Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,351 bioRxiv papers from 296,699 authors.
Most tweeted bioRxiv papers, last 7 days
554 results found. For more information, click each entry to expand.
1 tweet neuroscience
Ruiyao Cai, Chenchen Pan, Alireza Ghasemigharagoz, Mihail I. Todorov, Benjamin Förstera, Shan Zhao, Harsharan S. Bhatia, Leander Mrowka, Delphine Theodorou, Markus Rempfler, Anna Xavier, Benjamin T. Kress, Corinne Benakis, Arthur Liesz, Bjoern Menze, Martin Kerschensteiner, Maiken Nedergaard, Ali Ertürk
Analysis of entire transparent rodent bodies could provide holistic information on biological systems in health and disease. However, it has been challenging to reliably image and quantify signal from endogenously expressed fluorescent proteins in large cleared mouse bodies due to the low signal contrast. Here, we devised a pressure driven, nanobody based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image subcellular details in transparent mouse bodies through bones and highly autofluorescent tissues, and perform quantifications. We visualized for the first-time whole-body neuronal connectivity of an entire adult mouse and discovered that brain trauma induces degeneration of peripheral axons. We also imaged meningeal lymphatic vessels and immune cells through the intact skull and vertebra in naive animals and trauma models. Thus, our new approach can provide an unbiased holistic view of biological events affecting the nervous system and the rest of the body.
1 tweet genetics
Iosif Lazaridis, Dani Nadel, Gary Rollefson, Deborah C Merrett, Nadin Rohland, Swapan Mallick, Daniel Fernandes, Mario Novak, Beatriz Gamarra, Kendra Sirak, Sarah Connell, Kristin Stewardson, Eadaoin Harney, Qiaomei Fu, Gloria Gonzalez-Fortes, Songül Alpaslan Roodenberg, György Lengyel, Fanny Bocquentin, Boris Gasparian, Janet M. Monge, Michael Gregg, Vered Eshed, Ahuva-Sivan Mizrahi, Christopher Meiklejohn, Fokke Gerritsen, Luminita Bejenaru, Matthias Blueher, Archie Campbell, Gianpero Cavalleri, David Comas, Philippe Froguel, Edmund Gilbert, Shona M. Kerr, Peter Kovacs, Johannes Krause, Darren McGettigan, Michael Merrigan, D. Andrew Merriwether, Seamus O’Reilly, Martin B. Richards, Ornella Semino, Michel Shamoon-Pour, Gheorghe Stefanescu, Michael Stumvoll, Anke Tönjes, Antonio Torroni, James F Wilson, Loic Yengo, Nelli A. Hovhannisyan, Nick Patterson, Ron Pinhasi, David Reich
We report genome-wide ancient DNA from 44 ancient Near Easterners ranging in time between ~12,000-1,400 BCE, from Natufian hunter-gatherers to Bronze Age farmers. We show that the earliest populations of the Near East derived around half their ancestry from a 'Basal Eurasian' lineage that had little if any Neanderthal admixture and that separated from other non-African lineages prior to their separation from each other. The first farmers of the southern Levant (Israel and Jordan) and Zagros Mountains (Iran) were strongly genetically differentiated, and each descended from local hunter-gatherers. By the time of the Bronze Age, these two populations and Anatolian-related farmers had mixed with each other and with the hunter-gatherers of Europe to drastically reduce genetic differentiation. The impact of the Near Eastern farmers extended beyond the Near East: farmers related to those of Anatolia spread westward into Europe; farmers related to those of the Levant spread southward into East Africa; farmers related to those from Iran spread northward into the Eurasian steppe; and people related to both the early farmers of Iran and to the pastoralists of the Eurasian steppe spread eastward into South Asia.
1 tweet genomics
Empathy is the ability to recognize and respond to the emotional states of other individuals. It is an important psychological process that facilitates navigating social interactions and maintaining relationships, which are important for wellbeing. Several psychological studies have identified difficulties in both self-report and performance-based measures of empathy in a range of psychiatric conditions. To date, no study has systematically investigated the genetic architecture of empathy using genome-wide association studies (GWAS). Here we report the results of the largest GWAS of empathy to date using a well-validated self-report measure of empathy, the Empathy Quotient (EQ), in 46,861 research participants from 23andMe, Inc. We identify 11 suggestive loci (P < 1x10-6), though none were significant at P < 2.5x10-8 after correcting for multiple testing. The most significant SNP was identified in the non-stratified analysis (rs4882760; P = 4.29x10-8), and is an intronic SNP in TMEM132C. The EQ had a modest but significant narrow-sense heritability (0.11 se = 0.014; P = 1.7x10-14). As predicted, based on earlier work, we confirmed a significant female-advantage on the EQ (P < 2x10-16 Cohens d = 0.65). We identified similar SNP heritability and high genetic correlation between the sexes. Also, as predicted, we identified a significant negative genetic correlation between autism and the EQ (rg = -0.27, se = 0.07, P = 1.63x10-4). We also identified a significant positive genetic correlation between the EQ and risk for schizophrenia (rg = 0.19, se = 0.04; P= 1.36x10-5), risk for anorexia nervosa (rg = 0.32, se =0.09; P = 6x10-4), and extraversion (rg = 0.45, se = 0.08; 5.7x10-8). This is the first GWAS of self-reported empathy. The results suggest that the genetic variations associated with empathy also play a role in psychiatric conditions and psychological traits.
1 tweet genomics
Predicting how transcription factors (TFs) interpret regulatory sequences to control gene expression remains a major challenge. Past studies have primarily focused on native or engineered sequences, and thus remained limited in scale. Here, we use random sequences as an alternative, measuring the expression output of over 100 million synthetic yeast promoters comprised of random DNA. Random sequences yield a broad range of reproducible expression levels, indicating that the fortuitous binding sites in random DNA are functional. From these data we learn models of transcriptional regulation that explain over 94% of expression variation of test data, recapitulate the organization of native chromatin in yeast, characterize the activity of TFs, and help refine cis-regulatory motifs. We find that strand, position, and helical face preferences of TFs are widespread and depend on interactions with neighboring chromatin. Such high-throughput regulatory assays of random DNA provide the large-scale data necessary to learn complex models of cis-regulatory logic.
1 tweet genomics
Although the molecular events required for the repair of double-strand breaks (DSB) have been well characterized, the role of epigenetic processes in the recognition and repair of DSBs has only been investigated at low resolution. We rapidly and synchronously induced a site-specific DSB in Saccharomyces cerevisiae upstream of the PHO5 locus, which has well-positioned nucleosomes. Utilizing MNase-seq epigenome mapping we interrogated the order of chromatin changes that occur immediately following a DSB by generating a base-pair resolution map of the chromatin landscape. In wild type cells, the first nucleosome left of the break was rapidly evicted. The eviction of this flanking nucleosome was dynamic and proceeded through an early intermediate chromatin structure where the nucleosome was repositioned in the adjacent linker DNA. Other nucleosomes bordering both sides of the break were also shifted away from the break; however, their loss was more gradual. These local changes preceded a broader loss of nucleosome eviction that was marked by increased MNase sensitivity in the regions ~8 kb on each side of the break, while the positioning of nucleosomes on the remaining unbroken chromosomes was largely unchanged. The broad loss of chromatin organization around the DSB was dependent on the end-processing complex, Mre11-Rad50-Xrs2 (MRX), but the early remodeling and repositioning of the nucleosome adjacent to the break was independent of the MRX and YKU70/80 complexes. We also examined the temporal dynamics of NHEJ-mediated repair in a G1-arrested population, where 5' to 3' end-resection of DSB ends is blocked. Concomitant with DSB repair, we observed the re-deposition and precise re-positioning of nucleosomes at the originally-occupied positions. This re-establishment of the pre-lesion chromatin landscape suggests that a DNA replication-independent mechanism exists in G1 cells to preserve epigenome organization following DSB repair.
1 tweet bioinformatics
In http://dx.doi.org/10.1101/079087, we presented adaptive models for calling somatic mutations in high-throughput sequencing data. These models were developed by training deep neural networks with semi-simulated data. In this continuation, I evaluate how such models can predict known somatic mutations in a real dataset. To address this question, I tested the approach using samples from the International Cancer Genome Consortium (ICGC) and the previously published ground-truth mutations (GoldSet). This evaluation revealed that training models with semi-simulation does produce models that exhibit strong performance in real datasets. I found a linear relationship between the performance observed on a semi-simulated validation set and independent ground-truth in the gold set (r^2=0.952, P<2-16). I also found that semi-simulation can be used to pre-train models before continuing training with true labels and that this pre-training improves model performance substantially on the real dataset compared to training models only with the real dataset. The best model pre-trained with semi-simulation achieved an AUC of 0.969 [0.957-0.982] (95% confidence interval) compared to 0.911 [0.890-0.932] when training with real labels only. These data demonstrate that semi-simulation can be a very effective approach to training filtering and ranking probabilistic models.
1 tweet bioinformatics
We have developed Ludicrous Speed Linear Mixed Models, a version of FaST-LMM optimized for the cloud. The approach can perform a genome-wide association analysis on a dataset of one million SNPs across one million individuals at a cost of about 868 CPU days with an elapsed time on the order of two weeks. A Python implementation is available at <https://fastlmm.github.io/>. Significance Identifying SNP-phenotype correlations using GWAS is difficult because effect sizes are so small for common, complex diseases. To address this issue, institutions are creating extremely large cohorts with sample sizes on the order of one million. Unfortunately, such cohorts are likely to contain confounding factors such as population structure and family/cryptic relatedness. The linear mixed model (LMM) can often correct for such confounding factors, but is too slow to use even with algebraic speedups known as FaST-LMM. We present a cloud implementation of FaST-LMM, called Ludicrous Speed LMM, that can process one million samples and one million test SNPs in a reasonable amount of time and at a reasonable cost.
1 tweet cell biology
Emerging evidence supports the hypothesis that pathogenic protein aggregates associated with many neurodegenerative diseases spread from cell to cell through the brain in a manner akin to infectious prions. Here, we show that mutant huntingtin (mHtt) aggregates associated with Huntington disease transfer anterogradely from presynaptic to postsynaptic neurons in the adult Drosophila olfactory system. Trans-synaptic transmission of mHtt aggregates is inversely correlated with neuronal activity and blocked by caspase inhibition in presynaptic neurons, implicating synaptic dysfunction and cell death in aggregate spreading. Remarkably, mHtt aggregate transmission across synapses requires the scavenger receptor Draper and involves a transient visit to the glial cytoplasm, indicating that phagocytic glia act as obligatory intermediates in aggregate spreading between synaptically-connected neurons. These findings expand our understanding of phagocytic glia as double-edged players in neurodegeneration—they clear neurotoxic protein aggregates, but also provide opportunities for prion-like seeds to evade phagolysosomal degradation and propagate further in the brain.
1 tweet cancer biology
The denitrosylating enzyme S-nitrosoglutathione reductase (GSNOR), has been reported to control the selective degradation of mitochondria through mitophagy, by modulating the extent of nitric oxide-modified proteins (S-nitrosylation). The accumulation of S-nitrosylated proteins due to GSNOR downregulation is a feature of hepatocellular carcinoma, causing mitochondrial defects that sensitize these tumors to mitochondrial toxins, in particular to mitochondrial complex II inhibitor alpha-tocopheryl succinate, αTOS). However, it is not known if mitophagy defects contribute to GSNOR-deficient cancer cells sensitivity to αTOS, nor if mitophagy inhibition could be used as a common mechanism to sensitize liver cancers to this toxin. Here, we provide evidence that GSNOR-deficient cancer cells show defective mitophagy. Furthermore, we show that αTOS is a mitophagy inducer and that mitophagy defects of GSNOR-deficient liver cancer cells contribute to its toxicity. We finally prove that the inhibition of mitophagy by depletion of Parkin, a pivotal ubiquitin ligase targeting mitochondria for degradation, enhances αTOS toxicity, thus suggesting that this drug could be effective in treating mitophagy-defective tumors.
1 tweet genomics
Background: Recent advances in genomics have addressed the challenge that divergent haplotypes pose to the reconstruction of haploid genomes. However for many organisms, the sequencing of either field-caught individuals or a pool of heterogeneous individuals is still the only practical option. Here we present methodological approaches to achieve three outcomes from pooled long read sequencing: the generation of a contiguous haploid reference sequence, the sequences of heterozygous haplotypes; and reconstructed genomic sequences of individuals related to the pooled material. Results: PacBio long read sequencing, Dovetail Hi-C scaffolding and linkage map integration yielded a haploid chromosome-level assembly for the diamondback moth (Plutella xylostella), a global pest of Brassica crops, from a pool of related individuals. The final assembly consisted of 573 scaffolds, with a total assembly size of 343.6Mbp a scaffold N50 value of 11.3Mbp (limited by chromosome size) and a maximum scaffold size of 14.4Mbp. This assembly was then integrated with an existing RAD-seq linkage map, anchoring 95% of the assembled sequence to defined chromosomal positions. Conclusions: We describe an approach to resolve divergent haplotype sequences and describe multiple validation approaches. We also reconstruct individual genomes from pooled long-reads, by applying a recently developed k-mer binning method.
1 tweet microbiology
Toxoplasma gondii is a ubiquitous, intracellular protozoan that extensively modifies infected host cells through secreted effector proteins. Many such effectors must be translocated across the parasitophorous vacuole (PV) in which the parasites replicate, ultimately ending up in the host cytosol or nucleus. This translocation has previously been shown to be dependent on five parasite proteins: MYR1, MYR2, MYR3, ROP17, and ASP5. We report here the identification of several MYR1-interacting and novel PV-localized proteins via affinity purification of MYR1, including TGGT1\_211460 (dubbed MYR4), TGGT1\_204340 (dubbed GRA54) and TGGT1_270320 (PPM3C). Further, we show that three of the MYR1-interacting proteins, GRA44, GRA45, and MYR4, are essential for the translocation of the Toxoplasma effector protein GRA16, and for the upregulation of human c-Myc and cyclin E1 in infected cells. GRA44 and GRA45 contain ASP5-processing motifs, but like MYR1, processing at these sites appears to be nonessential for their role in protein translocation. These results expand our understanding of the mechanism of effector translocation in Toxoplasma and indicate that the process is highly complex and dependent on at least eight discrete proteins.
1 tweet neuroscience
Objectives: Aberrant cortical development, inferred from cortical folding measures, is linked to the risk of schizophrenia. Cortical folds develop in a time-locked fashion during fetal growth. We leveraged this temporal specificity of sulcation to investigate the approximate timing of the prenatal insult linked to schizophrenia as well as the cognitive impairment seen in this illness. Methods: Anatomical T1 MRI scans from a publicly available dataset of 68 patients with schizophrenia and 72 controls were used to evaluate the sulcal depth. 5 major primary sulci that are invariable, representing lobar development (calcarine sulcus, superior temporal sulcus, superior frontal sulcus, intraparietal sulcus and inferior frontal sulcus) with formation representing distinct developmental periods were chosen. Sulcal depth was measured using BrainVISA software. Results: A repeated measure Analysis of Variance with 5 sulci and 2 hemispheres as within-subject factors and gender, age and intracranial volume as covariates revealed a significant effect of diagnosis (F[1,134]=14.8, p=0.0002). Control subjects had had deeper superior temporal (left t=3.2, p=0.002; right t=2.8, p=0.006), right inferior frontal (t=2.7, p=0.007) and left calcarine (t=2.2, p=0.03) sulci. A deeper superior frontal sulcus predicted better overall cognitive scores (F[1,54]=8.7, p=0.005) among patients. Conclusion: Our results suggest that the gestational cortical disruption underlying schizophrenia is likely to predate, if not, coincide with the appearance of calcarine sulcus (early 2nd trimester) and affects frontal, temporal and occipital lobes. Nevertheless, the burden of cognitive deficits may relate specifically to aberrant superior frontal development occurring in late 2nd trimester.
1 tweet microbiology
Brigitta Marcella Laksono, Paola Fortugno, Bernadien Maartje Nijmeijer, Rory Dylan de Vries, Sonia Cordisco, Stefan van Nieuwkoop, Thijs Kuiken, Theunis B.H. Geijtenbeek, W. Paul Duprex, Francesco Brancati, Rik L. de Swart
Measles is characterised by fever and a maculopapular skin rash, which is associated with immune clearance of measles virus (MV)-infected cells. Histopathological analyses of skin biopsies from humans and non-human primates (NHPs) with measles rash have identified MV-infected keratinocytes and mononuclear cells in the epidermis, around hair follicles and near sebaceous glands. Here, we address the pathogenesis of measles skin rash by combining data from experimentally infected NHPs, ex vivo infection of human skin sheets and in vitro infection of primary human keratinocytes. Longitudinal analysis of the skin of experimentally MV-infected NHPs demonstrated that infection in the skin precedes onset of rash by several days. MV infection was initiated in lymphoid and myeloid cells in the dermis before dissemination to the epidermal keratinocytes. These data were in good concordance with ex vivo MV infections of human skin sheets, in which dermal cells were more targeted than the epidermal ones. To address viral dissemination to the epidermis and to determine whether the dissemination is receptor-dependent, we performed experimental infections of primary keratinocytes collected from healthy or nectin-4-deficient donors. These experiments demonstrated that MV infection of keratinocytes is nectin-4-dependent, and nectin-4 expression was higher in differentiated than in proliferating keratinocytes. Based on these data, we hypothesise that measles skin rash is initiated by migrating MV-infected lymphocytes that infect dermal skin-resident CD150+ immune cells. The infection is subsequently disseminated from the dermal papillae to nectin-4+ keratinocytes in the basal epidermis. Lateral spread of MV infection is observed in the superficial epidermis, most likely due to the higher level of nectin-4 expression on differentiated keratinocytes. Finally, MV-infected cells are cleared by infiltrating immune cells, causing hyperaemia and oedema, which give the appearance of morbilliform skin rash.
1 tweet microbiology
HBV chronic infection is a critical risk factor for hepatocellular carcinoma. Although debated, the absence of innate immune response to HBV infection in hepatocytes is becoming the current view. However the underlying reasons are poorly understood. This study aims to define potential viral pathogen-associated molecular patterns (PAMPs) and the pattern recognition receptors (PRRs), and to elucidate whether HBV counteracts the innate pathways. The innate immune response to HBV infection was monitored by interferon-stimulated gene 54 (ISG54) mRNA, a direct downstream transcriptional target of Interferon Regulatory Factor 3 (IRF3), or IRF3 phosphorylation. The immunostimulatory potential of naked HBV DNAs or RNAs and the respective PRRs were determined upon viral nucleic acid transfection in immunocompetent cells including knockout cells lacking key molecules of innate pathways. The expression and functionality of DNA and RNA sensing pathways in primary human hepatocytes (PHH) were assessed. The inhibition of the DNA-sensing pathway by HBV was tested using IRF3 nuclear translocation assay. Our study revealed that HBV infection does not induce an innate response in infected hepatocytes, even in absence of HBV X protein. HBV relaxed-circular DNA (rcDNA) and DNA replication intermediates, but not HBV RNAs, are immunostimulatory and sensed by Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase (cGAS) and Stimulator of Interferon Genes (STING). Although PHH express DNA sensors to reduced levels compared to myeloid cells, they can respond to naked HBV rcDNA. However, we show that the absence of innate response to HBV infection in hepatocytes is not due to an active inhibition of the DNA sensing pathway by the virus. HBV passively evades the innate immune response in infected hepatocytes by (i) producing non-immunostimulatory RNAs, (ii) avoiding sensing of its DNAs by cGAS/STING without active inhibition of the pathway, possibly through shielding of the viral DNAs by the capsid.
1 tweet animal behavior and cognition
In mammals, goal-directed and planning processes support flexible behaviour usable to face new situations or changed conditions that cannot be tackled through more efficient but rigid habitual behaviours. Within the Bayesian modelling approach of brain and behaviour, probabilistic models have been proposed to perform planning as a probabilistic inference. Recently, some models have started to face the important challenge met by this approach: grounding such processes on the computations implemented by brain spiking networks. Here we propose a model of goal-directed behaviour that has a probabilistic interpretation and is centred on a recurrent spiking neural network representing the world model. The model, building on previous proposals on spiking neurons and plasticity rules having a probabilistic interpretation, presents these novelties at the system level: (a) the world model is learnt in parallel with its use for planning, and an arbitration mechanism decides when to exploit the world-model knowledge with planning, or to explore, on the basis of an entropy-based confidence on the world model knowledge; (b) the world model is a hidden Markov model (HMM) able to simulate sequences of states and actions, thus planning selects actions through the same neural generative process used to predict states; (c) the world model learns the hidden causes of observations, and their temporal dependencies, through a biologically plausible unsupervised learning mechanism. The model is tested with a visuomotor learning task and validated by comparing its behaviour with the performance and reaction times of human participants solving the same task. The model represents a further step towards the construction of an autonomous architecture bridging goal-directed behaviour as probabilistic inference to brain-like computations.
1 tweet neuroscience
When the two eyes are presented with incompatible images, the visual system fails to create a single, fused, coherent percept. Instead, it creates an ongoing alternation between each eye's image; a phenomenon dubbed binocular rivalry (BR). Such alternations in awareness are separated by brief, intermediate states during which a spatially mixed (incoherent) pattern of both images is perceived. A recent study proposed that the precedence of mixed percepts positively correlates with the degree of adaptation to conflict between the eyes. However, it neglected the role of visual transients, which covaried with the degree of conflict in the stimulus design. We here study whether the presence of visual transients drive adaptation to interocular conflict and explain incidence rates of spatially incoherent BR. Across three experiments we created several adaptation conditions in which we systematically varied the frequency of transients and the degree of conflict between the eyes . Transients consisted of grating orientation reversals, blanks, and plaids. The results showed that the pattern of variations in the fractions mixed percepts across conditions was best explained by variations in the frequency of visual transients, rather than the degree of conflict between the eyes. We propose that the prolonged presentation of transients to both eyes evokes a chain of events consisting of (1) the exogenous allocation of attention to both images, (2) the increase in perceptual dominance of both rivalling images, (3) the speed up of adaptation of interocular suppression, and eventually (4) the facilitation of mixed perception during BR after adaptation.
1 tweet microbiology
Murilo Sena Amaral, Ernesto Goulart, Luiz Carlos Caires-Júnior, David Abraham Morales-Vicente, Alessandra Soares-Schanoski, Roselane Paiva Gomes, Giovanna Gonçalves de Oliveira Olberg, Renato Mancini Astray, Jorge E. Kalil, Mayana Zatz, Sergio Verjovski-Almeida
Zika virus (ZIKV) causes congenital Zika syndrome (CZS), which is characterized by fetal demise, microcephaly and other abnormalities. ZIKV in the pregnant woman circulation must cross the placental barrier that includes fetal endothelial cells and trophoblasts, in order to reach the fetus. CZS occurs in ∼1-40% of cases of pregnant women infected by ZIKV, suggesting that mothers’ infection by ZIKV during pregnancy is not deterministic for CZS phenotype in the fetus. Therefore, other susceptibility factors might be involved, including the host genetic background. We have previously shown that in three pairs of dizygotic twins discordant for CZS, neural progenitor cells (NPCs) from the CZS-affected twins presented differential in vitro ZIKV susceptibility compared with NPCs from the non-affected. Here, we analyzed human-induced-pluripotent-stem-cell-derived (hiPSC-derived) trophoblasts from these twins and compared by RNA-Seq the trophoblasts from CZS-affected and non-affected twins. Following in vitro exposure to a Brazilian ZIKV strain (ZIKVBR), trophoblasts from CZS-affected twins were significantly more susceptible to ZIKVBR infection when compared with trophoblasts from the non-affected. Transcriptome profiling revealed no differences in gene expression levels of ZIKV candidate attachment factors, IFN receptors and IFN in the trophoblasts, either before or after ZIKVBR infection. Most importantly, ZIKVBR infection caused, only in the trophoblasts from CZS-affected twins, the downregulation of genes related to extracellular matrix organization and to leukocyte activation, which are important for trophoblast adhesion and immune response activation. In addition, only trophoblasts from non-affected twins secreted significantly increased amounts of chemokines RANTES/CCL5 and IP10 after infection with ZIKVBR. Overall, our results showed that trophoblasts from non-affected twins have the ability to more efficiently activate genes that are known to play important roles in cell adhesion and in triggering the immune response to ZIKV infection in the placenta, and this may contribute to predict protection from ZIKV dissemination into fetuses’ tissues. Author summary The Zika virus (ZIKV) infection in adults is usually characterized by mild flu-like symptoms, with most cases remaining asymptomatic. However, in the last years, widespread ZIKV infection was shown for the first time to be associated with congenital Zika syndrome (CZS) and death of neonates. CZS is a very debilitating condition that includes microcephaly and mental retardation, leading to a strong social and health impact. This dramatic condition calls for a careful evaluation of the molecular mechanisms involved in ZIKV infection in the maternal-fetal interface. It is estimated that CZS occurs in ∼1-40% of cases of pregnant women infected by ZIKV, which suggests that different susceptibility factors might be involved, including the host genetic background. By analyzing trophoblast cells that recapitulate the placenta from three pairs of dizygotic twins discordant for CZS, we were able to show that trophoblasts from CZS-affected twins were significantly more susceptible to ZIKV infection when compared with trophoblasts from the non-affected twins. We also provide a detailed picture of genes differentially expressed by trophoblasts from the discordant twins after infection with ZIKV. These genes can be further investigated as possible therapeutic targets to avoid viral dissemination into developing fetus’ tissues.
1 tweet microbiology
Shigella species are specialised lineages of Escherichia coli that have converged to become human-adapted and cause dysentery by invading human gut epithelial cells. Most studies of Shigella evolution have been restricted to comparisons of single representatives of each species; and population genomic studies of individual Shigella species have focused on genomic variation caused by single nucleotide variants and ignored the contribution of insertion sequences (IS) which are highly prevalent in Shigella genomes. Here, we investigate the distribution and evolutionary dynamics of IS within populations of Shigella dysenteriae Sd1, Shigella sonnei and Shigella flexneri. We find that five IS (IS1, IS2, IS4, IS600 and IS911) have undergone expansion in all Shigella species, creating substantial strain-to-strain variation within each population and contributing to convergent patterns of functional gene loss within and between species. We find that IS expansion and genome degradation are most advanced in S. dysenteriae and least advanced in S. sonnei; and using genome-scale models of metabolism we show that Shigella species display convergent loss of core E. coli metabolic capabilities, with S. sonnei and S. flexneri following a similar trajectory of metabolic streamlining to that of S. dysenteriae. This study highlights the importance of IS to the evolution of Shigella and provides a framework for the investigation of IS dynamics and metabolic reduction in other bacterial species.
1 tweet neuroscience
Zaixu Cui, Hongming Li, Cedric H Xia, Bart Larsen, Azeez Adebimpe, Graham L Baum, Matt Cieslak, Raquel E Gur, Ruben C Gur, Tyler M Moore, Desmond J Oathes, Aaron Alexander-Bloch, Armin Raznahan, David R. Roalf, Russell T Shinohara, Daniel H Wolf, Christos Davatzikos, Danielle S. Bassett, Damien A. Fair, Yong Fan, Theodore D Satterthwaite
The spatial distribution of large-scale functional networks on the anatomic cortex differs between individuals, and is particularly variable in networks responsible for executive function. However, it remains unknown how this functional topography evolves in development and supports cognition. Capitalizing upon advances in machine learning and a large sample of youth (n=693, ages 8-23y) imaged with 27 minutes of high-quality fMRI data, we delineate how functional topography evolves during youth. We found that the functional topography of association networks is refined with age, allowing accurate prediction of an unseen individual's brain maturity. Furthermore, the cortical representation of executive networks predicts individual differences in executive function. Finally, variability of functional topography is associated with fundamental properties of brain organization including evolutionary expansion, cortical myelination, and cerebral blood flow. Our results emphasize the importance of considering both the plasticity and diversity of functional neuroanatomy during development, and suggest advances in personalized therapeutics.
1 tweet neuroscience
Resting-state functional brain networks demonstrate dynamic changes on the scale of seconds. However, their genetic mechanisms and profound cognitive relevance remain less explored. We identified 459 Bonferroni-corrected genes, by associating temporal variability of regional functional connectivity patterns with Allen Brain gene expression profiles across the whole brain. These genes are partially verified in developing human brain gene expression in the BrainSpan Atlas, and are found to be involved in the enrichment of short- and long-term plasticity processes. The former process depends on synaptic plasticity, involving ion transmembrane transport, action potential propagation, and modulation. The latter process depends on structural plasticity, including axonal genesis, development, and guidance. Results from a longitudinal cognitive training study further revealed that baseline variability of the hippocampal network predicted cognitive ability changes after three months of training. Our genetic association results suggest that the short-term plasticity processes may account for the rapid changes of regional functional connectivity, while the underlying long-term plasticity processes explain why temporal variability can predict long-term learning outcomes. To our knowledge, this is the first demonstration that measuring the dynamic brain network can lead to a non-invasive quantification of neuroplasticity in humans.
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