate Apollin , Verspoor Rudi L. , Tamò Manuele , Tchuinkam Timoleon , Lehman Gustave Leopold , Lines Jo , Wondji Charles S. , Djouaka Rousseau
Published: April 2020

The use of agrochemicals in vegetable production could influence the selection for insecticide resistance in malaria vectors. Unfortunately, there is a dearth of information on the potential contribution of agrochemicals to insecticide resistance in Anopheles mosquitoes breeding on vegetable farms in southern Benin. A Knowledge, Attitudes and Practices study was conducted with 75 vegetable farmers from Houeyiho and Seme to determine the main agrochemicals used in vegetable production, and the concentration and frequency of application, among other details. Mosquitoes and breeding water were sampled from the farms for analysis. Bioassays were conducted on mosquitoes, while breeding water was screened for heavy metal and pesticide residue contamination. Lambda-cyhalothrin was the main insecticide (97.5%) used by farmers, and Anopheles coluzzii was the main mosquito identified. This mosquito species was resistant (30–63% mortality rate) to λ-cyhalothrin. It was also observed that 16.7% of the examined breeding sites were contaminated with λ-cyhalothrin residues. Furthermore, copper contamination detected in mosquito breeding sites showed a positive correlation (r = 0.81; P = 0.0017) with mosquito resistance to λ-cyhalothrin. The presence of copper in λ-cyhalothrin-free breeding sites, where mosquitoes have developed resistance to λ-cyhalothrin, suggests the involvement of copper in the insecticide resistance of malaria vectors; this, however, needs further investigation.
Metabolomics Adaptation of Juvenile Pacific Abalone Haliotis discus hannai to Heat Stress
Authors: Xu Fei , Gao Tingting , Liu Xiao
Published: April 2020

Temperature fluctuation is a key abiotic factor for the growth and survival of Pacific abalone Haliotis discus hannai, particularly during climate change. However, the physiological mechanism underlying the abalones’ response to heat stress remains unknown. We sought to understand the metabolic adaptation mechanism of Pacific abalone to heat stress for further analyzing its heat tolerance capacity. For two groups experienced different acclimate temperature (10 °C and 30 °C for 62 days), the Pacific abalone juveniles displayed significantly different survival rates under 31 °C acute heat treatment. A total of 1815 and 1314 differential metabolites were identified from the 10 °C and 30 °C acclimate groups respectively, by comparing mass spectrometry data of the samples before and after heat stimulation. Heat stress led to mitochondrial failure, resulting in incomplete oxidative metabolism of amino acids and fatty acids in the mitochondria, and massive accumulation of unstable metabolic intermediates in cells. The 10 °C acclimated group accumulated more harmful substances after heat stimulation, provoking further stress responses and pathophysiological processes. In comparison, the 30 °C acclimated group showed stronger regulation capacity to produce beneficial substances for metabolic homeostasis. The findings provided insight into the heat response of marine animals, especially concerning mitochondrial metabolism.
Cell surface processing of the P1 adhesin of Mycoplasma pneumoniae identifies novel domains that bind host molecules
Authors: Widjaja Michael , Berry Iain James , Jarocki Veronica Maria , Padula Matthew Paul , Dumke Roger , Djordjevic Steven Philip
Published: April 2020

Mycoplasma pneumoniae is a genome reduced pathogen and causative agent of community acquired pneumonia. The major cellular adhesin, P1, localises to the tip of the attachment organelle forming a complex with P40 and P90, two cleavage fragments derived by processing Mpn142, and other molecules with adhesive and mobility functions. LC-MS/MS analysis of M. pneumoniae M129 proteins derived from whole cell lysates and eluents from affinity matrices coupled with chemically diverse host molecules identified 22 proteoforms of P1. Terminomics was used to characterise 17 cleavage events many of which were independently verified by the identification of semi-tryptic peptides in our proteome studies and by immunoblotting. One cleavage event released 1597TSAAKPGAPRPPVPPKPGAPKPPVQPPKKPA1627 from the C-terminus of P1 and this peptide was shown to bind to a range of host molecules. A smaller synthetic peptide comprising the C-terminal 15 amino acids, 1613PGAPKPPVQPPKKPA1627, selectively bound cytoskeletal intermediate filament proteins cytokeratin 7, cytokeratin 8, cytokeratin 18, and vimentin from a native A549 cell lysate. Collectively, our data suggests that ectodomain shedding occurs on the surface of M. pneumoniae where it may alter the functional diversity of P1, Mpn142 and other surface proteins such as elongation factor Tu via a mechanism similar to that described in Mycoplasma hyopneumoniae.
Determination of the anti-yeast activity of Lactobacillus spp. isolated from traditional Iranian cheeses in vitro and in yogurt drink (Doogh)
Authors: Afzali Saeid , Edalatian Dovom Mohammad Reza , Habibi Najafi Mohammad Bagher , Mazaheri Tehrani Mostafa
Published: April 2020

The objective of this study was to determine the anti-yeast effect of Lactobacillus spp. isolated from two popular Iranian cheeses known as Lighvan and Motal against food spoilage yeasts known as Rhodotorula mucilaginosa, Saccharomyces cerevisiae and Kluyveromyces lactis. Twenty strains of Lactobacillus were selected from Motal (16 isolates) and Lighvan cheeses (4 isolates). Anti-yeast activity was studied by Agar Spot and Well Diffusion Assay. Effect of pasteurization on inhibitory compounds was also investigated. Results showed that two strains of Lactobacillus brevis (M4 and M2) exhibited the highest anti- yeast activity in aforementioned methods, as well as tolerated pasteurization. M4 and M2 strains were inoculated into Doogh (a fermented yogurt drink) at two levels (106 and 108 cfu/ml). All samples were incubated in three storage temperatures (4, 25 and 37 °C) and were then examined for microbial parameters (Mold and yeast counts, Coliform, E. coli and Staphylococcus aureus) at specific intervals. Sample with M4 (106cfu/ml) showed superiority rather than control sample in microbial point of view. At temperatures of 25 and 37 °C, inoculated samples were not contaminated up to day- 21 and day-14, respectively. The propionic acid content for M4 and M2, was 14576.11 and 11697.3 ppm, respectively. Results indicate that incorporation of strain M4 (Lb. brevis) at a level of 106 cfu/ml can potentially postpone the yeast spoilage in Doogh and prolong the stability of this product. In conclusion, these strains had the highest activity against experimented yeasts.
Post-operative radiation therapy to the surgical cavity with standard fractionation in patients with brain metastases
Authors: Byrne James D. , Botticello Thomas , Niemierko Andrzej , Shih Helen A. , Loeffler Jay S. , Oh Kevin S.
Published: April 2020

The paradigm for post-operative cavity radiation therapy has shifted to more targeted, less morbid approaches. Single-fraction or hypofractionated radiation therapy is a common approach to treating the postoperative cavity but is associated with a local failure rate 20–40%. We employed an alternative treatment strategy involving fractionated partial brain radiation therapy to the surgical cavity. Patients with brain metastases who underwent radiation treatment 30–42 Gy in 3 Gy/fraction regimens to surgical cavity were retrospectively identified. The 6-month and 12-month freedom from local failure rates were 97.0% and 88.2%. Three patients (7%) experienced local failure at 4, 6, and 22 months. Of these, the histologies were colorectal adenocarcinoma (N = 1) and breast adenocarcinoma (N = 2). The 6-month and 12-month freedom from distant brain metastases rates were 74.1% and 68.8%, respectively, and the 6-month and 12-month overall survival rates were 84.9% and 64.3% respectively. The median overall survival was 39 months, and there were no events of late radionecrosis. Fractionated partial brain irradiation to the surgical cavity of resected brain metastases results in low rates of local failure. This strategy represents an alternative to SRS and WBRT.
Publisher Correction: MUC4-ErbB2 Oncogenic Complex: Binding studies using Microscale Thermophoresis
Authors: Liberelle Maxime , Magnez Romain , Thuru Xavier , Bencheikh Yamina , Ravez Severine , Quenon Camille , Drucbert Anne-Sophie , Foulon Catherine , Melnyk Patricia , Van Seuningen Isabelle , Lebègue Nicolas
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Agro-industrial by-product in photoheterotrophic and mixotrophic culture of Tetradesmus obliquus: Production of ω3 and ω6 essential fatty acids with biotechnological importance
Authors: Piasecka Agata , Nawrocka Agnieszka , Wiącek Dariusz , Krzemińska Izabela
Published: April 2020

In recent years, researchers have highlighted the role of low cost-efficient agro-industrial by-products used as supplements in algal culture media. The aim of the study was to identify and characterize the basic metabolic pathways in Tetradesmus obliquus cells induced by supplementation with beet molasses in photoheterotrophic and mixotrophic culture conditions. To assess the impact of the nutritional strategy in unicellular algae, growth curves were plotted and lipid, carbohydrate, and protein levels were determined. Fourier Transform Infrared Spectroscopy was applied to measure the Tetradesmus obliquus cell composition. Additionally, the C16-C18 fatty acid profile of Tetradesmus obliquus was determined by gas chromatograph/mass spectrometry. The switch from autotrophy to photoheterotrophy and mixotrophy contributes to shortening of the adaptation growth phase. The highest protein content was obtained in the mixotrophic growth. This study has demonstrated high content of 18:1, cisΔ9, 18:2, cisΔ9,12, ω6, and 18:3, cisΔ9,12,15, ω3 in photoheterotrophic and mixotrophic culture conditions. High levels of proteins and essential fatty acids make Tetradesmus obliquus cell biomass important for human and animals health.