Comparative Transcriptomics of Fat Bodies between Symbiotic and Quasi-Aposymbiotic Adult Females of Blattella germanica with Emphasis on the Metabolic Integration with Its Endosymbiont Blattabacterium and Its Immune System.

We explored the metabolic integration of Blattella germanica and its obligate endosymbiont Blattabacterium cuenoti by the transcriptomic analysis of the fat body of quasi-aposymbiotic cockroaches, where the endosymbionts were almost entirely removed with rifampicin. Fat bodies from quasi-aposymbiotic insects displayed large differences in gene expression compared to controls. In quasi-aposymbionts, the metabolism of phenylalanine and tyrosine involved in cuticle sclerotization and pigmentation increased drastically to compensate for the deficiency in the biosynthesis of these amino acids by the endosymbionts. On the other hand, the uricolytic pathway and the biosynthesis of uric acid were severely decreased, probably because the reduced population of endosymbionts was unable to metabolize urea to ammonia. Metabolite transporters that could be involved in the endosymbiosis process were identified. Immune system and antimicrobial peptide (AMP) gene expression was also reduced in quasi-aposymbionts, genes encoding peptidoglycan-recognition proteins, which may provide clues for the maintenance of the symbiotic relationship, as well as three AMP genes whose involvement in the symbiotic relationship will require additional analysis. Finally, a search for AMP-like factors that could be involved in controlling the endosymbiont identified two orphan genes encoding proteins smaller than 200 amino acids underexpressed in quasi-aposymbionts, suggesting a role in the host-endosymbiont relationship.

An In-Depth Exploration of Unconventional Machining Techniques for INCONEL® Alloys.

Build-up-edge (BUE), high-temperature machining and tool wear (TW) are some of the problems associated with difficult-to-machine materials for high-temperature applications, contributing significantly to high-cost manufacturing and poor tool life (TL) management. A detailed review of non-traditional machining processes that ease the machinability of INCONEL®, decrease manufacturing costs and suppress assembly complications is thus of paramount significance. Progress taken within the field of INCONEL® non-conventional processes from 2016 to 2023, the most recent solutions found in the industry, and the prospects from researchers have been analysed and presented. In ensuing research, it was quickly noticeable that some techniques are yet to be intensely exploited. Non-conventional INCONEL® machining processes have characteristics that can effectively increase the mechanical properties of the produced components without tool-workpiece contact, posing significant advantages over traditional manufacturing.

Mechanical Strength and Surface Analysis of a Composite Made from Recycled Carbon Fibre Obtained via the Pyrolysis Process for Reuse in the Manufacture of New Composites.

This work aims to obtain recycled carbon fibre and develop an application for this new material. The carbon fibres were obtained by recycling aerospace prepreg waste via the pyrolysis process. The recycled fibres were combined with an Araldite LH5052/Aradur LY5053 epoxy resin/hardener system using manual lay-up and vacuum bagging processes. For comparison, the same resin/hardener system was used to produce a composite using commercial carbon fibre. The recycled and commercial composites were subjected to flexural, tensile and Mode I testing. Fracture aspects were analysed via scanning electron microscopy (SEM). The pyrolysis process did not affect the fibre surface as no degradation was observed. The fracture aspect showed a mixture of failure in the recycled composite laminate and interlaminar/translaminar failure near the surface of the commercial composite caused by flexural stress. Flexural and tensile tests showed a loss of mechanical strength due to the recycling process, but the tensile values were twice as high. The sand ladder platform was the project chosen for the development of a product made with recycled carbon fibres. The product was manufactured using the same manufacturing process as the specimens and tested with a 1243 kg car. The method chosen to design, manufacture and test the prototype sand ladder platform made of recycled carbon fibre was appropriate and gave satisfactory results in terms of high mechanical strength to bending and ease of use.

Investigations on the Surface Integrity and Wear Mechanisms of TiAlYN-Coated Tools in Inconel 718 Milling Operations.

Inconel 718 is a Ni superalloy with superior mechanical properties, even at high temperatures. However, due to its high hardness and low thermal conductivity, it is considered a difficult-to-machine material. This material is widely used in applications that require good dimensional stability, making the milling process the most used in machining this alloy. The wear resulting from this process and the quality of the machined surface are still challenging factors when it comes to Inconel 718. TiAlN-based coating has been used on cutting tools with Yttrium as a doping element to improve the process performance. Based on this, this work evaluated the machined surface integrity and wear resistance of cutting tools coated using Physical Vapor Deposition (PVD) HiPIMS with TiAlYN in the end milling of Inconel 718, varying the process parameters such as cutting speed (vc), feed per tooth (fz), and cutting length (Lcut). It was verified that the Lcut is the parameter that exerts the most significant influence since, even at small distances, Inconel 718 already generates high tool wear (TW). Furthermore, the main wear mechanisms were abrasive and adhesive wear, with the development of a built-up edge (BUE) under a125 m/min feed rate (f) and a Lcut = 15 m. Chipping, cracking, and delamination of the coating were also observed, indicating a lack of adhesion between the coating and the substrate, suggesting the need for a good interlayer or the adjustment of the PVD parameters.

Studying the Degradation of Three Polymers under Different Chlorine Concentrations and Exposure Times.

Due to chlorine's ability to kill bacteria and fungi through a chemical reaction, chlorine solutions are commonly used to clean and disinfect numerous public facilities, although these actions are also dependent to the equipment present in those facilities. Accordingly, the interest in studying its effect when in contact with different materials is obvious. This study was carried out through accelerated degradation tests and various analysis methods (optical microscope, scanning electron microscope, and tensile tests). The objective was to observe the wear presented by three polymeric materials, polyvinyl chloride (PVC), high-density polyethylene (HDPE), and polypropylene (PP), when exposed to chlorine's action in swimming pools and drinking water treatment plants. The resulting effect depends on the chlorine content and the type of contact between the chemical agent and the material. The aim was to select the material less likely to be affected by chlorine through tests and analyses, allowing a longer component life. The use of certain more resistant polymeric materials can drastically reduce maintenance, reducing fundamental factors such as costs, the downtime of municipal facilities, and also the risk to public health. It was concluded that PVC has the most stable behaviour overall when in contact with chlorine solutions.

Study on the Micro-Abrasion Wear Behavior of PVD Hard Coating under Different SiC Abrasive Particles/Distilled Water Ratios.

Microscale abrasion has been intensively used to study the wear behavior o several hard coatings, enabling the observation of different wear mechanisms. Recently, a study arguing whether the surface texture of the ball could influence the dynamics of abrasive particles throughout the contact was presented. In this work, the influence of the abrasive particles concentration able to change the texture of the ball was studied to understand its influence on the wear modes-rolling or grooving. Thus, tests were carried out using samples with a thin coating of TiN, deposited using the Physical Vapor Deposition (PVD) technique, and AISI 52100 steel balls etched over 60 s to induce a change in their texture and roughness were used. Three abrasive slurries were prepared with black silicon carbide (SiC) particles (average particle size of 4 µm) with different concentrations, 0.25, 0.35, and 0.45 g/cm3. The rotation speed used in the tests was 80 rpm and the normal loads applied in the study were 0.2 N and 0.5 N, and 1 N. After the wear tests, the coated samples and tracks on the surface of the balls were observed by SEM and 3D microscopy to understand the abrasive particle dynamics, evaluating the wear mode transition as well as the function of both applied load and slurry concentration. The tracks in the balls showed particles embedded on their surface. A lower concentration of abrasion was conducted to higher specific wear rate. Moreover, a predominant two-body wear mechanism was induced when the abrasive concentration was increased. There was an increase in the roughness of the scar and the surface of the balls with an increase in the abrasive particles' concentration.

Study of the Chlorine Influence on the Corrosion of Three Steels to Be Used in Water Treatment Municipal Facilities.

Many municipal facilities, such as pools and drinking water treatment facilities, are subject to ongoing maintenance due to the corrosion of their metallic materials caused by chlorine, leading to high costs and a possible risk to public health. A proper study of the employed product's effect could lead to the use of better materials, which significantly increase the lifetime of metallic equipment more attacked by corrosion, through studies evaluating their cost-effectiveness. This paper was carried out with the objective of studying the degradation of some metallic materials (AISI 316L, AISI 321 and Duplex 14462) used in the referred facilities in order to select the one that possessed a better behavior. It was observed that the introduction of some more adequate materials can drastically reduce maintenance operations, with Duplex 14462 showing the best results, ideal for greater chlorine concentrations, followed by AISI 321, which may be employed for components in less contact with chlorine, since it is more easily affordable.

The Impact of the Deterioration on Wood by Chlorine: An Experimental Study.

The use of disinfection and cleaning chemicals in several municipal facilities, such as swimming pools and drinking water treatment plants, causes the degradation of various types of wood, which leads to failures in equipment and the corresponding need for maintenance. This degradation creates added costs for municipalities, as well as the closure of certain facilities due to curative or preventive maintenance and, in many cases, public health issues, due to the water being contaminated with deteriorating products. Through a thorough study of the degradation effect on the products, more resistant materials can be found which are able to withstand these adversities and increase the lifespan of wood in regular contact with chemical agents. This is achievable by the determination of the cost-effectiveness of the substitute material to replace these components with alternative ones, with properties that better resist the deterioration effects promoted by aggressive environments. No studies have been found so far strictly focused on this matter. The objective of this study is to evaluate the degradation presented by two types of wood, beech and oak, which are exposed to the action of chlorine in municipal facilities. This degradation varies according to the chlorine content and the materials' time of contact with the chemical agent, allowing the selection of new materials which will provide an extended lifetime of the components, reducing maintenance drastically, as well as costs for the facilities and the risk to public health. The performed experimental tests have shown that the oak wood has the best results regarding chlorine degradation resistance.

Identification of the Gene Repertoire of the IMD Pathway and Expression of Antimicrobial Peptide Genes in Several Tissues and Hemolymph of the Cockroach Blattella germanica.

Antimicrobial peptide (AMP) genes, triggered by Toll and IMD pathways, are essential components of the innate immune system in the German cockroach Blattella germanica. Besides their role in killing pathogenic bacteria, AMPs could be involved in controlling its symbiotic systems (endosymbiont and microbiota). We found that the IMD pathway was active in the adult female transcriptomes of six tissues (salivary glands, foregut, midgut, hindgut, Malpighian tubules and fat body) and hemolymph. Total expression of AMP genes was high in hemolymph and salivary glands and much lower in the other sample types. The expression of specific AMP genes was very heterogeneous among sample types. Two genes, defensin_g10 and drosomycin_g5, displayed relevant expression in the seven sample types, although higher in hemolymph. Other genes only displayed high expression in one tissue. Almost no expression of attacin-like and blattellicin genes was observed in any sample type, although some of them were among the genes with the highest expression in adult female whole bodies. The expression of AMP genes in salivary glands could help control pathogens ingested with food and even determine gut microbiota composition. The low expression levels in midgut and hindgut are probably related to the presence of beneficial microbiota. Furthermore, a reduction in the expression of AMP genes in fat body could be the way to prevent damage to the population of the endosymbiont Blattabacterium cuenoti within bacteriocytes.

NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway contributing to pancreatic islet survival and function.

LRH-1/NR5A2 is implicated in islet morphogenesis postnatally, and its activation using the agonist BL001 protects islets against apoptosis, reverting hyperglycemia in mouse models of Type 1 Diabetes Mellitus. Islet transcriptome profiling revealed that the expression of PTGS2/COX2 is increased by BL001. Herein, we sought to define the role of LRH-1 in postnatal islet morphogenesis and chart the BL001 mode of action conferring beta cell protection. LRH-1 ablation within developing beta cells impeded beta cell proliferation, correlating with mouse growth retardation, weight loss, and hypoglycemia leading to lethality. LRH-1 deletion in adult beta cells abolished the BL001 antidiabetic action, correlating with beta cell destruction and blunted Ptgs2 induction. Islet PTGS2 inactivation led to reduced PGE2 levels and loss of BL001 protection against cytokines as evidenced by increased cytochrome c release and cleaved-PARP. The PTGER1 antagonist-ONO-8130-negated BL001-mediated islet survival. Our results define the LRH-1/PTGS2/PGE2/PTGER1 signaling axis as a key pathway mediating BL001 survival properties.

Construction and Analysis of the Complete Genome Sequence of Leprosy Agent Mycobacterium lepromatosis.

Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. We report construction and analyses of the complete genome sequence of M. lepromatosis FJ924. The genome contained 3,271,694 nucleotides to encode 1,789 functional genes and 1,564 pseudogenes. It shared 1,420 genes and 885 pseudogenes (71.4%) with M. leprae but differed in 1,281 genes and pseudogenes (28.6%). In phylogeny, the leprosy bacilli started from a most recent common ancestor (MRCA) that diverged ~30 million years ago (Mya) from environmental organism Mycobacterium haemophilum. The MRCA then underwent reductive evolution with pseudogenization, gene loss, and chromosomal rearrangements. Analysis of the shared pseudogenes estimated the pseudogenization event ~14 Mya, shortly before species bifurcation. Afterwards, genomic changes occurred to lesser extent in each species. Like M. leprae, four major types of highly repetitive sequences were detected in M. lepromatosis, contributing to chromosomal rearrangements within and after MRCA. Variations in genes and copy numbers were noted, such as three copies of the gene encoding bifunctional diguanylate cyclase/phosphodiesterase in M. lepromatosis, but single copy in M. leprae; 6 genes encoding the TetR family transcriptional regulators in M. lepromatosis, but 11 such genes in M. leprae; presence of hemW gene in M. lepromatosis, but absence in M. leprae; and others. These variations likely aid unique pathogenesis, such as diffuse lepromatous leprosy associated with M. lepromatosis, while the shared genomic features should explain the common pathogenesis of dermatitis and neuritis in leprosy. Together, these findings and the genomic data of M. lepromatosis may facilitate future research and care for leprosy. IMPORTANCE Leprosy is a dreaded infection that still affects millions of people worldwide. Mycobacterium lepromatosis is a recently recognized cause in addition to the well-known Mycobacterium leprae. M. lepromatosis is likely specific for diffuse lepromatous leprosy, a severe form of the infection and endemic in Mexico. This study constructed and annotated the complete genome sequence of M. lepromatosis FJ924 and performed comparative genomic analyses with related mycobacteria. The results afford new and refined insights into the genome size, gene repertoire, pseudogenes, phylogenomic relationship, genome organization and plasticity, process and timing of reductive evolution, and genetic and proteomic basis for pathogenesis. The availability of the complete M. lepromatosis genome may prove to be useful for future research and care for the infection.

Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice.

Peptide DIIADDEPLT (Pep19) has been previously suggested to improve metabolic parameters, without adverse central nervous system effects, in a murine model of diet-induced obesity. Here, we aimed to further evaluate whether Pep19 oral administration has anti-obesogenic effects, in a well-established high-fat diet-induced obesity model. Male Swiss mice, fed either a standard diet (SD) or high-fat diet (HFD), were orally administrated for 30 consecutive days, once a day, with saline vehicle or Pep19 (1 mg/kg). Next, several metabolic, morphological, and behavioral parameters were evaluated. Oral administration of Pep19 attenuated HFD body-weight gain, reduced in approximately 40% the absolute mass of the endocrine pancreas, and improved the relationship between circulating insulin and peripheral insulin sensitivity. Pep19 treatment of HFD-fed mice attenuated liver inflammation, hepatic fat distribution and accumulation, and lowered plasma alanine aminotransferase activity. The inguinal fat depot from the SD group treated with Pep19 showed multilocular brown-fat-like cells and increased mRNA expression of uncoupling protein 1 (UCP1), suggesting browning on inguinal white adipose cells. Morphological analysis of brown adipose tissue (BAT) from HFD mice showed the presence of larger white-like unilocular cells, compared to BAT from SD, Pep19-treated SD or HFD mice. Pep19 treatment produced no alterations in mice behavior. Oral administration of Pep19 ameliorates some metabolic traits altered by diet-induced obesity in a Swiss mice model.

Sensing Apps and Public Data Sets for Digital Phenotyping of Mental Health: Systematic Review.

BACKGROUND: Mental disorders are normally diagnosed exclusively on the basis of symptoms, which are identified from patients' interviews and self-reported experiences. To make mental health diagnoses and monitoring more objective, different solutions have been proposed such as digital phenotyping of mental health (DPMH), which can expand the ability to identify and monitor health conditions based on the interactions of people with digital technologies. OBJECTIVE: This article aims to identify and characterize the sensing applications and public data sets for DPMH from a technical perspective. METHODS: We performed a systematic review of scientific literature and data sets. We searched 8 digital libraries and 20 data set repositories to find results that met the selection criteria. We conducted a data extraction process from the selected articles and data sets. For this purpose, a form was designed to extract relevant information, thus enabling us to answer the research questions and identify open issues and research trends. RESULTS: A total of 31 sensing apps and 8 data sets were identified and reviewed. Sensing apps explore different context data sources (eg, positioning, inertial, ambient) to support DPMH studies. These apps are designed to analyze and process collected data to classify (n=11) and predict (n=6) mental states/disorders, and also to investigate existing correlations between context data and mental states/disorders (n=6). Moreover, general-purpose sensing apps are developed to focus only on contextual data collection (n=9). The reviewed data sets contain context data that model different aspects of human behavior, such as sociability, mood, physical activity, sleep, with some also being multimodal. CONCLUSIONS: This systematic review provides in-depth analysis regarding solutions for DPMH. Results show growth in proposals for DPMH sensing apps in recent years, as opposed to a scarcity of public data sets. The review shows that there are features that can be measured on smart devices that can act as proxies for mental status and well-being; however, it should be noted that the combined evidence for high-quality features for mental states remains limited. DPMH presents a great perspective for future research, mainly to reach the needed maturity for applications in clinical settings.

Abnormal cannabidiol ameliorates inflammation preserving pancreatic beta cells in mouse models of experimental type 1 diabetes and beta cell damage.

The atypical cannabinoid Abn-CBD improves the inflammatory status in preclinical models of several pathologies, including autoimmune diseases. However, its potential for modulating inflammation in autoimmune type 1 diabetes (T1D) is unknown. Herein we investigate whether Abn-CBD can modulate the inflammatory response during T1D onset using a mouse model of T1D (non-obese diabetic- (NOD)-mice) and of beta cell damage (streptozotocin (STZ)-injected mice). Six-week-old female NOD mice were treated with Abn-CBD (0.1-1 mg/kg) or vehicle during 12 weeks and then euthanized. Eight-to-ten-week-old male C57Bl6/J mice were pre-treated with Abn-CBD (1 mg/kg of body weight) or vehicle for 1 week, following STZ challenge, and euthanized 1 week later. Blood, pancreas, pancreatic lymph nodes (PLNs) and T cells were collected and processed for analysis. Glycemia was also monitored. In NOD mice, treatment with Abn-CBD significantly reduced the severity of insulitis and reduced the pro-inflammatory profile of CD4+ T cells compared to vehicle. Concomitantly, Abn-CBD significantly reduced islet cell apoptosis and improved glucose tolerance. In STZ-injected mice, Abn-CBD decreased circulating proinflammatory cytokines and ameliorated islet inflammation reducing intra-islet phospho-NF-κB and TXNIP. Abn-CBD significantly reduced 2 folds intra-islet CD8+ T cells and reduced Th1/non-Th1 ratio in PLNs of STZ-injected mice. Islet cell apoptosis and intra-islet fibrosis were also significantly reduced in Abn-CBD pre-treated mice compared to vehicle. Altogether, Abn-CBD reduces circulating and intra-islet inflammation, preserving islets, thus delaying the progression of insulitis. Hence, Abn-CBD and related compounds emerge as new candidates to develop pharmacological strategies to treat the early stages of T1D.

Gut Microbiota Cannot Compensate the Impact of (quasi) Aposymbiosis in Blattella germanica.

Blattella germanica presents a very complex symbiotic system, involving the following two kinds of symbionts: the endosymbiont Blattabacterium and the gut microbiota. Although the role of the endosymbiont has been fully elucidated, the function of the gut microbiota remains unclear. The study of the gut microbiota will benefit from the availability of insects deprived of Blattabacterium. Our goal is to determine the effect of the removal (or, at least, the reduction) of the endosymbiont population on the cockroach's fitness, in a normal gut microbiota community. For this purpose, we treated our cockroach population, over several generations, with rifampicin, an antibiotic that only affects the endosymbiont during its extracellular phase, and decreases its amount in the following generation. As rifampicin also affects gut bacteria that are sensitive to this antibiotic, the treatment was performed during the first 12 days of the adult stage, which is the period when the endosymbiont infects the oocytes and lacks bacteriocyte protection. We found that after this antibiotic treatment, the endosymbiont population remained extremely reduced and only the microbiota was able to recover, although it could not compensate for the endosymbiont role, and the host's fitness was drastically affected. This accomplished reduction, however, is not homogenous and requires further study to develop stable quasi-aposymbiotic cockroaches.

Wear Behavior and Machining Performance of TiAlSiN-Coated Tools Obtained by dc MS and HiPIMS: A Comparative Study.

Duplex stainless steels are being used on applications that require high corrosion resistance and excellent mechanical properties, such as the naval and oil-gas exploration industry. The components employed in these industries are usually obtained by machining; however, these alloys have low machinability when compared to conventional stainless steels, usually requiring the employment of tool coatings. In the present work, a comparative study of TiAlSiN coating performance obtained by these two techniques in the milling of duplex stainless-steel alloy LDX 2101 was carried out. These coatings were obtained by the conventional direct current magnetron sputtering (dc MS) and the novel high power impulse magnetron sputtering (HiPIMS). The coatings were analyzed and characterized, determining mechanical properties for both coatings, registering slightly higher mechanical properties for the HiPIMS-obtained coating. Machining tests were performed with varying cutting length and feed-rate, while maintaining constant values for axial and radial depth of cut and cutting speed. The surface roughness of the material after machining was assessed, as well as the wear sustained by each of the tool types, identifying the wear mechanisms and behavior of these tools, as well as registering the flank wear values presented for each of the tested tools. The HiPIMS-obtained coating exhibited a very similar behavior when compared to the other, producing similar surface roughness quality. However, the HiPIMS coating exhibited less wear for higher cutting lengths, proving to be a better choice in this case, especially regarding tool life.

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity.

Rationale: We recently demonstrated that the 'Metabesity' factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. The impact of ORY1001, an inhibitor of the LSD1-CoREST complex, on HMG20A expression, reactive astrogliosis and glucose metabolism was evaluated in vitro and in vivo in high-fat high-sucrose fed mice. Results: We show that Hmg20a is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. HMG20A expression was upregulated in diet-induced obesity and glucose intolerant mice, correlating with increased transcript levels of Gfap and Il1b indicative of inflammation and reactive astrogliosis. Hmg20a transcript levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways which are hallmarks of reactive astrogliosis. Accordingly, HMG20A depleted astrocytes exhibited reduced mitochondrial bioenergetics and increased susceptibility to apoptosis. Neuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. ORY1001 treatment rescued expression of reactive astrogliosis-linked genes in HMG20A ablated astrocytes while enhancing cell surface area, GFAP intensity and STAT3 expression in healthy astrocytes, mimicking the effect of HMG20A. Furthermore, ORY1001 treatment protected against obesity-associated glucose intolerance in mice correlating with a regression of hypothalamic HMG20A expression, indicative of reactive astrogliosis attenuation with improved health status. Conclusion: HMG20A coordinates the astrocyte polarization state. Under physiological pressure such as obesity and insulin resistance that induces low grade inflammation, HMG20A expression is increased to induce reactive astrogliosis in an attempt to preserve the neuronal network and re-establish glucose homeostasis. Nonetheless, a chronic metabesity state or functional mutations will result in lower levels of HMG20A, failure to promote reactive astrogliosis and increase susceptibility of neurons to stress-induced apoptosis. Such effects could be reversed by ORY1001 treatment both in vitro and in vivo, paving the way for a new therapeutic approach for Type 2 Diabetes Mellitus.

(+)-trans-Cannabidiol-2-hydroxy pentyl is a dual CB1R antagonist/CB2R agonist that prevents diabetic nephropathy in mice.

Natural cannabidiol ((-)-CBD) and its derivatives have increased interest for medicinal applications due to their broad biological activity spectrum, including targeting of the cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). Herein, we synthesized the (+)-enantiomer of CBD and its derivative (+)-CBD hydroxypentylester ((+)-CBD-HPE) that showed enhanced CB1R and CB2R binding and functional activities compared to their respective (-) enantiomers. (+)-CBD-HPE Ki values for CB1R and CB2R were 3.1 ± 1.1 and 0.8 ± 0.1 nM respectively acting as CB1R antagonist and CB2R agonist. We further tested the capacity of (+)-CBD-HPE to prevent hyperglycemia and its complications in a mouse model. (+)-CBD-HPE significantly reduced streptozotocin (STZ)-induced hyperglycemia and glucose intolerance by preserving pancreatic beta cell mass. (+)-CBD-HPE significantly reduced activation of NF-κB by phosphorylation by 15% compared to STZ-vehicle mice, and CD3+ T cell infiltration into the islets was avoided. Consequently, (+)-CBD-HPE prevented STZ-induced apoptosis in islets. STZ induced inflammation and kidney damage, visualized by a significant increase in plasma proinflammatory cytokines, creatinine, and BUN. Treatment with (+)-CBD-HPE significantly reduced 2.5-fold plasma IFN-γ and increased 3-fold IL-5 levels compared to STZ-treated mice, without altering IL-18. (+)-CBD-HPE also significantly reduced creatinine and BUN levels to those comparable to healthy controls. At the macroscopy level, (+)-CBD-HPE prevented STZ-induced lesions in the kidney and voided renal fibrosis and CD3+ T cell infiltration. Thus, (+)-enantiomers of CBD, particularly (+)-CBD-HPE, have a promising potential due to their pharmacological profile and synthesis, potentially to be used for metabolic and immune-related disorders.

Correction to: Rules of Conduct for Behavior Analysts in the Presence of Hypothetical Constructs: A Commentary on Eckard and Lattal (2020).

[This corrects the article DOI: 10.1007/s40614-020-00272-w.].

Blattella germanica displays a large arsenal of antimicrobial peptide genes.

Defence systems against microbial pathogens are present in most living beings. The German cockroach Blattella germanica requires these systems to adapt to unhealthy environments with abundance of pathogenic microbes, in addition to potentially control its symbiotic systems. To handle this situation, four antimicrobial gene families (defensins, termicins, drosomycins and attacins) were expanded in its genome. Remarkably, a new gene family (blattellicins) emerged recently after duplication and fast evolution of an attacin gene, which is now encoding larger proteins with the presence of a long stretch of glutamines and glutamic acids. Phylogenetic reconstruction, within Blattellinae, suggests that this duplication took place before the divergence of Blattella and Episymploce genera. The latter harbours a long attacin gene (pre-blattellicin), but the absence of the encoded Glx-region suggests that this element evolved recently in the Blattella lineage. A screening of AMP gene expression in available transcriptomic SR projects of B. germanica showed that, while some AMPs are expressed during almost the whole development, others are restricted to shorter periods. Blattellicins are highly expressed only in adult females. None of the available SR tissue projects could be associated with blattellicins' expression, suggesting that it takes place in other tissues, maybe the gut.