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Cortical proprioceptive processing of intermittent, passive movements can be assessed by extracting evoked and induced electroencephalographic (EEG) responses to somatosensory stimuli. Although the existent prior research on somatosensory stimulations, it remains unknown to what extent ongoing volitional muscle activation modulates the proprioceptive cortical processing of passive ankle-joint rotations. Twenty-five healthy volunteers (28.8 ± 7 yr, 14 males) underwent a total of 100 right ankle-joint passive rotations (4° dorsiflexions, 4 ± 0.25 s inter-stimulus interval, 30°/s peak angular velocity) evoked by a movement actuator during passive condition with relaxed ankle and active condition with a constant plantarflexion torque of 5 ± 2.5 Nm. Simultaneously, EEG, electromyographic (EMG) and kinematic signals were collected. Spatiotemporal features of evoked and induced EEG responses to the stimuli were extracted to estimate the modulation of the cortical proprioceptive processing between the active and passive conditions. Proprioceptive stimuli during the active condition elicited robustly ∼26 % larger evoked response and ∼38 % larger beta suppression amplitudes, but ∼42 % weaker beta rebound amplitude over the primary sensorimotor cortex than the passive condition, with no differences in terms of response latencies. These findings indicate that the active volitional motor task during naturalistic proprioceptive stimulation of the ankle joint enhances related cortical activation and reduces related cortical inhibition with respect to the passive condition. Possible factors explaining these results include mechanisms occurring at several levels of the proprioceptive processing from the peripheral muscle (i.e. mechanical, muscle spindle status, etc.) to the different central (i.e. spinal, sub-cortical and cortical) levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Microplastics (MPs) are dangerous and ubiquitous in the environment. The urgency to contrast plastic pollution is prompting the scientific community to offer new proposals. Recently, bioremediation using filter feeders is gaining consent as a nature-based solution. Herein four filter feeders (Mytilus galloprovincialis Lamarck, 1819, Sabella spallanzanii Gmelin, 1791, Phallusia mammillata Cuvier, 1815, Paraleucilla magna Klautau, Monteiro & Borojevic, 2004), studied in a previous laboratory experiment as MPs bioremediators, are evaluated in field conditions within 1-year. These organisms are part of an established fouling community growing on eco-friendly ropes in an Integrated Multi-Trophic Aquaculture (IMTA) in the Mar Grande of Taranto. After digesting the animal tissue, the MPs content was quantified by optical microscopy and spectroscopically characterized in the four seasons: highest values were measured in Autumn and lowest in Spring. M. galloprovincialis and P. mammillata were the most contaminated, but S. spallanzanii removed more MPs, due to its high density on the ropes. The whole community removed 3.15 × 10 7 MPs/season, with the amount of microfibers corresponding to a bottle cap/season., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite the progress in the development of innovative EEG acquisition systems, their use in dynamic applications is still limited by motion artifacts compromising the interpretation of the collected signals. Therefore, extensive research on the genesis of motion artifacts in EEG recordings is still needed to optimize existing technologies, shedding light on possible solutions to overcome the current limitations. We identified three potential sources of motion artifacts occurring at three different levels of a traditional biopotential acquisition chain: the skin-electrode interface, the connecting cables between the detection and the acquisition systems, and the electrode-amplifier system. The identified sources of motion artifacts were modelled starting from experimental observations carried out on EEG signals. Consequently, we designed customized EEG electrode systems aiming at experimentally disentangling the possible causes of motion artifacts. Both analytical and experimental observations indicated two main residual sites responsible for motion artifacts: the connecting cables between the electrodes and the amplifier and the sudden changes in electrode-skin impedance due to electrode movements. We concluded that further advancements in EEG technology should focus on the transduction stage of the biopotentials amplification chain, such as the electrode technology and its interfacing with the acquisition system.

Children with Cerebral Palsy (CP) exhibit less-selective, simplified muscle activation during gait due to injury of the developing brain. Abnormal motor unit recruitment, altered excitation-inhibition balance, and muscle morphological changes all affect the CP electromyogram. High-density surface electromyography (HDsEMG) has potential to reveal novel manifestations of CP neuromuscular pathology and functional deficits by assessing spatiotemporal details of myoelectric activity. We used HDsEMG to investigate spatial-EMG distribution and temporal-EMG complexity of gastrocnemius medialis (GM) muscle during treadmill walking in 11 adolescents with CP and 11 typically developed (TD) adolescents. Our results reveal more-uniform spatial-EMG amplitude distribution across the GM in adolescents with CP, compared to distal emphasis in TD adolescents. More-uniform spatial-EMG was associated with stronger ankle co-contraction and spasticity. CP adolescents exhibited a non-significant trend towards elevated EMG-temporal complexity. Homogenous spatial distribution and disordered temporal evolution of myoelectric activity in CP suggests less-structured and desynchronized recruitment of GM motor units, in combination with muscle morphological changes. Using HDsEMG, we uncovered novel evidence of atypical spatiotemporal activation during gait in CP, opening paths towards deeper understanding of motor control deficits and better characterization of changes in muscular activation from interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Macrophages constitute the first defense line against the non-self, but their ability to remodel their environment in organ development/homeostasis is starting to be appreciated. Early-wave macrophages (EMs), produced from hematopoietic stem cell (HSC)-independent progenitors, seed the mammalian fetal liver niche wherein HSCs expand and differentiate. The involvement of niche defects in myeloid malignancies led us to identify the cues controlling HSCs. In Drosophila, HSC-independent EMs also colonize the larva when late hematopoiesis occurs. The evolutionarily conserved immune system allowed us to investigate whether/how EMs modulate late hematopoiesis in two models. We show that loss of EMs in Drosophila and mice accelerates late hematopoiesis, which does not correlate with inflammation and does not rely on macrophage phagocytic ability. Rather, EM-derived extracellular matrix components underlie late hematopoiesis acceleration. This demonstrates a developmental role for EMs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Proprioception refers to the ability to perceive the position and movement of body segments in space. The cortical aspects of the proprioceptive afference from the body can be investigated using corticokinematic coherence (CKC). CKC accurately quantifies the degree of coupling between cortical activity and limb kinematics, especially if precise proprioceptive stimulation of evoked movements is used. However, there is no evidence on how volitional muscle activation during proprioceptive stimulation affects CKC strength. Twenty-five healthy volunteers (28.8 ± 7 yr, 11 females) participated in the experiment, which included electroencephalographic (EEG), electromyographic (EMG), and kinematic recordings. Ankle-joint rotations (2-Hz) were elicited through a movement actuator in two conditions: passive condition with relaxed ankle and active condition with constant 5-Nm plantar flexion exerted during the stimulation. In total, 6 min of data were recorded per condition. CKC strength was defined as the maximum coherence value among all the EEG channels at the 2-Hz movement frequency for each condition separately. Both conditions resulted in significant CKC peaking at the Cz electrode over the foot area of the primary sensorimotor (SM1) cortex. Stronger CKC was found for the active (0.13 ± 0.14) than the passive (0.03 ± 0.04) condition ( P < 0.01). The results indicated that volitional activation of the muscles intensifies the neuronal proprioceptive processing in the SM1 cortex. This finding could be explained both by peripheral sensitization of the ankle joint proprioceptors and central modulation of the neuronal proprioceptive processing at the spinal and cortical levels. NEW & NOTEWORTHY The current study is the first to investigate the effect of volitional muscle activation on CKC-based assessment of cortical proprioception of the ankle joint. Results show that the motor efference intensifies the neuronal processing of proprioceptive afference of the ankle joint. This is a significant finding as it may extend the use of CKC method during active tasks to further evaluate the motor efference-proprioceptive afference relationship and the related adaptations to exercise, rehabilitation, and disease.

Hemocytes, the myeloid-like immune cells of Drosophila , fulfill a variety of functions that are not completely understood, ranging from phagocytosis to transduction of inflammatory signals. We here show that downregulating the hemocyte-specific Glial cell deficient/Glial cell missing (Glide/Gcm) transcription factor enhances the inflammatory response to the constitutive activation of the Toll pathway. This correlates with lower levels of glutathione S-transferase, suggesting an implication of Glide/Gcm in reactive oxygen species (ROS) signaling and calling for a widespread anti-inflammatory potential of Glide/Gcm. In addition, our data reveal the expression of acetylcholine receptors in hemocytes and that Toll activation affects their expressions, disclosing a novel aspect of the inflammatory response mediated by neurotransmitters. Finally, we provide evidence for acetylcholine receptor nicotinic acetylcholine receptor alpha 6 (nAchRalpha6) regulating hemocyte proliferation in a cell autonomous fashion and for non-cell autonomous cholinergic signaling regulating the number of hemocytes. Altogether, this study provides new insights on the molecular pathways involved in the inflammatory response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bazzi, Monticelli, Delaporte, Riet, Giangrande and Cattenoz.)

Tumors constantly interact with their microenvironment. Here, we present data on a Notch-induced neural stem cell (NSC) tumor in Drosophila, which can be immortalized by serial transplantation in adult hosts. This tumor arises in the larva by virtue of the ability of Notch to suppress early differentiation-promoting factors in NSC progeny. Guided by transcriptome data, we have addressed both tumor-intrinsic and microenvironment-specific factors and how they contribute to tumor growth and host demise. The growth promoting factors Myc, Imp, and Insulin receptor in the tumor cells are important for tumor expansion and killing of the host. From the host's side, hemocytes, professional phagocytic blood cells, are found associated with tumor cells. Phagocytic receptors, like NimC1, are needed in hemocytes to enable them to capture and engulf tumor cells, restricting their growth. In addition to their protective role, hemocytes may also increase the host's morbidity by their propensity to produce damaging extracellular reactive oxygen species.

Integrated Multitrophic Aquaculture (IMTA) seems to be one of the best solutions for sustainable aquaculture. Within the Remedia LIFE Project, an experimental IMTA plant was put in place in the Mar Grande of Taranto (Mediterranean Sea, Southern Italy). The polyculture of several bioremediating organisms, such as mussels, tubeworms, sponges, and seaweeds, was combined with a coastal cage fish farm, in order to remove organic and inorganic wastes coming from the fish's metabolism. To verify the effectiveness of the system, the ex ante measurement of chemical-physical variables, trophic status, microbial contamination, and zoobenthos community health was compared with the results of the same measurement performed one year and two years after the implementation of the experimental IMTA plant. The results were encouraging, since a reduction in total nitrogen concentration in the seawater (from 43.4 ± 8.9 to 5.6 ± 3.7 μM/l), a reduction in microbial pollution indicators in the seawater (total coliforms: from 280 ± 18 MPN/100 mL to 0; E. coli: from 33 ± 1.3 MPN/100 mL to 0) and in the sediments (total coliforms: from 230 ± 6.2 MPN/100 g to 170 ± 9; E. coli: from 40 ± 9.4 MPN/100 g to 0), an enhancement of the trophic status (TRIX: from 4.45 ± 1.29 to 3.84 ± 0.18), and an increase in the zoobenthic quality indices and biodiversity were recorded (AMBI: from 4.8 to 2.4; M-AMBI: from 0.14 to 0.7). These results prove that the Remedia LIFE project's purpose was achieved. The selected bioremediators worked synergistically, improving water and sediments quality within the fish farm area. Moreover, bioremediating organisms increased their weight as a result of wastes uptake, producing, as co-products, large amounts of additional biomass. This could be commercially exploited, thus being an added value of the IMTA plant. Based on our findings, the promotion of eco-friendly practices to ameliorate ecosystem health should be encouraged., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adriana Giangrande reports financial support was provided by LIFE programme., (Copyright © 2023. Published by Elsevier B.V.)

Microplastics (MPs) are a serious threat to the marine environment affecting ecosystem functioning and biodiversity. There is a vast literature about the uptake of MPs at different trophic levels, mainly focused on ecotoxicological effects in commercially relevant species. Little is still known about possible strategies to face MP pollution. Bioremediation is recently gaining attention in this framework. The clearance rate and particle retention of Sabella spallanzanii, Mytilus galloprovincialis, Phallusia mammillata, Paraleucilla magna at three MP concentrations (C1: 1.4 · 10 1 p/L; C2: 1.4 · 10 2 p/L; C3: 1.4 · 10 3 p/L) were investigated to test their potential as MP remover. Digestion protocol removed 98 % of tissues simplifying the MP quantification. P. magna clearance rate decreased with increasing concentration while P. mammillata showed no significant variations. S. spallanzanii and M. galloprovincialis instead exhibited the highest values of clearance rate. Yet, unlike mussels, S. spallanzanii can inhibit particle return to the surrounding water storing them in the tube, resulting to be the best candidate for bioremediation purposes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Innate immunity is an ancestral process that can induce pro- and anti-inflammatory states. A major challenge is to characterize transcriptional cascades that modulate the response to inflammation. Since the Drosophila glial cells missing (Gcm) transcription factor has an anti-inflammatory role, we explored its regulation and evolutionary conservation. Here, we show that the murine Gcm2 (mGcm2) gene is expressed in a subpopulation of aged microglia (chronic inflammation) and upon lysophosphatidylcholine (LPC)-induced central nervous system (CNS) demyelination (acute inflammation). Moreover, mGcm2 conditional knockout mice show an increased inflammatory phenotype upon aging or LPC injection, and hGCM2 is expressed in active demyelinating lesions of patients with multiple sclerosis. Finally, Drosophila Gcm expression is induced upon aging and acute challenge, and its overexpression decreases the inflammatory phenotype. Altogether, these data indicate that the inducible Gcm cascade is conserved from flies to humans and represents a potential therapeutic target in the control of the inflammatory response., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 CNRS. Published by Elsevier Inc. All rights reserved.)

Corticokinematic coherence (CKC) is computed between limb kinematics and cortical activity (e.g. MEG, EEG), and it can be used to detect, quantify and localize the cortical processing of proprioceptive afference arising from the body. EEG-based studies on CKC have been limited to lab environments due to bulky, non-portable instrumentations. We recently proposed a wireless and miniaturized EEG acquisition system aimed at enabling EEG studies outside the laboratory. The purpose of this work is to compare the EEG-based CKC values obtained with this device with a conventional wired-EEG acquisition system to validate its use in the quantification of cortical proprioceptive processing. Eleven healthy right-handed participants were recruited (six males, four females, age range: 24-40 yr). A pneumatic-movement actuator was used to evoke right index-finger flexion-extension movement at 3 Hz for 4 min. The task was repeated both with the wireless-EEG and wired-EEG devices using the same 30-channel EEG cap preparation. CKC was computed between the EEG and finger acceleration. CKC peaked at the movement frequency and its harmonics, being statistically significant (p < 0.05) in 8-10 out of 11 participants. No statistically significant differences (p < 0.05) were found in CKC strength between wireless-EEG (range 0.03-0.22) and wired-EEG (0.02-0.33) systems, that showed a good agreement between the recording systems (3 Hz: r = 0.57, p = 0.071, 6 Hz: r = 0.82, p = 0.003). As expected, CKC peaked in sensors above the left primary sensorimotor cortex contralateral to the moved right index finger. As the wired-EEG device, the tested wireless-EEG system has proven feasible to quantify CKC, and thus can be used as a tool to study proprioception in the human neocortex. Thanks to its portability, the wireless-EEG used in this study has the potential to enable the examination of cortical proprioception in more naturalistic conditions outside the laboratory environment. Clinical Relevance-Our study will contribute to provide innovative technological foundations for future unobtrusive EEG recordings in naturalistic conditions to examine human sensorimotor system.

The results of an ex-ante survey aiming to assess the impact of a fish farm in the Mar Grande of Taranto (southern Italy, Mediterranean Sea) on the surrounding environment are reported. There, the implementation of an innovative IMTA plant was planned, with the goals of environment bioremediation and commercially exploitable biomass production. Analyses were conducted in February and July 2018. Both seawater and sediments were sampled at the four corners of the fish farm to detect the existing biological and physico-chemical features. The investigation was performed to identify the best area of the farming plant for positioning the bioremediating system, but also to obtain a data baseline, to compare to the environmental status after the bioremediating action. Data were also analyzed by canonical analysis of principal coordinates (CAP). All the measurements, in particular, microbiology and macrobenthic community characterization using AZTI's Marine Biotic Index (AMBI) and the Multivariate-AMBI (M-AMBI) indices, suggest that the effect of fish farm waste was concentrated and limited to a small portion of the investigated area in relation to the direction of the main current. A site named A3, which was found to be the most impacted by the aquaculture activities, especially during the summer season, was chosen to place the bioremediation system.

Harmful algal blooms (HABs) are extreme biological events representing a major issue in marine, brackish, and freshwater systems worldwide. Their proliferation is certainly a problem from both ecological and socioeconomic contexts, as harmful algae can affect human health and activities, the marine ecosystem functioning, and the economy of coastal areas. Once HABs establish, valuable and environmentally friendly control actions are needed to reduce their negative impacts. In this study, the influence exerted by the filter-feeding activity of the two sabellid polychaetes Branchiomma luctuosum (Grube) and Sabella spallanzanii (Gmelin) on a harmful dinoflagellate was investigated. Clearance rates (C) and retention efficiencies were estimated by employing the microalga Amphidinium carterae Hulburt. The C max was 1.15 ± 0.204 L h -1 g -1 DW for B. luctuosum and 0.936 ± 0.151 L h -1 g -1 DW for S. spallanzanii . The retention efficiency was 72% for B. luctuosum and 68% for S. spallanzanii . Maximum retention was recorded after 30 min for both species. The obtained results contribute to the knowledge of the two polychaetes' filtration activity and to characterize the filtration process on harmful microalgae in light of the protection of water resources and human health. Both species, indeed, were extremely efficient in removing A. carterae from seawater, thus suggesting their employment as a new tool in mitigation technologies for the control of harmful algae in marine environments, as well as in the aquaculture facilities where HABs are one of the most critical threats.

Sensorimotor integration is the process through which the human brain plans the motor program execution according to external sources. Within this context, corticomuscular and corticokinematic coherence analyses are common methods to investigate the mechanism underlying the central control of muscle activation. This requires the synchronous acquisition of several physiological signals, including EEG and sEMG. Nevertheless, physical constraints of the current, mostly wired, technologies limit their application in dynamic and naturalistic contexts. In fact, although many efforts were made in the development of biomedical instrumentation for EEG and High Density-surface EMG (HD-sEMG) signal acquisition, the need for an integrated wireless system is emerging. We hereby describe the design and validation of a new fully wireless body sensor network for the integrated acquisition of EEG and HD-sEMG signals. This Body Sensor Network is composed of wireless bio-signal acquisition modules, named sensor units, and a set of synchronization modules used as a general-purpose system for time-locked recordings. The system was characterized in terms of accuracy of the synchronization and quality of the collected signals. An in-depth characterization of the entire system and an head-to-head comparison of the wireless EEG sensor unit with a wired benchmark EEG device were performed. The proposed device represents an advancement of the State-of-the-Art technology allowing the integrated acquisition of EEG and HD-sEMG signals for the study of sensorimotor integration.

We report the description of nine new taxa of sabellid polychaetes belonging to the genus Amphiglena, of which diversity in the Mediterranean Sea has been widely underestimated. Examined material derived from both new collections along the Italian coast, including four CO2 vents/hydrothermal systems, and from a re-examination of older material previously attributed to A. mediterranera (Leydig, 1851) which was so far the only species of the genus reported for the Mediterranean area. The analysis revealed the presence of different taxa also consistent with a previous molecular analysis conducted on material from the Gulf of Naples and the Salento coast (Ionian Sea). This led to an increase in the number of species in the genus and to highlight the occurrence in the Mediterranean Sea of a high diversity within the genus. A key to the Mediterranean Sea species of Amphiglena is also provided. Some taxa, however, remain for the moment undescribed due to the poor preservation of the old material, and the lack of the type material for this taxon. A major revision of all the Mediterranean material previously attributed to A. mediterranea from both morphological and molecular points of view is needed.

The catalog of the Drosophila immune cells was until recently limited to three major cell types, based on morphology, function and few molecular markers. Three recent single cell studies highlight the presence of several subgroups, revealing a large diversity in the molecular signature of the larval immune cells. Since these studies rely on somewhat different experimental and analytical approaches, we here compare the datasets and identify eight common, robust subgroups associated to distinct functions such as proliferation, immune response, phagocytosis or secretion. Similar comparative analyses with datasets from different stages and tissues disclose the presence of larval immune cells resembling embryonic hemocyte progenitors and the expression of specific properties in larval immune cells associated with peripheral tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cattenoz, Monticelli, Pavlidaki and Giangrande.)

The development and the maintenance of an efficient immune system represents a considerable metabolic investment for the organism. Ramond et al. have characterized a new molecular and cellular pathway, inhibiting the immune system in poor diet conditions in the Drosophila larva. Low nutrient conditions lead to the secretion of the adipokine NimB5 by the fat body, which inhibits the proliferation of the immune cells, hence preventing the exhaustion of the resources., (© 2020 Federation of European Biochemical Societies.)

Immune cells provide defense against non-self and have recently been shown to also play key roles in diverse processes such as development, metabolism, and tumor progression. The heterogeneity of Drosophila immune cells (hemocytes) remains an open question. Using bulk RNA sequencing, we find that the hemocytes display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single-cell RNA sequencing, we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct processes, e.g., proliferation, phagocytosis, metabolic homeostasis, and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation, which triggers the differentiation of a novel hemocyte type, the lamellocyte. This first molecular atlas of hemocytes provides insights and paves the way to study the biology of the Drosophila immune cells in physiological and pathological conditions., (© 2020 The Authors.)

Objective: Soldiers' lower limbs and feet are frequently affected by overload- and overuse-related injuries. In order to prevent or limit the incidence of these injuries, the use of foot orthoses is often recommended. The aim of this study is to assess the effects of shock-absorbing insoles on in-shoe plantar pressure magnitude and distribution in a group of professional infantry soldiers wearing military boots during standard indoor military training., Methods: Twenty male professional soldiers of the Italian Army (age 35.1 ± 6.1 years; BMI 25.2 ± 2.3 kg/m2) were recruited for this study. Each subject underwent clinical examination to assess possible overuse-related diseases of the lower limb and trunk. Subjects with altered foot morphology according to the Foot Posture Index (FPI) were excluded from this study. Twelve subjects were considered eligible and therefore underwent an indoor training routine comprised of marching, running, jumping inside parallel bars and jumping from different heights. Soldiers repeated the training session twice wearing standard military boots along with two types of insoles: the standard prefabricated insole within the boots (STI), and a special shock-absorbing insole (SAI) featuring an elastic medial arch support. A 99-capacitive sensor insole system was used to record plantar pressure distribution in both feet. Analysis of in-shoe pressure parameters at rearfoot, midfoot and forefoot and in the total foot was performed via a custom-software application developed in MATLAB. Perceived foot comfort (VAS 0-15) was also assessed., Results: Pressure parameters recorded during walking and running were considered suitable for statistical analysis. In the whole foot region, pressure parameters were 18-22% lower in military boots fitted with the SAI during walking and 14-18% lower during running. SAI resulted in better comfort (+25%) with respect to the prefabricated boot orthotics (median comfort: SAI = 15/15; STI = 12/15; p = 0.0039) both during walking and running., Conclusions: Shock-absorbing insoles can be an effective solution when fitted inside military boots. The present functional evaluation shows that wearing a prefabricated shock-absorbing insole can provide a significant amelioration of perceived foot comfort and plantar pressure parameters. Further studies are now needed with a larger population and more demanding exercises., (© The Association of Military Surgeons of the United States. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The present paper provides a multidisciplinary fine-scale description of a Mediterranean mesophotic new habitat dominated by the bivalve Neopycnodonte cochlear (Poli, 1795), building large and thick pinnacles on vertical cliffs at two study areas along the southern Italian coast. The pinnacles, constituted by a multilayered aggregation of living and dead specimens of N. cochlear, were interconnected with each other to form a framework of high structural complexity, never observed before for this species. The bioconstruction, considerably extended, resulted very complex and diversified in the associated community of structuring organisms. This latter included 165 taxa attributable to different ecological groups occurring in different microhabitats of the bioconstruction. Among the secondary structuring taxa there were scleractinians, serpulids and bryozoans, all contributing to the deposition of calcium carbonate, and poriferans, helping to bind shells together or eroding carbonate by boring species. In comparison with coralligenous sensu stricto and the recently described Mediterranean mesophotic coral reef, the Neopycnodonte bioconstruction showed peculiar features, since it lacked the major contribution of encrusting coralline algae and scleractinians as reef builders, respectively.

Social impairment is frequently associated with mitochondrial dysfunction and altered neurotransmission. Although mitochondrial function is crucial for brain homeostasis, it remains unknown whether mitochondrial disruption contributes to social behavioral deficits. Here, we show that Drosophila mutants in the homolog of the human CYFIP1, a gene linked to autism and schizophrenia, exhibit mitochondrial hyperactivity and altered group behavior. We identify the regulation of GABA availability by mitochondrial activity as a biologically relevant mechanism and demonstrate its contribution to social behavior. Specifically, increased mitochondrial activity causes gamma aminobutyric acid (GABA) sequestration in the mitochondria, reducing GABAergic signaling and resulting in social deficits. Pharmacological and genetic manipulation of mitochondrial activity or GABA signaling corrects the observed abnormalities. We identify Aralar as the mitochondrial transporter that sequesters GABA upon increased mitochondrial activity. This study increases our understanding of how mitochondria modulate neuronal homeostasis and social behavior under physiopathological conditions., Competing Interests: Declaration of Interests The authors declare no competing financial interests. A patent application has been filed in the name of the University of Lausanne (Switzerland)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aquaculture expansion is limited by the negative environmental impact of the waste and the need for alternative sources in the diet of reared fish. In this framework, for the first time, the survival rates, biomass gain, and fatty acid profiles of the polychaete Sabella spallanzanii and the macroalga Chaetomorpha linum , reared/cultivated as bioremediators in an integrated multitrophic aquaculture system (IMTA), were evaluated for their potential reuse applications. Results showed that these organisms represent a natural source of omega-3 and omega-6. On account of the overall results and the high biomass obtained as by-products, a preliminary study was performed employing both S. spallanzanii and C. linum as new dietary ingredients to feed different sized Dicentrarchus labrax . Fish survival rate, biomass growth, and specific growth rate were determined resulting in no significant differences between control and treated fishes. Histological analyses showed no alterations of the stomach tunica mucosa and submucosa in treated fishes. The eco-friendly approaches applied in the here-realized IMTA system could guarantee the achievement of sustainable by-products represented by the bioremediators S. spallanzanii and C. linum, as well as their reliability as a natural source of compounds beneficial to fish and human health.

Synaptic structure and activity are sensitive to environmental alterations. Modulation of synaptic morphology and function is often induced by signals from glia. However, the process by which glia mediate synaptic responses to environmental perturbations such as hypoxia remains unknown. Here, we report that, in the mutant for Trachealess (Trh), the Drosophila homolog for NPAS1 and NPAS3, smaller synaptic boutons form clusters named satellite boutons appear at larval neuromuscular junctions (NMJs), which is induced by the reduction of internal oxygen levels due to defective tracheal branches. Thus, the satellite bouton phenotype in the trh mutant is suppressed by hyperoxia, and recapitulated in wild-type larvae raised under hypoxia. We further show that hypoxia-inducible factor (HIF)-1α/Similar (Sima) is critical in mediating hypoxia-induced satellite bouton formation. Sima upregulates the level of the Wnt/Wingless (Wg) signal in glia, leading to reorganized microtubule structures within presynaptic sites. Finally, hypoxia-induced satellite boutons maintain normal synaptic transmission at the NMJs, which is crucial for coordinated larval locomotion., Competing Interests: The authors have declared that no competing interests exist.

Many marine organisms, including invertebrates, produce mucosal matrices having different functions. Besides mechanical protection, the mucus of many invertebrates contains specific compounds to make the animal poisonous and/or distasteful or irritating. The presence of antibiotic molecules is more advantageous for some invertebrates to contrast bacterial attack. In the present study we investigated the mucus of the Mediterranean annelid species Myxicola infundibulum living in a gelatinous envelope made up of dense mucus. Antimicrobial lysozyme-like and antioxidant activities were investigated to highlight the potential interest of the worm mucus as a source of bioactive compounds for biotechnological applications. In order to understand which kind of compounds could be responsible for the detected activities, the mucus of M. infundibulum was chemically characterized in terms of elemental composition, protein, lipid and carbohydrate content. Further chemical characterization was achieved by the advanced analytical technique of multinuclear and multidimensional NMR spectroscopy. NMR spectroscopy revealed the scarcity of lipids which preferentially resulted of alcoholic origin, or otherwise hydroxylate and several aminoacids (valine, leucine and alanine) in the aqueous extract in relation to the protein nature of M. infundibulum mucus. The mucus indeed is mainly composed by water (94% ± 0.7%) whereas its dry weight is made of proteins (36% ± 2.3%) followed by lipids (2.9% ± 0.07%) and carbohydrates (2% ± 0.31%). The mucus exerted a natural antibacterial lysozyme-like activity corresponding to 1.14 mg mL -1 of hen egg-white lysozyme and an antioxidant activity corresponding to 483.00 ± 79.22 nmolTE (Trolox equivalent)/mL sample as Trolox Equivalent Antioxidant Capacity (TEAC) and 276.26 ± 50.76 nmolTE/mL sample as Oxygen Radical Absorbance Capacity (ORAC). Therefore, our findings have potential implications due to the ongoing explosion of antibiotic resistant infections and the need to discover antibacterial agents. Additionally, the observed antioxidant activity is intriguing taking into account the need to find natural antioxidants useful for human health.

The fruitfly Drosophila melanogaster has been extensively used as a genetic model for the maintenance of nervous system's functions. Glial cells are of utmost importance in regulating the neuronal functions in the adult organism and in the progression of neurological pathologies. Through a microRNA-based screen in adult Drosophila glia, we uncovered the essential role of a major glia developmental determinant, repo , in the adult fly. Here, we report that Repo expression is continuously required in adult glia to transcriptionally regulate the highly conserved function of neurotransmitter recycling in both males and females. Transient loss of Repo dramatically shortens fly lifespan, triggers motor deficits, and increases the sensibility to seizures, partly due to the impairment of the glutamate/GABA/glutamine cycle. Our findings highlight the pivotal role of transcriptional regulation of genes involved in the glutamate/GABA/glutamine cycle in glia to control neurotransmitter levels in neurons and their behavioral output. The mechanism identified here in Drosophila exemplifies how adult functions can be modulated at the transcriptional level and suggest an active synchronized regulation of genes involved in the same pathway. The process of neurotransmitter recycling is of essential importance in human epileptic and psychiatric disorders and our findings may thus have important consequences for the understanding of the role that transcriptional regulation of neurotransmitter recycling in astrocytes has in human disease. SIGNIFICANCE STATEMENT Glial cells are an essential support to neurons in adult life and have been involved in a number of neurological disorders. What controls the maintenance and modulation of glial functions in adult life is not fully characterized. Through a miR overexpression screen in adult glia in Drosophila , we identify an essential role in adult glia of repo , which directs glial differentiation during embryonic development. Repo levels modulate, via transcriptional regulation, the ability of glial cells to support neurons in the glutamate/GABA/glutamine cycle. This leads to significant abnormalities in motor behavior as assessed through a novel automated paradigm. Our work points to the importance of transcriptional regulation in adult glia for neurotransmitter recycling, a key process in several human neurological disorders., (Copyright © 2019 Mazaud et al.)

The oncoprotein BCR-ABL1 triggers chronic myeloid leukemia. It is clear that the disease relies on constitutive BCR-ABL1 kinase activity, but not all the interactors and regulators of the oncoprotein are known. We describe and validate a Drosophila leukemia model based on inducible human BCR-ABL1 expression controlled by tissue-specific promoters. The model was conceived to be a versatile tool for performing genetic screens. BCR-ABL1 expression in the developing eye interferes with ommatidia differentiation and expression in the hematopoietic precursors increases the number of circulating blood cells. We show that BCR-ABL1 interferes with the pathway of endogenous dAbl with which it shares the target protein Ena. Loss of function of ena or Dab , an upstream regulator of dAbl, respectively suppresses or enhances both the BCR-ABL1-dependent phenotypes. Importantly, in patients with leukemia decreased human Dab1 and Dab2 expression correlates with more severe disease and Dab1 expression reduces the proliferation of leukemia cells. Globally, these observations validate our Drosophila model, which promises to be an excellent system for performing unbiased genetic screens aimed at identifying new BCR-ABL1 interactors and regulators in order to better elucidate the mechanism of leukemia onset and progression., (Copyright© 2019 Ferrata Storti Foundation.)

This is the first description of a Mediterranean mesophotic coral reef. The bioconstruction extended for 2.5 km along the Italian Adriatic coast in the bathymetric range -30/-55 m. It appeared as a framework of coral blocks mostly built by two scleractinians, Phyllangia americana mouchezii (Lacaze-Duthiers, 1897) and Polycyathus muellerae (Abel, 1959), which were able to edify a secondary substrate with high structural complexity. Scleractinian corallites were cemented by calcified polychaete tubes and organized into an interlocking meshwork that provided the reef stiffness. Aggregates of several individuals of the bivalve Neopycnodonte cochlear (Poli, 1795) contributed to the compactness of the structure. The species composition of the benthic community showed a marked similarity with those described for Mediterranean coralligenous communities and it appeared to be dominated by invertebrates, while calcareous algae, which are usually considered the main coralligenous reef-builders, were poorly represented. Overall, the studied reef can be considered a unique environment, to be included in the wide and diversified category of Mediterranean bioconstructions. The main reef-building scleractinians lacked algal symbionts, suggesting that heterotrophy had a major role in the metabolic processes that supported the production of calcium carbonate. The large amount of available suspended organic matter in the area could be the main nutritional source for these species, as already suggested in the literature referred to Mediterranean cold-water corals.

Fragile-X syndrome is one of the most common forms of inherited mental retardation and autistic behaviors. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Patients exhibit a variety of symptoms predominantly linked to the function of FMRP protein in the nervous system like autistic behavior and mild-to-severe intellectual disability. Fragile-X (FraX) individuals also display cellular and morphological traits including branched dendritic spines, large ears, and macroorchidism. The dFmr1 gene is the Drosophila ortholog of the human Fmr1 gene. dFmr1 mutant flies exhibit synaptic abnormalities, behavioral defects as well as an altered germline development, resembling the phenotypes observed in FraX patients. Therefore, Drosophila melanogaster is considered a good model to study the physiopathological mechanisms underlying the Fragile-X syndrome. In this review, we explore how the multifaceted roles of the FMRP protein have been addressed in the Drosophila model and how the gained knowledge may open novel perspectives for understanding the molecular defects causing the disease and for identifying novel therapeutical targets.

The aim of this study was to test the effects of short- and long-term exposure to high pCO 2 on the invasive polychaete Branchiomma boholense (Grube, 1878), (Sabellidae), through the implementation of a transplant experiment at the CO 2 vents of the Castello Aragonese at the island of Ischia (Italy). Analysis of carbonic anhydrase (CA) activity, protein tissue content and morphometric characteristics were performed on transplanted individuals (short-term exposure) as well as on specimens resident to both normal and low pH/high pCO 2 environments (long-term exposure). Results obtained on transplanted worms showed no significant differences in CA activity between individuals exposed to control and acidified conditions, while a decrease in weight was observed under short-term acclimatization to both control and low pH, although at low pH the decrease was more pronounced (∼20%). As regard individuals living under chronic exposure to high pCO 2 , the morphometric results revealed a significantly lower (70%) wet weight of specimens from the vents with respect to animals living in high pH/low pCO 2 areas. Moreover, individuals living in the Castello vents showed doubled values of enzymatic activity and a significantly higher (50%) protein tissue content compared to specimens native from normal pH/low pCO 2 . The results of this study demonstrated that B. boholense is inclined to maintain a great homeostatic capacity when exposed to low pH, although likely at the energetic expense of other physiological processes such as growth, especially under chronic exposure to high pCO 2 ., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system, whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside (hemocytes) the nervous system require the same transcription factor glial cells deficient/glial cells missing (Glide/Gcm) for their development. This raises the issue of how do glia specifically differentiate in the nervous system, and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and panglial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us to understand the bases of cell specification. Both sexes were analyzed. SIGNIFICANCE STATEMENT Distinct cell types often require the same pioneer transcription factor, raising the issue of how one factor triggers different fates. In Drosophila , glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the glial cells deficient/glial cells missing (Glide/Gcm) transcription factor, glia originate from the ectoderm, and hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification., (Copyright © 2019 the authors 0270-6474/19/390238-18$15.00/0.)

Recent lineage tracing analyses have significantly improved our understanding of immune system development and highlighted the importance of the different hematopoietic waves. The current challenge is to understand whether these waves interact and whether this affects the function of the immune system. Here we report a molecular pathway regulating the immune response and involving the communication between embryonic and larval hematopoietic waves in Drosophila . Down-regulating the transcription factor Gcm specific to embryonic hematopoiesis enhances the larval phenotypes induced by over-expressing the pro-inflammatory Jak/Stat pathway or by wasp infestation. Gcm works by modulating the transduction of the Upd cytokines to the site of larval hematopoiesis and hence the response to chronic (Jak/Stat over-expression) and acute (wasp infestation) immune challenges. Thus, homeostatic interactions control the function of the immune system in physiology and pathology. Our data also indicate that a transiently expressed developmental pathway has a long-lasting effect on the immune response., Competing Interests: WB, PC, CD, VD, RS, YY, AG No competing interests declared, (© 2018, Bazzi et al.)

Despite their great importance for biomedical research, the intricate network of relationships between macro- and microglia, in terms of development, function and evolution, remains poorly understood. Drawing inspiration from the recent meeting "Of Glia and Microglia", held at the University of Strasbourg in December 2017, we here discuss the outstanding questions in the seemingly disparate fields of glial development, physiology and evolution, and also provide suggestions for how the field should move forward., Competing Interests: The authors declare no competing interests.

This study was performed to analyse the genetic and morphological diversity of the sabellid annelid genus Branchiomma, with special emphasis on a taxon so far identified as Branchiomma bairdi. This species, originally described from Bermuda, has frequently been reported as an invader in the Mediterranean, the Atlantic and the Eastern Pacific, but recent observations have raised some taxonomic questions. Samples of this taxon were collected from five sites in the Mediterranean Sea, two sites in the original distribution area of B. bairdi in the Gulf of Mexico and four localities in the east Pacific and Atlantic Oceans where B. bairdi has been reported as invasive. The molecular results revealed a conspicuous genetic divergence (18.5% K2P) between the sampled Mediterranean populations and all the other ones that led to a re-evaluation of their morphological characters. The latter showed that the Mediterranean and extra-Mediterranean populations also differ in some discrete morphological and reproductive features. Consequently, the Mediterranean samples were re-designated as B. boholense, another non-indigenous species originally described from Philippines. Branchiomma bairdi and B. boholense differ in body size, development and shape of micro and macrostylodes, size of radiolar eyes and body pigmentation. Genetic diversity was high in B. boholense from the Mediterranean as well as in B. bairdi from the Gulf of Mexico, but low in B. bairdi populations outside their native range. The phylogenetic analysis revealed the presence of connections between the Mediterranean localities as well as between native and introduced B. bairdi populations that focus the attention on the Panama Canal as important passage for the introduction of the species from the Gulf of Mexico to the north-east Pacific Ocean.

[This corrects the article DOI: 10.1371/journal.pone.0195352.].

Aquaculture is increasing rapidly to meet global seafood demand. Some hydroid populations have been linked to mortality and health issues in finfish and shellfish, but their dynamics in and around aquaculture farms remain understudied. In the present work, two experiments, each with 36 panels, tested colonization (factors: depth, season of immersion) and succession (factors: depth, submersion duration) over one year. Hydroid surface cover was estimated for each species, and data were analyzed with multivariate techniques. The assemblage of hydrozoans was species-poor, although species richness, frequency and abundance increased with time, paralleling the overall increase in structural complexity of fouling assemblages. Submersion duration and season of immersion were particularly important in determining the species composition of the assemblages in the succession and colonization experiments, respectively. Production of water-borne propagules, including medusae, from the hydroids was observed from locally abundant colonies, among them the well-known fouling species Obelia dichotoma, potentially representing a nuisance for cultured fish through contact-driven envenomations and gill disorders. The results illustrate the potential importance of fouling hydroids and their medusae to the health of organisms in the aquaculture industry.

Marine bioconstructions are biodiversity-rich, three-dimensional biogenic structures, regulating key ecological functions of benthic ecosystems worldwide. Tropical coral reefs are outstanding for their beauty, diversity and complexity, but analogous types of bioconstructions are also present in temperate seas. The main bioconstructions in the Mediterranean Sea are represented by coralligenous formations, vermetid reefs, deep-sea cold-water corals, Lithophyllum byssoides trottoirs, coral banks formed by the shallow-water corals Cladocora caespitosa or Astroides calycularis, and sabellariid or serpulid worm reefs. Bioconstructions change the morphological and chemicophysical features of primary substrates and create new habitats for a large variety of organisms, playing pivotal roles in ecosystem functioning. In spite of their importance, Mediterranean bioconstructions have not received the same attention that tropical coral reefs have, and the knowledge of their biology, ecology and distribution is still fragmentary. All existing data about the spatial distribution of Italian bioconstructions have been collected, together with information about their growth patterns, dynamics and connectivity. The degradation of these habitats as a consequence of anthropogenic pressures (pollution, organic enrichment, fishery, coastal development, direct physical disturbance), climate change and the spread of invasive species was also investigated. The study of bioconstructions requires a holistic approach leading to a better understanding of their ecology and the application of more insightful management and conservation measures at basin scale, within ecologically coherent units based on connectivity: the cells of ecosystem functioning., (© 2018 Elsevier Ltd. All rights reserved.)

Cytoplasmic FMRP interacting protein 1 ( CYFIP1 ) is a candidate gene for intellectual disability (ID), autism, schizophrenia and epilepsy. It is a member of a family of proteins that is highly conserved during evolution, sharing high homology with its Drosophila homolog, dCYFIP. CYFIP1 interacts with the Fragile X mental retardation protein (FMRP, encoded by the FMR1 gene), whose absence causes Fragile X syndrome, and with the translation initiation factor eIF4E. It is a member of the WAVE regulatory complex (WRC), thus representing a link between translational regulation and the actin cytoskeleton. Here, we present data showing a correlation between mRNA levels of CYFIP1 and other members of the WRC. This suggests a tight regulation of the levels of the WRC members, not only by post-translational mechanisms, as previously hypothesized. Moreover, we studied the impact of loss of function of both CYFIP1 and FMRP on neuronal growth and differentiation in two animal models - fly and mouse. We show that these two proteins antagonize each other's function not only during neuromuscular junction growth in the fly but also during new neuronal differentiation in the olfactory bulb of adult mice. Mechanistically, FMRP and CYFIP1 modulate mTor signaling in an antagonistic manner, likely via independent pathways, supporting the results obtained in mouse as well as in fly at the morphological level. Collectively, our results illustrate a new model to explain the cellular roles of FMRP and CYFIP1 and the molecular significance of their interaction., (© 2017. Published by The Company of Biologists Ltd.)

The present work analyzed three hard-bottom and two soft-bottom species of sabellid polychaetes to determine the content of several heavy metals in their branchial crown and body. The highest concentrations of heavy metals were recorded in the hard-bottom species Branchiomma bairdi, a recent Mediterranean introduction. Differences in the metal concentrations were most notable in the high trace metal levels of the branchial crown for all the studied species. Statistical analysis showed that the Mediterranean hard-bottom species were similar each other in their heavy metal content in the body as well as in the branchial crown and appeared separated from all the other species. Arsenic and vanadium hyperaccumulation in the branchial crowns of the considered sabellid species probably acts as a deterrent for predation. The observed differences among the examined species were discussed not only at the light of habitat colonization but also in terms of the phylogeny.

We investigated and compared, by laboratory experiments, the filter-feeding activity on bacteria by the solitary ascidian Styela plicata and the colonial ascidian Polyandrocarpa zorritensis. Clearance rates and retention efficiencies were estimated by using, as only food source, the bacterial species Vibrio alginolyticus selected on account of its importance in aquaculture pathogenicity. The Cmax was 1.4±0.17Lh -1 g -1 DW for S. plicata and 1.745Lh -1 g -1 DW for P. zorritensis. The highest retention efficiency was 41% corresponding to a removed bacterial biomass of 16.34+1.71 μgCL -1 g -1 DW for P. zorritensis and 81% corresponding to a bacterial biomass of 32.28+2.15 μgCL -1 g -1 DW for S. plicata. Styela plicata resulted higher efficient than P. zorritensis in removing V. alginolyticus from seawater in experimental tanks, thus representing a more suitable biofilter to restore the quality of microbiologically contaminated waters including those where aquaculture is practiced. Present laboratory experiments represent the first contribution to the comparison of the filtration activity of the two ascidians, as well as to characterize the filtration process on bacterioplankton and pone the basis for future field works aimed to restore bacteriological polluted seawater., (Copyright © 2016 Elsevier B.V. All rights reserved.)

NR5A1 is essential for the development and for the function of steroid producing glands of the reproductive system. Moreover, its misregulation is associated with endometriosis, which is the first cause of infertility in women. Hr39, the Drosophila ortholog of NR5A1, is expressed and required in the secretory cells of the spermatheca, the female exocrine gland that ensures fertility by secreting substances that attract and capacitate the spermatozoids. We here identify a direct regulator of Hr39 in the spermatheca: the Gcm transcription factor. Furthermore, lack of Gcm prevents the production of the secretory cells and leads to female sterility in Drosophila. Hr39 regulation by Gcm seems conserved in mammals and involves the modification of the DNA methylation profile of mNr5a1. This study identifies a new molecular pathway in female reproductive system development and suggests a role for hGCM in the progression of reproductive tract diseases in humans.

Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination., Competing Interests: KV: Senior editor, eLife. The other authors declare that no competing interests exist.

Health and safety regulations in many countries require workers at risk to wear safety shoes in a factory environment. These shoes are often heavy, rigid, and uncomfortable. Wearing safety shoes daily leads to foot problems, discomfort and fatigue, resulting also in the loss of numerous working days. Currently, knowledge of the biomechanical effects of insoles in safety shoes, during working activities, is very limited. Seventeen workers from a metalworking factory were selected and clinically examined for any foot conditions. Workers feet were 3D scanned, with regards to their plantar view, and the images used to design 34 custom-insoles, based on foot and safety shoe models. Three insoles were blind-tested by each worker: custom (CUS); prefabricated with the safety-shoe (PSS), and off-the-shelf (OTS). Foot-to-insole pressure distribution was measured in seven motor tasks replicating typical working activities: single and double-leg standing; weight lifting; stair ascending and descending; normal and fast walking. Wearing CUS within safety shoes resulted in a greater uniform pressure distribution across plantar regions for most of the working activities. Peak pressure at the forefoot during normal walking was the lowest in the custom insole (CUS 275.9±55.3kPa; OTS 332.7±75.5kPa; PSS 304.5±54.2kPa). Normal and fast walking were found to be the most demanding activities in terms of peak pressure. Wearing safety shoes results in high pedobarographic parameters in several foot regions. The use of custom insoles designed on the foot morphology helps decrease peak pressure and pressure-time integral compared to prefabricated featureless insoles., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Master genes are known to induce the differentiation of a multipotent cell into a specific cell type. These molecules are often transcription factors that switch on the regulatory cascade that triggers cell specification. Gcm was first described as the master gene of the glial fate in Drosophila as it induces the differentiation of neuroblasts into glia in the developing nervous system. Later on, Gcm was also shown to regulate the differentiation of blood, tendon and peritracheal cells as well as that of neuronal subsets. Thus, the glial master gene is used in at least 4 additional systems to promote differentiation. To understand the numerous roles of Gcm, we recently reported a genome-wide screen of Gcm direct targets in the Drosophila embryo. This screen provided new insight into the role and mode of action of this powerful transcription factor, notably on the interactions between Gcm and major differentiation pathways such as the Hedgehog, Notch and JAK/STAT. Here, we discuss the mode of action of Gcm in the different systems, we present new tissues that require Gcm and we revise the concept of 'master gene'.

The efficient treatment of hematological malignancies as Acute Myeloid Leukemia, myelofibrosis and Chronic Myeloid Leukemia, requires the elimination of cancer-initiating cells and the prevention of disease relapse through targeting pathways that stimulate generation and maintenance of these cells. In mammals, inhibition of Smoothened, the key mediator of the Hedgehog signaling pathway, reduces Chronic Myeloid Leukemia progression and propagation. These findings make Smo a candidate target to inhibit maintenance of leukemia-initiating cells. In Drosophila melanogaster the same pathway maintains the hematopoietic precursor cells of the lymph gland, the hematopoietic organ that develops in the larva. Using Drosophila as an in vivo model, we investigated the mode of action of PF-04449913, a small-molecule inhibitor of the human Smo protein. Drosophila larvae fed with PF-04449913 showed traits of altered hematopoietic homeostasis. These include the development of melanotic nodules, increase of circulating hemocytes, the size increase of the lymph gland and accelerated differentiation of blood cells likely due to the exit of multi-potent precursors from quiescence. Importantly, the Smo inhibition can lead to the complete loss of hematopoietic precursors. We conclude that PF-04449913 inhibits Drosophila Smo blocking the Hh signaling pathway and causing the loss of hematopoietic precursor cells. Interestingly, this is the effect expected in patients treated with PF-04449913: number decrease of cancer initiating cells in the bone marrow to reduce the risk of leukemia relapse. Altogether our results indicate that Drosophila comprises a model system for the in vivo study of molecules that target evolutionary conserved pathways implicated in human hematological malignancies.

Aubergine is an RNA-binding protein of the Piwi clade, functioning in germline in the piRNA pathway that silences transposons and repetitive sequences. Several mutations of this gene exist, but they mostly result in truncated proteins or correspond to mutations that also affect neighboring genes. We have generated complete aubergine knock-out mutants that do not disrupt the neighboring genes. These novel mutants are characterized by PCR and sequencing. Their nature is confirmed by female sterility and by the presence of crystals in testes, common to the aubergine loss of function mutations. These mutants provide novel and more appropriate tools for the study of the piRNA pathway that controls genome stability.

Ultraviolet (UV) radiation can produce biological damage, leading the cell to apoptosis by the p53 pathway. This study evaluated some molecular markers of the apoptosis pathway induced by UVA, UVB and UVA+ UVB (Solar Simulator, SIM) in environmental doses, during five consecutive days of exposure, in the brain of the crab Ucides cordatus. We evaluated the central nervous system (CNS) by immunoblotting the content of proteins p53, p21, phosphorylated AKT, BDNF, GDNF, activated caspase-3 (C3) and phosphohistone H3 (PH3); and by immunohistochemical tests of the cells labeled for PH3 and C3. After the fifth day of exposure, UVB radiation and SIM increased the protein content of p53, increasing the content of AKT and, somehow, blocking p21, increasing the content of activated caspase-3, which led the cells to apoptosis. The signs of death affected the increase in neurotrophins, such as BDNF and GDNF, stimulating the apoptotic cascade of events. Immunohistochemical assays and immunoblotting showed that apoptosis was present in the brains of all UV groups, while the number of mitotic cells in the same groups decreased. In conclusion, environmental doses of UV can cause apoptosis by increasing p53 and decreasing p21, revealing an UV-damage pathway for U. cordatus., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Throughout evolution, glia have key regulatory roles in neural development and function. Typically, they control the response to developmental and/or pathological signals, thereby affecting neural proliferation, remodeling, survival, and regeneration. Such complex biology depends on the plastic features of glial cells, but also on the presence of different classes of glial cells, hence the importance of understanding the cellular and the molecular mechanisms underlying their development. The fly community has made major breakthroughs by characterizing the bases of gliogenesis and here we describe the glial lineages as well as the glial promoting factor active in the embryo of Drosophila melanogaster. WIREs Dev Biol 2016, 5:67-84. doi: 10.1002/wdev.200 For further resources related to this article, please visit the WIREs website., (© 2015 Wiley Periodicals, Inc.)

High-throughput screens allow us to understand how transcription factors trigger developmental processes, including cell specification. A major challenge is identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates identification of conserved transcriptional programs. Here we show the results and the validation of a DNA adenine methyltransferase identification (DamID) genome-wide screen that identifies the direct targets of Glide/Gcm, a potent transcription factor that controls glia, hemocyte, and tendon cell differentiation in Drosophila. The screen identifies many genes that had not been previously associated with Glide/Gcm and highlights three major signaling pathways interacting with Glide/Gcm: Notch, Hedgehog, and JAK/STAT, which all involve feedback loops. Furthermore, the screen identifies effector molecules that are necessary for cell-cell interactions during late developmental processes and/or in ontogeny. Typically, immunoglobulin (Ig) domain-containing proteins control cell adhesion and axonal navigation. This shows that early and transiently expressed fate determinants not only control other transcription factors that, in turn, implement a specific developmental program but also directly affect late developmental events and cell function. Finally, while the mammalian genome contains two orthologous Gcm genes, their function has been demonstrated in vertebrate-specific tissues, placenta, and parathyroid glands, begging questions on the evolutionary conservation of the Gcm cascade in higher organisms. Here we provide the first evidence for the conservation of Gcm direct targets in humans. In sum, this work uncovers novel aspects of cell specification and sets the basis for further understanding of the role of conserved Gcm gene regulatory cascades., (Copyright © 2016 Cattenoz et al.)