Nuclear and cytoplasmic features in the diagnosis of Clark's nevi

Background

Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions.

Methods

This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity.

Results

Clark's nevi showed a significantly higher frequency of absent‐or‐inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas.

Conclusion

Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.     

Catalysis-dependent stabilization of Bre1 fine-tunes histone H2B ubiquitylation to regulate gene transcription

Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes, yet the mechanistic details by which this modification is regulated are not fully elucidated. Here we show in yeast that H2BK123ub1 is regulated in part through the protein stability of the E3 ubiquitin ligase Bre1. We found that Bre1 stability is controlled by the Rtf1 subunit of the polymerase-associated factor (PAF) complex and through the ability of Bre1 to catalyze H2BK123ub1. Using a domain in Rtf1 that stabilizes Bre1, we show that inappropriate Bre1 levels lead to defects in gene regulation. Collectively, these data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression.     

Toxicity and effects of the neonicotinoid thiamethoxam on Scaptotrigona bipunctata lepeletier, 1836 (Hymenoptera: Apidae)

The neonicotinoid thiamethoxam is widely used in different agricultural crops, and it has a spectrum of action against insects, affecting both pests and pollinators, such as bees. In this study, the effects of exposure to sublethal concentrations of thiamethoxam on stingless bees Scaptotrigona bipunctata were evaluated. Foragers bees were exposed to the insecticide and subjected to genetic biochemical, histochemical, and morphological analyses after 24, 48, and 72 h of ingestion. Analysis of isoenzyme esterases revealed significant alterations in the relative activity of EST‐4, a type II cholinesterase. Evaluation of the S. bipunctata brain revealed changes in the state of chromatin condensation according to the exposure time and concentration of neonicotinoid compared with the control. Morphological changes were observed in the midgut of this species at all concentrations and exposure times, which may interfere with various physiological processes of these insects. We can conclude that, although thiamethoxam at the concentrations evaluated did not cause high mortality, it induced concentration‐dependent changes in bees by activating enzymes related with the protection for xenobiotic, internal morphology and probably these changes may lead to alterations in the activity of bees.     

Oncogenomics: prospects for the future

Genomics has generated a wealth of data that is now being used to identify additional molecular alterations associated with cancer development. Mapping these alterations in the cancer genome is a critical first step in dissecting oncological pathways. There are two ways in which cancer research has changed in recent years. The first is the progressive elucidation of the genomic basis of cancer. This has been accomplished by the generation of detailed information using procedures such as global expression profiling. The second is a renewed emphasis on the role of epigenetic modifications in the etiology of cancer. Changes in DNA methylation and chromatin modification patterns are some of the epigenetic factors that cause gene deregulation in cancer. In this article, current and evolving genomic applications and the hypotheses underlying the modality for cancer therapy will be reviewed.     

The Role of Chromatin in Adenoviral Vector Function

Vectors based on adenovirus (Ad) are one of the most commonly utilized platforms for gene delivery to cells in molecular biology studies and in gene therapy applications. Ad is also the most popular vector system in human clinical gene therapy trials, largely due to its advantageous characteristics such as high cloning capacity (up to 36 kb), ability to infect a wide variety of cell types and tissues, and relative safety due to it remaining episomal in transduced cells. The latest generation of Ad vectors, helper‑dependent Ad (hdAd), which are devoid of all viral protein coding sequences, can mediate high-level expression of a transgene for years in a variety of species ranging from rodents to non-human primates. Given the importance of histones and chromatin in modulating gene expression within the host cell, it is not surprising that Ad, a nuclear virus, also utilizes these proteins to protect the genome and modulate virus- or vector‑encoded genes. In this review, we will discuss our current understanding of the contribution of chromatin to Ad vector function.     

Vapor condensation with daytime radiative cooling

A radiative vapor condenser sheds heat in the form of infrared radiation and cools itself to below the ambient air temperature to produce liquid water from vapor. This effect has been known for centuries, and is exploited by some insects to survive in dry deserts. Humans have also been using radiative condensation for dew collection. However, all existing radiative vapor condensers must operate during the nighttime. Here, we develop daytime radiative condensers that continue to operate 24 h a day. These daytime radiative condensers can produce water from vapor under direct sunlight, without active consumption of energy. Combined with traditional passive cooling via convection and conduction, radiative cooling can substantially increase the performance of passive vapor condensation, which can be used for passive water extraction and purification technologies.

Energy and clean water are global challenges that are intertwined in an unfavorable way: even in areas where water is abundant, energy may not be available to purify it for human use (1, 2). There has been strong interest in developing passive technologies to purify or harvest water without using fuel or electricity. In this context, passive vapor condensation becomes particularly important because many passive water technologies go through the vapor phase of water in their harvesting or purification processes.Traditional vapor condensation technique is based on convective and conductive heat exchange with ambient environments. This technique is widely used in systems with hot vapors (3–6). However, with ever-increasing emphasis on passive systems, there are many situations in which warm- or even room-temperature vapor needs to be effectively condensed, such as extracting water from atmosphere (7–9) and warm vapor generated from high-efficiency solar evaporation (10). For vapor at such temperatures, most traditional condensers fail. For this reason, there is a clear need for a condensation technique to complement traditional condensers.A different technique is based on radiative vapor condensation. Darkling beetles in the Namib desert (11) use this technique to collect water. Their bodies function as a cooling surface by shedding thermal energy through midinfrared (mid-IR) radiation toward a clear nighttime sky, generating dew from humid air. This mechanism is also used by commercial radiative dew condensers (7–9). However, neither Namib beetle nor existing dew condensers can operate in the daytime (7). Those nighttime radiative condensers are incompatible with many emerging water technologies that require 24 h operation or direct access to sunlight.Recently, Fan et al. showed that passive radiative cooling to subambient temperatures can be realized even during the daytime, by integrating a high-efficiency solar reflector with a high-emissivity thermal emitter in the mid-IR atmospheric transparency window (12). Using this work as a basis, here we demonstrate a daytime radiative condenser. Compared to existing radiative vapor condensers (7–9), our condenser can function even in the presence of sunlight, which is essential for integration into passive water-harvesting systems that mainly operate during daytime.