bluuebunny/crossref_metadata_2025 huggingface dataset:
Composition and Genealogical Relation Network of the Medical Family in the Late Joseon Dynasty
Authors: KWON Kiseok
Published: October 2021

Uiyeokju Palsebo is a genealogy record that contains the eighth generation of patrilineal ancestors, maternal grandfathers, and fathers-in-law of technical officials who worked in three fields: medicine, linguistics, and mathematics. This book covers members of influential families who monopolized the positions of technical officers. In that respect, it seems to have had an effect like a kind of 'white list'. This paper identifies the range of families based on common ancestors above eight generations according to the editing method of this book, attempting various statistical analysis. The results of the analysis shows that it is possible to determine the size of the medical families, which varied according to the number of medical bureaucrats and the distance of kinship between them. Most of the families had workers in the three fields of medicine, linguistics, and mathematics, but there were also ‘families more specialized in medicine’ that produced a large number of medical figures. The ancestors of medical figures were mainly engaged in the three fields of medicine, linguistics, and mathematics, but there were also a small number of officials in charge of “unhak(including astronomy, geography, and fortune-telling),” law, art, and transcription. For distant ancestors from common ancestors to the fifth generation, the proportion of technical officers was small, but for relatively close ancestors, the proportion of technical officers, especially medical officers, increased. It can be seen that the status as a medical officer tends to be hereditary further down the generations. The fields of activity of the maternal grandfathers and fathers-in-law of medical figures were more concentrated in the medical field. This can be the result of confirming the influence of the marital relationship network that was formed in the close period with the medical persons being investigated. In this paper, only medical figures were considered as primary research subjects, but their macroscopic networks were relatively evenly spread out in the three fields of medicine, linguistics, and mathematics. In this network, Uiyeokju Palsebo contained homogeneous hierarchies that could continuously dominate a specific field of government office.
Measurement of chromatic aberrations using phase retrieval
Authors: Bergkoetter Matthew D. , Kruschwitz Brian E. , Bahk Seung-Whan , Fienup James R.
Published: October 2021

We explore the feasibility of measuring chromatic aberrations using a
technique based on phase retrieval, primarily for the purpose of
diagnostics on the OMEGA EP laser. A computational model and
optimization strategy are described, issues of numerical efficiency
are addressed, and the potential limitations of the method are studied
using mathematical analysis and Monte Carlo simulations. The algorithm
performs well in simulation and yields encouraging results in a
small-scale laboratory experiment.
Resolution limit in quantum imaging with undetected photons using position correlations
Authors: Viswanathan Balakrishnan , Barreto Lemos Gabriela , Lahiri Mayukh
Published: October 2021

Quantum imaging with undetected photons (QIUP) is a unique method of image acquisition where the photons illuminating the object are not detected. This method relies on quantum interference and spatial correlations between the twin photons to form an image. Here we present a detailed study of the resolution limits of position correlation enabled QIUP. We establish a quantitative relation between the spatial resolution and the twin-photon position correlation. Furthermore, we also quantitatively establish the roles that the wavelength of the undetected illumination field and the wavelength of the detected field play in the resolution. Like ghost imaging and unlike conventional imaging, the resolution limit imposed by the spatial correlation between the twin photons in QIUP cannot be further improved by conventional optical techniques.
Universal dwell time optimization for deterministic optics fabrication
Authors: Wang Tianyi , Huang Lei , Vescovi Matthew , Kuhne Dennis , Zhu Yi , Negi Vipender S. , Zhang Zili , Wang Chunjin , Ke Xiaolong , Choi Heejoo , Pullen Weslin C. , Kim Daewook , Kemao Qian , Nakhoda Kashmira , Bouet Nathalie , Idir Mourad
Published: October 2021

Computer-Controlled Optical Surfacing (CCOS) has been greatly developed and widely used for precision optical fabrication in the past three decades. It relies on robust dwell time solutions to determine how long the polishing tools must dwell at certain points over the surfaces to achieve the expected forms. However, as dwell time calculations are modeled as ill-posed deconvolution, it is always non-trivial to reach a reliable solution that 1) is non-negative, since CCOS systems are not capable of adding materials, 2) minimizes the residual in the clear aperture 3) minimizes the total dwell time to guarantee the stability and efficiency of CCOS processes, 4) can be flexibly adapted to different tool paths, 5) the parameter tuning of the algorithm is simple, and 6) the computational cost is reasonable. In this study, we propose a novel Universal Dwell time Optimization (UDO) model that universally satisfies these criteria. First, the matrix-based discretization of the convolutional polishing model is employed so that dwell time can be flexibly calculated for arbitrary dwell points. Second, UDO simplifies the inverse deconvolution as a forward scalar optimization for the first time, which drastically increases the solution stability and the computational efficiency. Finally, the dwell time solution is improved by a robust iterative refinement and a total dwell time reduction scheme. The superiority and general applicability of the proposed algorithm are verified on the simulations of different CCOS processes. A real application of UDO in improving a synchrotron X-ray mirror using Ion Beam Figuring (IBF) is then demonstrated. The simulation indicates that the estimated residual in the 92.3 mm × 15.7 mm CA can be reduced from 6.32 nm Root Mean Square (RMS) to 0.20 nm RMS in 3.37 min. After one IBF process, the measured residual in the CA converges to 0.19 nm RMS, which coincides with the simulation.
Recursive MAGUS: Scalable and accurate multiple sequence alignment
Authors: Smirnov Vladimir
Published: October 2021

Multiple sequence alignment tools struggle to keep pace with rapidly growing sequence data, as few methods can handle large datasets while maintaining alignment accuracy. We recently introduced MAGUS, a new state-of-the-art method for aligning large numbers of sequences. In this paper, we present a comprehensive set of enhancements that allow MAGUS to align vastly larger datasets with greater speed. We compare MAGUS to other leading alignment methods on datasets of up to one million sequences. Our results demonstrate the advantages of MAGUS over other alignment software in both accuracy and speed. MAGUS is freely available in open-source form at https://github.com/vlasmirnov/MAGUS.
Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes
Authors: Zhao Bill , Zhang Kehan , Chen Christopher S. , Lejeune Emma
Published: October 2021

A better fundamental understanding of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has the potential to advance applications ranging from drug discovery to cardiac repair. Automated quantitative analysis of beating hiPSC-CMs is an important and fast developing component of the hiPSC-CM research pipeline. Here we introduce “Sarc-Graph,” a computational framework to segment, track, and analyze sarcomeres in fluorescently tagged hiPSC-CMs. Our framework includes functions to segment z-discs and sarcomeres, track z-discs and sarcomeres in beating cells, and perform automated spatiotemporal analysis and data visualization. In addition to reporting good performance for sarcomere segmentation and tracking with little to no parameter tuning and a short runtime, we introduce two novel analysis approaches. First, we construct spatial graphs where z-discs correspond to nodes and sarcomeres correspond to edges. This makes measuring the network distance between each sarcomere (i.e., the number of connecting sarcomeres separating each sarcomere pair) straightforward. Second, we treat tracked and segmented components as fiducial markers and use them to compute the approximate deformation gradient of the entire tracked population. This represents a new quantitative descriptor of hiPSC-CM function. We showcase and validate our approach with both synthetic and experimental movies of beating hiPSC-CMs. By publishing Sarc-Graph, we aim to make automated quantitative analysis of hiPSC-CM behavior more accessible to the broader research community.
A metric for evaluating biological information in gene sets and its application to identify co-expressed gene clusters in PBMC
Authors: Bennett Jason , Pomaznoy Mikhail , Singhania Akul , Peters Bjoern
Published: October 2021

Recent technological advances have made the gathering of comprehensive gene expression datasets a commodity. This has shifted the limiting step of transcriptomic studies from the accumulation of data to their analyses and interpretation. The main problem in analyzing transcriptomics data is that the number of independent samples is typically much lower (<100) than the number of genes whose expression is quantified (typically >14,000). To address this, it would be desirable to reduce the gathered data’s dimensionality without losing information. Clustering genes into discrete modules is one of the most commonly used tools to accomplish this task. While there are multiple clustering approaches, there is a lack of informative metrics available to evaluate the resultant clusters’ biological quality. Here we present a metric that incorporates known ground truth gene sets to quantify gene clusters’ biological quality derived from standard clustering techniques. The GECO (Ground truth Evaluation of Clustering Outcomes) metric demonstrates that quantitative and repeatable scoring of gene clusters is not only possible but computationally lightweight and robust. Unlike current methods, it allows direct comparison between gene clusters generated by different clustering techniques. It also reveals that current cluster analysis techniques often underestimate the number of clusters that should be formed from a dataset, which leads to fewer clusters of lower quality. As a test case, we applied GECO combined with k-means clustering to derive an optimal set of co-expressed gene modules derived from PBMC, which we show to be superior to previously generated modules generated on whole-blood. Overall, GECO provides a rational metric to test and compare different clustering approaches to analyze high-dimensional transcriptomic data.
Investigation of neglected protists Blastocystis sp. and Dientamoeba fragilis in immunocompetent and immunodeficient diarrheal patients using both conventional and molecular methods
Authors: Sarzhanov Fakhriddin , Dogruman-Al Funda , Santin Monica , Maloney Jenny G. , Gureser Ayse Semra , Karasartova Djursun , Taylan-Ozkan Aysegul
Published: October 2021

Introduction

The clinical significance ofBlastocystissp. andDientamoeba fragilisin patients with gastrointestinal symptoms is a controversial issue. Since the pathogenicity of these protists has not been fully elucidated, testing for these organisms is not routinely pursued by most laboratories and clinicians. Thus, the prevalence of these organisms and the subtypes ofBlastocystissp. in human patients in Turkey are not well characterized. This study aimed to determine the prevalence ofBlastocystissp. andD.fragilisin the diarrheic stool samples of immunodeficient and immunocompetent patients using conventional and molecular methods and to identifyBlastocystissp. subtypes using next generation sequencing.

Material and methods

Individual stool specimens were collected from 245 immunodeficient and 193 immunocompetent diarrheic patients between March 2017 and December 2019 at the Gazi University Training and Research Hospital in Ankara, Turkey. Samples were screened forBlastocystissp. andD.fragilisby conventional and molecular methods. Molecular detection of both protists was achieved by separate qPCRs targeting a partial fragment of theSSUrRNA gene. Next generation sequencing was used to identifyBlastocystissp. subtypes.

Results

The prevalence ofBlastocystissp. andD.fragiliswas 16.7% and 11.9%, respectively as measured by qPCR. The prevalence ofBlastocystissp. andD.fragiliswas lower in immunodeficient patients (12.7% and 10.6%, respectively) compared to immunocompetent patients (21.8% and 13.5%, respectively). FiveBlastocystissp. subtypes were identified and the following subtype distribution was observed: ST3 54.4% (n = 37), ST2 16.2% (n = 11), ST1 4.4% (n = 3), ST6 2.9% (n = 2), ST4 1.5% (n = 1), ST2/ST3 11.8% (n = 8) and ST1/ST3 8.8% (n = 6). There was no statistically significant difference in the distribution ofBlastocystissp. subtypes between immunocompetent and immunodeficient patients.

Conclusion and recommendation

Our findings demonstrated thatBlastocystissp. andD.fragilisare commonly present in immunocompetent and immunodeficient patients with diarrhea. This study is the first to use next generation sequencing to address the presence ofBlastocystissp. mixed subtypes and intra-subtype variability in clinical samples in Turkey.
Searching for a sign of exotic Aedes albopictus (Culicidae) introduction in major international seaports on Kyushu Island, Japan
Authors: Yang Chao , Sunahara Toshihiko , Hu Jinping , Futami Kyoko , Kawada Hitoshi , Minakawa Noboru
Published: October 2021

Background

The Asian tiger mosquito,Aedes albopictus, has spread around the world. The migration was mainly mediated by maritime transportations. This species is known as an efficient vector for arboviruses, and it was responsible for the recent dengue outbreak in Tokyo, Japan. As the vector competence varies among geographical populations, and insecticide resistant populations have emerged, it is important to reveal their movements. The present study uses molecular techniques to search for a sign of introduction of an exotic population in three major international seaports on Kyushu Island.

Methodology/principal findings

Adults ofAe.albopictuswere sampled around the international seaports of Fukuoka, Kitakyushu, and Nagasaki. Pairwise fixation indexes were estimated between the sampled populations based on 13 microsatellite markers. There was no clear genetic differentiation between distant and port populations in Kitakyushu and Nagasaki. However, the analysis found one distinct group near the container terminal in Fukuoka, which handles international freight containers mainly from adjacent countries. DNA samples were also obtained from Goto, Tsushima, Honshu, Ryukyu, Thailand, and the Philippines; and a cluster analysis and discriminant analysis revealed that the distinct group in Fukuoka did not belong to these groups. Combined with the results of phylogenetic analysis based on CO1, these results implied that this group originated from one Asian temperate region outside of Japan. Neutrality test and mismatch distribution analysis suggested that the establishment of this group was not recent.

Conclusions/significance

The present study found a sign ofAe.albopictusintroduction from a temperate region of Asia through maritime freight container transportation. The genetically distinct group found in Fukuoka likely originated from a temperate region outside of Japan. Maritime container transportation may introduce to Japan mosquitoes with greater vector competence/insecticide resistance. This is the first study to describe the spatial population structure ofAe.albopictusin Japan using molecular techniques.
Hospital-level factors associated with death during pneumonia-associated hospitalization among adults—New York City, 2010–2014
Authors: Whittemore Kate , Garcia Kristian M. , Huang Chaorui C. , Lim Sungwoo , Daskalakis Demetre C. , Vora Neil M. , Lucero David E.
Published: October 2021

Background

In New York City (NYC), pneumonia is a leading cause of death and most pneumonia deaths occur in hospitals. Whether the pneumonia death rate in NYC reflects reporting artifact or is associated with factors during pneumonia-associated hospitalization (PAH) is unknown. We aimed to identify hospital-level factors associated with higher than expected in-hospital pneumonia death rates among adults in NYC.

Methods

Data from January 1, 2010–December 31, 2014 were obtained from the New York Statewide Planning and Research Cooperative System and the American Hospital Association Database. In-hospital pneumonia standardized mortality ratio (SMR) was calculated for each hospital as observed PAH death rate divided by expected PAH death rate. To determine hospital-level factors associated with higher in-hospital pneumonia SMR, we fit a hospital-level multivariable negative binomial regression model.

Results

Of 148,172 PAH among adult NYC residents in 39 hospitals during 2010–2014, 20,820 (14.06%) resulted in in-hospital death. In-hospital pneumonia SMRs varied across NYC hospitals (0.77–1.23) after controlling for patient-level factors. An increase in average daily occupancy and membership in the Council of Teaching Hospitals were associated with increased in-hospital pneumonia SMR.

Conclusions

Differences in in-hospital pneumonia SMRs between hospitals might reflect differences in disease severity, quality of care, or coding practices. More research is needed to understand the association between average daily occupancy and in-hospital pneumonia SMR. Additional pneumonia-specific training at teaching hospitals can be considered to address higher in-hospital pneumonia SMR in teaching hospitals.
Transcriptional profiling of equine endometrium before, during and after capsule disintegration during normal pregnancy and after oxytocin-induced luteostasis in non-pregnant mares
Authors: Klein Claudia , Bruce Phoebe , Hammermueller Jutta , Hayes Tony , Lillie Brandon , Betteridge Keith
Published: October 2021

The current study used RNA sequencing to determine transcriptional profiles of equine endometrium collected 14, 22, and 28 days after ovulation from pregnant mares. In addition, the transcriptomes of endometrial samples obtained 20 days after ovulation from pregnant mares, and from non-pregnant mares which displayed and failed to display extended luteal function following the administration of oxytocin, were determined and compared in order to delineate genes whose expressions depend on the presence of the conceptus as opposed to elevated progesterone alone. A mere fifty-five transcripts were differentially expressed between samples collected from mares at Day 22 and Day 28 of pregnancy. This likely reflects the longer-term exposure to a relatively constant, progesterone-dominated environment with little change in factors secreted by the conceptus that would affect endometrial gene expression. The complement system was amongst the canonical pathways significantly enriched in transcripts differentially expressed between Day 14 and Day 22/28 of pregnancy. The expression of complement components 7 and 8 was confirmed using in situ hybridization. The expression of SERPING1, an inhibitor of the complement system, was confirmed by immunohistochemistry. In line with the resumed capacity of the endometrium to produce prostaglandin, prostaglandin G/H synthase 1 was expressed at higher levels at Days 22 and 28 than at Day 14 of pregnancy. Our data suggest that this up-regulation is enhanced by the presence of the conceptus; samples obtained from mares at Day 20 of pregnancy had significantly higher levels of prostaglandin G/H synthase 1 transcript than mares with extended luteal function.
4-Coumaroyl-CoA ligases in the biosynthesis of the anti-diabetic metabolite montbretin A
Authors: Sunstrum Frederick G. , Liu Hannah L. , Jancsik Sharon , Madilao Lufiani L. , Bohlmann Joerg , Irmisch Sandra
Published: October 2021

Background

Montbretins are rare specialized metabolites found in montbretia (Crocosmia x crocosmiiflora) corms. Montbretin A (MbA) is of particular interest as a novel therapeutic for type-2 diabetes and obesity. There is no scalable production system for this complex acylated flavonol glycoside. MbA biosynthesis has been reconstructed in Nicotiana benthamiana using montbretia genes for the assembly of MbA from its various different building blocks. However, in addition to smaller amounts of MbA, the therapeutically inactive montbretin B (MbB) was the major product of this metabolic engineering effort. MbA and MbB differ in a single hydroxyl group of their acyl side chains, which are derived from caffeoyl-CoA and coumaroyl-CoA, respectively. Biosynthesis of both MbA and MbB also require coumaroyl-CoA for the formation of the myricetin core. Caffeoyl-CoA and coumaroyl-CoA are formed in the central phenylpropanoid pathway by acyl activating enzymes (AAEs) known as 4-coumaroyl-CoA ligases (4CLs). Here we investigated a small family of montbretia AAEs and 4CLs, and their possible contribution to montbretin biosynthesis.

Results

Transcriptome analysis for gene expression patterns related to montbretin biosynthesis identified eight different montbretia AAEs belonging to four different clades. Enzyme characterization identified 4CL activity for two clade IV members, Cc4CL1 and Cc4CL2, converting different hydroxycinnamic acids into the corresponding CoA thioesters. Both enzymes preferred coumaric acid over caffeic acid as a substrate in vitro. While expression of montbretia AAEs did not enhance MbA biosynthesis in N. benthamiana, we demonstrated that both Cc4CLs can be used to activate coumaric and caffeic acid towards flavanone biosynthesis in yeast (Saccharomyces cerevisiae).

Conclusions

Montbretia expresses two functional 4CLs, but neither of them is specific for the formation of caffeoyl-CoA. Based on differential expression analysis and phylogeny Cc4CL1 is most likely involved in MbA biosynthesis, while Cc4CL2 may contribute to lignin biosynthesis. Both Cc4CLs can be used for flavanone production to support metabolic engineering of MbA in yeast.
An ethnographic study of how health system, socio-cultural and individual factors influence uptake of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in a Ghanaian context
Authors: Aberese-Ako Matilda , Magnussen Pascal , Ampofo Gifty D. , Gyapong Margaret , Ansah Evelyn , Tagbor Harry
Published: October 2021

Background

Intermittent preventive treatment of malaria among pregnant women with sulfadoxine-pyrimethamine (IPTp-SP), is one of the three recommended interventions for the prevention of malaria in pregnancy (MiP) in sub-Sahara Africa. The World Health Organisation recommended in 2012 that SP be given at each scheduled ANC visit except during the first trimester and can be given a dose every month until the time of delivery, to ensure that a high proportion of women receive at least three doses of SP during pregnancy. Despite implementation of this policy, Ghana did not attain the target of 100% access to IPTp-SP by 2015. Additionally, negative outcomes of malaria infection in pregnancy are still recurring. This ethnographic study explored how health system, individual and socio-cultural factors influence IPTp-SP uptake in two Ghanaian regions.

Methods

The study design was ethnographic, employing non-participant observation, case studies and in depth interviews in 8 health facilities and 8 communities, from April 2018 to March 2019, in two Ghanaian regions. Recommended ethical procedures were observed.

Results

Health system factors such as organization of antenatal care (ANC) services and strategies employed by health workers to administer SP contributed to initial uptake. Women’s trust in the health care system contributed to continued uptake. Inadequate information provided to women accessing ANC, stock-outs and fees charged for ANC services reduced access to IPTp-SP. Socio-cultural factor such as encouragement from social networks influenced utilization of ANC services and IPTp-SP uptake. Individual factors such as refusing to take SP, skipping ANC appointments and initiating ANC attendance late affected uptake.

Conclusion

Health system, socio-cultural and individual factors influence uptake of optimum doses of IPTp-SP. Consequently, interventions that aim at addressing IPTp-SP uptake should focus on regular and sufficient supply of SP to health facilities, effective implementation of free ANC, provision of appropriate and adequate information to women and community outreach programmes to encourage early and regular ANC visits.
Association between self-esteem and efficacy and mental health in people with disabilities
Authors: Moon Jong Youn , Kim Jae-Hyun
Published: October 2021

This study aimed to investigate the association among self-evaluations—such as self-esteem and self-efficacy—self report of depression, and perceived stress among Korean individuals with disabilities. Data from the second wave of the Panel Survey of Employment for the Disabled (collected from 2016–2018) were used. In 2016 and the follow-up in 2018, 4,033 participants were included. We estimated the annual change in both independent variables and the probability of self-report of depression and stress. Generalized estimating equation model and chi-square test were used. Compared with those whose self-esteem and self-efficacy scores were ≥30, those with scores ≤19 were, respectively, 5.825 (95% Confidence Interval [CI]: 4.235–8.011; p < .0001) and 1.494 times (95% CI: 1.233–1.810; p < .0001) more likely to have self-report of depression. The perceived stress of those with self-esteem scores ≤19 or ranging from 20–24 were, respectively, 2.036 (95% CI: 1.510–2.747; p < .0001) and 1.451 times higher (95% CI: 1.269–1.659; p < .0001) than those with self-esteem scores ≥30. There exists an inverse correlation between self-evaluations, such as self-efficacy and self-esteem, and mental health in people with disabilities. The results of this study can be used as a basis for developing interventional strategies and training and intervention programs for people with disabilities. Future research is needed to investigate potential mediating factors among Korean individuals.
Impact of COVID-19 on residency choice: A survey of New York City medical students
Authors: Lee Kate E. , Lim Francesca , Silver Elisabeth R. , Faye Adam S. , Hur Chin
Published: October 2021

Objectives

The Coronavirus disease 2019 (COVID-19) pandemic disrupted medical student education, particularly in New York City (NYC). We aimed to assess the impact of the COVID-19 pandemic on medical students’ residency choices.

Methods

The authors conducted a cross-sectional survey of medical students in all years of study at four NYC medical schools (Columbia, Cornell, NYU, and SUNY Downstate). The survey was fielded from 19 Aug 2020 to 21 Sep 2020. Survey questions included items assessing COVID-19 impact on residency choices, personal impact of COVID-19, residency/specialty choices, and factors influencing these choices.

Results

A total of 2310 students received the survey, with 547 (23.7%) providing partial responses and 212 (9.2%) providing valid responses for our primary analysis. 59.0% of participants thought that COVID-19 influenced their choice of residency/specialty, with 0.9% saying the influence was to a great extent, 22.2% to some extent, and 35.8% very little. On multivariable analysis, factors that were independently associated with COVID-19 impacting residency choice included low debt ($1 to $99,999: adjOR 2.23, 95%CI 1.02–5.03) compared with no debt and Other race/ethnicity (adjOR 0.26, 95%CI 0.10–0.63) compared with White race/ethnicity. On secondary analysis of all participants answering survey items for logistic regression regardless of survey completion, direct personal impact of COVID-19 was significantly associated with COVID-19 impacting specialty choice (adjOR 1.90, 95%CI 1.04–3.52). Moreover, 24 students (11.6%) reported a change in their top residency choice from before to during/after COVID-19, citing concerns about frontline work, work-life balance, and risk of harm.

Conclusions

Our study found that 3 in 5 (59.0%) participants felt that COVID-19 impacted their residency choice, with 11.6% of respondents explicitly changing their top specialty choice. Investigating the impact of the pandemic on medical student residency considerations is crucial to understand how medical career outlooks may change in the future.
C. elegans genome-wide analysis reveals DNA repair pathways that act cooperatively to preserve genome integrity upon ionizing radiation
Authors: Meier Bettina , Volkova Nadezda V. , Wang Bin , González-Huici Víctor , Bertolini Simone , Campbell Peter J. , Gerstung Moritz , Gartner Anton
Published: October 2021

Ionizing radiation (IR) is widely used in cancer therapy and accidental or environmental exposure is a major concern. However, little is known about the genome-wide effects IR exerts on germ cells and the relative contribution of DNA repair pathways for mending IR-induced lesions. Here, usingC.elegansas a model system and using primary sequencing data from our recent high-level overview of the mutagenic consequences of 11 genotoxic agents, we investigate in detail the genome-wide mutagenic consequences of exposing wild-type and 43 DNA repair and damage response defectiveC.elegansstrains to a Caesium (Cs-137) source, emitting γ-rays. Cs-137 radiation induced single nucleotide variants (SNVs) at a rate of ~1 base substitution per 3 Gy, affecting all nucleotides equally. In nucleotide excision repair mutants, this frequency increased 2-fold concurrently with increased dinucleotide substitutions. As observed for DNA damage induced by bulky DNA adducts, small deletions were increased in translesion polymerase mutants, while base changes decreased. Structural variants (SVs) were augmented with dose, but did not arise with significantly higher frequency in any DNA repair mutants tested. Moreover, 6% of all mutations occurred in clusters, but clustering was not significantly altered in any DNA repair mutant background. Our data is relevant for better understanding how DNA repair pathways modulate IR-induced lesions.
Small but mighty: Functional landscape of the versatile geminivirus-encoded C4 protein
Authors: Medina-Puche Laura , Orílio Anelise F. , Zerbini F. Murilo , Lozano-Durán Rosa
Published: October 2021

The fast-paced evolution of viruses enables them to quickly adapt to the organisms they infect by constantly exploring the potential functional landscape of the proteins encoded in their genomes. Geminiviruses, DNA viruses infecting plants and causing devastating crop diseases worldwide, produce a limited number of multifunctional proteins that mediate the manipulation of the cellular environment to the virus’ advantage. Among the proteins produced by the members of this family, C4, the smallest one described to date, is emerging as a powerful viral effector with unexpected versatility. C4 is the only geminiviral protein consistently subjected to positive selection and displays a number of dynamic subcellular localizations, interacting partners, and functions, which can vary between viral species. In this review, we aim to summarize our current knowledge on this remarkable viral protein, encompassing the different aspects of its multilayered diversity, and discuss what it can teach us about geminivirus evolution, invasion requirements, and virulence strategies.
Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence
Authors: Diehl Mathias , Roling Lena , Rohland Lukas , Weber Sebastian , Cyrklaff Marek , Sanchez Cecilia P. , Beretta Carlo A. , Simon Caroline S. , Guizetti Julien , Hahn Julia , Schulz Norma , Mayer Matthias P. , Przyborski Jude M.
Published: October 2021

The pathology associated with malaria infection is largely due to the ability of infected human RBCs to adhere to a number of receptors on endothelial cells within tissues and organs. This phenomenon is driven by the export of parasite-encoded proteins to the host cell, the exact function of many of which is still unknown. Here we inactivate the function of one of these exported proteins, PFA66, a member of the J-domain protein family. Although parasites lacking this protein were still able to grow in cell culture, we observed severe defects in normal host cell modification, including aberrant morphology of surface knobs, disrupted presentation of the cytoadherence molecule PfEMP1, and a total lack of cytoadherence, despite the presence of the knob associated protein KAHRP. Complementation assays demonstrate that an intact J-domain is required for recovery to a wild-type phenotype and suggest that PFA66 functions in concert with a HSP70 to carry out host cell modification. Strikingly, this HSP70 is likely to be of host origin. ATPase assays on recombinant protein verify a functional interaction between PFA66 and residual host cell HSP70. Taken together, our data reveal a role for PFA66 in host cell modification, strongly implicate human HSP70s as being essential in this process and uncover a new KAHRP-independent molecular factor required for correct knob biogenesis.
The novel ORFV protein ORFV113 activates LPA-p38 signaling
Authors: Khatiwada Sushil , Delhon Gustavo , Chaulagain Sabal , Rock Daniel L.
Published: October 2021

Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OV-IA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. Infection of cells with ORFV in the presence of a p38 kinase inhibitor markedly diminished ORFV replication, highlighting importance of p38 signaling during ORFV infection. ORFV113 enhancement of p38 activation was prevented in cells in which LPA1 expression was knocked down and in cells treated with LPA1 inhibitor. Infection of sheep with OV-IA82Δ113 led to a strikingly attenuated disease phenotype, indicating that ORFV113 is a major virulence determinant in the natural host. Notably, ORFV113 represents the first viral protein that modulates p38 signaling via interaction with LPA1 receptor.
Transformación universitaria. Retos y oportunidades
Authors: Márquez Carmen
Published: October 2021

Los Objetivos del Desarrollo Sostenible de Naciones Unidas han reconocido el papel fundamental que poseen las instituciones de Educación Superior en el desarrollo socioeconómico, ambiental y tecnológico de nuestras sociedades. Como respuesta a esta invitación, comunidades universitarias de todo el mundo están trascendiendo sus antiguas funciones y avanzan hacia nuevos modelos de educación, investigación, innovación y cultura al servicio de las comunidades. Desde este marco contextual, el 6º Congreso Internacional CLIE 2021 USAL-PALECH ha querido ofrecer al personal docente, investigador, estudiantes, empresarios y resto de agentes sociales una plataforma de encuentro y reflexión conjunta acerca de esta necesaria transformación universitaria, sus retos y oportunidades. En esta obra, se recogen las contribuciones más destacadas sobre responsabilidad social, internacionalización e inclusión universitaria presentadas en este encuentro científico. Todas ellas apelan a la construcción de universidades más inclusiva, donde la diversidad de género, clase social, capacidad y etnia sea reconocida y valorada. Universidades flexibles, capaces de mantener entornos físicos y virtuales de aprendizaje que garanticen la calidad de los procesos de enseñanza y aprendizaje. Y universidades más responsables y comprometidas con el desarrollo sostenible de sus entornos. Con este misión compartida avanzamos hacia una Educación Superior sostenible, inclusiva e innovadora.
Potentially predictive factors for hearing function improvement in pediatric cytomegalovirus infection therapy
Authors: Triono Agung , Herini Elisabeth Siti , Widya Braghmandita , Nurputra Dian Kesumapramudya
Published: October 2021

Background Symptomatic congenital cytomegalovirus (CMV) infection has an impact mainly on neurological sequelae, including sensorineural deafness. Because of the long-term impact, early treatment of CMV infection is mandatory. However, predictive factors for hearing function improvement in CMV infection therapy remain unexamined.

Objective To evaluate potential predictive factors for hearing improvement in pediatric CMV infection therapy.

Methods All medical record data of patients aged 0-6 years with CMV infection who completed a 6-week course of ganciclovir therapy or a combination of a 4-week course of ganciclovir and a 2-week course valganciclovir from January 2013 to December 2017 were collected. Age at onset of therapy, gender, gestational age, nutritional status, multi-organ involvement, and neurological symptoms were studied as potential predictive factors of hearing improvement in CMV therapy. The effectiveness of CMV infection therapy on improving hearing function was measured with the brainstem evoked response audiometry (BERA) test.

Results BERA tests proportion in the right, left, and best ear showed significant improvement after therapy. All variables analyzed were not statistically significant as predictive factors for hearing improvement in CMV infection therapy.

Conclusion Ganciclovir/valganciclovir therapy in CMV infection patients accounted for the improvement of hearing impairment. However, none of the assessed factors were considered predictive for improving hearing function in CMV infection therapy.
Inflammatory markers and lipid profiles in obese children
Authors: Juliaty Aidah , Kurniasih Dina
Published: October 2021

Background Over 340 million children and adolescents aged 5-19 were overweight or obese in the year 2016. Individuals with obesity are at risk for metabolic disorders and lipid abnormalities. Adipose tissue is a major source of pro-inflammatory cytokines.

Objective To evaluate possible correlations between inflammatory markers IL-6, TNFa, and hs-CRP with lipid profiles between obese and non obese children.

Methods Eighty children, aged 13 to 15 years, were enrolled in this study (40 normoweight  and 40 obese). All participants’s ( obese and normoweight children) total plasma cholesterol, HDL cholesterol, triglycerides, as well as circulating levels of inflammatory factors, such as TNF-α, IL-6, and high sensitivity-C-reactive protein (hs-CRP) level were measured.

Results Obese children had significantly higher triglycerides (TG) and cholesterol, as well as lower HDL than normoweight subjects. Mean LDL levels were not significantly different between groups. The IL-6, TNFa, hs-CRP levels were significantly positively correlated with waist circumference. Analysis of the 4 blood lipid parameters and 3 inflammatory markers revealed significant positive correlations of triglycerides to TNFa and hs-CRP. In addition, HDL had significant negative correlations to both TNFa and hs-CRP.  No correlations were found between IL-6 and the 4 lipid parameters, nor between TNFa or hs-CRP to LDL and cholesterol. Multivariate regression analysis revealed a significant association between weight-height ratio with hs-CRP (R2 0.118; 95%CI 1.65 to 191; P=0.046). Obesity is associated with adverse lipid and inflammations markers in children.

Conclusion Obesity was associated with higher TG, cholesterol, TNF, and hs-CRP levels, as well as lower HDL.
Halaman Belakang
Authors: Editor Editor
Published: October 2021

Pedoman Penulisan, Cover Belakang
Learning Predictors from Multidimensional Data with Tensor Factorizations
Authors: Kwon Soo Min , Sarwate Anand D.
Published: October 2021

Statistical machine learning algorithms often involve learning a linear relationship between dependent and independent variables. This relationship is modeled as a vector of numerical values, commonly referred to as weights or predictors. These weights allow us to make predictions, and the quality of these weights influence the accuracy of our predictions. However, when the dependent variable inherently possesses a more complex, multidimensional structure, it becomes increasingly difficult to model the relationship with a vector. In this paper, we address this issue by investigating machine learning classification algorithms with multidimensional (tensor) structure. By imposing tensor factorizations on the predictors, we can better model the relationship, as the predictors would take the form of the data in question. We empirically show that our approach works more efficiently than the traditional machine learning method when the data possesses both an exact and an approximate tensor structure. Additionally, we show that estimating predictors with these factorizations also allow us to solve for fewer parameters, making computation more feasible for multidimensional data.
Ethical Implications of Biohacking as Activism: Democratized Health Care, Danger, or What?
Authors: Zheng Julia
Published: October 2021

Biohacking refers to optimizing one’s body through modifying biology. In the 20th century, do-it-yourself (DIY) biology emerged as a type of biohacking involving biotechnology. Current high- healthcare costs promote DIY -biology insulin and EpiPens as ways to challenge norms in healthcare, thus serving as forms of activism. Biohacked insulin is part of the #WeAreNotWaiting movement to support improved treatment of Type 1 diabetes, whereas biohacked EpiPens allow people to make lifesaving autoinjectors at low costs. Social media acts as a catalyst and aids in the spread of insulin and EpiPen biohacking as activism. In 1979, Principles of Biomedical Ethics by Beauchamp and Childress proposed four principles that continue to guide decision-making in clinical medicine: beneficence, nonmaleficence, autonomy, and justice. This paper applies these principles to explore whether the benefits of performing DIY biology outweigh the potential health risks. Examining biohacking with a biomedical ethics frame, as outlined by Beauchamp and Childress, reveals that biohacking acts as a response to current issues but cannot serve as a solution in its current form. However, biohacking can grant patients more power in their relationship with the healthcare system, therefore lessening the dominance of formal institutions. Out of the four principles, autonomy applies most differently when regarding biohacking than traditional medicine. Accordingly, a model of ethics for biohacking, such as of Beauchamp and Childress’ with the autonomy altered to acknowledge the additional implications of biohacking, should be developed in the future.
Level of hM4D(Gi) DREADD Expression Determines Inhibitory and Neurotoxic Effects in the Hippocampus
Authors: Goossens Marie-Gabrielle , Larsen Lars Emil , Vergaelen Marijke , Wadman Wytse , Van den Haute Chris , Brackx Wayra , Proesmans Silke , Desloovere Jana , Christiaen Emma , Craey Erine , Vanhove Christian , Vonck Kristl , Boon Paul , Raedt Robrecht
Published: October 2021

Selective neuromodulation using designer receptors exclusively activated by designer drugs (DREADDs) has become an increasingly important research tool, as well as an emerging therapeutic approach. However, the safety profile of DREADD expression is unknown. Here, different titers of adeno-associated viral (AAV) vector were administered in an attempt to vary total expression levels of the inhibitory DREADD hM4D(Gi) in excitatory hippocampal neurons. Male Sprague Dawley rats were injected with AAV2/7 encoding DREADD-mCherry, DREADD, or mCherry. Pronounced neuronal loss and neuroinflammatory reactions were observed after transduction with the high titer DREADD AAV, which also resulted in the highest DREADD expression levels. No such effects were observed in the mCherry control group, despite an equally high titer, nor in conditions where lower viral vector titers were injected. In the high titer DREADD conditions, dentate gyrus (DG) evoked potentials were inhibited on clozapine-induced activation of hM4D(Gi), while in low titer conditions DG evoked potentials were enhanced. Recordings of single neuronal activity nevertheless indicated a reduction in spontaneous firing of granule cell layer neurons. Our results indicate that prolonged, high levels of DREADD expression can have neurotoxic effects and that chemogenetic suppression of excitatory hippocampal neurons can paradoxically enhance DG evoked potentials.
Endocannabinoids Tune Intrinsic Excitability in O-LM Interneurons by Direct Modulation of Postsynaptic Kv7 Channels
Authors: Incontro Salvatore , Sammari Malika , Azzaz Fodil , Inglebert Yanis , Ankri Norbert , Russier Michael , Fantini Jacques , Debanne Dominique
Published: October 2021

KCNQ-Kv7 channels are found at the axon initial segment of pyramidal neurons, where they control cell firing and membrane potential. In oriens lacunosum moleculare (O-LM) interneurons, these channels are mainly expressed in the dendrites, suggesting a peculiar function of Kv7 channels in these neurons. Here, we show that Kv7 channel activity is upregulated following induction of presynaptic long-term synaptic depression (LTD) in O-LM interneurons from rats of both sex, thus resulting in a synergistic long-term depression of intrinsic excitability (LTD-IE). Both LTD and LTD-IE involve endocannabinoid (eCB) biosynthesis for induction. However, although LTD is dependent on cannabinoid type 1 receptors, LTD-IE is not. Molecular modeling shows a strong interaction of eCBs with Kv7.2/3 channel, suggesting a persistent action of these lipids on Kv7 channel activity. Our data thus unveil a major role for eCB synthesis in triggering both synaptic and intrinsic depression in O-LM interneurons.

SIGNIFICANCE STATEMENTIn principal cells, Kv7 channels are essentially located at the axon initial segment. In contrast, in O-LM interneurons, Kv7 channels are highly expressed in the dendrites, suggesting a singular role of these channels in O-LM cell function. Here, we show that LTD of excitatory inputs in O-LM interneurons is associated with an upregulation of Kv7 channels, thus resulting in a synergistic LTD of LTD-IE. Both forms of plasticity are mediated by the biosynthesis of eCBs. Stimulation of CB1 receptors induces LTD, whereas the direct interaction of eCBs with Kv7 channels induces LTD-IE. Our results thus provide a previously unexpected involvement of eCBs in long-lasting plasticity of intrinsic excitability in GABAergic interneurons.
FARKLI ÇÖZGEN VE ÇÖZGEN KARIŞIMLARI İLE EKSTRAKSİYONUN SAFRANIN (Crocus sativus L.) TOPLAM BİYOAKTİF BİLEŞEN MİKTARINA ETKİSİ
Authors: CHOBDAR RAHIM Saeid , HOSSEİN ZADEH Janan , PAZIR Fikret , OVA Gülden
Published: October 2021

Safran Standardına göre (TS/ISO 3632, 2011) kalite açısından birinci derece bir safran baharatının, 13 farklı çözgen sistemi (saf su, metanol, etanol, asetonun farklı oranlarda karışımı) kullanılarak elde edilen ekstraktlarının toplam fenolik ve flavonoid madde miktarlarıyla antioksidan aktiviteleri üzerine etkileri incelenmiştir. Sonuçlar incelendiğinde en yüksek toplam fenolik madde miktarı 2265.00 mg GAE/100 g KM ile su/etanol/metanol (v/v/v, 30/30/40) ekstraktında saptanırken, en düşük toplam fenolik madde miktarı 40.00 mg GAE/100 g KM ile aseton ekstraktında saptanmıştır. Toplam flavonoid madde açısından en yüksek miktar 587.14 mg KE/100 g KM ile su/etanol/metanol (v/v/v, 30/30/40) ekstraktında tespit edilirken, aseton ekstraktında flavonoid bileşeni tespit edilememiştir. Antioksidan aktivite açısından DPPH ve ABTS+ analiz yöntemlerinde en yüksek değerler sırasıyla 1202.68 mg TE/100 g KM ve 1383.74 mg TE/100 g KM ile su/etanol/metanol (v/v/v, 30/30/40) ekstraktında saptanırken, en düşük miktar DPPH için 232.43 mg TE/100 g KM etanolde ve ABTS+ için 251.23 mg TE/100 g KM aseton ekstraktında saptanmıştır.