bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating bobcat (Lynx rufus) abundance in Wisconsin during 1981-2015
Authors: Allen Maximilian L. , Roberts Nathan , Bauder Javan
Published: March 2020

Quantifying and estimating trends in wildlife abundance is critical for their management and conservation. Harvest-based indices are often used as a surrogate index for wildlife population. Sex-Age-Kill (SAK) models generally use the age-at-harvest of males and females, combined with annual mortality and reproduction rates to calculate a preharvest population estimate. We used and SAK model to estimate abundance for bobcats from 1981-2015. Pre-hunt population size ranged from approximately 1630-2148 during 1981-1995 after which the population increased to a maximum of 4439 in 2005 before declining to 2598 in 2013. Pre-hunt population size was highly correlated an index of abundance from winter track counts (r= 0.93). We found that the model, as currently implemented by WNDR, appears to provide an accurate trend of statewide bobcat abundance. SAK models more logistically feasible for long-term evaluations of population trends overbroad spatial extents than more intensive methods. While SAK models may be the only technique available to wildlife managers for estimating the abundance of harvested species, we encourage additional research to evaluate the effects of potential biases on estimates of abundance.
Potential evolutionary body size reduction in a Malagasy primate (Propithecus verreauxi) in response to human size-selective hunting pressure
Authors: Sullivan Alexis P. , Godfrey Laurie R. , Lawler Richard R. , Randrianatoandro Heritiana , Eccles Laurie , Culleton Brendan , Ryan Timothy M. , Perry George H.
Published: March 2020

The Holocene arrival of humans on Madagascar precipitated major changes to the island’s biodiversity. The now-extinct, endemic “subfossil” megafauna of Madagascar were likely hunted by the island’s early human inhabitants. Perhaps in part due to preferential hunting of larger prey, no surviving species on Madagascar is larger than 10 kg. Outside of Madagascar, size-selective hunting pressure has resulted in the phyletic dwarfism of many still-living species across a diversity of phyla. On Madagascar, some subfossil bones of extant lemurs are considerably larger than those of the modern members of their species, but relatively large distances between the subfossil localities and modern samples that have been compared to date makes it impossible to reject the possibility that these size differences more simply reflect pre-existing ecogeographic variation. Here, we used high-resolution 3D scan data to conduct comparative morphological analyses of subfossil and modern skeletal remains of one of the larger extant lemurs, Verreaux’s sifakas (Propithecus verreauxi) from subfossil and modern sites ∼10 km adjacent: Taolambiby (bones dated to 725-560 – 1075-955 cal. years before present) and Beza Mahafaly Special Reserve, respectively. We found that the average subfossil sifaka bone (n=12) is 9% and significantly larger than that of modern sifakas (n=31 individuals; permutation test; p=0.037). When restricting the analysis to the single element and side with the largest representation in the subfossil sample (n=4 right distal femora), the average subfossil bone is 10% larger (p=0.046). While we cannot yet conclude whether this size difference reflects evolutionary change or an archaeological aggregation/taphonomic process, if this is a case of phyletic dwarfism in response to human size-selective harvesting pressures then the estimated rate of evolutionary change is slightly higher than that previously calculated for other archaeological cases of this phenomenon.
SerraNA: a program to determine nucleic acids elasticity from simulation data
Authors: Velasco-Berrelleza Victor , Burman Matthew , Shepherd Jack W. , Leake Mark C. , Golestanian Ramin , Noy Agnes
Published: March 2020

The resistance of DNA to stretch, twist and bend is broadly well estimated by experiments and is important for gene regulation and chromosome packing. However, their sequence-dependence and how bulk elastic constants emerge from local fluctuations is less understood. Here, we presentSerraNA, which is an open software that calculates elastic parameters of double-stranded nucleic acids from dinucleotide length up to the whole molecule using ensembles from numerical simulations. The program reveals that global bendability emerge from local periodic bending angles in phase with the DNA helicoidal shape. We also applySerraNAto the whole set of 136 tetra-bp combinations and we observe a high degree of sequence-dependence for all elastic parameters with differences over 200%. Tetramers with TA and CA base-pair steps are especially flexible, while tetramers containing AA and AT tend to be the most rigid. Our results thus suggest AT-rich motifs generate extreme mechanical properties depending of the exact sequence ordering, which seems critical for creating strong global bendability on longer sequences when phased properly.SerraNAis a tool to be applied in the next generation of interdisciplinary investigations to further understand what determines the elasticity of DNA.

Graphical TOC Entry
Event-related potentials reflect prediction errors and pop-out during comprehension of degraded speech
Authors: Banellis Leah , Sokoliuk Rodika , Wild Conor J , Bowman Howard , Cruse Damian
Published: March 2020

Comprehension of degraded speech requires higher-order expectations informed by prior-knowledge. Accurate top-down expectations of incoming degraded speech cause a subjective semantic “pop-out” or conscious breakthrough experience. Indeed, the same stimulus can be perceived as meaningless when no expectations are made in advance. We investigated the ERP correlates of these top-down expectations, their error signals, and the subjective pop-out experience in healthy participants. We manipulated expectations in a word-pair priming noise-vocoded speech task and investigated the role of top-down expectation with a between-groups attention manipulation. Consistent with the role of expectations in comprehension, repetition priming significantly enhanced perceptual intelligibility of the noise-vocoded degraded targets for attentive participants. An early ERP was larger for mismatched (i.e. unexpected) targets than matched targets, indicative of an initial error signal not reliant on top-down expectations. Subsequently, a P3a-like ERP was larger to matched targets than mismatched targets only for attending participants - i.e. a pop-out effect. Rather than relying on complex post hoc interactions between prediction error and precision to explain this apredictive pattern, we consider our data to be consistent with prediction error minimisation accounts for early stages of processing followed by Global Neuronal Workspace-like breakthrough and processing in service of task goals.
Non-random association of MHC-I alleles in favor of high diversity haplotypes in wild songbirds revealed by computer-assisted MHC haplotype inference using the R package MHCtools
Authors: Roved Jacob , Hansson Bengt , Stervander Martin , Hasselquist Dennis , Westerdahl Helena
Published: March 2020

Major histocompatibility complex (MHC) genes play a central role for pathogen recognition by the adaptive immune system. The MHC genes are often duplicated and tightly linked within a small genomic region. This structural organization suggests that natural selection acts on the combined property of multiple MHC gene copies in segregating haplotypes, rather than on single MHC genes. This may have important implications for analyses of patterns of selection on MHC genes. Here, we present a computer-assisted protocol to infer segregating MHC haplotypes from family data, based on functions in the R package MHCtools. We employed this method to identify 107 unique MHC class I (MHC-I) haplotypes in 116 families of wild great reed warblers (Acrocephalus arundinaceus). In our data, the MHC-I genes were tightly linked in haplotypes and inherited as single units, with only two observed recombination events among 334 offspring. We found substantial variation in the number of different MHC-I alleles per haplotype, and the divergence between alleles in MHC-I haplotypes was significantly higher than between randomly assigned alleles in simulated haplotypes. This suggests that selection has favored non-random associations of divergent MHC-I alleles in haplotypes to increase the range of pathogens that can be recognized by the adaptive immune system. Further studies of selection on MHC haplotypes in natural populations is an interesting avenue for future research. Moreover, inference and analysis of MHC haplotypes offers important insights into the structural organization of MHC genes, and may improve the accuracy of the MHC region inde novogenome assemblies.
Assessing anaerobic gut fungal (Neocalliamstigomycota) diversity using PacBio D1/D2 LSU rRNA amplicon sequencing and multi-year isolation
Authors: Hanafy Radwa A. , Johnson Britny , Youssef Noha H. , Elshahed Mostafa S.
Published: March 2020

The anaerobic gut fungi (AGF, Neocallimastigomycota) reside in the alimentary tracts of herbivores where they play a central role in the breakdown of ingested plant material. Accurate assessment of AGF diversity has been hampered by inherent deficiencies of the internal transcribed spacer1 (ITS1) region as a phylogenetic marker. Here, we report on the development and implementation of the D1/D2 region of the large ribosomal subunit (D1/D2 LSU) as a novel marker for assessing AGF diversity in culture-independent surveys. Sequencing a 1.4-1.5 Kbp amplicon encompassing the ITS1-5.8S rRNA-ITS2-D1/D2 LSU region in the ribosomal RNA locus from fungal strains and environmental samples generated a reference D1/D2 LSU database for all cultured AGF genera, as well as the majority of candidate genera encountered in prior ITS1-based diversity surveys. Subsequently, a D1/D2 LSU-based diversity survey using long read PacBio SMRT sequencing technology was conducted on fecal samples from 21 wild and domesticated herbivores. Twenty-eight genera and candidate genera were identified in the 17.7 K sequences obtained, including multiple novel lineages that were predominantly, but not exclusively, identified in wild herbivores. Association between certain AGF genera and animal lifestyles, or animal host family was observed. Finally, to address the current paucity of AGF isolates, concurrent isolation efforts utilizing multiple approaches to maximize recovery yielded 216 isolates belonging to twelve different genera, several of which have no prior cultured-representatives. Our results establish the utility of D1/D2 LSU and PacBio sequencing for AGF diversity surveys, and the culturability of a wide range of AGF taxa, and demonstrate that wild herbivores represent a yet-untapped reservoir of AGF diversity.
A Fully Automatic Deep Learning System for COVID-19 Diagnostic and Prognostic Analysis
Authors: Wang Shuo , Zha Yunfei , Li Weimin , Wu Qingxia , Li Xiaohu , Niu Meng , Wang Meiyun , Qiu Xiaoming , Li Hongjun , Yu He , Gong Wei , Bai Yan , Li Li , Zhu Yongbei , Wang Liusu , Tian Jie
Published: March 2020

Coronavirus disease 2019 (COVID-19) has spread globally, and medical resources become insufficient in many regions. Fast diagnosis of COVID-19, and finding high-risk patients with worse prognosis for early prevention and medical resources optimization is important. Here, we proposed a fully automatic deep learning system for COVID-19 diagnostic and prognostic analysis by routinely used computed tomography.

We retrospectively collected 5372 patients with computed tomography images from 7 cities or provinces. Firstly, 4106 patients with computed tomography images and gene information were used to pre-train the DL system, making it learn lung features. Afterwards, 1266 patients (924 with COVID-19, and 471 had follow-up for 5+ days; 342 with other pneumonia) from 6 cities or provinces were enrolled to train and externally validate the performance of the deep learning system.

In the 4 external validation sets, the deep learning system achieved good performance in identifying COVID-19 from other pneumonia (AUC=0.87 and 0.88) and viral pneumonia (AUC=0.86). Moreover, the deep learning system succeeded to stratify patients into high-risk and low-risk groups whose hospital-stay time have significant difference (p=0.013 and 0.014). Without human-assistance, the deep learning system automatically focused on abnormal areas that showed consistent characteristics with reported radiological findings.

Deep learning provides a convenient tool for fast screening COVID-19 and finding potential high-risk patients, which may be helpful for medical resource optimization and early prevention before patients show severe symptoms.

Take-home message

Fully automatic deep learning system provides a convenient method for COVID-19 diagnostic and prognostic analysis, which can help COVID-19 screening and finding potential high-risk patients with worse prognosis.
COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome
Authors: Zhang Dan , Guo Rui , Lei Lei , Liu Hongjuan , Wang Yawen , Wang Yili , Qian Hongbo , Dai Tongxin , Zhang Tianxiao , Lai Yanjun , Wang Jingya , Liu Zhiqiang , Chen Tianyan , He Aili , O’Dwyer Michael , Hu Jinsong
Published: March 2020

Background

Excessive monocyte/macrophage activation with the development of a cytokine storm and subsequent acute lung injury, leading to acute respiratory distress syndrome (ARDS) is a feared consequence of infection with COVID-19. The ability to recognize and potentially intervene early in those patients at greatest risk of developing this complication could be of great clinical utility.

Methods

We performed detailed flow cytometric analysis of peripheral blood samples from 28 COVID-19 patients treated at Xian No.8 Hospital and the First Affiliated Hospital of Xian Jiaotong University in early 2020 in an attempt to identify factors that could help predict severity of disease and patient outcome.

Findings

While we did not detect significant differences in the number of monocytes between patients with COVID-19 and normal healthy individuals,we did identify significant morphological and functional differences, which are more pronounced in patients requiring prolonged hospitalization and ICU admission. Patients with COVID-19 have larger than normal monocytes, easily identified on forward scatter, side scatter analysis by routine flow cytometry,with the presence of a distinct population of monocytes with high forward scatter (FSC-high). On more detailed analysis, these FSC-high monocytes are CD11b+, CD14+, CD16+, CD68+, CD80+, CD163+, CD206+and secrete IL-6, IL-10 and TNF-alpha, consistent with an inflammatory phenotype.

Conclusions

The detection and serial monitoring of this subset of inflammatory monocytes using flow cytometry could be of great help in guiding the prognostication and treatment of patients with COVID-19 and merits further evaluation.
DDX5 targets tissue-specific RNAs to promote intestine tumorigenesis
Authors: Abbasi Nazia , Long Tianyun , Li Yuxin , Ma Evelyn , Yee Brian A. , Patel Parth R. , Sayed Ibrahim M , Varki Nissi , Das Soumita , Ghosh Pradipta , Yeo Gene W. , Huang Wendy J.M.
Published: March 2020

Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that an RNA binding protein DDX5 augments C3 and FABP1 expressions post-transcriptionally to promote tumorigenesis in the colon and small intestine, respectively. Mice with epithelial-specific knockout of DDX5 are protected from intestine tumorigenesis. The identification of DDX5 as the common upstream regulator of tissue-specific oncogenic molecules provides a new therapeutic target for intestine cancers.
Dually localized proteins found in both the apicoplast and mitochondrion utilize the Golgi-dependent pathway for apicoplast targeting inToxoplasma gondii
Authors: Prasad Aparna , Mastud Pragati , Patankar Swati
Published: March 2020

Like other apicomplexan parasites,Toxoplasma gondiiharbours a four-membraned endosymbiotic organelle - the apicoplast. Apicoplast proteins are nuclear-encoded and trafficked to the organelle through the endoplasmic reticulum (ER). From the ER to the apicoplast, two distinct protein trafficking pathways can be used. One such pathway is the cell’s secretory pathway involving the Golgi, while the other is a unique Golgi-independent pathway. Using different experimental approaches, many apicoplast proteins have been shown to utilize the Golgi-independent pathway, while a handful of reports show that a few proteins use the Golgi-dependent pathway. This has led to an emphasis towards the unique Golgi-independent pathway when apicoplast protein trafficking is discussed in the literature. Additionally, the molecular features that drive proteins to each pathway are not known. In this report, we systematically test eight apicoplast proteins, using a C-terminal HDEL sequence to assess the role of the Golgi in their transport. We demonstrate that dually localised proteins of the apicoplast and mitochondrion (TgSOD2,TgTPx1/2 andTgACN) are trafficked through the Golgi while proteins localised exclusively to the apicoplast are trafficked independent of the Golgi. Mutants of the dually localised proteins that localised exclusively to the apicoplast also showed trafficking through the Golgi. Phylogenetic analysis ofTgSOD2,TgTPx1/2 andTgACN suggested that the evolutionary origins ofTgSOD2,TgTPx1/2 lie in the mitochondrion whileTgACN appears to have originated from the apicoplast. Collectively, with these results, for the first time, we establish that the driver of the Golgi-dependent trafficking route to the apicoplast is the dual localisation of the protein to the apicoplast and the mitochondrion.
Persistent Epigenetic Reprogramming of Sweet Taste by Diet
Authors: Vaziri Anoumid , Khabiri Morteza , Genaw Brendan T. , May Christina E. , Freddolino Peter L. , Dus Monica
Published: March 2020

Diets rich in sugar, salt, and fat alter taste perception and food intake, leading to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the sensory neurons ofD. melanogasterflies to reduce sweet sensation and promote obesity. In animals fed high sugar, the binding of PRC2.1 to the chromatin of the sweet gustatory neurons is redistributed to repress a developmental transcriptional network that modulates the responsiveness of these cells to sweet stimuli, reducing sweet sensation. Importantly, half of these transcriptional changes persist despite returning the animals to a control diet, causing a permanent decrease in sweet taste. Our results uncover a new epigenetic mechanism that, in response to the dietary environment, regulates neural plasticity and feeding behavior to promote obesity.
Androgen signaling connects short isoform production to breakpoint formation at Ewing sarcoma breakpoint region 1 via an R-loop-dependent mechanism
Authors: Nicholas Taylor R. , Hollenhorst Peter C.
Published: March 2020

Ewing sarcoma breakpoint region 1 (EWSR1) encodes a multifunctional protein that can cooperate with the transcription factor ERG to promote prostate cancer. The EWSR1 gene is also commonly involved in oncogenic gene rearrangements in Ewing sarcoma. Despite the cancer relevance ofEWSR1, its regulation is poorly understood. Here we find that in prostate cancer, androgen signaling upregulates a 5’EWSR1isoform by promoting usage of an intronic polyadenylation site. This isoform encodes a cytoplasmic protein that can strongly promote cell migration and clonogenic growth. Deletion of an Androgen Receptor (AR) binding site near the 5’EWSR1polyadenylation site abolished androgen-dependent upregulation. This polyadenylation site is also near the Ewing sarcoma breakpoint hotspot, and androgen signaling promoted R-loop and breakpoint formation. RNase H overexpression reduced breakage and 5’EWSR1isoform expression suggesting an R-loop dependent mechanism. These data suggest that androgen signaling can promote R-loops internal to theEWSR1gene leading to early transcription termination and breakpoint formation.
Identification of sulfenylated cysteines inArabidopsis thalianaproteins using a disulfide-linked peptide reporter
Authors: Wei Bo , Willems Patrick , Huang Jingjing , Tian Caiping , Yang Jing , Messens Joris , Van Breusegem Frank
Published: March 2020

In proteins, hydrogen peroxide (H2O2) reacts with redox-sensitive cysteines to form cysteine sulfenic acid, also known asS-sulfenylation. These cysteine oxidation events can steer diverse cellular processes by altering protein interactions, trafficking, conformation, and function. Previously, we had identifiedS-sulfenylated proteins by using a tagged proteinaceous probe based on the yeast AP-1–like (Yap1) transcription factor that specifically reacts with sulfenic acids and traps them through a mixed disulfide bond. However, the identity of theS-sulfenylated amino acid residues remained enigmatic. Here, we present a technological advancement to identifyin situsulfenylated cysteines directly by means of the transgenic Yap1 probe. InArabidopsis thalianacells, after an initial affinity purification and a tryptic digestion, we further enriched the mixed disulfide-linked peptides with an antibody targeting the YAP1C-derived peptide (C598SEIWDR) that entails the redox-active cysteine. Subsequent mass spectrometry analysis with pLink 2 identified 1,745 YAP1C cross-linked peptides, indicating sulfenylated cysteines in over 1,000 proteins. Approximately 55% of these YAP1C-linked cysteines had previously been reported as redox-sensitive cysteines (S-sulfenylation,S-nitrosylation, and reversibly oxidized cysteines). The presented methodology provides a noninvasive approach to identify sulfenylated cysteines in any species that can be genetically modified.
Emergence of a hybrid PKS‐NRPS secondary metabolite cluster in a clonal population of the rice blast fungus Magnaporthe oryzae
Authors: Zhong Zhenhui , Lin Lianyu , Zheng Huakun , Bao Jiandong , Chen Meilian , Zhang Limei , Tang Wei , Ebbole Daniel J. , Wang Zonghua
Published: March 2020

Secondary metabolites (SMs) are crucial for fungi and vary in function from beneficial antibiotics to pathogenicity factors. To generate diversified SMs that enable different functions, SM‐coding regions rapidly evolve in fungal genomes. However, the driving force and genetic mechanism of fungal SM diversification in the context of host‐pathogen interactions remain largely unknown. Previously, we grouped field populations of the rice blast fungus Magnaporthe oryzae (syn: Pyricularia oryzae) into three major globally distributed clades based on population genomic analyses. Here, we characterize a recent duplication of an avirulent gene‐containing SM cluster, ACE1, in a clonal M. oryzae population (Clade 2). We demonstrate that the ACE1 cluster is specifically duplicated in Clade 2, a dominant clade in indica rice‐growing areas. With long‐read sequencing, we obtained chromosome‐level genome sequences of four Clade 2 isolates, which displayed differences in genomic organization of the ACE1 duplication process. Comparative genomic analyses suggested that the original ACE1 cluster experienced frequent rearrangement in Clade 2 isolates and revealed that the new ACE1 cluster is located in a newly formed and transposable element‐rich region. Taken together, these results highlight the frequent mutation and expansion of an avirulent gene‐containing SM cluster through transposable element‐mediated whole‐cluster duplication in the context of host‐pathogen interactions.
Prospective study of the safety and effectiveness of droperidol in elderly patients for pre‐hospital acute behavioural disturbance
Authors: Page Colin B , Parker Lachlan E , Rashford Stephen J , Kulawickrama Sanjeewa , Isoardi Katherine Z , Isbister Geoffrey K
Published: March 2020

Objective

Acute behavioural disturbance in the elderly (≥65 years) is a significant issue for emergency medical services with increasing prevalence of dementia and aging populations. We investigated the pre‐hospital safety and effectiveness of droperidol in the elderly with acute behavioural disturbance.

Methods

This was a pre‐hospital prospective observational 1‐year study of elderly patients with acute behavioural disturbance. The primary outcome was proportion of adverse events (AEs) (airway intervention, oxygen saturation <90% and/or respiratory rate <12/min, systolic blood pressure <90 mmHg, sedation assessment tool score of −3 and dystonic reactions). Secondary outcomes included time to sedation, additional sedation, proportion with successful sedation.

Results

There were 149 patients (males 78 [52%], median age 78 years; 65–101 years) presenting on 162 occasions. Dementia was the commonest cause (107/164 [65%]) of acute behavioural disturbance. There were six AEs in five patients (5/162 [3%]; 95% confidence interval 1–7). Three had hypotension, one with associated hypoxia (80%); and two had respiratory AEs (respiratory rate, 10/min [no hypoxia] and hypoxia [88%] which required oxygen). Median time to sedation was 19 min (interquartile range 12–29 min). Additional sedation was given in 2/162 patients during ambulance transfer and 16/162 within an hour of hospital arrival; 24/162 (15%) failed to sedate in the ambulance; 16 subsequently settled in ED and 8/24 received additional sedation. Of 162, 123 (76%) patients successfully sedated, without AEs or additional sedation. Of 162, 114 (70%) patients received 5 mg, 46 (29%) received two doses of 5 mg and two patients (1%) received three doses.

Conclusions

Droperidol appeared to be safe and effective for pre‐hospital sedation of acute behavioural disturbance in elderly patients.
Portable heaters for microhabitat heating experiments
Authors: Baer Christina S. , Dierick Diego , Garcia‐Robledo Carlos
Published: March 2020

Global warming will likely cause more ecological change by altering how species interact with each other than by directly affecting individual species. Field heating experiments are essential to test how warming will change species interactions. However, such experiments pose many logistical challenges, including heater construction and accuracy and accessing necessary infrastructure.

To facilitate these experiments, we developed portable active heaters suitable for heating microhabitats and sites of species interactions. We validated heater performance using two different target microhabitats: rolled leaf refugia and aquatic microcosms.

Using plastic mesh, resistive heating wire and an Arduino UNO microcontroller system with a custom shield, we built adjustable heaters that can dynamically heat small targets to at least 5°C above ambient temperature. Leaf target systems were heated with mean absolute errors (MAE) of 0.40–1.06°C. Water target systems were heated with MAE of 0.02–0.04°C.

These heaters can be customized to accurately heat a wide range of target sites (leaves, flowers, nests, small pools of water, etc.), many of which cannot be easily heated with traditional heaters. They can be easily constructed and require less field site infrastructure than many active heaters. These heaters' adjustability and portability mean that they can help test the effects of global warming in many situations, particularly in remote and lightly developed areas.
Comparative analysis of occlusion methods for artificial sphincters
Authors: Marziale Leonardo , Lucarini Gioia , Mazzocchi Tommaso , Ricotti Leonardo , Menciassi Arianna
Published: March 2020

An artificial sphincter is a device that replaces the function of the biological sphincter by occluding the relative biological lumen. The investigation of occlusion methods for artificial sphincters is crucial for a reliable and effective design of such devices. The compression induced onto the tissue by a certain pressure depends on the biomechanical and physiological features of the lumen and on the specific occlusion method. A numerical model and an experimental evaluation are presented here to assess the efficiency of different occlusion methods. Numerical models of circumferential occlusion and clamping occlusion methods to simulate the compression of the biological lumen were developed. Results revealed a relationship between the efficiency of the occlusion method and the physiological condition of the lumen. With differences related to the testing setup, this relationship was also confirmed experimentally by conducting tests on biological simulators. We analyzed the occlusion method to adopt as the physiological pressure (ie, leakage pressure values) changed. In particular, we focused on the urinary incontinence, which is a dysfunction involving the external sphincter surrounding the urethra. In this scenario, we demonstrated that a clamping occlusion is an efficient method to compress the urethra, whose physiological pressures range between 4 and 12 kPa. The clamping occlusion method resulted up to 35% more efficient in terms of sealing pressure than the circumferential one for a closing pressure varying between 2.3 and 11.5 kPa.
Fluid‐structure interaction analysis of a collapsible axial flow blood pump impeller and protective cage for Fontan patients
Authors: Hirschhorn Matthew , Bisirri Evan , Stevens Randy , Throckmorton Amy L.
Published: March 2020

Limited donor organs and alternative therapies have led to a growing interest in the use of blood pumps as a treatment strategy for patients with single functional ventricle. The present study examines the use of collapsible and flexible impeller, cage, and diffuser designs of an axial blood pump for Fontan patients. Using one‐way fluid‐structure interaction (FSI) studies, the impact of blade deformation on blood damage and pump performance was investigated for flexible impellers. We evaluated biocompatible materials, including Nitinol, Bionate 80A polyurethane, and silicone for flow rates between 2.0‐4.0 L/min and rotational speeds of 3000‐9000 rpm. The level of deformation experienced by a cage and diffuser made of surgical stainless steel (control), Nitinol, and Bionate 80A polyurethane was also predicted using one‐way FSI. The fluid pressure on the surface of the impeller, cage, and diffuser was determined using computational fluid dynamics (CFD), and then, the surface pressure was exported and used to investigate the impeller, cage, and diffuser deformation using finite element analysis. Finally, deformed impeller geometries were imported into the CFD software to determine the implication of deformation on pressure generation, blood damage index, and fluid streamlines. It was found that rotational speed, and not flow rate, is the largest determinant of impeller deformation, occurring at the blade trailing edges. The models predicted the maximum impeller deformation for Nitinol to be 40 nm, Bionate 80A polyurethane to be 106 μm, and silicone to be 2.8 mm, all occurring at 9000 rpm. The effects of silicone deformation on performance were significant, particularly at speeds above 5000 rpm where a decrease in pressure generation of more than 10% was observed. Despite this loss, the pressure generation at 5000 rpm exceeded the level required to alleviate Fontan complications. A blood damage estimation was performed and levels remained low. The effect of significant impeller deformation on blood damage was inconsistent and requires additional investigation. Cage and diffuser geometries made of steel and Nitinol deformed minimally but Bionate 80A experienced unacceptable levels of deformation, particularly in the free‐flow case without a spinning impeller. These results support the continued evaluation of a flexible, pitch‐adjusting, axial‐flow, mechanical assist device as a clinical therapeutic option for patients with dysfunctional Fontan physiology.
Quantifying sand delivery to deep water during changing sea‐level: Numerical models from the Quaternary Brazos Icehouse continental margin
Authors: Falivene Oriol , Prather Bradford E. , Martin John
Published: March 2020

Sequence stratigraphy for clastic continental margins predicts the development of sand‐rich turbidite deposits during specific times in relation to base‐level cycles. It is now widely understood that deltas can extend to the shelf‐edge forced by high sediment flux and/or base level, providing a direct connection to transfer sediment and sand to the slope and basin floor even during high base level periods. Herein, we build a stratigraphic forward model for the last 120 kyr of the fluvio‐deltaic to deep‐water Brazos system (USA) where sediment partitioning along an Icehouse continental margin can be evaluated. The reduced‐complexity stratigraphic forward model employs geologically constrained input parameters and mass balance. The modelled architecture is consistent with the location of depositional units previously mapped in the shelf. Sand bypasses the shelf and upper slope between 35 to 15 kyr before present and only about 20%–30% of all the sediment and sand supplied to the system is transferred to deep water. Several scenarios based on the initial Brazos model investigate the relationships between base level and deep‐water sand ratio (DWSR). DWSR is defined as the relative amount of sand transferred to the deep‐water portions of the system subdivided by the total sand input to the model. Linear correlations between DWSR and base level change rates or base level are very poor. Short‐term variability due to local processes (for example avulsions) is superimposed to the long‐term trends and mask the base level signal. DWSR for an entire base‐level cycle is mainly controlled by the proportion of time the delta stays docked at the shelf‐edge. Stratigraphic forward models are useful to complement field observations and quantify how different processes control stratigraphy, which is important for making predictions in areas with limited information.
Reactive dyeing of silk using commercial acid dyes based on a three‐component Mannich‐type reaction
Authors: Guo Qing , Chen Wei‐guo , Cui Zhi‐hua , Jiang Hua
Published: March 2020

Acid dyes are employed for commercially dyeing silk, which results in ionic bonds between the silk fibroin and the dye. This generally leads to low wet fastness properties for dyed silk fabrics. In this work, three commercial acid dyes with aromatic primary amine structures were selected to dye silk using a Mannich‐type reaction, resulting in improved wet fastness of dyed silk by forming covalent bonds between silk fibroin and dye. The Mannich‐type reactive dyeing was applied to silk fabrics at both 30 and 90°C in trials. Dyeing at 90°C can shorten the dyeing time compared with dyeing at 30°C, even although dye exhaustion and relative fixation at 90°C were a little lower. The dyeing process was optimised when the dyeing temperature was 90°C, dyebath pH 4, dye‐to‐formaldehyde ratio 1:30 and holding dyeing time 60 minutes. The results showed that the dye exhaustion on silk fabrics for the three aromatic primary amine‐containing acid dyes exceeded 94% and their relative fixation was over 80%. Their washing and rubbing fastness reached grade 4 or higher. Hence, the colour fastness properties of dyed silk fabrics using the Mannich‐type reactive dyeing method is superior to the conventional acid dyeing method using the same aromatic primary amine‐containing acid dyes. The Mannich‐type reactive dyeing for silk fabrics at 90°C can be developed into a novel and rapid reactive dyeing method, promising an effective dyeing process with excellent colour fastness.
p75NTR−/− mice exhibit an alveolar bone loss phenotype and inhibited PI3K/Akt/β‐catenin pathway
Authors: Wang Yingying , Yang Kun , Li Gang , Liu Rui , Liu Junyu , Li Jun , Tang Mengying , Zhao Manzhu , Song Jinlin , Wen Xiujie
Published: March 2020

Objectives

The aim of this study was to investigate the role of p75 neurotrophin receptor (p75NTR) in regulating the mouse alveolar bone development and the mineralization potential of murine ectomesenchymal stem cells (EMSCs). Moreover, we tried to explore the underlying mechanisms associated with the PI3K/Akt/β‐catenin pathway.

Materials and methods

p75NTR knockout (p75NTR−/−) mice and wild‐type (WT) littermates were used. E12.5d p75NTR−/− and WT EMSCs were isolated in the same pregnant p75NTR‐/+ mice from embryonic maxillofacial processes separately. Mouse alveolar bone mass was evaluated using micro‐CT. Differential osteogenic differentiation pathways between p75NTR−/− and WT EMSCs were analysed by RNA‐sequencing. The PI3K inhibitor LY294002 and PI3K agonist 740Y‐P were used to regulate the PI3K/Akt pathway in EMSCs. p75NTR overexpression lentiviruses, p75NTR knock‐down lentiviruses and recombined mouse NGF were used to transfect cells.

Results

The alveolar bone mass was found reduced in the p75NTR knockout mouse comparing to the WT mouse. During mineralization induction, p75NTR−/− EMSCs displayed decreased osteogenic capacity and downregulated PI3K/Akt/β‐catenin signalling. The PI3K/Akt/β‐catenin pathway positively regulates the potential of differential mineralization in EMSCs. The promotive effect of p75NTR overexpression can be attenuated by LY294002, while the inhibitory effect of p75NTR knock‐down on Runx2 and Col1 expression can be reversed by 740Y‐P.

Conclusion

Deletion of p75NTR reduced alveolar bone mass in mice. P75NTR positively regulated the osteogenic differentiation of EMSCs via enhancing the PI3K/Akt/β‐catenin pathway.
Enhanced Characterization of Drug Metabolism and the Influence of the Intestinal Microbiome: A Pharmacokinetic, Microbiome, and Untargeted Metabolomics Study
Authors: Jarmusch Alan K. , Vrbanac Alison , Momper Jeremiah D. , Ma Joseph D. , Alhaja Maher , Liyanage Marlon , Knight Rob , Dorrestein Pieter C. , Tsunoda Shirley M.
Published: March 2020

Determining factors that contribute to interindividual and intra‐individual variability in pharmacokinetics (PKs) and drug metabolism is essential for the optimal use of drugs in humans. Intestinal microbes are important contributors to variability; however, such gut microbe‐drug interactions and the clinical significance of these interactions are still being elucidated. Traditional PKs can be complemented by untargeted mass spectrometry coupled with molecular networking to study the intricacies of drug metabolism. To show the utility of molecular networking on metabolism we investigated the impact of a 7‐day course of cefprozil on cytochrome P450 (CYP) activity using a modified Cooperstown cocktail and assessed plasma, urine, and fecal data by targeted and untargeted metabolomics and molecular networking in healthy volunteers. This prospective study revealed that cefprozil decreased the activities of CYP1A2, CYP2C19, and CYP3A, decreased alpha diversity and increased interindividual microbiome variability. We further demonstrate a relationship between the loss of microbiome alpha diversity caused by cefprozil and increased drug and metabolite formation in fecal samples. Untargeted metabolomics/molecular networking revealed several omeprazole metabolites that we hypothesize may be metabolized by both CYP2C19 and bacteria from the gut microbiome. Our observations are consistent with the hypothesis that factors that perturb the gut microbiome, such as antibiotics, alter drug metabolism and ultimately drug efficacy and toxicity but that these effects are most strongly revealed on a per individual basis.
From British mandate to post Anglo‐American invasion: Reproduction of ethno‐sectarian divides and the breakdown of social cohesion in Mosul
Authors: Özekin Muhammed Kürşad
Published: March 2020

The invasion of Iraq in 2003 ushered in an era of great uncertainty and turbulence that left the country in an economically crippled, politically unstable, and socially desperate situation. While the built‐in ethno‐sectarian divides have been widely used as analytical categories to address the enduring violence in both Mosul and the rest of Iraq, little attention has been paid to the connection between the long‐term Anglo‐American invasion of Iraq and the ethno‐sectarian violence that currently characterizes Mosul. This study argues that while ethnic and sectarian loyalties have historically persisted in their social forms since the rule of the Ottoman Empire, the highly politicized and violent forms of ethno‐sectarian conflict are modern phenomena, produced and reproduced under the conditions of the decades‐long British and American interventions. The study retrospectively evaluates the current dynamics of ethno‐sectarian confrontations in Mosul through two stages in the long historiography of modern Iraq. The first section reveals how Britain’s mismanagement of colonial Iraq set the initial conditions for communal cleavages and instability in today’s Mosul. Later, the second section turns its attention toward the contemporary manifestation of ethno‐sectarian violence, particularly under the U.S.‐led occupation.
Iran's global reach: The Islamic Republic of Iran's policy, involvement, and activity in Africa
Authors: Shahvar Soli
Published: March 2020

The aim of this study is to analyze the Islamic Republic of Iran (IRI)'s policy toward and involvement in the African continent as a case study of the IRI's global policy and reach. The aspiration of the IRI's leadership for international standing and support coupled with a desire to export its revolutionary model and extend its influence beyond its borders have shaped its activity on many continents, including Africa. Africa's strategic location, past colonial experience, political position, rich resources, large Muslim population, and economic attractiveness have all contributed to shaping the IRI's activity within it. This study analyzes IRI's foreign policy in general and its implementation in Africa in particular, identifying the different historical phases of its activity in Africa, distinguishing between the various African regions, the main Iranian organizations involved therein, the means of and channels for Iranian involvement in Africa, and the reasons for IRI's gains and losses on that continent. The study shows how the Islamic regime has managed, during its 40 years of rule, through pragmatism and resilience, to gain influence and support, has endeavored to balance its losses, and has adapted to new circumstances in the African continent.
Life cycles, phenology and genetic structure of endangered Megacrania tsudai Shiraki (Phasmatodea: Phasmatidae): Male individuals from a geographic parthenogenesis species
Authors: Wu I‐Hsin , Liu Hsui‐Huei , Chen Yu‐Yen , Tsai Cheng‐Lung , Yu Yi‐Ching , Hsiao Chung‐Yi , Yeh Wen‐Bin
Published: March 2020

Megacrania tsudai, a peripherally distributed member of Megacrania, requires conservation in Taiwan; it has limited distribution in Taiwan and its eastern offshore islands. It feeds on screw pines (Pandanus odoratissimus) in nature and has demonstrated a specific defensive mechanism involving actinidine secretion from the prothoracic gland. However, details of its distribution area, life cycle and developmental phenology remain largely unknown. In this study, a field survey and review of published works revealed M. tsudai distribution in coastal zones and along river shores near estuaries. At room temperature, the egg period was 128 days. The development of the first to sixth instars required 17, 26, 27, 26, 34 and 43 days, respectively, on average; and a generation cycle required approximately 204 days. The phenology of the mesonotal granules was recorded. Moreover, genetic analysis of the mitochondrial cytochrome oxidase I (COI), 16S ribosomal DNA (16S rDNA) and the nuclear ribosomal spacer indicated the occurrence of genetic drift. Therefore, the rearing procedures proposed in this study for the primary and last instars of M. tsudai can facilitate its conservation. Megacrania tsudai was previously recorded as parthenogenetic; however, two male individuals were fostered unexpectedly. The male body length was 91 mm, which is shorter than the female length (120 mm). During mating, the male climbs onto the female's back and protrudes its genitalia downward. Geographical parthenogenesis is likely the reproductive strategy among peripheral M. tsudai; however, the rarely found M. tsudai male could be an intermediate link of reproductive strategy in the transition from tychoparthenogenesis to parthenogenesis.
Discovery of Buprestidae rock art in central Iran suggests historical relationship between jewel beetles and mankind
Authors: Kolnegari Mahmood , Naserifard Mohammad , Hazrati Mandana
Published: March 2020

An extensive field survey was undertaken by a group of archaeologists and entomologists to discover arthropod‐like petroglyphs in the center of Iran during 2017 to 2018. A remarkable motif approximately 13 × 5 cm in size was found in the Teymareh rock art site, located in Markazi province, which has yet to be reported. The single rock art distinctly represents a hexapod organism with small antenna, a streaked narrow body and a tapering abdomen. Based on distinguishing aspects of the inspected motif and morphological information of species within the class Insecta, we identified it as a jewel beetle (Coleoptera: Buprestidae). We propose that the buprestid drawing was derived from a historic artist who admired the aesthetic value of the jewel beetle. The jewel beetle's characters within Persian Plateau folklore are also briefly discussed.
Qualitative Ras pathway signature for cetuximab therapy reveals resistant mechanism in colorectal cancer
Authors: Song Kai , Lu Haibo , Jin Liangliang , Wang Kai , Guo Wenbing , Zheng Hailong , Li Keru , He Chuchu , You Tianyi , Fu Yelin , Yang Jing , Zhao Wenyuan , Guo Zheng
Published: March 2020

Cetuximab therapy, which heavily relies on the activation of Ras pathway, has been used in KRAS, NRAS, BRAF, and PIK3CA wild‐type colorectal cancer (CRC) (Ras‐normal). However, the response rate only reached 60%, due to false‐negative mutation detection and mutation‐like transcriptome features in wild‐type patients. Herein, by integrating RNA‐seq, microarray, and mutation data, we developed a Ras pathway signature by characterizing KRAS/NRAS/BRAF/PIK3CA mutations to identify the hidden nonresponders from the Ras‐normal patients by mutation detection. Using public and in‐house data of CRC patients treated with cetuximab, discovery of the signature could identify cetuximab‐resistant samples from the Ras‐normal samples. Cetuximab resistance‐related genes, such as PTEN, were significantly and frequently mutated in the identified Ras‐activated samples, whereas two cetuximab sensitivity‐related genes, APC and TP53, showed comutation and significantly higher mutation frequencies in the remaining Ras‐normal samples. Furthermore, all the NF1‐ and BCL2L1‐mutated samples were identified as Ras‐activated from the Ras‐normal samples by the Ras pathway signature with significantly under‐regulated expression. Genes co‐expressed with the two genes were both involved in Ras signaling pathway, the out‐of‐control of which could be attributed by the genes' loss‐of‐function mutations. To improve the treatment of cetuximab in CRC, NF1 and BCL2L1 could be used as complementary detection technique to those applied in clinical. In conclusion, the proposed Ras pathway signature could identify the hidden CRC patients resistant to cetuximab therapy and help to reveal resistance mechanisms.