Towards Therapeutic Applications of Arthropod Venom K+-Channel Blockers in CNS Neurologic Diseases Involving Memory Acquisition and Storage

Potassium channels are the most heterogeneous and widely distributed group of ion channels and play important functions in all cells, in both normal and pathological mechanisms, including learning and memory processes. Being fundamental for many diverse physiological processes, K+-channels are recognized as potential therapeutic targets in the treatment of several Central Nervous System (CNS) diseases, such as multiple sclerosis, Parkinson's and Alzheimer's diseases, schizophrenia, HIV-1-associated dementia, and epilepsy. Blockers of these channels are therefore potential candidates for the symptomatic treatment of these neuropathies, through their neurological effects. Venomous animals have evolved a wide set of toxins for prey capture and defense. These compounds, mainly peptides, act on various pharmacological targets, making them an innumerable source of ligands for answering experimental paradigms, as well as for therapeutic application. This paper provides an overview of CNS K+-channels involved in memory acquisition and storage and aims at evaluating the use of highly selective K+-channel blockers derived from arthropod venoms as potential therapeutic agents for CNS diseases involving learning and memory mechanisms

The Erv41–Erv46 Complex Serves as a Retrograde Receptor to Retrieve Escaped ER Proteins

Signal-dependent sorting of proteins in the early secretory pathway is required for dynamic retention of endoplasmic reticulum (ER) and Golgi components. In this study, we identify the Erv41–Erv46 complex as a new retrograde receptor for retrieval of non–HDEL-bearing ER resident proteins. In cells lacking Erv41–Erv46 function, the ER enzyme glucosidase I (Gls1) was mislocalized and degraded in the vacuole. Biochemical experiments demonstrated that the luminal domain of Gls1 bound to the Erv41–Erv46 complex in a pH-dependent manner. Moreover, in vivo disturbance of the pH gradient across membranes by bafilomycin A1 treatment caused Gls1 mislocalization. Whole cell proteomic analyses of deletion strains using stable isotope labeling by amino acids in culture identified other ER resident proteins that depended on the Erv41–Erv46 complex for efficient localization. Our results support a model in which pH-dependent receptor binding of specific cargo by the Erv41–Erv46 complex in Golgi compartments identifies escaped ER resident proteins for retrieval to the ER in coat protein complex I–formed transport carriers

A role for eisosomes in maintenance of plasma membrane phosphoinositide levels

The plasma membrane delineates the cell and mediates its communication and material exchange with the environment. Many processes of the plasma membrane occur through interactions of proteins with phosphatidylinositol(4,5)-bisphosphate (PI(4,5)P2), which is highly enriched in this membrane and is a key determinant of its identity. Eisosomes function in lateral organization of the plasma membrane, but the molecular function of their major protein subunits, the BAR domain–containing proteins Pil1 and Lsp1, is poorly understood. Here we show that eisosomes interact with the PI(4,5)P2 phosphatase Inp51/Sjl1, thereby recruiting it to the plasma membrane. Pil1 is essential for plasma membrane localization and function of Inp51 but not for the homologous phosphatidylinositol bisphosphate phosphatases Inp52/Sjl2 and Inp53/Sjl3. Consistent with this, absence of Pil1 increases total and available PI(4,5)P2 levels at the plasma membrane. On the basis of these findings, we propose a model in which the eisosomes function in maintaining PI(4,5)P2 levels by Inp51/Sjl1 recruitment

Exposing the human nude phenotype [4]

Peer reviewedSubmitted Versio

A model of a small open economy integrated in a monetary union

This paper develops a model of a small open economy integrated in a monetary union, which is a nontrivial technical extension of the existing small open economy model. The model is used to study the monetary transmission mechanism in Portugal.info:eu-repo/semantics/publishedVersio

Pulses protein quality control at different storage conditions for further protein extraction – a review: Poster

The storage conditions are of extreme importance with regards to grains (cereal & pulses) components (carbohydrates, lipids, proteins) preservation and quality for industry (that may interfere to whole process and quality of the final product). In addition, the vegetarian consumers’ interest of protein supplement (capsules) from pulses such as beans (Phaseolus vulgaris L.), chickpeas (Cicer arietinum L.), lentils (Lens culinaris L.), peas (Pisum sativum L.), peanuts (Arachis hypogaea L.), also soybeans (Glycine max L.) has grown considerably, mainly due to their non-lactose&non-animal-based ingredients and also non-transgenic in some of the pulses. Therefore, there is a need of information regarding pulses storage conditions on their components’ quality/quantity and so for safety of the raw material utilized for protein extract purposes. In addition, to get safe pulses raw materials for protein extraction aimed for vegetarian supplements, one needs to take into account (a) quite controlled storage conditions, apart from (b) pesticide residues and mycotoxins contamination control. Therefore, the present reviewgathers and compiles the characterization of six different pulses by evaluating amino acids profile as indicators of protein quality, and compares them with different varieties for further protein extraction.The storage conditions are of extreme importance with regards to grains (cereal & pulses) components (carbohydrates, lipids, proteins) preservation and quality for industry (that may interfere to whole process and quality of the final product). In addition, the vegetarian consumers’ interest of protein supplement (capsules) from pulses such as beans (Phaseolus vulgaris L.), chickpeas (Cicer arietinum L.), lentils (Lens culinaris L.), peas (Pisum sativum L.), peanuts (Arachis hypogaea L.), also soybeans (Glycine max L.) has grown considerably, mainly due to their non-lactose&non-animal-based ingredients and also non-transgenic in some of the pulses. Therefore, there is a need of information regarding pulses storage conditions on their components’ quality/quantity and so for safety of the raw material utilized for protein extract purposes. In addition, to get safe pulses raw materials for protein extraction aimed for vegetarian supplements, one needs to take into account (a) quite controlled storage conditions, apart from (b) pesticide residues and mycotoxins contamination control. Therefore, the present reviewgathers and compiles the characterization of six different pulses by evaluating amino acids profile as indicators of protein quality, and compares them with different varieties for further protein extraction

Pharmacologic inhibition of JAK-STAT signaling promotes hair growth

Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells