Front Cover: Implantable self‐aligning fiber‐optic optomechanical devices for in vivo intraocular pressure‐sensing in artificial cornea

This work addresses an unmet clinical need, that of glaucoma monitoring through intraocular pressure (IOP) interrogation in patients with artificial corneas (keratoprost hesis). We demonstrate direct integration of a low‐drift, fiber‐optic Fabry‐Perot pressure sensor embedded in the keratoprosthesis via rapid, non‐contact micromagnetic fiber alignment. IOP interrogation is achieved by using white‐light interferometry, which provides sub‐mmHg IOP sensitivity. Further details can be found in the article by Pui‐Chuen Hui, Katia Shtyrkova, Chengxin Zhou, et al. ( e202000031 ).

     

Athletic humans and horses: Comparative analysis of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) expression in peripheral blood mononuclear cells in trained and untrained subjects at rest

Background  

Horses and humans share a natural proclivity for athletic performance. In this respect, horses can be considered a reference species in studies designed to optimize physical training and disease prevention. In both species, interleukin-6 (IL-6) plays a major role in regulating the inflammatory process induced during exercise as part of an integrated metabolic regulatory network. The aim of this study was to compare IL-6 and IL-6 receptor (IL-6R) mRNA expression in peripheral blood mononuclear cells (PBMCs) in trained and untrained humans and horses.     

Evaluation of Extracts Produced by Some Tropical Fungi as Potential Cholinesterase Inhibitors

Summary Extracts of culture filtrates of fungal taxa belonging to Chaetomium sp., Guignardia mangiferae, Pestalotiopsis guepinii, Phomopsis sp., Physalospora sp., Xylaria sp., and sterile mycelium isolated as endophytes from leaves of members of the plant families Anacardiaceae, Apocynaceae, Leguminosae and Palmae; and seven different species of Penicillium isolated from insects were tested for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity using Ellman’s colorimetric method adapted for thin layer chromatography. The results showed high rate of cholinesterase inhibitory activity, with the best result being obtained with Penicillium extracts, indicating that they might represent a valuable source for pharmaceutical applications and are worthy of further study.     

Alpha-Linolenic Acid Treatment Reduces the Contusion and Prevents the Development of Anxiety-Like Behavior Induced by a Mild Traumatic Brain Injury in Rats

Approximately, 1.7 million Americans suffer a TBI annually and TBI is a major cause of death and disability. The majority of the TBI cases are of the mild type and while most patients recover completely from mild TBI (mTBI) about 10% result in persistent symptoms and some result in lifelong disability. Anxiety disorders are the second most common diagnosis post-TBI. Of note, TBI-induced anxiety disorders are difficult to treat and remain a chronic condition suggesting that new therapies are needed. Previous work from our laboratory demonstrated that a mild TBI induced an anxiety-like phenotype, a key feature of the human condition, associated with loss of GABAergic interneurons and hyperexcitability in the basolateral amygdala (BLA) in rodents 7 and 30 days after a controlled cortical impact (CCI) injury. We now confirm that animals display significantly increased anxiety-like behavior 30 days after CCI. The anxiety-like behavior was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABA_A-receptor-mediated inhibitory postsynaptic currents (IPSCs) in the BLA. Significantly, subchronic treatment with alpha-linolenic acid (ALA) after CCI prevents the development of anxiety-like behavior, the loss of GABAergic interneurons, hyperexcitability in the BLA and reduces the impact injury. Taken together, administration of ALA after CCI is a potent therapy against the neuropathology and pathophysiological effects of mTBI in the BLA.     

The Tropical managed Forests Observatory: a research network addressing the future of tropical logged forests

While attention on logging in the tropics has been increasing, studies on the long-term effects of silviculture on forest dynamics and ecology remain scare and spatially limited. Indeed, most of our knowledge on tropical forests arises from studies carried out in undisturbed tropical forests. This bias is problematic given that logged and disturbed tropical forests are now covering a larger area than the so-called primary forests. A new network of permanent sample plots in logged forests, the Tropical managed Forests Observatory (TmFO), aims to fill this gap by providing unprecedented opportunities to examine long-term data on the resilience of logged tropical forests at regional and global scales. TmFO currently includes 24 experimental sites distributed across three tropical regions, with a total of 490 permanent plots and 921 ha of forest inventories.     

Solid-state synthesis of cyclo LD-diphenylalanine: A chiral phase built from achiral subunits

The solid-state structure of LL/DD or LD/DL diphenylalanine diluted in KBr pellets is studied by infrared (IR) absorption and vibrational circular dichroism (VCD) spectroscopy. The structure depends on the absolute configuration of the residues. The natural LL diphenylalanine exists as a mixture of neutral and zwitterionic structures, depending on the humidity of the sample, while mostly the zwitterion is observed for LD diphenylalanine whatever the experimental conditions. The system undergoes spontaneous cyclization upon heating at 125°C, resulting to the formation of a diketopiperazine (DKP) dipeptide as the only product. The reaction is faster for LD than for LL diphenylalanine. As expected, LL and DD diphenylalanine react to form the LL and DD enantiomers of cyclo diphenylalanine. Interestingly, the DKP dipeptides formed from the LD or DL diphenylalanine show unexpected optical activity, with opposite VCD spectra for the products formed from the LD and DL reagents. This is explained in terms of chirality synchronization between the monomers within the crystal, which retain the symmetry of the reagent, resulting to the formation of a new chiral phase made from transiently chiral molecules.     

Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids

The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/β-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are “addicted” to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display reduced disease-free and progression-free survival. Extensive molecular analysis in patient-derived CRC-SC tumorspheres and APC^Min/+ mice intestinal organoids revealed that p38α acts as a β-catenin chromatin-associated kinase required for the regulation of a signaling platform involved in tumor proliferation, metastatic dissemination, and chemoresistance in these CRC model systems. In particular, the p38α kinase inhibitor ralimetinib, which has already entered clinical trials, promoted sensitization of patient-derived CRC-SCs to chemotherapeutic agents commonly used for CRC treatment and showed a synthetic lethality effect when used in combination with the MEK1 inhibitor trametinib. Taken together, these results suggest that p38α may be targeted in CSCs to devise new personalized CRC treatment strategies.Subject terms: Cancer stem cells, Colorectal cancer, Post-translational modifications     

PvD1 defensin,a plant antimicrobial peptide with inhibitory activity against Leishmania amazonensis

Plant defensins are small cysteine-rich peptides and exhibit antimicrobial activity against a variety of both plant and human pathogens. Despite the broad inhibitory activity that plant defensins exhibit against different micro-organisms, little is known about their activity against protozoa. In a previous study, we isolated a plant defensin named PvD₁ from Phaseolus vulgaris (cv. Pérola) seeds, which was seen to be deleterious against different yeast cells and filamentous fungi. It exerted its effects by causing an increase in the endogenous production of ROS (reactive oxygen species) and NO (nitric oxide), plasma membrane permeabilization and the inhibition of medium acidification. In the present study, we investigated whether PvD₁ could act against the protozoan Leishmania amazonensis. Our results show that, besides inhibiting the proliferation of L. amazonensis promastigotes, the PvD₁ defensin was able to cause cytoplasmic fragmentation, formation of multiple cytoplasmic vacuoles and membrane permeabilization in the cells of this organism. Furthermore, we show, for the first time, that PvD₁ defensin was located within the L. amazonensis cells, suggesting the existence of a possible intracellular target.