Characterization of the human ESC transcriptome by hybrid sequencing

Although transcriptional and posttranscriptional events are detected in RNA-Seq data from second-generation sequencing, fulllength mRNA isoforms are not captured. On the other hand, thirdgeneration sequencing, which yields much longer reads, has current limitations of lower raw accuracy and throughput. Here, we combine second-generation sequencing and third-generation sequencing with a custom-designed method for isoform identification and quantification to generate a high-confidence isoform dataset for human embryonic stem cells (hESCs). We report 8,084 RefSeq-annotated isoforms detected as full-length and an additional 5,459 isoforms predicted through statistical inference. Over one-third of these are novel isoforms, including 273 RNAs from gene loci that have not previously been identified. Further characterization of the novel loci indicates that a subset is expressed in pluripotent cells but not in diverse fetal and adult tissues; moreover, their reduced expression perturbs the network of pluripotency- associated genes. Results suggest that gene identification, even in well-characterized human cell lines and tissues, is likely far from complete

Review article: Drought as a continuum – memory effects in interlinked hydrological, ecological, and social systems

Droughts are often long-lasting phenomena, without a distinct start or end and with impacts cascading across sectors and systems, creating long-term legacies. Nevertheless, our current perceptions and management of droughts and their impacts are often event-based, which can limit the effective assessment of drought risks and reduction of drought impacts. Here, we advocate for changing this perspective and viewing drought as a hydrological–ecological–social continuum. We take a systems theory perspective and focus on how “memory” causes feedback and interactions between parts of the interconnected systems at different timescales. We first discuss the characteristics of the drought continuum with a focus on the hydrological, ecological, and social systems separately, and then we study the system of systems. Our analysis is based on a review of the literature and a study of five cases: Chile, the Colorado River basin in the USA, northeast Brazil, Kenya, and the Rhine River basin in northwest Europe. We find that the memories of past dry and wet periods, carried by both bio-physical (e.g. groundwater, vegetation) and social systems (e.g. people, governance), influence how future drought risk manifests. We identify four archetypes of drought dynamics: impact and recovery, slow resilience building, gradual collapse, and high resilience–big shock. The interactions between the hydrological, ecological, and social systems result in systems shifting between these types, which plays out differently in the five case studies. We call for more research on drought preconditions and recovery in different systems, on dynamics cascading between systems and triggering system changes, and on dynamic vulnerability and maladaptation. Additionally, we advocate for more continuous monitoring of drought hazards and impacts, modelling tools that better incorporate memories and adaptation responses, and management strategies that increase societal and institutional memory. This will help us to better deal with the complex hydrological–ecological–social drought continuum and identify effective pathways to adaptation and mitigation.</p

Cooperative Self‐Assembly of a Quaternary Complex Formed by Two Cucurbit[7]uril Hosts, Cyclobis(paraquat‐ p

The self-assembly in aqueous solution of the well-known cyclophane, cyclobis(paraquat-p-phenylene) (BB(4+) ), and two cucurbit[7]uril (CB7) hosts around a simple hydroquinol-based, diamine guest (GH2 (2+) ) was investigated by (1) H NMR and electronic absorption spectroscopies, electrospray mass spectrometry and DFT computations. The formation of a quaternary supramolecular assembly [GH2 (2+) ⋅BB(4+) ⋅ (CB7)2 ] was shown to be a very efficient process, which takes place not only because of the attractive forces between each of the hosts and the guest, but also because of the lateral interactions between the hosts in the final assembly. This complementary set of attractive interactions results in clear cooperative binding effects that help overcome the entropic barriers for multiple component assembly

The cucurbituril 'portal' effect

This work focuses on the effect of cucurbit[n]uril (CBn) hosts on the microenvironment of molecular subunits that are located adjacent to the CBn binding site in inclusion complexes. The set of data presented here includes previously reported electrochemical and electron paramagnetic resonance spectroscopic data, primarily obtained with ferrocene-containing guests, as well as new electrochemical data recorded with 4,4′-bipyridinium (viologen) derivatives. Most of the data were obtained with cucurbit[7]uril (CB7) complexes, and the rest were collected with cucurbit[8]uril (CB8) complexes. The experimental data compiled here clearly suggest that the microenvironment adjacent to the CBn portals in the complexes exhibits increased polarity compared with the bulk aqueous solution

Detection of Isomeric Microscopic Host–Guest Complexes. A Time-Evolving Cucurbit[7]uril Complex

The formation of inclusion complexes between the cucurbit[7]­uril host and a cationic guest containing ferrocenylmethyl and adamantyl residues connected to an ammonium nitrogen initially leads to an ∼1:1 mixture of two isomeric microscopic complexes, which evolves as a function of time toward the thermodynamically stable mixture, dominated by the adamantyl-included complex

Melatonin for gastric cancer treatment: where do we stand?

Gastric cancer (GC) is the third leading reason of death in men and the fourth in women. Studies have documented an inhibitory function of melatonin on the proliferation, progression and invasion of GC cells. MicroRNAs (miRNAs) are small, non-coding RNAs that play an important function in regulation of biological processes and gene expression of the cells. Some studies reported that melatonin can suppress the progression of GC by regulating the exosomal miRNAs. Thus, melatonin represents a promising potential therapeutic agent for subjects with GC. Herein, we evaluate the existing data of both in vivo and in vitro studies to clarify the molecular processes involved in the therapeutic effects of melatonin in GC. The data emphasize the critical function of melatonin in several signaling ways by which it may inhibit cancer cell proliferation, decrease chemo-resistance, induce apoptosis as well as limit invasion, angiogenesis, and metastasis. This review provides a resource that identifies some of the mechanisms by which melatonin controls GC enlargement. In light of the findings, melatonin should be considered a novel and testable therapeutic mediator for GC treatment