Miracle-dz/UniFAR-FTUs huggingface dataset:
CogVLM: Visual Expert for Pretrained Language Models

We introduce CogVLM, a powerful open-source visual language foundation model. Different from the popular shallow alignment method which maps image features into the input space of language model, CogVLM bridges the gap between the frozen pretrained language model and image encoder by a trainable visual expert module in the attention and FFN layers. As a result, CogVLM enables deep fusion of vision language features without sacrificing any performance on NLP tasks. CogVLM-17B achieves state-of-the-art performance on 10 classic cross-modal benchmarks, including NoCaps, Flicker30k captioning, RefCOCO, RefCOCO+, RefCOCOg, Visual7W, GQA, ScienceQA, VizWiz VQA and TDIUC, and ranks the 2nd on VQAv2, OKVQA, TextVQA, COCO captioning, etc., surpassing or matching PaLI-X 55B. Codes and checkpoints are available at https://github.com/THUDM/CogVLM.
Bias in MODIS cloud drop effective radius for oceanic water clouds as deduced from optical thickness variability across scattering angles

The Moderate Resolution Imaging Spectroradiometer (MODIS) represents our most advanced system for long‐term, global observations of cloud optical depth (τ) and cloud drop effective radius (Re). Here we show that the both zonal means of (1) MODIS‐retrieved τ and Re and (2) τ retrieved from the Multi‐angle Imaging Spectroradiometer (MISR) using MODIS‐retrieved Re as input exhibit a large, local negative bias in the rainbow scattering direction relative to adjacent scattering angles for oceanic water clouds. Using radiative transfer simulations, we demonstrate that these local biases are explained by overestimates in MODIS‐retrieved Re. While 3‐D factors on the angular variability of τ are evident, we conclude that a Re bias is itself an important contributor to this variability. With 3‐D factors present, we show that upper and lower bound estimates on the biases in the three MODIS Re products, namely Re1.6, Re2.1, and Re3.7 retrieved from 1.6, 2.1, and 3.7 µm channels, respectively, are possible from a combination of MISR and MODIS data. The midpoints of the upper and lower bounds in zonal mean biases are estimated to be 3–11 µm for Re2.1 and Re1.6 and 2–7 µm for Re3.7, depending on latitude, with smaller biases at latitudes where more stratiform clouds contribute to the total low cloud cover. Removing the bias from the zonal means reveals that Re1.6, Re2.1, and Re3.7 are more similar with each other compared to their original values. The change in zonal mean of Re as a function of latitude is also very different between original and bias‐corrected products. These differences change the interpretation of the vertical and horizontal distribution of Re from the original MODIS product.
Examination of the quantitative relationship between proteome- and transcriptome-level responses in larval guts of Frankliniella occidentalis infected with an orthotospovirus

The western flower thrips, Frankliniella occidentalis, is the principal thrips vector of Orthotospovirus tomatomaculae (order Bunyavirales, family Tospoviridae), a devastating plant-pathogenic virus commonly referred to as tomato spotted wilt virus (TSWV). The larval gut is the gateway for virus transmission by F. occidentalis adults to plants. In a previous report, gut expression at the transcriptome-level was subtle but significant in response to TSWV in L1s. Since it has been well documented that the relationship between the expression of mRNA and associated protein products in eukaryotic cells is often discordant, we performed identical, replicated experiments to identify and quantify virus-responsive larval gut proteins (427) to expand our understanding of insect host response to TSWV. While we documented statistically-significant, positive correlations between mRNA and protein abundance for genes (4,192) expressed in first and second instar guts, there was virtually no alignment of individual genes identified to be differentially modulated by virus infection at the transcriptome and proteome levels. Predicted protein-protein interaction networks associated with clusters of co-expressed proteins revealed wide variation in correlation strength between protein and cognate transcript abundance, which appeared to be associated with the type of cellular processes, cellular compartments, and network connectivity represented by the proteins. In total, our findings indicate distinct and dynamic regulatory mechanisms of transcript and protein abundance (expression, modifications, and/or turnover) in gut tissues regardless of virus-infection. This study provides molecular candidates for future functional analysis of thrips vector competence, and underscores the necessity of examining complex virus-vector interactions at a systems level.
Widespread changes in gene expression accompany body size evolution in nematodes

Body size is a fundamental trait that drives multiple evolutionary and ecological patterns. Caenorhabditis inopinata is a fig-associated nematode that is exceptionally large relative to other members of the genus, including C. elegans. We previously showed that C. inopinata is large primarily due to postembryonic cell size expansion that occurs during the larval-to-adult transition. Here, we describe gene expression patterns in C. elegans and C. inopinata throughout this developmental period to understand the transcriptional basis of body size change. We performed RNA-seq in both species across the L3, L4, and adult stages. Most genes are differentially expressed across all developmental stages, consistent with C. inopinata’s divergent ecology and morphology. We also used a model comparison approach to identify orthologs with divergent dynamics across this developmental period between the two species. This included genes connected to neurons, behavior, stress response, developmental timing, and small RNA/chromatin regulation. Multiple hypodermal collagens were also observed to harbor divergent developmental dynamics across this period, and genes important for molting and body morphology were also detected. Genes associated with TGF-β signaling revealed idiosyncratic and unexpected transcriptional patterns given their role in body size regulation in C. elegans. Widespread transcriptional divergence between these species is unexpected and may be a signature of the ecological and morphological divergence of C. inopinata. Alternatively, transcriptional turnover may be the rule in the Caenorhabditis genus, indicative of widespread developmental system drift among species. This work lays the foundation for future functional genetic studies interrogating the bases of body size evolution in this group.
Loss of Purkinje cells in the developing cerebellum strengthens the cerebellothalamic synapses

Cerebellar damage early in life often causes long-lasting motor, social, and cognitive impairments, suggesting the roles of the cerebellum in developing a broad spectrum of behaviors. This recent finding has promoted research on how cerebellar damage affects the development of the cerebral cortex, the brain region responsible for higher-order control of all behaviors. However, the cerebral cortex is not directly connected to the cerebellum. The thalamus is the direct postsynaptic target of the cerebellum, sending cerebellar outputs to the cerebral cortex. Despite its crucial position in cerebello-cerebral interaction, thalamic susceptibility to cerebellar damage remains largely unclear. Here, we studied the consequences of early cerebellar perturbation on thalamic development. Whole-cell patch-clamp recordings showed that the synaptic organization of the cerebellothlamic circuit is similar to that of the primary sensory thalamus, in which aberrant sensory activity alters synaptic circuit formation. The hemizygous deletion of the tuberous sclerosis complex-1 (Tsc1) gene in the Purkinje cell—known to cause Purkinje cell hypoactivity and autistic behaviors—did not alter cerebellothalamic synapses or intrinsic membrane properties of thalamic neurons. However, the ablation of Purkinje cells in the developing cerebellum strengthened the cerebellothalamic synapses and enhanced thalamic suprathreshold activities. These results suggest that the cerebellothalamic circuit is resistant to moderate perturbation in the developing cerebellum, such as the reduced firing rate of Purkinje cells, and that autistic behaviors are not necessarily linked to thalamic abnormality. Still, Purkinje cell loss alters the thalamic circuit, suggesting the vulnerability of the thalamus to substantial disturbance in the developing cerebellum.
Asymmetric roles for M2-M3 linkers of specific GABAA receptor subunits in the intrinsic closed-open equilibrium and its modulation by the benzodiazepine diazepam

GABAA receptors (GABAARs) are neurotransmitter-gated ion channels critical for inhibitory synaptic transmission as well as the molecular target for benzodiazepines (BZDs), one of the most widely prescribed class of psychotropic drugs today. Despite structural insight into the conformations underlying functional channel states, the detailed molecular interactions involved in conformational transitions and the physical basis for their modulation by BZDs are not fully understood. We previously identified that alanine substitution at the central residue in the α1 subunit M2-M3 linker (V279A) enhances the efficiency of linkage between the BZD site and the pore gate. Here, we expand on this work by investigating the effect of alanine substitutions at the analogous positions in the M2-M3 linkers of β2 (I275A) and γ2 (V290A) subunits, which together with α1 comprise typical heteromeric α1β2γ2 synaptic GABAARs. We find that these mutations confer subunit-specific effects on the intrinsic pore closed-open equilibrium and its modulation by the BZD diazepam (DZ). The mutations α1(V279A) or γ2(V290A) bias the channel toward a closed conformation, whereas β2(I275A) biases the channel toward an open conformation to the extent that the channel becomes leaky and opens spontaneously in the absence of agonist (e.g., GABA). In contrast, only α1(V279A) enhances the efficiency of DZ-to-pore linkage, whereas mutations in the other two subunits have no effect. These observations show that the central residue in the M2-M3 linkers of distinct subunits in synaptic α1β2γ2 GABAARs contribute asymmetrically to the intrinsic closed-open equilibrium and its modulation by DZ.
Proteomic evidence of astrocytic dysfunction in the olfactory bulb of depressed suicides

Brain regions involved in olfaction, including the olfactory bulb, have been implicated in the etiology of major depression mainly on the basis of rodent models of the illness. To explore more directly the molecular features of the olfactory bulb (OB) in major depression, a global comparative proteome analysis was carried out with human OB samples from 12 middle-aged male depressed suicides and 12 matched controls. Cases displayed a significant reduction in astrocytic proteins. Furthermore, using RNA-fluorescence in-situ hybridization, we observed a decrease in the percentage of ALDH1L1+ cells expressing canonical astrocytic markers including ALDOC, NFIA, GJA1 (connexin 43) and SLC1A3 (EAAT1). These results are consistent with previous reports of downregulated astrocytic marker expression in other brain regions in depressed suicides. We also conducted a comparative phosphoproteomic analysis of OB samples and found a dysregulation of proteins involved in neuronal and astrocytic functions. To determine whether OB astrocytic abnormalities can be observed in an animal model of depression, we also performed proteomics on the OB of socially defeated mice. Cell-type specific analysis revealed that in socially defeated animals, the most striking OB protein alterations were associated with oligodendrocyte-lineage cells rather than with astrocytes, highlighting an important species difference. Overall, this study further highlights cerebral astrocytic abnormalities as a consistent feature of depression and suicide in humans, and suggests that animal models of depression may not display all cellular and molecular features of depression, at least not in the OB.
Engineering microvascular networks using a KLF2 reporter to probe flow-dependent endothelial cell function

Shear stress generated by the flow of blood in the vasculature is a potent regulator of endothelial cell phenotype and vascular structure. While vascular responses to flow are complex and context-dependent, endothelial cell signaling in response to shear stress induced by laminar flows is coordinated by the transcription factor KLF2. The expression of KLF2 in endothelial cells is associated with a quiescent, anti-inflammatory phenotype and has been well characterized in two-dimensional systems, but has not been studied in three-dimensional in vitro systems. Here we develop engineered microvascular networks (MVNs) with a KLF2-based endothelial cell sensor within a microfluidic chip, apply continuous flow using an attached microfluidic pump, and study the effects of this flow on vascular structure and function. We found that culture of MVNs exposed to flow for 48 hours that resulted in increased expression of the KLF2-GFP-reporter display larger vessel diameters and decreased vascular branching and resistance. Additionally, vessel diameters after the application of flow were independent of initial MVN morphologies. Finally, we found that MVNs exposed to flow have improved vascular barrier function and decreased platelet adhesion. The MVNs with KLF2-based flow sensors represent a powerful tool for evaluating the structural and functional effects of flow on engineered three-dimensional vascular systems.
COMPARISON BETWEEN SANGER, ILLUMINA AND NANOPORE SEQUENCING EVIDENCING INTRA-HOST VARIATION OF FELINE LEUKEMIA VIRUS THAT INFECTS DOMESTIC CATS

Knowledge of Feline Leukemia Virus (FeLV) sequence variation has mainly been developed using Sanger sequencing methods. However, advances in next generation sequencing methods and their broad use in laboratories has been changing our understanding of viral genetics. FeLV sequencing has specific complications with the presence of both exogenous (exFeLV) and endogenous (enFeLV) virus with frequent recombination between them, limiting sequencing approaches. Here we report an FeLV-A and FeLV-B amplicon-based comparison between Sanger, Illumina, and Oxford Nanopore sequencing methods in Chilean domestic cats. We analysed the hypervariable envelope gene, where a higher number of variants as well as recombination with endogenous strains occurs. We detected multiple variants and viral quasispecies infecting the cats. We compared these three methods to evaluate the advantages and disadvantages between them. Although the Sanger method is highly reliable, it showed a high fail rate (many amplicons did not produce useable sequence) and the sequences obtained showed artificial sequence clustering when compared with the NGS methods. Illumina sequencing showed a lower error rate but could not discriminate between exogenous and endogenous viruses. Finally, Oxford Nanopore (MinION) sequencing could successfully detect low-abundance sequences and discriminate between FeLV-A and FeLV-B sequences, although its higher error-rate requires caution in interpretation of the results. Our results indicate advantages and disadvantages for each method, with the purpose of sequencing needing to be considered in the choice of method. Results of large viral phylogenetic trees combing sequences derived from mixed sequencing methods, such as those combining historical and contemporary sequencing need to be considered with some caution as artificial clustering by sequencing method may occur.
Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer disease

Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer Disease (AD). Given their essential role in neural communication, disruptions to these hubs have profound implications for overall brain network integrity and functionality. Hub disruption, or targeted impairment of functional connectivity at the hubs, is recognized in AD patients. Computational models paired with evidence from animal experiments hint at a mechanistic explanation, suggesting that these hubs may be preferentially targeted in neurodegeneration, due to their high neuronal activity levels—a phenomenon termed “activity-dependent degeneration”. Yet, two critical issues were unresolved. First, past research hasn’t definitively shown whether hub regions face a higher likelihood of impairment (targeted attack) compared to other regions or if impairment likelihood is uniformly distributed (random attack). Second, human studies offering support for activity-dependent explanations remain scarce. We applied a refined hub disruption index to determine the presence of targeted attacks in AD. Furthermore, we explored potential evidence for activity-dependent degeneration by evaluating if hub vulnerability is better explained by global connectivity or connectivity variations across functional systems, as well as comparing its timing relative to amyloid beta deposition in the brain. Our unique cohort of participants with autosomal dominant Alzheimer Disease (ADAD) allowed us to probe into the preclinical stages of AD to determine the hub disruption timeline in relation to expected symptom emergence. Our findings reveal a hub disruption pattern in ADAD aligned with targeted attacks, detectable even in pre-clinical stages. Notably, the disruption’s severity amplified alongside symptomatic progression. Moreover, since excessive local neuronal activity has been shown to increase amyloid deposition and high connectivity regions show high level of neuronal activity, our observation that hub disruption was primarily tied to regional differences in global connectivity and sequentially followed changes observed in Aβ PET cortical markers is consistent with the activity-dependent degeneration model. Intriguingly, these disruptions were discernible 8 years before the expected age of symptom onset. Taken together, our findings not only align with the targeted attack on hubs model but also suggest that activity-dependent degeneration might be the cause of hub vulnerability. This deepened understanding could be instrumental in refining diagnostic techniques and developing targeted therapeutic strategies for AD in the future.
Genes acquired by horizontal gene transfer share common regulatory proteins in Photorhabdus laumondii

Biosynthetic gene clusters are readily transferred between microbes through horizontal gene transfer, but to provide benefit to their host they must be induced to high levels during times of stress. Working with the insect pathogen Photorhabdus laumondii, here we study the effect of bacterial enhancer binding proteins (bEBPs) on natural product biosynthesis. We find that the AAA+ ATPase core of the Sinorhizobium meliloti bEBP DctD induces expression of five natural product classes in P. laumondii TTO1. Similar induction was also observed with truncated copies of bEBPs native to P. laumondii, revealing both repression and induction across six natural product classes. Overall, this indicates that bEBPs have the potential to regulate natural product biosynthesis in P. laumondii.
Stereo-anomaly is found more frequently in tasks that require discrimination between depths

Within the population of humans with otherwise normal vision, there exists some proportion whose ability to perceive depth from binocular disparity is poor or absent. The prevalence of this “stereoanomaly” has been investigated in previous studies, some finding the proportion to be as small as 2%, others finding it to be as great as 30%. In this study, we set out to investigate the possible reason for the wide range of results found in these studies. We used a digital stereoacuity measurement tool that could measure performance in tasks requiring either the detection of disparity or the discrimination of the sign of disparity. The stimulus design was otherwise similar between the two tasks. In a cohort of 228 participants, we found that 98% were able to consistently perform the detection task. In contrast, only 69% consistently performed the discrimination task. The 31% of participants who had difficulty with the discrimination task could further be divided into 17% who were consistently unable to perform the task (seeming to behave at chance), and 14% who showed some ability to perform the task. We propose that the greater prevalence of stereo-anomaly is revealed when tasks require the judgement of the direction of disparity.
Robust and Accurate Doublet Detection of Single-Cell Sequencing Data via Maximizing Area Under Precision-Recall Curve

Single-cell sequencing has revolutionized our understanding of cellular heterogeneity by offering detailed profiles of individual cells within diverse specimens. However, due to the limitations of sequencing technology, two or more cells may be captured in the same droplet and share the same barcode. These incidents, termed doublets or multiplets, can lead to artifacts in single-cell data analysis. While explicit experimental design can mitigate these issues with the help of auxiliary cell markers, computationally annotating doublets has a broad impact on analyzing the existing public single-cell data and reduces potential experimental costs. Considering that doublets form only a minor fraction of the total dataset, we argue that current doublet detection methods, primarily focused on optimizing classification accuracy, might be inefficient in performing well on the inherently imbalanced data in the area under the precision-recall curve (AUPRC) metric. To address this, we introduce RADO (Robust and Accurate DOublet detection) - an algorithm designed to annotate doublets by maximizing the AUPRC, effectively tackling the imbalance challenge. Benchmarked on 18 public datasets, RADO outperforms other methods in terms of doublet score and achieves similar performance to the current best methods in doublet calling. Furthermore, beyond its application in single-cell RNA-seq data, we demonstrate RADO’s adaptability to single-cell assays for transposase-accessible chromatin sequencing (scATAC-seq) data, where it outperforms other scATAC-seq doublet detection methods. RADO’s open-source implementation is available at: https://github.com/poseidonchan/RADO.
Climate-Change Driven Decline of an Insect Pathogen Increases the Risk of Defoliation by a Forest Pest Insect

The effects of climate change on forest-defoliating insects are poorly understood, a problem that is especially urgent in the case of the spongy moth (formerly “the gypsy moth”, Lymantria dispar). For decades following its introduction in 1869, the spongy moth severely defoliated North American forests, but the introduction of the pathogen Entomophaga maimaiga in 1989 drastically lowered defoliation levels. E. maimaiga, however, needs cool, moist conditions, whereas climate change is bringing hot, dry conditions to the range of the spongy moth. Here we use an empirically validated mathematical model to project that climate change will sharply reduce E. maimaiga infection rates, greatly increasing spongy moth defoliation. Recent data show that defoliation has strongly rebounded, supporting our projections. Our work shows that the effects of climate change on insect pathogens can have dire consequences for forests, and demonstrates the importance of understanding how climate change can alter species interactions.