bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenomics and evolutionary diversification of the subfamily Polygonoideae
Authors: Zhang Lu‐Shui , Chen Chun‐Lin , Mao Xing‐Xing , Liu Jian‐Quan
Published: September 2022

Many species of the subfamily Polygonoideae are economically important. However, phylogenetic relationships and taxonomic treatments of these species remain disputed. In this study, we used highly orthologous nuclear genes and plastome sequence variation extracted from transcriptomes from 98 species of 26 genera of Polygonaceae mainly from the subfamily Polygonoideae to construct a robust phylogeny. We discerned six successively diverged and well‐defined clades and both nuclear and plastome phylogenies are highly consistent with each other in this subfamily. Phylogenetic relationships between all clades and subclades were well resolved within Polygonoideae. Our analyses revealed that the shrub tribe Atraphaxideae and the herbal genera Polygonum, Persicaria, and Fallopia are polyphyletic. The sampled species of Polygonoideae started to diversify around the Cretaceous/Tertiary boundary (70 Ma) when the global climate exhibited large oscillations. Further origins of more herbal and woody species were found to have clearly increased during later climatic oscillations. We found that woody habits, especially shrubs, originated multiple times from ancestral herbs in this subfamily. Local dry climates may have favored such habit shifts from ancestral herbs. Our results deepen our understanding of evolutionary diversification of Polygonoideae.
Safe co‐administration of direct‐acting antivirals and direct oral anticoagulants among patients with hepatitis C virus infection: An international multicenter retrospective cohort study
Authors: McDaniel Kathryn , Utz Alyssa E. , Akbashev Mikhail , Fuller Katherine G. , Boyle Alison , Davidson Katherine , Marra Fiona , Shah Sital , Cartwright Emily J. , Arora Aakriti A. , DuPont Sarah , Miller Lesley S.
Published: September 2022

Treatment for hepatitis C virus (HCV) with direct‐acting antivirals (DAA) is advantageous over previous treatment options due to high efficacy, short treatment duration, and relatively few drug interactions. Similarly, direct oral anticoagulants (DOAC) are generally preferred over warfarin for the management of thrombosis and atrial fibrillation due to a favourable safety profile. Direct‐acting antivirals inhibit DOAC transport through P‐glycoprotein inhibition leading to a theoretical increase in bleeding risk. We evaluated the incidence of bleeding in patients who received concurrent DAA and DOAC therapy and stratified the analysis based on the patient's cirrhosis status. We conducted a multicenter, retrospective cohort study to evaluate bleeding in patients with HCV and cirrhosis compared to patients with HCV without cirrhosis. Patients receiving at least 1 month of overlapping DAA and DOAC therapy between May 2017 and August 2020 at 11 medical centers in the United Kingdom and three medical centers in the United States were included. Charts were manually reviewed to identify baseline characteristics as well as thromboembolic or bleeding events. Bleeding events were categorized as major bleeding (MB) and clinically relevant non‐major bleeding (CRNMB). Of 204 total patients, 36 patients (18%) had cirrhosis and 168 patients (82%) did not have cirrhosis. The majority of patients were male (79%) and Caucasian (75%). Sofosbuvir/velpatasvir (32%) and rivaroxaban (57%) were the most commonly prescribed DAA and DOAC, respectively. Leading indications for anticoagulation included thrombosis (75%) and atrial fibrillation (21%). There were three MB events (1.5%) all of which occurred in patients with additional risk factors (age over 65 and on antiplatelet therapy) and no CRNMB occurred while on DOAC and DAA therapy. Of the three MB, one occurred in a patient with cirrhosis and two in patients without cirrhosis, RR 1.23 (0.56–2.76). In conclusion, in this multicenter cohort study of concurrent DAA and DOAC use, MB was uncommon and there was no CRNMB. There was no significant difference in bleeding events among patients with cirrhosis compared to those without cirrhosis. These findings support the use of DAA among patients requiring DOAC.
Mary Wortley Montagu and the metaphors of journey
Authors: Duran Jane
Published: September 2022

In this paper, the work of Cynthia Lowenthal, Barbara Taylor, and others is adduced to support the notion that Lady Mary Wortley Montagu accomplished something remarkably progressive in her Turkish letters and her British “Spectatress” letters; part of the conclusion is that feminist work may proceed by metaphor as well as by argument and debate. Some of the innovation of her work is signaled by her use of comparison and contrast in describing her travels: she does not hesitate to juxtapose unusual items and situations. In addition, Lady Mary's work is briefly contrasted with that of Mary Astell and Mary Wollstonecraft.
To stripe or not to stripe: the origin of a novel foliar pigmentation pattern in monkeyflowers (Mimulus)
Authors: LaFountain Amy M. , McMahon Hayley E. , Reid Noah M. , Yuan Yao‐Wu
Published: September 2022

The origin of phenotypic novelty is one of the most challenging problems in evolutionary biology. Although genetic regulatory network rewiring or co‐option has been widely recognised as a major contributor, in most cases how such genetic rewiring/co‐option happens is completely unknown.

We have studied a novel foliar pigmentation pattern that evolved recently in the monkeyflower species Mimulus verbenaceus. Through genome‐wide association tests using wild‐collected samples, experimental crosses of laboratory inbred lines, gene expression analyses, and functional assays, we identified an anthocyanin‐activating R2R3‐MYB gene, STRIPY, as the causal gene triggering the emergence of the discrete, mediolateral anthocyanin stripe in the M. verbenaceus leaf.

Chemical mutagenesis revealed the existence of upstream activators and repressors that form a ‘hidden’ prepattern along the leaf proximodistal axis, potentiating the unique expression pattern of STRIPY. Population genomics analyses did not reveal signatures of positive selection, indicating that nonadaptive processes may be responsible for the establishment of this novel trait in the wild.

This study demonstrates that the origin of phenotypic novelty requires at least two separate phases, potentiation and actualisation. The foliar stripe pattern of M. verbenaceus provides an excellent platform to probe the molecular details of both processes in future studies.
Systemic control of plant regeneration and wound repair
Authors: Omary Moutasem , Matosevich Rotem , Efroni Idan
Published: September 2022

Plants have a broad capacity to regenerate damaged organs. The study of wounding in multiple developmental systems has uncovered many of the molecular properties underlying plants' competence for regeneration at the local cellular level. However, in nature, wounding is rarely localized to one place, and plants need to coordinate regeneration responses at multiple tissues with environmental conditions and their physiological state. Here, we review the evidence for systemic signals that regulate regeneration on a plant‐wide level. We focus on the role of auxin and sugars as short‑ and long‐range signals in natural wounding contexts and discuss the varied origin of these signals in different regeneration scenarios. Together, this evidence calls for a broader, system‐wide view of plant regeneration competence.
Osa‐miR160a confers broad‐spectrum resistance to fungal and bacterial pathogens in rice
Authors: Feng Qin , Wang He , Yang Xue‐Mei , Hu Zhang‐Wei , Zhou Xin‐Hui , Xiang Ling , Xiong Xiao‐Yu , He Xiao‐Rong , Zhu Yong , Li Guo‐Bang , Zhao Jing‐Hao , Ji Yun‐Peng , Hu Xiao‐Hong , Pu Mei , Zhou Shi‐Xin , Zhao Zhi‐Xue , Zhang Ji‐Wei , Huang Yan‐Yan , Fan Jing , Wang Wen‐Ming , Li Yan
Published: September 2022

Rice production is threatened by multiple pathogens. Breeding cultivars with broad‐spectrum disease resistance is necessary to maintain and improve crop production. Previously we found that overexpression of miR160a enhanced rice blast disease resistance. However, it is unclear whether miR160a also regulates resistance against other pathogens, and what the downstream signaling pathways are.

Here, we demonstrate that miR160a positively regulates broad‐spectrum resistance against the causative agents of blast, leaf blight and sheath blight in rice. Mutations of miR160a‐targeted Auxin Response Factors result in different alteration of resistance conferred by miR160a. miR160a enhances disease resistance partially by suppressing ARF8, as mutation of ARF8 in MIM160 background partially restores the compromised resistance resulting from MIM160.

ARF8 protein binds directly to the promoter and suppresses the expression of WRKY45, which acts as a positive regulator of rice immunity. Mutation of WRKY45 compromises the enhanced blast resistance and bacterial leaf blight resistance conferred by arf8 mutant.

Overall, our results reveal that a microRNA coordinates rice broad‐spectrum disease resistance by suppressing multiple target genes that play different roles in disease resistance, and uncover a new regulatory pathway mediated by the miR160a‐ARF8 module. These findings provide new resources to potentially improve disease resistance for breeding in rice.
Minimally Invasive Full‐endoscopic Posterior Cervical Foraminotomy and Discectomy: Introducing a Simple and Useful Localization Technique of the “V” Point
Authors: Zhong Guibin , Feng Fan , Su Xinjin , Chen Xiuyuan , Zhao Junduo , Shen Hongxing , Chen Jianwei , Lao Lifeng
Published: September 2022

Objective

Conventional localization technique of V point for full‐endoscopic posterior cervical foraminotomy and discectomy (FPCD) required repeated fluoroscopies, especially in patients with short and thick necks. To address this issue, the present study aimed to introduce a new localization technique of V point, and further evaluate its efficacy.

Methods

A K‐wire was inserted and fixed at the pedicle eye under A/P fluoroscopy, then a working channel was established quickly along with it. Thirty‐four patients who underwent minimally invasive FPCD assisted by the new technique were included in this study. The clinical and radiological data were collected and analyzed, including radiation dose, operative time, positioning time, visual analog scale (VAS) for neck and arm pain, neck disability index (NDI) scores, Cobb angle of operative level and range of motion of the cervical spine.

Results

All operations were performed successfully, and no iatrogenic nerve or vascular injury occurred. None of the patients needed to be transferred to open surgery or revision surgery. The mean radiation dose was found to be1.68 ± 0.36 mSv. The mean positioning time observed was 10.68 ± 5.42 min and the average operation time was 81.18 ± 10.87 min. The operation time significantly declined as the number of patients increased. A significant difference in operation time between the first (96.22 ± 10.36 min) and last quartile (75.00 ± 3.84 min) of cases was observed (t = 4.82, P < 0.001). The VAS scores for neck and arm pain, and NDI scores were significantly improved after surgery (PVAS−Neck<0.0001, PVAS−Arm<0.0001, PNDI<0.0001). Based on MacNab criteria, the excellent plus good rate was 91.17%. The Cobb angle of operative level and range of motion of the cervical spine were significantly improved postoperatively (t = 2.846, POA = 0.015; t = 2.232, PROM−CA = 0.026).

Conclusion

The new image‐assisted V point localization technique is simple and useful with little radiation exposure and short positioning time. FPCD assisted by the new technique could be a safe and effective alternative on properly selected patients.
Distal Humerus Morphological Analysis of Chinese Individuals: A Statistical Shape Modeling Approach
Authors: Zhao Wei , Guo Yao , Xu Chuangye , Pei Guoxian , Basnet Shiva , Pei Yanjun , Su Xiuyun
Published: September 2022

Objective

A detailed analysis of the morphology of distal humeral articulation can help in the creation of anatomic prostheses of hemiarthroplasty. This study used statistical shape modeling to evaluate the 3D morphology of the distal humerus in healthy Chinese individuals and to investigate the proper articular morphology differences.

Methods

A statistical shape model (SSM) of the distal humerus was created using CT scans of 106 survey‐confirmed nonpathologic elbows. In addition, the articular components of each principal component (PC) were selected and fitted on the mean mode. The Euclidean point‐to‐mesh distance of articular modes was calculated as a measurement the proper change in the morphology of the articulation.

Results

The first seven PCs jointly accounted for 80.9% of the total variation (44.4%, 12.2%, 7.9%, 5.9%, 4.1%, 3.4% and 3%, respectively). In the mean model, the distance between the medial and lateral epicondyles was 57.4 mm, the width of the articulation was 42.1 mm, and the angle of the transepicondylar line (TEL) and C line was 4.8°. The articular surface differences of the first PC were significant (RMS: 1.43 mm in the −3 SD model and 2.38 mm in the +3 SD model), whereas under other conditions, the differences were not remarkable despite the maximum deformation not exceeding 1 mm.

Conclusion

A novel method (SSM) was used to evaluate the 3D morphology of the distal humerus in healthy Chinese individuals and investigate the proper articular shape differences. We found the proper shape of articular surface basically transformed into one variation pattern which was relevant to the bone size, even though the morphology of distal humerus possessed complicated variation modes. The findings of this study can be helpful to design the next generation of elbow hemiarthroplasty in the future.
A pragmatic approach to infant feeding for food allergy prevention
Authors: McWilliam Vicki , Venter Carina , Greenhawt Matthew , Perrett Kirsten P. , Tang Mimi L. K. , Koplin Jennifer J. , Peters Rachel L.
Published: September 2022

Early introduction of allergenic foods into an infant's diet is currently the most promising strategy to prevent food allergy, with infant guidelines around the world shifting from promoting avoidance to actively encourage the introduction of allergenic foods in the infant diet. Infant feeding guidelines vary according to regional public health priorities, and knowledge gaps remain, resulting in ongoing challenges for clinicians and families to translate guidelines into practical strategies for the introduction of complementary foods for food allergy prevention. Evidence from Australia demonstrates high community support and uptake of revised guidelines with most parents introducing allergenic foods in the first year of life, although this has not had the expected impact on substantially reducing food allergy prevalence. To uptake of guidelines from other countries is less clear, and several barriers have been noted in infant feeding RCTs, which may warrant intervention strategies. Further research is needed to understand additional strategies for food allergy prevention, particularly in infants who develop food allergy prior to when they are developmentally ready to commence solids. Several RCTs are underway investigating preventative strategies that target the window before allergen ingestion, such as vitamin D supplementation, emollient use, and immunizations that prime the immune response away from a Th2‐driven allergic phenotype. Further research is also needed to understand the role of the environment and the host environment in the development of tolerance to foods.
Electronic Characterization of Vis–NIR Absorbing Noninnocent Ruthenium Oxyquinolate–merocyanine Complexes and their Photoacoustic Emission in Aqueous Micellar Solution†
Authors: Catsoulis Peter , Wang Shengwei , Yelleswarapu Chandra , Rochford Jonathan
Published: September 2022

The electronic and photophysical properties for a series of ruthenium(II) polypyridyl dyes are presented where a π‐accepting 5‐(vinyl‐cyanine)‐8‐oxyquinolate class of ligand is incorporated to yield an improved vis–NIR absorption. A combination of computational, UV–vis–NIR absorption, phosphorescence emission and cyclic voltammetry studies are used to probe the influence of these ligands on complex electronic and photophysical properties. To assess their potential as vis–NIR photoacoustic contrast agents, select complexes were formulated in a PBS buffer/Tween® 20 solvent system. The p‐quinolin‐1‐ium, 1,3,3‐trimethyl‐3H‐indol‐1‐ium and 1,1,3‐trimethyl‐1H‐benzo[e]indol‐3‐ium acceptor groups each impart a strong 680 nm optical absorption and photoacoustic emission on par with the performance exhibited by both the methylene blue and cryptocyanine commercial dyes.
The Relative Importance of Self‐Focused and Society‐Focused Values in Explaining Political Attitudes in Europe
Authors: Abdallah Saamah
Published: September 2022

Personal values predict political attitudes. Previous research in the United States suggests that so‐called “society‐focused” personal values such as universalism or conservation do so more than “self‐focused” values such as self‐direction and power. This study seeks to test the relevance of this distinction in a different context with four political attitudes using the European Social Survey. Three mechanisms are suggested to explain effects of self‐focused values on political attitudes. Although society‐focused values were generally found to be more important in predicting political attitudes, self‐focused values made a significant and often substantial contribution. On average, self‐focused values were able to predict around half of the variance in political attitudes that society‐focused values were. Power in particular played a role in predicting political attitudes, especially support for economic redistribution. Further analyses support the ideas that (1) even the most self‐focused value (i.e., hedonism) can play a relevant role in predicting political attitudes, and (2) self‐interest may play a role in explaining the effect of self‐focused values on political attitudes. Together, these findings highlight that a priori excluding self‐focused values from analyses of political attitudes—as studies have done in the past—may lead to important effects being overlooked.
Does federal flood hazard mitigation assistance affect community rating system participation?
Authors: Frimpong Eugene , Reilly Allison C. , Niemeier Deb
Published: September 2022

With the inexorable march of climate change, increased flooding is inevitable. Understanding the feedback between federal flood mitigation policies and the ways in which local governments build flood resilience is a significant gap in the literature. In particular, the effect that federal flood mitigation grants have on the intensity of local flood mitigation is nonexistent. This work measures flood risk mitigation by using the level of participation in FEMA's Community Rating System (CRS). Communities that participate in the CRS and undertake mitigation are awarded points; more points imply a higher level of participation. Since its inception in 1990, CRS communities have received considerably more federal pre‐disaster flood mitigation grants compared to non‐CRS communities. This study assesses the effect of federal pre‐disaster flood mitigation grants on the level of participation in the CRS program. We use data on Hazard Mitigation Assistance programs and CRS participation data between 2010 and 2015. We link these data to flood risk and socioeconomic information. Our results indicate (i) federal pre‐disaster flood mitigation grants do not appear to significantly influence the level of CRS participation, (ii) the effect of flood risk and socioeconomic factors on the level of CRS participation are mixed, and (iii) the current level of CRS participation is influenced by the previous level of CRS participation, which is not tied to federal pre‐disaster flood mitigation grant. These findings add to the growing discussions on the drivers and barriers of local flood risk mitigation.
Genetic background of anti‐Xga producers in Japanese blood donors
Authors: Watanabe‐Okochi Naoko , Uchikawa Makoto , Tsuneyama Hatsue , Ogasawara Kenichi , Shiraishi Risako , Masuno Atsuko , Onodera Takayuki , Tsuno Nelson‐Hirokazu , Muroi Kazuo
Published: September 2022

Background and Objectives

The Xg blood group is composed of two antigens, Xga (XG1) and CD99 (XG2 and MIC2). The XG and CD99 are homologous genes located on pseudoautosomal region 1 of the X and Y chromosomes. The expressions of Xga and CD99 are co‐regulated by a single nucleotide polymorphism (rs311103) in the GATA‐1 binding region. Another mechanism of the Xg(a−) phenotype is the genomic deletion of approximately 114 kb, including the XG gene. Anti‐Xga seems to be naturally occurring by detection in males who have never been transfused.

Materials and Methods

In this study, we identified 23 anti‐Xga producers among 580,115 donors (0.004%). Additional 12 anti‐Xga producers were also identified from a separate cohort.

Results

All 35 anti‐Xga producers were male. Genomic DNA was obtained from 34 of 35 producers, and all 34 producers were confirmed to carry the XG‐gene‐deficient allele (XGdel). The breakpoints of all 34 producers were identical. The XGdel was also identified in 12 non‐producers of anti‐Xga among 860 donors who have no antibodies against RBCs, and the breakpoints were also identical with the anti‐Xga producers.

Conclusion

Our results will serve as the basis for a more complete understanding of Xg blood group polymorphisms.
Leaving or rescuing the (story) map? – commentary to Saxinger, Sancho Reinoso and Wentzel
Authors: Lo Presti Laura
Published: September 2022

This paper reflects on some issues raised by the reading of Saxinger, Sancho Reinoso and Wentzel essay (published in the last issue of Fennia) and their theoretical and methodological concerns on how to conciliate geographic information systems (GIS) ontology with the representation of spatial-fuzzy qualitative data emerging out of ethnographic research. Recalling the intense debate between cartographers, GIS scientists and human geographers on the limits and failures of cartographic representation, the counterfactual doubt raised by Pickles in his book A History of Spaces: Cartographic Reason, Mapping, and the Geo-coded World, published in 2004, resonates strongly: “What if, after all, cartography and maps were not what we thought they were . . . or at least not only what we thought they were?” (page 194). Restoring such a question for the sake of this commentary is a way to rework the issue in an era of pervasive digital mapping, not by replacing the “quantitative” map with the “story” map – the dialectical model that has accompanied the critique of geographers during the 1980s and 1990s – but by multiplying the theoretical perspectives on the humanistic potential of maps, moving beyond the narrowed normative focus on “effective” storytelling as put by the recent The ESRI Story Map.
Modeling, Nonlinear Dynamics, and Bifurcation Analysis of the Rotor–Seal System Using a Subharmonic Sampling Strategy
Authors: Vashisht Rajiv Kumar
Published: September 2022

Rotors are used to transfer power from one component to the other component in various rotor dynamics applications like steam turbines, aerospace systems, and power generators. In certain applications, the seal is an important and inevitable component of the rotor dynamic system. The linear dynamics of the rotor is converted into nonlinear in the presence of a seal. The presence of a seal, can sometimes, trigger self-excited vibrations in rotor/seal systems. Generally, the amplitude of vibration during such vibrations is several times higher than normal steady-state vibrations. Due to this, other faults like transverse crack initialization and rotor/stator rub get accelerated. The rotating machinery working at high spinning speeds is more prone to this type of instability. Hence, the stability limits of the rotor/seal system must be known in advance for the safe operation of the rotating machinery. The dynamic behavior of such a system qualitatively varies corresponding to different system parameters of the rotating machinery. Cumbersome analytical methods have been used in the past for bifurcation analysis of rotor/seal systems. In the present work, system bifurcations have been investigated using a subharmonic sampling rate strategy. The proposed method is easy to implement and numerically efficient. The effect of various parameters like the spinning speed of the rotor, unstable mass, and seal clearance is investigated for the stability of the rotor/seal system. Experimental testing is done to verify the simulation results.
The Effect of Self-Rewetting Fluids and Surface Wettability Modification on the Thermal Performance of a Two-Phase Flat-Shaped Thermosyphon
Authors: Kalantarpour Raha , Vafai Kambiz
Published: September 2022

Two-phase flat-shaped thermosyphons have been studied to optimize their thermal performance and reduce the hot spot temperature. A two-dimensional model was employed to observe the evaporation and condensation process in the thermosyphon. Simulating the phase change process was achieved through an in-house user-defined function (UDF), which obtains mass and energy source terms, added to ansysfluent code. Utilizing 1-Buthanol aqueous solution instead of water as the working fluid induces a Marangoni flow to a hotter region and prevents the dry-out phenomenon in the evaporator section. Also, employing a super hydrophilic evaporator makes the liquid spread on the evaporator more evenly, and hinders drying out. Using a super hydrophobic condenser accelerates the detachment of the condensed liquid from the condenser and reduces the accumulation of liquid on the condenser. Furthermore, it accelerates the return of the liquid to the evaporator section to recharge the liquid and prevent the dry-out phenomenon. It has been observed that by using the 1-Buthaol solution, the condensed liquid is more likely to fall back on the center part of the evaporator, which has the highest temperature. Altering the working fluid to 1-Buthanol aqueous solution yields a temperature drop of 10 K for the maximum temperature for a 100 W heat input. The temperature drop increased to 39 K by utilizing a super hydrophobic condenser and super hydrophilic evaporator instead of a bare copper. It has been observed that increasing the filling ratio in the thermosyphon increases the thermal inertia and reduces the hot spot temperature.
Effects of temperature on immature development of Transeius montdorensis (Schicha) (Acari: Phytoseiidae) fed on Bemisia tabaci Gennadius (Hemiptera, Aleyrodidae) biotype Q
Authors: Sun Li , Liao Zhang-Xuan , Zheng Yue-Qiong , Chen Da-Song , Gao Gai-Gai , Chen Xia
Published: September 2022

The Australian predatory mite, Transeius montdorensis, is an important natural enemy of Bemisia tabaci, thrips, spider mites, and many other pests, and thus might be important for their biological control. Therefore, we aimed to determine whether temperature influences the development of T. montdorensis when preying on B. tabaci. The survival rate and development time of T. montdorensis under different temperature conditions were compared when fed with 1 st to 3 rd instar nymphs of B. tabaci as its prey. We analyzed the association between temperature and the growth rate of T. montdorensis. The results show that the developmental period of T. montdorensis was significantly affected by temperature. The development period of T. montdorensis was the longest (23.23 days) at 15 ℃ and the shortest (4.62 days) at 35 ℃. From 15–35 ℃, the developmental period of T. montdorensis correlated negatively with temperature. In addition, increasing temperature (15–30 ℃) promoted T. montdorensis survival. The survival rate was 64% at 15 ℃ and was highest (92%) at 30 ℃; however, survival was reduced as the temperature increased from 30 to 35 ℃; with only 66% survival at 35 ℃. The logistic equation is better at correlating temperature and development than the linear one. The different developmental stages of T. Montdorensis varied in the temperature thresholds of development and effective thermal summation. The temperature threshold of development was 10.45 ℃ at the immature stage, which had an effective thermal summation of 99.87 d ·℃.
A new species of the genus Cheylostigmaeus Willmann (Acari: Trombidiformes: Stigmaeidae) from Turkey
Authors: Doğan Salih , Doğan Sibel
Published: September 2022

Adult female, male and all immature life stages of Cheylostigmaeus occultatus sp. nov. are described and illustrated from Sansa Gorge and Pülümür Valley in Turkey. The female of the family Stigmaeidae is ordinarily used for identification purposes, but, to the contrary, the identification of species in the genus Cheylostigmaeus is mainly and unusually dependent on the male’s characters. However, the new species described in this paper has been identified from the female due to its distinctive characters: suranal shield is completely tucked under the body, suranal setae are slimmer and without hyaline sheath, subcapitulum is hyalinised distally, setae or2 are thickened, curved and spinulate distally.
Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction
Authors: Fujihara Kenji M. , Zhang Bonnie Z. , Jackson Thomas D. , Ogunkola Moses O. , Nijagal Brunda , Milne Julia V. , Sallman David A. , Ang Ching-Seng , Nikolic Iva , Kearney Conor J. , Hogg Simon J. , Cabalag Carlos S. , Sutton Vivien R. , Watt Sally , Fujihara Asuka T. , Trapani Joseph A. , Simpson Kaylene J. , Stojanovski Diana , Leimkühler Silke , Haupt Sue , Phillips Wayne A. , Clemons Nicholas J.
Published: September 2022

The mechanism of action of eprenetapopt (APR-246, PRIMA-1
MET
) as an anticancer agent remains unresolved, although the clinical development of eprenetapopt focuses on its reported mechanism of action as a mutant-p53 reactivator. Using unbiased approaches, this study demonstrates that eprenetapopt depletes cellular antioxidant glutathione levels by increasing its turnover, triggering a nonapoptotic, iron-dependent form of cell death known as ferroptosis. Deficiency in genes responsible for supplying cancer cells with the substrates for de novo glutathione synthesis (
SLC7A11
,
SHMT2
, and
MTHFD1L
), as well as the enzymes required to synthesize glutathione (
GCLC
and
GCLM
), augments the activity of eprenetapopt. Eprenetapopt also inhibits iron-sulfur cluster biogenesis by limiting the cysteine desulfurase activity of NFS1, which potentiates ferroptosis and may restrict cellular proliferation. The combination of eprenetapopt with dietary serine and glycine restriction synergizes to inhibit esophageal xenograft tumor growth. These findings reframe the canonical view of eprenetapopt from a mutant-p53 reactivator to a ferroptosis inducer.
An AMPK phosphoregulated RhoGEF feedback loop tunes cortical flow–driven amoeboid migration in vivo
Authors: Lin Benjamin , Luo Jonathan , Lehmann Ruth
Published: September 2022

Development, morphogenesis, immune system function, and cancer metastasis rely on the ability of cells to move through diverse tissues. To dissect migratory cell behavior in vivo, we developed cell type–specific imaging and perturbation techniques for
Drosophila
primordial germ cells (PGCs). We find that PGCs use global, retrograde cortical actin flows for orientation and propulsion during guided developmental homing. PGCs use RhoGEF2, a RhoA-specific RGS-RhoGEF, as a dose-dependent regulator of cortical flow through a feedback loop requiring its conserved PDZ and PH domains for membrane anchoring and local RhoA activation. This feedback loop is regulated for directional migration by RhoGEF2 availability and requires AMPK rather than canonical Gα
12/13
signaling. AMPK multisite phosphorylation of RhoGEF2 near a conserved EB1 microtubule-binding SxIP motif releases RhoGEF2 from microtubule-dependent inhibition. Thus, we establish the mechanism by which global cortical flow and polarized RhoA activation can be dynamically adapted during natural cell navigation in a changing environment.
Identification of immunomodulatory drugs that inhibit multiple inflammasomes and impair SARS-CoV-2 infection
Authors: de Almeida Letícia , da Silva Alexandre L. N. , Rodrigues Tamara S. , Oliveira Samuel , Ishimoto Adriene Y. , Seribelli Amanda A. , Becerra Amanda , Andrade Warrison A. , Ataide Marco A. , Caetano Camila C. S. , de Sá Keyla S. G. , Pelisson Natália , Martins Ronaldo B. , de Paula Souza Juliano , Arruda Eurico , Batah Sabrina S. , Castro Ricardo , Frantz Fabiani G. , Cunha Fernando Q. , Cunha Thiago M. , Fabro Alexandre T. , Cunha Larissa D. , Louzada-Junior Paulo , de Oliveira Rene D. R. , Zamboni Dario S.
Published: September 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces mild or asymptomatic COVID-19 in most cases, but some patients develop an excessive inflammatory process that can be fatal. As the NLRP3 inflammasome and additional inflammasomes are implicated in disease aggravation, drug repositioning to target inflammasomes emerges as a strategy to treat COVID-19. Here, we performed a high-throughput screening using a 2560 small-molecule compound library and identified FDA-approved drugs that function as pan-inflammasome inhibitors. Our best hit, niclosamide (NIC), effectively inhibits both inflammasome activation and SARS-CoV-2 replication. Mechanistically, induction of autophagy by NIC partially accounts for inhibition of NLRP3 and AIM2 inflammasomes, but NIC-mediated inhibition of NAIP/NLRC4 inflammasome are autophagy independent. NIC potently inhibited inflammasome activation in human monocytes infected in vitro, in PBMCs from patients with COVID-19, and in vivo in a mouse model of SARS-CoV-2 infection. This study provides relevant information regarding the immunomodulatory functions of this promising drug for COVID-19 treatment.
In situ diagnosis and simultaneous treatment of cardiac diseases using a single-device platform
Authors: Hwang Jae Chul , Kim Moohyun , Kim Sumin , Seo Hunkyu , An Soohwan , Jang Eui Hwa , Han Seung Yeop , Kim Mi Jung , Kim Nam Kyun , Cho Seung-Woo , Lee Sak , Park Jang-Ung
Published: September 2022

The in situ diagnosis of cardiac activities with simultaneous therapeutic electrical stimulation of the heart is key to preventing cardiac arrhythmia. Here, we present an unconventional single-device platform that enables in situ monitoring even in a wet condition and control of beating heart motions without interferences to the recording signal. This platform consists of the active-matrix array of pressure-sensitive transistors for detecting cardiac beatings, biocompatible, low-impedance electrodes for cardiac stimulations, and an alginate-based hydrogel adhesive for attaching this platform conformally to the epicardium. In contrast to conventional electrophysiological sensing using electrodes, the pressure-sensitive transistors measured mechanophysiological characteristics by monitoring the spatiotemporal distributions of cardiac pressures during heart beating motions. In vivo tests show mechanophysiological readings having good correlation with electrocardiography and negligible interference with the electrical artifacts caused during cardiac stimulations. This platform can therapeutically synchronize the rhythm of abnormal heartbeats through efficient pacing of cardiac arrhythmia.
Observation of robust zero-energy state and enhanced superconducting gap in a trilayer heterostructure of MnTe/Bi
2
Te
3
/Fe(Te, Se)
Authors: Ding Shuyue , Chen Chen , Cao Zhipeng , Wang Di , Pan Yongqiang , Tao Ran , Zhao Dongming , Hu Yining , Jiang Tianxing , Yan Yajun , Shi Zhixiang , Wan Xiangang , Feng Donglai , Zhang Tong
Published: September 2022

The interface between magnetic material and superconductors has long been predicted to host unconventional superconductivity, such as spin-triplet pairing and topological nontrivial pairing state, particularly when spin-orbital coupling (SOC) is incorporated. To identify these unconventional pairing states, fabricating homogenous heterostructures that contain such various properties are preferred but often challenging. Here, we synthesized a trilayer-type van der Waals heterostructure of MnTe/Bi
2
Te
3
/Fe(Te, Se), which combined s-wave superconductivity, thickness-dependent magnetism, and strong SOC. Via low-temperature scanning tunneling microscopy, we observed robust zero-energy states with notably nontrivial properties and an enhanced superconducting gap size on single unit cell (UC) MnTe surface. In contrast, no zero-energy state was observed on 2-UC MnTe. First-principle calculations further suggest that the 1-UC MnTe has large interfacial Dzyaloshinskii-Moriya interaction and a frustrated AFM state, which could promote noncolinear spin textures. It thus provides a promising platform for exploring topological nontrivial superconductivity.
Asymmetric multifunctionalization of alkynes via photo-irradiated organocatalysis
Authors: Dai Lei , Guo Jiami , Huang Qingqin , Lu Yixin
Published: September 2022

Alkynes represent a family of pivotal and sustainable feedstocks for various industries such as pharmaceuticals, agrochemicals, and materials, and they are widely used as important starting materials for the production of a broad range of chemical entities. Nevertheless, efficient structural elaborations of alkynes in chemical synthesis, especially asymmetric multifunctionalization of alkynes, remain largely unexplored. It is thus imperative to develop new asymmetric synthetic approaches, making use of these richly available chemical feedstocks, and enabling their conversion to value-added chiral molecules. Here, we disclose our findings on highly enantioselective multifunctionalization of alkynes by merging photochemistry and chiral phosphoric acid catalysis. Our reported one-pot synthetic protocol is applicable to all types of alkyne substrates, incorporating all three reactants in a fully atom-economic fashion to produce optically enriched tetrasubstituted triaryl- and diarylmethanes, important structural scaffolds in medicinal chemistry and biological sciences.
A lipoglycopeptide antibiotic for Gram-positive biofilm-related infections
Authors: Blaskovich Mark A. T. , Hansford Karl A. , Butler Mark S. , Ramu Soumya , Kavanagh Angela M. , Jarrad Angie M. , Prasetyoputri Anggia , Pitt Miranda E. , Huang Johnny X. , Lindahl Fredrik , Ziora Zyta M. , Bradford Tanya , Muldoon Craig , Rajaratnam Premraj , Pelingon Ruby , Edwards David J. , Zhang Bing , Amado Maite , Elliott Alysha G. , Zuegg Johannes , Coin Lachlan , Woischnig Anne-Kathrin , Khanna Nina , Breidenstein Elena , Stincone Anna , Mason Clive , Khan Nawaz , Cho Hye-Kyung , Karau Melissa J. , Greenwood-Quaintance Kerryl E. , Patel Robin , Wootton Mandy , James Meagan L. , Hutton Melanie L. , Lyras Dena , Ogunniyi Abiodun D. , Mahdi Layla K. , Trott Darren J. , Wu Xiaoqian , Niles Samantha , Lewis Kim , Smith Jordan R. , Barber Katie E. , Yim Juwon , Rice Seth Alan , Rybak Michael J. , Ishmael Chad R. , Hori Kellyn R. , Bernthal Nicholas M. , Francis Kevin P. , Roberts Jason A. , Paterson David L. , Cooper Matthew A.
Published: September 2022

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria (
Staphylococcus aureus
and
Streptococcus pneumoniae
) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally. We have developed a preclinical glycopeptide antibiotic, MCC5145, that has excellent potency (MIC
90
≤ 0.06 μg/ml) against hundreds of isolates of methicillin-resistant
S. aureus
(MRSA) and other Gram-positive bacteria, with a greater than 1000-fold margin over mammalian cell cytotoxicity values. The antibiotic has therapeutic in vivo efficacy when dosed subcutaneously in multiple murine models of established bacterial infections, including thigh infection with MRSA and blood septicemia with
S. pneumoniae
, as well as when dosed orally in an antibiotic-induced
Clostridioides difficile
infection model. MCC5145 exhibited reduced nephrotoxicity at microbiologically active doses in mice compared to vancomycin. MCC5145 also showed improved activity against biofilms compared to vancomycin, both in vitro and in vivo, and a low propensity to select for drug resistance. Characterization of drug action using a transposon library bioinformatic platform showed a mechanistic distinction from other glycopeptide antibiotics.
Cold shock domain–containing protein E1 is a posttranscriptional regulator of the LDL receptor
Authors: Smith Geoffrey A. , Padmanabhan Arun , Lau Bryan H. , Pampana Akhil , Li Li , Lee Clara Y. , Pelonero Angelo , Nishino Tomohiro , Sadagopan Nandhini , Xia Vivian Q. , Jain Rajan , Natarajan Pradeep , Wu Roland S. , Black Brian L. , Srivastava Deepak , Shokat Kevan M. , Chorba John S.
Published: September 2022

The low-density lipoprotein receptor (LDLR) controls cellular delivery of cholesterol and clears LDL from the bloodstream, protecting against atherosclerotic heart disease, the leading cause of death in the United States. We therefore sought to identify regulators of the LDLR beyond the targets of current therapies and known causes of familial hypercholesterolemia. We found that cold shock domain–containing protein E1 (CSDE1) enhanced hepatic
LDLR
messenger RNA (mRNA) decay via its 3′ untranslated region and regulated atherogenic lipoproteins in vivo. Using parallel phenotypic genome-wide CRISPR interference screens in a tissue culture model, we identified 40 specific regulators of the LDLR that were not previously identified by observational human genetic studies. Among these, we demonstrated that, in HepG2 cells, CSDE1 regulated the LDLR at least as strongly as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In addition, we showed that hepatic gene silencing of
Csde1
treated diet-induced dyslipidemia in mice to a similar degree as
Pcsk9
silencing. These results suggest the therapeutic potential of targeting CSDE1 to manipulate the posttranscriptional regulation of the
LDLR
mRNA for the prevention of cardiovascular disease. Our approach of modeling a clinically relevant phenotype in a forward genetic screen, followed by mechanistic pharmacologic dissection and in vivo validation, may serve as a generalizable template for the identification of therapeutic targets in other human disease states.
Ceftazidime-Avibactam plus Aztreonam for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria
Authors: Sempere Abiu , Viñado Belén , Los-Arcos Ibai , Campany David , Larrosa Nieves , Fernández-Hidalgo Nuria , Rodríguez-Pardo Dolors , González-López Juan José , Nuvials Xavier , Almirante Benito , Escolà-Vergé Laura
Published: September 2022

This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were
Enterobacterales
in 22 patients and
Pseudomonas aeruginosa
in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24).
Genotypic Resistance Testing of HIV-1 DNA in Peripheral Blood Mononuclear Cells
Authors: Chu Carolyn , Armenia Daniele , Walworth Charles , Santoro Maria M. , Shafer Robert W.
Published: September 2022

HIV-1 DNA exists in nonintegrated linear and circular episomal forms and as integrated proviruses. In patients with plasma viremia, most peripheral blood mononuclear cell (PBMC) HIV-1 DNA consists of recently produced nonintegrated virus DNA while in patients with prolonged virological suppression (VS) on antiretroviral therapy (ART), most PBMC HIV-1 DNA consists of proviral DNA produced months to years earlier.
An Unexpected Encounter: Respiratory Syncytial Virus Nonstructural Protein 1 Interacts with Mediator Subunit MED25
Authors: Van Royen Tessa , Sedeyn Koen , Moschonas George D. , Toussaint Wendy , Vuylsteke Marnik , Van Haver Delphi , Impens Francis , Eyckerman Sven , Lemmens Irma , Tavernier Jan , Schepens Bert , Saelens Xavier
Published: September 2022

Innate immune responses, including the production of type I and III interferons, play a crucial role in the first line of defense against RSV infection. However, only a poor induction of type I IFNs is observed during RSV infection, suggesting that RSV has evolved mechanisms to prevent type I IFN expression by the infected host cell.
Heritable and Nonheritable Rumen Bacteria Are Associated with Different Characters of Lactation Performance of Dairy Cows
Authors: Zang Xin-Wei , Sun Hui-Zeng , Xue Ming-Yuan , Zhang Zhe , Plastow Graham , Yang Tianfu , Guan Le Luo , Liu Jian-Xin
Published: September 2022

Rumen bacteria produce volatile fatty acids which exert a far-reaching influence on hepatic metabolism, mammary gland metabolism, and animal production. In the current study, 32 heritable and 674 nonheritable bacterial taxa at species level were identified, and shown to have different microbiability (overall community contribution) and mean microbiability (the average of a single taxon’s contribution) for lactation performance.
Supplemental Material: The Late Triassic Longmenshan lateral foreland thrusting: New insights from geological evidence and 3-D particle discrete-element simulation
Authors: Zhao Haonan , Guo Zhaojie , al. et
Published: September 2022

Figures of simulation results, U-Pb data set for syn-tectonic calcite veins and codes for the simulation of the lateral foreland thrusting model created for this study using PFC3D 5.0.
Outcomes of incoming and outgoing second opinions from a UK liver transplant centre
Authors: Parente Alessandro , Boyd Alexander , Mahgoub Sara , Morris Sean , Webb Kerry , Neuberger James , Armstrong Matthew J , Rajoriya Neil
Published: September 2022

Objective

Second transplant centre opinions (STCOs) for patients declined for liver transplantation are infrequent. We aimed to identify STCOs outcomes from a tertiary transplant centre.

Design

Referrals between 2012 and 2020 to Birmingham Unit were reviewed. Incoming: all referrals from out-of-region centres were collated. Outgoing: patients not listed in Birmingham were reviewed to identify referrals for STCOs to the other UK centres (A–F).

Results

2535 patients were assessed for liver transplantation during the study period. Incoming: among 1751 referrals, 23 STCOs (17 unit A, 3 unit B, 1 unit C, 1 unit D and 1 unit E) were provided by Birmingham. Of the STCOs, 13/23 (57%) patients remained unsuitable for transplantation. Therefore, 10/23 (43%) underwent a second liver transplant assessment, of whom five (50%) were still deemed unsuitable, three (30%) listed (one transplanted) and two (20%) died preassessment. Outgoing: among 426 patients not listed, eight (1.8%) patients were referred for STCO (4 unit E, 2 unit B, 1 unit D, 1 unit A). Three (38%) were listed, two (25%) were assessed and declined, two (25%) were unsuitable for assessment and one (12.5%) died while waiting. Combining incoming and outgoing Birmingham STCOs (n=31), six (19%) of STCOs were listed in a second centre.

Conclusion

Second transplant centre opinions are rare with the majority still deemed unsuitable for liver transplantation. This highlights potential resource implications especially when undergoing a full second formal assessment. A streamlined STCO process with sharing of investigations and use of telemedicine in appropriate patients may allow for greater transparency, quicker decision making and less use of labour-intensive resources.