bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood and lymphatic systems are segregated by the FLCN tumor suppressor
Authors: Tai-Nagara Ikue , Hasumi Yukiko , Kusumoto Dai , Hasumi Hisashi , Okabe Keisuke , Ando Tomofumi , Matsuzaki Fumio , Itoh Fumiko , Saya Hideyuki , Liu Chang , Li Wenling , Mukouyama Yoh-suke , Marston Linehan W. , Liu Xinyi , Hirashima Masanori , Suzuki Yutaka , Funasaki Shintaro , Satou Yorifumi , Furuya Mitsuko , Baba Masaya , Kubota Yoshiaki
Published: December 2020

Blood and lymphatic vessels structurally bear a strong resemblance but never share a lumen, thus maintaining their distinct functions. Although lymphatic vessels initially arise from embryonic veins, the molecular mechanism that maintains separation of these two systems has not been elucidated. Here, we show that genetic deficiency of Folliculin, a tumor suppressor, leads to misconnection of blood and lymphatic vessels in mice and humans. Absence of Folliculin results in the appearance of lymphatic-biased venous endothelial cells caused by ectopic expression of Prox1, a master transcription factor for lymphatic specification. Mechanistically, this phenotype is ascribed to nuclear translocation of the basic helix-loop-helix transcription factor Transcription Factor E3 (TFE3), binding to a regulatory element of Prox1, thereby enhancing its venous expression. Overall, these data demonstrate that Folliculin acts as a gatekeeper that maintains separation of blood and lymphatic vessels by limiting the plasticity of committed endothelial cells.
PMO-based let-7c site blocking oligonucleotide (SBO) mediated utrophin upregulation in mdx mice, a therapeutic approach for Duchenne muscular dystrophy (DMD)
Authors: Sengupta Kasturi , Loro Emanuele , Khurana Tejvir S.
Published: December 2020

Upregulation of utrophin, a dystrophin related protein, is considered a promising therapeutic approach for Duchenne muscular dystrophy (DMD). Utrophin expression is repressed at the post-transcriptional level by a set of miRNAs, among which let-7c is evolutionarily highly conserved. We designed PMO-based SBOs complementary to the let-7c binding site in UTRN 3′UTR, with the goal of inhibiting let-7c interaction with UTRN mRNA and thus upregulating utrophin. We used the C2C12UTRN5′luc3′ reporter cell line in which the 5′- and 3′-UTRs of human UTRN sequences flank luciferase, for reporter assays and the C2C12 cell line for utrophin western blots, to independently evaluate the site blocking efficiency of a series of let-7c PMOs in vitro. Treatment of one-month old mdx mice with the most effective let-7c PMO (i.e. S56) resulted in ca. two-fold higher utrophin protein expression in skeletal muscles and the improvement in dystrophic pathophysiology in mdx mice, in vivo. In summary, we show that PMO-based let-7c SBO has potential applicability for upregulating utrophin expression as a therapeutic approach for DMD.
Longer apneas and hypopneas are associated with greater ultra-short-term HRV in obstructive sleep apnea
Authors: Hietakoste Salla , Korkalainen Henri , Kainulainen Samu , Sillanmäki Saara , Nikkonen Sami , Myllymaa Sami , Duce Brett , Töyräs Juha , Leppänen Timo
Published: December 2020

Low long-term heart rate variability (HRV), often observed in obstructive sleep apnea (OSA) patients, is a known risk factor for cardiovascular diseases. However, it is unclear how the type or duration of individual respiratory events modulate ultra-short-term HRV and beat-to-beat intervals (RR intervals). We aimed to examine the sex-specific changes in RR interval and ultra-short-term HRV during and after apneas and hypopneas of various durations. Electrocardiography signals, recorded as a part of clinical polysomnography, of 758 patients (396 men) with suspected OSA were analysed retrospectively. Average RR intervals and time-domain HRV parameters were determined during the respiratory event and the 15-s period immediately after the event. Parameters were analysed in three pooled sex-specific subgroups based on the respiratory event duration (10–20 s, 20–30 s, and > 30 s) separately for apneas and hypopneas. We observed that RR intervals shortened after the respiratory events and the magnitude of these changes increased in both sexes as the respiratory event duration increased. Furthermore, ultra-short-term HRV generally increased as the respiratory event duration increased. Apneas caused higher ultra-short-term HRV and a stronger decrease in RR interval compared to hypopneas. In conclusion, the respiratory event type and duration modulate ultra-short-term HRV and RR intervals. Considering HRV and the respiratory event characteristics in the diagnosis of OSA could be useful when assessing the cardiac consequences of OSA in a more detailed manner.
Enhancing malaria control using Lagenaria siceraria and its mediated zinc oxide nanoparticles against the vector Anopheles stephensi and its parasite Plasmodium falciparum
Authors: Kalpana V. N. , Alarjani Khaloud Mohammed , Rajeswari V. Devi
Published: December 2020

In many developing countries, there are certain health problems faced by the public, one among them is Malaria. This tropical disease is mainly caused by Plasmodium falciparum. It is categorized as a disaster to public health, which increases both mortality and morbidity. Numerous drugs are in practice to control this disease and their vectors. Eco-friendly control tools are required to battle against vector of this significant disease. Nanotechnology plays a major role in fighting against malaria. The present paper synthesized Zinc oxide nanoparticles (ZnO NPs) using zinc nitrate via simple green routes with the help of aqueous peel extract of Lagenaria siceraria (L. siceraria). The synthesized ZnO NPs were characterized by various biophysical methods. Moreover, the extract of L. siceraria and their mediated ZnO NPs was experimented against III instar larvae of An. stephensi. The impact of the treatment based on ZnO NPs concerning histology and morphology of mosquito larval was further observed. In the normal laboratory environment, the efficiency of predation of Poeciliareticulata (P. reticulata) against An. Stephensi larvae was found to be 44%, whereas in aqueous L. siceraria extract and its mediated ZnO NPs contaminated environment, P. reticulate showed predation efficiency of about 45.8% and 61.13% against An. Stephensi larva. L. siceraria synthesized ZnO NPs were examined against the Plasmodium falciparum CQ-sensitive strains. The L. siceraria extract and its mediated ZnO NPs showed the cytotoxic effects against HeLa cell lines with an IC50 value of 62.5 µg/mL. This study concludes that L. siceraria peel extract and L. siceraria synthesized ZnO NPs represent a valuable green option to fight against malarial vectors and parasites.
Accelerated nucleophilic substitution reactions of dansyl chloride with aniline under ambient conditions via dual-tip reactive paper spray
Authors: Sarih Norfatirah Muhamad , Romero-Perez David , Bastani Behnam , Rauytanapanit Monrawat , Boisdon Cedric , Praneenararat Thanit , Tajuddin Hairul Anuar , Abdullah Zanariah , Badu-Tawiah Abraham K. , Maher Simon
Published: December 2020

Paper spray ionization (PSI) mass spectrometry (MS) is an emerging tool for ambient reaction monitoring via microdroplet reaction acceleration. PSI-MS was used to accelerate and monitor the time course of the reaction of dansyl chloride with aniline, in acetonitrile, to produce dansyl aniline. Three distinct PSI arrangements were explored in this study representing alternative approaches for sample loading and interaction; conventional single tip as well as two novel setups, a dual-tip and a co-axial arrangement were designed so as to limit any on-paper interaction between reagents. The effect on product abundance was investigated using these different paper configurations as it relates to the time course and distance of microdroplet travel. It was observed that product yield increases at a given distance and then decreases thereafter for all PSI configurations. The fluorescent property of the product (dansyl aniline) was used to visually inspect the reaction progress on the paper substrate during the spraying process. Amongst the variety of sample loading methods the novel dual-tip arrangement showed an increased product yield and microdroplet density, whilst avoiding any on-paper interaction between the reagents.
Vegetal diamine oxidase alleviates histamine-induced contraction of colonic muscles
Authors: Neree Armelle Tchoumi , Soret Rodolphe , Marcocci Lucia , Pietrangeli Paola , Pilon Nicolas , Mateescu Mircea Alexandru
Published: December 2020

Excess of histamine in gut lumen generates a pronounced gastrointestinal discomfort, which may include diarrhea and peristalsis dysfunctions. Deleterious effects of histamine can be alleviated with antihistamine drugs targeting histamine receptors. However, many antihistamine agents come with various undesirable side effects. Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Mammalian intestinal mucosa contains an endogenous DAO, yet possessing lower activity compared to that of vDAO preparation. Moreover, in several pathological conditions such as inflammatory bowel disease and irritable bowel syndrome, this endogenous DAO enzyme can be lost or inactivated. Here, we tested the therapeutic potential of vDAO by focusing on the well-known effect of histamine on gut motility. Using ex vivo and in vitro assays, we found that vDAO is more potent than commercial anti-histamine drugs at inhibiting histamine-induced contraction of murine distal colon muscles. We also identified pyridoxal 5′-phosphate (the biologically active form of vitamin B6) as an effective enhancer of vDAO antispasmodic activity. Furthermore, we discovered that rectally administered vDAO can be retained on gut mucosa and remain active. These observations make administration of vDAO in the gut lumen a valid alternative treatment for histamine-induced intestinal dysfunctions.
Engineering pericyte-supported microvascular capillaries in cell-laden hydrogels using stem cells from the bone marrow, dental pulp and dental apical papilla
Authors: Parthiban S. Prakash , He Wenting , Monteiro Nelson , Athirasala Avathamsa , França Cristiane Miranda , Bertassoni Luiz E.
Published: December 2020

Engineered tissue constructs require the fabrication of highly perfusable and mature vascular networks for effective repair and regeneration. In tissue engineering, stem cells are widely employed to create mature vascularized tissues in vitro. Pericytes are key to the maturity of these vascular networks, and therefore the ability of stem cells to differentiate into pericyte-like lineages should be understood. To date, there is limited information regarding the ability of stem cells from the different tissue sources to differentiate into pericytes and form microvascular capillaries in vitro. Therefore, here we tested the ability of the stem cells derived from bone marrow (BMSC), dental pulp (DPSC) and dental apical papilla (SCAP) to engineer pericyte-supported vascular capillaries when encapsulated along with human umbilical vein endothelial cells (HUVECs) in gelatin methacrylate (GelMA) hydrogel. Our results show that the pericyte differentiation capacity of BMSC was greater with high expression of α-SMA and NG2 positive cells. DPSC had α-SMA positive cells but showed very few NG2 positive cells. Further, SCAP cells were positive for α-SMA while they completely lacked NG2 positive cells. We found the pericyte differentiation ability of these stem cells to be different, and this significantly affected the vasculogenic ability and quality of the vessel networks. In summary, we conclude that, among stem cells from different craniofacial regions, BMSCs appear more suitable for engineering of mature vascularized networks than DPSCs or SCAPs.
Cognitive performance and behavior across idiopathic/genetic epilepsies in children and adolescents
Authors: Moorhouse Frederik Jan , Cornell Sonia , Gerstl Lucia , Tacke Moritz , Roser Timo , Heinen Florian , Bonfert Michaela , von Stülpnagel Celina , Wagner Matias , Borggraefe Ingo
Published: December 2020

We investigated the cognitive and behavioral profile of three distinct groups of epilepsies with a genetic background for intergroup differences: (1) idiopathic/genetic generalized epilepsies (IGE/GGE group); (2) idiopathic focal epilepsies (IFE group); and (3) epilepsies with proven or strongly suggested monogenic or structural/numeric chromosomal etiology (genetic epilepsies, GE group). Cognitive (total IQ and subcategories) and behavioral parameters (CBCL) were assessed at the tertiary epilepsy center of the University of Munich (Germany). We used ANOVA with post-hoc Bonferroni-correction to explore significant mean differences and Fisher’s exact test for significant proportional differences of intelligence impairment and behavioral problems. 126 (56 IGE/GGE, 26 IFE, 44 GE) patients were available. Total IQ was 89.0 ± 15.9 (95% CI 84.5–93.4) for IGE/GGE, 94.8 ± 18.1 (95% CI 87.3–102.3) for IFE and 76.4 ± 22.4 (95% CI 67.6–85.3) for GE (p = 0.001). The same trend was significant for all but one IQ subcategory. The rate of patients with an intelligence impairment (total IQ < 70) was higher for GE (40%) than for IGE/GGE (14%) and for IFE (7%) patients (p = 0.033). There were no significant differences between groups for behavior scores and behavioral problems. This study shows that the current ILAE classification of epilepsies with genetic etiology creates a heterogeneous group of patients with respect to cognitive performance but not behavior. These findings may help in further delineating epilepsies as regards cognitive performance, notwithstanding their closely related etiological classification.
Amplitude of low frequency fluctuations (ALFF) of spontaneous and induced rumination in major depression: An fNIRS study
Authors: Rosenbaum David , Int-Veen Isabell , Kroczek Agnes , Hilsendegen Paula , Velten-Schurian Kerstin , Bihlmaier Isabel , Fallgatter Andreas J. , Ehlis Ann-Christine
Published: December 2020

In the current study, we investigated the amplitude of low frequency fluctuations (ALFF) at rest and during a rumination induction. Specifically, we explored the differences of cortical blood oxygenation using fNIRS in subjects with Major Depressive Disorder (MDD) and healthy controls (HC). Rumination was assessed as state and trait measure, as well as with a qualitative semi-structured interview. Qualitative and quantitative measures of rumination indicated that the MDD group showed elevated rumination regarding state and trait measures. Furthermore, rumination differed qualitatively between the groups. The MDD group showed higher levels of general rumination and increased rumination during the rumination induction. However, the MDD group did not show a carry-over effect of elevated rumination after the induction paradigm to the following resting-state measurement. On a neuronal level, we observed a general hypoactivity in the MDD group compared to the HC group. Moreover, both groups showed increased ALFF during the rumination induction compared to the rest phase, especially in temporo-parietal areas. However, no interaction effect of MDD status and rumination induction was found. The current findings are discussed with respect to the literature of paradigms used in the investigation of rumination and suggestions on general improvements in rumination research are given.
Biomass potential of novel interspecific and intergeneric hybrids of Saccharum grown in sub-tropical climates
Authors: Meena Mintu Ram , Kumar Ravinder , Ramaiyan Karuppaiyan , Chhabra Manohar Lal , Raja Arun Kumar , Krishnasamy Mohanraj , Kulshreshtha Neeraj , Pandey Shashi Kant , Ram Bakshi
Published: December 2020

Sugarcane-derived biomass is a promising source of renewable energy to meet the growing demands for biofuel. Currently, modern sugarcane cultivars are unable to provide enough biomass due to their narrow genetic base and susceptibility to abiotic and biotic stresses. We have evaluated total of 23 hybrids derived from diverse genetic backgrounds of different Saccharum spp. and allied genera, one inbred and compared with commercial checks. Intergeneric hybrids (IGHs) KGS 99-100 and GU 04-432, produced significantly higher biomass (43.37 t ha−1 and 35.24 t ha−1, respectively) than commercial sugarcane have genes derived from Erianthus arundinaceus. Interspecific hybrids (ISHs) GU 07-3704 and 99-489, also produced significantly higher amounts of biomass (37.24 t ha−1 and 33.25 t ha−1, respectively) than commercial checks have genes from S. officinarum and S. spontaneum backgrounds. ISHs recorded significantly higher biomass yield, number of stalks and total dry matter percentage whereas, IGH group recorded significantly higher fibre percent. Furthermore, the clones resistant to red rot and sugarcane borers were identified. The estimated energy value for seven hybrid clones was found to be very high. Cluster analysis of genetic traits revealed two major clusters in traits improving biomass. Our study has revealed that the genetic diversity present in these hybrids could be used for improving biomass production and tolerance to abiotic and biotic stresses in cultivated sugarcanes.
Fine-tuning of lysine side chain modulates the activity of histone lysine methyltransferases
Authors: Al Temimi Abbas H. K. , Merx Jona , van Noortwijk Christian J. , Proietti Giordano , Buijs Romano , White Paul B. , Rutjes Floris P. J. T. , Boltje Thomas J. , Mecinović Jasmin
Published: December 2020

Histone lysine methyltransferases (KMTs) play an important role in epigenetic gene regulation and have emerged as promising targets for drug discovery. However, the scope and limitation of KMT catalysis on substrates possessing substituted lysine side chains remain insufficiently explored. Here, we identify new unnatural lysine analogues as substrates for human methyltransferases SETD7, SETD8, G9a and GLP. Two synthetic amino acids that possess a subtle modification on the lysine side chain, namely oxygen at the γ position (KO, oxalysine) and nitrogen at the γ position (KN, azalysine) were incorporated into histone peptides and tested as KMTs substrates. Our results demonstrate that these lysine analogues are mono-, di-, and trimethylated to a different extent by trimethyltransferases G9a and GLP. In contrast to monomethyltransferase SETD7, SETD8 exhibits high specificity for both lysine analogues. These findings are important to understand the substrate scope of KMTs and to develop new chemical probes for biomedical applications.
Eight years of homicide evolution in Monterrey, Mexico: a network approach
Authors: Dorantes-Gilardi Rodrigo , García-Cortés Diana , Hernández-Ramos Hiram , Espinal-Enríquez Jesús
Published: December 2020

Homicide is without doubt one of Mexico’s most important security problems, with data showing that this dismal kind of violence sky-rocketed shortly after the war on drugs was declared in 2007. Since then, violent war-like zones have appeared and disappeared throughout Mexico, causing unfathomable human, social and economic losses. One of the most emblematic of these zones is the Monterrey metropolitan area (MMA), a central scenario in the narco-war. Being an important metropolitan area in Mexico and a business hub, MMA has counted hundreds to thousands of casualties. In spite of several approaches being developed to understand and analyze crime in general, and homicide in particular, the lack of accurate spatio-temporal homicide data results in incomplete descriptions. In order to describe the manner in which violence has evolved and spread in time and space through the city, here we propose a network-based approach. For this purpose, we define a homicide network where nodes are geographical entities that are connected through spatial and temporal relationships. We analyzed the time series of homicides in different municipalities and neighborhoods of the MMA, to observe whether or not a global correlation appeared. We studied the spatial correlation between neighborhoods where homicides took place, to observe whether distance is a factor of influence in the frequency of homicides. We constructed yearly co-occurrence networks, by correlating neighborhoods with homicides happening within a same week, and counting the co-occurrences of these neighborhood pairs in 1 year. We also constructed a crime network by aggregating all data of homicides, eliminating the temporal correlation, in order to observe whether homicide clusters appeared, and what those clusters were distributed geographically. Finally, we correlated the location and frequency of homicides with roads, freeways and highways, to observe if a trend in the homicidal violence appeared. Our network approach in the homicide evolution of MMA allows us to identify that (1) analyzing the whole 86-month period, we observed a correlation between close cities, which decreases in distant places. (2) at neighborhood level, correlations are not distance-dependent, on the contrary, highest co-occurrences appeared between distant neighborhoods and a polygon formed by close neighborhoods in downtown Monterrey. Moreover, (3) An elevated number of homicides occur close to the 85th freeway, which connects MMA with the US border. (4) Some socioeconomic barriers determine the presence of homicide violence. Finally, (5) we show a relation between homicidal crime and the urban landscape by studying the distance of safe and violent neighborhoods to the closest highway and by studying the evolution of highway and crime distance over the cartel-related years and the following period. With this approach, we are able to describe the spatial and temporal evolution of homicidal crime in a metropolitan area.
Exploring of new natural Saudi nanoparticles: investigation and characterization
Authors: El-Sheikhy Refat
Published: December 2020

A new natural nanomaterial in Saudi Arabian soil has been explored. It is green nanoclay consisting of two-dimensional nanoparticles with special properties and dimensions. These nanoparticles are called Saudi halloysite-like nanotubes (SHNTs) because they are similar to halloysite nanotubes (HNTs). SHNTs are transparent having a special cross-section in polygonal shapes, such as hexagonal, with unique dimensions in comparison to that of HNTs. Additionally, external width of SHNTs is 20–50 nm, length is 50–600 nm and can reach 10,000 nm while lumen width of SHNTs is larger than that of HNT, along with SHNTs having thinner walls; these attributes make SHNTs good as nanocontainer. Surface area of SHNTs (168 m2/g) is larger than surface area of HNTs (65 m2/g). SHNTs are bendable with a slight curvature, while HNTs are always straight. Geometry, dimensions, microstructure, chemical composition, surface area and zeta potential of SHNTs are characterized using SEM, TEM, EDX, Langmuir surface area technique, a laser particle size analyser and ZP analysis. SHNTs have many applications in industrial, medical and advanced nanocomposite production. Experimental work has been carried out on nanocomposites made of HDPE reinforced with 5% SHNTs, proving enhancements in mechanical, fracture and thermal properties of original HDPE materials.
New information of dopaminergic agents based on quantum chemistry calculations
Authors: Goode-Romero Guillermo , Winnberg Ulrika , Domínguez Laura , Ibarra Ilich A. , Vargas Rubicelia , Winnberg Elisabeth , Martínez Ana
Published: December 2020

Dopamine is an important neurotransmitter that plays a key role in a wide range of both locomotive and cognitive functions in humans. Disturbances on the dopaminergic system cause, among others, psychosis, Parkinson’s disease and Huntington’s disease. Antipsychotics are drugs that interact primarily with the dopamine receptors and are thus important for the control of psychosis and related disorders. These drugs function as agonists or antagonists and are classified as such in the literature. However, there is still much to learn about the underlying mechanism of action of these drugs. The goal of this investigation is to analyze the intrinsic chemical reactivity, more specifically, the electron donor–acceptor capacity of 217 molecules used as dopaminergic substances, particularly focusing on drugs used to treat psychosis. We analyzed 86 molecules categorized as agonists and 131 molecules classified as antagonists, applying Density Functional Theory calculations. Results show that most of the agonists are electron donors, as is dopamine, whereas most of the antagonists are electron acceptors. Therefore, a new characterization based on the electron transfer capacity is proposed in this study. This new classification can guide the clinical decision-making process based on the physiopathological knowledge of the dopaminergic diseases.
Force enhancement after stretch of isolated myofibrils is increased by sarcomere length non-uniformities
Authors: Haeger Ricarda M. , Rassier Dilson E.
Published: December 2020

When a muscle is stretched during a contraction, the resulting steady-state force is higher than the isometric force produced at a comparable sarcomere length. This phenomenon, also referred to as residual force enhancement, cannot be readily explained by the force-sarcomere length relation. One of the most accepted mechanisms for the residual force enhancement is the development of sarcomere length non-uniformities after an active stretch. The aim of this study was to directly investigate the effect of non-uniformities on the force-producing capabilities of isolated myofibrils after they are actively stretched. We evaluated the effect of depleting a single A-band on sarcomere length non-uniformity and residual force enhancement. We observed that sarcomere length non-uniformity was effectively increased following A-band depletion. Furthermore, isometric forces decreased, while the percent residual force enhancement increased compared to intact myofibrils (5% vs. 20%). We conclude that sarcomere length non-uniformities are partially responsible for the enhanced force production after stretch.
Vegetation structure determines the spatial variability of soil biodiversity across biomes
Authors: Durán Jorge , Delgado-Baquerizo Manuel
Published: December 2020

The factors controlling the spatial variability of soil biodiversity remain largely undetermined. We conducted a global field survey to evaluate how and why the within-site spatial variability of soil biodiversity (i.e. richness and community composition) changes across global biomes with contrasting soil ages, climates and vegetation types. We found that the spatial variability of bacteria, fungi, protists, and invertebrates is positively correlated across ecosystems. We also show that the spatial variability of soil biodiversity is mainly controlled by changes in vegetation structure driven by soil age and aridity. Areas with high plant cover, but low spatial heterogeneity, were associated with low levels of spatial variability in soil biodiversity. Further, our work advances the existence of significant, undescribed links between the spatial variability of soil biodiversity and key ecosystem functions. Taken together, our findings indicate that reductions in plant cover (e.g., via desertification, increases in aridity, or deforestation), are likely to increase the spatial variability of multiple soil organisms and that such changes are likely to negatively impact ecosystem functioning across global biomes.
The mineralogy and structure of use-wear polish on chert
Authors: Schmidt Patrick , Rodriguez Alice , Yanamandra Kaushik , Behera Rakesh K. , Iovita Radu
Published: December 2020

Polished edges of archaeological stone tools are commonly investigated to obtain information on the tools’ uses in prehistory. Yet to this day, it remains unclear what exactly such polishes are and how they form. Answering these questions should allow the elaboration of new interpretative methods based on objective measurements. Two major competing hypotheses of polish formation have been proposed: abrasion and the formation of a thin amorphous film on the chert or flint surface. We employ reflectance infrared spectroscopy, a technique particularly sensitive to thin amorphous films, to investigate these two hypotheses. We found no added amorphous layer that would have formed upon friction against bone, antler, ivory or wood. Our observations suggest polish formation by abrasion, notwithstanding previous claims of added amorphous surface structures. This has implications for our understanding of the physical processes taking place during friction of chert and flint against different materials. Our results also open the possibility to propose new pathways for identifying different use-wear processes, based on the degree of abrasion.
Reflectarray antennas: a smart solution for new generation satellite mega-constellations in space communications
Authors: Imaz-Lueje Borja , Prado Daniel R. , Arrebola Manuel , Pino Marcos R.
Published: December 2020

One of the most ambitious projects in communications in recent years is the development of the so-called satellite mega-constellations. Comprised of hundreds or thousands of small and low-cost satellites, they aim to provide internet services in places without existing broadband access. For the antenna subsystem, reflectarrays have been proposed as a cheap solution due to their low profile and manufacturing costs, while still providing good performance. This paper presents a full design of a reflectarray antenna for mega-constellation satellites with a shaped-beam isoflux pattern for constant power flux in the surface of the Earth. A unit cell consisting of two stacked rectangular microstrip patches backed by a ground plane is employed, providing more than 360° of phase-shift. The generalized intersection approach optimization algorithm is employed to synthesize the required isoflux pattern in a 2 GHz bandwidth in Ku-band. To that purpose, a full-wave electromagnetic analysis is employed for the wideband design. The optimized reflectarray layout complies with the specifications of the isoflux pattern in the frequency band 16 GHz–18 GHz, demonstrating the capabilities of this type of antenna to provide a low-cost, low-profile solution for the user beam segment, including different types of shaped beams.
BEX2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma
Authors: Tamai Keiichi , Nakamura-Shima Mao , Shibuya-Takahashi Rie , Kanno Shin-Ichiro , Yasui Akira , Mochizuki Mai , Iwai Wataru , Wakui Yuta , Abue Makoto , Yamamoto Kuniharu , Miura Koh , Mizuma Masamichi , Unno Michiaki , Kawamura Sadafumi , Sato Ikuro , Yasuda Jun , Yamaguchi Kazunori , Sugamura Kazuo , Satoh Kennichi
Published: December 2020

Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274lowfraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274lowcells, and that BEX2 knockdown decreased the tumorigenicity and G0phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma.
Late Quaternary range shifts of marcescent oaks unveil the dynamics of a major biogeographic transition in southern Europe
Authors: Vila-Viçosa Carlos , Gonçalves João , Honrado João , Lomba Ângela , Almeida Rubim S. , Vázquez Francisco Maria , Garcia Cristina
Published: December 2020

Marcescent forests are ecotones distributed across southern Europe that host increased levels of biodiversity but their persistence is threatened by global change. Here we study the range dynamics of these forests in the Iberian Peninsula (IP) during the Late Quaternary, a period of profound climate and anthropic changes. We modeled and compared the distribution of eight oak taxa for the present and two paleoclimatic environments, the Last Glacial Maximum (LGM, ~ 21 kya) and the Mid-Holocene (MH, ~ 6 kya). Presence records were combined with bioclimatic and topographic data in an ensemble modelling framework to obtain spatial projections for present and past conditions across taxa. Substantial distribution shifts were projected between the three studied periods, that were explained by precipitation, winter cold and terrain ruggedness. Results were congruent with paleoclimatic records of the IP and showed that range shifts of these contact zones concurred with range dynamics of both Submediterranean and Temperate oaks. Notably, the distribution ranges of hybrid oaks and marcescent forests matched throughout the late Quaternary. This study contributes to unveil the complex Late-Quaternary biogeography of the ecotone belt occupied by marcescent forests and, more broadly, of Mediterranean oaks. Improved knowledge of species’ responses to climate dynamics will allow us to anticipate and manage future range shifts driven by climate change.
Phage lysin that specifically eliminates Clostridium botulinum Group I cells
Authors: Zhang Zhen , Lahti Meeri , Douillard François P. , Korkeala Hannu , Lindström Miia
Published: December 2020

Clostridium botulinum poses a serious threat to food safety and public health by producing potent neurotoxin during its vegetative growth and causing life-threatening neuroparalysis, botulism. While high temperature can be utilized to eliminate C. botulinum spores and the neurotoxin, non-thermal elimination of newly germinated C. botulinum cells before onset of toxin production could provide an alternative or additional factor controlling the risk of botulism in some applications. Here we introduce a putative phage lysin that specifically lyses vegetative C. botulinum Group I cells. This lysin, called CBO1751, efficiently kills cells of C. botulinum Group I strains at the concentration of 5 µM, but shows little or no lytic activity against C. botulinum Group II or III or other Firmicutes strains. CBO1751 is active at pH from 6.5 to 10.5. The lytic activity of CBO1751 is tolerant to NaCl (200 mM), but highly susceptible to divalent cations Ca2+ and Mg2+ (50 mM). CBO1751 readily and effectively eliminates C. botulinum during spore germination, an early stage preceding vegetative growth and neurotoxin production. This is the first report of an antimicrobial lysin against C. botulinum, presenting high potential for developing a novel antibotulinal agent for non-thermal applications in food and agricultural industries.
Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo
Authors: Kurosu Takeshi , Hanabara Keiko , Asai Azusa , Pambudi Sabar , Phanthanawiboon Supranee , Omokoko Magot Diata , Ono Ken-ichiro , Saijo Masayuki , Ramasoota Pongrama , Ikuta Kazuyoshi
Published: December 2020

In a secondary dengue virus (DENV) infection, the presence of non-neutralizing antibodies (Abs), developed during a previous infection with a different DENV serotype, is thought to worsen clinical outcomes by enhancing viral production. This phenomenon is called antibody-dependent enhancement (ADE) of infection, and it has delayed the development of therapeutic Abs and vaccines against DENV, as they must be evaluated for the potential to induce ADE. Unfortunately, limited replication of DENV clinical isolates in vitro and in experimental animals hinders this evaluation process. We have, therefore, constructed a recombinant chimeric flavivirus (DV2ChimV), which carries premembrane (prM) and envelope (E) genes of type 2 DENV (DENV-2) R05-624 clinical (Thai) isolate in a backbone of Japanese encephalitis virus (Nakayama strain). DENV E-protein is the most important viral target, not only for neutralizing Abs, but also for infection-enhancing Abs. In contrast to DENV-2 R05-624, DV2ChimV replicated efficiently in cultured mammalian cells and was lethal in interferon-α/β–γ-receptor double-knockout mice. With DV2ChimV, we were able to perform neutralization assays, in vitro and in vivo ADE assays, and in vivo protection assays. These results suggest that the chimeric virus is a powerful tool for evaluation of Abs against DENV.
Effect of straw and inhibitors on the fate of nitrogen applied to paddy soil
Authors: Yu Chunxiao , Xie Xueshi , Yang Hengzhe , Yang Lijie , Li Wentao , Wu Kaikuo , Zhang Weiming , Feng Chen , Li Dongpo , Wu Zhijie , Zhang Lili
Published: December 2020

A pot experiment was used to explore the distribution of fertilizer N and agronomic effects in a paddy soil-rice (Oryza sativa L.) system. Five treatments were set: without nitrogen, straw and inhibitor (C), urea (U), urea + straw (US), urea + urease + nitrification inhibitor (UI) and urea + urease + nitrification inhibitor + straw (UIS). Soil and urea-derived microbial biomass N increased significantly in US and UIS compared with straw-free treatments at seedling and tillering, indicating that biotic process play an important role in the retention of fertilizer N with straw addition. About 10% urea-N was recovered as fixed ammonium (FA) at seedling stage, subsequently released at tillering and maturation regardless of treatments, which emphasizes the importance of FA in the retention and supply of fertilizer N in paddy soils. Compared with U, rice yield and N uptake in US decreased by 7.8% and 25.2% respectively, while inhibitors (UIS) alleviated the reduction by 16.4% and 31.6%. The current research indicated UIS is recommended as the most appropriate management strategy in paddy soils of Northeast China based on N dynamics. But the economic effect as well as the field-scale validation need to be further evaluated.
Microbubble formulation influences inflammatory response to focused ultrasound exposure in the brain
Authors: McMahon Dallan , Lassus Anne , Gaud Emmanuel , Jeannot Victor , Hynynen Kullervo
Published: December 2020

Focused ultrasound and microbubble (FUS + MB)-mediated blood–brain barrier (BBB) permeability enhancement can facilitate targeted brain-drug delivery. While controlling the magnitude of BBB permeability enhancement is necessary to limit tissue damage, little work has attempted to decouple these concepts. This work investigated the relationship between BBB permeability enhancement and the relative transcription of inflammatory mediators 4 h following sonication. Three microbubble formulations, Definity, BG8774, and MSB4, were compared, with the dose of each formulation normalized to gas volume. While changes in the transcription of key proinflammatory mediators, such as Il1b, Ccl2, and Tnf, were correlated to the magnitude of BBB permeability enhancement, these correlations were not independent of microbubble formulation; microbubble size distribution may play an important role, as linear regression analyses of BBB permeability magnitude versus differential gene expression for these proinflammatory mediators revealed significantly greater slopes for MSB4, a monodisperse microbubble with mean diameter of 4 μm, compared to Definity or BG8774, both polydisperse microbubbles with mean diameters below 2 μm. Additionally, the function of an acoustic feedback control algorithm, based on the detection threshold of ultraharmonic emissions, was assessed. While this control strategy was effective in limiting both wideband emissions and red blood cell extravasation, microbubble formulation was found to influence the magnitude of BBB leakage and correlations to acoustic emissions. This work demonstrates that while the initial magnitude of FUS + MB-mediated BBB permeability enhancement has a clear influence on the subsequent inflammatory responses, microbubble characteristics influence these relationships and must also be considered.
Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni
Authors: Amaral Murilo S. , Maciel Lucas F. , Silveira Gilbert O. , Olberg Giovanna G. O. , Leite João V. P. , Imamura Lucas K. , Pereira Adriana S. A. , Miyasato Patricia A. , Nakano Eliana , Verjovski-Almeida Sergio
Published: December 2020

Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects more than 200 million people worldwide. There is only one drug indicated for treatment, praziquantel, which may lead to parasite resistance emergence. The ribonucleoside analogue 5-azacytidine (5-AzaC) is an epigenetic drug that inhibits S. mansoni oviposition and ovarian development through interference with parasite transcription, translation and stem cell activities. Therefore, studying the downstream pathways affected by 5-AzaC in S. mansoni may contribute to the discovery of new drug targets. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein coding potential that have been involved in reproduction, stem cell maintenance and drug resistance. We have recently published a catalog of lncRNAs expressed in S. mansoni life-cycle stages, tissues and single cells. However, it remains largely unknown if lncRNAs are responsive to epigenetic drugs in parasites. Here, we show by RNA-Seq re-analyses that hundreds of lncRNAs are differentially expressed after in vitro 5-AzaC treatment of S. mansoni females, including intergenic, antisense and sense lncRNAs. Many of these lncRNAs belong to co-expression network modules related to male metabolism and are also differentially expressed in unpaired compared with paired females and ovaries. Half of these lncRNAs possess histone marks at their genomic loci, indicating regulation by histone modification. Among a selected set of 8 lncRNAs, half of them were validated by RT-qPCR as differentially expressed in females, and some of them also in males. Interestingly, these lncRNAs are also expressed in other life-cycle stages. This study demonstrates that many lncRNAs potentially involved with S. mansoni reproductive biology are modulated by 5-AzaC and sheds light on the relevance of exploring lncRNAs in response to drug treatments in parasites.
Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels
Authors: Kawai Masanobu , Kinoshita Saori , Ozono Keiichi , Michigami Toshimi
Published: December 2020

Fibroblast growth factor 23 (FGF23) has been centric to the regulation of phosphate (Pi) metabolism; however, the regulatory network of FGF23 in osteocytes has not yet been defined in detail. We herein investigated the role of PTEN (phosphatase and tensin homolog deleted from chromosome 10) in this regulation. We created mice lacking PTEN expression mainly in osteocytes by crossingPten-flox mice withDmp1-Cre mice. The lack of PTEN in the osteocytes of these mice was associated with decreased skeletal and serum intact FGF23 levels, which, in turn, resulted in reductions of urinary Pi excretion and elevations of serum Pi levels. Mechanistically, the knockdown of PTEN expression in osteoblastic UMR106 cells activated the AKT/mTORC1 (mechanistic target of rapamycin complex 1) pathway and this was associated with reductions inFgf23expression. Furthermore, the suppression ofFgf23expression by PTEN knockdown or insulin simulation in UMR106 cells was partially restored by the treatment with the mTORC1 inhibitor, rapamycin. These results suggest that FGF23 expression in osteoblastic cells is in part regulated through the AKT/mTORC1 pathway and provide new insights into our understanding of the regulatory network of Pi metabolism.
Early immune innate hallmarks and microbiome changes across the gut during Escherichia coli O157: H7 infection in cattle
Authors: Larzábal Mariano , Da Silva Wanderson Marques , Multani Anmol , Vagnoni Lucas E. , Moore Dadin P. , Marin Maia S. , Riviere Nahuel A. , Delgado Fernando O. , Vilte Daniel A. , Victorica Matias Romero , Ma Tao , Le Guan Luo , Talia Paola , Cataldi Angel , Cobo Eduardo R.
Published: December 2020

The zoonotic enterohemorrhagicEscherichia coli(EHEC) O157: H7 bacterium causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS) in humans. Cattle are primary reservoirs and EHEC O157: H7; the bacteria predominately inhabit the colon and recto-anal junctions (RAJ). The early innate immune reactions in the infected gut are critical in the pathogenesis of EHEC O157: H7. In this study, calves orally inoculated with EHEC O157: H7 showed infiltration of neutrophils in the lamina propria of ileum and RAJ at 7 and 14 days post-infection. Infected calves had altered mucin layer and mast cell populations across small and large intestines. There were differential transcription expressions of key bovine β defensins, tracheal antimicrobial peptide (TAP) in the ileum, and lingual antimicrobial peptide (LAP) in RAJ. The main Gram-negative bacterial/LPS signaling Toll-Like receptor 4 (TLR4) was downregulated in RAJ. Intestinal infection with EHEC O157: H7 impacted the gut bacterial communities and influenced the relative abundance ofNegativibacillusandErysipelotrichaceaein mucosa-associated bacteria in the rectum. Thus, innate immunity in the gut of calves showed unique characteristics during infection with EHEC O157: H7, which occurred in the absence of major clinical manifestations but denoted an active immunological niche.
Solid State Chemistry: Computational Chemical Analysis for Materials Science
Authors: Lora da Silva Estelina , Galmarini Sandra , Maurizi Lionel , Cesar dos Santos Mario Jorge , Yang Tao , Cooke David J. , Molinari Marco
Published: December 2020

We present an overview of computational analytical methodologies and protocols applied to materials analysis, and their surfaces and interfaces with the surrounding environments. As we discuss the current advances and limitations of in-silico measurements applied to materials science, we highlight their complementary achievements and their innovative predictions in view of their experimental counterparts. We focus on elemental, structural and chemical analyses of complex advanced materials, for either homogeneous or heterogeneous targets.
Nanoparticle-mediated gene therapy strategies for mitigating inflammatory bowel disease
Authors: Verma Priyanka , Srivastava Aasheesh , Srikanth C. V. , Bajaj Avinash
Published: December 2020

Review presents the advances in design of biomaterials for gene therapy to mitigate the inflammatory bowel disease, and challenges associated with oral delivery of gene therapeutics.
Photocatalytic water oxidation with a Prussian blue modified brown TiO2
Authors: Gundogdu Gulsum , Ulusoy Ghobadi T. Gamze , Sadigh Akbari Sina , Ozbay Ekmel , Karadas Ferdi
Published: December 2020

A CoFe Prussian blue analogue is coupled with brown TiO2 nanoparticles to achieve an earth-abundant photocatalytic water oxidation assembly.
Carbon (sp3) tetrel bonding mediated BODIPY supramolecular assemblyviaunprecedented synergy of Csp3⋯N and Csp3⋯F pair interactions
Authors: Ayhan Mehmet Menaf , Özcan Emrah , Dedeoglu Burcu , Chumakov Yurii , Zorlu Yunus , Coşut Bünyemin
Published: December 2020

Here, we present the first example of sp3hybridized carbon centered (Csp3) tetrel bonding mediated 3D BODIPY assemblyviathe exceptional synergy of Csp3⋯N and Csp3⋯F pair interactions.
Comparative study of the elastic properties of adamantane and 1-chloroadamantane at high pressure and different temperatures and at order–disorder transitions
Authors: Gromnitskaya Elena L. , Danilov Igor V. , Brazhkin Vadim V.
Published: December 2020

The disorder–order phase transition is easily detected by jumps in the volume and velocities of ultrasound, while the bulk modulus B practically does not change.