bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Photothermal/Chemotherapy of Melanoma Cells with Albumin Nanoparticles Carrying Indocyanine Green and Doxorubicin Leads to Immunogenic Cell Death
Authors: Heshmati Aghda Niloofar , Torres Hurtado Susana , Abdulsahib Shahad M. , Lara Emilio J. , Tunnell James W. , Betancourt Tania
Published: November 2021

Recent focus on cancer immunotherapies has led to significant interest in the development of therapeutic strategies that can lead to immunogenic cell death (ICD), which can cause activation of an immune response against tumor cells and improve immunotherapy outcomes by enhancing the immunogenicity of the tumor microenvironment. In this work, a nanomedicine‐mediated combination therapy is used to deliver the ICD inducers doxorubicin (Dox), a chemotherapeutic agent, and indocyanine green (ICG), a photothermal agent. These agents are loaded into nanoparticles (NPs) of bovine serum albumin (BSA) that are prepared through a desolvation process. The formulation of BSA NPs is optimized to achieve NPs of 102.6  nm in size and loadings of 8.55 % and 5.69 % (w/w) for ICG and Dox, respectively. The controlled release of these agents from the BSA NPs is confirmed. Upon laser irradiation for 2.5 min, NPs at a dose of 62.5 μg mL−1 are able to increase the temperature of the cells by 7 °C and thereby inhibit the growth of B16F10 melanoma cells in vitro. Surface presentation of heat shock proteins and calreticulin from the cells after treatment confirmed the ability of the Dox/ICG loaded BSA NPs to induce ICD in the melanoma cells.
Synthesis of Precisely Structured Olefin Copolymers by Phenylseleno Oxidation Elimination
Authors: Xu Bin , Liu Shaoxiang , Li Yingying , Zhang Jiandong , Pan Xiangqiang , Zhu Jian
Published: November 2021

Selenium‐containing polymers have attracted considerable attention due to their unique redox responsiveness. Here, phenyl vinyl selenide (PVSe), as a functional selenium‐containing monomer, is polymerized with maleimide (MI) or its derivatives by reversible addition–fragmentation chain transfer polymerization. The resulting polymers are characterized by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy and proton nuclear magnetic resonance spectra, which particularly prove the obtaining of alternating polymers through the polymerization of PVSe and MI or its derivatives. Properties of the resulting polymers are systematically investigated, such as glass transition temperature, thermal performance, and refractive indices. What's more, based on phenylseleno oxidation elimination, the alternating polymers are oxidized through 30% H2O2 to form precisely structured olefin copolymers with carboncarbon (CC) double bonds. The selective generation of double bonds in the alternating polymers is systematically studied. The efficiency of such oxidation is very high under mild conditions due to low electronegativity and bond energy of carbonselenium (CSe) bond, which provides a novel method to prepare precisely structured olefin copolymers with MI or its derivatives.
Almost sectorial operators on Ψ‐Hilfer derivative fractional impulsive integro‐differential equations
Authors: Karthikeyan Kulandhivel , Karthikeyan Panjaiyan , Baskonus Haci Mehmet , Venkatachalam Kuppusamy , Chu Yu‐Ming
Published: November 2021

This paper is concerned with the existence results of Ψ‐Hilfer fractional impulsive integro‐differential equations involving almost sectorial operators. The mild solutions of the problems are proved by using Schauder fixed‐point theorem along with measure of noncompactness. We have discussed the two cases of operators associated semigroup. Also, we consider an abstract application via Hilfer fractional derivative system to verify the results.
An iterative prediction method for designing the moderator used for the boron neutron capture therapy
Authors: Zhang Ruiqin , Yu Yangyi , Zhang Zhi , Yang Yigang
Published: November 2021

Purpose

To conduct research related to slow neutrons, fast neutrons must be mode‐rated and shifted to the desired energy region.

Methods

In this research, an iterated prediction method, in which the neutron transportation properties of all materials were characterized by a reflection matrix, , and a transmission matrix, , was proposed to bypass a time‐consuming Monte Carlo simulation and predict the performance of the moderator, including the epithermal neutron flux and the dose of fast neutrons and gamma rays, used for boron neutron capture therapy (BNCT). To find the optimal solution in the huge parameter space, a genetic algorithm combined with transmission and reflection matrices was utilized.

Results

The results showed that a 70‐loop iteration was able to find a design for the moderator of BNCT with almost 80 higher epithermal neutron flux per kilowatt than that of the empirically optimized moderator that was previously reported in the literature. Compared with the Monte Carlo method, this method had the advantage of reducing the calculation time and statistical errors.

Conclusion

The genetic algorithm with matrices (GAM) method can be used to find an optimal solution in a huge parameter space without brute‐force calculations. It could be a promising method for designing the moderator for thermal or epithermal neutron usages.
Fundraiser turnover in higher education capital campaigns: Employment fluctuations by campaign phase
Authors: Swatek Chloe M. , Lindsey Angela B. , Jones Jennifer A.
Published: November 2021

Comprehensive capital campaigns are used throughout the nonprofit sector and are a particularly important fundraising mechanism for institutions of higher education. These campaigns typically have goals ranging from the millions to the billions and last anywhere from 2 to 5 years, sometimes longer. This explanatory sequential mixed‐methods case study examined employment fluctuation during a 7‐year capital campaign at a foundation for a university in the Southwestern United States. Specifically, we used three methods to reconstruct and explain employment fluctuation (quantitative analysis, document review, and key informant interviews). Employment did indeed fluctuate throughout the campaign: most new hires occurred in the beginning of the campaign and most terminations occurred toward the end. Senior fundraisers were terminated at a greater rate. Most of the exiting employees transitioned to jobs in the traditional nonprofit sector or continued in higher education fundraising. Potential reasons for and implications of the turnover are discussed.
A route towards high‐efficiency silicon heterojunction solar cells
Authors: Duan Weiyuan , Lambertz Andreas , Bittkau Karsten , Qiu Depeng , Qiu Kaifu , Rau Uwe , Ding Kaining
Published: November 2021

In this work, we propose a route to achieve a certified efficiency of up to 24.51% for silicon heterojunction (SHJ) solar cell on a full‐size n‐type M2 monocrystalline‐silicon Cz wafer (total area, 244.53 cm2) by mainly improving the design of the hydrogenated intrinsic amorphous silicon (a‐Si:H) on the rear side of the solar cell and the back reflector. A dense second intrinsic a‐Si:H layer with an optimized thickness can improve the vertical carrier transport, resulting in an improved fill factor (FF). In order to reduce the plasmonic absorption at the back reflector, a low‐refractive‐index magnesium fluoride (MgF2) is deposited before the Ag layer; this leads to an improved gain of short circuit current density (Jsc). In total, together with MgF2 double antireflection coating and other fine optimizations during cell fabrication process, ~1% absolute efficiency enhancement is finally obtained. A detailed loss analysis based on Quokka3 simulation is presented to confirm the design principles, which also gives an outlook of how to improve the efficiency further.
A structural feature of Dda helicase which enhances displacement of streptavidin and trp repressor from DNA
Authors: Byrd Alicia K. , Malone Emory G. , Hazeslip Lindsey , Zafar Maroof Khan , Harrison David K. , Thompson Matthew D. , Gao Jun , Perumal Senthil K. , Marecki John C. , Raney Kevin D.
Published: November 2021

Helicases are molecular motors with many activities. They use the energy from ATP hydrolysis to unwind double‐stranded nucleic acids while translocating on the single‐stranded DNA. In addition to unwinding, many helicases are able to remove proteins from nucleic acids. Bacteriophage T4 Dda is able to displace a variety of DNA binding proteins and streptavidin bound to biotinylated oligonucleotides. We have identified a subdomain of Dda that when deleted, results in a protein variant that has nearly wild type activity for unwinding double‐stranded DNA but exhibits greatly reduced streptavidin displacement activity. Interestingly, this domain has little effect on displacement of either gp32 or BamHI bound to DNA but does affect displacement of trp repressor from DNA. With this variant, we have identified residues which enhance displacement of some proteins from DNA.
Structure–activity relationship studies of allosteric inhibitors of EYA2 tyrosine phosphatase
Authors: Anantharajan Jothi , Baburajendran Nithya , Lin Grace , Loh Yong Yao , Xu Weijun , Ahmad Nur Huda Binte , Liu Shuang , Jansson Anna E. , Kuan John Wee Liang , Ng Elizabeth Yihui , Yeo Yee Khoon , Hung Alvin W. , Joy Joma , Hill Jeffrey , Ford Heide L. , Zhao Rui , Keller Thomas H. , Kang CongBao
Published: November 2021

Human eyes absent (EYA) proteins possess Tyr phosphatase activity, which is critical for numerous cancer and metastasis promoting activities, making it an attractive target for cancer therapy. In this work, we demonstrate that the inhibitor‐bound form of EYA2 does not favour binding to Mg2+, which is indispensable for the Tyr phosphatase activity. We further describe characterization and optimization of this class of allosteric inhibitors. A series of analogues were synthesized to improve potency of the inhibitors and to elucidate structure–activity relationships. Two co‐crystal structures confirm the binding modes of this class of inhibitors. Our medicinal chemical, structural, biochemical, and biophysical studies provide insight into the molecular interactions of EYA2 with these allosteric inhibitors. The compounds derived from this study are useful for exploring the function of the Tyr phosphatase activity of EYA2 in normal and cancerous cells and serve as reference compounds for screening or developing allosteric phosphatase inhibitors. Finally, the co‐crystal structures reported in this study will aid in structure‐based drug discovery against EYA2.
Elucidating important structural features for the binding affinity of spike ‐ SARS‐CoV‐2 neutralizing antibody complexes
Authors: Sharma Divya , Rawat Puneet , Janakiraman Vani , Gromiha M. Michael
Published: November 2021

The coronavirus disease 2019 (COVID‐19) has affected the lives of millions of people around the world. In an effort to develop therapeutic interventions and control the pandemic, scientists have isolated several neutralizing antibodies against SARS‐CoV‐2 from the vaccinated and convalescent individuals. These antibodies can be explored further to understand SARS‐CoV‐2 specific antigen–antibody interactions and biophysical parameters related to binding affinity, which can be utilized to engineer more potent antibodies for current and emerging SARS‐CoV‐2 variants. In the present study, we have analyzed the interface between spike protein of SARS‐CoV‐2 and neutralizing antibodies in terms of amino acid residue propensity, pair preference, and atomic interaction energy. We observed that Tyr residues containing contacts are highly preferred and energetically favorable at the interface of spike protein–antibody complexes. We have also developed a regression model to relate the experimental binding affinity for antibodies using structural features, which showed a correlation of 0.93. Moreover, several mutations at the spike protein–antibody interface were identified, which may lead to immune escape (epitope residues) and improved affinity (paratope residues) in current/emerging variants. Overall, the work provides insights into spike protein–antibody interactions, structural parameters related to binding affinity and mutational effects on binding affinity change, which can be helpful to develop better therapeutics against COVID‐19.
Topical and dietary toxicity of emamectin benzoate, chlorantraniliprole, cyantraniliprole and indoxacarb to larvae of the common armyworm Mythimna convecta (Lepidoptera: Noctuidae)
Authors: Stevens Mark M , Warren Glen N , Mo Jianhua
Published: November 2021

BACKGROUND

The common armyworm Mythimna convecta is an important pest of pastures and graminaceous crops in Australia, but materials currently registered for its control are limited to broad‐spectrum compounds incompatible with integrated pest management (IPM) systems. In this study we assessed the response of M. convecta larvae to four alternative compounds using topical and dietary bioassays.

RESULTS

Emamectin benzoate [LC50 (lethal concentration for 50% of insects tested) values 2.69 μg mL−1 topical, 0.017 μg active ingredient (AI) g−1 dietary] and chlorantraniliprole (LC50 values 4.87 μg mL−1 topical, 0.080 μg AI g−1 dietary) were significantly more active than either indoxacarb or cyantraniliprole. Our results showed strong parallels with data on the more extensively studied Australian strains of Helicoverpa armigera, with the most notable differences being the higher contact toxicity of emamectin benzoate to M. convecta and the lower acute dietary activity of formulated cyantraniliprole to this species, which was linked to feeding deterrence. Cyantraniliprole at dietary concentrations of ≥0.02 μg AI g−1 significantly reduced the weight of surviving larvae and frass production (an indirect measure of food consumption) over the seven‐day exposure period. There was also some evidence of chlorantraniliprole deterring larval feeding, although to a much more limited extent.

CONCLUSIONS

Both emamectin benzoate and chlorantraniliprole are suitable for use against M. convecta. The decision as to which of these compounds should be prioritized for further development should be based on their potential effects on beneficial species once their optimal field rates have been determined.
Hydrologic connectivity and land cover affect floodplain lake water quality, fish abundance, and fish diversity in floodplain lakes of the Wabash‐White River basin
Authors: Carlson Mazur Martha L. , Smith Bradley , Bird Broxton , McMillan Sara , Pyron Mark , Hauswald Cassie
Published: November 2021

Floodplain lakes are important aquatic resources for supporting ecosystem services, such as organismal habitat, biodiversity, and the retention of nutrients and sediment. Due to geomorphic alteration of river channels and land‐cover change, degradation to floodplain lakes in the Ohio River basin is occurring at a rate that will escalate as climate change causes increased flood intensity and the seasonal redistribution of rainfall. A better understanding of the local drivers that affect oxbow lakes is needed for targeted floodplain restoration efforts designed to slow degradation. We examined the effects of land cover, topography, and hydrologic connectivity on water quality and fish diversity and abundance in nine floodplain lakes with potentially high remnant ecological function in the Wabash‐White watershed (Indiana, Ohio, and Illinois). Data collection included water‐quality parameters; stable water isotopes; total phosphorus, total nitrogen, and chlorophyll‐a; and fish community diversity and abundance. Results indicate that hay/pasture land cover and decreased topographic relief in the local oxbow watersheds, along with reduced river hydrologic connectivity, were related to an increase in total phosphorus, total nitrogen, and chlorophyll‐a. Greater biodiversity and abundance in fish assemblages were evident in oxbow lakes that were more disconnected from the main channel. The results of this study suggest that hydrologic connectivity of oxbow lakes with the contributing drainage area and the main channel influence nutrients and fish communities. Knowing the influencing factors can help ecosystem managers better protect these valuable floodplain lake ecosystems and prioritize restoration efforts amidst increasing stressors due to climate and land‐use changes.
On‐field test campaign performance of VDE‐SAT Link ID 20 over Norsat‐2 LEO satellite
Authors: Andreotti Riccardo , Nanna Leonardo , Andrenacci Marco , Isca Agostino , Haugli Hans‐Christian , Alagha Nader
Published: November 2021

The latest technical recommendation by the International Telecommunication Union (ITU) for a data exchange system in the VHF maritime mobile band defines a random access channel (RAC) for communications on the uplink channel between vessels and satellites. The physical layer frame for random uplink channel is designed to allow for a more efficient use of the power amplifiers and includes features to assist the satellite receivers to resolve overlapping reception of multiple messages. This paper presents the performance results of an over‐the‐air test campaign carried out exploiting the NorSat‐2 Low Earth orbit (LEO) satellite. After a review of the VDE‐SAT RAC and Link ID 20 burst, a possible demodulator implementation is shown. Then, the VDE‐SAT transmitter platform, located in Pisa, Italy, emulating a population of vessels transmitting to the NorSat‐2 LEO satellite is introduced, and the test cases are described. Afterward, the analysis of the recorded signals is provided. The post‐analysis first focuses on the demodulation performance in terms of probability of successful demodulation of the interfering bursts. Further investigation has also been carried out to better understand the interference environment in this frequency band for satellite signal reception. Tests indicate promising results of successfully detecting and demodulating up to 22 overlapping RAC messages, confirming the robustness of the protocol. Finally, capitalizing on the above analysis, conclusions suggest possible improvements.
First occurrence of Nyssa endocarps and associated fungi in the Oligocene of South China: palaeogeographical and palaeoecological significance
Authors: Xu Sheng‐Lan , Kodrul Tatiana M. , Maslova Natalia P. , Song Han‐Zhang , Tobias Anna V. , Wu Xin‐Kai , Quan Cheng , Jin Jian‐Hua
Published: November 2021

Co‐evolutionary relationships of plants and fungi are of great importance for the phylogeny of both groups. Nyssa was widely distributed in the northern hemisphere during the Cenozoic. Extant species of Nyssa exhibit a disjunct distribution between eastern North America, Central America and East Asia. Here, a new species, Nyssa nanningensis Xu & Jin, is described based on fruit endocarps from the upper Oligocene Yongning Formation of the Nanning Basin, South China. This new fossil record of Nyssa expands the known palaeogeographical distribution of the genus to the low latitudes of East Asia. Associated fossil fungal fruiting bodies on Nyssa endocarps are assigned to the new fossil genus and species, Yongnicta nyssae Tobias & Maslova. This new genus is similar to some members of extant wood destructor taxa Coronophorales and Amphisphaeriales (Sordariomycetes, Ascomycota). About 3% of the Nyssa endocarps studied were affected by Yongnicta nyssae. Low frequency of fruit damage indicates that endocarps could be released from mesocarps by animals eating fleshy parts of fruits, making them potentially available to wood‐destroying fungi.
IKEA Wien Westbahnhof – Eine nachhaltige Oase im Großstadtdschungel
Authors: Mühl Bernd , Salzer Christian
Published: November 2021

Am Wiener Westbahnhof entstand ein innovatives und einladendes Einrichtungshaus. Mit seinen begrünten Fassaden und viel Raum für die Menschen – von ansprechender Gastronomie bis zur allgemein zugänglichen begrünten Dachterrasse – ist es so viel mehr als nur ein Einrichtungshaus. Insgesamt umfasst das Gebäude 25.000 m2 auf sieben Geschossen. Der Möbelriese selbst nutzt fünf der Geschosse – in den beiden obersten Etagen befindet sich ein Hotel mit 345 Betten, das Konzept ist besonders auf junge Geschäftsreisende ausgerichtet. Als besonderer Kontrapunkt zu historisch massiven Fassaden stellt „das Hus“, wie es liebevoll von IKEA genannt wird, mit seiner umhüllenden und frei sichtbaren Stahlkonstruktion eine Besonderheit im städtischen Raum dar. Sein offenes, transparentes Regalsystem spendet Schatten, reduziert die sommerliche Überhitzung der Fassaden und beeinflusst durch die umfangreiche Bepflanzung das Mikroklima der Umgebung nachweislich. In der Dachzone trägt die Stahl‐Pergola eine 800 m2 große Photovoltaikanlage. Das Gebäude ist ein Vorreiter in Sachen Nachhaltigkeit und wurde deshalb mit dem Greenpass‐Platinum‐Zertifikat ausgezeichnet. Das nachhaltige Einrichtungshaus am Wiener Westbahnhof ist auf Fußgänger, U‐ und Straßenbahnfahrer sowie Radfahrer ausgerichtet – für Autos gibt es dort keinen Platz. Sperrgut wird frei Haus geliefert, den Rest nimmt man in der bekannten blauen Tasche mit. Zusammenfassend gibt es viel Erlebnis, Gastronomie, Raum zum Bummeln bzw. Schauen und mehr Grün, als es ein ebener Park auf dieser Fläche bieten könnte, denn auf allen Etagen sind Freiflächen mit Grünpflanzen, begrünte Fassadenelemente, Vogelnester, Bienenstöcke und lichtdurchflutete Bereiche.
Fabrication of Oleic Acid Grafted Starch‐based Hybrid Carriers forl‐Asparaginase Encapsulation
Authors: Hafızosmanoğlu Gülşah , Ulu Ahmet , Köytepe Süleyman , Ateş Burhan
Published: November 2021

In this study, artificial red blood cells (RBCs) for immobilization ofl‐asparaginase are developed. The artificial red blood cells are prepared via a self‐assembly method and characterized by various methods. The prepared material shows a small hydrodynamic size of nearly 120 nm and a zeta potential of ‐7.2 ± 0.2 mV. Afterl‐asparaginase encapsulation, the particle size is nearly 295 nm and the zeta potential value is ‐9.8 ± 0.1. As expected, the immobilized enzyme shows better pH stability and thermal stability than the free enzyme. For instance, at 60 °C, the immobilized enzyme maintains 63.5% of the original activity, while the free enzyme retains only 27.6% of the original activity. Furthermore, the immobilized enzyme exhibits excellent reusability and storage stability, retaining 46.1% of its initial activity after 15 reuses. Overall, the developed artificial RBCs can potentially be applied as a novel support for immobilization ofl‐asparaginase.
Chemical Induction of Neurogenic Properties in Mammalian Müller Glia
Authors: Xia Xiaohuan , Teotia Pooja , Patel Hiren , Van Hook Matthew J. , Ahmad Iqbal
Published: November 2021

Müller glia (MG), cells that maintain homeostasis in the retina, are dormant stem cells that can regenerate neurons upon injury. However, the regenerative property of MG, which is reproducibly displayed in the lower vertebrates, is not readily observed in the mammals even upon forced expression of regulatory genes or exposure to growth factors. Here, we demonstrate a reproducible unmasking of the neurogenic properties of enriched rodent MG by serial exposure to different combinations of small molecules. The enriched MG, in response to changing culture conditions, silenced glia-specific genes and acquired transcriptional signature of neurons, accompanied by upregulation of genes known to regulate neuronal potential of MG. The MG-derived neurons expressed immunoreactivities corresponding to neuronal proteins and displayed electrophysiological features of immature neurons. Our study presents a proof of principle of pharmacological activation of neurogenic properties of mammalian MG, which may be utilized for therapeutic regeneration.
Radiotherapy and the immune system: More than just immune suppression
Authors: Rückert Michael , Flohr Ann-Sophie , Hecht Markus , Gaipl Udo S.
Published: November 2021

Radiotherapy (RT) is still one of the standard cancer therapies, with up to two third of all cancer patients with solid tumors being irradiated in the course of their disease. The aim of using ionizing radiation in fractionated treatment schedules was always to achieve local tumor control by inducing DNA damage which can be repaired by surrounding normal tissue but leads to cell death in tumor cells. Meanwhile, it is known that RT also has immunological effects reshaping the tumor microenvironment. Nevertheless, RT alone often fails to elicit potent antitumor immune responses as these effects can be immunostimulatory as well as immunosuppressive. Here, we discuss how immunotherapies can be exploited in combined therapies to boost RT-induced antitumor immune responses or to counteract preexisting and RT-mediated immunosuppression to improve local and systemic tumor control. Furthermore, we highlight some parameters of radioimmunotherapies (RITs) which are under investigation for potential optimizations and how RIT approaches are tested in first phases II and III trials. Finally, we discuss how RT might affect normal and cancer stem cells.
Zbtb46-Dependent Altered Developmental Program in Embryonic Stem Cell-Derived Blood Cell Progenitors
Authors: Boto Pal , Gerzsenyi Timea Beatrix , Lengyel Adel , Szunyog Balint , Szatmari Istvan
Published: November 2021

Zbtb46 is a recently identified dendritic cell (DC)-specific transcription factor with poorly defined biology. Although Zbtb46 is highly expressed in conventional DCs, evidence also points to its presence in erythroid progenitors and endothelial cells suggesting that this factor might influence the early hematopoietic development. Here, we probe the effect of this transcription factor in embryonic stem cell (ESC)-derived blood cell progenitors using chemically inducible mouse cell lines. Unexpectedly, forced expression of this protein elicited a broad repressive effect at the early stage of ESC differentiation. Ectopic expression of Zbtb46 interfered with the mesoderm formation and cell proliferation was also negatively impacted. More importantly, reduced number of CD11b+ myeloid blood cells were generated from ESC-derived Flk1+ mesoderm cells in the presence of Zbtb46. Consistent with this finding, our gene expression profiling revealed that numerous myeloid and immune response related genes, including Irf8, exhibited lower expression in the Zbtb46-primed cells. Despite these repressive effects, however, Zbtb46 overexpression was associated with enhanced formation of erythroid blood cell colonies and increased adult hemoglobin (Hbb-b1) expression at the early phase of ESC differentiation. Moreover, elevated percent of CD105 (Endoglin) positive cells were detected in the Zbtb46-primed samples. In summary, our results support that Zbtb46 suppresses the ESC-derived myeloid development and diverts mesoderm cells toward erythroid developmental pathway. Moreover, our transcriptomic data provide a resource for exploration of the Zbtb46 regulatory network in ESC-derived progenitors.
Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases
Authors: Brunetti Dario , Dykstra Werner , Le Stephanie , Zink Annika , Prigione Alessandro
Published: November 2021

Mitochondria are organelles with recognized key roles in cellular homeostasis, including bioenergetics, redox, calcium signaling, and cell death. Mitochondria are essential for neuronal function, given the high energy demands of the human brain. Consequently, mitochondrial diseases affecting oxidative phosphorylation (OXPHOS) commonly exhibit neurological impairment. Emerging evidence suggests that mitochondria are important not only for mature postmitotic neurons but also for the regulation of neural progenitor cells (NPCs) during the process of neurogenesis. These recent findings put mitochondria as central regulator of cell fate decisions during brain development. OXPHOS mutations may disrupt the function of NPCs and thereby impair the metabolic programming required for neural fate commitment. Promoting the mitochondrial function of NPCs could therefore represent a novel interventional approach against incurable mitochondrial diseases.
DUSP5 Promotes Osteogenic Differentiation Through SCP1/2-Dependent Phosphorylation of SMAD1
Authors: Liu Xuejiao , Liu Xuenan , Du Yangge , Hu Menglong , Tian Yueming , Li Zheng , Lv Longwei , Zhang Xiao , Liu Yunsong , Zhou Yongsheng , Zhang Ping
Published: November 2021

Dual-specificity phosphatases (DUSPs) are defined by their capability to dephosphorylate both phosphoserine/phosphothreonine (pSer/pThr) and phosphotyrosine (pTyr). DUSP5, a member of DUSPs superfamily, is located in the nucleus and plays crucially regulatory roles in the signaling pathway transduction. In our present study, we discover that DUSP5 significantly promotes osteogenic differentiation of mesenchymal stromal cells (MSCs) by activating SMAD1 signaling pathway. Mechanistically, DUSP5 physically interacts with the phosphatase domain of small C-terminal phosphatase 1/2 (SCP1/2, SMAD1 phosphatases) by the linker region. In addition, we further confirm that DUSP5 activates SMAD1 signaling through a SCP1/2-dependent manner. Specifically, DUSP5 attenuates the SCP1/2-SMAD1 interaction by competitively binding to SCP1/2, which is responsible for the SMAD1 dephosphorylation, and thus results in the activation of SMAD1 signaling. Importantly, DUSP5 expression in mouse bone marrow MSCs is significantly reduced in ovariectomized (OVX) mice in which osteogenesis is highly passive, and overexpression of Dusp5 via tail vein injection reverses the bone loss of OVX mice efficiently. Collectively, this work demonstrates that the linker region of DUSP5 maybe a novel chemically modifiable target for controlling MSCs fate choices and for osteoporosis treatment.
Human Multipotent Adult Progenitor Cells Effectively Reduce Graft-vs-Host Disease While Preserving Graft-Vs-Leukemia Activity
Authors: Metheny Leland , Eid Saada , Wuttisarnwattana Patiwet , Auletta Jeffery J. , Liu Chen , Van Dervort Alana , Paez Conner , Lee ZhengHong , Wilson David , Lazarus Hillard M. , Deans Robert , Vant Hof Wouter , Ktena Yiouli , Cooke Kenneth R.
Published: November 2021

Graft-vs-host disease (GvHD) limits successful outcomes following allogeneic blood and marrow transplantation (allo-BMT). We examined whether the administration of human, bone marrow-derived, multipotent adult progenitor cells (MAPCs™) could regulate experimental GvHD. The immunoregulatory capacity of MAPC cells was evaluated in vivo using established murine GvHD models. Injection of MAPC cells on day +1 (D1) and +4 (D4) significantly reduced T-cell expansion and the numbers of donor-derived, Tumor Necrosis Factor Alpha (TNFα) and Interferon Gamma (IFNγ)-producing, CD4+ and CD8+ cells by D10 compared with untreated controls. These findings were associated with reductions in serum levels of TNFα and IFNγ, intestinal and hepatic inflammation and systemic GvHD as measured by survival and clinical score. Biodistribution studies showed that MAPC cells tracked from the lung and to the liver, spleen, and mesenteric nodes within 24 hours after injection. MAPC cells inhibited mouse T-cell proliferation in vitro and this effect was associated with reduced T-cell activation and inflammatory cytokine secretion and robust increases in the concentrations of Prostaglandin E2 (PGE2) and Transforming Growth Factor Beta (TGFβ). Indomethacin and E-prostanoid 2 (EP2) receptor antagonism both reversed while EP2 agonism restored MAPC cell-mediated in vitro T-cell suppression, confirming the role for PGE2. Furthermore, cyclo-oxygenase inhibition following allo-BMT abrogated the protective effects of MAPC cells. Importantly, MAPC cells had no effect on the generation cytotoxic T lymphocyte activity in vitro, and the administration of MAPC cells in the setting of leukemic challenge resulted in superior leukemia-free survival. Collectively, these data provide valuable information regarding the biodistribution and regulatory capacity of MAPC cells, which may inform future clinical trial design.
Downregulation of Augmenter of Liver Regeneration Impairs the Therapeutic Efficacy of Liver Epithelial Progenitor Cells Against Acute Liver Injury by Enhancing Mitochondrial Fission
Authors: Dong Yuan , Kong Weining , An Wei
Published: November 2021

Cell-based therapeutic approaches have been proven to be effective strategies for the treatment of acute liver injury (ALI). However, widespread application of these procedures is limited by several key issues, including rapid loss of stemness in vitro, aberrant differentiation into undesirable cell types, and low engraftment in vivo. In this study, liver epithelial progenitor cells (LEPCs) were characterized and transfected with augmenter of liver regeneration (ALR). The results revealed that in ALI mice with CCl4, the transplantation of ALR-bearing LEPCs into the liver markedly protected mice against ALI by decreasing the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), thus relieving hepatic tissue injury and attenuating inflammatory infiltration. Mechanistically, the knockdown of ALR in LEPCs activated the phosphorylation of dynamin-related protein 1 (Drp1) at the S616 site and thereby enhanced mitochondrial fission. In contrast, the transfection of ALR into LEPCs significantly inhibited Drp1 phosphorylation, thereby favoring the maintenance of mitochondrial integrity and the preservation of adenosine triphosphate contents in LEPCs. Consequently, the ALR-bearing LEPCs transplanted into ALI mice exhibited substantially greater homing ability to the injured liver via the SDF-1/CXCR4 axis than that of LEPCs-lacking ALR. In conclusion, we demonstrated that the transplantation of ALR-transfected LEPCs protected mice against CCl4-induced ALI, thus offering immense curative potential in the clinic.
State-Of-Play for Cellular Therapies in Cardiac Repair and Regeneration
Authors: Vaka Ramana , Davis Darryl R.
Published: November 2021

Cardiovascular disease is the primary cause of death around the world. For almost two decades, cell therapy has been proposed as a solution for heart disease. In this article, we report on the “state-of-play” of cellular therapies for cardiac repair and regeneration. We outline the progression of new ideas from the preclinical literature to ongoing clinical trials. Recent data supporting the mechanics and mechanisms of myogenic and paracrine therapies are evaluated in the context of long-term cardiac engraftment. This discussion informs on promising new approaches to indicate future avenues for the field.
Design‐oriented elasto‐plastic analysis of reinforced concrete structures with in‐plane forces applying convex optimization
Authors: Vestergaard Daniel , Larsen Kasper Paaske , Hoang Linh Cao , Poulsen Peter Noe , Feddersen Bent
Published: November 2021

Assessment of the cracked behavior at service load and verification of sufficient deformation capacity in the ultimate state are often required when designing reinforced concrete structures. Most existing methods dedicated to nonlinear analysis of reinforced concrete, however, are not well‐suited in practice for use in design processes involving large‐scale structural problems due to an enormous modeling effort and lack of numerical stability. This paper presents a new finite element framework for efficient elasto‐plastic analysis of two‐dimensional reinforced concrete structures subjected to in‐plane forces. The basic concept is to adopt a stress‐based finite element formulation and cast the problem as a convex optimization problem where energy principles are invoked through a formalistic application of nonlinear‐elastic material models. The method accounts for reinforcement yielding and concrete crushing, including the strength reduction due to cracking, and can be used to imitate the elasto‐plastic response of fully‐cracked structures subjected to monotonic loading. The efficiency of the method is demonstrated, inter alia, by an analysis of a complex structure, where the discretized problem has more than 1 million variables and is solved within a few minutes on a standard personal computer.
Enhanced dielectric performance of polydimethylsiloxane‐based ternary composites films via tailored hydrogen bonds between carbon nanotube and barium titanate as modified fillers
Authors: Tang Yaokai , Liu Hongfu , Wang Xincheng , Cheng Shangru , Gao Qiangmin , Liu Jiwen , Guan Shanshan , Zhao Shugao
Published: November 2021

A series of BT–cCNT/PDMS and BT–aCNT/PDMS composites were developed by incorporating barium titanate (BT) nanoparticles together with carboxylic functionalized multiwalled carbon nanotubes (cCNT) and amino functionalization multiwalled carbon nanotubes (aCNT) in polydimethylsiloxane (PDMS). Benefitting from the abundant active groups, CNTs and BTs can be in situ “bridged” by hydrogen bond in all of the BT–cCNT/PDMS and BT–aCNT/PDMS composites. Here, we studied the effect of hydrogen bonds (type and amount) between BTs and CNTs at the interface and dielectric properties of the composites. The results indicated that the BT–cCNT/PDMS composite exhibited higher dielectric constant and comparable dielectric loss than the BT–aCNT/PDMS composite, especially when weightCNT < 1 wt%. Also, the dielectric properties of BT–cCNT/PDMS composite show stronger temperature dependence than BT–aCNT/PDMS composite. Finally, the tailorable performance of the polymer‐based dielectric composites can be obtained by regulating the interface with the help of hydrogen bonds.
Flood legislation and land policy framework of EU and non‐EU countries in Southern Europe
Authors: Kapović Solomun Marijana , Ferreira Carla S. S. , Zupanc Vesna , Ristić Ratko , Drobnjak Aleksandar , Kalantari Zahra
Published: November 2021

Floods are a widespread natural hazard affecting people and their assets in regions worldwide, including Southern Europe. Besides coastal floods, the Mediterranean region is highly prone to flash floods driven by short but intense precipitation events. With increasing flood risk due to climate change and socio‐economic conditions, governments are under pressure to reinforce flood protection measures, which could be a great challenge for the weak economies of non‐EU developing countries. This is of particular relevance to achieving international commitments such as the United Nations Sustainable Development Goals. Several policy frameworks have been developed to mitigate flooding risk, at European Union (EU) and global level. These frameworks call for a holistic risk reduction approach where governments, institutions, and households are all responsible for reducing risk. In practice, however, gray infrastructure remains the prevailing flood risk management measure in many countries. Incorporation into national legislation and implementation of the EU policy framework will increase constraints and pressures for non‐EU countries, particularly those strongly committed to becoming EU members in future. This article provides a comprehensive review of policies and measures implemented in four different southern European countries to mitigate flood hazard, and compares governance aspects between EU (Portugal and Slovenia) and non‐EU countries (B&H and Serbia). Understanding governance aspects and the status of flood‐related policy implementation is of critical importance in protecting people and enhancing resilience to climate change impacts. Programs of improvement measures and further integration of sustainable water management with other sectoral policies are required to reduce flood risks.

This article is categorized under:

Engineering Water > Planning Water

Human Water > Water Governance

Science of Water > Water Extremes
Chapter 3: The Role of Food Exports in Russia’s Economy
Authors: Svetlov Nikolai M.
Published: November 2021

As Russia’s agri-food exports have increased in recent years, the role of food exports has evolved from being negligible at the beginning of the 2000s to almost 30 percent of agricultural production in recent years. Agri-food exports account for a substantial amount of growth in the agricultural sector. The contribution of food exports to the national economy, however, is minor. Food exports’ net contribution to the national budget is about zero. Technical advances suggest that the role of agricultural exports in the national economy will keep gradually growing but will remain a secondary factor in national welfare.
Chapter 5: Russia’s Role in International Fish and Seafood Trade
Authors: Nilssen Frode
Published: November 2021

This chapter sheds light on Russia’s changed role in the international seafood trade system and discusses to what extent the new more export-oriented turn is sustainable. Russia’s seafood trade policy has changed significantly over time, from directing just about all of the production to the domestic market during the Soviet period, to increasingly pursuing a dual strategy as both an importer and exporter from 2000 onwards. The first section gives a brief account of Soviet-era seafood production and trade. The second part offers a perspective on seafood trade during the early post-Soviet period. The third part examines how the introduction of Food Security Doctrines and the 2014 embargo have influenced Russia’s seafood trade. The final section provides an outlook for the future. Similar to agriculture, concerns over food security are likely to lead to a reduced role as a seafood importer and a larger role as a seafood exporter. The structure of Russia’s seafood exports will continue to tilt towards Asian markets, with European markets assuming a secondary role.
Conversion of viridicatic acid to crustosic acid by cytochrome P450 enzyme-catalysed hydroxylation and spontaneous cyclisation
Authors: Zhou Jenny , Li Shu-Ming
Published: November 2021

Cytochrome P450 monooxygenases (P450s) are considered nature’s most versatile catalysts and play a crucial role in regio- and stereoselective oxidation reactions on a broad range of organic molecules. The oxyfunctionalisation of unactivated carbon-hydrogen (C-H) bonds, in particular, represents a key step in the biosynthesis of many natural products as it provides substrates with increased reactivity for tailoring reactions. In this study, we investigated the function of the P450 enzyme TraB in the terrestric acid biosynthetic pathway. We firstly deleted the gene coding for the DNA repair subunit protein Ku70 by using split marker-based deletion plasmids for convenient recycling of the selection marker to improve gene targeting in Penicillium crustosum. Hereby, we reduced ectopic DNA integration and facilitated genetic manipulation in P. crustosum. Afterward, gene deletion in the Δku70 mutant of the native producer P. crustosum and heterologous expression in Aspergillus nidulans with precursor feeding proved the involvement of TraB in the formation of crustosic acid by catalysing the essential hydroxylation reaction of viridicatic acid.

Key points

•Deletion of Ku70 by using split marker approach for selection marker recycling.

•Functional identification of the cytochrome P450 enzyme TraB.

•Fulfilling the reaction steps in the terrestric acid biosynthesis.
Emergency Neurosurgery Performed by General Surgeons: A Systematic Review
Authors: Hewitt Joseph N. , Ovenden Christopher D. , Glynatsis John M. , Sabab Ahad , Gupta Aashray K. , Kovoor Joshua G. , Wells Adam J. , Maddern Guy J.
Published: November 2021

Background

In under‐resourced settings, general surgeons may be called upon to perform emergency operations within other specialties. Accordingly, we aimed to characterise patient outcomes after emergency neurosurgery performed by a general surgeon or general surgery trainee.

Methods

PubMed, Embase and the Cochrane Library were searched to 30 May 2021 for observational studies reporting outcomes after emergency neurosurgery performed by a general surgeon. Study screening, data extraction, and risk of bias using the Downs and Black checklist were performed in duplicate. Data on setting, operation undertaken, mortality rates and complications were extracted. Meta‐analysis was planned but not possible due to heterogeneity. This study is registered with PROSPERO, CRD42021258097.

Results

From 632 records, 14 retrospective observational studies were included, covering a total sample of 1,988 operations. Four studies were from Australia, and the remaining 10 were, respectively, from 10 other countries. Most common operations performed were decompressive surgery with burr holes or craniectomy for head trauma and insertion of intracranial pressure monitors. Rural hospitals were the most common settings. Mortality rates for procedures performed by general surgeons at latest follow‐up were heterogenous, ranging from 5% for evacuation of chronic subdural haematoma in Kenya to 81% in head injured patients in a Hong Kong study.

Conclusions

This is the first systematic review that synthesises the literature to characterise patient outcomes after neurosurgical operations performed by a general surgeon. Findings from this study may benefit global surgery performed in rural, remote, military or humanitarian settings.
Effect of the perception of breakfast consumption on subsequent appetite and energy intake in healthy males
Authors: Slater Tommy , Mode William J. A. , Hough John , James Ruth M. , Sale Craig , James Lewis J. , Clayton David J.
Published: November 2021

Purpose

This study aimed to assess the effects of consuming a very-low-energy placebo breakfast on subsequent appetite and lunch energy intake.

Methods

Fourteen healthy males consumed water-only (WAT), very-low-energy, viscous placebo (containing water, low-calorie flavoured squash, and xanthan gum; ~ 16 kcal; PLA), and whole-food (~ 573 kcal; FOOD) breakfasts in a randomised order. Subjects were blinded to the energy content of PLA and specific study aims. Venous blood samples were collected pre-breakfast, 60- and 180-min post-breakfast to assess plasma acylated ghrelin and peptide tyrosine tyrosine concentrations. Subjective appetite was measured regularly, and energy intake was assessed at an ad libitum lunch meal 195-min post-breakfast.

Results

Lunch energy intake was lower during FOOD compared to WAT (P < 0.05), with no further differences between trials (P ≥ 0.132). Cumulative energy intake (breakfast plus lunch) was lower during PLA (1078 ± 274 kcal) and WAT (1093 ± 249 kcal), compared to FOOD (1554 ± 301 kcal; P < 0.001). Total area under the curve (AUC) for hunger, desire to eat and prospective food consumption were lower, and fullness was greater during PLA and FOOD compared to WAT (P < 0.05). AUC for hunger was lower during FOOD compared to PLA (P < 0.05). During FOOD, acylated ghrelin was suppressed compared to PLA and WAT at 60 min (P < 0.05), with no other hormonal differences between trials (P ≥ 0.071).

Conclusion

Consuming a very-low-energy placebo breakfast does not alter energy intake at lunch but may reduce cumulative energy intake across breakfast and lunch and attenuate elevations in subjective appetite associated with breakfast omission.

Trial registration

NCT04735783, 2nd February 2021, retrospectively registered.