bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)
Authors: Liu Lu , Shao Yiming , Zhang Yixuan , Yang Yunxi , Huang Jiamin , Li Linbin , Sun Ran , Zhou Yuying , Su Yicheng , Sun Bingwei
Published: July 2021

Background

Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury. However, the pathophysiological mechanism of vascular leakage is still unclear. The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.

Methods

Neutrophils were isolated from human peripheral blood by magnetic beads sorting. ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma. The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice, and high-quality video were provided. Adhesion-related molecules were investigated by qRT-PCR. The damage to glycocalyx of mice vascular endothelial cells was observed by transmission electron microscope and scanning electron microscope. Proteomic analysis, flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite (HOCl) and CD44 of human vascular endothelial cells.

Results

In this study, we found that rapidly increasing activated neutrophils secrete heparin binding protein (HBP) and myeloperoxidase (MPO) after severe burn injury. Increased HBP triggers vascular leakage with synergy of MPO, results in systemic edema and burn shock. Furthermore, we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx. Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage. However, MPO inhibitors partially protect the glycocalyx of vascular endothelial cells. The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.

Conclusions

Taken together, these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns. Targeted intervention in these two biomolecules may introduce new strategies for helping to reduce large amount of fluid loss and subsequent burn shock.
Real-time machine learning-based intensive care unit alarm classification without prior knowledge of the underlying rhythm
Authors: Au-Yeung Wan-Tai M , Sevakula Rahul K , Sahani Ashish K , Kassab Mohamad , Boyer Richard , Isselbacher Eric M , Armoundas Antonis A
Published: July 2021

Aims

This work attempts to develop a standalone heart rhythm alerting system for the intensive care unit (ICU), where life-threatening arrhythmias have to be identified/alerted more precisely and more instantaneously (i.e. with lower latency) than existing bedside monitors.

Methods and results

We use the dataset from the PhysioNet 2015 Challenge, which contains records that led to true and false arrhythmic alarms in the ICU. These records have been re-annotated as one of eight classes, namely (i) asystole, (ii) extreme bradycardia, (iii) extreme tachycardia, (iv) ventricular fibrillation (VF), (v) ventricular tachycardia (VT), (vi) normal sinus rhythm, (vii) sinus tachycardia, and (viii) noise/artefacts. Arrhythmia-specific features and features that measure the signal quality were extracted from all the records. To improve VF detection, an improved, over an existing, single-lead R-wave detection was developed that takes into account the R-waves detected in all electrocardiographic (ECG) leads. To avoid false R-wave detection due to pacing spikes, ECG signals were filtered with a low pass filter prior to R-wave detection, while the raw signals were used for feature extraction. Random forest was used as the classifier, and 10-time five-fold cross-validation, resulted in a macro-average sensitivity of 81.54%.

Conclusions

In conclusion, comparing with the bedside monitors used in the PhysioNet 2015 competition, we find that our method achieves higher positive predictive values for asystole, extreme bradycardia, VT, and VF; furthermore, our method is able to alert the presence of arrhythmia instantaneously, i.e. up to 4 s earlier.
Diversion or Inclusion? Alternative Routes to Higher Education Eligibility and Inequality in Educational Attainment in Germany
Authors: Schindler Steffen , Bittmann Felix
Published: July 2021

In the 1960s, educational reforms have been initiated in Germany to make the rigid stratified school system more permeable. While maintaining between-school tracking in secondary education, several second-chance options have been introduced that established alternative routes to higher education. This study aims to evaluate whether these alternative routes were successful in reducing the levels of social inequality in both higher education eligibility and higher education attainment. We draw on life-course data from the German National Educational Panel Study and conduct simulation analyses. We conclude that it is very unlikely that the reforms had any substantive influence on the level of inequality in both outcome variables.
Evaluating the Positive Experience of Caregiving: A Systematic Review of the Positive Aspects of Caregiving Scale
Authors: Lee Yeonjung , Li Lun
Published: July 2021

Background and Objectives

As attention to positive caregiving experience increases, there is growing evidence concerning how the identification of the positive aspects of caregiving can be beneficial in supporting caregivers. The purpose of the current study is to review the literature where the Positive Aspects of Caregiving Scale (PACS) was used, identify the ways studies have used the PACS, and summarize the relationship between PACS and the contextual factors as well as outcomes of caregiving.

Research Design and Methods

A systematic literature review was conducted. Electronic databases were searched, and empirical research studies written in English that were published in a peer-reviewed journal after 2004 were identified. After a careful review of the 194 abstracts yielded from the databases and the reference lists of the associated articles, 52 eligible studies were identified, and relevant findings were extracted.

Results

Some commonality in terms of how studies have used the PACS emerged. The literature reviewed was further grouped into 3 categories depending on whether the study tested the PACS as a valid and reliable measurement, examined the PACS as outcomes of caregiving, or as a predictor of certain outcomes.

Discussion and Implications

This review suggests that PACS is utilized for multiple purposes and yields considerable evidence supporting the importance of understanding the positive experience of caregiving. However, there is limited adaptation of the PACS in a large survey, and studies were heavily focused in the United States with little evidence from other countries. Further studies to address these limitations will be needed.
Sensitivity kernels for body tides on laterally heterogeneous planets based on adjoint methods
Authors: Lau Harriet C P , Al-Attar David
Published: July 2021

We apply the adjoint method to efficiently calculate the linearized sensitivity of body tide observations to perturbations in density, elastic/anelastic moduli and boundary topography. This theory is implemented practically within the context of normal mode coupling calculations, with an advantage of this approach being that much of the necessary technical machinery is present in existing coupling codes. A range of example sensitivity kernels are calculated relative to both spherically symmetric and laterally heterogeneous background models. These results reaffirm the conclusions of earlier studies that the M2 body tide is strongly sensitive to spherical harmonic degree-2 density variations at the base of the mantle. Moreover, it is found that the sensitivity kernels are only weakly dependent on the background model, and hence linearized methods are likely to be effective within inversions of body tide observations.
Relocating microseismicity from downhole monitoring of the Decatur CCS site using a modified double-difference algorithm
Authors: Dando B D E , Goertz-Allmann B P , Kühn D , Langet N , Dichiarante A M , Oye V
Published: July 2021

The injection of CO2 at the Decatur carbon capture and storage site has generated significant microseismic activity, which occurs in distinct spatial clusters up to approximately 2.2 km from the primary injection well. Accurate and precise event locations are vital for the characterization of the microseismicity to help understand the reservoir response to the CO2 injection, whilst enabling the identification of minor faults and fractures below the resolution of conventional active seismic imaging. However, microseismic monitoring of fluid injection sites, such as Decatur, is often performed using a network of borehole sensors often from a single well. While these downhole sensors have excellent detection capabilities, their poor azimuthal coverage limits the ability to precisely determine event locations. We have developed a modified double-difference relocation algorithm suitable for both 1-D and 3-D velocity models, and which incorporates differential back azimuth observations to allow the benefits of the original double-difference algorithm to be applicable to a downhole microseismic monitoring setting. Applying the modified double-difference algorithm to the microseismicity at Decatur, we have successfully relocated 4293 events. The relocation included over 59 million observations for 757 285 event pairs, split across seven geographic regions. Despite the majority of observations being recorded in only two boreholes, with an almost identical azimuthal coverage, the results have shown to be reliable with significantly reduced residuals and low uncertainties associated with the final locations. We have analysed the residuals in terms of their association with each geographic region, data type, station and individual events, to fully appreciate their influence in the inversion and the fit of the data to the final set of event locations. For each region, the relocated seismicity has become less diffuse with improved clustering, and with newly visible linear features often orientated in a NE–SW direction. These results show the potential improvements that can be made to microseismic event locations recorded by a borehole network with a limited and variable azimuthal distribution.
Redefining the PTEN promoter: identification of novel upstream transcription start regions
Authors: Grencewicz Dennis J , Romigh Todd , Thacker Stetson , Abbas Ata , Jaini Ritika , Luse Donal , Eng Charis
Published: July 2021

Germline mutation of PTEN is causally observed in Cowden syndrome (CS) and is one of the most common, penetrant risk genes for autism spectrum disorder (ASD). However, the majority of individuals who present with CS-like clinical features are PTEN-mutation negative. Reassessment of PTEN promoter regulation may help explain abnormal PTEN dosage, as only the minimal promoter and coding regions are currently included in diagnostic PTEN mutation analysis. Therefore, we reanalyzed the architecture of the PTEN promoter using next-generation sequencing datasets. Specifically, run-on sequencing assays identified two additional transcription start regions (TSRs) at −2053 and −1906 basepairs from the canonical start of PTEN, thus extending the PTEN 5'UTR and redefining the PTEN promoter. We show that these novel upstream TSRs are active in cancer cell lines, human cancer and normal tissue. Furthermore, these TSRs can produce novel PTEN transcripts due to the introduction of new splice donors at −2041, −1826 and −1355, which may allow for splicing out of the PTEN 5'UTR or the first and second exon in upstream-initiated transcripts. Combining ENCODE ChIP-seq and pertinent literature, we also compile and analyze all transcription factors (TFs) binding at the redefined PTEN locus. Enrichment analyses suggest that TFs bind specifically to the upstream TSRs may be implicated in inflammatory processes. Altogether, these data redefine the architecture of the PTEN promoter, an important step toward a comprehensive model of PTEN transcription regulation, a basis for future investigations into the new promoters’ role in disease pathogenesis.
More flexibility in favor of constitutional stability? What breaking amendment rules in Ecuador can teach us
Authors: Fröhlich Johanna
Published: July 2021

Latin America has provided a fertile ground for constitutional experimentation. The Ecuadorean Constitution of 2008 purported to change the entire liberal constitutional model and replace it with one in which indigenous concepts from the Andean region are central. At the same time, the constitutionalization of the legal order was not repudiated, and a reinforced procedure for constitutional amendments was still included. It seems, however, that even an extended rights catalogue and reinforced amendment procedures could fail to induce a real paradigm change if the commitment to protect the constitution as higher law is missing. The present article seeks to show that more flexible amendment rules might foster the rule of law and stability better than those that are unrealistic or bluntly ideological, especially where the value of constitution-as-higher-law is not authentically reflected in the governed society. In these cases, flexible amendment rules could help restore trust in law’s authority and constitutional institutions, and they could also assist in guiding political actions under the guise of law, instead of surrendering them to a mere political power struggle. Building on the experience of a series of constitutional substitutions from Ecuador’s three main constitutional phases, the article strives to enrich our understanding of issues related to amendment difficulty, institutional design, and constitutional culture.
Revision of the spider crab genusLibiniaLeach, 1815 (Decapoda: Brachyura: Epialtidae: Pisinae)
Authors: Tamburus Ana F , Mantelatto Fernando L
Published: July 2021

The majoid genus LibiniaLeach, 1815 currently contains 10 valid species, all inhabiting mostly tropical waters in the Western Hemisphere. Three occur in the Eastern Pacific (L. mexicanaRathbun, 1892, L. peruanaGarth & Méndez, 1983, L. setosaLockington, 1877) and seven in the Western Atlantic (L. cavirostrisChace, 1942, L. dubia H. Milne Edwards, 1834, L. emarginataLeach, 1815, L. erinacea (A. Milne-Edwards, 1878), L. ferreiraeBrito Capello, 1871, L. rhomboideaStreets, 1870, L. spinosa Guérin, 1832). The genus is revised using morphological data and the examination of the type series. Sister taxa from the Eastern Pacific are morphologically distinguishable from their Western Atlantic congeners. The present revision recognizes the 10 species, adding new diagnoses and a key to their identification.
Regenerated claws of the virile crayfishFaxonius virilis(Hagen, 1870) (Decapoda: Astacidea: Cambaridae) generate weaker pinching forces compared to original claws
Authors: Graham Zackary A , Vargas Cindy , Angilletta Michael J , Palaoro Alexandre V
Published: July 2021

Crustaceans are known for their ability to autotomize and regenerate their appendages. The appendages that are most often autotomized are their chela, often specialized as claws, which serve essential functions including foraging, fighting, mating, and predator defense. Crustaceans with autotomized or regenerated chelae may suffer decreases in their ability to perform these functions compared to individuals with intact or original claws. It is noteworthy that although regenerated claws can grow back to the expected size of an original claw, regenerated claws often differ from original claws in external morphology and internal musculature. Both male and female crayfishes wield a pair of enlarged claws. It surprisingly remains unknown how the regeneration of crayfish claws influences the claws’ ability to generate pinching forces, which has previously been shown to influence the outcome of territorial contests. We investigated the relationship between claw regeneration and claw strength among male and female virile crayfish, Faxonius virilis (Hagen 1870). We found that maximal pinching forces of regenerated claws were weaker than the maximal pinching forces of original claws in both sexes (36% and 40% weaker in males and females, respectively). Further, regenerated claws had proportionally less muscle mass compared to original claws of equivalent size. These results present evidence of how claw regeneration influences pinching strength in crayfishes and suggest that such regeneration may be the functional mechanism that produces dishonest (large but weak) claws in crayfishes, but behavioral observations are required to support this hypothesis.
Reproductive and Morphological Quality of Commercial Honey Bee (Hymenoptera: Apidae) Drones in the United States
Authors: Metz Bradley N , Tarpy David R
Published: July 2021

Exploration into reproductive quality in honey bees (Apis mellifera Linneaus (Hymenoptera: Apidae) largely focuses on factors that affect queens, with drones primarily being considered insofar as they pass on effects of environmental stressors to the queen and subsequent offspring. In those studies that consider drone quality explicitly, a primary focus has been on the dimorphic nature of drones laid in worker cells (either through rare queen error or worker reproduction) as compared to drones laid by the queen in the slightly larger drone cells. The implication from these studies is that that there exists a bimodality of drone morphological quality that is related to reproductive quality and competitive ability during mating. Our study quantifies the presence of such small drones in commercial populations, finding that rates of ‘low-quality’ drones are far higher than theoretically predicted under optimum conditions. Observations from commercial colonies also show significant inter-colony variation among the size and fecundity of drones produced, prompting speculation as to the mechanisms inducing such variation and the potential use of drone-quality variation for the colony- or apiary-level exposure to nutrition, agrichemical, or parasitic stressors.
Multiple Genetic Mutations Related to Insecticide Resistance are Detected in Field Kazakhstani House Flies (Muscidae: Diptera)
Authors: Qu Ruina , Zhu Jiang , Li Mei , Jashenko Roman , Qiu Xinghui
Published: July 2021

The house fly (Musca domestica Linnaeus) is an important disease vector. Insecticide resistance is an obstacle to effective house fly control. Previous studies have demonstrated that point mutations in acetylcholinesterase (Ace), carboxylesterase (MdαE7) and voltage-sensitive sodium channel (Vssc), and over-expression of CYP6D1v1 confer insecticide resistance in the house fly. However, information about the status and underlying mechanisms of insecticide resistance in Kazakhstani house flies is lacking. In this study, we investigated the occurrence of genetic mutations associated with insecticide resistance in field house flies collected at six different locations in southern Kazakhstan. Four mutations (V260L, G342A/V, and F407Y) in Ace and three mutations (G137D and W251L/S) in MdαE7 were detected with appreciable frequencies. Notably, haplotypes carrying triple-loci mutations in Ace and double mutations in MdαE7 were found in Kazakhstan. The L1014H and L1014F mutations in Vssc, and CYP6D1v1 resistance allele were detected at a low frequency in some of the six investigated house fly populations. Phylogenetic analyses of haplotypes supported multiple origins of resistance mutations in Ace and MdαE7. These observations suggest that house flies in southern Kazakhstan may exhibit significant resistance to organophosphates and carbamates. Regular monitoring of insecticide resistance is recommended to achieve effective house fly control by chemical agents in southern Kazakhstan.
Internal Passports, Counterfeiting, and Subversive Practices in Early Postcolonial Peru
Authors: Ragas José
Published: July 2021

Counterfeit identity papers have accompanied many Peruvians over the past two centuries as they moved within their own country. Through these documents, they have embraced numerous personalities and eluded strict controls to the dismay of policymakers and experts who envisioned building a robust surveillance system based on identity cards. This article analyzes counterfeiting as a set of objects, practices, and knowledge that emerged in the aftermath of the Wars of Independence during the transition to an autonomous Republic. Committed to establishing social and political order in this chaotic scenario, Peruvian authorities relied on low-tech devices known as internal passports to regulate mobility within the convoluted territory. Nonetheless, internal passports proved more fragile and less effective than expected. Peruvians rapidly learned to produce their own internal passports or to adulterate their information, developing a particular expertise that enabled them to navigate the nascent biometric system. Forged internal passports thus illustrate the enduring tensions between governments, citizens, and technology, as well as early efforts of individuals to regain control of their personal data.
Phenomenal Knowledge and Martyrdom: Endō’s Silence
Authors: Pagan Nicholas O
Published: July 2021

This article examines Endō Shūsaku’s Silence from the perspective of ‘phenomenal knowledge’, which can only be derived from experience. First turning to philosopher Michel Henry’s discussion of phenomenologies of Christ, the article traces Endō’s protagonist Sebastian Rodrigues’ initial failure to access the phenomenology of Jesus-as-the-Christ. While the all-important fumie tests in Silence appear to offer the possibility of martyrdom and an opportunity to demonstrate faith, the article contends that Endō’s novel implies that among other factors that make up the discourse of martyrdom, a special place should be reserved for phenomenal knowledge.
Buddhist Reception in Pulp Science Fiction
Authors: Clarke Jim
Published: July 2021

Science fiction has a lengthy history of irreligion. In part, this relates to its titular association with science itself, which, as both methodology and ontological basis, veers away from revelatory forms of knowledge in order to formulate hypotheses of reality based upon experimental praxis. However, during science fiction’s long antipathy to faith, Buddhism has occupied a unique and sustained position within the genre. This article charts the origins of that interaction, in the pulp science fiction magazines of the late 1920s and early 1930s, in which depictions of Buddhism quickly evolve from ‘Yellow Peril’ paranoia towards something much more intriguing and accommodating, and in so doing, provide a genre foundation for the environmental concerns of much 21st-century science fiction.
The distribution of mutual inclinations arising from the stellar quadrupole moment
Authors: Schultz Kathleen , Spalding Christopher , Batygin Konstantin
Published: July 2021

A large proportion of transiting planetary systems appear to possess only a single planet as opposed to multiple transiting planets. This excess of singles is indicative of significant mutual inclinations existing within a large number of planetary systems, but the origin of these misalignments is unclear. Moreover, recent observational characterization reveals that mutual inclinations tend to increase with proximity to the host star. These trends are both consistent with the dynamical influence of a strong quadrupolar potential arising from the host star during its early phase of rapid rotation, coupled with a non-zero stellar obliquity. Here, we simulate a population of planetary systems subject to the secular perturbation arising from a tilted, oblate host star as it contracts and spins down subsequent to planet formation. We demonstrate that this mechanism can reproduce the general increase in planet-planet mutual inclinations with proximity to the host star, and delineate a parameter space wherein the host star can drive dynamical instabilities. We suggest that approximately 5–10 per cent of low-mass Kepler systems are susceptible to this instability mechanism, suggesting that a significant number of single-transiting planets may truly be intrinsically single. We also report a novel connection between instability and stellar obliquity reduction and make predictions that can be tested within upcoming TESS observations.
RNAi and Ino80 complex control rate limiting translocation step that moves rDNA to eroding telomeres
Authors: Apte Manasi S , Masuda Hirohisa , Wheeler David Lee , Cooper Julia Promisel
Published: July 2021

The discovery of HAATIrDNA, a telomerase-negative survival mode in which canonical telomeres are replaced with ribosomal DNA (rDNA) repeats that acquire chromosome end-protection capability, raised crucial questions as to how rDNA tracts ‘jump’ to eroding chromosome ends. Here, we show that HAATIrDNA formation is initiated and limited by a single translocation that juxtaposes rDNA from Chromosome (Chr) III onto subtelomeric elements (STE) on Chr I or II; this rare reaction requires RNAi and the Ino80 nucleosome remodeling complex (Ino80C), thus defining an unforeseen relationship between these two machineries. The unique STE-rDNA junction created by this initial translocation is efficiently copied to the remaining STE chromosome ends, independently of RNAi or Ino80C. Intriguingly, both RNAi and Ino80C machineries contain a component that plays dual roles in HAATI subtype choice. Dcr1 of the RNAi pathway and Iec1 of Ino80C both promote HAATIrDNA formation as part of their respective canonical machineries, but both also inhibit formation of the exceedingly rare HAATISTE (where STE sequences mobilize throughout the genome and assume chromosome end protection capacity) in non-canonical, pathway-independent manners. This work provides a glimpse into a previously unrecognized crosstalk between RNAi and Ino80C in controlling unusual translocation reactions that establish telomere-free linear chromosome ends.
Percutaneous Full-Endoscopic C2 Ganglionectomy for the Treatment of Intractable Occipital Neuralgia: Technical Note
Authors: Yu Yong , Jiang Ye , Xu Fulin , Mao Yuhang , Yuan Lutao , Li Chen
Published: July 2021

BACKGROUND

The C-2 dorsal root ganglionectomy procedure can provide effective treatment for intractable occipital neuralgia (ON). However, the traditional microsurgery of C2 ganglionectomy needs a wide incision and significant paraspinous muscle dissection for adequate visualization. The indications of endoscopic spine surgery are ever expanding, with the development of endoscopic armamentaria and technological innovations.

OBJECTIVE

To validate the feasibility of the approach and describe several operative nuances based on the authors’ experience. In this paper, the authors describe a patient with intractable ON who was successfully treated with a percutaneous full-endoscopic C2 ganglionectomy.

METHODS

We describe the case of an 83-yr-old female with a 2-yr history of left ON who did not respond to a series of treatments, including physical therapy, drug therapy, injection therapy, and radiofrequency therapy. After careful examination, we performed a percutaneous, full-endoscopic left C2 ganglionectomy.

RESULTS

The patient was successfully treated with a percutaneous full-endoscopic ganglionectomy. Afterwards, her intractable and constant pain was relieved. There was no cerebrospinal fluid leakage, incision infection, neck deformity, or other complications.

CONCLUSION

C2 ganglionectomy can be accomplished successfully using a full-endoscopic uniportal surgical technique under continuous irrigation, which has the advantages of excellent illumination and visualization, reduced surgery-related trauma, and reduced bleeding.
Nuances of Olfactory Groove Meningioma Surgery: 2-Dimensional Operative Video
Authors: Mooney Michael A , Ibn Essayed Walid , Al-Mefty Ossama
Published: July 2021

Olfactory groove meningiomas frequently present as large or giant-size tumors associated with marked frontal lobe edema and significant frontal lobe dysfunction. Simpson grade I removal was rare in early reports due to their invasion of the ethmoid sinuses and skull base bone,
1
which resulted in high recurrence rates.
2,3
Indeed, recurrence occurred in the most celebrated case of olfactory groove meningioma.
4,5

 To achieve Simpson grade I removal (tumor, dura, bone), protect the frontal lobes from additional injury, and provide the best chance for recovery, we demonstrate a few nuances for olfactory groove meningioma surgery: Utilizing a skull base approach with a low dural opening, the frontal veins are preserved, and the frontal lobe is protected from retraction, manipulation, and venous injury. By the time of diagnosis, although the patient's olfaction is often absent, there still remains a role to preserve at least 1 olfactory tract, which might yield some preservation in a limited number of patients. Emphasis has been rightly made on the preservation of the A2 segments, which can be dissected using microsurgical technique. Lastly, multilayer reconstruction of the skull base is required, using an inlay graft, resting on a vascularized pericranial flap, and occlusion of the sinuses with a fat graft. The endonasal endoscopic approach has fallen out of favor due to limitations for complete tumor resection and higher complication rates.
6

 We present a case of a relatively small olfactory groove meningioma in a 36-yr-old male with partial olfactory loss. The patient consented for surgery.

 Images at 2:07, 2:29, and 2:54 from Al-Mefty O, Operative Atlas of Meningiomas, © LWW, 1997, with permission. Image at 8:31 public domain by age.
Defects in meiotic chromosome segregation lead to unreduced male gametes in Arabidopsis SMC5/6 complex mutants
Authors: Yang Fen , Fernández-Jiménez Nadia , Tučková Martina , Vrána Jan , Cápal Petr , Díaz Mariana , Pradillo Mónica , Pecinka Ales
Published: July 2021

Structural maintenance of chromosome 5/6 (SMC5/6) complex is a crucial factor for preserving genome stability. Here, we show that mutants for several Arabidopsis (Arabidopsis thaliana) SMC5/6 complex subunits produce triploid offspring. This phenotype is caused by a meiotic defect leading to the production of unreduced male gametes. The SMC5/6 complex mutants show an absence of chromosome segregation during the first and/or the second meiotic division, as well as a partially disorganized microtubule network. Importantly, although the SMC5/6 complex is partly required for the repair of SPO11-induced DNA double-strand breaks, the nonreduction described here is SPO11-independent. The measured high rate of ovule abortion suggests that, if produced, such defects are maternally lethal. Upon fertilization with an unreduced pollen, the unbalanced maternal and paternal genome dosage in the endosperm most likely causes seed abortion observed in several SMC5/6 complex mutants. In conclusion, we describe the function of the SMC5/6 complex in the maintenance of gametophytic ploidy in Arabidopsis.
Safeguarding Children: Early Trends of a Police School-Based Intervention Programme
Authors: Halford Eric , Davies Amanda
Published: July 2021

As communities and law enforcement officers across the globe grapple with the ever-increasing spread of cyber-crime combined with child sexual exploitation a myriad of strategies are emerging to combat the escalating crimes. This paper presents the development, implementation, and results of an educational intervention strategy applied by Lancashire Police. The strategy underpinned by comprehensive research of existing factors in the Lancashire community and determining an intervention to target the potential victim demographic culminated in a school-based education programme. The results of the pilot programme revealed positive early trends in self-assessed increased knowledge of potential risks, potential positive improvements in reducing the vulnerability of children, increase in avoidance mechanisms, and increasing personal safety. For the wider policing and general community, the intervention model is replicable and offers an additional tool to build the immunity of the most vulnerable victims, children in the global fight against arguably one of the most inhumane criminal activities.
The effect of collagen hydrogels on chondrocyte behaviors through restricting the contraction of cell/hydrogel constructs
Authors: Dong Longpeng , Liu Qingli , Gao Yongli , Jia Hengxing , Dai Wenling , Guo Likun , Fan Hongsong , Fan Yujiang , Zhang Xingdong
Published: July 2021

Collagen is a promising material for tissue engineering, but the poor mechanical properties of collagen hydrogels, which tend to cause contraction under the action of cellular activity, make its application challengeable. In this study, the amino group of type I collagen (Col I) was modified with methacrylic anhydride (MA) and the photo-crosslinkable methacrylate anhydride modified type I collagen (CM) with three different degrees of substitution (DS) was prepared. The physical properties of CM and Col I hydrogels were tested, including micromorphology, mechanical properties and degradation properties. The results showed that the storage modulus and degradation rate of hydrogels could be adjusted by changing the DS of CM. In vitro, chondrocytes were seeded into these four groups of hydrogels and subjected to fluorescein diacetate/propidium iodide (FDA/PI) staining, cell counting kit-8 (CCK-8) test, histological staining and cartilage-related gene expression analysis. In vivo, these hydrogels encapsulating chondrocytes were implanted subcutaneously into nude mice, then histological staining and sulfated glycosaminoglycan (sGAG)/DNA assays were performed. The results demonstrated that contraction of hydrogels affected behaviors of chondrocytes, and CM hydrogels with suitable DS could resist contraction of hydrogels and promote the secretion of cartilage-specific matrix in vitro and in vivo.
Does the inclusion of non-academic reviewers make any difference for grant impact panels?
Authors: Luo Junwen , Ma Lai , Shankar Kalpana
Published: July 2021

Broader impact of scientific research beyond academia has become increasingly important in research evaluation. To evaluate broader impact of research proposals, some funding agencies compose mixed panels that include peer experts and non-academic stakeholders. Whether and how non-academic reviewers bring any difference to panel discussions has been understudied. We analysed 164 review reports (2014–6) from the Investigators Programme (funding Science, Technology, Engineering, and Mathematics fields) at Science Foundation Ireland, where two types of panels, with and without non-academics, were composed for impact assessments. We find that the mixed panel reviews were longer and touched upon broader and more concrete impact topics. Also, mixed panels commented on causality and attribution of impact towards characteristics of applicants and research process more than scientific excellence. A survey of the same reviewer pool supplements our understanding of the pros and cons of the inclusion of non-academic reviewers. We discuss some policy recommendations for funding agencies to organise review panels.
A novel career development course for animal science students pursuing veterinary college admissions
Authors: Trivedi Shweta , Clark Jessica C , Deprospero Dylan , Royal Kenneth , See Miles Todd
Published: July 2021

A one-credit hour, elective, professional development course was created at North Carolina State University to introduce pre-veterinary track students to the admissions process and the breadth of the veterinary profession. The course was designed to facilitate career exploration while building self-efficacy through vicarious learning, interacting with speakers in various veterinary subfields, and addressing misperceptions about veterinary admissions. To evaluate the student learning objectives and improve upon the current practices of the course, data from two pretest and posttest course surveys for 235 course participants between Spring 2014 and 2017 were analyzed. The results of the study showed that students experienced significant gains in self-appraisal (Cohen’s d ranged 1.88 to 2.53), gathering occupational information (Cohen’s d ranged 1.59 to 2.53), goal selection (Cohen’s d ranged 2.14 to 2.53), and planning and problem-solving (Cohen’s d ranged 1.88 to 2.77) as well as experienced a decrease in five misperceptions about veterinary admissions. This novel course is presented as a prospective course for other universities.
Ethical implications of next-generation sequencing and the future of newborn screening
Authors: White-Corey Shelley , Peck Jessica L. , Pérez Rosa I.
Published: July 2021

Over the last 50 years, routine newborn blood screening for congenital disorders has been hailed as a miracle of modern science, saving countless lives by providing a means to detect and treat life-threatening disorders before symptoms present. Despite progress made with more than 5,000 babies effectively identified with rare conditions each year, congenital anomalies collectively remain at the top of the list as the cause of death for babies under 1 year of age, accounting for more than 20% of all infant mortalities. Rapid technological advances have seen the original singular newborn screen for phenylketonuria expand to a core set of 34 conditions and an additional 26 secondary conditions on the Recommended Uniform Screening Panel, with wide state-to-state variation for implementation. As genomic analysis evolves to enable next-generation sequencing, debates continue over the ethical, legal, and social implications of identifying conditions for which there is no effective treatment. Nurse practitioners should be engaged and informed in providing evidence-based support to families engaging in ethical complex decision making surrounding newborn screening while effectively balancing risk–benefit analysis with individual beliefs and values.
Towards a general model for predicting minimal metal concentrations co-selecting for antibiotic resistance plasmids
Authors: Arya Sankalp , Williams Alexander , Reina Saul Vazquez , Knapp Charles W. , Kreft Jan-Ulrich , Hobman Jon L. , Stekel Dov J.
Published: July 2021

Many antibiotic resistance genes co-occur with resistance genes for transition metals, such as copper, zinc, or mercury. In some environments, a positive correlation between high metal concentration and high abundance of antibiotic resistance genes has been observed, suggesting co-selection due to metal presence. Of particular concern is the use of copper and zinc in animal husbandry, leading to potential co-selection for antibiotic resistance in animal gut microbiomes, slurry, manure, or amended soils. For antibiotics, predicted no effect concentrations have been derived from laboratory measured minimum inhibitory concentrations and some minimal selective concentrations have been investigated in environmental settings. However, minimal co-selection concentrations for metals are difficult to identify. Here, we use mathematical modelling to provide a general mechanistic framework to predict minimal co-selective concentrations for metals, given knowledge of their toxicity at different concentrations. We apply the method to copper (Cu), Zinc (Zn), mercury (Hg), lead (Pb) and silver (Ag), predicting their minimum co-selective concentrations in mg/L (Cu: 5.5, Zn: 1.6, Hg: 0.0156, Pb: 21.5, Ag: 0.152). To exemplify use of these thresholds, we consider metal concentrations from slurry and slurry-amended soil from a UK dairy farm that uses copper and zinc as additives for feed and antimicrobial footbath: the slurry is predicted to be co-selective, but not the slurry-amended soil. This modelling framework could be used as the basis for defining standards to mitigate risks of antimicrobial resistance applicable to a wide range of environments, including manure, slurry and other waste streams.
Rapid generation of homozygous fluorescent knock-in human cells using CRISPR/Cas9 genome editing and validation by automated imaging and digital PCR screening
Authors: Kueblbeck Moritz , Callegari Andrea , Serrano-Solano Beatriz , Ellenberg Jan
Published: July 2021

We have previously described a protocol for genome engineering of mammalian cultured cancer cells with CRISPR/Cas9 to generate homozygous knock-ins of fluorescent tags into endogenous genes1. Here, we are updating this protocol to reflect major improvements in the workflow regarding efficiency and throughput. In brief, we have improved our method by combining high efficiency electroporation of optimized CRISPR/Cas9 reagents, screening of single cell derived clones by automated bright field and fluorescence imaging, rapidly assessing the number of tagged alleles and potential off-targets using digital PCR (dPCR) and automated data analysis. Compared to the original protocol1, our current procedure (i) significantly increases the efficiency of tag integration, (ii) automates the identification of clones derived from single cells with correct subcellular localization of the tagged protein and (iii) provides a quantitative and high throughput assay to measure the number of on- and off-target integrations with dPCR. The increased efficiency of the new procedure reduces the number of clones that need to be analysed in- depth by more than ten-fold, and yields up to 20% of homozygous clones in polyploid cancer cell lines in a single genome engineering round. Overall, we were able to dramatically reduce the hands-on time from 30 days to 10 days during the overall ∼10 weeks procedure, allowing a single person to process up to 5 genes in parallel, assuming that validated reagents – e.g. PCR-primers, dPCR-assays, Western Blot antibodies – are available.
Side Effects and Perceptions Following Sinopharm COVID-19 Vaccination
Authors: Saeed Balsam Qubais , Al-Shahrabi Rula , Alhaj Shaikha Salah , Alkokhardi Zainab Mansour , Adrees Ahmed Omar
Published: July 2021

Background

Vaccines are one of the best interventions developed for eradicating COVID-19, the rapid creation of vaccinations was increased the risk of vaccine safety problems. The aim of this study to provide evidence on Sinopharm COVID-19 vaccine side effects which is approved by the United Arab Emirates (UAE).

Methods

A cross-sectional survey study was conducted between January and April 2021 to collect data on the effects of COVID-19 vaccine among individuals in the UAE. Demographic data, chronic conditions, side effects of the 1st and 2nd dose toward the vaccination, and the response of unwilling taking COVID-19 vaccine were reported.

Results

The most common side effects of post 1st dose vaccination among participants (≤49 years old vs >49 years) were normal injection site pain 42.2%, fatigue 12.2%, and headache 9.6%, while pain at the vaccination site 32.6%, fatigue16.3%, lethargy13.7%, headache10%, and tenderness 10% were the most side effects of the post 2nd dose of vaccination in both groups. All the side effects in both doses were more prevalent among the participants ≤ 49-year-old group.

Among two groups (females vs males), the study revealed the increase in the number of females that suffered from the vaccine side effects compared with males in both doses. The most prevalence adverse reactions of first dose in (female’s vs males) were fatigue (15.8% vs 3.75%), lethargy (12.6% vs 1.25%), headache (10.5% vs 7.5%), while in 2nd dose were fatigue (20% vs 7.5%), sever injection site pain (10.5% vs 2.5%). The most common reason of not willing to take the COVID-19 vaccine among the participants were the vaccines are not effective, and the participants were not authorized to take vaccine.

Conclusion

The 1st and 2nd dose post-vaccination side effects were mild, predictable, and there were no hospitalization cases, this data will help to reduce the vaccine hesitancy.
Optogenetic tools for public goods control in Saccharomyces cerevisiae
Authors: Morales Neydis Moreno , Patel Michael T. , Stewart Cameron J. , Sweeney Kieran , McClean Megan N.
Published: July 2021

Microorganisms live in dense and diverse communities, with interactions between cells guiding community development and phenotype. The ability to perturb specific intercellular interactions in space and time provides a powerful route to determining the critical interactions and design rules for microbial communities. Approaches using optogenetic tools to modulate these interactions offer promise, as light can be exquisitely controlled in space and time. We report new plasmids for rapid integration of an optogenetic system into Saccharomyces cerevisiae to engineer light-control of expression of a gene of interest. In a proof-of-principle study, we demonstrate the ability to control a model cooperative interaction, namely the expression of the enzyme invertase (SUC2) which allows S. cerevisiae to hydrolyze sucrose and utilize it as a carbon source. We demonstrate that the strength of this cooperative interaction can be tuned in space and time by modulating light intensity and through spatial control of illumination. Spatial control of light allows cooperators and cheaters to be spatially segregated, and we show that the interplay between cooperative and inhibitory interactions in space can lead to pattern formation. Our strategy can be applied to achieve spatiotemporal control of expression of a gene of interest in Saccharomyces cerevisiae to perturb both intercellular and interspecies interactions.

Importance

Recent advances in microbial ecology have highlighted the importance of intercellular interactions in controlling the development, composition and resilience of microbial communities. In order to better understand the role of these interactions in governing community development it is critical to be able to alter them in a controlled manner. Optogenetically-controlled interactions offer advantages over static perturbations or chemically-controlled interactions as light can be manipulated in space and time and doesn’t require the addition of nutrients or antibiotics. Here we report a system for rapidly achieving light-control of a gene of interest in the important model organism Saccharomyces cerevisiae and demonstrate that by controlling expression of the enzyme invertase we can control cooperative interactions. This approach will be useful for understanding intercellular and interspecies interactions in natural and synthetic microbial consortia containing Saccharomyces cerevisiae and serves as a proof-of-principle for implementing this approach in other consortia.