bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributions of Cambridge College Life to Structural Biology: Peterhouse as an Exemplar
Authors: Meurig Thomas John
Published: March 2020

How does university life add depth and quality and also opportunity to professional research? This is the key question discussed in this chapter. In answering it, the pre-eminent work of Aaron Klug and his cross-fertilizing interactions with his colleagues in the Cambridge College Peterhouse are analysed. Klug, who won the Chemistry Nobel Prize outright, made many revolutionary discoveries in structural molecular biology, especially the determination of the structure of viruses. He also devised new techniques in electron microscopy that are now of great importance in present-day research in molecular biology. Klug’s indebtedness to colleagues of Peterhouse, including Kendrew and Perutz, and his early mentor at the Cavendish Laboratory Lawrence Bragg, as well as a brief account of the current research pursued by members of Peterhouse and the famous confrontation in 1952 between Erwin Chargaff and Crick and Watson are also described.
The Summing Up: The Astonishing Successes of the LMB and the Dawn of a New Structural Biological Era
Authors: Meurig Thomas John
Published: March 2020

The contrast between the related pre-World War II attitudes to scientific research and those of the current era are described and how this affects modern research. There follows a summary of the numerous major achievements in advanced research conducted at the Laboratory of Molecular Biology (LMB) from its existence as a biological unit at the Cavendish Laboratory from 1957 onwards. The impressive commercial successes of the LMB, made possible by recent changes in the policy of the Medical Research Council, are also outlined. The second half of the chapter describes the arrival, importance, and immense potential of electron cryo-microscopy (which is described in a non-technical manner) in structural molecular biology, with examples drawn from the study of neurodegenerative diseases and other areas of biology.
Clouds in current and in a warming climate
Authors: Muller Caroline
Published: March 2020

We see them in our everyday lives. They make skies and sunsets even more beautiful, inspiring painters all over the world. But what are clouds? What are the physical processes occurring within a cloud? Do they all look alike, or are there different types of clouds? Why? Beyond our small human scale, how are clouds distributed at large, planetary scales? How do they couple and interact with the large-scale circulation of the atmosphere? What do the physics of cloud formation tell us about the hydrological cycle, including mean and extreme precipitation, in our current climate and in a warming world? What role do they play in the global energetics of the planet, for instance by reflecting the incoming shortwave radiation from the Sun, and by reducing the outgoing longwave radiation to space, because of their high altitudes and thus cold temperatures? These are the questions that will be addressed in these five lectures.
Investigation of the Unit-1 nuclear reactor of Fukushima Daiichi by cosmic muon radiography
Authors: Fujii Hirofumi , Hara Kazuhiko , Hayashi Kohei , Kakuno Hidekazu , Kodama Hideyo , Nagamine Kanetada , Sato Kotaro , Kim Shin-Hong , Suzuki Atsuto , Sumiyoshi Takayuki , Takahashi Kazuki , Takasaki Fumihiko , Tanaka Shuji , Yamashita Satoru
Published: March 2020

We have investigated the status of the nuclear fuel assemblies in the Unit-1 reactor of the Fukushima Daiichi nuclear power plant by cosmic muon radiography. In this study, muon tracking detectors were placed outside the reactor building. We succeeded in identifying the inner structure of the reactor complex, such as the reactor containment vessel, pressure vessel, and other structures of the reactor building, through the concrete wall of the reactor building. We found that a large number of fuel assemblies were missing in the original fuel loading zone inside the pressure vessel. The natural interpretation is that most of the nuclear fuel was melted and dropped down to the bottom of the pressure vessel or even below.
Communication within Banking Organizations and Small Business Lending
Authors: Levine Ross , Lin Chen , Peng Qilin , Xie Wensi
Published: March 2020

We investigate how communication within banks affects small business lending. Using travel times between a bank’s headquarters and its branches to proxy for the costs of communicating soft information, we exploit shocks to these travel times—the introduction of new airline routes—to evaluate the impact of within-bank communication costs on small business loans. We find that reducing headquarters-branch travel time boosts small business lending in the branch’s county. Several extensions suggest that new airline routes facilitate in-person communications that boost small-firm lending.
Identification of highly active systemic lupus erythematosus by combined type I interferon and neutrophil gene scores vs classical serologic markers
Authors: Chasset François , Ribi Camillo , Trendelenburg Marten , Huynh-Do Uyen , Roux-Lombard Pascale , Courvoisier Delphine S , Chizzolini Carlo ,   for the Swiss SLE Cohort Study (SSCS
Published: March 2020

Objectives

In SLE, heterogeneous clinical expression and activity may reflect diverse pathogenic and/or effector mechanisms. We investigated SLE heterogeneity by assessing the expression of three gene sets representative of type I IFN (IFN-I), polymorphonuclear neutrophil (PMN) and plasmablast (PB) signatures in a well-characterized, multidisciplinary cohort of SLE patients. We further assessed whether individual gene products could be representative of these three signatures.

Methods

Whole blood, serum and clinical data were obtained from 140 SLE individuals. Gene expression was assessed by NanoString technology, using a panel of 37 probes to compute six IFN-I, one PMN and one PB scores. Protein levels were measured by ELISA.

Results

Depending on the score, 45–50% of SLE individuals showed high IFN-I gene expression. All six IFN-I scores were significantly associated with active skin involvement, and two of six were associated with arthritis. IFN-induced Mx1 protein (MX1) level was correlated with IFN-I score (P < 0.0001) and associated with a similar clinical phenotype. In all, 25% of SLE individuals showed high PMN gene expression, associated with SLE fever, serositis, leukopoenia and glucocorticoid use. PB gene expression was highly affected by immunosuppressant agents, with no association with SLE features. Combined IFN-I and PMN gene scores were significantly associated with high disease activity and outperformed anti-dsDNA and anti-C1q autoantibody and complement levels for predicting SLE activity.

Conclusion

IFN-I and PMN gene scores segregate with distinct SLE clinical features, and their combination may identify high disease activity. MX1 protein level performed similar to IFN-I gene expression.
‘Millions of Eyes Were Turned Skywards’: The Air League of the British Empire, Empire Air Day, and the Promotion of Air-mindedness, 1934–9
Authors: Thompson Rowan G E
Published: March 2020

This article investigates the Air League of the British Empire and its attempts to promote air-mindedness within British society in the late 1930s. It draws attention to the Air League’s construction of a distinctly militarized aerial theatre—in the form of Empire Air Day (EAD)—and highlights the extent to which the event was embedded in popular civic ritual. Linking the themes of nation, empire, youth, and air-mindedness, the case of EAD provides important insights into the ways in which British society interacted with—and ascribed meaning to—technology, technological change, and modernity, in a period of high international tensions. The article shows that the Air Ministry valued the display as a vehicle for recruitment, propaganda, and as a way to project an image of military strength to domestic and foreign audiences. The display enabled the League to place before the British public a form of ‘popular’ militarism that was supported by large sections of British society, key military figures, members of the royal family, newspapers across the political spectrum, and by politicians of all stripes. EAD was a politically and culturally acceptable way of promoting rearmament and the military capabilities of the British state.
Is a 14-day quarantine period optimal for effectively controlling coronavirus disease 2019 (COVID-19)?
Authors: Jiang Xue , Niu Yawei , Li Xiong , Li Lin , Cai Wenxiang , Chen Yucan , Liao Bo , Wang Edwin
Published: March 2020

Background

The outbreak of a new coronavirus (SARS-CoV-2) disease (Covid-19) has become pandemic. To be more effectively controlling the disease, it is critical to set up an optimal quarantine period so that about 95% of the cases developing symptoms will be retained for isolation. At the moment, the WHO-established quarantine period is 14 days based on previous reports which had studied small sizes of hospitalized cases (10 and ∼100, respectively), however, over 80% of adult- and 95% of child-cases were not necessary to stay in hospitals, and therefore, had not been hospitalized. Therefore, we are questioning if the current-inferred median incubation time is representative for the whole Covid-19 population, and if the current quarantine period is optimal.

Methods

We compiled and analyzed the patient-level information of 2015 laboratory-confirmed Covid-19 cases including 99 children in 28 Chinese provinces. This cohort represents a wide-range spectrum of Covid-19 disease with both hospitalized and non-hospitalized cases.

Results

The full range of incubation periods of the Covid-19 cases ranged from 0 to 33 days among 2015 cases. There were 6 (0.13%) symptom-free cases including 4 females with a median age of 25.5 years and 2 males with a median age of 36 years. The median incubation period of both male and female adults was similar (7-day) but significantly shorter than that (9-day) of child cases (P=0.02). This cohort contained 4 transmission generations, and incubation periods of the cases between generations were not significantly different, suggesting that the virus has not been rapidly adapted to human beings. Interestingly, incubation periods of 233 cases (11.6%) were longer than the WHO-established quarantine period (14 days). Data modeling suggested that if adults take an extra 4-day or 7-day of isolation (i.e., a quarantine period of 18 or 21 days), 96.2% or 98.3%, respectively, of the people who are developing symptoms will be more effectively quarantined. Patients transmitted via lunch/dinner parties (i.e., gastrointestinal tract infection through oral transmission) had a significantly longer incubation period (9-day) than other adults transmitted via respiratory droplets or contaminated surfaces and objects (P<0.004).

Conclusions

The whole Covid-19 population including both hospitalized and non-hospitalized cases had a median incubation period of 7-day for adults, which is 1.8-day longer than the hospitalized cases reported previously. An extension of the adult quarantine period to 18 days or 21 days could be more effective in preventing virus-spreading and controlling the disease. The cases transmitted by lunch/dinner parties could be infected first in the gastrointestinal tract through oral transmission and then infected in the respiratory system so that they had a longer incubation period.
Deletion of Sphingosine 1-Phosphate Receptor 1 in cardiomyocytes during development leads to abnormal ventricular conduction and fibrosis
Authors: Jorgensen Ryan , Katta Meghna , Wolfe Jayne , Leach Desiree F. , Chun Jerold , Wilsbacher Lisa D.
Published: March 2020

Sphingosine 1-phosphate receptor 1 (S1P1, encoded byS1pr1) is a G protein-coupled receptor that signals in multiple cell types including endothelial cells and cardiomyocytes. Cardiomyocyte-specific deletion ofS1pr1during development leads to ventricular noncompaction, with one-third of mutant mice surviving to adulthood. Adult survivors of embryonic cardiomyocyteS1pr1deletion showed cardiac hypertrabeculation consistent with ventricular noncompaction. Surprisingly, systolic function in mutant mice was preserved through at least one year of age. Cardiac conduction was abnormal in cardiomyocyteS1pr1mutant mice, with prolonged QRS intervals in mutants as compared with littermate control mice. Immunostaining of hearts fromS1pr1mutant embryos displayed a zone of intermediate Connexin 40 expression in the trabecular myocardium. However, we observed no significant differences in Connexin 40 and Connexin 43 immunostaining in hearts from adult survivors of embryonic cardiomyocyteS1pr1deletion, which suggests normalized development of the ventricular conduction system in mutant mice. By contrast, the adult survivors of embryonic cardiomyocyteS1pr1deletion showed increased cardiac fibrosis as compared with littermate controls. These results demonstrate that ventricular hypertrabeculation caused by embryonic deletion of cardiomyocyteS1pr1leads to cardiac fibrosis, which contributes to abnormal ventricular conduction. These results also reveal conduction abnormalities in the setting of hypertrabeculation with normal systolic function, which may be of clinical relevance in humans with ventricular hypertrabeculation.
A simple and reliable method for longitudinal assessment of untethered mosquito induced flight activity
Authors: Gaviraghi Alessandro , Oliveira Marcus F.
Published: March 2020

Aedes aegyptiadult females are key vectors of several arboviruses and flight activity plays a central role in mosquito biology and disease transmission. Available methods to quantify mosquito flight usually require special devices and mostly assess spontaneous locomotor activity at individual level. Here, we developed a new method to determine longitudinal untethered adultA. aegyptiinduced flight activity: the INduced FLight Activity TEst (INFLATE). This method was an adaptation of the “rapid iterative negative geotaxis” assay to assess locomotor activity inDrosophilaand explore the spontaneous behavior of mosquito to fly upon a physical stress. Insects were placed on a plastic cage previously divided in four vertical quadrants and flight performance was carried out by tapping cages towards the laboratory bench. After one minute, the number of insects per quadrant was registered by visual inspection and categorized in five different scores. By using INFLATE, we observed that flight performance was not influenced by repeated testing, sex or 5 % ethanol intake. However, induced flight activity was strongly affected by aging, blood meal and inhibition of mitochondrial complex I. This simple and rapid method allows the longitudinal assessment of induced flight activity of multiple untethered mosquitoes and may contribute to a better understanding ofA. aegyptidispersal biology.
Comparison of long read methods for sequencing and assembly of a plant genome
Authors: Murigneux Valentine , Rai Subash Kumar , Furtado Agnelo , Bruxner Timothy J.C. , Tian Wei , Ye Qianyu , Wei Hanmin , Yang Bicheng , Harliwong Ivon , Anderson Ellis , Mao Qing , Drmanac Radoje , Wang Ou , Peters Brock A. , Xu Mengyang , Wu Pei , Topp Bruce , Coin Lachlan J.M. , Henry Robert J.
Published: March 2020

Sequencing technologies have advanced to the point where it is possible to generate high accuracy, haplotype resolved, chromosome scale assemblies. Several long read sequencing technologies are available on the market and a growing number of algorithms have been developed over the last years to assemble the reads generated by those technologies. When starting a new genome project, it is therefore challenging to select the most cost-effective sequencing technology as well as the most appropriate software for assembly and polishing. For this reason, it is important to benchmark different approaches applied to the same sample. Here, we report a comparison of three long read sequencing technologies applied to the de novo assembly of a plant genome,Macadamia jansenii. We have generated sequencing data using Pacific Biosciences (Sequel I), Oxford Nanopore Technologies (PromethION) and BGI (single-tube Long Fragment Read) technologies for the same sample. Several assemblers were benchmarked in the assembly of PacBio and Nanopore reads. Results obtained from combining long read technologies or short read and long read technologies are also presented. The assemblies were compared for contiguity, accuracy and completeness as well as sequencing costs and DNA material requirements. Overall, the three long read technologies produced highly contiguous and complete genome assemblies ofMacadamia jansenii. At the time of sequencing, the cost associated with each method was significantly different but continuous improvements in technologies have resulted in greater accuracy, increased throughput and reduced costs. We propose updating this comparison regularly with reports on significant iterations of the sequencing technologies.
Variation in developmental rates is not linked to environmental unpredictability in annual killifishes
Authors: Rowiński P. K. , Sowersby W. , Näslund J. , Eckerström-Liedholm S. , Gotthard K. , Rogell B.
Published: March 2020

Comparative evidence suggests that adaptive plasticity may evolve as a response to predictable environmental variation. However, less attention has been placed on unpredictable environmental variation, which is considered to affect evolutionary trajectories by increasing phenotypic variation (or bet-hedging). Here, we examine the occurrence of bet-hedging in egg developmental rates in seven species of annual killifish, which originate from a gradient of variation in precipitation rates, under three treatment incubation temperatures (21°C, 23°C, and 25°C). In the wild, these species survive regular and seasonal habitat desiccation, as dormant eggs buried in the soil. At the onset of the rainy season, embryos must be sufficiently developed in order to hatch and complete their life-cycle. We found substantial differences among species in both the mean and variation of egg development rates, as well as species-specific plastic responses to incubation temperature. Yet, there was no clear relationship between variation in egg development time and variation in precipitation rate (environmental predictability). The exact cause of these differences therefore remains enigmatic, possibly depending on differences in other natural environmental conditions in addition to precipitation predictability. Hence, if species-specific variances are adaptive, the relationship between development and variation in precipitation is complex, and does not diverge in accordance with simple linear relationships.
The utility of a metagenomics approach for marine biomonitoring
Authors: Singer Gregory A. C. , Shekarriz Shahrokh , McCarthy Avery , Fahner Nicole , Hajibabaei Mehrdad
Published: March 2020

1

The isolation and analysis of environmental DNA (eDNA) for ecosystem assessment and monitoring has become increasingly popular. A majority of studies have taken a metabarcoding approach—that is, amplifying and sequencing one or more gene targets of interest. Shotgun sequencing of eDNA—also called metagenomics—while popular in microbial community analysis has not seen much adoption for the analysis of other groups of organisms. Especially in light of the existence of extremely high-capacity DNA sequencers, we decided to test the performance of a shotgun approach side-by-side with a metabarcoding approach on marine water samples obtained from offshore Newfoundland. We found that metabarcoding remains the most efficient technique, but that metagenomics also has significant power to reveal biodiversity patterns, and in fact can be treated as an independent confirmation of ecological gradients. Moreover, we show that metagenomics can also be used to infer factors related to ecosystem health and function.
Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain
Authors: Heithoff Benjamin P. , George Kijana K. , Phares Aubrey N. , Zuidhoek Ivan A. , Munoz-Ballester Carmen , Robel Stefanie
Published: March 2020

In the adult brain, multiple cell types are known to produce factors that regulate blood-brain barrier properties, including astrocytes. Yet several recent studies disputed a role for mature astrocytes at the blood-brain barrier. To determine if astrocytes contribute a non-redundant and necessary function in maintaining the adult blood-brain barrier, we used a mouse model of tamoxifen-inducible astrocyte ablation. In adult mice, tamoxifen induction caused sparse apoptotic astrocyte cell death within 2 hours. Indicative of BBB damage, leakage of the small molecule Cadaverine and the large plasma protein fibrinogen into the brain parenchyma indicative of BBB damage was detected as early as astrocyte ablation was present. Vessels within and close to regions of astrocyte loss had lower expression of the tight junction protein zonula occludens-1 while endothelial glucose transporter 1 expression was undisturbed. Cadaverine leakage persisted for several weeks suggesting a lack of barrier repair. This is consistent with the finding that ablated astrocytes were not replaced. Adjacent astrocytes responded with partial non-proliferative astrogliosis, characterized by morphological changes and delayed phosphorylation of STAT3, which restricted dye leakage to the brain and vessel surface areas lacking coverage by astrocytes one month after ablation. In conclusion, astrocytes are necessary to maintain blood-brain barrier integrity in the adult brain. Blood-brain barrier-regulating factors secreted by other cell types, such as pericytes, are not sufficient to compensate for astrocyte loss.

Main Points

Mature astrocytes are necessary for maintenance of endothelial tight junctions in the adult brain. Ablated astrocytes are not replaced by proliferation or process extension of neighboring astrocytes resulting in long-term blood-brain barrier damage.
Individual variability in functional connectivity architecture of the mouse brain
Authors: Bergmann Eyal , Gofman Xenia , Kavushansky Alexandra , Kahn Itamar
Published: March 2020

The functional organization of brain networks can be estimated using fMRI by examining the coherence of spontaneous fluctuations in the fMRI signal, a method known as resting-state functional connectivity MRI. Previous studies in humans reported that such functional networks are dominated by stable group and individual factors, demonstrating that fMRI is suited to measuring subject-specific characteristics, and suggesting the utility of such precision fMRI approach in personalized medicine. However, mechanistic investigations to the sources of individual variability in health and disease are limited in humans and thus require animal models. Here, we used repeated-measurement resting-state fMRI in awake mice to quantify the contribution of individual variation to the functional architecture of the mouse cortex. Comparing the organization of functional networks across the group, we found dominant common organizational principles. The data also revealed stable individual features, which create a unique fingerprint that allow identification of individual mice from the group. Examining the distribution of individual variation across the mouse cortex, we found it is homogeneously distributed in both sensory and association networks. Finally, connectome-based predictive modeling of motor behavior in the rotarod task revealed that individual variation in functional connectivity explained behavioral variability. Collectively, these results show that mouse functional networks are characterized by individual variations suggesting that individual variation characterizes the mammalian cortex in general, and not only the primate cortex. These findings lay the foundation for future mechanistic investigations of individual brain organization and pre-clinical studies of brain disorders in the context of personalized medicine.
Self-paced treadmills do not allow for valid observation of linear and non-linear gait variability outcomes in patients with Parkinson’s disease
Authors: Rohafza Maryam , Soangra Rahul , Smith Jo Armour , Ignasiak Niklas König
Published: March 2020

Background

Due to the imposed constant belt speed, motorized treadmills are known to change linear and non-linear gait variability outcomes. This is particularly true of patients with Parkinson’s disease where the treadmill can act as an external pacemaker. Therefore, the use of treadmills is generally not recommended when quantifying gait variability. Self-paced treadmills allow for updating the belt speed relative to the walking speed of the subject and might, therefore, be a useful tool for the collection of long consecutive walking trials, necessary for gait variability observations.

Research question

To validate gait variability measures collected on a self-paced treadmill as compared to overground walking.

Methods

Thirteen healthy subjects and thirteen patients with Parkinson’s disease performed 5 – 8 minute long walking trials: overground, on a treadmill at a constant speed, as well as in three different self-paced treadmill modes. Stride times and stride lengths were recorded using a validated IMU-system and variability was quantified using the coefficient of variation, sample entropy, and detrended fluctuation analysis. Overground and treadmill trials were compared using Pearson’s correlation coefficient, method error, and Bland and Altman analysis.

Results

For healthy subjects, the self-paced treadmill resulted in increased correlation coefficients of 0.57 – 0.74 as compared to a constant speed treadmill. Correlation coefficients for stride length variability between overground and treadmill walking were not significant. For patients, generally, large errors of 33-40% of stride time variability were observed between overground and treadmill walking. Stride length variability is most similar at a constant belt speed and shows errors of 14-39%.

Significance

Despite an improvement of temporal gait variability validity in the self-paced mode for healthy subjects, the large systematic and random errors between overground and self-paced treadmill walking prohibit meaningful gait variability observations in patients with Parkinson’s disease using self-paced treadmills.
Alterations in the gut microbiome by HIV-1 infection or a high-fat diet associates with systemic immune activation and inflammation in double humanized-BLT mice
Authors: Daharsh Lance , Ramer-Tait Amanda E. , Li Qingsheng
Published: March 2020

Background

While the translatability of gut microbiome studies utilizing animal models to humans has proven difficult, studying the gut microbiome directly in humans is also challenging due to the existence of many confounding variables. Therefore, we utilized double humanized mice, which have both an engrafted stable human-like gut microbiome and functional human immune system. With this model, we were able to determine the in vivo impact of HIV-1 infection or a high-fat diet (HFD) on gut human microbiome composition, and its relationship with human immune cell activation and systemic inflammation.

Results

Surgery was performed on NSG mice to create humanized bone-marrow, liver, thymus mice (hu-mice). In order to create double hu-mice, the hu-mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and subsequently transplanted with human fecal material from healthy human donors. We characterized 262 fecal samples from hu-mice, double hu-mice, and human fecal donors to determine the impact of HIV-1 infection or HFD on the gut microbiome and systemic immune activation and inflammation. We found that HIV-1 infection altered the human-like gut microbiome of double hu-mice, which was associated with decreased human CD4 T cells and increased systemic inflammation and immune activation. Further, using a HFD we induced gut microbial dysbiosis in double hu-mice which corresponded with increased systemic immune activation and inflammation.

Conclusions

Here, we describe the changes in the human gut microbiome and human immune system due to HIV-1 infection or HFD using our double hu-mice model. HIV-1 infection led to changes in the composition of the human-like gut microbiome that was associated with human CD4 T cell loss and high levels of inflammation and immune activation. The HFD quickly changed the composition of the gut microbiome and led to systemic immune activation and inflammation. We further identified a subset of gut bacteria in HIV-1 infected and HFD fed double hu-mice that was closely associated with systemic inflammation and immune activation. This study demonstrated how double humanized mice can be used to study the complex in vivo interactions of the gut microbiome and human immune system in the context of both disease and diet.
Excessive visual crowding effects in developmental dyscalculia
Authors: Castaldi Elisa , Turi Marco , Gassama Sahawanatou , Piazza Manuela , Eger Evelyn
Published: March 2020

Visual crowding refers to the inability to identify objects when surrounded by other similar items. Crowding-like mechanisms are thought to play a key role in numerical perception by determining the sensory mechanisms through which ensembles are perceived. Enhanced visual crowding might hence prevent the normal development of a system involved in segregating and perceiving discrete numbers of items and ultimately the acquisition of more abstract numerical skills. Here, we investigated whether excessive crowding occurs in developmental dyscalculia (DD), a neurodevelopmental disorder characterized by difficulty in learning the most basic numerical and arithmetical concepts, and whether it is found independently of associated major reading and attentional difficulties. We measured spatial crowding in two groups of adult individuals with DD and control subjects. In separate experiments, participants were asked to discriminate the orientation of a Gabor patch either in isolation or under spatial crowding. Orientation discrimination thresholds were comparable across groups when stimuli were shown in isolation, yet they were much higher for the DD group with respect to the control group when the target was crowded by closely neighbouring flanking gratings. The difficulty in discriminating orientation (as reflected by the combination of accuracy and reaction times) in the DD compared to the control group persisted over several larger target flanker distances. Finally, we found that the degree of such spatial crowding correlated with impairments in mathematical abilities even when controlling for visual attention and reading skills. These results suggest that excessive crowding effects might be a characteristic of DD, independent of other associated neurodevelopmental disorders.

Bullet points

People with DD have difficulty learning about numbers and arithmetics.

Perception of non-symbolic number seems to be modulated by visual crowding.

Can stronger than normal crowding effects contribute to the origin of DD?

We measured crowding with orientation discrimination tasks using Gabor gratings.

Abnormal crowding characterizes DD independently of other developmental deficits.
Loss of α7 nicotinic acetylcholine receptors in GABAergic interneurons causes sex-dependent impairments in postnatal neurogenesis and cognitive and social behavior
Authors: Nacer Samir A. , Otto Simone , Letsinger Ayland C. , DeFilipp Jemma Strauss , Nikolova Viktoriya D. , Riddick Natallia V. , Stevanovic Korey D. , Cushman Jesse D. , Yakel Jerrel L.
Published: March 2020

Neural stem cells within the subgranular zone of the dentate gyrus (DG) generate new neurons that form the granule cell layer during embryonic development and continue to generate new neurons throughout life. The maturation process of newly generated granule cells is modulated by nicotinic acetylcholine receptors (nAChRs), which have been shown to play a role in cell survival, signal modulation, dendritic integration, and memory formation. Disrupted nAChR signaling has been implicated in neuropsychiatric and neurodegenerative disorders, potentially via alterations in DG neurogenesis. GABAergic interneurons are known to express nAChRs, particularly the α7 subunit, and have been shown to shape development, integration, and circuit reorganization of DG granule cells. Therefore, we examined the effects of conditional deletion of α7 nAChRs in GABAergic interneurons on measures of postnatal neurogenesis and behavioral outcomes. Loss of α7 nAChRs resulted in a decrease of postnatal granule cells, as indicated by reduced GFAP+ cells in the DG, specifically in male mice, as well as sex-dependent changes in several behaviors, including social recognition, object investigation, and spatial learning. Overall, these findings suggest α7 nAChRs expressed in GABAergic interneurons play an important role in regulating postnatal neurogenesis and behavior in a sex-dependent manner. This provides important insight into the mechanisms by which cholinergic dysfunction contributes to the cognitive and behavioral changes associated with neurodevelopmental and neurodegenerative disorders.
A RNA-seq characterization of the porcine sperm microbiome
Authors: Gòdia M. , Ramayo-Caldas Y. , Zingaretti L. M. , López S. , Rodriguez-Gil J. E. , Yeste M. , Sánchez A. , Clop A.
Published: March 2020

The microbiome plays a key role in homeostasis and health and it has been also linked to fertility and semen quality in several animal species including swine. Despite the more than likely importance of sperm bacteria on the boar’s reproductive ability and the dissemination of pathogens and antimicrobial resistance genes, a high throughput characterization of the swine sperm microbiome remains undone. The current study aimed at profiling the boar sperm bacterial population and its relationship with seven semen quality traits.

We carried RNA-seq on 40 ejaculates and we found that it contains a broad population of bacteria. The most abundant phyla wereProteobacteria(39.1%),Firmicutes(27.5%),Actinobacteria(14.9%) andBacteroidetes(5.7%). The predominant species contaminated sperm after ejaculation from soil, faeces and water sources (Bacillus megaterium,Brachybacterium faecium,Bacillus coagulans). Some potential pathogens were also found but at relatively low levels (Escherichia coli,Clostridioides difficile,Clostridium perfringens,Clostridium botulinumandMycobacterium tuberculosis). We also identified 3 potential antibiotic resistant genes fromE. coliagainst chloramphenicol,Neisseria meningitidisagainst spectinomycin andStaphylococcus aureusagainst linezolid. None of these genes were highly abundant. Finally, we classified the ejaculates into categories according to their bacterial features and semen quality parameters and identified two categories that significantly differed for 5 semen quality traits and 13 bacterial features including the generaAcinetobacter,StenotrophomonasandRhodobacter. Our results show that boar semen contains a rich microbiome with potential pathogens and antibiotic resistance genes which may affect its reproductive performance.
LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate
Authors: Jin Run , Klasfeld Samantha , Garcia Meilin Fernandez , Xiao Jun , Han Soon-Ki , Konkol Adam , Zhu Yang , Wagner Doris
Published: March 2020

Master transcription factors reprogram cell fate in multicellular eukaryotes. Pioneer transcription factors have prominent roles in this process because of their ability to contact their cognate binding motifs in closed chromatin. Reprogramming is pervasive in plants, whose development is plastic and tuned by the environment, yet no bonafide pioneer transcription factor has - been identified in this kingdom. Here we show that the master transcription factor LEAFY (LFY), which promotes floral fate through upregulation of the floral commitment factorAPETALA1(AP1), is a pioneer transcription factor. In vitro, LFY binds in a sequence-specific manner and with high affinity to the endogenousAP1target locus DNA assembled into a nucleosome. In vivo, LFY associates with nucleosome occupied binding sites at the majority of its target loci, includingAP1,where it co-occupies DNA with histones. Moreover, the LFY DNA contact helix shares defining properties with those of strong nucleosome binding pioneer factors. At theAP1locus, LFY unlocks chromatin locally by displacing the H1 linker histone and by recruiting SWI/SNF chromatin remodelers, but broad changes in chromatin accessibility occur later and require activity of additional, non-pioneer transcription, factors. Our study provides a mechanistic framework for patterning of inflorescence architecture and uncovers striking similarities between plant and animal pioneer transcription factors. Further analyses aimed at elucidating the defining characteristics of pioneer transcription factors will allow harnessing these for enhanced cell fate reprogramming.
Industrial Waste based Bio-manufacturing of Synthetic Tandem Repeat Protein Fibers
Authors: Mazeed Tarek El-Sayed , Jung Huihun , Kikuchi Yusuke , Allen Benjamin D. , Wood David W. , Demirel Melik C.
Published: March 2020

Protein-based fibers are lightweight, biodegradable, have excellent moisture and temperature regulation, and exceptional mechanical properties, but they are limited in production capacity. Biosynthetic protein-based fibers have the potential to overcome these concerns, but large-scale production with high yield (>1g/L) and purity (>%80), as well as low cost (<$50/kg), must be achieved. Here we developed an optimized expression and purification method for biosynthetic tandem repeat proteins, that are inspired from squid ring tooth (SRT) protein using three wetwaste feedstock, corn steep liquor, molasses, and soybean extract. SRT is composed of a highly stiff, naturally occurring bioplastic and these properties arise from the molecular architecture of the constituant proteins, which are segmented co-polymers with alternating semicrystalline and amorphous domains similar to silk. We have developed protocols to use liquid industrial and agricultural waste as feedstock for SRT production, which has the potential to divert waste streams into useful products. We also show that our biosynthetic protein powder, produced at 1 g/L yield and greater than 80% purity, can be manufactured into fibers using conventional split film or wet-spinning approaches.
Potential Functions of Histone H3.3K56 Acetylation in Mammals
Authors: Fang Lei , Chen Danqi , Zhang Jingzi , Li Hongjie , Bradford Beatrix , Jin Chunyuan
Published: March 2020

H3K56 acetylation (H3K56Ac) was first identified in yeast and has recently been reported to play important roles in maintaining genomic stability, chromatin assembly, DNA replication, cell cycle progression and DNA repair. Although H3.1K56Ac has been relatively well studied, the function of H3.3K56Ac remains mostly unknown in mammals. In this study, we used H3.3K56Q and H3.3K56R mutants to study the possible function of H3.3K56 acetylation. The K-to-Q substitution mimics a constitutively acetylated lysine, while the K-to-R replacement mimics a constitutively unmodified lysine. We report that cell lines harboring mutation of H3.3K56R exhibit dramatic morphology changes and cell death. Using Tet-Off inducible system, we show an increased population of polyploid/aneuploid cells and a decreased cell viability in H3.3K56R mutant cells. In consistence with these results, H3.3K56R mutant compromised H3.3 incorporation into several pericentric and centric heterochromatin regions we tested. Moreover, mass spectrometry analysis coupled with label free quantification reveal that biological processes regulated by the H3.3-associating proteins, whose interaction with H3.3 is markedly increased by H3.3K56Q mutation but decreased by H3.3K56Q mutation, include sister chromatid cohesion, mitotic nuclear division, and mitotic nuclear envelope disassembly. These results suggest that H3.3K56 acetylation is crucial for chromosome segregation and cell division in mammals.
Molecular determinants of SR-B1-dependentPlasmodiumsporozoite entry into hepatocytic cells
Authors: Langlois Anne-Claire , Manzoni Giulia , Vincensini Laetitia , Coppée Romain , Marinach Carine , Guérin Maryse , Huby Thierry , Carrière Véronique , Cosset François-Loïc , Dreux Marlène , Rubinstein Eric , Silvie Olivier
Published: March 2020

Sporozoite forms of the malaria parasitePlasmodiumare transmitted by mosquitoes and first infect the liver for an initial round of replication before parasite proliferation in the blood. The molecular mechanisms involved during sporozoite invasion of hepatocytes remain poorly understood. Two receptors of the Hepatitis C virus (HCV), the tetraspanin CD81 and the scavenger receptor class B type 1 (SR-B1), play an important role during the entry ofPlasmodiumsporozoites into hepatocytic cells. In contrast to HCV entry, which requires both CD81 and SR-B1 together with additional host factors, CD81 and SR-B1 operate independently during malaria liver infection. Sporozoites from human-infectingP. falciparumandP. vivaxrely respectively on CD81 or SR-B1. Rodent-infectingP. bergheican use SR-B1 to infect host cells as an alternative pathway to CD81, providing a tractable model to investigate the role of SR-B1 duringPlasmodiumliver infection. Here we show that mouse SR-B1 is less functional as compared to human SR-B1 duringP. bergheiinfection. We took advantage of this functional difference to investigate the structural determinants of SR-B1 required for infection. Using a structure-guided strategy and chimeric mouse/human SR-B1 constructs, we could map the functional region of human SR-B1 within apical loops, suggesting that this region of the protein may play a crucial role for interaction of sporozoite ligands with host cells and thus the very first step ofPlasmodiuminfection.

IMPORTANCE

Malaria is caused byPlasmodiumparasites and remains one of the deadliest parasitic diseases worldwide. The parasite is transmitted by a blood feeding mosquito and first invades the liver for an initial, obligatory and silent round of replication. The liver infection is an attractive target for antimalarial vaccine strategies, however the molecular mechanisms of parasite invasion of hepatocytes remain to be fully elucidated. Two hepatocyte surface proteins are known to be important for parasite entry into hepatocytes, the tetraspanin CD81 and the scavenger receptor class B type 1 (SR-B1). These receptors constitute independent gateways depending on thePlasmodiumspecies. Here, we identified the structural determinants of SR-B1, an important hepatocyte entry factor for human-infectingP. vivax. This study paves the way toward a better characterization of the molecular interactions underlying the crucial early stages of infection, a pre-requisite for the development of novel malaria vaccine strategies.
Single-cell RNA sequencing of human, macaque, and mouse testes uncovers conserved and divergent features of mammalian spermatogenesis
Authors: Shami Adrienne Niederriter , Zheng Xianing , Munyoki Sarah K. , Ma Qianyi , Manske Gabriel L. , Green Christopher D. , Sukhwani Meena , Orwig Kyle E. , Li Jun Z. , Hammoud Saher Sue
Published: March 2020

Spermatogenesis is a highly regulated process that produces sperm to transmit genetic information to the next generation. Although extensively studied in mice, our current understanding of primate spermatogenesis is limited to populations defined by state-specific markers defined from rodent data. As between-species differences have been reported in the process duration and cellular differentiation hierarchy, it remains unclear how molecular markers and cell states are conserved or have diverged from mice to man. To address this challenge, we employ single-cell RNA-sequencing to identify transcriptional signatures of major germ and somatic cell-types of the testes in human, macaque and mice. This approach reveals differences in expression throughout spermatogenesis, including the stem/progenitor pool of spermatogonia, classical markers of differentiation, potential regulators of meiosis, the kinetics of RNA turnover during spermatid differentiation, and germ cell-soma communication. These datasets provide a rich foundation for future targeted mechanistic studies of primate germ cell development andin vitrogametogenesis.
Anaerobic sulfur oxidation underlies adaptation of a chemosynthetic symbiont to oxic-anoxic interfaces
Authors: Paredes Gabriela F. , Viehboeck Tobias , Lee Raymond , Palatinszky Marton , Mausz Michaela A. , Reipert Siegfried , Schintlmeister Arno , Maier Andreas , Volland Jean-Marie , Hirschfeld Claudia , Wagner Michael , Berry David , Markert Stephanie , Bulgheresi Silvia , König Lena
Published: March 2020

Chemosynthetic symbioses occur worldwide in marine habitats, but comprehensive physiological studies of chemoautotrophic bacteria thriving on animals are scarce. Stilbonematinae are coated by monocultures of thiotrophic Gammaproteobacteria. As these nematodes migrate through the redox zone, their ectosymbionts experience varying oxygen concentrations. However, nothing is known about how these variations affect their physiology or metabolism. Here, by applying omics, Raman microspectroscopy and stable isotope labelling, we investigated the effect of oxygen onCandidatusThiosymbion oneisti. Unexpectedly, sulfur oxidation genes were upregulated in anoxic relative to oxic conditions, but carbon fixation genes and incorporation of13C-labeled bicarbonate were not. Instead, several genes involved in carbon fixation were upregulated in oxic conditions, together with genes involved in organic carbon assimilation, polyhydroxyalkanoate (PHA) biosynthesis, nitrogen fixation and urea utilization. Furthermore, in the presence of oxygen, stress-related genes were upregulated together with vitamin biosynthesis genes likely necessary to withstand its deleterious effects, and the symbiont appeared to proliferate less. Based on its physiological response to oxygen, we propose thatCa.T. oneisti may exploit anaerobic sulfur oxidation coupled to denitrification to proliferate in anoxic sand. However, the ectosymbiont would still profit from the oxygen available in superficial sand, as the energy-efficient aerobic respiration would facilitate carbon and nitrogen assimilation by the ectosymbiont.

IMPORTANCE

Chemoautotrophic endosymbionts are famous for exploiting sulfur oxidization to feed marine organisms with fixed carbon. However, the physiology of thiotrophic bacteria thriving on the surface of animals (ectosymbionts) is less understood. One long standing hypothesis posits that attachment to animals that migrate between reduced and oxic environments would boost sulfur oxidation, as the ectosymbionts would alternatively access sulfide and oxygen, the most favorable electron acceptor. Here, we investigated the effect of oxygen on the physiology ofCandidatusThiosymbion oneisti, a Gammaproteobacterium which lives attached to marine nematodes inhabiting shallow water sand. Surprisingly, sulfur oxidation genes were upregulated in anoxic relative to oxic conditions. Furthermore, under anoxia, the ectosymbiont appeared to be less stressed and to proliferate more. We propose that animal-mediated access to oxygen, rather than enhancing sulfur oxidation, would facilitate assimilation of carbon and nitrogen by the ectosymbiont.