bluuebunny/crossref_metadata_2025 huggingface dataset:
Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy
Authors: Lv Mengze , Chen Meixia , Zhang Rui , Zhang Wen , Wang Chenguang , Zhang Yan , Wei Xiaoming , Guan Yukun , Liu Jiejie , Feng Kaichao , Jing Miao , Wang Xurui , Liu Yun-Cai , Mei Qian , Han Weidong , Jiang Zhengfan
Published: August 2020

CD8+T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1, an interaction acts like brakes to prevent T cell overreaction under normal conditions but is exploited by tumor cells to escape the immune surveillance. Immune checkpoint inhibitors have revolutionized cancer therapeutics by removing such brakes. Unfortunately, only a minority of cancer patients respond to immunotherapies presumably due to inadequate immunity. Antitumor immunity depends on the activation of the cGAS-STING pathway, as STING-deficient mice fail to stimulate tumor-infiltrating dendritic cells (DCs) to activate CD8+T cells. STING agonists also enhance natural killer (NK) cells to mediate the clearance of CD8+T cell-resistant tumors. Therefore STING agonists have been intensively sought after. We previously discovered that manganese (Mn) is indispensable for the host defense against cytosolic dsDNA by activating cGAS-STING. Here we report that Mn is also essential in innate immune sensing of tumors and enhances adaptive immune responses against tumors. Mn-insufficient mice had significantly enhanced tumor growth and metastasis, with greatly reduced tumor-infiltrating CD8+T cells. Mechanically, Mn2+promoted DC and macrophage maturation and tumor-specific antigen presentation, augmented CD8+T cell differentiation, activation and NK cell activation, and increased memory CD8+T cells. Combining Mn2+with immune checkpoint inhibition synergistically boosted antitumor efficacies and reduced the anti-PD-1 antibody dosage required in mice. Importantly, a completed phase 1 clinical trial with the combined regimen of Mn2+and anti-PD-1 antibody showed promising efficacy, exhibiting type I IFN induction, manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors. We propose that this combination strategy warrants further clinical translation.
Strong ice-ocean interaction beneath Shirase Glacier Tongue in East Antarctica
Authors: Hirano Daisuke , Tamura Takeshi , Kusahara Kazuya , Ohshima Kay I. , Nicholls Keith W. , Ushio Shuki , Simizu Daisuke , Ono Kazuya , Fujii Masakazu , Nogi Yoshifumi , Aoki Shigeru
Published: August 2020

Mass loss from the Antarctic ice sheet, Earth’s largest freshwater reservoir, results directly in global sea-level rise and Southern Ocean freshening. Observational and modeling studies have demonstrated that ice shelf basal melting, resulting from the inflow of warm water onto the Antarctic continental shelf, plays a key role in the ice sheet’s mass balance. In recent decades, warm ocean-cryosphere interaction in the Amundsen and Bellingshausen seas has received a great deal of attention. However, except for Totten Ice Shelf, East Antarctic ice shelves typically have cold ice cavities with low basal melt rates. Here we present direct observational evidence of high basal melt rates (7–16 m yr−1) beneath an East Antarctic ice shelf, Shirase Glacier Tongue, driven by southward-flowing warm water guided by a deep continuous trough extending to the continental slope. The strength of the alongshore wind controls the thickness of the inflowing warm water layer and the rate of basal melting.
Uniaxial-strain control of nematic superconductivity in SrxBi2Se3
Authors: Kostylev Ivan , Yonezawa Shingo , Wang Zhiwei , Ando Yoichi , Maeno Yoshiteru
Published: August 2020

Nematic states are characterized by rotational symmetry breaking without translational ordering. Recently, nematic superconductivity, in which the superconducting gap spontaneously lifts the rotational symmetry of the lattice, has been discovered. In nematic superconductivity, multiple superconducting domains with different nematic orientations can exist, and these domains can be controlled by a conjugate external stimulus. Domain engineering is quite common in magnets but has not been achieved in superconductors. Here, we report control of the nematic superconductivity and their domains of SrxBi2Se3, through externally-applied uniaxial stress. The suppression of subdomains indicates that it is the Δ4y state that is most favoured under compression along the basal Bi-Bi bonds. This fact allows us to determine the coupling parameter between the nematicity and lattice distortion. These results provide an inevitable step towards microscopic understanding and future utilization of the unique topological nematic superconductivity.
Rhodium(II)-catalyzed multicomponent assembly of α,α,α-trisubstituted esters via formal insertion of O–C(sp3)–C(sp2) into C–C bonds
Authors: Ba Dan , Wen Si , Tian Qingyu , Chen Yanhui , Lv Weiwei , Cheng Guolin
Published: August 2020

The direct cleavage of C(CO)−C single bonds, delivering otherwise inaccessible compounds, is a significant challenge. Although the transition metal-catalyzed insertion of functional groups into C(CO)−C bonds has been studied, strained ketone substrates or chelating assistance were commonly required. In this article, we describe a rhodium(II)-catalyzed three-component reaction of 1,3-diones, diazoesters, and N,N-dimethylformamide (DMF), leading to an unusual formal insertion of O–C(sp3)–C(sp2) into unstrained C(CO)−C bonds. This procedure provides a rapid entry to a gamut of otherwise inaccessible α,α,α-trisubstituted esters/amide from relatively simple substrates in a straightforward manner. 55 examples of highly decorated products demonstrate the broad functional group tolerance and substrate scope. The combination of control experiments and isotope-labeling reactions support that O, C(sp3), and C(sp2) units derive from 1,3-diones, diazoesters, and DMF, respectively.
A discrete serotonergic circuit regulates vulnerability to social stress
Authors: Zou Wen-Jun , Song Yun-Long , Wu Min-Yi , Chen Xiang-Tian , You Qiang-Long , Yang Qian , Luo Zheng-Yi , Huang Lang , Kong Yin , Feng Jing , Fang Dong-Xiang , Li Xiao-Wen , Yang Jian-Ming , Mei Lin , Gao Tian-Ming
Published: August 2020

Exposure to social stress and dysregulated serotonergic neurotransmission have both been implicated in the etiology of psychiatric disorders. However, the serotonergic circuit involved in stress vulnerability is still unknown. Here, we explored whether a serotonergic input from the dorsal raphe (DR) to ventral tegmental area (VTA) influences vulnerability to social stress. We identified a distinct, anatomically and functionally defined serotonergic subpopulation in the DR that projects to the VTA (5-HTDR→VTA neurons). Moreover, we found that susceptibility to social stress decreased the firing activity of 5-HTDR→VTA neurons. Importantly, the bidirectional manipulation of 5-HTDR→VTA neurons could modulate susceptibility to social stress. Our findings reveal that the activity of 5-HTDR→VTA neurons may be an essential factor in determining individual levels of susceptibility to social stress and suggest that targeting specific serotonergic circuits may aid the development of therapies for the treatment of stress-related disorders.
Probing nanoscale spatial distribution of plasmonically excited hot carriers
Authors: Huang Sheng-Chao , Wang Xiang , Zhao Qing-Qing , Zhu Jin-Feng , Li Cha-Wei , He Yu-Han , Hu Shu , Sartin Matthew M. , Yan Sen , Ren Bin
Published: August 2020

Surface plasmons (SPs) of metals enable the tight focusing and strong absorption of light to realize an efficient utilization of photons at nanoscale. In particular, the SP-generated hot carriers have emerged as a promising way to efficiently drive photochemical and photoelectric processes under moderate conditions. In situ measuring of the transport process and spatial distribution of hot carriers in real space is crucial to efficiently capture the hot carriers. Here, we use electrochemical tip-enhanced Raman spectroscopy (EC-TERS) to in situ monitor an SP-driven decarboxylation and resolve the spatial distribution of hot carriers with a nanometer spatial resolution. The transport distance of about 20 nm for the reactive hot carriers is obtained from the TERS imaging result. The hot carriers with a higher energy have a shorter transport distance. These conclusions can be guides for the design and arrangement of reactants and devices to efficiently make use of plasmonic hot carriers.
Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans
Authors: Jin Jae-Hyung , Lee Kyung-Tae , Hong Joohyeon , Lee Dongpil , Jang Eun-Ha , Kim Jin-Young , Lee Yeonseon , Lee Seung-Heon , So Yee-Seul , Jung Kwang-Woo , Lee Dong-Gi , Jeong Eunji , Lee Minjae , Jang Yu-Byeong , Choi Yeseul , Lee Myung Ha , Kim Ji-Seok , Yu Seong-Ryong , Choi Jin-Tae , La Jae-Won , Choi Haneul , Kim Sun-Woo , Seo Kyung Jin , Lee Yelin , Thak Eun Jung , Choi Jaeyoung , Averette Anna F. , Lee Yong-Hwan , Heitman Joseph , Kang Hyun Ah , Cheong Eunji , Bahn Yong-Sun
Published: August 2020

Phosphatases, together with kinases and transcription factors, are key components in cellular signalling networks. Here, we present a systematic functional analysis of the phosphatases inCryptococcus neoformans, a fungal pathogen that causes life-threatening fungal meningoencephalitis. We analyse 230 signature-tagged mutant strains for 114 putative phosphatases under 30 distinct in vitro growth conditions, revealing at least one function for 60 of these proteins. Large-scale virulence and infectivity assays using insect and mouse models indicate roles in pathogenicity for 31 phosphatases involved in various processes such as thermotolerance, melanin and capsule production, stress responses,O-mannosylation, or retromer function. Notably, phosphatases Xpp1, Ssu72, Siw14, and Sit4 promote blood-brain barrier adhesion and crossing byC. neoformans. Together with our previous systematic studies of transcription factors and kinases, our results provide comprehensive insight into the pathobiological signalling circuitry ofC. neoformans.
Band insulator to Mott insulator transition in 1T-TaS2
Authors: Wang Y. D. , Yao W. L. , Xin Z. M. , Han T. T. , Wang Z. G. , Chen L. , Cai C. , Li Yuan , Zhang Y.
Published: August 2020

1T-TaS2 undergoes successive phase transitions upon cooling and eventually enters an insulating state of mysterious origin. Some consider this state to be a band insulator with interlayer stacking order, yet others attribute it to Mott physics that support a quantum spin liquid state. Here, we determine the electronic and structural properties of 1T-TaS2 using angle-resolved photoemission spectroscopy and X-Ray diffraction. At low temperatures, the 2π/2c-periodic band dispersion, along with half-integer-indexed diffraction peaks along the c axis, unambiguously indicates that the ground state of 1T-TaS2 is a band insulator with interlayer dimerization. Upon heating, however, the system undergoes a transition into a Mott insulating state, which only exists in a narrow temperature window. Our results refute the idea of searching for quantum magnetism in 1T-TaS2 only at low temperatures, and highlight the competition between on-site Coulomb repulsion and interlayer hopping as a crucial aspect for understanding the material’s electronic properties.
Author Correction: Possible ground states and parallel magnetic-field-driven phase transitions of collinear antiferromagnets
Authors: Li Hai-Feng
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Whole-genome sequencing and gene network modules predict gemcitabine/carboplatin-induced myelosuppression in non-small cell lung cancer patients
Authors: Björn Niclas , Badam Tejaswi Venkata Satya , Spalinskas Rapolas , Brandén Eva , Koyi Hirsh , Lewensohn Rolf , De Petris Luigi , Lubovac-Pilav Zelmina , Sahlén Pelin , Lundeberg Joakim , Gustafsson Mika , Gréen Henrik
Published: August 2020

Gemcitabine/carboplatin chemotherapy commonly induces myelosuppression, including neutropenia, leukopenia, and thrombocytopenia. Predicting patients at risk of these adverse drug reactions (ADRs) and adjusting treatments accordingly is a long-term goal of personalized medicine. This study used whole-genome sequencing (WGS) of blood samples from 96 gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients and gene network modules for predicting myelosuppression. Association of genetic variants in PLINK found 4594, 5019, and 5066 autosomal SNVs/INDELs with p ≤ 1 × 10−3 for neutropenia, leukopenia, and thrombocytopenia, respectively. Based on the SNVs/INDELs we identified the toxicity module, consisting of 215 unique overlapping genes inferred from MCODE-generated gene network modules of 350, 345, and 313 genes, respectively. These module genes showed enrichment for differentially expressed genes in rat bone marrow, human bone marrow, and human cell lines exposed to carboplatin and gemcitabine (p < 0.05). Then using 80% of the patients as training data, random LASSO reduced the number of SNVs/INDELs in the toxicity module into a feasible prediction model consisting of 62 SNVs/INDELs that accurately predict both the training and the test (remaining 20%) data with high (CTCAE 3–4) and low (CTCAE 0–1) maximal myelosuppressive toxicity completely, with the receiver-operating characteristic (ROC) area under the curve (AUC) of 100%. The present study shows how WGS, gene network modules, and random LASSO can be used to develop a feasible and tested model for predicting myelosuppressive toxicity. Although the proposed model predicts myelosuppression in this study, further evaluation in other studies is required to determine its reproducibility, usability, and clinical effect.
Athermal strength of pure aluminum is significantly decreased by severe plastic deformation and it is markedly augmented by subsequent annealing
Authors: Koizumi Takayuki , Kurumatani Anna , Kuroda Mitsutoshi
Published: August 2020

Over the last two decades, it has been considered that fine crystal grains produced by severe plastic deformation (SPD) lead to an extraordinarily high metal strength. The present study reveals that this understanding is basically incorrect. In our uniaxial tensile tests on industrial pure aluminum at an ultralow strain rate of $$\sim 10^{ - 7} /{\text{s}}$$

∼

10

-
7

/
s

, we observed that SPD accompanied by grain refining significantly softened the material. The fundamental strength effective for real structures and structural materials should mean an eternal capability to bear stresses caused by external forces, which is independent of time, that is, athermal. We tried to extract quantitatively the athermal (time-independent) strength from the total strength measured in uniaxial tensile tests under the assumption that the total stress can be additively divided into athermal and thermal (time-dependent) components. As a result of systematic experimental investigation, we found that the athermal strength is significantly reduced by SPD and then markedly increased by subsequent low-temperature annealing. In addition, we confirmed that SPD promotes an increase in the time dependence (viscosity) of the material and that subsequent annealing removes most of the viscosity caused by SPD. The material processed by SPD acquires its prominent time-independent strength after low-temperature annealing.
Full use of factors promoting catalytic performance of chitosan supported manganese porphyrin
Authors: Mo Lin-Qiang , Huang Xian-Fei , Wang Gao-Cai , Huang Guan , Liu Peng
Published: August 2020

In order to make full use of the impact of internal and external factors on the performance of title catalyst for ethyl benzene oxidation, the key internal influencing factors on the catalytic performance were modulated by coordinating and grafting manganese porphyrin to mesoporous and macroporous chitosan, and the important external factors (i.e. oxidation reaction conditions) were optimized using Response Surface Methodology. Under the Response Surface Methodology optimized oxidation reaction conditions (176.56 °C, 0.59 MPa, and 0.25 mg amount of manganese porphyrin), the catalyst could be used at least five times. The ethyl benzene conversion, catalyst turnover numbers, and yields reached up to 51.2%, 4.37 × 106 and 36.4% in average, respectively. Compared with the other optimized oxidation reaction conditions, the corresponding values increased 17%, 26% and 53%. Relative to the manganese porphyrin, the catalytic performance and efficiency of the immobilized catalyst had notably increased.
Identification of tidal trapping of microplastics in a temperate salt marsh system using sea surface microlayer sampling
Authors: Stead Jessica L. , Cundy Andrew B. , Hudson Malcolm D. , Thompson Charlie E. L. , Williams Ian D. , Russell Andrea E. , Pabortsava Katsiaryna
Published: August 2020

Microplastics are contaminants of increasing global environmental concern. Estuaries are a major transport pathway for land-derived plastics to the open ocean but are relatively understudied compared to coastal and open marine environments. The role of the “estuarine filter”, by which the supply of sediments and contaminants to the sea is moderated by processes including vegetative trapping and particle flocculation, remains poorly defined for microplastics land to sea transfer. Here, we focus on the sea surface microlayer (SML) as a vector for microplastics, and use SML sampling to assess microplastic trapping in a temperate marsh system in Southampton Water, UK. The SML is known to concentrate microplastics relative to the underlying water and is the first part of rising tidal waters to traverse intertidal and upper tidal surfaces. Sampling a salt marsh creek at high temporal resolution allowed assessment of microplastics in-wash and outflow from the salt marsh, and its relationship with tidal state and bulk suspended sediment concentrations (SSC), over spring and neap tides. A statistically significant decrease in microplastics abundance from the flood tide to the ebb tide was found, and a weak positive relationship with SSC observed.
Efficient light harvesting using simple porphyrin-oxide perovskite system
Authors: Sharma Shalu , Chhoker Sandeep
Published: August 2020

Here, we report the systematic studies on photoanodes of phase pure polycrystalline microrods of Barium Stannate (BaSnO3) microrods for application in porphyrin dye-sensitized solar cell (DSSC). We were able to establish the effect of vacuum annealing on BaSnO3 thin films on its electrical, optical and adsorption properties using XPS, UV–Vis, photoluminescence and adsorption isotherm studies. Increase in oxygen vacancy with annealing is found to increase the room temperature (RT) electron mobility from 49.1 to 82.4 cm2/V sec whereas macroporous nature of samples were found suitable for faster dye adsorption (~ 30 min). Post TiCl4 treatment studies, the maximum efficiency (η) of 4.7% is achieved in BSO films with current density Jsc ~ value as 10.4 mA/cm2; whereas DSSC fabricated using annealed BSO films gave maximum efficiency of 6.1% with Jsc value as 12.2 mA/cm2, during which the value of FF increased from 73.4 to 81%. The IPCE and proposed electron transfer mechanism suggested the potential application of macroporous BSO with unconventional dyes such as metallised-porphyrin. Our results strengthen the idea of using phase-pure, visible transparent porous BSO nanostructures with induced oxygen vacancies due to annealing process post-synthesis which eventually increased DSSC performance from by 84%.
Universal size ratios of Gaussian polymers with complex architecture: radius of gyration vs hydrodynamic radius
Authors: Haydukivska Khristine , Blavatska Viktoria , Paturej Jarosław
Published: August 2020

We study the impact of arm architecture of polymers with a single branch point on their structure in solvents. Many physical properties of polymer liquids strongly dependent on the size and shape measures of individual macromolecules, which in turn are determined by their topology. Here, we use combination of analytical theory, based on path integration method, and molecular dynamics simulations to study structural properties of complex Gaussian polymers containing $$f^c$$

f
c

linear branches and $$f^r$$

f
r

closed loops grafted to the central core. We determine size measures such as the gyration radius $$R_g$$

R
g

and the hydrodynamic radii $$R_H$$

R
H

, and obtain the estimates for the size ratio $$R_g /R_H$$

R
g

/

R
H

with its dependence on the functionality $$f=f^c+f^r$$

f
=

f
c

+

f
r

of grafted polymers. In particular, we obtain the quantitative estimate of the degree of compactification of these polymers with increasing number of closed loops $$f^r$$

f
r

as compared to linear or star-shape molecules of the same total molecular weight. Numerical simulations corroborate theoretical prediction that $$R_g /R_H$$

R
g

/

R
H

decreases towards unity with increasing f. These findings provide qualitative description of polymers with complex architecture in $$\theta $$
θ
solvents.
DNA damage response and preleukemic fusion genes induced by ionizing radiation in umbilical cord blood hematopoietic stem cells
Authors: Kosik Pavol , Durdik Matus , Jakl Lukas , Skorvaga Milan , Markova Eva , Vesela Gabriela , Vokalova Lenka , Kolariková Lucia , Horvathova Eva , Kozics Katarina , Belyaev Igor
Published: August 2020

There is clear evidence that ionizing radiation (IR) causes leukemia. For many types of leukemia, the preleukemic fusion genes (PFG), as consequences of DNA damage and chromosomal translocations, occur in hematopoietic stem and progenitor cells (HSPC) in utero and could be detected in umbilical cord blood (UCB) of newborns. However, relatively limited information is available about radiation-induced apoptosis, DNA damage and PFG formation in human HSPC. In this study we revealed that CD34+ HSPC compared to lymphocytes: (i) are extremely radio-resistant showing delayed time kinetics of apoptosis, (ii) accumulate lower level of endogenous DNA damage/early apoptotic γH2AX pan-stained cells, (iii) have higher level of radiation-induced 53BP1 and γH2AX/53BP1 co-localized DNA double stranded breaks, and (iv) after low dose of IR may form very low level of BCR-ABL PFG. Within CD34+ HSPC we identified CD34+CD38+ progenitor cells as a highly apoptosis-resistant population, while CD34+CD38− hematopoietic stem/multipotent progenitor cells (HSC/MPP) as a population very sensitive to radiation-induced apoptosis. Our study provides critical insights into how human HSPC respond to IR in the context of DNA damage, apoptosis and PFG.
Acapsular Staphylococcus aureus with a non-functional agr regains capsule expression after passage through the bloodstream in a bacteremia mouse model
Authors: Suligoy Carlos M. , Díaz Rocío E. , Gehrke Ana-Katharina , Ring Natalie , Yebra Gonzalo , Alves Joana , Gómez Marisa I. , Wendler Sindy , FITZGERALD J. Ross , Tuchscherr Lorena , Löffler Bettina , Sordelli Daniel O. , Llana Mariángeles Noto , Buzzola Fernanda R.
Published: August 2020

Selection pressures exerted onStaphylococcus aureusby host factors during infection may lead to the emergence of regulatory phenotypes better adapted to the infection site. Traits convenient for persistence may be fixed by mutation thus turning these mutants into microevolution endpoints. The feasibility that stable, non-encapsulatedS. aureusmutants can regain expression of key virulence factors for survival in the bloodstream was investigated.S. aureus agrmutant HU-14 (IS256insertion inagrC) from a patient with chronic osteomyelitis was passed through the bloodstream using a bacteriemia mouse model and derivative P3.1 was obtained. Although IS256remained inserted inagrC, P3.1 regained production of capsular polysaccharide type 5 (CP5) and staphyloxanthin.Furthermore, P3.1 expressed higher levels ofasp23/SigB when compared with parental strain HU-14. Strain P3.1 displayed decreased osteoclastogenesis capacity, thus indicating decreased adaptability to bone compared with strain HU-14 and exhibited a trend to be more virulent than parental strain HU-14. Strain P3.1 exhibited the loss of one IS256copy, which was originally located in the HU-14 noncoding region betweendnaG(DNA primase) andrpoD(sigA). This loss may be associated with the observed phenotype change but the mechanism remains unknown. In conclusion,S. aureusorganisms that escape the infected bone may recover the expression of key virulence factors through a rapid microevolution pathway involving SigB regulation of key virulence factors.
Physical fitness status modulates the inflammatory proteins in peripheral blood and circulating monocytes: role of PPAR-gamma
Authors: Antunes Barbara Moura , Rosa-Neto José Cesar , Batatinha Helena Angélica Pereira , Franchini Emerson , Teixeira Ana Maria , Lira Fábio Santos
Published: August 2020

The aim of this study was to analyze the metabolic and molecular profile according to physical fitness status (Low or High VO2max) and its impacts on peripheral and cellular inflammatory responses in healthy men. First (Phase I), inflammatory profile (TNF-α, IL-6, IL-10) was analyzed at baseline and post-acute exercise sessions performed at low (< 60% VO2max) and high (> 90% VO2max) intensities considering the individual endotoxin concentrations. Next (Phase II), monocyte cell cultures were treated with LPS alone or associated with Rosiglitazone (PPAR-γ agonist drug) to analyze cytokine production and gene expression. Monocyte subsets were also evaluated by flow cytometry. A positive relationship was observed between LPS concentrations and oxygen uptake (VO2max) (r = 0.368; p = 0.007); however, in the post-exercise an inverse correlation was found between LPS variation (Δ%) and VO2max (r = -0.385; p = 0.004). With the low-intensity exercise session, there was inverse correlation between LPS and IL-6 concentrations post-exercise (r = -0.505; p = 0.046) and a positive correlation with IL-10 in the recovery (1 h post) (r = 0.567; p = 0.011), whereas with the high-intensity exercise an inverse correlation was observed with IL-6 at pre-exercise (r = -0.621; p = 0.013) and recovery (r = -0.574; p = 0.016). When monocyte cells were treated with LPS, High VO2max individuals showed higher PPAR-γ gene expression whereas Low VO2max individuals displayed higher IL-10 production. Additionally, higher TLR-4, IKK1, and PGC-1α gene expression were observed in the High VO2max group than Low VO2max individuals. In conclusion, even with elevated endotoxemia, individuals with High VO2max exhibited higher IL-6 concentration in peripheral blood post-acute aerobic exercise and lower IL-10 concentration during recovery (1 h post-exercise). The anti-inflammatory effects linked with exercise training and physical fitness status may be explained by a greater gene expression of IKK1, TLR-4, and PGC-1α, displaying an extremely efficient cellular framework for the PPAR-γ responses.
Palaeontological evidence reveals convergent evolution of intervertebral joint types in amniotes
Authors: Wintrich Tanja , Scaal Martin , Böhmer Christine , Schellhorn Rico , Kogan Ilja , van der Reest Aaron , Sander P. Martin
Published: August 2020

The intervertebral disc (IVD) has long been considered unique to mammals. Palaeohistological sampling of 17 mostly extinct clades across the amniote tree revealed preservation of different intervertebral soft tissue types (cartilage, probable notochord) seen in extant reptiles. The distribution of the fossilised tissues allowed us to infer the soft part anatomy of the joint. Surprisingly, we also found evidence for an IVD in fossil reptiles, including non-avian dinosaurs, ichthyosaurs, plesiosaurs, and marine crocodiles. Based on the fossil dataset, we traced the evolution of the amniote intervertebral joint through ancestral character state reconstruction. The IVD evolved at least twice, in mammals and in extinct diapsid reptiles. From this reptilian IVD, extant reptile groups and some non-avian dinosaurs independently evolved a synovial ball-and-socket joint. The unique birds dorsal intervertebral joint evolved from this dinosaur joint. The tuatara and some geckos reverted to the ancestral persisting notochord.
Synchronized moulting behaviour in trilobites from the Cambrian Series 2 of South China
Authors: Corrales-García Alejandro , Esteve Jorge , Zhao Yuanlong , Yang Xinglian
Published: August 2020

The study of moulting behaviour in the fossil record is relatively well known in arthropods and this is especially true for trilobites. Nevertheless, while studies focusing on the style of moulting in social and semi-social groups of modern animals (e.g. arthropods) are common, very few works investigate moulting adaptations in deep time. Here we report a trilobite assemblage from the Cambrian Series 2 “Tsinghsutung” Formation of South China. Around 850 specimens were used for this study from three different levels across one section near Balang (SE Guizhou Province, South China). These levels preserve numerous trilobite clusters in some cases containing around 400 individual specimens. Up to four species have been found in these clusters, but two species are more common. Trilobite clusters bear a high percentage of disarticulated specimens that we interpret as moults. Additionally, measurements of bioclast orientation and the dorsoventral attitude suggests very quiet water conditions followed by rapid burial events, prior to scavenger disturbance. Together, this indicates that the fossil assemblages were a result of a biological phenomenon rather than mechanical processes, allowing us to interpret the position of the fossil parts as different moulting configurations. Since the trilobite assemblage seems to be in situ, the large number of exuviae suggests a local place of migration. This was triggered by the need for group protection while moulting, which is suggestive of gregarious behaviour, possibly synchronized. These trilobites from the Cambrian Epoch 2, Age 4 constitute one of the earliest known gregarious community of trilobites and has important implications for understanding the ecology of this group during their emergence in the Cambrian.
Salinity-independent dissipation of antibiotics from flooded tropical soil: a microcosm study
Authors: Sentek Valerie , Braun Gianna , Braun Melanie , Sebesvari Zita , Renaud Fabrice G. , Herbst Michael , Frindte Katharina , Amelung Wulf
Published: August 2020

River deltas are frequently facing salinity intrusion, thus challenging agricultural production in these areas. One adaption strategy to increasing salinity is shrimp production, which however, heavily relies on antibiotic usage. This study was performed to evaluate the effect of increasing salinity on the dissipation rates of antibiotics in tropical flooded soil systems. For this purpose, paddy top soil from a coastal Vietnamese delta was spiked with selected frequently used antibiotics (sulfadiazine, sulfamethazine, sulfamethoxazole, trimethoprim) and incubated with flood water of different salt concentrations (0, 10, 20 g L−1). Antibiotic concentrations were monitored in water and soil phases over a period of 112 days using liquid chromatography and tandem mass spectrometry. We found that sulfamethazine was the most persistent antibiotic in the flooded soil system (DT50 = 77 days), followed by sulfadiazine (DT50 = 53 days), trimethoprim (DT50 = 3 days) and sulfamethoxazole (DT50 = 1 days). With the exception of sulfamethoxazole, the apparent distribution coefficient increased significantly (p < 0.05) for all antibiotics in course of the incubation, which indicates an accumulation of antibiotics in soil. On a whole system basis, including soil and water into the assessment, there was no overall salinity effect on the dissipation rates of antibiotics, suggesting that common e-fate models remain valid under varying salinity.
Myotendinous junction adaptations to ladder-based resistance training: identification of a new telocyte niche
Authors: Pimentel Neto Jurandyr , Rocha Lara Caetano , Barbosa Gabriela Klein , Jacob Carolina dos Santos , Krause Neto Walter , Watanabe Ii-sei , Ciena Adriano Polican
Published: August 2020

The present study shows chronic adjustments in the myotendinous junction (MTJ) in response to different ladder-based resistance training (LRT) protocols. Thirty adult male Wistar rats were divided into groups: sedentary (S), calisthenics (LRT without additional load [C]), and resistance-trained (LRT with extra weight [R]). We demonstrated longer lengths of sarcoplasmatic invaginations in the trained groups; however, evaginations were seen mainly in group R. We showed a greater thickness of sarcoplasmatic invaginations in groups C and R, in addition to greater evaginations in R. We also observed thinner basal lamina in trained groups. The support collagen layer (SCL) adjacent to the MTJ and the diameters of the transverse fibrils were larger in R. We also discovered a niche of telocytes in the MTJ with electron micrographs of the plantar muscle and with immunostaining with CD34+ in the gastrocnemius muscle near the blood vessels and pericytes. We concluded that the continuous adjustments in the MTJ ultrastructure were the result of tissue plasticity induced by LRT, which is causally related to muscle hypertrophy and, consequently, to the remodeling of the contact interface. Also, we reveal the existence of a collagen layer adjacent to MTJ and discover a new micro anatomic location of telocytes.
Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA
Authors: Duranti Sabrina , Ruiz Lorena , Lugli Gabriele Andrea , Tames Héctor , Milani Christian , Mancabelli Leonardo , Mancino Walter , Longhi Giulia , Carnevali Luca , Sgoifo Andrea , Margolles Abelardo , Ventura Marco , Ruas-Madiedo Patricia , Turroni Francesca
Published: August 2020

Gamma aminobutyric acid (GABA) is the principal inhibitory neurotransmitter playing a key role in anxiety and depression disorders in mammals. Recent studies revealed that members of the gut microbiota are able to produce GABA modulating the gut–brain axis response. Among members of the human gut microbiota, bifidobacteria are well known to establish many metabolic and physiologic interactions with the host. In this study, we performed genome analyses of more than 1,000 bifidobacterial strains publicly available revealing that Bifidobacterium adolescentis taxon might represent a model GABA producer in human gastrointestinal tract. Moreover, the in silico screening of human/animal metagenomic datasets showed an intriguing association/correlation between B. adolescentis load and mental disorders such as depression and anxiety. Interestingly, in vitro screening of 82 B. adolescentis strains allowed identifying two high GABA producers, i.e. B. adolescentis PRL2019 and B. adolescentis HD17T2H, which were employed in an in vivo trial in rats. Feeding Groningen rats with a supplementation of B. adolescentis strains, confirmed the ability of these microorganisms to stimulate the in vivo production of GABA highlighting their potential implication in gut–brain axis interactions.
Ten years of vaccinovigilance in Italy: an overview of the pharmacovigilance data from 2008 to 2017
Authors: Moretti F. , Gonella L. , Gironi S. , Marra A. R. , Santuccio C. , Felicetti P. , Petronzelli F. , Marchione P. , Barnaba S. A. , Poli A. , Zanoni G. , Moretti U.
Published: August 2020

Reporting and analysis of Adverse Events Following Immunization (AEFIs) are the cornerstones of vaccine safety surveillance prompting causality assessment and signal detection. This paper describes the impact of the Italian Pharmacovigilance System of vaccines over a 10-year period (2008–2017). The reporting rate (RR) per all distributed dose was calculated. Serious AEFIs and causality assessments for fatal cases were described. The main results from signal detection were reported. During the study period, 46,430 AEFIs were reported with an overall RR of 17.2 per 100,000 distributed doses. Italy showed the highest number of reports among European countries. Only 4.4% of the reports came from citizens. Of the total, 12.7% were classified as serious with a RR over the study period of 2.20 per 100,000 distributed doses. They were mainly related to hyperpyrexia and usually had a positive outcome. Fatal outcomes were reported in 0.3% of the cases and were primarily associated with the influenza vaccine in elderly patients. None of these outcomes had a consistent causal association with the vaccination. Febrile convulsions by the measles, mumps, rubella and varicella vaccines and intussusception by the rotavirus vaccine were among the highlighted signals. The reporting rate and the analysis of serious events from 10 years support the good risk/benefit profiles of vaccines.
Global identification of a marine diatom long noncoding natural antisense transcripts (NATs) and their response to phosphate fluctuations
Authors: Cruz de Carvalho Maria Helena , Bowler Chris
Published: August 2020

Often ignored and regarded as mere transcriptional noise, long noncoding RNAs (lncRNAs) are starting to be considered key regulators of gene expression across the Eukarya domain of life. In the model diatom Phaeodactylum tricornutum, we have previously reported the occurrence of 1,510 intergenic lncRNAs (lincRNAs), many of which displaying specific patterns of expression under phosphate fluctuation (Pi). Using strand-specific RNA-sequencing data we now expand the repertoire of P. tricornutum lncRNAs by identifying 2,628 novel natural antisense transcripts (NATs) that cover 21.5% of the annotated genomic loci. We found that NAT expression is tightly regulated by phosphate depletion and other naturally occurring environmental stresses. Furthermore, we identified 121 phosphate stress responsive NAT-mRNA pairs, the great majority of which showing a positive correlation (concordant pairs) and a small fraction with negative correlation (discordant pairs). Taken together our results show that NATs are highly abundant transcripts in P. tricornutum and that their expression is under tight regulation by nutrient and environmental stresses. Furthermore, our results suggest that in P. tricornutum Pi stress response NAT pairs predominantly regulate positively the expression of their cognate sense genes, the latter being involved in several biological processes underlying the control of cellular homeostasis under stress.
Revealing the thermal oxidation stability and its mechanism of rice bran oil
Authors: Rahmania Halida , Kato Shunji , Sawada Kazue , Hayashi Chieko , Hashimoto Hiroyuki , Nakajima Shigeo , Otoki Yurika , Ito Junya , Nakagawa Kiyotaka
Published: August 2020

Although the stability of rice bran oil (RBO) has been showed on several studies, the factors which make it capable on maintaining its stability under thermal oxidation has not been sure yet. We hypothesized that its fatty acid composition [high composition of oleic acid (OA), lower composition of linoleic acid (LA) and α-linolenic acid (LnA)] and/or its antioxidant agents [γ-oryzanol (OZ)] and vitamin E [tocopherol (Toc), tocotrienol (T3)] might be the biggest factor.

To prove the hypothesis, we thermally oxidized RBO under 40 °C for 17 days to mimic the harsh daily storage condition, and compared it with soybean oil (SO) and rapeseed oil (RPO) then monitoring their primary oxidation products [triacylglycerol hydroperoxide (TGOOH)] from easily oxidized fatty acid contained in triacylglycerol (TG) and the amount loss of antioxidant agents. As a result, RBO showed the lowest TGOOH/TG ratio, followed by RPO and SO. The superior stability RPO compared SO might occur due to because of the influence of the fatty acid profile (higher OA and lower LA). For RBO’s case, besides its fatty acid profile, the existence of OZ and the synergistic effect of OZ and vitamin E might have a greater contribution in maintaining its stability under thermal oxidation.
An ancient tropical origin, dispersals via land bridges and Miocene diversification explain the subcosmopolitan disjunctions of the liverwort genus Lejeunea
Authors: Lee Gaik Ee , Condamine Fabien L. , Bechteler Julia , Pérez-Escobar Oscar Alejandro , Scheben Armin , Schäfer-Verwimp Alfons , Pócs Tamás , Heinrichs Jochen
Published: August 2020

Understanding the biogeographical and diversification processes explaining current diversity patterns of subcosmopolitan-distributed groups is challenging. We aimed at disentangling the historical biogeography of the subcosmopolitan liverwort genus Lejeunea with estimation of ancestral areas of origin and testing if sexual system and palaeotemperature variations can be factors of diversification. We assembled a dense taxon sampling for 120 species sampled throughout the geographical distribution of the genus. Lejeunea diverged from its sister group after the Paleocene-Eocene boundary (52.2 Ma, 95% credibility intervals 50.1–54.2 Ma), and the initial diversification of the crown group occurred in the early to middle Eocene (44.5 Ma, 95% credibility intervals 38.5–50.8 Ma). The DEC model indicated that (1) Lejeunea likely originated in an area composed of the Neotropics and the Nearctic, (2) dispersals through terrestrial land bridges in the late Oligocene and Miocene allowed Lejeunea to colonize the Old World, (3) the Boreotropical forest covering the northern regions until the late Eocene did not facilitate Lejeunea dispersals, and (4) a single long-distance dispersal event was inferred between the Neotropics and Africa. Biogeographical and diversification analyses show the Miocene was an important period when Lejeunea diversified globally. We found slight support for higher diversification rates of species with both male and female reproductive organs on the same individual (monoicy), and a moderate positive influence of palaeotemperatures on diversification. Our study shows that an ancient origin associated with a dispersal history facilitated by terrestrial land bridges and not long-distance dispersals are likely to explain the subcosmopolitan distribution of Lejeunea. By enhancing the diversification rates, monoicy likely favoured the colonisations of new areas, especially in the Miocene that was a key epoch shaping the worldwide distribution.
Diabetes and Obesity: An Overview of Nutritional Effects
Authors: De Alwis Sonia , Via Michael A.
Published: August 2020

Type 2 diabetes (T2D) and obesity are well known for their capacity to induce extensive morbidity, costly medical care, and ultimately, shortened lifespan. Of further urgency, these conditions have reached epidemic proportions globally, owing largely to the modern-day lifestyle. In conjunction with weight loss, dietary interventions afford the opportunity to both prevent T2D and mitigate its potential complications. Though no single universal diet has been recommended, several proposed dietary patterns have demonstrated modest benefit in T2D as well as in other conditions associated with insulin resistance, such as the metabolic syndrome, non-alcoholic hepatosteatosis, and polycystic ovary syndrome. Most favorable dietary patterns are consistent in endorsing ample fruits, vegetables, and nuts, while limiting processed foods high in fructose and saturated fat, and those with high glycemic indices.
Nutritional Regulation of Mitochondrial Health and Its Implication in Treating Obesity and Diabetes: Lessons Learned From the Resveratrol–Sirt1 Axis
Authors: Tao Z. , Shi L. , Cheng Z.
Published: August 2020

The epidemic of obesity and diabetes is growing rapidly. One of the hallmarks of metabolic disease is compromised quality of mitochondria, the key energy producer. Research has demonstrated that mitochondrial biogenesis and autophagy (mitophagy) work in concert to regulate the homeostasis of this organelle in the cell. As a nutraceutical found in grapes, berries, peanuts, and associated foods, resveratrol (RSV) can improve mitochondrial health through activating an energy sensor Sirt1. In this chapter, we review the evidence of the RSV–Sirt1 axis in the regulation of mitochondrial and metabolic homeostasis, with a focus on the molecular network that links RSV and Sirt1 to mitochondrial biogenesis, dynamics, and autophagy in different tissues. Results from preclinical studies and clinical trials have demonstrated the potential of RSV in curbing metabolic disorders, while further studies are warranted to establish the dosage, effectiveness, and toxicity.
The Role of Intestinal Microbiota and Microbial Metabolites in the Development of Host Metabolic Syndrome
Authors: Lazar Veronica , Vasilescu Iulia Magdalena , Holban Alina Maria , Chifiriuc Mariana Carmen
Published: August 2020

The emerging role of the intestinal microbiota and of microbial metabolites in both host health and different pathological conditions, including the metabolic syndrome, has opened new avenues for the development of novel diagnosis and therapeutic tools targeting gut microbiota. However, the complex causal mechanisms, interactions between microbiota, host and environmental factors (particularly diet), as well as the involved bioactive metabolites have not been unveiled yet. Most of the performed studies have demonstrated this causality in animal models, and less in humans. The purpose of this chapter is to present a brief overview regarding the role of microbial metabolites in the development of host metabolic syndrome.
Personalized Nutrition to Treat and Prevent Obesity and Diabetes
Authors: Panduro Arturo , Roman Sonia , Milán Ricardo G. , Torres-Reyes Luis Alberto , Gonzalez-Aldaco Karina
Published: August 2020

Obesity and Type 2 diabetes are chronic diseases that are increasing rapidly in many countries going through a nutrition transition. Namely, traditional societies that have shifted towards a Western-culture diet and lifestyle are mainly at risk for obesity-related chronic disease. On the other hand, diet-related adaptive genes encoding alternative alleles may be related to modern-day chronic diseases. Notably, the risk of dyslipidemias and insulin resistance will depend upon the predominance of the “non-risk” or “risk” allele and the surrounding nutrients (food habits). Under this perspective, obesity and Type 2 diabetes are complex diseases that arise from the interaction between a specific risk allele and obesogenic environmental factors. In this chapter, genes encoding receptors for sugar and fat taste perception, lipid transporters, starch, and milk digestive enzymes, energy homeostasis, and food reward systems, as well as epigenetics and host–gut microbiota interactions, will be reviewed. Populations worldwide differ in both the distribution of metabolic risk alleles and dietary patterns; therefore, one standard diet will not fit all. Currently, personalized treatment strategies should aim to customize nutritional needs based on the individual’s or population’s genetic background, food resources, and culture to treat or prevent obesity and Type 2 diabetes.