Mechanisms regulating nutrition-dependent developmental plasticity through organ-specific effects in insects

Nutrition, via the insulin/insulin-like growth factor (IIS)/Target of Rapamycin (TOR) signaling pathway, can provide a strong molding force for determining animal size and shape. For instance, nutrition induces a disproportionate increase in the size of male horns in dung and rhinoceros beetles, or mandibles in staghorn or horned flour beetles, relative to body size. In these species, well-fed male larvae produce adults with greatly enlarged horns or mandibles, whereas males that are starved or poorly fed as larvae bear much more modest appendages. Changes in IIS/TOR signaling plays a key role in appendage development by regulating growth in the horn and mandible primordia. In contrast, changes in the IIS/TOR pathway produce minimal effects on the size of other adult structures, such as the male genitalia in fruit flies and dung beetles. The horn, mandible and genitalia illustrate that although all tissues are exposed to the same hormonal environment within the larval body, the extent to which insulin can induce growth is organ specific. In addition, the IIS/TOR pathway affects body size and shape by controlling production of metamorphic hormones important for regulating developmental timing, like the steroid molting hormone ecdysone and sesquiterpenoid hormone juvenile hormone. In this review, we discuss recent results from Drosophila and other insects that highlight mechanisms allowing tissues to differ in their sensitivity to IIS/TOR and the potential consequences of these differences on body size and shape.FCT fellowships, Fundação Calouste Gulbenkian

Developing a methodology for XPS profiling of biofilms and biological materials

Films of cells on solid substrates are encountered in a variety of biological and biomedical environments, including cells in biofilms that spontaneously colonize medical devices and multilayers of cells filtered from suspensions for analysis. Understanding the chemical properties of cells in such films is important for providing clues about the behavior of the cells or about the effects of treatments that had been applied to the cells. X-ray Photoelectron Spectroscopy (XPS), with its combination of chemical selectivity and surface specificity, is an ideal technique for analysing these biofilms and multilayers, but it needs to be combined with profiling to more fully characterise the samples. It is well known that profiling with traditionally used argon monomers results in a high degree of chemical modification for most organic materials. Recent studies have shown, however, that argon cluster beams may be used for depth profiling of organic materials while preserving the chemical information. This poster will present data from cluster profiling studies of biofilms and biomaterials. The methodology required for optimum profiling of these samples will be discussed, including an evaluation of XPS data acquisition protocols, as well as sputtering conditions

Dynamic mechanical properties of hydroxyapatite-reinforced and porous starch-based degradable biomaterials

It has been shown that blends of starch with a poly(ethylene-vinyl-alcohol) copolymer, EVOH, designated as SEVA-C, present an interesting combination of mechanical, degradation and biocompatible properties, specially when filled with hydroxyapatite (HA). Consequently, they may find a range of applications in the biomaterials field. This work evaluated the influence of HA fillers and of blowing agents (used to produce porous architectures) over the viscoelastic properties of SEVA-C polymers, as seen by dynamic mechanical analysis (DMA), in order to speculate on their performances when withstanding cyclic loading in the body. The composite materials presented a promising performance under dynamic mechanical solicitation conditions. Two relaxations were found being attributed to the starch and EVOH phases. The EVOH relaxation process may be very useful in vivo improving the implants performance under cyclic loading. DMA results also showed that it is possible to produce SEVA-C compact surface/porous core architectures with a mechanical performance similar to that of SEVA-C dense materials. This may allow for the use of these materials as bone replacements or scaffolds that must withstand loads when implanted

Moving towards personalized medicine - the broad use of aptamers for targeted theranostic

Aptamers are short, single-stranded oligonucleotides synthesized in vitro from a randomized oligonucleotide library against a specific target. These molecules are capable of binding to a wide range of biological targets with high specificity and affinity. They present great advantages over antibodies with potential applications in research, diagnosis, and therapeutics. Specifically for tumors with late-stage identification and poor prognosis, like pancreatic cancer, the study of novel aptamers holds tremendous potential for cancer diagnosis and treatment. Along with cancer treatment, aptamers have also shown high potential in regulating the immune response and modulating several critical steps of signaling cascades, such as in immune checkpoints. In the context of microbiota and infection, aptamers are being studied to identify microbes and their metabolites. This assessment has the potential to improve the detection and management of infectious diseases while assisting us in better understanding health risks and treatment outcomes by tracking changes in the microbiota. In this review, the potential of aptamers is explored regarding their applications in cancer, immune, and microbiota therapy.Pilar Baylina (P.B.) acknowledges on the behalf of the authors the support of Fundação para a Ciência e Tecnologia (FCT), Portuguese Government, under the Strategic Project Reference: UID/BIM/04293/2013. Pilar Baylina (P.B.) and R.F. was also supported by FEDER/02/SAICT/2020/072560. Ana Cláudia Pereira (A.C.P.) acknowledges the support of Fundação para a Ciência e Tecnologia (FCT), Portuguese Government, under the Strategic Project Reference: 2022.09032.PTDC. André P. Sousa acknowledges FCT for the PhD grant 2022.12441.BD. Ana C. Rocha acknowledges FCT for the PhD grant 2021.06521.BD. Patrick P. Pais acknowledges FCT for the PhD grant 2021.09498.BD. Susana Ramalho acknowledges LaBMI for the PhD grant LABMI/BI/2021/01 (NEURO4COVID).info:eu-repo/semantics/publishedVersio

The OBAA Standard for Developing Repositories of Learning Objects: the Case of Ocean Literacy in Azores

This paper describes the existing web resources of learning objects to promote ocean literacy. The several projects and sites are explored, and the shortcomings revealed. The limitations identified include insufficient metadata about registered learning objects and lack of support for intelligent applications. As solution, we promote the seaThings project that relies on a multi-disciplinary approach to promote literacy in the marine environment by implementing a specific Learning Objects repositories (LOR) and a federation of repositories (FED), supported by a OBAA, a versatile and innovative standard that will provide the necessary support for intelligent applications for education purposes, to be used in schools and other educational institutions.info:eu-repo/semantics/publishedVersio

Phytochemical screening, cytotoxicity and acute toxicity of Annona vepretorum Mart (Annonaceae) leaf extracts

Purpose: To investigate the phytochemistry, cytotoxicity and acute toxicity of leaf extracts from Annona vepretorum.Methods: The crude extracts were obtained by maceration with hexane and  methanol. The crude methanol extract was suspended in a 3:7 (v/v) mixture of methanol (MeOH) and water (H2O) and partitioned with hexane, chloroform (CHCl3) and ethyl acetate (AcOEt) in ascending order of polarity to obtain the respective  extracts. In the investigation of phytochemical profile, the extracts were evaluated on thin layer chromatography (TLC) plates of silica gel. Cytotoxicity was tested using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assays against tumor cell lines, viz,HCT-116 (colon), SF-295 (brain), HL-60 (leukemic) and Sarcoma-180. Acute toxicity study was performed by administration of a single oral dose of 2 g/kg body weight of the extracts to mice and the animals were observed for 14 days.Results: Phytochemical screening results showed that A. vepretorum extracts contain alkaloids, flavonoids and terpenes. Methanol and chloroform extracts exhibited high cytotoxic activity against HCT-116, HL-60 and Sarcoma-180. Moreover, the extracts displayed low toxicity in mice, as no deaths and pronounced toxic effects were observed.Conclusion: A. vepretorum contains a variety of secondary metabolites which may confer on this species high cytotoxic activity. In addition, the oral administration of the extracts produced low toxicity in mice.Keywords: Annonaceae, Annona vepretorum, Phytochemistry, Tumor cell lines, Acute toxicit

GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain.

Extracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication, and potential as drug delivery vehicles. Here we demonstrate a role for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in EV assembly and secretion. We observe high levels of GAPDH binding to the outer surface of EVs via a phosphatidylserine binding motif (G58), which promotes extensive EV clustering. Further studies in a Drosophila EV biogenesis model reveal that GAPDH is required for the normal generation of intraluminal vesicles in endosomal compartments, and promotes vesicle clustering. Fusion of the GAPDH-derived G58 peptide to dsRNA-binding motifs enables highly efficient loading of small interfering RNA (siRNA) onto the EV surface. Such vesicles efficiently deliver siRNA to multiple anatomical regions of the brain in a Huntington's disease mouse model after systemic injection, resulting in silencing of the huntingtin gene in different regions of the brain

tartan underlies the evolution of male Drosophila genital morphology

Male genital structures are among the most rapidly evolving morphological traits and are often the only features that can distinguish closely related species. This process is thought to be driven by sexual selection and may reinforce species separation. However, while the genetic bases of many phenotypic differences have been identified, we still lack knowledge about the genes underlying evolutionary differences in male genital organs and organ size more generally. The claspers (surstyli) are periphallic structures that play an important role in copulation in insects. Here, we show that divergence in clasper size and bristle number between Drosophila mauritiana and Drosophila simulans is caused by evolutionary changes in tartan (trn), which encodes a transmembrane leucine-rich repeat domain protein that mediates cell–cell interactions and affinity. There are no fixed amino acid differences in trn between D. mauritiana and D. simulans, but differences in the expression of this gene in developing genitalia suggest that cis-regulatory changes in trn underlie the evolution of clasper morphology in these species. Finally, analyses of reciprocal hemizygotes that are genetically identical, except for the species from which the functional allele of trn originates, determined that the trn allele of D. mauritiana specifies larger claspers with more bristles than the allele of D. simulans. Therefore, we have identified a gene underlying evolutionary change in the size of a male genital organ, which will help to better understand not only the rapid diversification of these structures, but also the regulation and evolution of organ size more broadly

Ficolin-1 and Ficolin-3 Plasma Levels Are Altered in HIV and HIV/HCV Coinfected Patients From Southern Brazil

The complement system is a key component of the innate immune system, participating in the surveillance against infectious agents. Once activated by one of the three different pathways, complement mediates cell lysis, opsonization, signalizes pathogens for phagocytosis and induces the adaptive immune response. The lectin pathway is constituted by several soluble and membrane bound proteins, called pattern recognition molecules (PRM), including mannose binding lectin (MBL), Ficolins-1, -2, and -3, and Collectin 11. These PRMs act on complement activation as recognition molecules of pathogen-associated molecular patterns (PAMPs) such as N-acetylated, found in glycoproteins of viral envelopes. In this study, Ficolin-1 and Ficolin-3 plasma levels were evaluated in 178 HIV patients (93 HIV; 85 HIV/HCV) and 85 controls from southern Brazil. Demographic and clinical-laboratory findings were obtained during medical interview and from medical records. All parameters were assessed by logistic regression, adjusted for age, ancestry, and sex. Significantly lower levels of Ficolin-1 were observed in HIV/HCV coinfected when compared to HIV patients (p = 0.005, median = 516 vs. 667 ng/ul, respectively) and to controls (p < 0.0001, 1186 ng/ul). Ficolin-1 levels were lower in males than in females among HIV patients (p = 0.03) and controls (p = 0.0003), but no association of Ficolin-1 levels with AIDS was observed. On the other hand, Ficolin-3 levels were significantly lower in controls when compared to HIV (p < 0.0001, medians 18,240 vs. 44,030 ng/ml, respectively) and HIV/HCV coinfected (p < 0.0001, 40,351 ng/ml) patients. There was no correlation between Ficolin-1 and Ficolin-3 levels and age, HIV viral load or opportunistic infections. However, Ficolin-3 showed a positive correlation with T CD4 cell counts in HIV monoinfected patients (p = 0.007). We provide here the first assessment of Ficolin-1 and−3 levels in HIV and HIV/HCV coinfected patients, which indicates a distinct role for these pattern recognition molecules in both viral infections