bluuebunny/crossref_metadata_2025 huggingface dataset:
Pineal Region Hemangioblastoma Resection Through Paramedian Supracerebellar Approach: 2-Dimensional Operative Video
Authors: Essayed Walid I B N , Aboud Emad , Al-Mefty Ossama
Published: May 2021

Pineal region tumors remain challenging lesions to safely resect because of their central location.
1
Patients frequently present with symptoms associated with hydrocephalus and brainstem compression.
2
Local anatomy, primarily the tentorium angle and venous anatomy, plays a central role in the selection of the approach.
3
The paramedian supracerebellar approach pioneered by Yaşargil in 1984
4
allows to access the pineal region through a less steep angle while avoiding the central thickened arachnoid and midline cerebellar and vermian veins.
3

Although the author strongly prefers the advantageous three-quarter concord position, this early case was performed in a sitting position, which requires a bubble test to rule out the presence of a persistent foramen ovale. The preoperative pineal differential diagnosis should be exhaustive, including blood and cerebrospinal fluid (CSF) tumor markers in suitable cases. Hemangioblastomas are seldom found or expected in the pineal area, and the surgeon must be alarmed by their typical “cherry nodule” appearance.
2

,

5
Their recognition prior to resection is paramount in avoiding excessive blood loss from tumor entry. Similar to arteriovenous malformations, hemangioblastoma surgical tenets include en bloc resection and preservation of the main draining veins until the last steps of the resection. Von Hippel-Lindau (VHL) syndrome genetic workup is necessary is similar patients, as more than 25% of hemangioblastomas are associated with VHL tumor suppressor gene mutations in chromosome 3.
2
The patient consented to the surgery and use of her photography.

Image at 2:41 from Ueyama et al, Bridging veins on the tentorial surface of the cerebellum: a microsurgical anatomic study and operative considerations, Neurosurgery, 1998, 43(5),
3
used with permission from the Congress of Neurological Surgeons.
Prone Single-Position Lateral Lumbar Interbody Fusion With Posterior Decompression and Pedicle Screw Fixation for the Treatment of Grade II Spondylolisthesis: 2-Dimensional Operative Video
Authors: Naeem Komal , Farber S Harrison , Bhargava Malika , Porter Randall W
Published: May 2021

Lateral lumbar interbody fusion (LLIF) provides indirect decompression without disruption of the posterior elements. It involves a larger implant footprint than that of posterior approaches. LLIF is typically performed with the patient in the lateral decubitus position. When a posterior fixation is indicated, a second-stage procedure is performed with the patient in the prone position. Single-position surgery provides the potential advantage of decreased operative time because both procedures can be performed without patient repositioning. Single-position LLIF and posterior fixation in the prone position have not been well validated to date. Herein, techniques for LLIF, percutaneous pedicle screw fixation, and facetectomy in the prone position are shown.

A 76-yr-old woman with osteoporosis presented with severe back and bilateral leg pain refractory to conservative management and imaging findings of grade 2 dynamic anterolisthesis at L4-L5 with severe stenosis. She underwent LLIF with percutaneous pedicle screw fixation and facetectomy. She was placed on a Jackson table in the prone position for the entire procedure, which was performed in a single stage. Percutaneous pedicle screws were placed, followed by a left-sided minimally invasive facetectomy. A left-sided retroperitoneal transpsoas approach was used to perform the LLIF in standard fashion. Finally, the rods were locked into place.

Postoperatively, the patient was neurologically stable, and imaging confirmed good hardware placement. At the 6-wk follow-up, the patient was doing well. This case demonstrates the feasibility of performing LLIF and posterior fixation in a single stage in the prone position. The patient provided informed consent. Used with permission from Barrow Neurological Institute.
Loss of inner-envelope K+/H+ exchangers impairs plastid rRNA maturation and gene expression
Authors: DeTar Rachael Ann , Barahimipour Rouhollah , Manavski Nikolay , Schwenkert Serena , Höhner Ricarda , Bölter Bettina , Inaba Takehito , Meurer Jörg , Zoschke Reimo , Kunz Hans-Henning
Published: May 2021

The inner-envelope K+ EFFLUX ANTIPORTERS (KEA) 1 and 2 are critical for chloroplast development, ion homeostasis, and photosynthesis. However, the mechanisms by which changes in ion flux across the envelope affect organelle biogenesis remained elusive. Chloroplast development requires intricate coordination between the nuclear genome and the plastome. Many mutants compromised in plastid gene expression (PGE) display a virescent phenotype, that is delayed greening. The phenotypic appearance of Arabidopsis thaliana kea1 kea2 double mutants fulfills this criterion, yet a link to PGE has not been explored. Here, we show that a simultaneous loss of KEA1 and KEA2 results in maturation defects of the plastid ribosomal RNAs. This may be caused by secondary structure changes of rRNA transcripts and concomitant reduced binding of RNA-processing proteins, which we documented in the presence of skewed ion homeostasis in kea1 kea2. Consequently, protein synthesis and steady-state levels of plastome-encoded proteins remain low in mutants. Disturbance in PGE and other signs of plastid malfunction activate GENOMES UNCOUPLED 1-dependent retrograde signaling in kea1 kea2, resulting in a dramatic downregulation of GOLDEN2-LIKE transcription factors to halt expression of photosynthesis-associated nuclear-encoded genes (PhANGs). PhANG suppression delays the development of fully photosynthesizing kea1 kea2 chloroplasts, probably to avoid progressing photo-oxidative damage. Overall, our results reveal that KEA1/KEA2 function impacts plastid development via effects on RNA-metabolism and PGE.
Blue light-dependent interactions of CRY1 with GID1 and DELLA proteins regulate gibberellin signaling and photomorphogenesis in Arabidopsis
Authors: Xu Peng , Chen Huiru , Li Ting , Xu Feng , Mao Zhilei , Cao Xiaoli , Miao Langxi , Du Shasha , Hua Jie , Zhao Jiachen , Guo Tongtong , Kou Shuang , Wang Wenxiu , Yang Hong-Quan
Published: May 2021

Cryptochromes are blue light photoreceptors that mediate various light responses in plants and mammals. In Arabidopsis (Arabidopsis thaliana), cryptochrome 1 (CRY1) mediates blue light-induced photomorphogenesis, which is characterized by reduced hypocotyl elongation and enhanced anthocyanin production, whereas gibberellin (GA) signaling mediated by the GA receptor GA-INSENSITIVE DWARF1 (GID1) and DELLA proteins promotes hypocotyl elongation and inhibits anthocyanin accumulation. Whether CRY1 control of photomorphogenesis involves regulation of GA signaling is largely unknown. Here, we show that CRY1 signaling involves the inhibition of GA signaling through repression of GA-induced degradation of DELLA proteins. CRY1 physically interacts with DELLA proteins in a blue light-dependent manner, leading to their dissociation from SLEEPY1 (SLY1) and the inhibition of their ubiquitination. Moreover, CRY1 interacts directly with GID1 in a blue light-dependent but GA-independent manner, leading to the inhibition of the interaction between GID1 with DELLA proteins. These findings suggest that CRY1 controls photomorphogenesis through inhibition of GA-induced degradation of DELLA proteins and GA signaling, which is mediated by CRY1 inhibition of the interactions of DELLA proteins with GID1 and SCFSLY1, respectively.
PROBABILISTIC ANALYSES OF 131I THYROID ACTIVITY IN PERSONS WITH SURFACE CONTAMINATION IN DIRECT MEASUREMENT WITH A STANDING-TYPE WHOLE-BODY COUNTER AS AN EMERGENCY RESPONSE IN A RADIOLOGICAL INCIDENT
Authors: Tani Kotaro , Igarashi Yu , Kim Eunjoo , Kowatari Munehiko , Iimoto Takeshi , Kurihara Osamu
Published: May 2021

The authors’ previous study suggested that a simple standing-type whole-body counter called FASTSCAN (Canberra, Meriden, CT, USA), widely installed throughout Japan after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in March 2011, could be used for thyroid measurements in internal dose assessment after a future radiological incident accompanied by the release of 131I into the environment. The present study performed Monte-Carlo simulations using a computational human phantom with several patterns of body surface contamination and used the results to formulate a method for probabilistic analyses of 131I thyroid activity in persons with surface contamination. The major advantage of this method is that the upper limit of the thyroid activity can be determined from the relative frequency distribution without identifying where body surface contamination remains. Therefore, this method is especially effective for use in the early phase of a radiological incident when time and resources are limited, making it difficult to physically remove all body surface contamination for the purpose of gaining more accurate population-wide thyroid screening measurements. As a case study of the FDNPP accident, the proposed method was applied to the results of in vivo measurements for a male subject with body surface contamination. In comparing the probabilistic analyses before and after removal of the subject’s contaminated work clothes, the uncertainty of the relative frequency distribution of 131I thyroid activity was reduced by their removal. Therefore, in terms of accurate estimates and avoidance of radiation exposure from their contaminated clothes, efforts to remove body surface contamination still should be made as much as possible in the chaotic situation of the early phase of a radiological incident.
Analysis of the influence of BMI on the outcome after total knee arthroplasty
Authors: Wang Huan , Qiong Ma , Ma Baoan
Published: May 2021

Background:

A meta-analysis of published cohort studies was used to evaluate differences in outcome measures after total knee arthroplasty (TKA) among thinnish, normal, overweight, obese, and morbidly obese patients.

Materials and methods:

Manual retrieval of the results of patients with different body mass index (BMI) in primary TKA from the self-built Chinese and English databases such as PubMed, EMBASE, Cochrane, Sinomed, CnKI, Wanfang, and Vip from November 2020 was performed. Include retrospective or prospective cohort studies, according to the World Health Organization BMI packet primary TKA special surgical hospital in New York, the knee joint function assessment used in patients with knee scoring criteria (HSS) or the knee society score (KSS) as well as the operation time, intraoperative blood transfusion volume, length of hospital stay, postoperative complications of literature, literature including repeat, system evaluation, meta-analysis, case report, BMI groups not strictly and outcome indicators of incomplete documents. After independent literature screening, data extraction, and quality evaluation by 2 researchers, meta-analysis was carried out with Revman5.4 software. In the end, 20 literatures were included.

Results:

The preoperative score decreased with the increase of BMI in each group, while the postoperative knee joint function score in the normal group, overweight group, obese group, and in the morbidly obese group were all higher than that before the surgery (P<0.00001), and the changes were more obvious in the morbidly obese group. The length of stay in the normal group was the shortest, followed by the overweight and obese group. The operative time and intraoperative blood transfusion showed that the thinnish group was less than the normal group, while the overweight and the obese group was higher than the normal group. Finally, postoperative complications in the other groups were all higher than the normal group, with significant differences. We can see the preoperative knee function score decreased with the increase of BMI, the operation time, intraoperative blood transfusion volume, length of hospital stay, presents the opposite trend, the postoperative complications in each group were higher than in normal group, here also pay special attention to thinnish group compared with normal group complications increase.

Conclusion:

The present meta-analysis demonstrated that BMI higher than normal can affect intraoperative risk of TKA and postoperative recovery, and increase the risk of complications.
Genomics of aging: The role of sirtuin and metabolic health
Authors: Wysocki Kenneth , Seibert Diane
Published: May 2021

Healthy aging is not the result of a single factor. Genes, dietary choices/options, exercise, and environmental exposures all play a role. A family of seven nicotinamide adenine dinucleotide (NAD)–dependent sirtuin proteins are very involved in various metabolic functions, such as glucose and fat regulation, and polymorphisms in these genes have been associated with the development of obesity, type 2 diabetes, cancer, cardiovascular disease, and longevity. Nutraceuticals (i.e., resveratrol, quercetin, kaempferol, and curcumin) and other therapies (i.e., synthetic sirtuin-activating compounds, NAD, nicotinamide mononucleotide) are all being explored as in potential therapies in the sirtuin pathway and point to promising treatments to promote metabolic health and reduce obesity and age-related disease. For the clinician looking to reduce the risk of age-related metabolic disorders, evidence points to these supplements and appropriate food choices as the next generation of pharmaceutical grade therapies continue to be researched for human use.
Rethinking DNP education: Just another mountain to climb
Authors: Beauchesne Michelle A.
Published: May 2021

The World Health Organization designated 2020 as the International Year of the Nurse and Midwife in celebration of the 200th birthday of Florence Nightingale, the founder of modern nursing. This article considers the future of nurse practitioner education in light of nursing history. First, a brief overview describes the progression of nursing education since the founding of the Nightingale School in 1860. Then, current challenges in NP education are discussed. Potential solutions to these issues are presented.
Wastewater-based estimation of the effective reproductive number of SARS-CoV-2
Authors: Huisman Jana S. , Scire Jérémie , Caduff Lea , Fernandez-Cassi Xavier , Ganesanandamoorthy Pravin , Kull Anina , Scheidegger Andreas , Stachler Elyse , Boehm Alexandria B. , Hughes Bridgette , Knudson Alisha , Topol Aaron , Wigginton Krista R. , Wolfe Marlene K. , Kohn Tamar , Ort Christoph , Stadler Tanja , Julian Timothy R.
Published: May 2021

Background

The effective reproductive number, Re, is a critical indicator to monitor disease dynamics, inform regional and national policies, and estimate the effectiveness of interventions. It describes the average number of new infections caused by a single infectious person through time. To date, Re estimates are based on clinical data such as observed cases, hospitalizations, and/or deaths. These estimates are temporarily biased when clinical testing or reporting strategies change.

Objectives

We show that the dynamics of SARS-CoV-2 RNA in wastewater can be used to estimate Re in near real-time, independent of clinical data and without the associated biases.

Methods

We collected longitudinal measurements of SARS-CoV-2 RNA in wastewater in Zurich, CH, and San Jose (CA), USA. We combined this data with information on the temporal dynamics of shedding (the shedding load distribution) to estimate a time series proportional to the daily COVID-19 infection incidence. We estimated a wastewater-based Re from this incidence.

Results

The method to estimate Re from wastewater works robustly on data from two different countries and two wastewater matrices. The resulting estimates are as similar to the Re estimates from case report data as Re estimates based on observed cases, hospitalizations, and deaths are among each other. We further provide details on the effect of sampling frequency and the shedding load distribution on the ability to infer Re.

Discussion

To our knowledge, this is the first time Re has been estimated from wastewater. This method provides a low cost, rapid, and independent way to inform SARS-CoV-2 monitoring during the ongoing pandemic and is applicable to future wastewater-based epidemiology targeting other pathogens.
Original antigenic sin responses to heterologous Betacoronavirus spike proteins are observed in mice following intramuscular administration, but are not apparent in children following SARS-CoV-2 infection
Authors: Lapp Stacey A. , Edara Venkata Viswanadh , Lu Austin , Lai Lilin , Hussaini Laila , Chahroudi Ann , Anderson Larry J. , Suthar Mehul S. , Anderson Evan J. , Rostad Christina A.
Published: May 2021

Background

The effects of pre-existing endemic human coronavirus (HCoV) immunity on SARS-CoV-2 serologic and clinical responses are incompletely understood.

Objectives

We sought to determine the effects of prior exposure to HCoV Betacoronavirus HKU1 spike protein on serologic responses to SARS-CoV-2 spike protein after intramuscular administration in mice. We also sought to understand the baseline seroprevalence of HKU1 spike antibodies in healthy children and to measure their correlation with SARS-CoV-2 binding and neutralizing antibodies in children hospitalized with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C).

Methods

Groups of 5 mice were injected intramuscularly with two doses of alum-adjuvanted HKU1 spike followed by SARS-CoV-2 spike; or the reciprocal regimen of SARS-Cov-2 spike followed by HKU1 spike. Sera collected 21 days following each injection was analyzed for IgG antibodies to HKU1 spike, SARS-CoV-2 spike, and SARS-CoV-2 neutralization. Sera from children hospitalized with acute COVID-19, MIS-C or healthy controls (n=14 per group) were analyzed for these same antibodies.

Results

Mice primed with SARS-CoV-2 spike and boosted with HKU1 spike developed high titers of SARS-CoV-2 binding and neutralizing antibodies; however, mice primed with HKU1 spike and boosted with SARS-CoV-2 spike were unable to mount neutralizing antibodies to SARS-CoV-2. HKU1 spike antibodies were detected in all children with acute COVID-19, MIS-C, and healthy controls. Although children with MIS-C had significantly higher HKU1 spike titers than healthy children (GMT 37239 vs. 7551, P=0.012), these titers correlated positively with both SARS-CoV-2 binding (r=0.7577, P<0.001) and neutralizing (r=0.6201, P=0.001) antibodies.

Conclusions

Prior murine exposure to HKU1 spike protein completely impeded the development of neutralizing antibodies to SARS-CoV-2, consistent with original antigenic sin. In contrast, the presence of HKU1 spike IgG antibodies in children with acute COVID-19 or MIS-C was not associated with diminished neutralizing antibody responses to SARS-CoV-2.
Single-tube collection and nucleic acid analysis of clinical samples: a rapid approach for SARS-CoV-2 saliva testing
Authors: Cole Kyle H. , Bouin Alexis , Ruiz Caila , Semler Bert L. , Inlay Matthew A. , Lupták Andrej
Published: May 2021

The SARS-CoV-2 pandemic has brought to light the need for expedient diagnostic testing. Cost and availability of large-scale testing capacity has led to a lag in turnaround time and hindered contact tracing efforts, resulting in a further spread of SARS-CoV-2. To increase the speed and frequency of testing, we developed a cost-effective single-tube approach for collection, denaturation, and analysis of clinical samples. The approach utilizes 1 µL microbiological inoculation loops to collect saliva, sodium dodecyl sulfate (SDS) to inactivate and release viral genomic RNA, and a diagnostic reaction mix containing polysorbate 80 (Tween 80). In the same tube, the SDS-denatured clinical samples are introduced to the mixtures containing all components for nucleic acids detection and Tween 80 micelles to absorb the SDS and allow enzymatic reactions to proceed, obviating the need for further handling of the samples. The samples can be collected by the tested individuals, further decreasing the need for trained personnel to administer the test. We validated this single-tube sample- to-assay method with RT-qPCR and RT-LAMP and discovered little-to-no difference between Tween- and SDS-containing reaction mixtures, compared to CDC-approved reagents. This approach significantly reduces the logistical burden of traditional large-scale testing and provides a method of deployable point-of-care diagnostics to increase testing frequency.
Modular effects of gene promoters and chromatin environments on noise in gene expression
Authors: Zhao Siqi , Pincus Zachary , Cohen Barak A
Published: May 2021

Genetically identical cells growing in the same environment can have large differences in gene expression. Both locally actingcis-regulatory sequences (CRS) and the regional properties of chromosomal environments influence the noisiness of a gene’s expression. Whether or not local CRS and regional chromosomal environments act independently on noise, or whether they interact in complex ways is unknown. To address this question, we measured the expression mean and noise of reporter genes driven by different CRS at multiple chromosomal locations. While a strong power law relationship between mean expression and noise explains ~60% of noise for diverse promoters across chromosomal locations, modeling the residual mean-independent noise suggests that chromosomal environments have strong effects on expression noise by influencing how quickly genes transition from their inactive states to their active states and that the effects of local CRS and regional chromatin on noise are largely independent. Our results support a modular genome in which regional chromatin modifies the inherent relationship between the mean and noise of expression regardless of the identity of the promoter sequence.
Best practices for analyzing imputed genotypes from low-pass sequencing in dogs
Authors: Buckley Reuben M. , Harris Alex C. , Wang Guo-Dong , Whitaker D. Thad , Zhang Ya-Ping , Ostrander Elaine A.
Published: May 2021

Although DNA array-based approaches for genome wide association studies (GWAS) permit the collection of thousands of low-cost genotypes, it is often at the expense of resolution and completeness, as SNP chip technologies are ultimately limited by SNPs chosen during array development. An alternative low-cost approach is low-pass whole genome sequencing (WGS) followed by imputation. Rather than relying on high levels of genotype confidence at a set of select loci, low-pass WGS and imputation relies on the combined information from millions of randomly sampled low confidence genotypes. To investigate low-pass WGS and imputation in the dog, we assessed accuracy and performance by downsampling 97 high-coverage (>15x) WGS datasets from 51 different breeds to approximately 1x coverage, simulating low-pass WGS. Using a reference panel of 676 dogs from 91 breeds, genotypes were imputed from the downsampled data and compared to a truth set of genotypes generated from high coverage WGS. Using our truth set, we optimized a variant quality filtering strategy that retained approximately 80% of 14M imputed sites and lowered the imputation error rate from 3.0% to 1.5%. Seven million sites remained with a MAF > 5% and an average imputation quality score of 0.95. Finally, we simulated the impact of imputation errors on outcomes for case-control GWAS, where small effect sizes were most impacted and medium to large effect sizes were minorly impacted. These analyses provide best practice guidelines for study design and data post-processing of low-pass WGS imputed genotypes in dogs.
Genetic and ecomorphological divergence between sympatricAstyanaxmorphs from Central America
Authors: Garita-Alvarado Carlos A. , Garduño-Sánchez Marco , Barluenga Marta , Ornelas-García C. Patricia
Published: May 2021

Ecological and morphological divergence within populations can be a signal of adaptive divergence, which can maintain intraspecific polymorphisms and promote ecological speciation in the event of reproductive isolation. Here, we evaluate correlations among morphology, trophic ecology, and genetic differentiation between two divergent morphs (elongate and deep-body) of the fish genusAstyanaxin the San Juan River basin in Central America, to infer the putative evolutionary mechanism shaping this system. We collected the two morphs from three water bodies and analyzed: 1) the correlation between body shape and the shape of the premaxilla, a relevant trophic structure, 2) the trophic level and niche width of each morph, 3) the correspondence between trophic level and body and premaxillary shape, and 4) the genetic differentiation between morphs using mitochondrial and nuclear markers. We found a strong correlation between the body and premaxillary shape of the morphs. The elongate-body morph had a streamlined body, a premaxilla with acuter angles and a narrower ascending process, and a higher trophic level, characteristic of species with predatorial habits. By contrast, the deep-body morph had a higher body depth, a premaxilla with less acute angles, and a broader trophic niche, suggesting generalist habits. Despite the strong correlation between morphological and ecological divergence, the morphs showed limited genetic differentiation, supporting the idea that morphs may be undergoing incipient ecological speciation, although alternative scenarios such as stable polymorphism or plasticity should also be considered. This study provides evidence about the role of ecological factors in the diversification processes inAstyanax.
VirusTaxo: Taxonomic classification of virus genome using multi-class hierarchical classification by k-mer enrichment
Authors: Raju Rajan Saha , Nahid Abdullah Al , Shuvo Preonath , Islam Rashedul
Published: May 2021

Taxonomic classification of viruses is a multi-class hierarchical classification problem, as taxonomic ranks (e.g., order, family and genus) of viruses are hierarchically structured and have multiple classes in each rank. Classification of biological sequences which are hierarchically structured with multiple classes is challenging. Here we developed a machine learning architecture, VirusTaxo, using a multi-class hierarchical classification by k-mer enrichment. VirusTaxo classifies DNA and RNA viruses to their taxonomic ranks using genome sequence. To assign taxonomic ranks, VirusTaxo extracts k-mers from genome sequence and creates bag-of-k-mers for each class in a rank. VirusTaxo uses a top-down hierarchical classification approach and accurately assigns the order, family and genus of a virus from the genome sequence. The average accuracies of VirusTaxo for DNA viruses are 99% (order), 98% (family) and 95% (genus) and for RNA viruses 97% (order), 96% (family) and 82% (genus). VirusTaxo can be used to detect taxonomy of novel viruses using full length genome or contig sequences.

Availability

Online version of VirusTaxo is available athttps://omics-lab.com/virustaxo/.
Watching Death in the Gerbil Cochlea Using Optical Coherence Tomography
Authors: Cho Nam Hyun , Wang Haobing , Puria Sunil
Published: May 2021

Because it is difficult to directly observe the morphology of the living cochlea, our ability to infer the mechanical functioning of the living ear has been limited. Nearly all of our knowledge about cochlear morphology comes from postmortem tissue that was fixed and processed using procedures that possibly distort the structures and fluid spaces of the organ of Corti. In this study, optical coherence tomography was employed to obtain in vivo and postmortem micron-scale volumetric images of the high-frequency hook region of the gerbil cochlea through the round-window membrane. The anatomical structures and fluid spaces of the organ of Corti were segmented and quantified in vivo and over a 90-minute postmortem period. The results show that some aspects of the organ of Corti are significantly altered over the course of death, such as the volumes of the fluid spaces, whereas the dimensions of other features change very little. We postulate that the fluid space of the outer tunnel and its surrounding tectal cells form a resonant structure that can affect the motion of the reticular lamina and thereby have a profound effect on outer-hair-cell transduction and thus cochlear amplification. In addition, the in vivo fluid pressure of the inner spiral sulcus is postulated to effectively inflate the connected sub-tectorial gap between the tectorial membrane and the reticular lamina. This gap height decreases after death, which is hypothesized to reduce and disrupt hair-cell transduction
An inexpensive, high-precision, modular spherical treadmill setup optimized forDrosophilaexperiments
Authors: Loesche Frank , Reiser Michael B.
Published: May 2021

To pursue a more mechanistic understanding of the neural control of behavior, many neuroethologists study animal behavior in controlled laboratory environments. One popular approach is to measure the movements of restrained animals while presenting controlled sensory stimulation. This approach is especially powerful when applied to genetic model organisms, such asDrosophila melanogaster,where modern genetic tools enable unprecedented access to the nervous system for activity monitoring or targeted manipulation. While there is a long history of measuring the behavior of body- and head-fixed insects walking on an air-supported ball, the methods typically require complex setups with many custom components. Here we present a compact, simplified setup for these experiments that achieves high-performance at low cost.

The simplified setup combines existing hardware and software solutions with new component designs. We replaced expensive optomechanical and custom machined components with off-the-shelf and 3D-printed parts. We built the system around an inexpensive camera that achieves 180 Hz imaging and use an inexpensive tablet computer for presenting view-angle-corrected stimuli updated through a local network. We quantify the performance of the integrated system and characterize the visually guided behavior of flies in response to a range of visual stimuli. The improved system is thoroughly documented. This publication is accompanied by CAD files, parts lists, source code, and step-by-step instructions for setting up the system and analyzing behavioral data. We detail a complete ~$.300 system, including a cold-anesthesia tethering stage, that is ideal for hands-on teaching laboratories. This represents a nearly 50-fold cost reduction as compared to a typical system used in research laboratories, yet is fully featured and yields excellent performance.

We report the current state of this system, which started with a one-day teaching lab for which we built seven parallel setups and continues towards a setup in our lab for larger-scale analysis of visual-motor behavior in flies. Because of the simplicity, compactness, and low cost of this system, we believe that high-performance measurements of tethered insect behavior should now be widely accessible and suitable for integration into many systems. This access enables broad opportunities for comparative work across labs, species, and behavioral paradigms.
PeakVI: A Deep Generative Model for Single Cell Chromatin Accessibility Analysis
Authors: Ashuach Tal , Reidenbach Daniel A. , Gayoso Adam , Yosef Nir
Published: May 2021

Abstract

Single-cell ATAC sequencing (scATAC-seq) is a powerful and increasingly popular technique to explore the regulatory landscape of heterogeneous cellular populations. However, the high noise levels, degree of sparsity, and scale of the generated data make its analysis challenging. Here we present PeakVI, a probabilistic framework that leverages deep neural networks to analyze scATAC-seq data. PeakVI fits an informative latent space that preserves biological heterogeneity while correcting batch effects and accounting for technical effects such as library size and region-specific biases. Additionally, PeakVI provides a technique for identifying differential accessibility at a single region resolution, which can be used for cell-type annotation as well as identification of key cis-regulatory elements. We use public datasets to demonstrate that PeakVI is scalable, stable, robust to low-quality data, and outperforms current analysis methods on a range of critical analysis tasks. PeakVI is publicly available and implemented in the scvi-tools framework: https://docs.scvi-tools.org/.
Non-preferred contrast responses in the Drosophila motion pathways reveal a receptive field structure that explains a common visual illusion
Authors: Gruntman Eyal , Reimers Pablo , Romani Sandro , Reiser Michael B.
Published: May 2021

Diverse sensory systems, from audition to thermosensation, feature a separation of inputs into ON (increments) and OFF (decrements) signals. In the Drosophila visual system, separate ON and OFF pathways compute the direction of motion, yet anatomical and functional studies have identified some crosstalk between these channels. We used this well-studied circuit to ask whether the motion computation depends on ON-OFF pathway crosstalk. Using whole-cell electrophysiology we recorded visual responses of T4 (ON) and T5 (OFF) cells and discovered that both cell types are also directionally selective in response to non-preferred contrast motion. We mapped T4s’ and T5s’ composite ON-OFF receptive fields and found they share a similar spatiotemporal structure. We fit a biophysical model to these receptive fields that accurately predicts directionally selective T4 and T5 responses to both ON and OFF moving stimuli. This model also provides a detailed mechanistic explanation for the directional-preference inversion in response to a prominent visual illusion, a result we corroborate with electrophysiological recordings and behavioral responses of flying flies.
Genomic consequences of domestication of the Siamese fighting fish
Authors: Kwon Young Mi , Vranken Nathan , Hoge Carla , Lichak Madison R , Francis Kerel X , Camacho-Garcia Julia , Bista Iliana , Wood Jonathan , McCarthy Shane , Chow William , Tan Heok Hui , Howe Kerstin , Bandara Sepalika , von Lintig Johannes , Rüber Lukas , Durbin Richard , Svardal Hannes , Bendesky Andres
Published: May 2021

Siamese fighting fish, commonly known as betta, are among the world’s most popular and morphologically diverse pet fish, but the genetic processes leading to their domestication and phenotypic diversification are largely unknown. We assembled de novo the genome of a wildBetta splendensand whole-genome sequenced multiple individuals across five species within theB. splendensspecies complex, including wild populations and domesticated ornamental betta. Given our estimate of the mutation rate from pedigrees, our analyses suggest that betta were domesticated at least 1,000 years ago, centuries earlier than previously thought. Ornamental betta individuals have variable contributions from otherBettaspecies and have also introgressed into wild populations of those species. We identifydmrt1as the main sex determination gene in ornamental betta but not in wildB. splendens, and find evidence for recent directional selection at the X-allele of the locus. Furthermore, we find genes with signatures of recent, strong selection that have large effects on color in specific parts of the body, or the shape of individual fins, and are almost all unlinked. Our results demonstrate how simple genetic architectures paired with anatomical modularity can lead to vast phenotypic diversity generated during animal domestication, and set the stage for using betta as a modern system for evolutionary genetics.

One-Sentence Summary

Genomic analyses reveal betta fish were domesticated more than 1,000 years ago and the genes that changed in the process.
ACE2 glycans preferentially interact with the RBD of SARS-CoV-2 over SARS-CoV
Authors: Acharya Atanu , Lynch Diane L. , Pavlova Anna , Pang Yui Tik , Gumbart James C.
Published: May 2021

We report a distinct difference in the interactions of the glycans of the host-cell receptor, ACE2, with SARS-CoV-2 and SARS-CoV S-protein receptor-binding domains (RBDs). Our analysis demonstrates that the ACE2 glycan at N90 may offer protection against infections of both coronaviruses, while the ACE2 glycan at N322 enhances interactions with the SARS-CoV-2 RBD. The interactions of the ACE2 glycan at N322 with SARS-CoV RBD are blocked by the presence of the RBD glycan at N357 of the SARS-CoV RBD. The absence of this glycosylation site on SARS-CoV-2 RBD may enhance its binding with ACE2.
Characterizing stored red blood cells using ultra-high throughput holographic cytometry
Authors: Park Han Sang , Price Hillel , Ceballos Silvia , Chi Jen-Tsan , Wax Adam
Published: May 2021

Holographic cytometry is introduced as an ultra-high throughput implementation of quantitative phase image based on off-axis interferometry of cells flowing through parallel microfluidic channels. Here, it is applied for characterizing morphological changes of red blood cells during storage under regular blood bank condition. The approach allows high quality phase imaging of a large number of cells greatly extending our ability to study cellular phenotypes using individual cell images. Holographic cytology measurements show multiple physical traits of the cells, including optical volume and area, which are observed to consistently change over the storage time. In addition, the large volume of cell imaging data can serve as training data for machine learning algorithms. For the study here, logistic regression is used to classify the cells according to the storage time points. The results of the classifiers demonstrate the potential of holographic cytometry as a diagnostic tool.
Environmental filtering in marine fish communities is weakened during severe hypoxia season
Authors: Shinohara Naoto , Hongo Yuki , Ichinokawa Momoko , Nishijima Shota , Sawayama Shuhei , Kurogi Hiroaki , Uto Yasuyuki , Mita Hisanori , Ishii Mitsuhiro , Kusano Akane , Akimoto Seiji
Published: May 2021

Compositional variation among local communities reflects the differences in abiotic environments, though the extent of the influence varies in natural systems. Generally, the environmental filtering is expected to be strong if the environmental gradient encompasses severe habitats where species sorting is highly likely to work. However, this hypothesis has rarely been tested in dynamic systems, where the higher dispersal ability of species allows them to easily respond to stressful environments. Here, with the dynamics of fish communities in a Japanese bay revealed by environmental DNA analyses as a model case, we examined how harmful seasonal hypoxia (low concentration of oxygen in bottom waters in summer) affected the strength of environmental filtering. We found that, in summer, dissolved oxygen (DO) concentration was significantly low and fish species richness decreased in the bottom water compared to the surface, suggesting that the organisms were adversely affected by the hypoxia. At the same time, the between-depths heterogeneity in DO concentration was larger, but species composition was less divergent and the influence of DO on species composition appeared weaker during summer. These results imply that environmental filtering is weakened when the bottom water was characterized by extremely severe environments. Furthermore, there was a shift in the species occurrence from bottom to surface waters in summer that was consistent across species, suggesting that the extremely severe hypoxia adversely affected fish species irrespective of their identity. These results collectively suggest that environmental filtering is weaker during summer despite more severity and heterogeneity in environments, most likely because individual movements to avoid unpreferable environments in the bottom waters occurred quasi-neutrally. By providing evidence against the prevailing understanding that environmental filtering strongly works in severe environments, these findings invoke further investigation on how the filtering acts in various conditions.
Sequence-based correction of barcode bias in massively parallel reporter assays
Authors: Lee Dongwon , Kapoor Ashish , Lee Changhee , Mudgett Michael , Beer Michael A. , Chakravarti Aravinda
Published: May 2021

Massively parallel reporter assays (MPRA) are a high-throughput method for evaluatingin vitroactivities of thousands of candidate cis-regulatory elements (CREs). In these assays, candidate sequences are cloned upstream or downstream of a reporter gene tagged by unique DNA sequences. However, tag sequences may themselves affect reporter gene expression and lead to major potential biases in the measured cis-regulatory activity. Here, we present a sequence-based method for correcting tag sequence-specific effects and demonstrate that our method can significantly reduce this source of variation, and improve the identification of functional regulatory variants by MPRAs. We also show that our model captures sequence features associated with post-transcriptional regulation of mRNA. Thus, this new method helps to not only improve detection of regulatory signals in MPRA experiments but also to design better MPRA protocols.
Missingness Adapted Group Informed Clustered (MAGIC)-LASSO: A novel paradigm for prediction in data with widespread non-random missingness
Authors: Gentry Amanda Elswick , Kirkpatrick Robert M. , Peterson Roseann E. , Webb B. Todd
Published: May 2021

The availability of large-scale biobanks linking rich phenotypes and biological measures is a powerful opportunity for scientific discovery. However, real-world collections frequently have extensive non-random missingness. While missing data prediction is possible, performance is significantly impaired by block-wise missingness inherent to many biobanks. To address this, we developed Missingness Adapted Group-wise Informed Clustered (MAGIC)-LASSO which performs hierarchical clustering of variables based on missingness followed by sequential Group LASSO within clusters. Variables are pre-filtered for missingness and balance between training and target sets with final models built using stepwise inclusion of features ranked by completeness. This research has been conducted using the UK Biobank (n>500k) to predict unmeasured Alcohol Use Disorders Identification Test (AUDIT) scores. The phenotypic correlation between measured and predicted total score was 0.67 while genetic correlations between independent subjects was high >0.86, demonstrating the method has significant accuracy and utility.
Decitabine Reactivation of FoxM1-Dependent Endothelial Regeneration and Vascular Repair for Potential Treatment of Elderly ARDS and COVID-19 Patients
Authors: Huang Xiaojia , Zhang Xianming , Machireddy Narsa , Mutlu Gökhan M. , Fang Yun , Wu David , Zhao You-Yang
Published: May 2021

Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS) and COVID-19. We repot that aging impairs the intrinsic FoxM1-dependent endothelial regeneration and vascular repair program and causes persistent lung injury and high mortality following sepsis. Therapeutic gene transduction ofFOXM1in vascular endothelium or treatment with FDA-approved drug Decitabine was sufficient to reactivate FoxM1-dependent lung endothelial regeneration in aged mice, reverse aging-impaired resolution of inflammatory injury, and promote survival. In COVID-19 lung autopsy samples, FOXM1 expression was not induced in vascular endothelial cells of elderly patients in contrast to mid-age patients. Thus, Decitabine reactivation of FoxM1-dependent vascular repair represents a potential effective therapy for elderly COVID-19 and non-COVID-19 ARDS patients.
Comparing Expression of OAS-RNaseL Pathway-Related Genes in SARS-CoV-2 and Similar Viruses
Authors: Chakravarty Nikhil , Edillor Penelope A. , Huang Andy P. , Torres Giovanni A. , Usmani Manal T. , Kadandale Pavan
Published: May 2021

The COVID-19 pandemic, caused by the virus SARS-CoV-2, has been a major public health emergency and has caused millions of deaths worldwide to date. Due to the novel nature of the virus, efforts across the world are underway to better understand the molecular pathogenesis of SARS-CoV-2 and how it interacts with host immune responses. One important branch of the innate immune response, the interferon system, triggers the expression of many effector mechanisms known to be powerful antagonists against many pathogenic viruses. One such interferon stimulated mechanism is the OAS-RNaseL pathway, which is known to trigger the degradation of viral RNA in infected host cells. Our study seeks to utilize publicly available transcriptomic data to analyze the host cell OAS-RNaseL pathway to SARS-CoV-2 infection. We hoped to gain an understanding of the importance of the pathway in controlling SARS-CoV-2 infection and whether or not the pathway could be exploited therapeutically. Our findings demonstrated that upregulation of OAS-RNaseL pathway genes in response to SARS-CoV-2 infection varies based on cell type and appeared to correlate with ACE2 receptor expression. Pathway responses to other viruses like SARS-CoV and MERS-CoV were found to parallel those to SARS-CoV-2, suggesting common response patterns by the pathway to these viruses. Overall, these results demonstrate that the OAS-RNaseL pathway could contribute to control of SARS-CoV-2 infection. Further studies on various mechanistic actions by the pathway would need to be conducted to fully understand its role in host defense and therapy.
3C-seq-captured chromosome conformation of the hyperthermophilic archaeon Thermofilum adornatum
Authors: Sobolev Andrey , Solovyev Mikhail , Ivanova Valeria , Kochetkova Tatiana , Merkel Alexandr , Razin Sergey , Ulianov Sergey , Tyakht Alexander
Published: May 2021

Three-dimensional structure of chromosomes displays diverse patterns across the tree of life, with compartments, interaction domains and loops being quite universally observed. The archaeal kingdom remains understudied to this extent so far, despite representing an interesting area from evolutionary and other perspectives.

Here we describe the spatial chromosomal organization of a hyperthermophilic crenarchaeon Thermofilum adornatum strain 1910b based on high-throughput chromosome conformation capture (3C-seq) approach. The chromosome contact map showed a curved secondary diagonal almost orthogonal to the main one. No evidence of chromosome loops was present. We were able to identify boundaries of different strengths between chromosome interaction domains (CIDs) albeit moderate. The plaid-like patterns previously reported for Sulfolobus archaea were not observed. However, the calculation of A/B compartments divided the genome into 2 domains that were different by the density of predicted highly expressed genes and location of origins.

Further comparison of these domains with whole-genome gene expression profiles will allow to test whether these domains represent expression-associated compartments. If so, it is possible that they represent primitive compartments evolutionarily older than the plaid patterns of Sulfolobus and higher eukaryotes. Further exploration of 3D chromatin in all branches of archaeal diversity will elucidate the evolution of the links between structural and functional organization in live organisms.