Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptome analysis for the development of cell-type specific labeling to study olfactory circuits

In each sensory system of the brain, mechanisms exist to extract distinct features from stimuli to generate a variety of behavioural repertoires. These often correspond to different cell types at some stage in sensory processing. In the mammalian olfactory system, complex information processing starts in the olfactory bulb, whose output is conveyed by mitral and tufted cells (MCs and TCs). Despite many differences between them, and despite the crucial position they occupy in the information hierarchy, little is known how these two types of projection neurons differ at the mRNA level. Here, we sought to identify genes that are differentially expressed between MCs and TCs, with an ultimate goal to generate a cell-type specific Cre-driver line, starting from a transcriptome analysis using a large and publicly available single-cell RNA-seq dataset (Zeisel et al., 2018). Despite many genes showing differential expressions, we identified only a few that were abundantly and consistently expressed only in MCs. After further validating these putative markers using in-situ hybridization, two genes, namely Pkib and Lbdh2, remained as promising candidates. Using CRISPR/Cas9-mediated gene editing, we generated Cre-driver lines and analysed the resulting recombination patterns. This analysis indicated that our new inducible Cre-driver line, Lbhd2-CreERT2, can be used to genetically label MCs in a tamoxifen dose-dependent manner, as assessed by soma locations, projection patterns and sensory-evoked responses. Hence this line is a promising tool for future investigations of cell-type specific contributions to olfactory processing and demonstrates the power of publicly accessible data in accelerating science.
The Infrared Spectra of Oriented Rhombic Sulfur Crystals with Polarized Radiation

The infrared spectra, in the rock salt region, of oriented sections of single rhombic sulfur crystal have been obtained. The spectra of sections perpendicular to the c axis of the crystal, the 001 type planes, have been compared, under ordinary radiation with those of sections parallel to the c axis, 110 type planes. Most bands in the region investigated, 700 to 1500 cm−1, show differences in intensity in the two spectra. With a 110 section and radiation polarized at various angles, similar changes in intensity were observed. Both experiments lead to similar conclusions regarding the direction of the oscillating dipole in the vibrations giving rise to the observed bands. Assignments of the infrared active species (B2 or E1) in these bands are given but no attempt is made to explain them in terms of the fundamental vibrations.
Learning differentially shapes prefrontal and hippocampal activity during classical conditioning

The ability to use sensory cues to inform goal directed actions is a critical component of intelligent behavior. To study how sound cues are translated into anticipatory licking during classical appetitive conditioning, we employed high-density electrophysiological recordings from the hippocampal CA1 area and the prefrontal cortex (PFC). CA1 and PFC neurons undergo distinct learning dependent changes at the single cell level and maintain representations of cue identity during anticipatory behavior at the population level. In addition, reactivation of task-related neuronal assemblies during hippocampal awake Sharp-Wave Ripples (aSWR) changed within individual sessions in CA1 and over the course of multiple sessions in PFC. Despite both areas being highly engaged and synchronized during the task, we found no evidence for coordinated single cell or assembly activity during conditioning trials or aSWR.
A single heat-stress bout induces rapid and prolonged heat acclimation in the California mussel, Mytilus californianus

Climate change is not only causing steady increases in average global temperatures but also increasing the frequency with which extreme heating events occur. These extreme events may be pivotal in determining the ability of organisms to persist in their current habitats. Thus, it is important to understand how quickly an organism's heat tolerance can be gained and lost relative to the frequency with which extreme heating events occur in the field. We show that the California mussel, Mytilus californianus—a sessile intertidal species that experiences extreme temperature fluctuations and cannot behaviourally thermoregulate—can quickly (in 24–48 h) acquire improved heat tolerance after exposure to a single sublethal heat-stress bout (2 h at 30 or 35°C) and then maintain this improved tolerance for up to three weeks without further exposure to elevated temperatures. This adaptive response improved survival rates by approximately 75% under extreme heat-stress bouts (2 h at 40°C). To interpret these laboratory findings in an ecological context, we evaluated 4 years of mussel body temperatures recorded in the field. The majority (approx. 64%) of consecutive heat-stress bouts were separated by 24–48 h, but several consecutive heat bouts were separated by as much as 22 days. Thus, the ability of M. californianus to maintain improved heat tolerance for up to three weeks after a single sublethal heat-stress bout significantly improves their probability of survival, as approximately 33% of consecutive heat events are separated by 3–22 days. As a sessile animal, mussels likely evolved the capability to rapidly gain and slowly lose heat tolerance to survive the intermittent, and often unpredictable, heat events in the intertidal zone. This adaptive strategy will likely prove beneficial under the extreme heat events predicted with climate change.
African-Lineage Zika Virus Replication Dynamics and Maternal-Fetal Interface Infection in Pregnant Rhesus Macaques

ZIKV was first identified in 1947 in Africa, but most of our knowledge of ZIKV is based on studies of the distinct Asian genetic lineage, which caused the outbreak in the Americas in 2015 to 2016. In its most recent update, the WHO stated that improved understanding of African-lineage ZIKV pathogenesis during pregnancy must be a priority. ABSTRACT Following the Zika virus (ZIKV) outbreak in the Americas, ZIKV was causally associated with microcephaly and a range of neurological and developmental symptoms, termed congenital Zika syndrome (CZS). The viruses responsible for this outbreak belonged to the Asian lineage of ZIKV. However, in vitro and in vivo studies assessing the pathogenesis of African-lineage ZIKV demonstrated that African-lineage isolates often replicated to high titers and caused more-severe pathology than Asian-lineage isolates. To date, the pathogenesis of African-lineage ZIKV in a translational model, particularly during pregnancy, has not been rigorously characterized. Here, we infected four pregnant rhesus macaques with a low-passage-number strain of African-lineage ZIKV and compared its pathogenesis to those for a cohort of four pregnant rhesus macaques infected with an Asian-lineage isolate and a cohort of mock-inoculated controls. The viral replication kinetics for the two experimental groups were not significantly different, and both groups developed robust neutralizing antibody titers above levels considered to be protective. There was no evidence of significant fetal head growth restriction or gross fetal harm at delivery (1 to 1.5 weeks prior to full term) in either group. However, a significantly higher burden of ZIKV viral RNA (vRNA) was found in the maternal-fetal interface tissues of the macaques exposed to an African-lineage isolate. Our findings suggest that ZIKV of any genetic lineage poses a threat to pregnant individuals and their infants. IMPORTANCE ZIKV was first identified in 1947 in Africa, but most of our knowledge of ZIKV is based on studies of the distinct Asian genetic lineage, which caused the outbreak in the Americas in 2015 to 2016. In its most recent update, the WHO stated that improved understanding of African-lineage ZIKV pathogenesis during pregnancy must be a priority. The recent detection of African-lineage isolates in Brazil underscores the need to understand the impact of these viruses. Here, we provide the first comprehensive assessment of African-lineage ZIKV infection during pregnancy in a translational nonhuman primate model. We show that African-lineage isolates replicate with kinetics similar to those of Asian-lineage isolates and can infect the placenta. However, there was no evidence of more-severe outcomes with African-lineage isolates. Our results highlight both the threat that African-lineage ZIKV poses to pregnant individuals and their infants and the need for epidemiological and translational in vivo studies with African-lineage ZIKV.
Glycan-Protein Interactions Determine Kinetics of N-Glycan Remodeling

A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins. To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes. As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes. In addition, altering the tertiary structure context of N-glycan substrates affected N-glycan remodeling in a site-specific way. We propose that differential, tertiary structure context dependent N-glycan reactivities lead to different glycan structures in the same protein through kinetically controlled processing pathways.
Structural Spine Plasticity in Olfaction: Memory and Forgetting, Enhanced vs. Reduced Discriminability after Learning

How animals learn to discriminate between different sensory stimuli is an intriguing question. An important, common step towards discrimination is the enhancement of differences between the representations of relevant stimuli. This can be part of the learning process. In rodents, the olfac-tory bulb, which is known to contribute to this pattern separation, exhibits extensive structural synaptic plasticity even in adult animals: reciprocal connections between excitatory mitral cells and inhibitory granule cells are persistently formed and eliminated, correlated with mitral cell and granule cell activity. Here we present a Hebbian-type model for this plasticity. It captures the experimental observation that the same learning protocol that enhanced the discriminability of similar stimuli actually reduced that of dissimilar stimuli. The model predicts that the learned bulbar network structure is remembered across training with additional stimuli, unless the new stimuli interfere with the representations of previously learned ones.
Event-related potentials reveal limited readiness to access phonetic details during word processing in dogs

While dogs have remarkable abilities for social cognition and communication, the number of words they learn to recognize typically remains very low. The reason for this limited capacity is still unclear. We hypothesized that despite their human-like auditory abilities for analysing speech sounds, their word processing capacities might be less ready to access phonetic details. To test this, we developed procedures for non-invasive measurement of event-related potentials (ERPs) for language stimuli in awake dogs (n = 17). Dogs listened to familiar instruction words and phonetically similar and dissimilar nonsense words. We compared two different artefact cleaning procedures on the same data; they led to similar results. An early (200–300 ms; only after one of the cleaning procedures) and a late (650–800 ms; after both cleaning procedures) difference was present in the ERPs for known versus phonetically dissimilar nonsense words. There were no differences between the ERPs for known versus phonetically similar nonsense words. ERPs of dogs who heard the instructions more often also showed larger differences between instructions and dissimilar nonsense words. The study revealed not only dogs' sensitivity to known words, but also their limited capacity to access phonetic details. Future work should confirm the reported ERP correlates of word processing abilities in dogs.
Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models

The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of Topotecan (TPT), a FDA-approved Top1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as four days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of Top1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing Top1 inhibitors for COVID-19 in humans.
Consequences of human cytomegalovirus infection on small extracellular vesicles isolated from first trimester placental histocultures

Currently, research on the use of non-invasive biomarkers as diagnosis and prognosis tools during pathological pregnancies is in full development. Among these, the placenta-derived small extracellular vesicles (sEVs) are considered as serious candidates. As such, their composition is modified during many pregnancy pathologies and they can be easily purified from a simple blood sample, as they are found in maternal serum. In this study, we describe the isolation of sEVs from a histoculture model of first trimester placental explants. We characterized these sEVs by a combination of biochemical, bead-based multiplex cytometry and electron microscopy approaches and defined their associated markers and ultrastructure. We next examined the consequences for sEVs secretion and characteristics of placenta infection by the human cytomegalovirus. Under these conditions, the secretion and integrity of sEVs was preserved. However, an increase in the expression level of several surface markers was detected, opening up the prospect for the search for biomarkers predicting the severity and the outcome of this congenital infection early during the pregnancy, which are still sorely lacking.
Fossils improve phylogenetic analyses of morphological characters

Fossils provide our only direct window into evolutionary events in the distant past. Incorporating them into phylogenetic hypotheses of living clades can help elucidate macroevolutionary patterns and processes, such as ancestral states and diversification dynamics. However, the effect fossils have on phylogenetic inference from morphological data remains controversial. Previous studies have highlighted their strong impact on topologies inferred from empirical data, but have not demonstrated that they improve accuracy. The consequences of explicitly incorporating the stratigraphic ages of fossils using tip-dated inference are also unclear. Here we employ a simulation approach to explore how fossil sampling and missing data affect tree reconstruction across a range of inference methods. Our results show that fossil taxa improve phylogenetic analysis of morphological datasets, even when highly fragmentary. Irrespective of inference method, fossils improve the accuracy of phylogenies and increase the number of resolved nodes. They also induce the collapse of ancient and highly uncertain relationships that tend to be incorrectly resolved when sampling only extant taxa. Furthermore, tip-dated analyses which simultaneously infer tree topology and divergence times outperform all other methods of inference, demonstrating that the stratigraphic ages of fossils contain vital phylogenetic information. Fossils help to extract true phylogenetic signals from morphology, an effect that is mediated by both their unique morphology and their temporal information, and their incorporation in total-evidence phylogenetics is necessary to faithfully reconstruct evolutionary history.
A review of reaction rates and thermodynamic and transport properties for the 11-species air model for chemical and thermal nonequilibrium calculations to 30000 K

Reaction rate coefficients and thermodynamic and transport properties are reviewed and supplemented for the 11-species air model which can be used for analyzing flows in chemical and thermal nonequilibrium up to temperatures of 3000 K. Such flows will likely occur around currently planned and future hypersonic vehicles. Guidelines for determining the state of the surrounding environment are provided. Curve fits are given for the various species properties for their efficient computation in flowfield codes. Approximate and more exact formulas are provided for computing the properties of partially ionized air mixtures in a high energy environment. Limitations of the approximate mixing laws are discussed for a mixture of ionized species. An electron number-density correction for the transport properties of the charged species is obtained. This correction has been generally ignored in the literature.
ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation

Loss-of-function of ADAR1 causes the severe autoinflammatory disease Aicardi-Goutières Syndrome (AGS). ADAR1 converts adenosines into inosines within double-stranded (ds) RNA. This process called A-to-I editing masks self-dsRNA from detection by the antiviral dsRNA sensor MDA5. ADAR1 binds to dsRNA in both the canonical A-form and in the poorly defined Z-conformation (Z-RNA). Mutations in the Z-RNA binding Zα-domain of ADAR1 are common in AGS patients. How loss of ADAR1/Z-RNA interaction contributes to disease development is unknown. Using ADAR1 Zα-domain mutant human cells and knock-in mice, we demonstrate that abrogated binding of ADAR1 to Z-RNA leads to reduced A-to-I editing of dsRNA structures formed by pairing of inversely oriented SINEs. As a result, ADAR1 Zα-domain mutant human cells and transgenic mice develop a spontaneous MDA5-dependent immune response. This shows that the interaction between ADAR1 and Z-RNA restricts sensing of self-dsRNA and prevents AGS development.
Biocontrol in store: spatial and behavioural aspects of foraging by Uscana lariophaga, egg parasitoid of Callosobruchus maculatus, in stored cowpea

Cowpea ( Vigna unguiculata Walpers), an important crop for West African subsistence farmers, is often infested in storage by the bruchid beetle Callosobruchus maculatus Fabricius. The indigenous egg parasitoid Uscana lariophaga Steffan (Hym.: Trichogrammatidae) is responsible for substantial mortality of C. maculatus eggs and might therefore be used in a conservation strategy of biological control. This thesis focuses on foraging behaviour of U. lariophaga females in a spatial context. In stored cowpea, the bruchid oviposits in clusters. Uscana lariophaga is well adapted to such clusters, since it shows a strong arrestment response after an encounter with an unparasitized host. Previous investigations had already shown attraction of the parasitoid to host-related odours; it is now shown that directed search probably occurs at a short distance (4-6 beans) from the host patch. The probability that a host patch in stored cowpea is found decreases rapidly with increasing distance between the host patch and the site of release of the parasitoid. The 'critical distance' within which the host patch is quickly found by the parasitoid increases if more searching time is allowed. If an experienced parasitoid arrives in a host patch and encounters parasitized hosts, it is likely to superparasitize, but it will stop superparasitizing as soon as an unparasitized host has been encountered in the same patch. Superparasitism by experienced females is not due to failure in host discrimination, as appears from the fact that females adapt the sex ratio of their offspring during superparasitism. If no or few hosts are available, the parasitoid lives shorter than when many hosts are available. This reduced longevity at low host densities may be due to an increased walking activity at low host densities. Finally, the potential of a simulation model of U. lariophaga behaviour is shown, and consequences of behaviour for the prospects of biological control are discussed.
Quantitative electron microprobe mapping of otoliths suggests elemental incorporation is affected by organic matrices: implications for the interpretation of otolith chemistry

In an effort to understand the mechanism of otolith elemental incorporation, the distribution of strontium (Sr) and sulfur (S) in otoliths of Platycephalus bassensis was investigated in conjunction with otolith growth patterns. Optimisation of electron probe microanalysis (EPMA) quantitative mapping achieved both high spatial resolution (<3µm) and two-dimensional visualisation of the fine scale Sr and S distributions in otoliths of P. bassensis with minimal damage. Electron backscatter diffraction (EBSD) mapping confirmed that grain growth is aligned with the otolith c-axis, with grain orientation independent of both otolith elemental composition and growth patterns. Results showed a linear correlation between Sr and S distribution (R2=0.86), and a clear association with the otolith growth patterns determined by scanning electron microscopy. Further examination by laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) showed that incorporation of Mg and Ba appeared independent of both S distribution and the growth patterns. The results suggest that element incorporation into the otolith is linked to the organic composition in the endolymph during mineralisation, and the organic matrices may assist, in part, the uptake of Sr. Thus, these findings may have significant implications for the interpretation of otolith Sr chemistry.
Study of the mechanism of microwave-assisted extraction of Mahonia bealei (Fort.) leaves and Chrysanthemum morifolium (Ramat.) petals

A study of microwave-assisted extraction (MAE) for berberine in Mahonia bealei (Fort.) was carried out with batch equipment, in order to investigate the mechanism of the extraction related to structural changes in the glands. The extracts were analysed by ultraviolet-visible spectrophotometry at 347 nm. The parameters investigated were solvent types, the intensity of microwave energy and the process ratio (g/ml) of materials to solvent volume. The microwave-assisted extraction of different moisture content of materials was developed and optimized by means of three-factor and three-level orthogonal designs. Electron and optical micrographs of M. bealei (Fort.) leaves and Chrysanthemum morifolium (Ramat.) petals showed that the mechanism of the extractions was related to structural changes in the plant cells. Copyright © 2004 John Wiley & Sons, Ltd.