Miracle-dz/UniFAR-FTUs huggingface dataset:
Unsupervised cell interaction profiling reveals major architectural differences between small intestinal and colonic epithelial crypts

Cellular identity in complex multicellular organisms is strictly maintained over the course of life. This control is achieved in part by the organ structure itself, such that neighboring cells influence each other’s identity. However, large-scale investigation of the cellular interactome has been technically challenging. Here, we develop CIM-seq, an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between every cell type in a given tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution of these into their constituent cell types using machine learning. We use CIM-seq to define the cell interaction landscape of the mouse small intestinal and colonic epithelium, uncovering both known and novel interactions. Specifically, we find that the general architecture of the stem cell niche is radically different between the two tissues. In small intestine, the stem-Paneth cell interaction forms an exceptionally strong and exclusive niche, in which Paneth cells provide Wnt ligands1. In colonic epithelium, no similar compartment exists to support stem cells, and Wnt signaling is provided by a mesenchymal cell layer2,3. However, colonic stem cells are supported by an adjacent, previously unrecognized goblet cell subtype expressing the wound-healing marker Plet1, which is also highly upregulated during regeneration of colon epithelium. These results identify novel cellular interactions specific for the colonic stem cell niche and suggest an additional level of structural control in the colon. CIM-seq is broadly applicable to studies that aim to simultaneously investigate the constituent cell types and the global interaction profile in a specific tissue.
High-throughput mapping of long-range neuronal projection using in situ sequencing

Understanding neural circuits requires deciphering the interactions of myriad cell types defined by connectivity, spatial organization, gene expression, and other properties. Resolving these cell types requires both single neuron resolution and high throughput, a combination that is challenging to achieve with conventional anatomical methods. Here we introduce BARseq, a method for mapping the projections of thousands of spatially resolved neurons by RNA barcoding. We used BARseq to determine the projections of 1309 neurons in mouse auditory cortex to 11 targets. We observed 264 distinct projection patterns. Hierarchical clustering confirmed the major classical classes of projection neurons, as well as further subdivisions within each class. We further combined BARseq with in situ detection of mRNA to relate neuronal gene expression with projections. By bridging high-throughput neuroanatomy with high spatial resolution, BARseq provides a path towards a systematic multi-modal description of the nervous system.
The mechanisms of gene regulatory networks constrain evolution: A lesson from synthetic circuits

Phenotypic variation is the raw material of adaptive Darwinian evolution. The phenotypic variation found in organismal development is biased towards certain phenotypes, but the molecular mechanisms behind such restrictions are still poorly understood. Gene regulatory networks have been proposed as one cause of constrained phenotypic variation. However, most of the evidence for this is theoretical rather than experimental. Here, we study evolutionary biases in two synthetic gene regulatory circuits expressed in E. coli that produce a gene expression stripe; a pivotal pattern in embryonic development. The two parental circuits produce the same phenotype, but create it through different regulatory mechanisms. We show that mutations cause distinct novel phenotypes in the two networks and use a combination of experimental measurements, mathematical modelling and DNA sequencing to understand why mutations bring forth only some but not other novel gene expression phenotypes. Our results reveal that the regulatory mechanisms of networks restrict the possible phenotypic variation upon mutation. Consequently, seemingly equivalent networks can indeed be distinct in how they constrain the outcome of further evolution.
CytoCensus: mapping cell identity and division in tissues and organs using machine learning

A major challenge in cell and developmental biology is the automated identification and quantitation of cells in complex multilayered tissues. We developed CytoCensus: an easily deployed implementation of supervised machine learning that extends convenient 2D “point- and-click” user training to 3D detection of cells in challenging datasets with ill-defined cell boundaries. In tests on these datasets, CytoCensus outperforms other freely available image analysis software in accuracy and speed of cell detection. We used CytoCensus to count stem cells and their progeny, and to quantify individual cell divisions from time-lapse movies of explanted Drosophila larval brains, comparing wild-type and mutant phenotypes. We further illustrate the general utility and future potential of CytoCensus by analysing the 3D organisation of multiple cell classes in Zebrafish retinal organoids and cell distributions in mouse embryos. CytoCensus opens the possibility of straightforward and robust automated analysis of developmental phenotypes in complex tissues. Summary Hailstone et al. develop CytoCensus, a “point-and-click” supervised machine-learning image analysis software to quantitatively identify defined cell classes and divisions from large multidimensional data sets of complex tissues. They demonstrate its utility in analysing challenging developmental phenotypes in living explanted Drosophila larval brains, mammalian embryos and zebrafish organoids. They further show, in comparative tests, a significant improvement in performance over existing easy-to-use image analysis software. Highlights CytoCensus: machine learning quantitation of cell types in complex 3D tissues Single cell analysis of division rates from movies of living Drosophila brains in 3D Diverse applications in the analysis of developing vertebrate tissues and organoids Outperforms other image analysis software on challenging, low SNR datasets tested
Ghosts of a Structured Past: Impacts of Ancestral Patterns of Isolation-by-Distance on Divergence-Time Estimation

Isolation by distance is a widespread pattern in nature that describes the reduction of genetic correlation between subpopulations with increased geographic distance. In the population ancestral to modern sister species, this pattern may hypothetically inflate population divergence time estimation due to the potential for allele frequency differences in subpopulations at the ends of the ancestral population. In this study, we analyze the relationship between the time to the most recent common ancestor and the population divergence time when the ancestral population model is a linear stepping-stone. Using coalescent simulations, we compare the coalescent time to the population divergence time for various ratios of the divergence time over the product of the population size and the deme number. Next, we simulate whole genomes to obtain SNPs, and use the Bayesian coalescent program SNAPP to estimate divergence times. We find that as the rate of migration between neighboring demes decreases, the coalescent time becomes significantly greater than the population divergence time when sampled from end demes. Divergence-time overestimation in SNAPP becomes severe when the divergence-to-population size ratio < 10 and migration is low. We conclude that studies estimating divergence times be cognizant of the potential ancestral population structure in an explicitly spatial context or risk dramatically overestimating the timing of population splits.
QTL mapping of leaf angle on eight nodes in maize enable the optimize canopy by differential operating of leaf angle at different levels of plant

Leaf angle (LA) is one of the most important canopy architecture traits of maize (Zea mays L.). To date, there is an urgent need to characterize the genetic control of LA at multiple nodes to bridge the information gap remain in optimizing canopy architecture for maximum yield at different canopy levels. In this study, through the cross between B73 (compact plant architecture) and SICAU1212 (expanded plant architecture), 199 derived RIL families were used to perform QTL mapping for LA from eight leaves at different nodes in three environments, utilizing single-environment analysis and joint mapping. Combining the results of two mapping strategies, we identified 15 common QTL associated with LA at eight nodes. The phenotypic variation explained by the individual QTL ranged from 0.39% to 20.14% and the number of leaves controlled by a single QTL varied from 1 to 8. Among them, QTL qLA2.1 and qLA5.1 simultaneously controlled LA of all the eight nodes; however, qLA2.2 only affected that of 1stLA. The total phenotypic variation explained by all QTL identified for LA at eight nodes ranged from 15.69% (8thLA) to 51.73% (1stLA). The number of QTL detected for LA at each nodes ranged from 4 (7thLA) to 11 (1stLA). These results provide comprehensive insights into the molecular bases of regulatory networks in LA morphogenesis, and will benefit the molecular design breeding of ideotype and further cloning of LA QTL at different plant levels in maize. Highlight QTL were identified for maize Leaf angle on different nodes, which has illuminated the genetic control networks of maize LA and empowered canopy ideotype design by manipulate leaf angle at individual leaves.
The dominance hierarchy of the female Yunnan snub-nosed monkeys (Rhinopithecus bieti)

Dominance hierarchies are common in social mammals, especially primates. The formation of social hierarchies is conducive to solving the problem of the allocation of scarce resources among individuals. From August 2015 to July 2016, we observed a wild, provisioned Yunnan snub-nosed monkey (Rhinopithecus bieti) group at Xiangguqing in Baimaxueshan National Nature Reserve, Yunnan Province, China. Aggressive and submissive behaviors were used to investigate dominance hierarchies between female individuals in the same one-male unit (OMU), and the grooming reciprocity index was used to detect reciprocal relationships between these females within the OMU. The results showed that loose social hierarchies exist among the females in each OMU, and more dominant individuals have higher grooming incomes. These results are consistent with the aggressive-submissive hypothesis and the resource control hypothesis.
Task-specific, dimension-based attentional shaping of motion processing in area MT

Non-spatial selective attention is based on the notion that specific features or objects in the visual environment are effectively prioritized in cortical visual processing. Feature-based attention (FBA) in particular, is a well-studied process that dynamically and selectively enhances neurons preferentially processing the attended feature attribute (e.g. leftward motion). In everyday life, however, behavior may require high sensitivity for an entire feature dimension (e.g. motion). Yet, evidence for feature dimension-specific attentional modulation on a cellular level is lacking. We here investigate neuronal activity in macaque motion-selective medio-temporal area (MT) in an experimental setting requiring the monkeys to detect either a motion change or a color change. We hypothesized that neural activity in MT is enhanced if the task requires perceptual sensitivity to motion. Despite identical visual stimulation, we found that mean firing rates were higher in the motion task, and response variability and latency were lower as compared to the color task. This task-specific response modulation in the processing of visual motion was independent from the relation between attended and stimulating motion direction. It emerged already in the absence of visual input, and consisted of a spatially global and tuning-independent shift of the MT baseline activity. The results provide single cell support for the hypothesis of a feature dimension-specific top-down signal emphasizing the processing of an entire feature class.
Concomitant duplication of the Cid and Cenp-C genes in Drosophila

Despite their essential role in the process of chromosome segregation in eukaryotes, kinetochore proteins are highly diverse across species, being lost, duplicated, invented, or diversified on the sequence level. Based on comparative genomics, the duplication of the inner kinetochore proteins CenH3 and Cenp-C, which are interdependent in their roles of stablishing centromere identity and function, can be said to be rare in animals. Surprisingly, the Drosophila CenH3 homolog Cid underwent four independent duplication events during evolution. Particularly interesting are the highly diverged and subfunctionalized Cid1 and Cid5 paralogs of the Drosophila subgenus, which reveal that over one thousand Drosophila species encode two Cid genes, making those with a single copy a minority. Given that CenH3 and Cenp-C likely co-evolve as a functional unit, we investigated the molecular evolution of Cenp-C in species of Drosophila. We report yet another Cid duplication within the Drosophila subgenus and that not only Cid, but also Cenp-C is duplicated in the entire Drosophila subgenus. The Cenp-C paralogs, which we named Cenp-C1 and Cenp-C2, are highly divergent. The retention of key motifs involved in centromere localization by both Cenp-C1 and Cenp-C2 makes neofunctionalization unlikely. In contrast, the alternate conservation of some functional motifs between the proteins is highly indicative of subfunctionalization. Interestingly, both Cid5 and Cenp-C2 are male germline-biased and evolved adaptively. Our findings point towards a specific inner kinetochore composition to a specific context (i.e., spermatogenesis), which could prove valuable for the understanding of how the extensive kinetochore diversity is related to essential cellular functions.
Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis

In 11 patients with decompensated cirrhosis and deteriorating renal function, the effect of the vasoconstrictor substance 8-ornithin vasopressin (ornipressin; POR 8; Sandoz, Basel, Switzerland) on renal function, hemodynamic parameters, and humoral mediators was studied. Ornipressin was infused at a dose of 6 IU/h over a period of 4 hours. During ornipressin infusion an improvement of renal function was achieved as indicated by significant increases in inulin clearance (+65%), paraaminohippuric acid clearance (+49%), urine volume (+45%), sodium excretion (+259%), and fractional elimination of sodium (+130%). The hyperdynamic circulation was reversed to a nearly normal circulatory state. The increase in systemic vascular resistance (+60%) coincided with a decrease of a previously elevated renal vascular resistance (-27%) and increase in renal blood flow (+44%). The renal fraction of the cardiac output increased from 2.3% to 4.7% (P less than 0.05). A decline of the elevated plasma levels of noradrenaline (2.08-1.13 ng/mL; P less than 0.01) and renin activity (27.6-14.2 ng.mL-1.h-1; P less than 0.01) was achieved. The plasma concentration of the atrial natriuretic factor increased in most of the patients, but slightly decreased in 3 patients. The decrease of renal vascular resistance and the increase of renal blood flow and of the renal fraction of cardiac output play a key role in the beneficial effect of ornipressin on renal failure. These changes develop by an increase in mean arterial pressure, the reduction of the sympathetic activity, and probably of an extenuation of the splanchnic vasodilation. A significant contribution of atrial natriuretic factor is less likely. The present findings implicate that treatment with ornipressin represents an alternative approach to the management of functional renal failure in advanced liver cirrhosis.
The effects of Nurses’ Empathy Skills on Attitudes towards Patients with Cancer

Objective: The purpose of this study is to evaluate the predictors of empathy skills and attitude towards cancer patients and association between nurses’ empathy skills on attitudes towards patients with cancer Patients and Methods: A structured questionnaire was used to evaluate the nurses’ empathy skills and their attitudes towards to patients with cancer. Jefferson Scale of Empathy (JSE) and Attitudes towards Cancer Scale (ATCS) were used. The predictors of JSE/ATCS scores and correlation between JSE and ATCS were analyzed. Results: 305 nurses participated in the study (84.2% of all nurses). The median age was 33 (20- 52) and most of the nurses were female (82.6%). Most of the participants were married (188, 61.6%) and 40.3% of nurses had a job experience more than 10 years. Female sex, being married, having job experience more than 10 years or caring more cancer patients were associated with higher JSE scores. Nurses caring more cancer patients weekly, experience with cancer patients, participation in educational activities about cancer care or presence of relative with a diagnosis of cancer were found to have more positive attitudes towards cancer patients. Spearman correlation analysis showed a positive, weak correlation between JSE and ATCS (r= 0.017, P= 0.38) Conclusion: Empathy skills are important while caring patients, especially in oncology practice. Although a direct correlation between empathy skills and attitudes towards cancer patients couldn’t be demonstrated, health care workers caring cancer patients should be both evaluated for empathy skills and educated.
Phase analysis for the assessment of left ventricular dyssynchrony by gated myocardial perfusion SPECT. Importance of clinical and technical parameters

Introduction: Phase analysis (PA) of the left ventricle is a new tool in nuclear cardiology studies used to assess left ventricular mechanical timing based on different clinical applications. However, the use of this tool is relatively unknown. Objective: To expose the feasibility of the new PA tool in myocardial perfusion (Gated-SPECT) to assess left ventricle mechanical timing, and to verify the differences between values depending on clinical and technical conditions. Materials and methods: The study included consecutive patients evaluated by Gated-SPECT. The main variables were different depending on clinical and technical conditions. PA was assessed using the PHASE tool of the QPS-QGS program (Cedars-Sinai Medical Center, Los Angeles, USA). The following parameters were obtained: histogram bandwith (HB), standard deviation (SD) and entropy (E). A descriptive and analytical analysis of means and/or medians was performed using parametric or non-parametric tests. Statistical significance was p 35% (p=0.001), E (p=0.001)] normal or necrosis study [HB (p=0.001), SD (p=0.001), E (p=0.001)], and gender [HB (p=0.002), SD (p=0.006), E (p=0.005)]. Conclusions: The new PA tool of nuclear medicine is feasible in our context. The type of stress, the administered dose, the study phase or the gamma camera used did not affect the parameters. However, gender, interventricular conduction disorders, necrosis and systolic dysfunction did have an impact on them.
B-Cell Non-Hodgkin Lymphoma

0 Acute myeloblastic leukemia 1 Chronic myeloid leukemia, BCR/ABLpositive 2 Atypical chronic myeloid leukemia, BCR/ABL-negative 3 Myeloid sarcoma 4 Acute promyelocytic leukemia 5 Acute myelomonocytic leukemia 6 -Acute myeloid leukemia with 11q23abnormality A Acute myeloid leukemia with multilineage dysplasia Z Other myeloid leukemia 9 Unspecified C92. 0 Acute monoblastic/monocytic leukemia 1 Chronic myelomonocytic leukemia 3 Juvenile myelomonocytic leukemia Z Other monocytic leukemia 9 Unspecified 0 Not having achieved remission 1In remission 2– In relapse Leukemia, MONOCYTIC C93.
Dynamics of protein binding to sites of nascent unscheduled DNA repair synthesis in non-proliferating cells

The analysis of DNA repair mechanisms is of fundamental importance to understand how cells remove DNA damage and maintain their genome stability. Investigating the dynamic association of proteins at sites of active DNA synthesis has been successfully performed at DNA replication forks, providing important information on the process, and allowing the identification of new players acting at these sites. However, the applicability of these studies to DNA repair events at sites of nascent unscheduled DNA synthesis (UDS) in non-proliferating cells has been never tested. Here, we describe the analysis of dynamics association of protein participating in nucleotide excision repair (NER), and in other DNA repair processes, at sites of nascent UDS in non-proliferating cells, to avoid interference by DNA replication. Labeling with 5-ethynyl-2’-deoxyuridine (EdU) after DNA damage, followed by click reaction to biotinylate these sites, permits the analysis of dynamic association of proteins, such as DNA polymerases δ and κ, as well as PCNA, to active DNA repair synthesis sites. The suitability of this technique to identify new factors present at active UDS sites is illustrated by two examples of proteins previously unknown to participate in the UV-induced DNA repair process.
Assessing the effects of thinning on stem growth allocation of individual Scots pine trees

Forest management alters the growing conditions and thus further development of trees. However, quantitative assessment of forest management on tree growth has been demanding as methodologies for capturing changes comprehensively in space and time have been lacking. Terrestrial laser scanning (TLS) has shown to be capable of providing three-dimensional (3D) tree stem reconstructions required for revealing differences between stem shapes and sizes. In this study, we used 3D reconstructions of tree stems from TLS and an unmanned aerial vehicle (UAV) to investigate how varying thinning treatments and the following growth effects affected stem shape and size of Scots pine (Pinus sylvestris L.) trees. The results showed that intensive thinning resulted in more stem volume and therefore total biomass allocation and carbon uptake compared to the moderate thinning. Relationship between tree height and diameter at breast height (i.e. slenderness) varied between both thinning intensity and type (i.e. from below and above) indicating differing response to thinning and allocation of stem growth of Scots pine trees. Furthermore, intensive thinning, especially from below, produced less variation in relative stem attributes characterizing stem shape and size. Thus, it can be concluded that thinning intensity, type, and the following growth effects have an impact on post-thinning stem shape and size of Scots pine trees. Our study presented detailed measurements on post-thinning stem growth of Scots pines that have been laborious or impracticable before the emergence of detailed 3D technologies. Moreover, the stem reconstructions from TLS and UAV provided variety of attributes characterizing stem shape and size that have not traditionally been feasible to obtain. The study demonstrated that detailed 3D technologies, such as TLS and UAV, provide information that can be used to generate new knowledge for supporting forest management and silviculture as well as improving ecological understanding of boreal forests.