Contribution to the Understanding of Particle Motion Perception in Marine Invertebrates.

Marine invertebrates potentially represent a group of species whose ecology may be influenced by artificial noise. Exposure to anthropogenic sound sources could have a direct consequence on the functionality and sensitivity of their sensory organs, the statocysts, which are responsible for their equilibrium and movements in the water column. The availability of novel laser Doppler vibrometer techniques has recently opened the possibility of measuring whole body (distance, velocity, and acceleration) vibration as a direct stimulus eliciting statocyst response, offering the scientific community a new level of understanding of the marine invertebrate hearing mechanism.

Statocyst Ultrastructure in the Norwegian Lobster (Nephrops norvegicus).

Statocyst anatomy and fine morphology in Norwegian lobster (Nephrops norvegicus) are studied for the first time using scanning and transmission electron microscopy. N. norvegicus exhibits sensory setae projecting from the statocyst inner cavity floor into a mass of sand granules (statoconia) embedded in a gelatinous substance. The setae are distributed in four areas: a curved field made up of an inner single row and an outer double row that run on a circle around the medial and lateral rim of the central depression, a small setal field in the posterior part, a large setal field, opposite to the small field, and a short row, running internally and lying parallel to the inner single row, next to the small setal field. A study of the fine morphology of the statocyst sensory setae shows that the structure of the setae in the different areas is similar, with a bulb (the proximal portion of the sensillum), a setal shaft, a tooth (the smooth portion of the bulb), a fulcrum (a transverse fold), and filamentous hairs. The hair cells are firmly implanted within the cuticular layer. Although the type of innervation of the statocyst was not determined in the present study, the close taxonomic position of the lobster to that of the crayfish and crab would suggest that the setae in N. norvegicus are pure mechanoreceptors rather than sensory cells.

Metabolomics and triple-negative breast cancer: A systematic review.

Triple-negative breast cancer stands out as the most aggressive subtype of breast malignancy and is characterized by an unfavourable prognosis. Objective: This systematic review summarizes the insights gleaned from metabolomic analyses of individuals afflicted with this cancer variant. The overarching goal was to delineate the molecular alterations associated with triple-negative breast cancer, pinpointing potential therapeutic targets and novel biomarkers. Methods: We systematically searched for evidence using the PubMed database and followed the PRISMA and STARLITE guidelines. The search parameters were delimited to articles published within the last 13 years. Results: From an initial pool of 148 scrutinized articles, 17 studies involving 1686 participants were deemed eligible for inclusion. The current body of research shows a paucity of studies, and the available evidence presents conflicting outcomes. Notwithstanding, Pathway Enrichment Analysis identified the urea and glucose-alanine cycles as the most affected metabolic pathways, followed by arginine, proline, and aspartate metabolism. Conclusion: Future investigations need to focus on elucidating which of those metabolites and/or pathways might be reliable candidates for novel therapeutic interventions or reliable biomarkers for diagnosis and prognosis of this subtype of breast cancer.

Artificial sound impact could put at risk hermit crabs and their symbiont anemones.

The sea anemone Calliactis parasitica, which is found in the East Atlantic (Portugal to Senegal) and the Mediterranean Sea, forms a symbiotic relationship with the red hermit crab, Dardanus calidus, in which the anemone provides protection from predators such as the octopus while it gains mobility, and possibly food scraps, from the hermit crab. Acoustic pollution is recognised by the scientific community as a growing threat to ocean inhabitants. Recent findings on marine invertebrates showed that exposure to artificial sound had direct behavioural, physiological and ultrastructural consequences. In this study we assess the impact of artificial sound (received level 157 ± 5 dB re 1 µPa2 with peak levels up to 175 dB re 1 µPa2) on the red hermit crab and its symbiotic sea anemone. Scanning electron microscopy analyses revealed lesions in the statocyst of the red hermit crab and in the tentacle sensory epithelia of its anemone when exposed to low-intensity, low-frequency sounds. These ultrastructural changes under situations of acoustic stress in symbiotic partners belonging to different phyla is a new issue that may limit their survival capacity, and a new challenge in assessing the effects of acoustic disturbance in the oceanic ecosystem. Despite the lesions found in the red hermit crab, its righting reflex time was not as strongly affected showing only an increase in the range of righting times. Given that low-frequency sound levels in the ocean are increasing and that reliable bioacoustic data on invertebrates is very scarce, in light of the results of the present study, we argue that anthropogenic sound effects on invertebrates species may have direct consequences in the entire ecosystem.

Cross-sensory interference assessment after exposure to noise shows different effects in the blue crab olfactory and sound sensing capabilities.

Underwater noise pollution is an increasing threat to marine ecosystems. Marine animals use sound in communication and orientation processes. The introduction of anthropogenic noise in their habitat can interfere with sound production and reception as well as with the acquisition of vital information through other sensory systems. In the blue crab (Callinectes sapidus), the statocyst is responsible for acoustic perception, and it is housed at the base of its first pair of antennae (antennule). The sensilla of the distal part of these antennule hosts the olfactory system, which is key for foraging. Given the anatomical proximity of the two sensory regions, we evaluated the possible interference of sound exposure with the crab ability to find food, by using an aquatic maze, and looked at the potential impairment of the righting reflex as well as at ultrastructural damages in statocysts. Although a significant effect was observed when looking at the time used by the animal to recover its habitual position ("righting reflex"), which was associated to lesions in the statocyst sensory epithelia, the time required to find food did not increase after the exposure to sound. When the crabs were exposed to natural sounds (marine background noise and sounds of their predators: Micropogonias undulates and Sciaenops ocellatus) they did not show significant differences in foraging behaviour. Although we found no unequivocal evidence of a negative impact of sound on olfactory capabilities, the study showed a clear righting reflex impairment correlated with ultrastructural damages of the statocysts. We argue that crab populations that cannot easily avoid noise sources due to their specific coastal distributions may incur in significant direct fitness costs (e.g. impairment of complex reflexes). This integrated approach to sound effect assessment could be used as a model for other invertebrate species to effectively monitor noise impact in marine environments.

[Comparison of digital and conventional life story books on mood, communication, cognition and quality of life in people with dementia in nursing homes: A pilot study]. / Comparación de los libros de historia de vida digitales y convencionales sobre el estado de ánimo, la comunicación, la cognición y la calidad de vida en personas con demencia en residencias: un estudio piloto.

INTRODUCTION: Person-centered care (PCC) includes life story, a form of reminiscence therapy that can be useful in the treatment of dementia. We compared the efficacy of using a digital or conventional life story book (LSB) on depressive symptoms, communication, cognition, and quality of life. MATERIAL AND METHODS: Thirty one persons with dementia living in 2 PCC nursing homes were randomly assigned to receive reminiscence therapy based on the Neural Actions digital LSB (n=16) or a conventional LSB (n=15). Both groups performed 2 weekly sessions of 45min for 5 weeks. Depressive symptoms were evaluated with the Cornell scale (CSDD); communication with the Holden scale (HCS), cognition with the Mini Mental State Examination (MMSE) and quality of life with the quality of life scale for Alzheimer's (QoL-AD). The results were analyzed using ANOVA of repeated measures with the jamovi 2.3 program. RESULTS: Both LSB improved communication skills (η2=0.115; p<0.001), with no differences between groups. No effects on quality of life, cognition, or mood were found. CONCLUSIONS: In PCC centres digital or conventional LSB can be useful in the treatment of people with dementia by facilitating communication. Its role on quality of life, cognition or mood is uncertain.

Commercial cuttlefish exposed to noise from offshore windmill construction show short-range acoustic trauma.

The installation of marine renewable energy devices (MREDs, wind turbines and converters of wave, tidal and ocean thermal energy) has increased quickly in the last decade. There is a lack of knowledge concerning the effects of MREDs on benthic invertebrates that live in contact with the seabed. The European common cuttlefish (Sepia officinalis) is the most abundant cephalopod in the Northeast Atlantic and one of the three most valuable resources for English Channel fisheries. A project to build an offshore wind farm in the French bay of Saint-Brieuc, near the English Channel, raised concern about the possible acoustic impact on local cuttlefish communities. In this study, consisting of six exposure experiments, three types of noise were considered: 3 levels of pile-driving and 3 levels of drilling. The objectives were to assess possible associated changes in hatching and larva survival, and behavioural and ultrastructural effects on sensory organs of all life stages of S. officinalis populations. After exposure, damage was observed in the statocyst sensory epithelia (hair cell extrusion) in adults compared to controls, and no anti-predator reaction was observed. The exposed larvae showed a decreased survival rate with an increasing received sound level when they were exposed to maximum pile-driving and drilling sound levels (170 dB re 1 µPa2 and 167 dB re 1 µPa2, respectively). However, sound pressure levels's lower than 163 dB re 1 µPa2 were not found to elicit severe damage. Simulating a scenario of immobile organisms, eggs were exposed to a combination of both pile driving and drilling as they would be exposed to all operations without a chance to escape. In this scenario a decrease of hatching success was observed with increasing received sound levels.

Seagrass Posidonia is impaired by human-generated noise.

The last hundred years have seen the introduction of many sources of artificial noise in the sea environment which have shown to negatively affect marine organisms. Little attention has been devoted to how much this noise could affect sessile organisms. Here, we report morphological and ultrastructural changes in seagrass, after exposure to sounds in a controlled environment. These results are new to aquatic plants pathology. Low-frequency sounds produced alterations in Posidonia oceanica root and rhizome statocysts, which sense gravity and process sound vibration. Nutritional processes of the plant were affected as well: we observed a decrease in the number of rhizome starch grains, which have a vital role in energy storage, as well as a degradation in the specific fungal symbionts of P. oceanica roots. This sensitivity to artificial sounds revealed how sound can potentially affect the health status of P. oceanica. Moreover, these findings address the question of how much the increase of ocean noise pollution may contribute in the future to the depletion of seagrass populations and to biodiversity loss.

A critical period of susceptibility to sound in the sensory cells of cephalopod hatchlings.

The cephalopod statocyst and lateral line systems are sensory organs involved in orientation and balance. Lateral lines allow cephalopods to detect particle motion and are used for locating prey or predators in low light conditions. Here, we show the first analysis of damaged sensory epithelia in three species of cephalopod hatchlings (Sepia officinalis, Loligo vulgaris and Illex coindetii) after sound exposure. Our results indicate lesions in the statocyst sensory epithelia, similar to what was found in adult specimens. The novelty is that the severity of the lesions advanced more rapidly in hatchlings than in adult animals; i.e. the degree of lesions seen in hatchlings immediately after noise exposure would develop within 48 h in adults. This feature suggests a critical period of increased sensitivity to acoustic trauma in those species as has been described in developing mammalian cochlea and avian basilar papilla. The hair cells in the lateral lines of S. officinalis followed the same pattern of damage occurrence, while those of L. vulgaris and I. coindetii displayed a decreasing severity of damage after 24 h. These differences could be due to dissimilarities in size and life stages between the three species.

Marine mammal acoustic detections in the Greenland and Barents Sea, 2013 - 2014 seasons.

While the Greenland and Barents Seas are known habitats for several cetacean and pinniped species there is a lack of long-term monitoring data in this rapidly changing environment. Moreover, little is known of the ambient soundscapes, and increasing off-shore anthropogenic activities can influence the ecosystem and marine life. Baseline acoustic data is needed to better assess current and future soundscape and ecosystem conditions. The analysis of a year of continuous data from three passive acoustic monitoring devices revealed species-dependent seasonal and spatial variation of a large variety of marine mammals in the Greenland and Barents Seas. Sampling rates were 39 and 78 kHz in the respective locations, and all systems were operational at a duty cycle of 2 min on, 30 min off. The research presents a description of cetacean and pinniped acoustic detections along with a variety of unknown low-frequency tonal sounds, and ambient sound level measurements that fall within the scope of the European Marine Strategy Framework (MSFD). The presented data shows the importance of monitoring Arctic underwater biodiversity for assessing the ecological changes under the scope of climate change.

Regeneration of lesioned entorhino-hippocampal axons in vitro by combined degradation of inhibitory proteoglycans and blockade of Nogo-66/NgR signaling.

Damaged axons do not regenerate after axotomy in the adult mammalian central nervous system (CNS). This may be due to local inhibitory factors at the site of injury, such as overexpression of chondroitin sulfate (CS) proteoglycans (CSPG), and the presence of myelin-associated inhibitors (MAI). To overcome CSPG- or myelin-induced inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For example, NEP1-40 is a synthetic peptide that promotes axonal regeneration by blocking Nogo-66/NgR interaction and chondroitinase ABC (ChABC), which degrades CS, thereby also promoting axon regrowth. Here, we examined whether the combination of these complementary strategies facilitates regeneration of the lesioned entorhino-hippocampal pathway (EHP) in slice cultures. In this model, overexpressed CSPG and MAI impaired axon regrowth, which mimics regeneration failure in vivo. Both CS cleavage with ChABC and NEP1-40 strongly facilitated the regrowth of entorhinal axons after axotomy, permitting the re-establishment of synaptic contacts with target cells. However, the combined treatment did not improve the regeneration induced by ChABC alone, and the delayed treatment of ChABC, but not NEP1-40, had a less pronounced effect on axonal regrowth compared with acute treatment. These results provide insight into the development of new assays and strategies to enhance axon regeneration in injured cortical connections.

Offshore exposure experiments on cuttlefish indicate received sound pressure and particle motion levels associated with acoustic trauma.

Recent findings on cephalopods in laboratory conditions showed that exposure to artificial noise had a direct consequence on the statocyst, sensory organs, which are responsible for their equilibrium and movements in the water column. The question remained about the contribution of the consequent near-field particle motion influence from the tank walls, to the triggering of the trauma. Offshore noise controlled exposure experiments (CEE) on common cuttlefish (Sepia officinalis), were conducted at three different depths and distances from the source and particle motion and sound pressure measurements were performed at each location. Scanning electron microscopy (SEM) revealed injuries in statocysts, which severity was quantified and found to be proportional to the distance to the transducer. These findings are the first evidence of cephalopods sensitivity to anthropogenic noise sources in their natural habitat. From the measured received power spectrum of the sweep, it was possible to determine that the animals were exposed at levels ranging from 139 to 142 dB re 1 µPa2 and from 139 to 141 dB re 1 µPa2, at 1/3 octave bands centred at 315 Hz and 400 Hz, respectively. These results could therefore be considered a coherent threshold estimation of noise levels that can trigger acoustic trauma in cephalopods.

[Results of a management plan for surgical waiting lists for hip and knee replacements]. / Resultados de un plan de gestión de listas de espera quirúrgica de prótesis articulares.

This study describes the implementation of a management plan for surgical joint replacement waiting lists and its results after 3 years. The plan was based on the following: unification of information and scheduling, periodic review, clinical guidelines, management of demand, prioritization according to need, and increasing the services provided. During the first year, the plan succeeded in revealing the real waiting list, with 23% more patients than previously included. Three years later, 16% of the patients had not turned up for surgery after being scheduled; the mean length of hospital stay for joint replacements had been reduced by 4 days; 59.5% of the patients joining the list had been assessed with a prioritization instrument, and the number of joint replacements had increased by 16% with a reduction of 14.7% in patients waiting for joint replacements. The resolution time for these procedures had also decreased by 3 months for knee arthroplasty and by 1 month for hip arthroplasty.

Evidence of Cnidarians sensitivity to sound after exposure to low frequency underwater sources.

Jellyfishes represent a group of species that play an important role in oceans, particularly as a food source for different taxa and as a predator of fish larvae and planktonic prey. The massive introduction of artificial sound sources in the oceans has become a concern to science and society. While we are only beginning to understand that non-hearing specialists like cephalopods can be affected by anthropogenic noises and regulation is underway to measure European water noise levels, we still don't know yet if the impact of sound may be extended to other lower level taxa of the food web. Here we exposed two species of Mediterranean Scyphozoan medusa, Cotylorhiza tuberculata and Rhizostoma pulmo to a sweep of low frequency sounds. Scanning electron microscopy (SEM) revealed injuries in the statocyst sensory epithelium of both species after exposure to sound, that are consistent with the manifestation of a massive acoustic trauma observed in other species. The presence of acoustic trauma in marine species that are not hearing specialists, like medusa, shows the magnitude of the problem of noise pollution and the complexity of the task to determine threshold values that would help building up regulation to prevent permanent damage of the ecosystems.

Bcl-2 overexpression does not promote axonal regeneration of the entorhino-hippocampal connections in vitro after axotomy.

CNS lesions trigger cell death in injured neurons and glia. Genes of the bcl-2 family play crucial roles in the control of apoptosis and cell survival in the CNS. Recently, it has been suggested that overexpression of bcl-2 induces axonal elongation and regeneration in vitro and in vivo. Here, we analyze the regenerative potential of bcl-2 overexpression in the axotomized entorhino-hippocampal connection in organotypic slice cocultures. Our results show that in slice cocultures from bcl-2-overexpressing mice, there is a decrease in the number of dead neurons in the entorhinal cortex. In addition, axonal regeneration is not enhanced after axotomy. Thus, in the entorhino-hippocampal formation in vitro, bcl-2 overexpression rescues neurons from axotomy-induced cell death but fails to enhance the regeneration of the entorhino-hippocampal connection.

Ultrastructural damage of Loligo vulgaris and Illex coindetii statocysts after low frequency sound exposure.

There is a considerable lack of information concerning marine invertebrate sensitivity to sound exposure. However, recent findings on cuttlefish and octopi showed that exposure to artificial noise had a direct consequence on the functionality and physiology of the statocysts, sensory organs, which are responsible for their equilibrium and movements in the water column. Owing to a lack of available data on deep diving cephalopod species, we conducted a noise exposure comparative experiment on one Mediterranean squid, Illex coindetii, and on the European squid Loligo vulgaris. Scanning electron microscopy (SEM) revealed similar injuries in the inner structure of the statocysts, as those found in cuttlefish and octopi. In addition to the ultrastructural description of the lesions, we publish here the first images of the crista-cupula system and inner statocyst cavity of I. coindetii.

Reelin and mDab1 regulate the development of hippocampal connections.

We analyze in this study the participation of Reelin and mDab1 in the development of hippocampal connections. We show that mDab1 is present in growth cones and axonal tracts of developing hippocampal afferents. mdab1-deficiency produces severe alterations in the entorhino-hippocampal and commissural connections identical to those described in reeler mice, including innervation of ectopic areas, formation of abnormal patches of fiber termination and a delay in the refinement of projections. Organotypic slice cultures combining tissue from mdab1-mutant and control mice demonstrate that the abnormalities observed in the mutant entorhino-hippocampal projection are caused by mdab1-deficiency in both the projecting neurons and target hippocampal cells. Axonal afferents that innervate the hippocampus react to Reelin by reducing axonal growth, and increasing growth cone collapse and axonal branching. Altogether these results indicate that Reelin and mDab1 participate in the development and refinement of hippocampal connections by regulating axonal extension, targeting and branching.

Involvement of Cajal-Retzius cells in robust and layer-specific regeneration of the entorhino-hippocampal pathways.

Severed adult CNS axons can extend over long distances when a permissive 'milieu', such as grafted Schwann cells or ensheathing cells, is provided. Moreover, functional blocking of endogenous inhibitory factors, such as Nogo-A or proteoglycans, enhances the regeneration of axotomized neurons. Here we examine whether guidance cues available during the development of axonal pathways could also potentiate the regeneration of lesioned adult circuits. The Cajal-Retzius cells in the hippocampus are transient pioneer neurons that guide entorhino-hippocampal afferents to their target layers. By using an in vitro model of axotomy of the entorhino-hippocampal pathway we show that Cajal-Retzius cells triggered the regeneration of the axotomized entorhino-hippocampal pathway. Furthermore, the regrowth induced by Cajal-Retzius cells was robust and its pattern was indistinguishable from that of the unlesioned entorhino-hippocampal pathway. Thus, regenerating axons regrew in a layer-specific fashion towards the appropriate target layers, making synaptic contacts with target pyramidal neurons. Interestingly, the ability of lesioned entorhinal axons to regrow was maintained for at least 9 days after axotomy. These results show that the growth-promoting cells controlling the development of neural circuits will be a relevant approach to promoting the regeneration of lesioned adult CNS pathways.

Regulation of Nogo and Nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions.

Axonal regeneration in the adult CNS is limited by the presence of several inhibitory proteins associated with myelin. Nogo-A, a myelin-associated inhibitor, is responsible for axonal outgrowth inhibition in vivo and in vitro. Here we study the onset and maturation of Nogo-A and Nogo receptor in the entorhino-hippocampal formation of developing and adult mice. We also provide evidence that Nogo-A does not inhibit embryonic hippocampal neurons, in contrast to other cell types such as cerebellar granule cells. Our results also show that Nogo and Nogo receptor mRNA are expressed in the adult by both principal and local-circuit hippocampal neurons, and that after lesion, Nogo-A is also transiently expressed by a subset of reactive astrocytes. Furthermore, we analyzed their regulation after kainic acid (KA) treatment and in response to the transection of the entorhino-hippocampal connection. We found that Nogo-A and Nogo receptor are differentially regulated after kainic acid or perforant pathway lesions. Lastly, we show that the regenerative potential of lesioned entorhino-hippocampal organotypic slice co-cultures is increased after blockage of Nogo-A with two IN-1 blocking antibodies. In conclusion, our results show that Nogo and its receptor might play key roles during development of hippocampal connections and that they are implicated in neuronal plasticity in the adult.