bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivophage display: identification of organ-specific peptides using deep sequencing and differential profiling across tissues
Authors: Pleiko Karlis , Põšnograjeva Kristina , Haugas Maarja , Paiste Päärn , Tobi Allan , Kurm Kaarel , Riekstina Una , Teesalu Tambet
Published: July 2020

In vivophage display is widely used for identification of organ- or disease-specific homing peptides. However, the currentin vivophage biopanning approaches fail to assess biodistribution of specific peptide phages across tissues during the screen, thus necessitating laborious and time-consuming post-screening validation studies on individual peptide phages. Here, we adopted bioinformatics tools used for RNA sequencing for analysis of high throughput sequencing (HTS) data to estimate the representation of individual peptides during biopanningin vivo. The data fromin vivophage screen were analyzed using differential binding – relative representation of each peptide in the target organ vs. in a panel of control organs. Application of this approach in a model study using low-diversity peptide T7 phage library with spiked-in brain homing phage, demonstrated brain-specific differential binding of brain homing phage and resulted in identification of novel lung and brain specific homing peptides. Our study provides a broadly applicable approach to streamlinein vivopeptide phage biopanning and to increase its reproducibility and success rate.

Graphic abstract

In vivophage display using differential binding approach
GsERFenhances aluminum tolerance through an ethylene-mediated pathway inArabidopsis thaliana
Authors: Li Lu , Li Xingang , Yang Ce , Cheng Yanbo , Cai Zhandong , Nian Hai , Ma Qibin
Published: July 2020

The ethylene response factor (ERF) transcription factor is a subfamily of AP2/ERF superfamily in plants, which plays multiple roles in plant growth and development as well as stress response. In this study, we found that theGsERFgene from BW69 line of wild soybean held a constitutive expression pattern and induced by aluminum stress with more transcripts in soybean root. The putative GsERF protein containing an AP2 domain was in the nucleus and transactivation activity. In addition, the overexpression of theGsERFgene enhanced root relative length rate in Arabidopsis and shallow staining by hematoxylin under the treatments of AlCl3. The ethylene synthesis related genes such asACS4, ACS5andACS6are upregulated in theGsERFoverexpressed plants than those in wild type plants under the treatment of AlCl3. Furthermore, expression levels of stress/ABA-responsive marker genes, includingABI1, ABI2, ABI4, ABI5, RD29BandRD22in transgenic lines compared with those in wild type Arabidopsis were affected by AlCl3treatments. Taken together, the results indicate that overexpression ofGsERFmay enhance aluminum tolerance through an ethylene-mediated pathway and/or ABA signaling pathway inArabidopsis thaliana.
A psychophysically-tuned computational model of human primary visual cortex produces geometric optical illusions
Authors: Retsa Chrysa , Ariza Ana Hernando , Noordanus Nathanael W. , Ruffoni Lorenzo , Murray Micah M. , Franceschiello Benedetta
Published: July 2020

Geometrical optical illusion (GOIs) are mismatches between physical stimuli and perception. GOIs provide an access point to study the interplay between sensation and perception, yet there is scant quantitative investigation of the extent to which different GOIs rely on similar or distinct brain mechanisms. We addressed this knowledge gap. First, 30 healthy adults reported quantitatively their perceptual biases with three GOIs, whose physical properties parametrically varied on a trial-by-trial basis. Biases observed with one GOI were unrelated to those observed with another GOI, suggestive of (partially) distinct underlying mechanisms. Next, we used these psychophysical results to tune a computational model of primary visual cortex that combines parameters of orientation, selectivity, intra-cortical connectivity, and long-range interactions. We showed that similar biases could be generatedin-silico, mirroring those observed in humans. Such results provide a roadmap whereby computational modelling, informed by human psychophysics, can reveal likely mechanistic underpinnings of perception.
TDP-43 proteinopathy alters the ribosome association of multiple mRNAs including the glypican Dally-like protein (Dlp)/GPC6
Authors: Lehmkuhl Erik M , Loganathan Suvithanandhini , Alsop Eric , Blythe Alexander D , Kovalik Tina , Mortimore Nicholas P , Barrameda Dianne , Kueth Chuol , Eck Randall J , Siddegowda Bhavani B , Joardar Archi , Ball Hannah , Macias Maria E , Bowser Robert , Van Keuren-Jensen Kendall , Zarnescu Daniela C
Published: July 2020

Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease in which 97% of patients exhibit cytoplasmic aggregates containing the RNA binding protein TDP-43. Using tagged ribosome affinity purifications inDrosophilamodels of TDP-43 proteinopathy, we identified TDP-43 dependent translational alterations in motor neurons impacting the spliceosome, pentose phosphate and oxidative phosphorylation pathways. A subset of the mRNAs with altered ribosome association are also enriched in TDP-43 complexes suggesting that they may be direct targets. Among these,dlpmRNA, which encodes the glypican Dally like protein (Dlp)/GPC6, a wingless (Wg/Wnt) signaling regulator is insolubilized both in flies and patient tissues with TDP-43 pathology. While Dlp/GPC6 forms puncta in theDrosophilaneuropil and ALS spinal cords, it is reduced at the neuromuscular synapse in flies suggesting compartment specific effects of TDP-43 proteinopathy. These findings together with genetic interaction data show that Dlp/GPC6 is a novel, physiologically relevant target of TDP-43 proteinopathy.
What are the gray and white matter volumes of the human spinal cord?
Authors: Henmar Simon , Simonsen Erik B. , Berg Rune W.
Published: July 2020

The gray matter of the spinal cord is the seat of somata of various types of neurons devoted to the sensory and motor activities of the limbs and trunk as well as a part of the autonomic nervous system. The volume of the spinal gray matter is an indicator of the local neuronal processing and this can decrease due to atrophy associated with degenerative diseases and injury. Nevertheless, the absolute volume of the human spinal cord has rarely been reported, if ever. Here, we use high–resolution magnetic resonance imaging, with a cross–sectional resolution of 50 × 50μm2and a voxel size of 0.0005mm3, to estimate the total gray and white matter volume of a post mortem human female spinal cord. Segregation of gray and white matter was accomplished using deep learning image segmentation. Further, we include data from a male spinal cord of a previously published study. The gray and white matter volumes were found to be 2.87 and 11.33 ml, respectively for the female and 3.55 and 19.33 ml, respectively for a male. The gray and white matter profiles along the vertebral axis were found to be strikingly similar and the volumes of the cervical, thoracic and lumbosacral sections were almost equal.

NEW AND NOTEWORTHY

Here, we combine high field MRI (9.4T) and deep learning for a post-mortem reconstruction of the gray and white matter in human spinal cords. We report a minuscule total gray matter volume of 2.87 ml for a female and 3.55 ml for a male. For comparison, these volumes correspond approximately to the distal digit of the little finger.
Milk losses and dynamics during perturbations in dairy cows differ with parity and lactation stage
Authors: Adriaens I. , van den Brulle I. , D’Anvers L. , Statham J.M.E. , Geerinckx K. , De Vliegher S. , Piepers S. , Aernouts B.
Published: July 2020

Milk yield dynamics during perturbations reflect how cows respond to challenges. This study investigated the characteristics of 62,406 perturbations from 16,604 lactation curves of dairy cows milked with an automated milking system at 50 Belgian, Dutch and English farms. The unperturbed lactation curve representing the theoretical milk yield dynamics was estimated with an iterative procedure fitting a Wood model on the daily milk yield data not part of a perturbation. Each perturbation was characterized and split in a development and a recovery phase. Based hereon, we calculated both the characteristics of the perturbation as a whole, and the duration, slopes and milk losses in the phases separately. A two-way analysis of variance followed by a pairwise comparison of group means was carried out to detect differences between these characteristics in different lactation stages (early, mid-early, mid-late and late) and parities (first, second and third or higher). On average, 3.8 ± 1.9 (mean ± standard deviation) perturbations were detected per lactation in the first 305 days after calving, corresponding to an estimated 92.1 ± 135.8 kg of milk loss. Only 1% of the lactations had no perturbations. The average development and recovery rates were respectively −2.3 and 1.5 kg per day, and these phases lasted on average 10.1 and 11.6 days. Perturbation characteristics were significantly different across parity and lactation stage groups, and early and mid-early perturbations in higher parities were found to be more severe, with faster development rates, slower recovery rates and higher milk losses. The method to characterize perturbations can be used for precision phenotyping purposes looking into the response of cows to challenges, or for monitoring applications, for example to evaluate the development and recovery of diseases and how these are affected by preventive actions or treatments.
Pinpointing the neural signatures of single-exposure visual recognition memory
Authors: Mehrpour Vahid , Meyer Travis , Simoncelli Eero P. , Rust Nicole C.
Published: July 2020

Memories of the images that we have seen are thought to be reflected in the reduction of neural responses in high-level visual areas such as inferotemporal (IT) cortex, a phenomenon known as repetition suppression (RS). We challenged this hypothesis with a task that required rhesus monkeys to report whether images were novel or repeated while ignoring variations in contrast, a stimulus attribute that is also known to modulate the overall IT response. The monkeys’ behavior was largely contrast-invariant, contrary to the predictions of an RS-inspired decoder, which could not distinguish responses to images that are repeated from those of lower contrast. However, the monkeys’ behavioral patterns were well-predicted by a linearly decodable variant in which the total spike count was corrected for contrast modulation. These results suggest that the IT neural activity pattern that best aligns with single-exposure visual recognition memory behavior is not RS but rather “sensory referenced suppression (SRS)”: reductions in IT population response magnitude, corrected for sensory modulation.

Significance statement

Memories of whether an image has been seen before are reflected in high-level visual cortex as “sensory referenced suppression (SRS)”: reductions in population response magnitude, corrected for sensory modulation.
The conserved elongation factor Spn1 is required for normal transcription, histone modifications, and splicing inSaccharomyces cerevisiae
Authors: Reim Natalia I. , Chuang James , Jain Dhawal , Alver Burak H. , Park Peter J. , Winston Fred
Published: July 2020

Spn1/Iws1 is a conserved protein involved in transcription and chromatin dynamics, yet its generalin vivorequirement for these functions is unknown. Using a Spn1 depletion system inS. cerevisiae,we demonstrate that Spn1 broadly influences several aspects of gene expression on a genome-wide scale. We show that Spn1 is globally required for normal mRNA levels and for normal splicing of ribosomal protein transcripts. Furthermore, Spn1 maintains the localization of H3K36 and H3K4 methylation across the genome and is required for normal histone levels at highly expressed genes. Finally, we show that the association of Spn1 with the transcription machinery is strongly dependent on its binding partner, Spt6, while the association of Spt6 and Set2 with transcribed regions is partially dependent on Spn1. Taken together, our results show that Spn1 affects multiple aspects of gene expression and provide additional evidence that it functions as a histone chaperonein vivo.
Using iCn3D and the World Wide Web for structure-based collaborative research: Analyzing molecular interactions at the root of COVID-19
Authors: Youkharibache Philippe , Cachau Raul , Madej Tom , Wang Jiyao
Published: July 2020

The COVID-19 pandemic took us ill-prepared and tackling the many challenges it poses in a timely manner requires world-wide collaboration. Our ability to study the SARS-COV-2 virus and its interactions with its human host in molecular terms efficiently and collaboratively becomes indispensable and mission-critical in the race to develop vaccines, drugs, and neutralizing antibodies. There is already a significant corpus of 3D structures related to SARS and MERS coronaviruses, and the rapid generation of new structures demands the use of efficient tools to expedite the sharing of structural analyses and molecular designs and convey them in their native 3D context in sync with sequence data and annotations. We developed iCn3D (pronounced “I see in 3D”)1to take full advantage of web technologies and allow scientists of different backgrounds to perform and share sequence-structure analyses over the Internet and engage in collaborations through a simple mechanism of exchanging “lifelong” web links (URLs). This approach solves the very old problem of “sharing of molecular scenes” in a reliable and convenient manner. iCn3D links are sharable over the Internet and make data and entire analyses findable, accessible, and reproducible, with various levels of interoperability. Links and underlying data are FAIR2and can be embedded in preprints and papers, bringing a 3D live and interactive dimension to a world of text and static images used in current publications, eliminating at the same time the need for arcane supplemental materials. This paper exemplifies iCn3D capabilities in visualization, analysis, and sharing of COVID-19 related structures, sequence variability, and molecular interactions.
Spatially distributed representation of taste quality in the gustatory insular cortex of awake behaving mice
Authors: Chen Ke , Kogan Joshua F. , Fontanini Alfredo
Published: July 2020

Visual, auditory and somatosensory cortices are topographically organized, with neurons responding to similar sensory features clustering in adjacent portions of the cortex. Such topography has not been observed in the piriform cortex, whose responses to odorants are sparsely distributed across the cortex. The spatial organization of taste responses in the gustatory insular cortex (GC) is currently debated, with conflicting evidence from anesthetized rodents pointing to alternative and mutually exclusive models. Here, we rely on calcium imaging to determine how taste and task-related variables are represented in the superficial layers of GC of alert, licking mice. Our data show that the various stimuli evoke sparse responses from a combination of broadly and narrowly tuned neurons. Analysis of the distribution of responses over multiple spatial scales demonstrates that taste representations are distributed across the cortex, with no sign of spatial clustering or topography. Altogether, data presented here support the idea that the representation of taste qualities in GC of alert mice is sparse and distributed, analogous to the representation of odorants in piriform cortex.
Mechanically stable knot formed by strand threading in Zika virus RNA confers RNase resistance
Authors: Zhao Meng , Woodside Michael T.
Published: July 2020

Exoribonuclease-resistant RNAs (xrRNAs) from viruses prevent digestion by host exoribonucleases, creating sub-genomic viral RNAs that can enhance infection and pathogenicity. Novel knotted structures in xrRNAs are proposed to act as mechanical road-blocks to RNases. Studying an xrRNA from Zika virus with optical tweezers, we found that it was the most mechanically stable RNA structure yet observed. The knot folded by threading the 5′ end into the cleft of a Mg2+-coordinated three-helix junction before pseudoknot interactions closed a ring around it. Both the threading and pseudoknot were required to generate the extremely force-resistant knot, whose formation correlated directly with RNase resistance both in the wild-type xrRNA and a low-resistance mutant. This work clarifies the folding and mechanism of action of an important new class of RNA.
Stitching together a nm thick peptide-based semiconductor sheet using UV light
Authors: Alvarez Alain Bolaño , Pino Marcelo , Petersen Steffen B. , Fidelio Gerardo Daniel
Published: July 2020

Langmuir monolayer allows for two-dimensional nano-scale organisation of amphiphilic molecules. We here report that two retro-isomers peptides carefully designed to form stable monolayers showed semiconductor-like behaviour. Both exhibit the same hydrophobicity and surface stability but differ in the lateral conductivity and current-voltage due to the asymmetric peptide bond backbone orientation at the interface. The two peptides contain several tyrosines that allow for UVB-induced lateral crosslinking of tyrosines in neighboring peptide molecules. UVB-light induces changes in the lateral conductivity and currentvoltage behaviour as well as monolayer heterogeneity monitored by Brewster angle microscopy that depends on the peptide bond backbone orientation and crosslinking of tyrosines. Our results indicate that one may design extended nano-sheets with particular electric properties, reminiscent of semiconductors. We propose to exploit such properties for biosensing and neural interfaces.
An Antibody to RGMa Promotes Regeneration of Cochlear Synapses after Noise Exposure
Authors: Nevoux Jerome , Alexandru Mihaela , Bellocq Thomas , Tanaka Lei , Hayashi Yushi , Watabe Takahisa , Lahlou Hanae , Tani Kohsuke , Edge Albert S.B.
Published: July 2020

Auditory neuropathy is caused by the loss of afferent input to the brainstem via the components of the neural pathway comprising inner hair cells and the first order neurons of the spiral ganglion. Recent work has identified the synapse between cochlear primary afferent neurons and sensory hair cells as a particularly vulnerable component of this pathway. Loss of these synapses due to noise exposure or aging results in the pathology identified as hidden hearing loss, an initial stage of cochlear dysfunction that goes undetected in standard hearing tests. We show here that repulsive axonal guidance molecule a (RGMa) acts to prevent regrowth and synaptogenesis of peripheral auditory nerve fibers with inner hair cells. Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy.
High-performance brain-to-text communication via imagined handwriting
Authors: Willett Francis R. , Avansino Donald T. , Hochberg Leigh R. , Henderson Jaimie M. , Shenoy Krishna V.
Published: July 2020

Brain-computer interfaces (BCIs) can restore communication to people who have lost the ability to move or speak. To date, a major focus of BCI research has been on restoring gross motor skills, such as reaching and grasping1–5or point-and-click typing with a 2D computer cursor6,7. However, rapid sequences of highly dexterous behaviors, such as handwriting or touch typing, might enable faster communication rates. Here, we demonstrate an intracortical BCI that can decode imagined handwriting movements from neural activity in motor cortex and translate it to text in real-time, using a novel recurrent neural network decoding approach. With this BCI, our study participant (whose hand was paralyzed) achieved typing speeds that exceed those of any other BCI yet reported: 90 characters per minute at >99% accuracy with a general-purpose autocorrect. These speeds are comparable to able-bodied smartphone typing speeds in our participant’s age group (115 characters per minute)8and significantly close the gap between BCI-enabled typing and able-bodied typing rates. Finally, new theoretical considerations explain why temporally complex movements, such as handwriting, may be fundamentally easier to decode than point-to-point movements. Our results open a new approach for BCIs and demonstrate the feasibility of accurately decoding rapid, dexterous movements years after paralysis.
Molecular characterization of a flatworm Girardia isolate from Guanajuato, Mexico
Authors: Duncan Elizabeth M. , Nowotarski Stephanie H. , Guerrero-Hernández Carlos , Ross Eric J. , D’Orazio Julia A. ,   Clubes de Ciencia México Workshop for Developmental Biology, McKinney Sean , McHargue Mark C. , Guo Longhua , McClain Melainia , Alvarado Alejandro Sánchez
Published: July 2020

Planarian flatworms are best known for their impressive regenerative capacity, yet this trait varies across species. In addition, planarians have other features that share morphology and function with the tissues of many other animals, including an outer mucociliary epithelium that drives planarian locomotion and is very similar to the epithelial linings of the human lung and oviduct. Planarians occupy a broad range of ecological habitats and are known to be sensitive to changes in their environment. Yet, despite their potential to provide valuable insight to many different fields, very few planarian species have been developed as laboratory models for mechanism-based research.

Here we describe a previously undocumented planarian isolate,Girardia sp. (Guanajuato). After collecting this isolate from a freshwater habitat in central Mexico, we characterized it at the morphological, cellular, and molecular level. We show thatGirardia sp. (Guanajuato) shares features with animals in theGirardiagenus but also possesses traits that appear unique to this isolate. By thoroughly characterizing this new planarian isolate, our work facilitates future comparisons to other flatworms and further molecular dissection of the unique and physiologically-relevant traits observed in thisGirardia sp. (Guanajuato) isolate.
Gastric metabolomics analysis supportsH. pylori’s catabolism of organic and amino acids in both the corpus and antrum
Authors: Keilberg Daniela , Steele Nina , Fan Sili , Yang Christina , Zavros Yana , Ottemann Karen M.
Published: July 2020

Helicobacter pyloriis a chronic bacterial pathogen that thrives in several regions of the stomach, causing inflammation that can vary by site and result in distinct disease outcomes. It is not known, however, whether the host-derived metabolites differ between the two main regions, the corpus and antrum. We thus characterized the metabolomes of mouse gastric corpus and antrum organoids and tissue. The secreted organoid metabolites differed significantly between the corpus and antrum in only seven metabolites: lactic acid, malic acid, phosphoethanolamine, alanine, uridine, glycerol, and isoleucine, with only lactic acid and phosphoethanolamine exceeding two-fold differences. Multiple chemicals were depleted uponH. pyloriinfection including urea, cholesterol, glutamine, fumaric acid, lactic acid, citric acid, malic acid, and multiple non-essential amino acids. Many are knownH. pylorinutrients and did not differ between the two regions. When tissue was examined, there was little overlap with the organoid metabolites. The two tissue regions were distinct, however, including in antrum-elevated 5-methoxytryptamine, lactic acid, and caprylic acid, and corpus-elevated phospholipid products. Over an 8 month infection time course, the corpus and antrum remained distinct. The antrum displayed no significant changes, in contrast to the corpus which exhibited metabolite changes indicating stress, tissue damage, and depletion of key nutrients such as glutamine and fructose-6-phosphate. Overall, our results suggest theH. pyloripreferentially uses carboxylic acids and amino acids in complex environments, and these are found in both the corpus and antrum.
Disentangling the relative roles of vertical transmission, subsequent colonizations and diet on cockroach microbiome assembly
Authors: Germer Kristjan , Renelies-Hamilton Justinn , Sillam-Dussès David , Bodawatta Kasun H. , Poulsen Michael
Published: July 2020

A multitude of factors affect the assemblies of complex microbial communities associated with animal hosts, with implications for community flexibility, resilience and long-term stability; however, their relative effects have rarely been deduced. Here, we use a tractable lab model to quantify the relative and combined effects of parental transmission (egg case microbiome present/reduced), gut inocula (cockroach vs. termite gut provisioned), and varying diets (matched with gut inoculum source) on gut microbiota structure of hatchlings of the omnivorous cockroachShelfordella lateralisusing 16S rDNA amplicon sequencing. We show that the presence of a pre-existing bacterial community via vertical transmission of microbes on egg cases reduces subsequent microbial invasion, suggesting priority effects that allow initial colonizers to take a stronghold and which stabilize the microbiome. However, the subsequent inoculation sources more strongly affect ultimate community composition, with distinct host-taxon-of-origin effects on which bacteria establish. While this is so, communities respond flexibly to specific diets that consequently strongly impact community functions predicted using PICRUSt2. In conclusion, our findings suggest that inoculations drive communities towards different stable states depending on colonization and extinction events, through ecological host-microbe relations and interactions with other gut bacteria, while diet in parallel shapes the functional capabilities of these microbiomes. These effects may lead to consistent microbial communities that maximize the extended phenotype that the microbiota provides the host, particularly if microbes spend most of their lives in host-associated environments.

Contribution to the field

When host fitness is dependent on gut microbiota, microbial community flexibility and reproducibility enhance host fitness by allowing fine-tuned environmental tracking and sufficient stability for host traits to evolve. Our findings lend support to the importance of vertically transmitted early-life microbiota as stabilizers through interactions with potential colonizers that may contribute to ensuring that the microbiota aligns within host fitness-enhancing parameters. Subsequent colonizations are driven by microbial composition of the sources available, and we confirm that host-taxon-of-origin affects stable subsequent communities, while communities at the same time retain sufficient flexibility to shift in response to available diets. Microbiome structure is thus the result of the relative impact and combined effects of inocula and fluctuations driven by environment-specific microbial sources and digestive needs. These affect short-term community structure on an ecological time scale, but could ultimately shape host species specificities in microbiomes across evolutionary time, if environmental conditions prevail.
Modeling the Stability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on Skin, Currency, and Clothing
Authors: Harbourt David E. , Haddow Andrew D. , Piper Ashley E. , Bloomfield Holly , Kearney Brian J. , Fetterer David , Gibson Kathleen , Minogue Timothy
Published: July 2020

A new coronavirus (SARS-CoV-2) emerged in the winter of 2019 in Wuhan, China, and rapidly spread around the world. The extent and efficiency of SARS-CoV-2 pandemic is far greater than previous coronaviruses that emerged in the 21st Century. Here, we modeled stability of SARS-CoV-2 on skin, paper currency, and clothing to determine if these surfaces may factor in the fomite transmission dynamics of SARS-CoV-2. Skin, currency, and clothing samples were exposed to SARS-CoV-2 under laboratory conditions and incubated at three different temperatures (4°C± 2°C, 22°C± 2°C, and 37°C ± 2°C). Stability was evaluated at 0 hours (h), 4 h, 8 h, 24 h, 72 h, 96 h, 7 days, and 14 days post-exposure. SARS-CoV-2 was shown to be stable on skin through the duration of the experiment at 4°C (14 days). Virus remained stable on skin for at least 96 h at 22°C and for at least 8h at 37°C. There were minimal differences between the tested currency samples. The virus remained stable on the $1 U.S.A. Bank Note for at least 96 h at 4°C while viable virus was not detected on the $20 U.S.A. Bank Note samples beyond 72 h. The virus remained stable on both Bank Notes for at least 8 h at 22°C and 4 h at 37°C. Clothing samples were similar in stability to the currency with the virus being detected for at least 96 h at 4°C and at least 4 h at 22°C. No viable virus was detected on clothing samples at 37°C after initial exposure. This study confirms the inverse relationship between virus stability and temperature. Furthermore, virus stability on skin demonstrates the need for continued hand hygiene practices to minimize fomite transmission both in the general population as well as workplaces where close contact is common.
Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study
Authors: Merzon Eugene , Tworowski Dmitry , Gorohovski Alessandro , Vinker Shlomo , Cohen Avivit Golan , Green Ilan , Morgenstern Milana Frenkel
Published: July 2020

Aim

To evaluate associations of plasma 25(OH)D status with the likelihood of coronavirus disease (COVID-19) infection and hospitalization.

Methods

The study population included the 14,000 members of Leumit Health Services who were tested for COVID-19 infection from February 1stto April 30th2020, and who had at least one previous blood test for plasma 25(OH)D level. “Suboptimal” or “low” plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below 30 ng/mL.

Results

Of 7,807 individuals, 782 (10.1%) were COVID-19-positive, and 7,025 (89.9%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval [CI] 18.41-19.59)vs. 20.55 (95% CI 20.32-20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24-2.01, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI 1.01-4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI 1.08-1.95, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI 0.98-4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19.

Conclusion

Low plasma 25(OH)D level appears to be an independent risk factor for COVID-19 infection and hospitalization.
Recombination of repeat elements generates somatic complexity in human genomes
Authors: Pascarella G. , Hashimoto K. , Busch A. , Luginbühl J. , Parr C. , Hon C. C. , Yip W. H. , Abe K. , Kratz A. , Bonetti A. , Agostini F. , Severin J. , Murayama S. , Suzuki Y. , Gustincich S. , Frith M. , Carninci P.
Published: July 2020

Millions of Alu and L1 copies in our genomes contribute to evolution and genetic disorders via non-allelic homologous recombination, but the somatic extent of these rearrangements has not been systematically investigated. Here we combine short and long DNA reads sequencing of repeat elements with a new bioinformatic pipeline to show that somatic recombination of Alu and L1 elements is common in human genomes. We report new tissue-specific recombination hallmarks, and show that retroelements acting as recombination hotspots are enriched in centromeres and cancer genes. We compare recombination profiles in human induced pluripotent stem cells and differentiated neurons and show that neuron-specific recombination of repeat elements accompanies chromatin changes during cell-fate determination. Finally, we find that somatic recombination profiles are altered in Parkinson’s and Alzheimer’s disease, indicating a link between retroelements recombination and genomic instability in neurodegeneration. This work shows that somatic recombination of repeat elements contributes massively to genomic diversity in health and disease.
Chromosome Compartments on the Inactive X Guide TAD Formation Independently of Transcription during X-Reactivation
Authors: Bauer Moritz , Vidal Enrique , Zorita Eduard , Pinter Stefan F. , Filion Guillaume J. , Payer Bernhard
Published: July 2020

A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments and into topologically associating domains (TADs). Both structures were regarded absent from the inactive X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC-reprogramming system and high-resolution Hi-C to produce the first time-course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we uncover A/B-like compartments on the inactive X harboring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, coinciding with acquisition of naive pluripotency, leading to downregulation ofXist. Importantly, we find that TAD formation precedes transcription, suggesting them to be causally independent. Instead, TADs form first within Xist-poor compartments, establishing Xist as common denominator, opposing both gene reactivation and TAD formation through separate mechanisms.

Graphical Summary
Mobbing-like response to secondary predator cues is not a form of teaching in meerkats
Authors: Driscoll Isabel , Manser Marta , Thornton Alex
Published: July 2020

Across many taxa, individuals learn how to detect, recognise and respond to predators via social learning. Learning to recognise and interpret predator cues is essential in the accurate assessment of risk. Cues can come directly from a predator’s presence (visual, acoustic) or from secondary predator cues (SPCs, such as hair/feathers, urine or faeces) left in the environment. Animals show various responses to encountering SPCs, which are thought to act in reducing risk to the individual. Meerkats, Suricata suricatta, show a response to SPCs not described in any other species: they display a mobbing-like behaviour. The function of this behaviour is unclear as unlike mobbing, the response it so closely resembles, it cannot serve to drive predators away. We used experiments to investigate whether adults may use this mobbing-like response to teach naïve young how to recognise and respond to predators. Meerkats are known to teach pups hunting skills, but there is as yet no evidence that any species other than humans teaches across multiple contexts. We used experimental presentations of SPCs to test whether wild adult meerkats respond more intensely to SPCs in the presence of naïve pups, as would be expected if the behaviour serves to promote learning. Contrary to this prediction, response intensity was lower when pups were present than when they were absent, and declined as the number of pups in the group increased, possibly due to costs associated with foraging with dependent young. Response intensity instead increased with increasing group size, number of group members interacting with the cue, and varied with predator cue type. These results suggest that the mobbing-like response to SPCs is not a form of teaching in meerkats. Instead, this behaviour may function to increase the recruitment of others to investigate the SPC. Exposing group members to SPCs may better inform them of the nature of the threat, facilitating more effective defensive group responses.
Realistic boundary conditions for perivascular pumping in the mouse brain reconcile theory, simulation, and experiment
Authors: Ladrón-de-Guevara Antonio , Shang Jessica K. , Nedergaard Maiken , Kelley Douglas H.
Published: July 2020

Cerebrospinal fluid (CSF) flows through the perivascular spaces (PVSs) surrounding cerebral arteries. Revealing the mechanisms driving that flow could bring improved understanding of brain waste transport and insights for disorders including Alzheimer’s disease and stroke. In vivo velocity measurements of CSF in surface PVSs in mice have been used to argue that flow is driven primarily by the pulsatile motion of artery walls — perivascular pumping. However, fluid dynamics theory and simulation have predicted that perivascular pumping produces flows differing from in vivo observations starkly, particularly in the phase and relative amplitude of flow oscillation. Here we show that coupling theoretical and simulated flows to realistic end boundary conditions, using resistance and compliance values measured in mice, results in velocities that match observations closely in phase, relative amplitude of oscillation, and mean flow speed. This new, quantitative agreement among theory, simulation, and in vivo measurement further supports the idea that perivascular pumping is a primary CSF driver in physiological conditions.
Distinct lipid profile, low-level inflammation and increased antioxidant defense as a signature in HIV-1 elite control status
Authors: Sperk Maike , Mikaeloff Flora , Svensson-Akusjärvi Sara , Ponnan Sivasankaran Munusamy , Nowak Piotr , Sönnerborg Anders , Neogi Ujjwal
Published: July 2020

HIV-1 elite controllers (EC) are a rare but heterogeneous group of HIV-1-infected individuals who are able to suppress viral replication in the absence of antiretroviral therapy. The mechanisms of how EC achieve undetectable viral loads remain unclear. This study aimed to investigate host plasma metabolomics and targeted plasma proteomics in a Swedish HIV-1 cohort including EC and treatment-naïve viremic progressors (VP) as well as HIV-negative individuals (HC) to get insights into mechanisms governing EC status. Metabolites belonging to antioxidant defense had higher levels in EC relative to VP while inflammation markers were increased in VP compared to EC. Only four plasma proteins (CCL4, CCL7, CCL20, and NOS3) were increased in EC compared to HC and CCL20/CCR6 axis can play important role. Our study suggests that low-level inflammation and oxidative stress at physiological levels could be important factors contributing to control of viral replication.

One Sentence Summary

HIV-1 elite controllers had a distinct lipid profile, reduced inflammation, and increased antioxidant defense that might contribute to elite control status.
Deep learning-based classification of resting-state fMRI independent-component analysis
Authors: Nozais Victor , Boutinaud Philippe , Verrecchia Violaine , Gueye Marie-Fateye , Hervé Pierre Yves , Tzourio Christophe , Mazoyer Bernard , Joliot Marc
Published: July 2020

Functional connectivity analyses of fMRI data have shown that the activity of the brain at rest is spatially organized into resting-state networks (RSNs). RSNs appear as groups of anatomically distant but functionally tightly connected brain regions. Inter-RSN intrinsic connectivity analyses may provide an optimal spatial level of integration to analyze the variability of the functional connectome. Here we propose a deep learning approach to enable the automated classification of individual independent-component (IC) decompositions into a set of predefined RSNs. Two databases were used in this work, BIL&GIN and MRi-Share, with 427 and 1811 participants, respectively. We trained a multilayer perceptron (MLP) to classify each IC as one of 45 RSNs, using the IC classification of 282 participants in BIL&GIN for training and a 5-dimensional parameter grid search for hyperparameter optimization. It reached an accuracy of 92%. Predictions for the remaining individuals in BIL&GIN were tested against the original classification and demonstrated good spatial overlap between the cortical RSNs. As a first application, we created an RSN atlas based on MRi-Share. This atlas defined a brain parcellation in 29 RSNs covering 96% of the gray matter. Second, we proposed an individualbased analysis of the subdivision of the default-mode network into 4 networks. Minimal overlap between RSNs was found except in the angular gyrus and potentially in theprecuneus. We thus provide the community with an individual IC classifier that can be used to analyze one dataset or to statistically compare different datasets for RSN spatial definitions.
Spatial Transcriptomics Inferred from Pathology Whole-Slide Images Links Tumor Heterogeneity to Survival in Breast and Lung Cancer
Authors: Levy-Jurgenson Alona , Tekpli Xavier , Kristensen Vessela N. , Yakhini Zohar
Published: July 2020

Digital analysis of pathology whole-slide images is fast becoming a game changer in cancer diagnosis and treatment. Specifically, deep learning methods have shown great potential to support pathology analysis, with recent studies identifying molecular traits that were not previously recognized on pathology H&E whole-slide images. Simultaneous to these developments, it is becoming increasingly evident that tumor heterogeneity is an important determinant of cancer prognosis and susceptibility to treatment, and should therefore play a role in the evolving practices of matching treatment protocols to patients. State of the art diagnostic procedures, however, do not provide automated methods for characterizing and/or quantifying tumor heterogeneity, certainly not in a spatial context. Further, existing methods for analyzing pathology whole-slide images from bulk measurements require many training samples and complex pipelines. Our work addresses these two challenges. First, we train deep learning models to spatially resolve bulk mRNA and miRNA expression levels on pathology whole-slide images (WSIs). Our models reach up to 0.95 AUC on held-out test sets from two cancer cohorts using a simple training pipeline and a small number of training samples. Using the inferred gene expression levels, we further develop a method to spatially characterize tumor heterogeneity. Specifically, we produce tumor molecular cartographies and heterogeneity maps of WSIs and formulate a heterogeneity index (HTI) that quantifies the level of heterogeneity within these maps. Applying our methods to breast and lung cancer slides, we show a significant statistical link between heterogeneity and survival. Our methods potentially open a new and accessible approach to investigating tumor heterogeneity and other spatial molecular properties and their link to clinical characteristics, including treatment susceptibility and survival.
Cis-regulatory evolution spotlights species differences in the adaptive potential of gene expression plasticity
Authors: He F. , Steige K. A. , Kovacova V. , Göbel U. , Bouzid M. , Keightley P. D. , Beyer A. , de Meaux J.
Published: July 2020

Phenotypic plasticity is the variation in phenotype that a single genotype can produce in different environments and, as such, is an important component of individual fitness. However, whether the effect of new mutations, and hence evolution, depends on the direction of plasticity remains controversial. Here, we identify the cis-acting modifications that have reshaped gene expression in response to dehydration stress in three Arabidopsis species. Our study shows that the direction of effects of most cis-regulatory variants differentiating the response betweenA. thalianaand the sister speciesA. lyrataandA. halleridepends on the direction of pre-existing plasticity in gene expression. A comparison of the rate of cis-acting variant accumulation in each lineage indicates that the selective forces driving adaptive evolution in gene expression favors regulatory changes that magnify the stress response inA. lyrata.The evolutionary constraints measured on the amino-acid sequence of these genes support this interpretation. In contrast, regulatory changes that mitigate the plastic response to stress evolved more frequently inA. halleri. Our results demonstrate that pre-existing plasticity can be a stepping stone for adaptation, but its selective remodeling differs between lineages.
The condensation of HP1-α/Swi6 imparts nuclear stiffness
Authors: Williams Jessica F. , Surovtsev Ivan V. , Schreiner Sarah M. , Chen Ziyuan , Raiymbek Gulzhan , Nguyen Hang , Hu Yan , Biteen Julie S. , Mochrie Simon G.J. , Ragunathan Kaushik , King Megan C.
Published: July 2020

The condensation of proteins and nucleic acids underlies the formation of membraneless organelles, which have emerged as major drivers of cellular organization. It remains largely unexplored, however, whether these condensates can impart mechanical function(s) to the cell. The heterochromatin protein HP1-α (Swi6 inS. pombe) crosslinks histone H3K9 methylated nucleosomes and has been proposed to undergo condensation to drive the liquid-like clustering of heterochromatin domains. Here we leverage the genetically tractableS. pombemodel and a separation-of-function Swi6 allele to elucidate a mechanical function imparted by its condensation. Using a combination of single-molecule imaging, force spectroscopy on individual nuclei, and high-resolution live-cell imaging, we show that Swi6 is critical for nuclear resistance to external force. Strikingly, it is this condensed yet dynamic pool of Swi6, rather than the chromatin-bound molecules, that is essential to imparting mechanical stiffness. Our findings suggest that Swi6 condensates embedded in the chromatin meshwork establish the emergent mechanical behavior of the nucleus as a whole, revealing that biomolecular condensation can influence organelle and cell mechanics.
Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike
Authors: Derking Ronald , Allen Joel D. , Cottrell Christopher A. , Sliepen Kwinten , Seabright Gemma E. , Lee Wen-Hsin , Rantalainen Kimmo , Antanasijevic Aleksandar , Copps Jeffrey , Yasmeen Anila , van der Woude Patricia , de Taeye Steven W. , van den Kerkhof Tom L.G.M. , Klasse P.J. , Ozorowski Gabriel , van Gils Marit J. , Moore John P. , Ward Andrew B. , Crispin Max , Sanders Rogier W.
Published: July 2020

The HIV-1 envelope glycoprotein (Env) trimer is decorated withN-linked glycans, which are attached to asparagine residues in the amino acid sequon NxT/S by oligosaccharyltransferases (OST). Artificial glycan “holes” exist when a PNGS is under-occupied on recombinant Env-based vaccines, but not on their viral counterpart. Native-like SOSIP trimers, including clinical candidates, have these artificial holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs. To increase PNGS occupancy, eliminate artificial glycan holes, and mimic the glycosylation of native BG505 Env, we replaced all 12 NxS sequons on the BG505 SOSIP trimer with NxT, thereby increasing the affinity of the sequons for OST. All PNGS, except N133 and N160, were nearly fully occupied on the modified trimer. Occupancy of the N133 site could be increased by changing N133 to NxS, while occupancy of the N160 site could be restored by reverting the nearby N156 sequon to NxS. Hence, OST affinity can influence glycan occupancy when two PNGS are in close proximity. Increasing glycan occupancy should reduce off-target immune responses to artificial glycan holes on vaccine antigens.