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This article discusses a study on the potential use of the FDA-approved drug salbutamol for the treatment of collagen VI-related myopathies, a group of progressive muscle disorders. The study, conducted on a mouse model, found that salbutamol administration improved neuromuscular junction defects and muscle atrophy. Salbutamol has previously shown positive effects on neuromuscular junction structure and function in other animal models and has been used successfully off-label in various diseases. The study also found that salbutamol treatment increased muscle mass and promoted muscle regeneration in both the mouse model and wild-type mice. However, the study noted that further research is needed to optimize salbutamol-based therapeutic strategies for clinical trials. The study was funded by various organizations and declared no conflicts of interest. [Extracted from the article]

Despite a number of studies providing evidence that the extracellular matrix (ECM) is an active player in the pathogenesis of intestinal inflammation, knowledge on the actual contribution of specific ECM molecules in the progression of inflammatory bowel disease (IBD) remains scant. Here, we investigated the role of a major ECM protein, collagen VI (ColVI), in gut homeostasis and elucidated the impact of its deregulation on the pathophysiology of IBD. To this end, we combined in vivo and ex vivo studies on wild type and ColVI‐deficient (Col6a1−/−) mice both under physiological conditions and during experimentally induced acute colitis and its subsequent recovery, by means of gut histology and immunostaining, gene expression, bone marrow transplantation, flow cytometry of immune cell subpopulations, and lymph flow assessment. We found that ColVI displayed dynamic expression and ECM deposition during the acute inflammatory and recovery phases of experimentally induced colitis, whereas the genetic ablation of ColVI in Col6a1 null mice impaired the functionality of lymphatic vessels, which in turn affected the resolution of inflammation during colitis. Based on these findings, we investigated ColVI expression and deposition in ileal specimens from two cohorts of patients affected by Crohn's disease (CD) and correlated ColVI abundance to clinical outcome. Our results show that high ColVI immunoreactivity in ileal biopsies of CD patients at diagnosis correlates with increased risk of surgery and that ColVI expression in biopsies taken at the resection margin during surgery, and showing inactive disease, predict disease recurrence. Our data unveil a key role for ColVI in the intestinal microenvironment, where it is involved in lymphangiogenesis and intestinal inflammation. Altogether, these findings point at the dysregulation of ColVI expression as a novel factor contributing to the onset and maintenance of inflammation in CD via mechanisms impinging on the modulation of inflammatory cell recruitment and function. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Until the beginning of the twentieth century, history, as a core concept of the political project of modernity, was highly concerned with the future. The many crimes, genocides, and wars perpetuated in the name of historical progress eventually caused unavoidable fractures in the way Western philosophies of history have understood change over time, leading to a depoliticization of the future and a greater emphasis on matters of the present. However, the main claim of the "Historical Futures" project is that the future has not completely disappeared from the focus of historical thinking, and some modalities of the future that have been brought to the attention of historical thought relate to a more‐than‐human reality. This article aims to confront the prospects of a technological singularity through the eyes of peoples who already live in a world of more‐than‐human agency. The aim of this confrontation is to create not just an alternative way to think about the future but a stance from which we can explore ways to inhabit and therefore repoliticize historical futures. This article contains a comparative study that has been designed to challenge our technologized imaginations of the future and, at the same time, to infuse the theoretical experiment with contingent historical experiences. Could we consider artificial intelligence as a new historical subject? What about as an agent in a "more‐than‐human" history? To what extent can we read this new condition through ancient Amerindian notions of time? Traditionally, the relationship between Western anthropocentrism and Amerindian anthropomorphism has been framed in terms of an opposition. We intend to prefigure a less hierarchical and more horizontal relation between systems of thought, one devoid of a fixed center or parameter of reference. Granting the same degree of intellectual dignity to the works of Google engineers and the views of Amazonian shamans, we nevertheless foster an intercultural dialogue (between these two "traditions of reasoning") about a future in which history can become more‐than‐human. We introduce potential history as the framework not only to conceptualize Amerindian experiences of time but also to start building an intercultural dialogue that is designed to discuss AI as a historical subject. [ABSTRACT FROM AUTHOR]

Organotins such as tributyltin chloride (TBT), are highly diffused environmental pollutants, which act as metabolism disrupting chemicals, i.e. may interfere with fat tissue differentiation, as well as with neuroendocrine circuits, thus impairing the control of energetic balance. We have previously demonstrated that adult exposure to TBT altered the expression of neuropeptides in the hypothalamus. In this study, we orally administered daily a solution containing oil, or TBT (0.25, 2.5, or 25 μg/kg body weight/day) to pregnant females from gestational day 8 until birth, and to their pups from day 0 until post‐natal day 21. Our results showed that TBT exposure of female mice during gestation and of pups during lactation permanently altered the feeding efficiency of pups of both sexes and subcutaneous fat distribution in adult males. In addition, the neuropeptide Y system was affected at the level of the paraventricular nucleus, with a decrease in immunoreactivity in both sexes (significant in females for all TBT doses and in males only for intermediate TBT doses), while no effect was observed in other hypothalamic areas (arcuate, ventromedial and dorsomedial nuclei). Metabolic syndrome, as well as obesity and diabetes, which are significant health issues, are considered multifactorial diseases and may be caused by exposure to metabolic disruptors, both in adults and during perinatal life. In addition, our work indicates that TBT doses defined as the tolerably daily intake had a profound and sex‐specific long‐term effect. [ABSTRACT FROM AUTHOR]

At the beginning of the COVID‐19 pandemic, worldwide attempts were made to identify potential drugs effective against the COVID‐19. Hydroxychloroquine was among the first receiving attention. However, following its use in therapy, it has been shown that hydroxychloroquine was not only ineffective but probably, due to its known side effects, even responsible of increased mortality of patients. The objective of this study was to review the safety profile of hydroxychloroquine used off‐label for the treatment of COVID‐19. We analyze the reports of suspected adverse drug reactions (ADRs) collected in EudraVigilance, the European database of ADR reports. We collected 2266 reports for 2019 and 6525 for 2020. The most reported ADRs during 2020 were those relating to cardiac, hepatic, renal toxicity such as QT prolongation with 400 cases in 2020 (of which, 345 cases—9.97%—with COVID‐19 as a therapeutic indication) versus 1 case only in 2019 (0.01%), long QT syndrome: 38 cases in 2020 (36 as COVID‐19 treatment) versus 0 in 2019, hepatitis: 13 cases in 2019 (0.11%) and 132 in 2020, and 32 cases (24, 0.69%) of acute kidney injury in 2020 and only 3 cases in 2019. Moreover, some important vision‐related ADRs also increased significantly during 2020, such as retinal toxicity with 92 cases in 2020 versus 7 in 2019. Even though with its intrinsic limitations, our results may be added to the most recent scientific evidence to confirm the unfavorable risk profile of hydroxychloroquine in its off‐label use in the treatment of COVID‐19 disease. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and compare the diagnostic test accuracy (DTA) of three-dimensional transvaginal ultrasound (3D-TVS) and magnetic resonance imaging (MRI) for deep myometrial infiltration (DMI) and cervical invasion for preoperative staging and surgery planning in patients with endometrial cancer (EC).Methods: This systematic review and meta-analysis investigated the DTA of MRI and 3D-TVS for DMI and cervical invasion in patients with EC. A literature search was performed using MEDLINE, Scopus, EMBASE, ScienceDirect, The Cochrane library, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform to identify relevant studies published between January 2000 and December 2021. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.Results: Five studies, including a total of 450 patients, were included in the systematic review. All five studies compared the DTA of 3D-TVS vs MRI for DMI, and three studies compared the DTA of 3D-TVS vs MRI for cervical invasion. Pooled sensitivity, positive likelihood ratio and negative likelihood ratio for detecting DMI using 3D-TVS were 77% (95% CI, 66-85%), 4.57 and 0.31, respectively. The respective values for detecting DMI on MRI were 80% (95% CI, 73-86%), 4.22 and 0.24. Bivariate metaregression indicated a similar DTA of 3D-TVS and MRI (P = 0.80) for the correct identification of DMI. Pooled ln diagnostic odds ratio for detecting cervical invasion was 3.11 (95% CI, 2.09-4.14) for 3D-TVS and 2.36 (95% CI, 0.90-3.83) for MRI. The risk of bias was low for most of the four domains assessed in QUADAS-2.Conclusion: 3D-TVS demonstrated good diagnostic accuracy in terms of sensitivity and specificity for the evaluation of DMI and cervical invasion, with results comparable with those of MRI. Thus, we confirmed the potential role of 3D-TVS in the preoperative staging and surgery planning in patients with EC. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Cyanobacteria morphotypes with simple morphology, mainly thin filamentous homocytous strains, comprise a taxonomically complex group and represent a challenge in systematic studies. However, the polyphasic approach applied nowadays to investigate the cyanobacterial diversity has emerged as a powerful tool to undercover cryptic taxa and to set up a more natural classification system. Yet, studies exploring the cultured diversity of cyanobacteria from extreme tropical environments have paved the way to the discovery of new cyanobacteria taxa, enabling the description of Pantanalinema, Alkalinema, and Cephalothrix as novel genera from saline–alkaline lakes in Pantanal wetlands (Brazil). The present study investigated a set of cyanobacterial strains resembling Leptolyngbya morphotypes by means of its morphology, 16S ribosomal RNA (16S rRNA) phylogeny, and ITS secondary structures. Based on the shape and structure of their trichomes, the low levels of 16S rRNA identity coupled with the distinct phylogenetic position with regard to well establish genera, and their divergent ecological feature, these strains must be accommodated into a novel genus, named as Monilinema gen. nov., described under the provisions of the International Code of Nomenclature for algae, fungi, and plants. Accordingly, based on the singularity of the D1–D1′ and V3 helixes, these strains should be considered as a single species, Monilinema alkalinum. [ABSTRACT FROM AUTHOR]

Aims: Human papilloma virus (HPV) is 1 of the most common sexually transmitted infection responsible for different types of cancer: cervical, penile, vulvar, anal and oropharyngeal. It can affect both males and females. Our aim was to enrich the knowledge on the safety profiles of HPV vaccines in the male population. Methods: We reviewed all the reports of adverse events following immunization (AEFI) present in the US Vaccine Adverse Event Reporting System from 1 January 2006 to 30 September 2018. Statistical data mining was performed using the reporting odds ratio with 95% confidence interval in order to detect disproportionality in reporting. Results: A total of 5493 reports of AEFI were retrieved. The events most reported and that proportionally occurred more frequently with HPV vaccines than with others in males were: syncope (n = 701, reporting odds ratio = 2.85, 95% confidence interval [1.41–5.76p), loss of consciousness (n = 425, 2.79 [1.36–5.72]) and fall (n = 272, 3.54 [2.00–6.26]). Conclusion: Most of the AEFIs were already reported in premarketing clinical trials and acknowledged for the corresponding vaccines. A disproportionate reporting was found for some of these events including syncope. The HPV vaccines are generally well tolerated in males, although limitations own of spontaneous reporting should be considered. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) in which inflammation plays a key pathological role. Recent evidences showed that systemic inflammation induces increasing cell infiltration within meninges and perivascular spaces in the brain parenchyma, triggering resident microglial and astrocytic activation. The anti‐inflammatory enzyme A20, also named TNF associated protein 3 (TNFAIP3), is considered a central gatekeeper in inflammation and peripheral immune system regulation through the inhibition of NF‐kB. The TNFAIP3 locus is genetically associated to MS and its transcripts is downregulated in blood cells in treatment‐naïve MS patients. Recently, several evidences in mouse models have led to hypothesize a function of A20 also in the CNS. Thus, here we aimed to unveil a possible contribution of A20 to the CNS human MS pathology. By immunohistochemistry/immunofluorescence and biomolecular techniques on post‐mortem brain tissue blocks obtained from control cases (CC) and progressive MS cases, we demonstrated that A20 is present in CC brain tissues in both white matter (WM) regions, mainly in few parenchymal astrocytes, and in grey matter (GM) areas, in some neuronal populations. Conversely, in MS brain tissues, we observed increased expression of A20 by perivascular infiltrating macrophages, resident‐activated astrocytes, and microglia in all the active and chronic active WM lesions. A20 was highly expressed also in the majority of active cortical lesions compared to the neighboring areas of normal‐appearing grey matter (NAGM) and control GM, particularly by activated astrocytes. We demonstrated increased A20 expression in the active MS plaques, particularly in macrophages and resident astrocytes, suggesting a key role of this molecule in chronic inflammation. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a flavivirus that can cause neuropathogenesis in adults and fetal neurologic malformation following the infection of pregnant women. We used a nonhuman primate model, the Indian‐origin Rhesus macaque (IRM), to gain insight into virus‐associated hallmarks of ZIKV‐induced adult neuropathology. We find that the virus causes prevalent acute and chronic neuroinflammation and chronic disruption of the blood‐brain barrier (BBB) in adult animals. ZIKV infection resulted in specific short‐ and long‐term augmented expression of the chemokine CXCL12 in the central nervous system (CNS)of adult IRMs. Moreover, CXCL12 expression persists long after the initial viral infection is apparently cleared. CXCL12 plays a key role both in regulating lymphocyte trafficking through the BBB to the CNS and in mediating repair of damaged neural tissue including remyelination. Understanding how CXCL12 expression is controlled will likely be of central importance in the definition of ZIKV‐associated neuropathology in adults. [ABSTRACT FROM AUTHOR]

Wave climate projections at global scales are often of little direct use for local or regional coastal applications, where bathymetric gradients and coastal geometry dominate onshore wave propagation and transformation. In such systems, and even more in the case of semi‐enclosed basins where coastal orography can play a major role in wind modulation, wave climate assessments require a specific effort, with particularly strict prescriptions in terms of model resolution and quality of the wind forcing. In this work, we provide a numerical modelling estimate of the expected variations of wave regime in the Adriatic Sea (a semi‐enclosed basin of the Mediterranean Sea) under an IPCC RCP 8.5 climate change scenario at the end of the current century, focusing on the implications for energy modulation in the coastal regions. Results tend to confirm the evolution towards an overall decrease of wave storminess in the basin, as suggested by previous studies, but show that some regions might experience a local increase in the severity of the sea states impacting the coast. The model resolution and the unprecedented directional skills of the climatological wind forcings allow to ascribe this behaviour to a shift in the directional wind regime that can be related to a northward translation of the Mediterranean cyclones trajectory. Although in the absence of a quantitative assessment of the uncertainty associated with the choice of the climate model, our results give an account of the possible extent of the spatial variability of the response of coastal dynamics to mid‐latitude storm tracks modification induced by climate change. [ABSTRACT FROM AUTHOR]

Understanding the interplay between processes operating at large and small spatiotemporal scales in shaping biotic interactions remains challenging. Recent studies illustrate how phenotypic specialization, species life‐history traits and/or resource partitioning recurrently underlie the structure of mutualistic interactions in terrestrial ecosystems along large latitudinal gradients of biodiversity. However, we know considerably less about how local processes interact with large‐scale patterns of biodiversity in modulating biotic interactions in the marine realm. Considering agonistic behaviour as a proxy for contest competition, we empirically investigate whether the structure of reef fish agonistic interactions is conserved across a 34 000‐km longitudinal gradient of biodiversity. By sampling coral reefs using standardized remote underwater video, we found recurrent patterns of fish agonistic behaviour in disparate communities distributed across five biogeographic provinces of the Pacific and Atlantic oceans. While the sheer number of species increases with regional richness, the number of aggressive disputes at the habitat scale is similar across communities. We then combined generalized linear models and network theory to reveal that, the emergent structure of local agonistic networks is not modular but instead recurrently display a nested structure, with a core of highly interactive site‐attached herbivores of the Pomacentridae family. Therefore, despite the increase in the number of species involved in agonistic interactions toward speciose communities, the network structure is conserved along the longitudinal richness gradient because local disputes are mostly driven by closely‐related, functionally‐similar species. These findings suggest that evolutionary and local processes interact in modulating reef fish agonistic behaviour and that fine‐scale niche‐partitioning can structure the ecological networks in marine ecosystems. [ABSTRACT FROM AUTHOR]

Rationale: Mycosporine‐like amino acids (MAAs) are UV‐absorbing compounds produced by fungi, algae, lichens, and cyanobacteria when exposed to UV radiation. These compounds have photoprotective and antioxidant functions and have been widely studied for possible use in sunscreens and anti‐aging products. This study aims to identify MAA‐producing cyanobacteria with potential application in cosmetics. Methods: A method for the identification of MAAs was developed using ultrahigh‐performance liquid chromatography with diode array detection coupled to quadrupole time‐of‐flight mass spectrometry (UHPLC‐DAD/QTOFMS). Chromatographic separation was carried out using a Synergi 4 μ Hydro‐RP 80A column (150 × 2,0 mm) at 30°C with 0.1% formic acid aqueous solution + 2 mM ammonium formate and acetonitrile/water (8:2) + 0.1% formic acid as a mobile phase. Results: Out of the 69 cyanobacteria studied, 26 strains (37%) synthesized MAAs. Nine different MAAs were identified using UHPLC‐DAD/QTOFMS. Iminomycosporines were the major group detected (7 in 9 MAAs). In terms of abundance, the most representative genera for MAA production were heterocyte‐forming groups. Oscilatoria sp. CMMA 1600, of homocyte type, produced the greatest diversity of MAAs. Conclusions: The UHPLC‐DAD/QTOFMS method is a powerful tool for identification and screening of MAAs in cyanobacterial strains as well as in other organisms such as dinoflagellates, macroalgae, and microalgae. The different cyanobacterial genera isolated from diverse Brazilian biomes and environments are prolific sources of MAAs. [ABSTRACT FROM AUTHOR]

Little is known about the administration of direct‐acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, seriousness and dechallenge/rechallenge outcome was carried out. For each report, the time‐to‐onset was evaluated and the causality was assessed by using Naranjo algorithm. Overall, 1316 reports were retrieved, most concerning rivaroxaban (58.8%); 80% of the reports were related to females, in particular to those aged ≥65 years (23.1%). The median value of the time‐to‐onset was 28 days, with an interquartile range of 63 days. In 54.3% of the reports the causality was assessed as possible. In conclusion, a possible association could exist between DOACs administration and alopecia, but further observational studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: The cardiovascular safety profile of macrolides and fluoroquinolones has been widely discussed. The aim of the present study is to provide the contribution of real‐world data onto the ongoing discussion about cardiovascular toxicity of both macrolides and fluoroquinolones. Methods: Reports of adverse drug reactions (ADRs) were retrieved from VigiBase. Macrolides and fluoroquinolones were compared with amoxicillin by using the reporting odds ratio (ROR) as a measure of disproportionality. Macrolides were then compared with fluoroquinolones. Results: Overall, 6810 reports of ADRs were retrieved: 62% of them were serious and 35% concerned female. Macrolides were more frequently associated with "atrial fibrillation" (ROR = 1.26, CI 1.02‐1.57) and "ventricular fibrillation" ROR = 2.60, CI 1.92‐3.54) than fluoroquinolones. Antimicrobials more frequently reported for "cardiac disorder" were azithromycin (375 reports) and clarithromycin (302) for macrolides and levofloxacin (470) and moxifloxacin (391) for fluoroquinolones. Conclusion: Our data highlighted that macrolides and fluoroquinolones may influence cardiac rhythm and suggest caution in the prescribing of these drugs to patients with hidden cardiovascular risk factors. Although these ADRs seem to be not common, they have a notable impact in clinical practice because of the huge number of the exposed subjects. [ABSTRACT FROM AUTHOR]

Aims: Human papilloma virus (HPV) is the cause of different types of carcinoma. Despite the remarkable effectiveness of the HPV vaccines, there have been many complaints about their risk–benefit profile due to adverse events following immunization (AEFI). The purpose of this study is to analyse the safety profile of the HPV vaccine basing on real‐life data derived from reports of suspected AEFIs collected in the US Vaccine Adverse Events Reporting System (VAERS) and assess if the searches on Google overlap with spontaneous reporting. Methods: We collected all the reports in VAERS between January 2007 to December 2017 related to the HPV vaccines. A disproportionality analysis using reporting odds ratio (ROR) with 95% confidence interval was performed. Results: Over the 10‐year period, 55 356 reports of AEFI related to HPV vaccines were retrieved in VAERS, corresponding to 224 863 vaccine‐event pairs. The highest number of reports was related to Gardasil (n = 42 244). The two events more frequently reported and statistically significant for HPV vaccines were dizziness (n = 6259; ROR = 2.60; 95% confidence interval 2.53–2.66) and syncope (n = 6004; ROR = 6.28; 95% confidence interval 6.12–6.44). The trends of spontaneous reporting and Google searches overlap. Conclusion: The AEFI analysis showed that the events most frequently reported were non‐serious and listed in the corresponding summary of product characteristics. Potential safety signals arose regarding less frequent AEFIs that would deserve further investigation. It is extremely important to disseminate correct and evidence‐based scientific information. [ABSTRACT FROM AUTHOR]

Skeletal muscle engineering aims at tissue reconstruction to replace muscle loss following traumatic injury or in congenital muscle defects. Skeletal muscle can be engineered by using biodegradable and biocompatible scaffolds that favor myogenic cell adhesion and subsequent tissue organization. In this study, we characterized scaffolds made of gelatin cross‐linked with genipin, a natural derived cross‐linking agent with low cytotoxicity and high biocompatibility, for tissue engineering of skeletal muscle. We generated gelatin–genipin hydrogels with a stiffness of 13 kPa to reproduce the mechanical properties characteristic of skeletal muscle and we show that their surface can be topographically patterned through soft lithography to drive myogenic cells differentiation and unidirectional orientation. Furthermore, we demonstrate that these biomaterials can be successfully implanted in vivo under dorsal mouse skin, showing good biocompatibility and slow biodegradation rate. Moreover, the grafting of this biomaterial in partially ablated tibialis anterior muscle does not impair muscle regeneration, supporting future applications of gelatin–genipin biomaterials in the field of skeletal muscle tissue repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2763–2777, 2018. [ABSTRACT FROM AUTHOR]

Abstract: Shallow reefs are among the most diverse ecosystems, and their substrate is densely occupied by sessile organisms that frequently contact physically and interact mutually. Nevertheless, the relative importance of species abundance in shaping physical contacts in these ecosystems remains largely unknown. The aim of this study was to evaluate physical contact interactions, by using tools derived from the complex network theory, between hard corals and other benthic organisms in four areas along the Brazilian coast comprising coral reefs and rocky shores with different physical and biotic structures. It was also investigated whether interactions with corals occurred as expected by the abundance of the benthic organisms in each area, and whether corals belonging to families known as more aggressive interacted less with other organisms. In all areas, the abundance of both corals and contacting organisms directly influenced the abundance of interactions between benthic organisms, regardless of the physical or biological characteristics of the habitat and of the interacting organisms. In addition, coral species interacted more with the most abundant benthic group, the epilithic algal matrix, in all areas. Nevertheless, some evidence was found about biological mechanisms helping to explain the structure of the studied interactions, although to a lesser extent. The obtained networks presented high nestedness and connectance, but low modularity. These patterns indicate the low specificity of the studied interactions and reinforce the role of abundance as an important driver of contacts between sessile organisms in shallow hard bottom ecosystems. [ABSTRACT FROM AUTHOR]

EMILIN3 is an extracellular matrix glycoprotein that displays a dynamic and restricted expression pattern in connective tissues during post-natal life. In this study, we report the characterization of EMILIN3 deposition in the skin. In addition, to unravel the functions of this protein in skin homeostasis, we generated Emilin3 null mice and provide evidence that EMILIN3 is dispensable for hair follicle growth and maintenance throughout adult life. [ABSTRACT FROM AUTHOR]

Objective Mechanical factors play a critical role in the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. We undertook this study to test the hypothesis that type VI collagen is necessary for mechanotransduction in articular cartilage by determining the effects of type VI collagen knockout on the activation of the mechano-osmosensitive, calcium-permeable channel TRPV4 (transient receptor potential vanilloid channel 4) as well as on osmotically induced chondrocyte swelling and pericellular matrix (PCM) mechanical properties. Methods Confocal laser scanning microscopy was used to image TRPV4-mediated calcium signaling and osmotically induced cell swelling in intact femora from 2- and 9-month-old wild-type (WT) and type VI collagen-deficient (Col6a1 −/−) mice. Immunofluorescence-guided atomic force microscopy was used to map PCM mechanical properties based on the presence of perlecan. Results Hypo-osmotic stress-induced TRPV4-mediated calcium signaling was increased in Col6a1−/− mice relative to WT controls at 2 months. Col6a1−/− mice exhibited significantly increased osmotically induced cell swelling and decreased PCM moduli relative to WT controls at both ages. Conclusion In contrast to our original hypothesis, type VI collagen was not required for TRPV4-mediated Ca2+ signaling; however, knockout of type VI collagen altered the mechanical properties of the PCM, which in turn increased the extent of cell swelling and osmotically induced TRPV4 signaling in an age-dependent manner. These findings emphasize the role of the PCM as a transducer of mechanical and physicochemical signals, and they suggest that alterations in PCM properties, as may occur with aging or osteoarthritis, can influence mechanotransduction via TRPV4 or other ion channels. [ABSTRACT FROM AUTHOR]

Contents The study of lipids and fatty acids ( FAs) has been used in the assessment of egg quality because their composition can influence the fertilization rate, hatching, survival and growth of marine fish larvae. For these reasons, the lipid content ( TL) and fatty acid composition of common sole ( Solea solea) eggs were measured and correlated to egg and larval viability parameters throughout an entire reproductive season. Seventeen batches of fertile eggs obtained from natural spawning of captive breeders were characterized for the TL, FA profile, hatching rate ( HR) and survival rate of larvae ( SR) at 0-6 days post-hatching (dph). The egg FA composition reflected the composition of the feed supplied to the broodstock during summer and autumn (before and during vitellogenesis) rather than that supplied during the spawning season. In general, the egg FA profile showed minimal differences among the early-, mid- and late-spawning periods (possibly due to the change of the diet and/or water temperature) indicating that it is possible to obtain a similar egg quality in terms of egg FA profile over 2 months of spawning. Saturated FAs and monounsaturated FAs ( MUFA) were positively correlated with HR, while TL, 22 : 6n-3 ( DHA), 20 : 4n-6 ( ARA), polyunsaturated FAs of the (n-3) series (n-3 PUFA) and polyunsaturated FAs of the (n-6) series were negatively correlated (p ≤ 0.05). MUFA, 20 : 5n-3 ( EPA), n-6/n-3 were positively correlated with SR, while DHA, n-3 PUFA, DHA/ EPA were negatively correlated (p ≤ 0.05). In conclusion, the feed supplied before and during vitellogenesis has a major role in determining the egg FA profile in common sole. The relationships found between TL and FAs with egg and larval viability parameters differ from many other farmed marine fish species, which may suggest the need for a specific broodstock feed for this species. [ABSTRACT FROM AUTHOR]

Saline-alkaline lakes are extreme environments that limit the establishment and development of life. The Nhecolândia, a subregion of the Pantanal wetland in Brazil, is characterized by the existence of ~500 saline-alkaline lakes, which support an underexplored and rich diversity of microorganisms. In this study, unicellular and homocytous cyanobacteria from five saline-alkaline lakes were accessed by culture-dependent approaches. Morphological evaluation and analyses of near complete sequences (~1400 nt) of the 16S r RNA genes were applied for phylogenetic and taxonomic placement. This polyphasic approach allowed for the determination of the taxonomic position of the isolated strains into the following genera: Cyanobacterium, Geminocystis, Phormidium, Leptolyngbya, Limnothrix, and Nodosilinea. In addition, fourteen Pseudanabaenales and Oscillatoriales representatives of putative novel taxa were found. These sequences fell into five new clades that could correspond to new generic units of the Pseudanabaenaceae and Phormidiaceae families. [ABSTRACT FROM AUTHOR]

Objectives The aim was to compare the efficacy of the electric versus the manual toothbrush in terms of the oral hygiene achieved by patients wearing rapid palatal expanders ( RPEs). Methods Forty patients were randomly divided into two groups; one equipped with a manual toothbrush (Group A), the other with an electric toothbrush (Group B). Each child's plaque index ( PI) and gingival index ( GI) were calculated at banded molar level at times T0 (before banding), T1 (a month later), T2 (3 months later) and T3 (when the expander was removed). At each appointment, the PI and GI were recorded and the patient was remotivated. Results The level of oral hygiene achieved by the group using an electric toothbrush produced a greater improvement in the two indexes than in the group using the manual toothbrush that showed no statistically significant improvement ( PI T0-T3: P = 0.309; GI T0-T3: P = 0.141). Both indexes dropped considerably in both groups from T0 to T2, but more so in the group B. From T2 to T3, although the electric toothbrush continued to be substantially more effective, Group B showed a statistically significant deterioration in the oral hygiene ( PI +20%; GI +33%). Other assessments conducted on particular areas of the tooth showed improvements in the PI (−33%) for the vestibular region, and for the GI (−57%) in the palatal region among the patients in Group B, while there were no significant changes in these indexes in Group A. Conclusions Our findings show that the electric toothbrush is statistically more efficient in performing an adequate level of oral hygiene in children wearing RPE. [ABSTRACT FROM AUTHOR]

EMILIN2 is an extracellular matrix ( ECM) protein that exerts contradictory effects within the tumour microenvironment: it induces apoptosis in a number of tumour cells, but it also enhances tumour neo-angiogenesis. In this study, we describe a new mechanism by which EMILIN2 attenuates tumour cell viability. Based on sequence homology with the cysteine-rich domain ( CRD) of the Frizzled receptors, we hypothesized that EMILIN2 could affect Wnt signalling activation and demonstrate direct interaction with the Wnt1 ligand. This physical binding leads to decreased LRP6 phosphorylation and to the down-modulation of β-catenin, TAZ and their target genes. As a consequence, EMILIN2 negatively affects the viability, migration and tumourigenic potential of MDA-MB-231 breast cancer cells in a number of two- and three-dimensional in vitro assays. EMILIN2 does not modulate Wnt signalling downstream of the Wnt-Frizzled interaction, since it does not affect the activation of the pathway following treatment with the GSK3 inhibitors LiCl and CHIR99021. The interaction with Wnt1 and the subsequent biological effects require the presence of the EMI domain, as there is no effect with a deletion mutant lacking this domain. Moreover, in vivo experiments show that the ectopic expression of EMILIN2, as well as treatment with the recombinant protein, significantly reduce tumour growth and dissemination of cancer cells in nude mice. Accordingly, the tumour samples are characterized by a significant down-regulation of the Wnt signalling pathway. Altogether, these findings provide further evidence of the complex regulations governed by EMILIN2 in the tumour microenvironment, and they identify a key extracellular regulator of the Wnt signalling pathway. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The aims of this work were to study cyanobacterial isolates resembling the genus Hydrocoryne using a combination of morphology and phylogeny of 16S r RNA and nifH sequences and to investigate genes involved in cyanotoxin and protease inhibitor production. Four new cyanobacterial strains, isolated from biofilm samples collected from King George Island, Antarctica, were studied. In terms of morphology, these new strains share traits similar to true Anabaena morphotypes (benthic ones), whereas phylogenetic analysis of their 16S r RNA gene sequences grouped them with the sequence of the type species Hydrocoryne spongiosa (H. Schwabe ex Bornet and Flahault 1886-1888), but not with sequences of the type species from the genus Anabaena. This cluster is the sister group of Anabaena morphotypes isolated only from the Gulf of Finland. In addition, this cluster is related to two other clusters formed by sequences of Anabaena isolated from different sites. Partial nifH genes were sequenced from two strains and the phylogenetic tree revealed that the Antarctic nifH sequences clustered with sequences from Anabaena. Furthermore, two strains were tested, using PCR with specific primers, for the presence of genes involved in cyanotoxins (microcystin and saxitoxin) and protease inhibitor (aeruginosin, and cyanopeptolin). Only cyanopeptolin was amplified using PCR. These four Hydrocoryne strains are the first to be isolated and sequenced from Antarctica, which improves our knowledge on this poorly defined cyanobacterial genus. [ABSTRACT FROM AUTHOR]

Microbial eukaryotes may extinguish much of their nuclear phylogenetic history due to endosymbiotic/horizontal gene transfer (E/HGT). We studied E/HGT in 32,110 contigs of expressed sequence tags (ESTs) from the dinoflagellate Alexandrium tamarense (Dinophyceae) using a conservative phylogenomic approach. The vast majority of predicted proteins (86.4%) in this alga are novel or dinoflagellate-specific. We searched for putative homologs of these predicted proteins against a taxonomically broadly sampled protein database that includes all currently available data from algae and protists, and reconstructed a phylogeny from each of the putative homologous protein sets. Of the 2,523 resulting phylogenies, 14%-17% are potentially impacted by E/HGT involving both prokaryote and eukaryote lineages, with 2%-4% showing clear evidence of reticulate evolution. The complex evolutionary histories of the remaining proteins, many of which may also have been affected by E/HGT, cannot be interpreted using our approach with currently available gene data. We present empirical evidence of reticulate genome evolution that combined with inadequate or highly complex phylogenetic signal in many proteins may impede genome-wide approaches to infer the tree of microbial eukaryotes. [ABSTRACT FROM AUTHOR]

Collagen VI myopathies (Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM), and myosclerosis myopathy) share a common pathogenesis, that is, mitochondrial dysfunction due to deregulation of the permeability transition pore (PTP). This effect was first identified in the Col6a1 −/− mouse model and then in muscle cell cultures from UCMD and BM patients; the normalizing effect of cyclosporin A (CsA) confirmed the pathogenic role of PTP opening. In order to determine whether mitochondrial performance can be used as a criterion for inclusion in clinical trials and as an outcome measure of the patient response to therapy, it is mandatory to establish whether mitochondrial dysfunction is conserved in primary cell cultures from UCMD and BM patients. In this study we report evidence that mitochondrial dysfunction and the consequent increase of apoptotic rate can be detected not only, as previously reported, in muscle, but also in fibroblast cell cultures established from muscle biopsies of collagen VI-related myopathic patients. However, the mitochondrial phenotype is no longer maintained after nine passages in culture. These data demonstrate that the dire consequences of mitochondrial dysfunction are not limited to myogenic cells, and that this parameter can be used as a suitable diagnostic criterion, provided that the cell culture conditions are carefully established. J. Cell. Physiol. 227: 2927-2935, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week) of 2′-O-methyl-phosphorothioate antisense oligoribonucleotides (AONs) adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres) were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage). In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdxmice. Our data therefore demonstrate the long-termresidual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules. [ABSTRACT FROM AUTHOR]

Aim: To estimate occurrence of non-specific musculoskeletal pain in a wide population sample of Italian adolescents, and to investigate their use of healthcare services (seeking of medical attention, referral for diagnostic tests and treatment use). Methods: We investigated 7542 high-school adolescents (aged between 12 and 16 years) by a structured questionnaire and consisting of personal data, presence of pain, health provider consulted, referral for diagnostic tests and compliance with the prescribed treatments. Results: In 3399 (45.1%) reported musculoskeletal pain (the most affected sites being the spine and knees), 2525 (74.2%) of whom had sought medical attention. Of the 2525 subjects who had sought healthcare, 1061 (42.0%) had consulted more than one health provider, 2410 (95.4%) had been referred for diagnostic tests, and some form of treatment had been recommended for 2445 (96.8%), but only 1694 (69.2%) had complied with prescribed therapies. The most important factors linked to health seeking behaviour were pain intensity, pain lasting longer than 3 months, injury, interruption to or absence of physical activity and localization in the spine and knee. Conclusion: Non-specific musculoskeletal pain is a frequent event in Italian adolescents and that a large number of these subjects consult a healthcare service. [ABSTRACT FROM AUTHOR]

Background and Purpose: We have investigated the therapeutic effects of the selective cyclophilin inhibitor D-MeAla(3)-EtVal(4)-cyclosporin (Debio 025) in myopathic Col6a1(-/-) mice, a model of muscular dystrophies due to defects of collagen VI.Experimental Approach: We studied calcineurin activity based on NFAT translocation; T cell activation based on expression of CD69 and CD25; propensity to open the permeability transition pore in mitochondria and skeletal muscle fibres based on the ability to retain Ca(2+) and on membrane potential, respectively; muscle ultrastructure by electronmicroscopy; and apoptotic rates by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assays in Col6a1(-/-) mice before after treatment with Debio 025.Key Results: Debio 025 did not inhibit calcineurin activity, yet it desensitizes the mitochondrial permeability transition pore in vivo. Treatment with Debio 025 prevented the mitochondrial dysfunction and normalized the apoptotic rates and ultrastructural lesions of myopathic Col6a1(-/-) mice.Conclusions and Implications: Desensitization of the mitochondrial permeability transition pore can be achieved by selective inhibition of matrix cyclophilin D without inhibition of calcineurin, resulting in an effective therapy of Col6a1(-/-) myopathic mice. These findings provide an important proof of principle that collagen VI muscular dystrophies can be treated with Debio 025. They represent an essential step towards an effective therapy for Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy, because Debio 025 does not expose patients to the potentially harmful effects of immunosuppression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Chondrocytes, the sole cell type in articular cartilage, maintain the extracellular matrix (ECM) through a homeostatic balance of anabolic and catabolic activities that are influenced by genetic factors, soluble mediators, and biophysical factors such as mechanical stress. Chondrocytes are encapsulated by a narrow tissue region termed the 'pericellular matrix' (PCM), which in normal cartilage is defined by the exclusive presence of type VI collagen. Because the PCM completely surrounds each cell, it has been hypothesized that it serves as a filter or transducer for biochemical and/or biomechanical signals from the cartilage ECM. The present study was undertaken to investigate whether lack of type VI collagen may affect the development and biomechanical function of the PCM and alter the mechanical environment of chondrocytes during joint loading. METHODS: Col6a1(-/-) mice, which lack type VI collagen in their organs, were generated for use in these studies. At ages 1, 3, 6, and 11 months, bone mineral density (BMD) was measured, and osteoarthritic (OA) and developmental changes in the femoral head were evaluated histomorphometrically. Mechanical properties of articular cartilage from the hip joints of 1-month-old Col6a1(-/-), Col6a1(+/-), and Col6a1(+/+) mice were assessed using an electromechanical test system, and mechanical properties of the PCM were measured using the micropipette aspiration technique. RESULTS: In Col6a1(-/-) and Col6a1(+/-) mice the PCM was structurally intact, but exhibited significantly reduced mechanical properties as compared with wild-type controls. With age, Col6a1(-/-) mice showed accelerated development of OA joint degeneration, as well as other musculoskeletal abnormalities such as delayed secondary ossification and reduced BMD. CONCLUSION: These findings suggest that type VI collagen has an important role in regulating the physiology of the synovial joint and provide indirect evidence that alterations in the mechanical environment of chondrocytes, due to either loss of PCM properties or Col6a1(-/-)-derived joint laxity, can lead to progression of OA. [ABSTRACT FROM AUTHOR]

Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM) are muscle diseases due to mutations in the genes encoding the extracellular matrix protein collagen VI. Generation of a dystrophic mouse model where collagen VI synthesis was prevented by genetic ablation of the Col6a1 gene allowed an investigation of pathogenesis, which revealed the existence of a Ca2+-mediated dysfunction of mitochondria and the sarcoplasmic reticulum. A key event appears to be inappropriate opening of the mitochondrial permeability transition pore, an inner membrane high-conductance channel. Consistently, the Col6a1−/− myopathic mice could be cured with cyclosporin A through inhibition of cyclophilin D, a matrix protein that sensitizes the pore to opening. Studies of myoblasts from UCMD and BM patients demonstrated the existence of a latent mitochondrial dysfunction irrespective of the genetic lesion responsible for the lack or the alteration of collagen VI. These studies suggest that PTP opening may represent the final common pathway for skeletal muscle fiber death; and provided a rationale for a pilot clinical trial with cyclosporin A in patients affected by UCMD and BM, a study that holds great promise for the future treatment of collagen VI myopathies. [ABSTRACT FROM AUTHOR]

The identification of high-performance indicator taxa that combine practical feasibility and ecological value requires an understanding of the costs and benefits of surveying different taxa. We present a generic and novel framework for identifying such taxa, and illustrate our approach using a large-scale assessment of 14 different higher taxa across three forest types in the Brazilian Amazon, estimating both the standardized survey cost and the ecological and biodiversity indicator value for each taxon. Survey costs varied by three orders of magnitude, and dung beetles and birds were identified as especially suitable for evaluating and monitoring the ecological consequences of habitat change in our study region. However, an exclusive focus on such taxa occurs at the expense of understanding patterns of diversity in other groups. To improve the cost-effectiveness of biodiversity research we encourage a combination of clearer research goals and the use of an objective evidence-based approach to selecting study taxa. [ABSTRACT FROM AUTHOR]

Emilins are a family of extracellular matrix proteins with common structural organization and containing a characteristic N-terminal cysteine-rich domain. The prototype of this family, Emilin-1, is found in human and murine organs in association with elastic fibers, and other emilins were recently isolated in mammals. To gain insight into these proteins in lower vertebrates, we investigated the expression of emilins in the fish Danio rerio. Using sequence similarity tools, we identified eight members of this family in zebrafish. Each emilin gene has two paralogs in zebrafish, showing conserved structure with the human ortholog. In situ hybridization revealed that expression of zebrafish emilin genes is regulated in a spatiotemporal manner during embryonic development, with overlapping and site-specific patterns mostly including mesenchymal structures. Expression of certain emilin genes in peculiar areas, such as the central nervous system or the posterior notochord, suggests that they may play a role in key morphogenetic processes. Developmental Dynamics 237:222-232, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The influence of a substratum-disturbing forager, the spotted goatfish Pseudupeneus maculatus on the assemblage of its escorting, opportunistic-feeding fishes was examined at Fernando de Noronha Archipelago (tropical west Atlantic). Followers attracted to spotted goatfish foraging singly differed from followers of spotted goatfish foraging in groups in several characteristics. The larger the nuclear fish group, the greater the species richness and number of individuals of followers. Moreover, groups of foraging spotted goatfish attracted herbivores, not recorded for spotted goatfish foraging singly. The size of follower individuals increased with the size and the number of foraging spotted goatfish. The zoobenthivorous habits of the spotted goatfish and its ability to disturb a variety of soft substrata render it an important nuclear fish for several follower species of the reef fish assemblage at Fernando de Noronha. [ABSTRACT FROM AUTHOR]

Tsetse flies (Diptera: Glossinidia) are vectors of pathogenic African trypanosomes. To develop a foundation for tsetse physiology, a normalized expressed sequence tag (EST) library was constructed from fat body tissue of immune-stimulated Glossina morsitans morsitans. Analysis of 20 257 high-quality ESTs yielded 6372 unique genes comprised of 3059 tentative consensus (TC) sequences and 3313 singletons (available at ). We analysed the putative fat body transcriptome based on homology to other gene products with known functions available in the public domain. In particular, we describe the immune-related products, reproductive function related yolk proteins and milk-gland protein, iron metabolism regulating ferritins and transferrin, and tsetse's major energy source proline biosynthesis. Expression analysis of the three yolk proteins indicates that all are detected in females, while only the yolk protein with similarity to lipases, is expressed in males. Milk gland protein, apparently important for larval nutrition, however, is primarily synthesized by accessory milk gland tissue. [ABSTRACT FROM AUTHOR]

Although goatfishes (Mullidae) include c. 50 specialized bottom foraging species, juvenile and adult spotted goatfish Pseudupeneus maculatus were recorded feeding on plankton on rocky reefs off southern and north-eastern Brazil, respectively. [ABSTRACT FROM AUTHOR]

Ultrastructural alterations of collagen VI in cultured fibroblasts and reduced collagen VI immunostaining in the papillary dermis and endomysium were detected in a patient with a mild form of Ullrich congenital muscular dystrophy caused by a COL6A3 gene mutation. The patient had been previously demonstrated to express an α3(VI) chain shorter than normal due to skipping of the mutated exon. We show that collagen VI filaments are not organized in a normal network in the extracellular matrix secreted by patient's cultured fibroblasts. Moreover, we demonstrate that in this patient the α3(VI) chain is produced in lower amounts and it is almost exclusively represented by the shorter, alternatively spliced N6-C5 isoform. These results suggest that different α3(VI) chain isoforms, containing also domains of the N10-N7 region, are required for assembling a proper collagen VI network in the extracellular matrix. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

As a component of an extensive network of microfibrils interwoven with large collagen fibers and in close contact with cell surfaces, type VI collagen plays an important role in cell - matrix interactions. To investigate the behaviour of chicken type VI collagen chains in heterologous host cells as a means to understanding the pattern of assembly of this collagen, we transfected murine NIH/3T3 cells with cDNAs encoding chicken α1(VI), α2(VI) and α3(VI) chains. Cell lines that constitutively expressed the individual chains were analyzed by metabolic labeling and immunoprecipitation with specific antibodies. No self-association was observed for either α1(VI) or α2(VI) chains which were secreted↓ as monomeric polypeptides. Furthermore, neither the chicken α1(VI) nor α2(VI) chains associated with the endogenous murine chains to form chimeric chicken/murine heterotrimers. In contrast, chimeric chicken/murine heterotrimers were detected in cell lines transfected with chicken α3(VI) cDNA. These chimeric forms appeared to be properly aligned since their triple helices were stable to pepsin digestion. In addition, the chimeric heterotrimers coassembled and gave rise to disulfide-linked type VI collagen molecules. [ABSTRACT FROM AUTHOR]

Investigates cis-acting regions regulating transcription of the alpha1(V1) collagen chain in vitro by transfection of promoter-chloramphenicol acetyltransferase (CAT) constructs in different types of cultured cells an in vivo in transgenic mice. Determination of the expression of minigenes by RNase protection assay; Comparison of the levels of messenger RNA per transgene copy to those of the chromosomal gene; Finding that the ratio of transgene/chromosomal gene expression was not constant.