bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice
Authors: Yamaguchi Takuya , Katano Ikumi , Otsuka Iyo , Ito Ryoji , Mochizuki Misa , Goto Motohito , Takahashi Takeshi
Published: July 2021

Despite recent advances in immunodeficient mouse models bearing human red blood cells (hRBCs), the elimination of circulating hRBCs by residual innate immune systems remains a significant challenge. In this study, we evaluated the role of mouse complement C3 in the elimination of circulating hRBCs by developing a novel NOG substrain harboring a truncated version of the murine C3 gene (NOG-C3ΔMG2-3). Genetic C3 deletion prolonged the survival of transfused hRBCs in the circulation. Chemical depletion and functional impairment of mouse macrophages, using clodronate liposomes (Clo-lip) or gadolinium chloride (GdCl3), respectively, further extended the survival of hRBCs in NOG-C3ΔMG2-3 mice. Low GdCl3 toxicity allowed the establishment of hRBC-bearing mice, in which hRBCs survived for more than 4 weeks with transfusion once a week. In addition, erythropoiesis of human hematopoietic stem cells (hHSCs) was possible in NOG-C3ΔMG2-3/human GM-CSF-IL-3 transgenic mice with Clo-lip treatment. These findings indicate that mouse models harboring hRBCs can be achieved using NOG-C3ΔMG2-3 mice, which could facilitate studies of human diseases associated with RBCs.
The Evolution and Diversity of Interleukin-17 Highlight an Expansion in Marine Invertebrates and Its Conserved Role in Mucosal Immunity
Authors: Saco Amaro , Rey-Campos Magalí , Rosani Umberto , Novoa Beatriz , Figueras Antonio
Published: July 2021

The interleukin-17 (IL-17) family consists of proinflammatory cytokines conserved during evolution. A comparative genomics approach was applied to examine IL-17 throughout evolution from poriferans to higher vertebrates. Cnidaria was highlighted as the most ancient diverged phylum, and several evolutionary patterns were revealed. Large expansions of the IL-17 repertoire were observed in marine molluscs and echinoderm species. We further studied this expansion in filter-fedMytilus galloprovincialis, which is a bivalve with a highly effective innate immune system supported by a variable pangenome. We recovered 379 unique IL-17 sequences and 96 receptors from individual genomes that were classified into 23 and 6 isoforms after phylogenetic analyses. Mussel IL-17 isoforms were conserved among individuals and shared between closely related Mytilidae species. Certain isoforms were specifically implicated in the response to a waterborne infection withVibrio splendidusin mussel gills. The involvement of IL-17 in mucosal immune responses could be conserved in higher vertebrates from these ancestral lineages.
Mycobacterium tuberculosis Specific Protein Rv1509 Evokes Efficient Innate and Adaptive Immune Response Indicative of Protective Th1 Immune Signature
Authors: P Manjunath , Ahmad Javeed , Samal Jasmine , Sheikh Javaid Ahmad , Arora Simran Kaur , Khubaib Mohd , Aggarwal Heena , Kumari Indu , Luthra Kalpana , Rahman Syed Asad , Hasnain Seyed E. , Ehtesham Nasreen Z.
Published: July 2021

Dissecting the function(s) of proteins present exclusively inMycobacterium tuberculosis(M.tb) will provide important clues regarding the role of these proteins in mycobacterial pathogenesis. Using extensive computational approaches, we shortlisted ORFs/proteins unique toM.tbamong 13 different species of mycobacteria and identified a hypothetical protein Rv1509 as a ‘signature protein’ ofM.tb. This unique protein was found to be present only inM.tband absent in all other mycobacterial species, including BCG.In silicoanalysis identified numerous putative T cell and B cell epitopes in Rv1509. Initialin vitroexperiments using innate immune cells demonstrated Rv1509 to be immunogenic with potential to modulate innate immune responses. Macrophages treated with Rv1509 exhibited higher activation status along with substantial release of pro-inflammatory cytokines. Besides, Rv1509 protein boosts dendritic cell maturation by increasing the expression of activation markers such as CD80, HLA-DR and decreasing DC-SIGN expression and this interaction was mediated by innate immune receptor TLR2. Further,in vivoexperiments in mice demonstrated that Rv1509 protein promotes the expansion of multifunctional CD4+ and CD8+T cells and induces effector memory response along with evoking a canonical Th1 type of immune response. Rv1509 also induces substantial B cell response as revealed by increased IgG reactivity in sera of immunized animals. This allowed us to demonstrate the diagnostic efficacy of this protein in sera of human TB patients compared to the healthy controls. Taken together, our results reveal that Rv1509 signature protein has immunomodulatory functions evoking immunological memory response with possible implications in serodiagnosis and TB vaccine development.
Marine Macrobenthos of NorthWest India-Reviewing the Known and Unknown
Authors: Sukumaran Soniya , Vijapure Tejal , Mulik Jyoti , Ridha Hurmine
Published: July 2021

Tropical ecosystems sustain higher biodiversity and face faster species extinction. However, baseline information of these areas is either inadequate or scattered due to various reasons. The 2,360 km long coast of North West India (NWI), is a heavily industrialized and urbanized zone. This coast with unique biogeographical and climatic features with two notified marine protected areas also supports rich biodiversity. This review was motivated by a need to construct a synoptic view on marine benthic ecology and functioning by consolidating available information of macrobenthos. Two thousand seventy-eight macrobenthic taxa belonging to 14 phyla were compiled from 147 references and were composed mostly by Polychaeta (n= 617), Gastropoda (n= 602), and Bivalvia (n= 216). Habitat wise, intertidal and subtidal zones were more intensely studied and contributed most to the diversity records. Sediment texture and salinity were the major drivers of macrobenthic community structure in the subtidal areas and estuaries, respectively. In the intertidal zones, zonation patterns related to the tidal levels and time of exposure were distinct with the high water zones being sparsely populated and lower intertidal zones sustaining higher species and functional diversities. All zones of NWI coast were distinctly impacted to various extent by anthropogenic activities affecting the resident macrobenthos. Decline in species richness and species substitution due to pollution were reported in urbanized zones. Non-monsoonal months favored a more conducive environment for the macrobenthic diversity and functionality. Hypoxia tolerant polychaete species mainly belonging to Spionidae and Cossuridae dominated during the low oxygen conditions of upwelling and OMZ zones of NWI. Inadequate identification and inconsistency of sampling methods were major deterrents for concluding trends of distributions. Suggestions for future macrobenthic research include focusing on lesser studied groups and areas, seasonal as well anthropogenic hypoxic zones and well planned long-term monitoring studies. Major data lacunae were identified in the taxonomy, molecular, functional aspects, and bioinvasive studies of macrobenthos in this geographical zone despite clear evidence of high diversity of extant macrofauna. This compendium should help prioritize research areas and objectives aimed at enhancing our understanding of macrobenthos and improve predictive capabilities of community shifts that may occur due to global climate change scenarios.
A Comparative Study on Low and High Salinity Tolerance of Two Strains of Pinctada fucata
Authors: Sun Jing , Chen Mingqiang , Fu Zhengyi , Yang Jingru , Zhou Shengjie , Yu Gang , Zhou Wenli , Ma Zhenhua
Published: July 2021

This study compares salinity tolerance between red and black shell Pinctada fucata salinity stress of 20 and 50‰, while 35‰ was used as a control. The hemolymph osmotic pressure, inorganic ion concentration, the activities of Na+-K+ -ATPase, respiratory metabolism related enzymes and liver tissue antioxidant related enzymes were measured at 12 and 24 h after salinity stress. The osmotic pressure and inorganic ion concentration of hemolymph of two strains P. fucata increased significantly with the increase of salinity. The activity of Na+-K+ -ATPase of red P. fucata only decreased under low salinity at 24 h, and was significantly higher than that the control under low salinity at 12 h and high salinity at 12 and 24 h. The succinate dehydrogenase (SDH) activities of the P. fucata treatment groups were significantly higher than those the control at 12 h. The lactate dehydrogenase (LDH) activity increased significantly with salinity at 12 h. and the black P. fucata LDH activity was significantly higher than the control at 24 h, while the LDH activity of red P. fucata was significantly lower than that the control in 50‰ salinity. The superoxide dismutase (SOD) activity of black P. fucata was significantly lower than that the control, while that of red P. fucata was significantly higher than that the control within 24. At 12 h, the catalase (CAT) activity of red P. fucata increased significantly with salinity, but decreased significantly with salinity at 24 h. The CAT activity of black P. fucata was highest at 24 h under low salinity. Glutathione peroxidase (GSH-Px) and alkaline phosphatase (AKP) activities of red P. fucata were significantly higher than those the control under low or high salinity. At high salinity for 24 h, the GSH-Px activity was lowest in black P. fucata, AKP activity was highest. The present study indicates that the physical responses of P. fucata to the salinity stress vary with shell colors. The red P. fucata can quickly respond positively to the change of environmental salinity and reduce the damage caused by the change of environmental salinity.
Calibration-Free Cuffless Blood Pressure Estimation Based on a Population With a Diverse Range of Age and Blood Pressure
Authors: Yamanaka Syunsuke , Morikawa Koji , Morita Hiroshi , Huh Ji Young , Yamamura Osamu
Published: July 2021

This study presents a new blood pressure (BP) estimation algorithm utilizing machine learning (ML). A cuffless device that can measure BP without calibration would be precious for portability, continuous measurement, and comfortability, but unfortunately, it does not currently exist. Conventional BP measurement with a cuff is standard, but this method has various problems like inaccurate BP measurement, poor portability, and painful cuff pressure. To overcome these disadvantages, many researchers have developed cuffless BP estimation devices. However, these devices are not clinically applicable because they require advanced preparation before use, such as calibration, do not follow international standards (81060-1:2007), or have been designed using insufficient data sets. The present study was conducted to combat these issues. We recruited 127 participants and obtained 878 raw datasets. According to international standards, our diverse data set included participants from different age groups with a wide variety of blood pressures. We utilized ML to formulate a BP estimation method that did not require calibration. The present study also conformed to the method required by international standards while calculating the level of error in BP estimation. Two essential methods were applied in this study: (a) grouping the participants into five subsets based on the relationship between the pulse transit time and systolic BP by a support vector machine ensemble with bagging (b) applying the information from the wavelet transformation of the pulse wave and the electrocardiogram to the linear regression BP estimation model for each group. For systolic BP, the standard deviation of error for the proposed BP estimation results with cross-validation was 7.74 mmHg, which was an improvement from 17.05 mmHg, as estimated by the conventional pulse-transit-time-based methods. For diastolic BP, the standard deviation of error was 6.42 mmHg for the proposed BP estimation, which was an improvement from 14.05mmHg. The purpose of the present study was to demonstrate and evaluate the performance of the newly developed BP estimation ML method that meets the international standard for non-invasive sphygmomanometers in a population with a diverse range of age and BP.
16S rRNA Gene Metabarcoding Indicates Species-Characteristic Microbiomes in Deep-Sea Benthic Foraminifera
Authors: Salonen Iines S. , Chronopoulou Panagiota-Myrsini , Nomaki Hidetaka , Langlet Dewi , Tsuchiya Masashi , Koho Karoliina A.
Published: July 2021

Foraminifera are unicellular eukaryotes that are an integral part of benthic fauna in many marine ecosystems, including the deep sea, with direct impacts on benthic biogeochemical cycles. In these systems, different foraminiferal species are known to have a distinct vertical distribution, i.e., microhabitat preference, which is tightly linked to the physico-chemical zonation of the sediment. Hence, foraminifera are well-adapted to thrive in various conditions, even under anoxia. However, despite the ecological and biogeochemical significance of foraminifera, their ecology remains poorly understood. This is especially true in terms of the composition and diversity of their microbiome, although foraminifera are known to harbor diverse endobionts, which may have a significant meaning to each species’ survival strategy. In this study, we used 16S rRNA gene metabarcoding to investigate the microbiomes of five different deep-sea benthic foraminiferal species representing differing microhabitat preferences. The microbiomes of these species were compared intra- and inter-specifically, as well as with the surrounding sediment bacterial community. Our analysis indicated that each species was characterized with a distinct, statistically different microbiome that also differed from the surrounding sediment community in terms of diversity and dominant bacterial groups. We were also able to distinguish specific bacterial groups that seemed to be strongly associated with particular foraminiferal species, such as the family Marinilabiliaceae for Chilostomella ovoidea and the family Hyphomicrobiaceae for Bulimina subornata and Bulimina striata. The presence of bacterial groups that are tightly associated to a certain foraminiferal species implies that there may exist unique, potentially symbiotic relationships between foraminifera and bacteria that have been previously overlooked. Furthermore, the foraminifera contained chloroplast reads originating from different sources, likely reflecting trophic preferences and ecological characteristics of the different species. This study demonstrates the potential of 16S rRNA gene metabarcoding in resolving the microbiome composition and diversity of eukaryotic unicellular organisms, providing unique in situ insights into enigmatic deep-sea ecosystems.
Cultivation of Dominant Freshwater Bacterioplankton Lineages Using a High-Throughput Dilution-to-Extinction Culturing Approach Over a 1-Year Period
Authors: Kim Suhyun , Islam Md. Rashedul , Kang Ilnam , Cho Jang-Cheon
Published: July 2021

Although many culture-independent molecular analyses have elucidated a great diversity of freshwater bacterioplankton, the ecophysiological characteristics of several abundant freshwater bacterial groups are largely unknown due to the scarcity of cultured representatives. Therefore, a high-throughput dilution-to-extinction culturing (HTC) approach was implemented herein to enable the culture of these bacterioplankton lineages using water samples collected at various seasons and depths from Lake Soyang, an oligotrophic reservoir located in South Korea. Some predominant freshwater bacteria have been isolated from Lake Soyang via HTC (e.g., the acI lineage); however, large-scale HTC studies encompassing different seasons and water depths have not been documented yet. In this HTC approach, bacterial growth was detected in 14% of 5,376 inoculated wells. Further, phylogenetic analyses of 16S rRNA genes from a total of 605 putatively axenic bacterial cultures indicated that the HTC isolates were largely composed of Actinobacteria, Bacteroidetes, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Verrucomicrobia. Importantly, the isolates were distributed across diverse taxa including phylogenetic lineages that are widely known cosmopolitan and representative freshwater bacterial groups such as the acI, acIV, LD28, FukuN57, MNG9, and TRA3–20 lineages. However, some abundant bacterial groups including the LD12 lineage, Chloroflexi, and Acidobacteria could not be domesticated. Among the 71 taxonomic groups in the HTC isolates, representative strains of 47 groups could either form colonies on agar plates or be revived from frozen glycerol stocks. Additionally, season and water depth significantly affected bacterial community structure, as demonstrated by 16S rRNA gene amplicon sequencing analyses. Therefore, our study successfully implemented a dilution-to-extinction cultivation strategy to cultivate previously uncultured or underrepresented freshwater bacterial groups, thus expanding the basis for future multi-omic studies.
Inhibited Methanogenesis in the Rumen of Cattle: Microbial Metabolism in Response to Supplemental 3-Nitrooxypropanol and Nitrate
Authors: van Lingen Henk J. , Fadel James G. , Yáñez-Ruiz David R. , Kindermann Maik , Kebreab Ermias
Published: July 2021

3-Nitrooxypropanol (3-NOP) supplementation to cattle diets mitigates enteric CH4 emissions and may also be economically beneficial at farm level. However, the wider rumen metabolic response to methanogenic inhibition by 3-NOP and the NO2- intermediary metabolite requires further exploration. Furthermore, NO3- supplementation potently decreases CH4 emissions from cattle. The reduction of NO3- utilizes H2 and yields NO2-, the latter of which may also inhibit rumen methanogens, although a different mode of action than for 3-NOP and its NO2- derivative was hypothesized. Our objective was to explore potential responses of the fermentative and methanogenic metabolism in the rumen to 3-NOP, NO3- and their metabolic derivatives using a dynamic mechanistic modeling approach. An extant mechanistic rumen fermentation model with state variables for carbohydrate substrates, bacteria and protozoa, gaseous and dissolved fermentation end products and methanogens was extended with a state variable of either 3-NOP or NO3-. Both new models were further extended with a NO2- state variable, with NO2- exerting methanogenic inhibition, although the modes of action of 3-NOP-derived and NO3--derived NO2- are different. Feed composition and intake rate (twice daily feeding regime), and supplement inclusion were used as model inputs. Model parameters were estimated to experimental data collected from the literature. The extended 3-NOP and NO3- models both predicted a marked peak in H2 emission shortly after feeding, the magnitude of which increased with higher doses of supplement inclusion. The H2 emission rate appeared positively related to decreased acetate proportions and increased propionate and butyrate proportions. A decreased CH4 emission rate was associated with 3-NOP and NO3- supplementation. Omission of the NO2- state variable from the 3-NOP model did not change the overall dynamics of H2 and CH4 emission and other metabolites. However, omitting the NO2- state variable from the NO3- model did substantially change the dynamics of H2 and CH4 emissions indicated by a decrease in both H2 and CH4 emission after feeding. Simulations do not point to a strong relationship between methanogenic inhibition and the rate of NO3- and NO2- formation upon 3-NOP supplementation, whereas the metabolic response to NO3- supplementation may largely depend on methanogenic inhibition by NO2-.
Whole Genome Analysis Detects the Emergence of a Single Salmonella enterica Serovar Chester Clone in Japan’s Kanto Region
Authors: Ando Naoshi , Sekizuka Tsuyoshi , Yokoyama Eiji , Aihara Yoshiyuki , Konishi Noriko , Matsumoto Yuko , Ishida Kumiko , Nagasawa Koo , Jourdan-Da Silva Nathalie , Suzuki Motoi , Kimura Hirokazu , Le Hello Simon , Murakami Koichi , Kuroda Makoto , Hirai Shinichiro , Fukaya Setsuko
Published: July 2021

In Japan’s Kanto region, the number of Salmonella enterica serovar Chester infections increased temporarily between 2014 and 2016. Concurrently with this temporal increase in the Kanto region, S. Chester isolates belonging to one clonal group were causing repetitive outbreaks in Europe. A recent study reported that the European outbreaks were associated with travelers who had been exposed to contaminated food in Morocco, possibly seafood. Because Japan imports a large amount of seafood from Morocco, we aimed to establish whether the temporal increase in S. Chester infections in the Kanto region was associated with imported Moroccan seafood. Short sequence reads from the whole-genome sequencing of 47 S. Chester isolates from people in the Kanto region (2014–2016), and the additional genome sequences from 58 isolates from the European outbreaks, were analyzed. The reads were compared with the complete genome sequence from a S. Chester reference strain, and 347 single nucleotide polymorphisms (SNPs) were identified. These SNPs were used in this study. Cluster and Bayesian cluster analyses showed that the Japanese and European isolates fell into two different clusters. Therefore, ΦPT and IAS values were calculated to evaluate genetic differences between these clusters. The results revealed that the Japanese and European isolates were genetically distinct populations. Our root-to-tip analysis showed that the Japanese isolates originating from one clone had accumulated mutations, suggesting that an emergence of this organism occurred. A minimum spanning tree analysis demonstrated no correlation between genetic and geographical distances in the Japanese isolates, suggesting that the emergence of the serovar in the Kanto region did not involve person-to-person contact; rather, it occurred through food consumption. The dN/dS ratio indicated that the Japanese strain has evolved under positive selection pressure. Generally, a population of bacterial clones in a reservoir faces negative selection pressure. Therefore, the Japanese strain must have existed outside of any reservoir during its emergence. In conclusion, S. Chester isolates originating from one clone probably emerged in the Kanto region via the consumption of contaminated foods other than imported Moroccan seafood. The emerging strain may have not established a reservoir for survival in the food supply chain resulting in its disappearance after 2017.
Deuteron Chemical Exchange Saturation Transfer for the Detection of Slow Motions in Rotating Solids
Authors: Vugmeyster Liliya , Ostrovsky Dmitry , Greenwood Alexander , Fu Riqiang
Published: July 2021

We utilized the 2H Chemical Exchange Saturation Transfer (CEST) technique under magic angle spinning (MAS) conditions to demonstrate the feasibility of the method for studies of slow motions in the solid state. For the quadrupolar anisotropic interaction, the essence of CEST is to scan the saturation pattern over a range of offsets corresponding to the entire spectral region(s) for all conformational states involved, which translates into a range of −60–+ 60 kHz for methyl groups. Rotary resonances occur when the offsets are at half-and full-integer of the MAS rates. The choice of the optimal MAS rate is governed by the condition to reduce the number of rotary resonances in the CEST profile patterns and retain a sufficiently large quadrupolar interaction active under MAS to maintain sensitivity to motions. As examples, we applied this technique to a well-known model compound dimethyl-sulfone (DMS) as well as amyloid-β fibrils selectively deuterated at a single methyl group of A2 belonging to the disordered domain. It is demonstrated that the obtained exchange rate between the two rotameric states of DMS at elevated temperatures fell within known ranges and the fitted model parameters for the fibrils agree well with the previously obtained value using static 2H NMR techniques. Additionally, for the fibrils we have observed characteristic broadening of rotary resonances in the presence of conformational exchange, which provides implications for model selection and refinement. This work sets the stage for future potential extensions of the 2H CEST under MAS technique to multiple-labeled samples in small molecules and proteins.
Cerebrovascular Disease and Depressive Symptomatology in Individuals With Subjective Cognitive Decline: A Community-Based Study
Authors: Diaz-Galvan Patricia , Cedres Nira , Figueroa Nerea , Barroso Jose , Westman Eric , Ferreira Daniel
Published: July 2021

Subjective cognitive decline (SCD) may be the first sign of Alzheimer's disease (AD), but it can also reflect other pathologies such as cerebrovascular disease or conditions like depressive symptomatology. The role of depressive symptomatology in SCD is controversial. We investigated the association between depressive symptomatology, cerebrovascular disease, and SCD. We recruited 225 cognitively unimpaired individuals from a prospective community-based study [mean age (SD) = 54.64 (10.18); age range 35–77 years; 55% women; 123 individuals with one or more subjective cognitive complaints, 102 individuals with zero complaints]. SCD was assessed with a scale of 9 memory and non-memory subjective complaints. Depressive symptomatology was assessed with established questionnaires. Cerebrovascular disease was assessed with magnetic resonance imaging markers of white matter signal abnormalities (WMSA) and mean diffusivity (MD). We combined correlation, multiple regression, and mediation analyses to investigate the association between depressive symptomatology, cerebrovascular disease, and SCD. We found that SCD was associated with more cerebrovascular disease, older age, and increased depressive symptomatology. In turn, depressive symptomatology was not associated with cerebrovascular disease. Variability in MD was mediated by WMSA burden, presumably reflecting cerebrovascular disease. We conclude that, in our community-based cohort, depressive symptomatology is associated with SCD but not with cerebrovascular disease. In addition, depressive symptomatology did not influence the association between cerebrovascular disease and SCD. We suggest that therapeutic interventions for depressive symptomatology could alleviate the psychological burden of negative emotions in people with SCD, and intervening on vascular risk factors to reduce cerebrovascular disease should be tested as an opportunity to minimize neurodegeneration in SCD individuals from the community.
vHIT Testing of Vertical Semicircular Canals With Goggles Yield Different Results Depending on Which Canal Plane Being Tested
Authors: Wittmeyer Cedervall Louise , Magnusson Måns , Karlberg Mikael , Fransson Per-Anders , Nyström Anastasia , Tjernström Fredrik
Published: July 2021

Objective: The use of goggles to assess vertical semicircular canal function has become a standard method in vestibular testing, both in clinic and in research, but there are different methods and apparatus in use. The aim of this study was to determine what the cause of the systematic differences is between gain values in testing of the vertical semicircular canals with two different video head impulse test (vHIT) equipment in subjects with normal vestibular function.

Study Design: Retrospective analysis of gain values on patients with clinically deemed normal vestibular function (absence of a corrective eye saccade), tested with either Interacoustics or Otometrics system. Prospective testing of subjects with normal vestibular function with the camera records the eye movements of both eyes. Finally, 3D sensors were placed on different positions on the goggles measuring the actual vertical movement in the different semicircular planes.

Results: In the clinical cohorts, the gain depended on which side and semicircular canal was tested (p < 0.001). In the prospective design, the combination between the stimulated side, semicircular canal, and position of the recording device (right/left eye) highly influenced the derived gain (p < 0.001). The different parts of the goggles also moved differently in a vertical direction during vertical semicircular canal testing.

Conclusion: The gain values when testing the function of the vertical semicircular canals seem to depend upon which eye is recorded and which semicircular plane is tested and suggests caution when interpreting and comparing results when different systems are used both clinically as well as in research. The results also imply that further research and development are needed to obtain accurate vertical semicircular canal testing, in regard to both methodology and equipment design.
Lateralization of Motor Signs Affects Symptom Progression in Parkinson Disease
Authors: Elkurd Mazen , Wang Jijia , Dewey Richard B.
Published: July 2021

Background: Asymmetry of motor signs is a cardinal feature of Parkinson disease which may impact phenotypic expression.

Objective: To investigate the relationship between lateralization of motor signs and symptom progression and severity during longitudinal observation for up to 4 years in a naturalistic study.

Methods: We analyzed data prospectively collected during the NINDS Parkinson Disease Biomarker Project (PDBP). We defined the Movement Disorder Society Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) part II as the primary measure of symptom progression. Left side predominant subjects were those whose lateralized motor scores on the MDS-UPDRS part III were ≥2 points higher on the left side than on the right side of the body. Multiple regression models (controlled for age, gender, education years, ethnicity, levodopa equivalent daily dose (LEDD) at baseline, and years with PD) were used to estimate the rate of symptom progression comparing left predominant (LPD) with non-left predominant (NLPD) subjects. A sensitivity analysis was performed using the same multiple regression models in the subgroups of low (0–26) or high (>27) MDS-UPDRS II score at baseline to determine if PD severity influenced the results.

Results: We included 390 participants, 177 LPD and 213 NLPD. We found that MDS-UPDRS part II progression from baseline to 48 months was faster in LPD compared to NLPD (0.6 points per year faster in LPD, p = 0.05). Additionally, the LPD group was statistically significantly worse at baseline and at 48 months in several subparts of the MDS-UPDRS and the Parkinson's Disease Questionnaire-39 (PDQ-39) mobility score. Significantly slower progression (difference of −0.8, p = 0.01) and lower score at 48 months (difference of −3.8, p = 0.003) was seen for NLPD vs. LPD in the group with lower baseline MDS-UPDRS part II score.

Conclusion: Left side lateralization was associated with faster symptom progression and worse outcomes in multiple clinical domains in our cohort. Clinicians should consider using motor predominance in their counseling regarding prognosis.
Event Camera Simulator Improvements via Characterized Parameters
Authors: Joubert Damien , Marcireau Alexandre , Ralph Nic , Jolley Andrew , van Schaik André , Cohen Gregory
Published: July 2021

It has been more than two decades since the first neuromorphic Dynamic Vision Sensor (DVS) sensor was invented, and many subsequent prototypes have been built with a wide spectrum of applications in mind. Competing against state-of-the-art neural networks in terms of accuracy is difficult, although there are clear opportunities to outperform conventional approaches in terms of power consumption and processing speed. As neuromorphic sensors generate sparse data at the focal plane itself, they are inherently energy-efficient, data-driven, and fast. In this work, we present an extended DVS pixel simulator for neuromorphic benchmarks which simplifies the latency and the noise models. In addition, to more closely model the behaviour of a real pixel, the readout circuitry is modelled, as this can strongly affect the time precision of events in complex scenes. Using a dynamic variant of the MNIST dataset as a benchmarking task, we use this simulator to explore how the latency of the sensor allows it to outperform conventional sensors in terms of sensing speed.
The Potential Effect of Nav1.8 in Autism Spectrum Disorder: Evidence From a Congenital Case With Compound Heterozygous SCN10A Mutations
Authors: Heinrichs Björn , Liu Baowen , Zhang Jin , Meents Jannis E. , Le Kim , Erickson Andelain , Hautvast Petra , Zhu Xiwen , Li Ningbo , Liu Yi , Spehr Marc , Habel Ute , Rothermel Markus , Namer Barbara , Zhang Xianwei , Lampert Angelika , Duan Guangyou
Published: July 2021

Apart from the most prominent symptoms in Autism spectrum disorder (ASD), namely deficits in social interaction, communication and repetitive behavior, patients often show abnormal sensory reactivity to environmental stimuli. Especially potentially painful stimuli are reported to be experienced in a different way compared to healthy persons. In our present study, we identified an ASD patient carrying compound heterozygous mutations in the voltage-gated sodium channel (VGSC) Nav1.8, which is preferentially expressed in sensory neurons. We expressed both mutations, p.I1511M and p.R512∗, in a heterologous expression system and investigated their biophysical properties using patch-clamp recordings. The results of these experiments reveal that the p.R512∗ mutation renders the channel non-functional, while the p.I1511M mutation showed only minor effects on the channel’s function. Behavioral experiments in a Nav1.8 loss-of-function mouse model additionally revealed that Nav1.8 may play a role in autism-like symptomatology. Our results present Nav1.8 as a protein potentially involved in ASD pathophysiology and may therefore offer new insights into the genetic basis of this disease.
Chinese Herbal Medicine for Irritable Bowel Syndrome: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials
Authors: Zheng Hui , Jin Song , Shen Yin-Li , Peng Wen-Yan , Ye Kun , Tang Tai-Chun , Zhao Jun , Chen Min , Li Zhi-Gang
Published: July 2021

Purpose: Chinese herbal medicine (CHM) is an important complementary and alternative therapy for the management of irritable bowel syndrome (IBS). Previous meta-analyses suggested that CHM is effective for IBS; nonetheless, its effectiveness is inconclusive owing to repeated significance testing. We aimed to examine the efficacy and safety of CHM for IBS through a meta-analysis and trial sequential analysis (TSA).

Methods: We searched OVID Medline, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from January 1, 1980, to September 20, 2020. The primary outcome was adequate relief of global IBS symptoms. The secondary outcomes included relief of abdominal pain and treatment-related adverse events. The relative ratio (RR) and required information size (RIS) were calculated for each outcome.

Results: Ten trials recruiting 2,501 participants were included. Seven (70%) trials were at low risk of bias (RoB). Compared with placebo, CHM was associated with a significantly higher proportion of adequate relief of global IBS symptoms [RR 1.76 (95% confidence interval (95%CI), 1.33–2.33); I2 = 81.1%; p < 0.001]. The RIS was 1,083 for the primary outcome, and the accrued information size was 1,716. The analysis of the relief of abdominal pain (three trials with 916 participants) showed similar results compared with placebo [RR 1.85 (95%CI, 1.59–2.14); I2 = 0%; p < 0.001; RIS = 197 participants]. CHM was associated with a higher proportion of adverse events compared with placebo [RR 1.51 (95%CI, 1.14–2); I2 = 0%; p = 0.004].

Conclusion: CHM was effective in relieving IBS symptoms but caused a higher adverse event rate than placebo. TSA analysis confirmed the findings with sufficient information size.
ALKBH10B, an mRNA m6A Demethylase, Modulates ABA Response During Seed Germination in Arabidopsis
Authors: Tang Jun , Yang Junbo , Duan Hongchao , Jia Guifang
Published: July 2021

As the most abundant and reversible chemical modification in eukaryotic mRNA, the epitranscriptomic mark N6-methyladenine (m6A) regulates plant development and stress response. We have previously characterized that ALKBH10B is an Arabidopsis mRNA m6A demethylase and regulates floral transition. However, it is unclear whether ALKBH10B plays a role in abiotic stress response. Here, we found that the expression of ALKBH10B is increased in response to abscisic acid (ABA), osmotic, and salt stress. The alkbh10b mutants showed hypersensitive to ABA, osmotic, and salt stress during seed germination. Transcriptome analysis revealed that the expression of several ABA response genes is upregulated in alkbh10b-1 than that of wild type, indicating ALKBH10B negatively affects the ABA signaling. Furthermore, m6A sequencing showed that ABA signaling genes, including PYR1, PYL7, PYL9, ABI1, and SnRK2.2 are m6A hypermethylated in alkbh10b-1 after ABA treatment. Taken together, our work demonstrated that ALKBH10B negatively modulates ABA response during seed germination in Arabidopsis.
The Effect of Orthographic Transparency on Auditory Word Recognition Across the Development of Reading Proficiency
Authors: Bakhtiar Mehdi , Mokhlesin Maryam , Pattamadilok Chotiga , Politzer-Ahles Stephen , Zhang Caicai
Published: July 2021

A question under debate in psycholinguistics is the nature of the relationship between spoken and written languages. Although it has been extensively shown that orthographic transparency, which varies across writing systems, strongly affects reading performance, its role in speech processing is much less investigated. The present study addressed this issue in Persian, whose writing system provides a possibility to assess the impact of orthographic transparency on spoken word recognition in young children at different stages of reading acquisition. In Persian, the long vowels are systematically present in the script, whereas the spelling correspondence of short vowels is progressively omitted from the script in the course of reading acquisition, thus, turning transparent into opaque spelling. Based on this unique characteristic, we tested 144 monolingual Persian-speaking nonreaders (i.e., preschoolers) and readers (second graders to fifth graders and young adults) in an auditory lexical decision task using transparent and opaque words. Overall, the results showed that, in accordance with the fact that the diacritics of short vowels are progressively omitted during the second year of schooling, the stimuli containing short vowels (opaque words) were recognized more slowly than transparent ones in third graders. Interestingly, there is a hint that the emergence of the transparency effect in the third graders was associated with an overall slower recognition speed in this group compared to their younger peers. These findings indicate that learning opaque spelling-sound correspondence might not only generate interference between the two language codes but also induce a general processing cost in the entire spoken language system.
Comparing Log-Linear and Best-Fit Models to Evaluate the Long-Term Persistence of Enteric Markers in Sewage Spiked River Water
Authors: Brooks Yolanda M. , Rose Joan B.
Published: July 2021

Water quality models use log-linear decay to estimate the inactivation of fecal indicator bacteria (FIB). The decay of molecular measurements of FIB does not follow a log-linear pattern. This study examined the factors associated with the persistence of Escherichia coli uidA, enterococci 23S rDNA, and Bacteroides thetataiotaomicron 1,6 alpha mannanase in microcosms containing 10% (vol/vol) sewage spiked river water stored at 4°C for up to 337 days. The study estimated the markers' persistence with log-linear models (LLMs) to the best-fit models, biphasic exponential decay (BI3) and log-logistic (JM2) and compared the estimates from the models. Concentrations of B. thetataiotaomicon decreased to levels below detection after 31 days in storage and were not fit to models. BI3 and JM2 were fit to E. coli and enterococci, respectively. LLMs had larger Bayesian information criterion values than best-fit models, indicating poor fit. LLMs over-estimated the time required for 90% reduction of the indicators (T90) and did not consider dynamic rates of decay. Time in storage and indicator species were associated with the persistence of the markers (p < 0.001). Using the T90 values of the best-fit models, enterococci was the most persistent indicator. Our data supports the use of best fit models with dynamic decay rates in water quality models to evaluate the decay of enteric markers.
Effects of Four-Week Kayak Training on Three-Dimensional Paddling Kinetics, Body Kinematics, and Electromyography Activity in a Novice Paddler: A Case Study
Authors: Kinugasa Ryuta , Kubo Shimpei , Endo Keiko
Published: July 2021

From a biomechanical viewpoint, no longitudinal quantitative studies have been conducted on inexperienced paddlers. The present study aimed to investigate changes in three-dimensional paddling kinetics and kinematics, whole-body kinematics, and muscle activity with four-week on-water kayak training in a novice paddler. The participant practiced kayak paddling on river for four weeks. Before and after training, paddling kinetics and kinematics, body kinematics, and electromyography (EMG) activity were measured using a kayak ergometer. After the four-week training, the time required for on-water paddling for 270 m was reduced by 7.3% from pre to post training, while the average impulse in the x-direction significantly (P < 0.001, partial eta squared [η2] = 0.82) increased from 71.9 ± 1.9 to 91.1 ± 5.4 N kg−1 s−1. Furthermore, with training, the stroke rate and stroke length in the x-direction significantly (P < 0.001, partial η2 = 0.80 and 0.79, respectively) increased from 62.8 ± 1.2 to 81.0 ± 2.9 spm and from 1.53 ± 0.04 to 1.71 ± 0.02 m, respectively. After training, the transition time significantly (P < 0.001, partial η2 = 0.32) decreased (from 0.04 ± 0.01 to 0.01 ± 0.01 s), and there was an increase in paddle catch position (from −0.88 ± 0.01 to −1.04 ± 0.03 m). The pull time was not significantly changed (P = 0.077, partial η2 = 0.08) because of the increasing stroke length after training, meaning that substantial pull time, which defined as pull time relative to the stroke displacement, was shorter in post-training than in pre-training. The relative change in average impulse in the x-direction with training was significantly (r = 0.857, P = 0.014) correlated with that of vastus lateralis EMG. These results indicated that after four-week kayak training of the novice paddler, the key mechanism underlying time reduction to perform on-water paddling for 270 m was associated with (1) increased average impulse along the propulsive direction caused by an increase in vastus lateralis EMG and (2) a higher stroke rate, which was attributed to a reduction in the pull and transition times.
A Functional Radiological and Soft Tissue Classification to Predict Outcomes in Orbital Fracture Surgery in a Multidisciplinary “Real-World” Setting
Authors: Yang Elizabeth , Chan Shu-Yi Claire , Al-Omari Yara , Ward Louise , Yap Timothy E. , Jhass Aneka , Pancholi Ravi , Aziz Ahmad , Bentley Christopher Richard , Perry Michael , Lee Vickie
Published: July 2021

Purpose: The decision for open reduction and internal fixation (ORIF) of orbital fractures is usually based on clinical severity and soft tissue and bony findings. This study aimed to identify prognostic factors for a successful surgical outcome.

Materials and Methods: We included all orbital fractures treated by ORIF referred to the Ophthalmology clinic for assessment over a 12-year period. A successful outcome was defined as (i) a single operation, (ii) improved diplopia and globe position at 6 months, (iii) no surgical complications, and (iv) patient satisfaction. Data was collected on presenting symptoms, orthoptic measurements, time interval from injury to surgery, fracture geometry and involvement of internal, and external bony landmarks. Univariate and multivariate regression was used to identify predictive factors for success.

Results: There were 143 cases with median age 35.4 years and 81.8% (117/143) male. 51% (73/143) were complex fractures involving multiple orbital walls. 63.6% (91/143) achieved significant improvement in both enophthalmos and diplopia at 6 months. 15.3% (22/143) had significant preoperative soft tissue or neurogenic injury. 11.8% (17/143) required orbital plate repositioning or removal. 1.4% (2/143) developed orbital haematoma and 4.2% (6/143) had cicatricial entropion. Pre-operative nerve or muscle damage (OR 0.05, p = 0.01) and infraorbital fissure fracture (OR 0.38, p = 0.04) were associated with poor outcomes, whereas an intact posterior ledge was associated with successful outcomes (OR 3.03, p = 0.02).

Conclusion: Careful ocular motility evaluation to ascertain neurogenic injury and muscle compartment syndrome, and radiological analysis of the integrity of the posterior ledge and the inferior orbital fissure can facilitate management and expectations of ORIF surgery.
Effects of Elevated Atmospheric CO2 Concentration and Water Regime on Rice Yield, Water Use Efficiency, and Arsenic and Cadmium Accumulation in Grain
Authors: Balbinot Andrisa , da Rosa Feijó Anderson , Fipke Marcus Vinicius , Rockenbach Dalvane , Massey Joseph Harry , Camargo Edinalvo Rabaioli , Mesko Marcia Foster , Scaglioni Priscila Tessmer , de Avila Luis Antonio
Published: July 2021

(1) Background: Elevated atmospheric CO2 concentration affects the growth and development of the rice crop. In Southern Brazil, rice is traditionally produced with continuous irrigation, implying a significant amount of water used. Besides, continuous flooding favors the uptake of toxic elements such as arsenic (As) and cadmium (Cd). In this work, one Brazilian rice cultivar (IRGA 424) was tested for the effects of elevated CO2 concentration and different water regimes on rice yield, and As and Cd accumulation in grain. (2) Methods: Rice was grown in two CO2 concentrations (400 and 700 µmol mol−1) and two irrigation regimes (continuous and intermittent). It was evaluated the number of tillers, plant height, aboveground dry weight (ADW), water use efficiency (WUE), rice yield components, and As and Cd concentration in rice grain. (3) Results: Rice plants were taller and had a higher WUE when cultivated at e[CO2]. The ADW and the rice yield component were not affected by CO2 levels nor water regimes. Intermittent flood regimes had a lower average As concentration. The Cd concentration in the samples in both growing seasons and all treatments was below the limit of quantitation (8.76 μg kg−1). (4) Conclusions: Enhanced CO2 concentration did not affect rice yield, increased the WUE, and reduced As concentration in grains. Regarding water management, the intermittent regime enhanced WUE and promoted a reduction in As concentration in grains.