Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers

Chromosomal translocations are important drivers of hematological malignancies whereby proto-oncogenes are activated by juxtaposition with super-enhancers, often called enhancer hijacking. We analysed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH) and proto-oncogene CCND1 that are common in B cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with super-enhancer hijacking of other common oncogenes in B cell (MAF, MYC and FGFR3/NSD2) and in T-cell malignancies (LMO2, TLX3 and TAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept of epigenomic translocation, where the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers.

BA2P : Bidirectional and Anonymous Auction Protocol with Dispute-Freeness

Electronic auction is a popular platform to sell goods, task assignment, and resources’ allocation due to reductions of transaction costs and has attracted a huge number of potential buyers. However, it is challenging to address the disputes between the buyer and the auctioneer. The main reason is, on the one hand, solving such problem leverages to the broad domain of research aspects, such as economic theory, engineering, and cryptography, and, on the other hand, it is difficult to arbitrate in a decentralized and anonymous setting. In this work, we consider a more general framework to solve the potential disputes by enforcing bidirectional confirmation and public verification. Hence, the bidding procedure is clear to inspect and potential disputes can be erased. To achieve this goal, we propose policy-driven chameleon hash and revised linkable-and-redactable ring signature as building blocks. We used these two tools to build a bidirectional and anonymous auction protocol called BA 2 P. In our BA 2 P protocol, the bidders can competitively and anonymously place their bids to outbid others. At the end of the auction protocol, everyone can verify the validity of the bidding proof and decide the winner. Thus, dispute-freeness feature is achieved. The analysis suggests that our proposal is provably secure and practically efficient, and it trades some efficiencies with dispute-freeness feature.

Prey Foraging Behavior After Predator Introduction Is Driven by Resource Knowledge and Exploratory Tendency

Predator reintroductions are often used as a means of restoring the ecosystem services that these species can provide. The ecosystem consequences of predator reintroduction depend on how prey species respond. Yet, to date, we lack a general framework for predicting these responses. To address this knowledge gap, we modeled the impacts of predator reintroduction on foragers as a function of predator characteristics (habitat domain; i.e., area threatened) and prey characteristics (knowledge of alternative habitat and exploratory tendency). Foraging prey had the capacity to both remember and return to good habitat and to remember and avoid predators. In general, we found that forager search time increased and consumption decreased after predator introduction. However, predator habitat domain played a key role in determining how much prey habitat use changed following reintroduction, and the forager's knowledge of alternative habitats and exploratory inclinations affected what types of habitat shifts occurred. Namely, habitat shifts and consumption sacrifices by prey were extreme in some cases, particularly when they were pushed far from their starting locations by broad-domain predators, whereas informed foragers spent less time searching and displayed smaller reductions to consumption than their naïve counterparts following predator exposure. More exploratory foragers exhibited larger habitat shifts, thereby sacrificing consumption but reducing encounters by relocating to refugia, whereas less exploratory foragers managed risk in place and consequently suffered increased encounters while consuming more resources. By implication, reintroductions of predators with broad habitat domains are especially likely to impose foraging and movements costs on prey, but forager spatial memory state can mitigate these effects, as informed foragers can better access alternate habitat and avoid predators with smaller reductions in consumption.

Dimensions of Psychotic and Other Problems of Thought and Affect

A third broad domain of correlated dimensions of frequently serious psychological problems is termed psychotic and related problems of thought and affect in this book, for want of a better term. The adjective “psychotic” refers to beliefs and experiences that essentially all members of a society consider to be baseless or false. Many of the dimensions of problems described in this domain involve psychotic beliefs (delusions), perceptual experiences (hallucinations), and other cognitive disturbances that can be said to put the person “out of touch with reality.” In addition, they often involve emotions and atypical energy levels that can be markedly inconsistent with the situation. Cognition, emotion, and energy levels that are not consistent with reality can sometimes take a very serious toll on people, but recent research strongly suggests that each of these problems lies on a continuum and can be viewed in dimensional terms. The Diagnostic and Statistical Manual of Mental Disorders categorical diagnoses that correspond to high levels of these problems include schizophrenia, schizotypal personality disorder, schizoid personality disorder, bipolar disorder, conversion disorders, and dissociative disorders (derealization and depersonalization). In addition, recent research suggests that obsessive and compulsive problems, compulsive rigidity, and some eating problems share features with this domain. Autistic spectrum problems are discussed in this chapter on the basis of limited current evidence regarding their best placement.

Deep Learning model to Automate the process of mapping Cancer Cells to Cell Lines & Cancer Types from Single Cell RNA-Seq Data

Single Cell RNA Sequencing has given us a broad domain to study heterogeneity & expression profiles of cells. Downstream analysis of such data has led us to important observation and classification of cell types. However, these approaches demand great exertion and effort added that it seems the only way to proceed ahead for the first time. Results of such verified analysis have led us to create labels from our dataset. We can use the same labeled data as an input to a neural network and this way we would be able to automate the tedious & time-consuming process of downstream analysis. In this paper, we have automated the process of mapping cancer cells to cancer cell lines & cancer types. For the same, we have used pan-cancer single cell sequencing data of 53513 cells from 198 cell lines reflecting 22 cancer types.

Successional change, restoration success, and resilience in boreal mixedwood vegetation communities over three decades

Long-term studies of vegetation succession can inform restoration of degraded forests. We examined resilience of a boreal mixedwood vegetation community, asking whether treatments employed to restore wood production in a degraded ecosystem could also restore diversity and composition of vegetation communities. The Inga Lake trial, established in 1987 in northeastern British Columbia, used mechanical, fire, and chemical and manual treatments, encompassing a gradient of restoration effort, and tree planting to restore a shrubland to white spruce (Picea glauca (Moench) Voss) forest. We monitored vascular plant, bryophyte, and macrolichen composition five times over 31 years on five to seven treatments replicated five times. We used mixed-effects models and nonmetric multidimensional scaling to compare diversity and composition among treatments and with mature reference forests. Low- to high-effort restoration created a gradient from broadleaf- to spruce-dominated overstories. Diversity increased with restoration effort. Four of 253 taxa occurred in mature forests only. There was no evidence that lower versus higher effort treatments followed divergent successional pathways toward broadleaved versus spruce reference communities. Our results suggest that these mixedwood vegetation communities lie within a broad domain of successional attraction that confers high ecological resilience to disturbance. Gap cuttings to stimulate understory re-initiation and provide woody debris are recommended to complete the restoration.

Raising the Bar: Improving Methodological Rigour in Cognitive Alcohol Research

Background & Aims: A range of experimental paradigms claim to measure the cognitive processes underpinning alcohol use, suggesting that heightened attentional bias, greater approach tendencies and reduced cue-specific inhibitory control are important drivers of consumption. This paper identifies substantial methodological shortcomings within this broad domain of research, however, and exemplifies them in studies focused specifically on alcohol-related attentional bias. Argument/Analysis: We highlight five main methodological issues: (i) the use of inappropriately matched control stimuli; (ii) opacity of stimulus selection and validation procedures; (iii) a credence in noisy measures; (iv) a reliance on unreliable tasks; and (v) variability in design and analysis. This is evidenced through a review of alcohol-related attentional bias (64 empirical articles, 68 tasks), which reveals the following: only 53% of tasks utilise appropriately matched control stimuli; as few as 38% report their stimulus selection and 19% their validation procedures; less than 28% used indices capable of disambiguating attentional processes; 22% assess reliability; and under 2% of studies were preregistered. Conclusions: Substantial improvements are required to improve the methodological rigour of cognitive alcohol research. To facilitate this, we provide a practical guide for future research: we advocate the use of well-matched and validated experimental stimuli, the development of reliable cognitive tasks and explicit assessment of their psychometric properties, and careful consideration of behavioural indices and their analysis. Further, we discuss open science principles that can facilitate replication and reproducibility in alcohol research, thereby enhancing trust in a field that has significant implications for public health and policy.

WNT responsive SUMOylation of ZIC5 promotes murine neural crest cell development via multiple effects on transcription

Zinc finger of the cerebellum (Zic) proteins act as classical transcription factors to promote transcription of the Foxd3 gene during neural crest cell specification. Additionally, they can act as co-factors that bind TCF molecules to repress WNT/β-catenin-dependent transcription without contacting DNA. Here, we show ZIC activity at the neural plate border is influenced by WNT-dependent SUMOylation. In a high WNT environment, a lysine within the highly conserved ZF-NC domain of ZIC5 is SUMOylated, which decreases formation of the TCF/ZIC co-repressor complex and shifts the balance towards transcription factor function. The modification is critical in vivo, as a ZIC5 SUMO-incompetent mouse strain exhibits neural crest specification defects. This work reveals the function of the ZIC ZF-NC domain, provides in vivo validation of target protein SUMOylation, and demonstrates that WNT/β-catenin signaling directs transcription at non-TCF DNA binding sites. Furthermore, it can explain how WNT signals convert a broad domain of Zic ectodermal expression into a restricted domain of neural crest cell specification.

Drosophila Fezf functions as a transcriptional repressor to direct layer-specific synaptic connectivity in the fly visual system

The layered compartmentalization of synaptic connections, a common feature of nervous systems, underlies proper connectivity between neurons and enables parallel processing of neural information. However, the stepwise development of layered neuronal connections is not well understood. The medulla neuropil of the Drosophila visual system, which comprises 10 discrete layers (M1 to M10), where neural computations underlying distinct visual features are processed, serves as a model system for understanding layered synaptic connectivity. The first step in establishing layer-specific connectivity in the outer medulla (M1 to M6) is the innervation by lamina (L) neurons of one of two broad, primordial domains that will subsequently expand and transform into discrete layers. We previously found that the transcription factor dFezf cell-autonomously directs L3 lamina neurons to their proper primordial broad domain before they form synapses within the developing M3 layer. Here, we show that dFezf controls L3 broad domain selection through temporally precise transcriptional repression of the transcription factor slp1 (sloppy paired 1). In wild-type L3 neurons, slp1 is transiently expressed at a low level during broad domain selection. When dFezf is deleted, slp1 expression is up-regulated, and ablation of slp1 fully rescues the defect of broad domain selection in dFezf-null L3 neurons. Although the early, transient expression of slp1 is expendable for broad domain selection, it is surprisingly necessary for the subsequent L3 innervation of the M3 layer. DFezf thus functions as a transcriptional repressor to coordinate the temporal dynamics of a transcriptional cascade that orchestrates sequential steps of layer-specific synapse formation.

Green finance for energy transition, climate action and sustainable development: overview of concepts, applications, implementation and challenges

<abstract> <p>The solutions to mankind's greatest problems today lie in the simultaneous development, adoption and deployment of a combination of technological, socio-political, cultural and financial initiatives and mechanisms. The present work serves as a brief compilation of concepts and information pertaining to the broad domain of green finance, particularly for a readership with non-financial background. Green finance indicates the deployment of private and public capital towards projects that not only prevent environmental degradation and related impacts such as climate change and air pollution but also generate a host of social benefits and adequate financial returns for the investors. Thus, green finance embodies several cross-cutting concepts. The various global events leading to the development of the current state of green finance, the typical forms and instruments involved, the regulatory framework and issuance process for these instruments and the various international agencies and organizations developing and making use of green finance schemes for identified beneficiary projects are briefly described in this work. Financial disclosures and the role of regulators and investors in strengthening green finance schemes are discussed, along with a summary of the current thought leadership and current academic research in this domain. The challenges in green finance are also enumerated and a few perspectives for the future are presented.</p> </abstract>