bluuebunny/crossref_metadata_2025 huggingface dataset:
Outgrowth of the axillary bud in rose is controlled by sugar metabolism and signalling
Authors: Wang Ming , Pérez-Garcia Maria-Dolores , Davière Jean-Michel , Barbier François , Ogé Laurent , Gentilhomme José , Voisine Linda , Péron Thomas , Launay-Avon Alexandra , Clément Gilles , Baumberger Nicolas , Balzergue Sandrine , Macherel David , Grappin Philippe , Bertheloot Jessica , Achard Patrick , Hamama Latifa , Sakr Soulaiman
Published: February 2021

Shoot branching is a pivotal process during plant growth and development, and is antagonistically orchestrated by auxin and sugars. In contrast to extensive investigations on hormonal regulatory networks, our current knowledge on the role of sugar signalling pathways in bud outgrowth is scarce. Based on a comprehensive stepwise strategy, we investigated the role of glycolysis/the tricarboxylic acid (TCA) cycle and the oxidative pentose phosphate pathway (OPPP) in the control of bud outgrowth. We demonstrated that these pathways are necessary for bud outgrowth promotion upon plant decapitation and in response to sugar availability. They are also targets of the antagonistic crosstalk between auxin and sugar availability. The two pathways act synergistically to down-regulate the expression of BRC1, a conserved inhibitor of shoot branching. Using Rosa calluses stably transformed with GFP-fused promoter sequences of RhBRC1 (pRhBRC1), glycolysis/TCA cycle and the OPPP were found to repress the transcriptional activity of pRhBRC1 cooperatively. Glycolysis/TCA cycle- and OPPP-dependent regulations involve the –1973/–1611 bp and –1206/–709 bp regions of pRhBRC1, respectively. Our findings indicate that glycolysis/TCA cycle and the OPPP are integrative parts of shoot branching control and can link endogenous factors to the developmental programme of bud outgrowth, likely through two distinct mechanisms.
TALE-triggered and iTALE-suppressed Xa1-mediated resistance to bacterial blight is independent of rice transcription factor subunits OsTFIIAγ1 or OsTFIIAγ5
Authors: Xu Xiameng , Xu Zhengyin , Ma Wenxiu , Haq Fazal , Li Ying , Shah Syed Mashab Ali , Zhu Bo , Zhu Changxiang , Zou Lifang , Chen Gongyou
Published: February 2021

Xa1-mediated resistance to rice bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is triggered by transcription activator-like effectors (TALEs) and suppressed by interfering TALEs (iTALEs). TALEs interact with the rice transcription factor OsTFIIAγ1 or OsTFIIAγ5 (Xa5) to activate expression of target resistance and/or susceptibility genes. However, it is not clear whether OsTFIIAγ is involved in TALE-triggered and iTALE-suppressed Xa1-mediated resistance. In this study, genome-edited mutations in OsTFIIAγ5 or OsTFIIAγ1 of Xa1-containing rice ‘IRBB1’ and Xa1-transgenic plants of xa5-containing rice ‘IRBB5’ did not impair the activation or suppression of Xa1-mediated resistance. Correspondingly, the expression pattern of Xa1 in mutated OsTFIIAγ5 and OsTFIIAγ1 rice lines and ‘IRBB1’ rice was similar. In contrast, the expression of OsSWEET11 was repressed in rice lines mutated in OsTFIIAγ5 and OsTFIIAγ1. Bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation assays showed that both TALE PthXo1 and iTALE Tal3a interacted with OsTFIIAγ1 and OsTFIIAγ5 in plant nuclei. These results indicated that TALE-triggered and iTALE-suppressed Xa1-mediated resistance to bacterial blight is independent of OsTFIIAγ1 or OsTFIIAγ5 in rice, and suggest that an unknown factor is potentially involved in the interaction of Xa1, TALEs and iTALEs.
Express Rights of Termination
Authors: Stannard John E , Capper David
Published: February 2021

This chapter discusses express rights of termination. It is not always easy for a party to know for certain whether they are entitled to terminate or not. This is particularly so where the right in question depends on proof of fundamental breach or repudiation. For this reason, parties to a contract frequently, in the interests of certainty, make express provision for this by agreeing in advance that one or both of them may terminate if certain conditions are met. Such express rights of termination can depend on a wide variety of contingencies, but very frequently these will include a breach by the other party. Where this is the case, it is often difficult to distinguish termination under the express right from termination under the general law, particularly where the latter involves termination for breach of condition. The chapter then assesses four key issues with regard to express rights of this sort, most notably: (1) the relationship between express rights of termination and conditions at common law; (2) the requirements for the exercise of such rights; (3) the effect of termination under such a right; and (4) the problem of concurrent rights of termination.
ITLOS and the Dispute Settlement System under UNCLOS
Authors: Kittichaisaree Kriangsak
Published: February 2021

This chapter discusses the dispute settlement system under the 1982 United Nations Convention on the Law of the Sea (UNCLOS). The dispute settlement system under UNCLOS was drafted with the main purpose of achieving the uniform and effective interpretation and application of UNCLOS, as the compromises it embodied would otherwise be vulnerable to unilateral interpretation. UNCLOS sets up two international organizations: the International Seabed Authority (Authority) and the International Tribunal for the Law of the Sea (ITLOS). The Authority is the organization through which States Parties to UNCLOS organize and control activities in the seabed and ocean floor and subsoil thereof, beyond the limits of national jurisdiction (the Area), particularly with a view to administering the resources of the Area. ITLOS, the dispute settlement mechanism specifically created by UNCLOS, allows urgent issues to be tackled swiftly through seeking provisional measures of protection from a court or tribunal as well as a functional approach. The chapter then considers ITLOS's place within the dispute settlement regime under UNCLOS; entities with access to ITLOS; other international agreements besides UNCLOS that confer jurisdiction on ITLOS; ITLOS's relationship and interaction with the other principal choices of dispute settlement mechanisms; and the pros and cons of using ITLOS instead of other forums.
Overview of ITLOS’s Composition, Organization, Structure, and Rules of Procedure
Authors: Kittichaisaree Kriangsak
Published: February 2021

This chapter provides an overview of the composition, organization, structure, and rules of procedure of the International Tribunal for the Law of the Sea (ITLOS). ITLOS is composed of 21 judges elected by secret ballot by the States Parties to the 1982 United Nations Convention on the Law of the Sea (UNCLOS) from among persons nominated by States Parties who enjoy the highest reputation for fairness and integrity and of recognized competence in the field of the law of the sea. The United Nations recognizes ITLOS as an autonomous international judicial body with jurisdiction as provided for in the relevant provisions of UNCLOS and its Statute (which is Annex VI to UNCLOS). The UN and ITLOS each undertakes to respect the status and mandate of the other and to establish cooperative working relations pursuant to the provisions of the Agreement on Cooperation and Relationship between the UN and ITLOS. With a view to facilitating the effective attainment of their objectives and the coordination of their activities, they shall consult and cooperate, whenever appropriate, on matters of mutual concern, and pursue, whenever appropriate, initiatives to coordinate their activities. Moreover, ITLOS's Registrar transmits to the UN information and documentation relating to ITLOS's work, including documentation relating to applications, pleadings, oral proceedings, orders, judgments, and other communications and documentation before ITLOS.
Applications for Provisional Measures
Authors: Kittichaisaree Kriangsak
Published: February 2021

This chapter assesses applications for provisional measures of protection under the 1982 United Nations Convention on the Law of the Sea (UNCLOS). At the Third UN Conference on the Law of the Sea, the need for courts or tribunals having jurisdiction under UNCLOS to have the power to prescribe provisional measures was beyond dispute although there was considerable debate concerning the details of the regime associated with such measures. The finally adopted Article 290 of UNCLOS, under the heading ‘Provisional measures’, represents the best possible compromise. Provisional measures are divided into provisional measures prescribed by the International Tribunal for the Law of the Sea (ITLOS) under Article 290(1) pending ITLOS’ judgment on the merits of the dispute, on the one hand, and provisional measures prescribed by ITLOS under Article 290(5) pending the constitution of an arbitral tribunal to which a dispute is being submitted, on the other hand. The request for the prescription of provisional measures shall be in writing and specify the measures requested, the reasons therefor, and the possible consequences, if the request is not granted, for the preservation of the respective rights of the parties or for the prevention of serious harm to the marine environment.
Good Deaths in Wendell Berry’s Short Stories
Authors: Ens Gerald
Published: February 2021

This article looks at how Wendell Berry’s short stories depicting good deaths offer a crucial exploration of the incarnate bonds of human affection. They do so, I argue, by pointing us to the vulnerable ordinariness of embodied love. I first describe these good deaths as ‘ordinary’ because of the way that they refuse a heroic mode of standing above the world and instead accept and live into the vulnerable connections that mark our materiality. I show also how this acceptance, and not any attempt to transcend the ordinary, is what opens these deaths up to the sacred, which I argue is a mark of belonging in love to the world and the love that moves the world. In the second section, I outline the relational role death plays in inaugurating and sustaining the gift-giving relational bonds that make up the life of affection in a place, such that there is a sense in which it is death that opens us up to love, even as death always marks an absence.
The Genomes of Two Billfishes Provide Insights into the Evolution of Endothermy in Teleosts
Authors: Wu Baosheng , Feng Chenguang , Zhu Chenglong , Xu Wenjie , Yuan Yuan , Hu Mingliang , Yuan Ke , Li Yongxin , Ren Yandong , Zhou Yang , Jiang Haifeng , Qiu Qiang , Wang Wen , He Shunping , Wang Kun
Published: February 2021

Endothermy is a typical convergent phenomenon which has evolved independently at least eight times in vertebrates, and is of significant advantage to organisms in extending their niches. However, how vertebrates other than mammals or birds, especially teleosts, achieve endothermy has not previously been fully understood. In this study, we sequenced the genomes of two billfishes (swordfish and sailfish), members of a representative lineage of endothermic teleosts. Convergent amino acid replacements were observed in proteins related to heat production and the visual system in two endothermic teleost lineages, billfishes and tunas. The billfish-specific genetic innovations were found to be associated with heat exchange, thermoregulation, and the specialized morphology, including elongated bill, enlarged dorsal fin in sailfish and loss of the pelvic fin in swordfish.
Endometrial stromal cell proteomic analysis reveals LIM and SH3 protein 1 (LASP1) plays important roles in the progression of adenomyosis
Authors: Liu Faying , Li Zengming , Guo Jiubai , Fang Shufen , Zhou Jiangyan , Cao Bianna , Liu Jun , Yi Yulan , Yuan Xiaoqun , Xu Xiaoyun , Huang Ouping , Wang Liqun , Zou Yang
Published: February 2021

Adenomyosis is one of the most common gynecological disorders that the molecular events underlying its pathogenesis remain not fully understood. Prior studies have shown that endometrial stromal cells (ESCs) played crucial roles in the pathogenesis of adenomyosis. In this study, we utilized two-dimensional gel electrophoresis combined with protein identification by mass spectrometry (2D/MS) proteomics analysis to compare the differential protein expression profile between the paired eutopic and ectopic ESCs (EuESCs and EcESCs) in adenomyosis, and a total of 32 significantly altered protein spots were identified. Among which, the expression of LIM and SH3 protein 1 (LASP1) was increased significantly in EcESCs compared to EuESCs. Immunohistochemical assay showed that LASP1 was overexpressed in the stromal cells of ectopic endometriums compared to eutopic endometriums; further functional analyses revealed that LASP1 overexpression could enhance cell proliferation, migration and invasion of EcESCs. Furthermore, we also showed that the dysregulated expression of LASP1 in EcESCs was associated with DNA hypermethylation in the promoter region of the LASP1 gene. However, the detailed molecular mechanisms of enhancing cell proliferation, invasion and migration caused by upregulated LASP1 in adenomyosis needs further study. For the first time, our data suggested that LASP1 plays important roles in the pathogenesis of adenomyosis, and could serve as a prognostic biomarker of adenomyosis.
Site-specific incorporation of 5′-methyl DNA enhances the therapeutic profile of gapmer ASOs
Authors: Vasquez Guillermo , Freestone Graeme C , Wan W Brad , Low Audrey , De Hoyos Cheryl Li , Yu Jinghua , Prakash Thazha P , Ǿstergaard Michael E , Liang Xue-hai , Crooke Stanley T , Swayze Eric E , Migawa Michael T , Seth Punit P
Published: February 2021

We recently showed that site-specific incorporation of 2′-modifications or neutral linkages in the oligo-deoxynucleotide gap region of toxic phosphorothioate (PS) gapmer ASOs can enhance therapeutic index and safety. In this manuscript, we determined if introducing substitution at the 5′-position of deoxynucleotide monomers in the gap can also enhance therapeutic index. Introducing R- or S-configured 5′-Me DNA at positions 3 and 4 in the oligodeoxynucleotide gap enhanced the therapeutic profile of the modified ASOs suggesting a different positional preference as compared to the 2′-OMe gap modification strategy. The generality of these observations was demonstrated by evaluating R-5′-Me and R-5′-Ethyl DNA modifications in multiple ASOs targeting HDAC2, FXI and Dynamin2 mRNA in the liver. The current work adds to a growing body of evidence that small structural changes can modulate the therapeutic properties of PS ASOs and ushers a new era of chemical optimization with a focus on enhancing the therapeutic profile as opposed to nuclease stability, RNA-affinity and pharmacokinetic properties. The 5′-methyl DNA modified ASOs exhibited excellent safety and antisense activity in mice highlighting the therapeutic potential of this class of nucleic acid analogs for next generation ASO designs.
Mechanism of forkhead transcription factors binding to a novel palindromic DNA site
Authors: Li Jun , Dai Shuyan , Chen Xiaojuan , Liang Xujun , Qu Lingzhi , Jiang Longying , Guo Ming , Zhou Zhan , Wei Hudie , Zhang Huajun , Chen Zhuchu , Chen Lin , Chen Yongheng
Published: February 2021

Forkhead transcription factors bind a canonical consensus DNA motif, RYAAAYA (R = A/G, Y = C/T), as a monomer. However, the molecular mechanisms by which forkhead transcription factors bind DNA as a dimer are not well understood. In this study, we show that FOXO1 recognizes a palindromic DNA element DIV2, and mediates transcriptional regulation. The crystal structure of FOXO1/DIV2 reveals that the FOXO1 DNA binding domain (DBD) binds the DIV2 site as a homodimer. The wing1 region of FOXO1 mediates the dimerization, which enhances FOXO1 DNA binding affinity and complex stability. Further biochemical assays show that FOXO3, FOXM1 and FOXI1 also bind the DIV2 site as homodimer, while FOXC2 can only bind this site as a monomer. Our structural, biochemical and bioinformatics analyses not only provide a novel mechanism by which FOXO1 binds DNA as a homodimer, but also shed light on the target selection of forkhead transcription factors.
In vivostructure of the Ty1 retrotransposon RNA genome
Authors: Andrzejewska Angelika , Zawadzka Małgorzata , Gumna Julita , Garfinkel David J , Pachulska-Wieczorek Katarzyna
Published: February 2021

Long terminal repeat (LTR)-retrotransposons constitute a significant part of eukaryotic genomes and influence their function and evolution. Like other RNA viruses, LTR-retrotransposons efficiently utilize their RNA genome to interact with host cell machinery during replication. Here, we provide the first genome-wide RNA secondary structure model for a LTR-retrotransposon in living cells. Using SHAPE probing, we explore the secondary structure of the yeast Ty1 retrotransposon RNA genome in its native in vivo state and under defined in vitro conditions. Comparative analyses reveal the strong impact of the cellular environment on folding of Ty1 RNA. In vivo, Ty1 genome RNA is significantly less structured and more dynamic but retains specific well-structured regions harboring functional cis-acting sequences. Ribosomes participate in the unfolding and remodeling of Ty1 RNA, and inhibition of translation initiation stabilizes Ty1 RNA structure. Together, our findings support the dual role of Ty1 genomic RNA as a template for protein synthesis and reverse transcription. This study also contributes to understanding how a complex multifunctional RNA genome folds in vivo, and strengthens the need for studying RNA structure in its natural cellular context.
Anti-myeloperoxidase and proteinase 3 antibodies for nephritis flare prediction in anti-neutrophil cytoplasmic antibody–associated vasculitis
Authors: Rodríguez Eva , Latzke Belén , Sierra Milagros , Romera Ana María , Siedel Diego , Agraz Irene , Soler María José , García-Carro Clara , Draibe Juliana , de la Prada Francisco José , Villacorta Javier , Buxeda Anna , Sierra-Ochoa Adriana , Lozano Inés , Durán Xavier , Barrios Clara , Pascual Julio
Published: February 2021

Background

The value of myeloperoxidase (MPO) and proteinase 3 (PR3) antibody titres in the assessment of renal disease activity and flare prediction in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) is not well known.

Methods

We performed a retrospective study including 113 AVV patients with renal biopsy–proven pauci-immune necrotizing glomerulonephritis from seven Spanish hospitals. The main inclusion criteria were assessment of MPO antibodies using multiplex flow immunoassay and PR3 antibody measurements using immunoassay chemiluminescence with an identical range of values for all participating centres.

Results

Serum MPO antibodies 3 ± 1.2 months before relapse were higher in patients who relapsed [19.2 ± 12.2 versus 3.2 ± 5.1 antibody index (AI); P < 0.001]. The discrimination value of MPO antibodies 3 months before renal relapse had an area under the receiver operating characteristics curve (AUC) of 0.82 [95% confidence interval (CI) 0.73–0.92; P < 0.001]. ΔMPO antibodies (change in antibodies titration 6 months before relapse) were higher in patients who relapsed (8.3 ± 12 versus 0.9 ± 3.1 AI; P = 0.001). The discrimination value of ΔMPO had an AUC of 0.76 (95% CI 0.63–0.88; P < 0.001). The positive predictive value of renal relapse in PR3 patients is 100% and the negative predictive value of renal relapse in patients with PR3-positive titres is 57.1%. Serum PR3 antibodies were higher in patients who relapsed 2.8 ± 1.4 months before relapse (58.6 ± 24.6 versus 2.0 ± 0.6 AI; P < 0.001).

Conclusions

MPO level monitoring using multiplex flow immunoassay and PR3 measurements using immunoassay chemiluminescence are useful and sensitive tools for the prediction of renal relapse in the follow-up of AAV patients with renal disease and relevant surrogate markers of renal disease activity.
Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2
Authors: Singh Prince , Viehman Jason K , Mehta Ramila A , Cogal Andrea G , Hasadsri Linda , Oglesbee Devin , Olson Julie B , Seide Barbara M , Sas David J , Harris Peter C , Lieske John C , Milliner Dawn S
Published: February 2021

Background

Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2.

Methods

Clinical information was obtained from the Rare Kidney Stone Consortium PH Registry (PH1, n = 384; PH2, n = 51; PH3, n = 62).

Results

PH3 patients presented with symptoms at a median of 2.7 years old compared with PH1 (4.9 years) and PH2 (5.7 years) (P = 0.14). Nephrocalcinosis was present at diagnosis in 4 (7%) PH3 patients, while 55 (89%) had stones. Median urine oxalate excretion was lowest in PH3 patients compared with PH1 and PH2 (1.1 versus 1.6 and 1.5 mmol/day/1.73 m2, respectively, P < 0.001) while urine calcium was highest in PH3 (112 versus 51 and 98 mg/day/1.73 m2 in PH1 and PH2, respectively, P < 0.001). Stone events per decade of life were similar across the age span and the three PH types. At 40 years of age, 97% of PH3 patients had not progressed to end-stage kidney disease compared with 36% PH1 and 66% PH2 patients.

Conclusions

Patients with all forms of PH experience lifelong stone events, often beginning in childhood. Kidney failure is common in PH1 but rare in PH3. Longer-term follow-up of larger cohorts will be important for a more complete understanding of the PH3 phenotype.
Structural Alteration of Rice Pectin Affects Cell Wall Mechanical Strength and Pathogenicity of the Rice Blast Fungus Under Weak Light Conditions
Authors: Ohara Takashi , Takeuchi Haruki , Sato Junya , Nakamura Atsuko , Ichikawa Hiroaki , Yokoyama Ryusuke , Nishitani Kazuhiko , Minami Eiichi , Satoh Shinobu , Iwai Hiroaki
Published: February 2021

Pectin, a component of the plant cell wall, is involved in cell adhesion and environmental adaptations. We generated OsPG-FOX rice lines with little pectin due to overexpression of the gene encoding a pectin-degrading enzyme [polygalacturonase (PG)]. Overexpression of OsPG2 in rice under weak light conditions increased the activity of PG, which increased the degradation of pectin in the cell wall, thereby reducing adhesion. Under weak light conditions, the overexpression of OsPG decreased the pectin content and cell adhesion, resulting in abnormally large intercellular gaps and facilitating invasion by the rice blast fungus. OsPG2-FOX plants had weaker mechanical properties and greater sensitivity to biotic stresses than wild-type (WT) plants. However, the expression levels of disease resistance genes in non-infected leaves of OsPG2-FOX were more than twice as high as those of the WT and the intensity of disease symptoms was reduced, compared with the WT. Under normal light conditions, overexpression of OsPG2 decreased the pectin content, but did not affect cell adhesion and sensitivity to biotic stresses. Therefore, PG plays a role in regulating intercellular adhesion and the response to biotic stresses in rice.
Mesozooplankton biomass, grazing and trophic structure in the bluefin tuna spawning area of the oceanic Gulf of Mexico
Authors: Landry Michael R , Swalethorp Rasmus
Published: February 2021

We investigated size-fractioned biomass, isotopes and grazing of mesozooplankton communities in the larval habitat of Atlantic bluefin tuna (ABT) in the oceanic Gulf of Mexico (GoM) during the peak spawning month of May. Euphotic-zone biomass ranged from 101 to 513 mg C m−2 during the day and 216 to 798 mg C m−2 at night. Grazing varied from 0.1 to 1.0 mg Chla m−2 d−1, averaging 1–3% of phytoplankton Chla consumed d−1. Carnivorous taxa dominated the biomass of > 1-mm zooplankton (78% day; 60% night), while only 13% of smaller zooplankton were carnivores. δ15N enrichment between small and large sizes indicates a 0.5–0.6 trophic-step difference. Although characteristics of GoM zooplankton are generally similar to those of remote oligotrophic subtropical regions, zooplankton stocks in the ABT larval habitat are disproportionately high relative to primary production, compared with HOT and BATS averages. Growth-grazing balances for phytoplankton were resolved with a statistically insignificant residual, and trophic fluxes from local productivity were sufficient to satisfy C demand of suspension feeding mesozooplankton. While carnivore C demand was met by local processes in the central GoM, experiments closer to the coastal margin suggest the need for a lateral subsidy of zooplankton biomass to the oceanic region.
COVID-19: transitioning from in class to online teaching in a heartbeat—Research Methods in Applied Biology
Authors: von Keyserlingk Marina A G
Published: February 2021

At the start of the COVID-19 pandemic, Universities around the world were forced to rapidly transition from face-to-face learning environments to online learning. This paper describes this transition through the lens of a professor responsible for a third year Applied Biology class focused on providing undergraduates with research experience. The paper also describes an innovative format used to engage undergraduates in research but also suggests that the creation of safe learning spaces in the virtual world may be key to successful delivery of these types of courses. Lastly, in times of rapid change professors need, on occasion, take a step back and simply listen to their students.
The scaling of ground reaction forces and duty factor in monitor lizards: implications for locomotion in sprawling tetrapods
Authors: Cieri Robert L. , Dick Taylor J. M. , Irwin Robert , Rumsey Daniel , Clemente Christofer J.
Published: February 2021

Geometric scaling predicts a major challenge for legged, terrestrial locomotion. Locomotor support requirements scale identically with body mass (α M1), while force-generation capacity should scaleα M2/3as it depends on muscle cross-sectional area. Mammals compensate with more upright limb postures at larger sizes, but it remains unknown how sprawling tetrapods deal with this challenge. Varanid lizards are an ideal group to address this question because they cover an enormous body size range while maintaining a similar bent-limb posture and body proportions. This study reports the scaling of ground reaction forces and duty factor for varanid lizards ranging from 7 g to 37 kg. Impulses (force×time) (α M0.99−1.34) and peak forces (α M0.73−1.00) scaled higher than expected. Duty factor scaledα M0.04and was higher for the hindlimb than the forelimb. The proportion of vertical impulse to total impulse increased with body size, and impulses decreased while peak forces increased with speed.
Reconstitution of the recombinant human γ-tubulin ring complex
Authors: Würtz Martin , Böhler Anna , Neuner Annett , Zupa Erik , Rohland Lukas , Liu Peng , Vermeulen Bram J. A. , Pfeffer Stefan , Eustermann Sebastian , Schiebel Elmar
Published: February 2021

Cryo-electron microscopy recently resolved the structure of the vertebrate γ-tubulin ring complex (γ-TuRC) purified from
Xenopus laevis
egg extract and human cells to near-atomic resolution. These studies clarified the arrangement and stoichiometry of γ-TuRC components and revealed that one molecule of actin and the small protein MZT1 are embedded into the complex. Based on this structural census of γ-TuRC core components, we developed a recombinant expression system for the reconstitution and purification of human γ-TuRC from insect cells. The recombinant γ-TuRC recapitulates the structure of purified native γ-TuRC and has similar functional properties in terms of microtubule nucleation and minus end capping. This recombinant system is a central step towards deciphering the activation mechanisms of the γ-TuRC and the function of individual γ-TuRC core components.
The impact of trace metal cations and absorbed water on colour transition of turquoise
Authors: Wang Xueding , Guo Ying
Published: February 2021

Thirty-five gem-quality turquoise samples with various colours were investigated using energy-dispersive X-ray fluorescence spectroscopy, ultraviolet–visible spectroscopy, Fourier-transform infrared spectroscopy and scanning electron microscopy. Sample chemical and spectral analyses indicate that Fe
3+
contributes to green hue of turquoise, whose absorption band exhibits a bathochromic shift from 426 to 428 nm with increasing V content in the solid-solution series turquoise-chalcosiderite. V
3+
enhances absorption in the blue and orange regions, and Cr
3+
increases absorption in the green region, both of which are responsible for the vivid greenish yellow in faustite. Substitutions of Al by medium-sized trivalent cations (primarily Fe
3+
and V
3+
) enhance polarity of the phosphate group (PO
4
)
3−
, resulting in strong absorption in the infrared spectra for analogues of turquoise. The reflectivity ratio (
R
OH
) of the double absorption peaks at 781 and 833 cm
−1
allows faustite to be distinguished from turquoise and chalcosiderite, with a value greater than 1, while V-rich faustite only has a single absorption peak at 798 cm
−1
. An increasing amount of absorbed water contributes to blue chroma in turquoise and has a negative effect on lightness based on the CIE 1976
L
*
a
*
b
* colour system. Loose turquoise with a low specific gravity tends to display greater colour differences with a significant decrease in lightness.
Dental microwear texture analysis along reptile tooth rows: complex variation with non-dietary variables
Authors: Bestwick Jordan , Unwin David M. , Henderson Donald M. , Purnell Mark A.
Published: February 2021

Dental microwear texture analysis (DMTA) is a powerful technique for reconstructing the diets of extant and extinct taxa. Few studies have investigated intraspecific microwear differences along with tooth rows and the influence of endogenous non-dietary variables on texture characteristics. Sampling teeth that are minimally affected by non-dietary variables is vital for robust dietary reconstructions, especially for taxa with non-occlusal (non-chewing) dentitions as no standardized sampling strategies currently exist. Here, we apply DMTA to 13 species of extant reptile (crocodilians and monitor lizards) to investigate intraspecific microwear differences along with tooth rows and to explore the influence of three non-dietary variables on exhibited differences: (i) tooth position, (ii) mechanical advantage, and (iii) tooth aspect ratio. Five species exhibited intraspecific microwear differences. In several crocodilians, the distally positioned teeth exhibited the ‘roughest' textures, and texture characteristics correlated with all non-dietary variables. By contrast, the mesial teeth of the roughneck monitor (
Varanus rudicollis
) exhibited the ‘roughest' textures, and texture characteristics did not correlate with aspect ratio. These results are somewhat consistent with how reptiles preferentially use their teeth during feeding. We argue that DMTA has the potential to track mechanical and behavioural differences in tooth use which should be taken into consideration in future dietary reconstructions.
Simultaneous estimation of troxerutin and calcium dobesilate in presence of the carcinogenic hydroquinone using green spectrofluorimetric method
Authors: Tolba M. M. , Salim M. M. , El-Awady M.
Published: February 2021

In the present study, we conducted two facile and highly sensitive spectrofluorimetric approaches in order to quantify the vasoprotective agents; troxerutin (TROX) and calcium dobesilate (DOB) in the presence of hydroquinone (HQ) (as a highly toxic impurity and potential degradation product of DOB) in commercial formulations and human plasma. The first approach relies simply on using ethanol as an eco-friendly solvent for the estimation of DOB at 345 nm after being excited at 305 nm. The linearity was carefully investigated between DOB concentration and the relative fluorescence intensity in the range of 0.05–0.8 µg ml
−1
. Due to the high method simplicity and sensitivity, applying the first approach to quality control analysis and spiked human plasma samples with mean % recoveries 100.74 ± 3.71 adds another merit. The second approach involved rapid conventional fluorimetric estimation of ethanolic TROX solution in TROX/DOB combined dosage forms at 455/350 nm (emission/excitation) with a linear calibration chart covering the range of 0.1–1.2 µg ml
−1
. Moreover, the second approach involved a comprehensive study in a trial to solve the problem of superposition of DOB and HQ graph adopting the first derivative synchronous fluorimetric mechanism in ethanol at Δ
λ
= 60 nm. Therefore, DOB was measured at 286 and 323 nm, while HQ could be quantitated at 301 nm. The Beer–Lambert Law has complied over the ranges of 0.1–1.0 and 0.02–0.4 µg ml
−1
for DOB and HQ, respectively. Guidelines adopted by the International Council of Harmonization (ICH) were used to validate the target approaches. The developed methods are more convenient for routine quality control laboratory instead of the time-consuming and sophisticated reported techniques. Moreover, different aspects of evaluating the greenness of the proposed approaches were conducted to have a complete image of their environmental impact.
Observation and modelling of solar jets
Authors: Shen Yuandeng
Published: February 2021

The solar atmosphere is full of complicated transients manifesting the reconfiguration of the solar magnetic field and plasma. Solar jets represent collimated, beam-like plasma ejections; they are ubiquitous in the solar atmosphere and important for our understanding of solar activities at different scales, the magnetic reconnection process, particle acceleration, coronal heating, solar wind acceleration, as well as other related phenomena. Recent high-spatio-temporal-resolution, wide-temperature coverage and spectroscopic and stereoscopic observations taken by ground-based and space-borne solar telescopes have revealed many valuable new clues to restrict the development of theoretical models. This review aims at providing the reader with the main observational characteristics of solar jets, physical interpretations and models, as well as unsolved outstanding questions in future studies.
Smartphone-enabled road condition monitoring: from accelerations to road roughness and excess energy dissipation
Authors: Botshekan Meshkat , Asaadi Erfan , Roxon Jake , Ulm Franz-Josef , Tootkaboni Mazdak , Louhghalam Arghavan
Published: February 2021

We develop a framework to address the shortcomings of current smartphone-based approaches for road roughness sensing and monitoring through combining vehicle dynamics, random vibration theory and a two-layer inverse analysis. The proposed approach uses in-cabin recordings of the vehicle’s vertical acceleration measured by a smartphone positioned inside the car for the estimation of road roughness. The mechanistic road roughness–vehicle interaction model at the core of the proposed framework links the frequency spectrum of the vehicle’s vertical acceleration to the road roughness power spectral density and lends itself to the quantitative characterization of roughness-induced energy dissipation. We demonstrate that the measure of roughness provided by the stochastic model of car dynamics interacting with a rough road is fully compatible, in a statistical sense, with the spatial but deterministic definition of road roughness, and validate the identification strategy that originates from it against laser measurements of road roughness. The critical crowdsourcing features of the proposed framework, such as the marginal impact of phone position and transferability, are examined and its utility to meld with big data analytics to identify the class of vehicles travelling on a roadway network is demonstrated.
Chiral triclinic metamaterial crystals supporting isotropic acoustical activity and isotropic chiral phonons
Authors: Chen Yi , Kadic Muamer , Wegener Martin
Published: February 2021

Recent work predicted the existence of isotropic chiral phonon dispersion relations of the lowest bands connected to isotropic acoustical activity in cubic crystalline approximants of three-dimensional (3D) chiral icosahedral metamaterial quasi-crystals. While these architectures are fairly broadband and presumably robust against fabrication tolerances due to orientation averaging, they are extremely complex, very hard to manufacture experimentally, and they show effects which are about an order of magnitude smaller compared with those of ordinary highly anisotropic chiral cubic metamaterial crystals. Here, we propose and analyse a chiral triclinic metamaterial crystal exhibiting broadband isotropic acoustical activity. These 3D truss lattices are much less complex and exhibit substantially larger effects than the 3D quasi-crystals at the price of being somewhat more susceptible to fabrication tolerances. This susceptibility originates from the fact that we have tailored the lowest two transverse phonon bands to exhibit an ‘accidental’ degeneracy in momentum space.
Shapes of large, static soap bubbles
Authors: Brubaker Nicholas D.
Published: February 2021

Standard predictions induced by the balance of surface tension and pressure dictate that static soap bubbles must be spherical. However, definite non-spherical shapes appear in large bubbles, where noticeable oblate or prolate deformations occur. Gravity is the principal cause of such deformations, and multiple approaches for including its influence appear in recent literature. This paper derives a general surface-theoretic model by applying asymptotic and variational methods to a fully three-dimensional set-up where the soap bubble is a finite-thickness film. The procedure illuminates implicit assumptions, clarifying the discrepancies seen in previous models. Then the model is studied in four physical situations. In three of these situations, results show that there is a maximum stable span and volume of the soap bubbles, implying that their behaviour is qualitatively more similar to liquid drops than standard soap bubbles. Also, the model presented is directly analogous to the two-dimensional version of a hanging chain, and the derived predictions give practical insights into the construction of heavy containment vessels.
Evolution of ACE2 and SARS-CoV-2 Interplay Across 247 Vertebrates
Authors: Zhang Tao , Wu Qunfu , Ma Yicheng , Liu Wenjing , Zhou Chengang , Zhang Zhigang
Published: February 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause the most serious pandemics of Coronavirus Disease 2019 (COVID-19), which threatens human health and public safety. SARS-CoV-2 spike (S) protein uses angiotensin-converting enzyme 2 (ACE2) as recognized receptor for its entry into host cell that contributes to the infection of SARS-CoV-2 to hosts. Using computational modeling approach, this study resolved the evolutionary pattern of bonding affinity of ACE2 in 247 jawed vertebrates to the spike (S) protein of SARS-CoV-2. First, high-or-low binding affinity phenotype divergence of ACE2 to the S protein of SARS-CoV-2 has appeared in two ancient species of jawed vertebrates,Scyliorhinus torazame(low-affinity, Chondrichthyes) andLatimeria chalumnae(high-affinity, Coelacanthimorpha). Second, multiple independent affinity divergence events recur in fishes, amphibians-reptiles, birds, and mammals. Third, high affinity phenotypes go up in mammals, possibly implying the rapid expansion of mammals might accelerate the evolution of coronaviruses. Fourth, we found natural mutations at eight amino acid sites of ACE2 can determine most of phenotype divergences of bonding affinity in 247 vertebrates and resolved their related structural basis. Moreover, we also identified high-affinity or low-affinity-associated concomitant mutation group.The group linked to extremely high affinity may provide novel potentials for the development of human recombinant soluble ACE2 (hrsACE2) in treating patients with COVID-19 or for constructing genetically modified SARS-CoV-2 infection models promoting vaccines studies. These findings would offer potential benefits for the treatment and prevention of SARS-CoV-2.
Dynamics of SARS-CoV-2-specific antibodies during and after COVID19: Lessons from a biobank in Argentina
Authors: Longueira Yésica , Polo María Laura ,   InViV working group, Turk Gabriela , Laufer Natalia ,   Biobanco de Enfermedades Infecciosas Colección COVID19 working group
Published: February 2021

Background

Biobanks are instrumental for accelerating research. Early in SARS-CoV-2 pandemic, the Argentinean Biobank of Infectious Diseases (BBEI) initiated the COVID19 collection and started its characterization.

Methods

Blood samples from subjects with confirmed SARS-CoV-2 infection either admitted to health institutions or outpatients, were enrolled. Highly exposed seronegative individuals, were also enrolled. Longitudinal samples were obtained in a subset of donors, including persons who donated plasma for therapeutic purposes (plasma donors). SARS-CoV-2-specific IgM and IgG levels, IgG titers and IgG viral neutralization capacity were determined.

Findings

Out of 825 donors, 57.1% were females and median age was 41 years (IQR 32-53 years). Donors were segregated as acute or convalescent donors, and mild versus moderate/severe disease donors. Seventy-eight percent showed seroconversion to SARS-CoV-2 specific antibodies. Specific IgM and IgG showed comparable positivity rates in acute donors. IgM detectability rate declined in convalescent donors while IgG detectability remained elevated in early (74,8%) and late (83%) convalescent donors. Among donors with follow-up samples, IgG levels seemed to decline more rapidly in plasma donors. IgG levels were higher with age, disease severity, number of symptoms, and was more durable in moderate/severe disease donors. Levels and titers of anti-spike/RBD IgG strongly correlated with neutralization activity against WT virus.

Interpretation

The BBEI-COVID19 collection served a dual role in this SARS-CoV-2 global crisis. First, it feed researchers and developers transferring samples and data to fuel research projects. Second, it generated highly needed local data to understand and frame the regional dynamics of the infection.

Funding

This work was supported by a grant from the Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Agencia I+D+i) from Argentina through an extraordinary funding opportunity to improve the national response to COVID19 (Proyecto COVID N° 11, IP 285).
Standard and anomalous waves of COVID-19: A multiple-wave growth model for epidemics
Authors: Vasconcelos Giovani L. , Brum Arthur A. , Almeida Francisco A. G. , Macêdo Antônio M. S. , Duarte-Filho Gerson C. , Ospina Raydonal
Published: February 2021

We apply a generalized logistic growth model, with time dependent parameters, to describe the fatality curves of the COVID-19 disease for several countries that exhibit multiple waves of infections. In the case of two waves only, the model parameters vary as a function of time according to a logistic function, whose two extreme values, i.e., for early and late times, characterize the first and second waves, respectively. For the multiple-wave model, the time-dependency of the parameters is likewise described by a multi-step logistic function with N intermediate plateaus, representing the N waves of the epidemic. We show that the theoretical curves are in excellent agreement with the empirical data for all countries considered here, namely: Brazil, Canada, Germany, Iran, Italy, Japan, Mexico, South Africa, Sweden, and US. The model also allows for predictions about the time of occurrence and severity of the subsequent waves. It is shown furthermore that the subsequent waves of COVID-19 can be generically classified into two main types, namely, standard and anomalous waves, according as to whether a given wave starts well after or well before the preceding one has subsided, respectively.
Site-specific decrease in cortical reactivity during sensory trick in cervical dystonia patients
Authors: Thirugnanasambandam Nivethida , Singh Shivangi , Cho Hyun Joo , Shitara Hitoshi , Panyakaew Pattamon , Lee Sang Wook , Hallett Mark
Published: February 2021

Background

Sensory tricks (SeT) are various maneuvers that can alleviate dystonic contractions and are a characteristic feature of cervical dystonia (CD). The neurophysiology underlying SeT, however, remains largely unknown. Reducing the abnormal cortical facilitation and modulating the abnormal cortical and subcortical oscillatory activity are mechanisms that have been proposed. The supplementary motor area (SMA) and primary sensorimotor cortices are thought to be relevant to this phenomenon.

Objective

In the current study, using concurrent EEG recording during transcranial magnetic stimulation (TMS) of the SMA and primary motor cortex (M1), we aimed at determining the changes in cortical reactivity and oscillatory changes induced by SeT.

Methods

We recruited 13 patients with CD who exhibited SeT and equal number of age- and gender-matched healthy controls. Single TMS pulses were delivered over the SMA and M1 either at rest or during SeT. 32-channel EEG was recorded, and TMS-evoked potentials (TEP) were obtained. Further, time-frequency analysis was performed on the induced data. Correlation analysis for significant neurophysiological parameters was done with clinical measures.

Results

We found that SeT induced a significant decrease in the amplitude of TEP elicited from M1 stimulation at ∼210-260ms in patients, which correlated with symptom duration. Post hoc analysis of EMG activity in the neck muscles revealed that this effect on TEP was present only in the subset of patients with effective SeT.

Conclusion

Our results suggest that SeT reduces cortical reactivity over M1 approximately 200ms after stimulation. This adds support to the idea that reduced cortical facilitation underlies the phenomenon.
Improving the Prediction of Clinical Success Using Machine Learning
Authors: Munos Bernard , Niederreiter Jan , Riccaboni Massimo
Published: February 2021

In pharmaceutical research, assessing drug candidates’ odds of success as they move through clinical research often relies on crude methods based on historical data. However, the rapid progress of machine learning offers a new tool to identify the more promising projects. To evaluate its usefulness, we trained and validated several machine learning algorithms on a large database of projects. Using various project descriptors as input data we were able to predict the clinical success and failure rates of projects with an average balanced accuracy of 83% to 89%, which compares favorably with the 56% to 70% balanced accuracy of the method based on historical data. We also identified the variables that contributed most to trial success and used the algorithm to predict the success (or failure) of assets currently in the industry pipeline. We conclude by discussing how pharmaceutical companies can use such model to improve the quantity and quality of their new drugs, and how the broad adoption of this technology could reduce the industry’s risk profile with important consequences for industry structure, R&D investment, and the cost of innovation