Venomics Reveals Venom Complexity of the Piscivorous Cone Snail, Conus tulipa.

The piscivorous cone snail Conus tulipa has evolved a net-hunting strategy, akin to the deadly Conus geographus, and is considered the second most dangerous cone snail to humans. Here, we present the first venomics study of C. tulipa venom using integrated transcriptomic and proteomic approaches. Parallel transcriptomic analysis of two C. tulipa specimens revealed striking differences in conopeptide expression levels (2.5-fold) between individuals, identifying 522 and 328 conotoxin precursors from 18 known gene superfamilies. Despite broad overlap at the superfamily level, only 86 precursors (11%) were common to both specimens. Conantokins (NMDA antagonists) from the superfamily B1 dominated the transcriptome and proteome of C. tulipa venom, along with superfamilies B2, A, O1, O3, con-ikot-ikot and conopressins, plus novel putative conotoxins precursors T1.3, T6.2, T6.3, T6.4 and T8.1. Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating α-, ω-, µ-, δ-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins. This venomic study confirms the potential for non-paralytic conotoxins to contribute to the net-hunting strategy of C. tulipa.

Mind the Gap! How the Digital Turn Upsets Intellectual Property.

Intellectual property is one of the highly divisive issues in contemporary philosophical and political debates. The main objective of this paper is to explore some sources of tension between the formal rules of intellectual property (particularly copyright and patents) and the emerging informal norms of file sharing and open access in online environments. We look into the file sharing phenomena not only to illustrate the deepening gap between the two sets of norms, but to cast some doubt on the current regime of intellectual property as an adequate frame for the new type of interactions in online environments. Revisiting the classic Arrow-Demsetz debate about intellectual property and the epistemological issues involved in assessing institutions, we suggest that seeking out new institutional arrangements aligned with the norms-in-use seems to be a more promising strategy in the new technological setting than attempting to reinforce the current legal framework. Moreover, such a strategy is less prone to committing the so-called 'Nirvana fallacies'. As a secondary task, we try to cast some doubt on the two most common moral justifications of intellectual property as being able to ground the full extent of the current intellectual property regime.

Specialized insulin is used for chemical warfare by fish-hunting cone snails.

More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that posttranslational modifications characteristic of conotoxins (hydroxyproline, γ-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snail's distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.

Effects of virtual reality-based training with BTs-Nirvana on functional recovery in stroke patients: preliminary considerations.

AIM OF THE STUDY: Cognitive impairment occurs frequently in post-stroke patients. This study aimed to determine the effects of a virtual reality training (VRT) with BTs-Nirvana (BTsN) on the recovery of cognitive functions in stroke patients, using the Interactive-Semi-Immersive Program (I-SIP). MATERIALS AND METHODS: We enrolled 12 subjects (randomly divided into two groups: experimental group (EG); and control group (CG)), who attended the Laboratory of Robotic and Cognitive Rehabilitation of IRCCS Neurolesi of Messina from January to June 2016. The EG underwent a VRT with BTsN, whereas CG received a standard cognitive treatment. Both the groups underwent the same conventional physiotherapy program. Each treatment session lasted 45 minutes and was repeated three times a week for 8 weeks. All the patients were evaluated by a specific clinical-psychometric battery before (T0), immediately (T1), and one month (T2) after the end of the training. RESULTS: At T1, the EG presented a greater improvement in the trunk control test (p = 0.03), the Montreal Cognitive Assessment (p = 0.01), the selective attention assessment scores (p = 0.01), the verbal memory (p = 0.03), and the visuospatial and constructive abilities (p = 0.01), as compared to CG. Moreover, such amelioration persisted at T2 only in the EG. CONCLUSIONS: According to these preliminary data, VRT with I-SIP can be considered a useful complementary treatment to potentiate functional recovery, with regard to attention, visual-spatial deficits, and motor function in patients affected by stroke.

Predatory and Defensive Strategies in Cone Snails.

Cone snails are carnivorous marine animals that prey on fish (piscivorous), worms (vermivorous), or other mollusks (molluscivorous). They produce a complex venom mostly made of disulfide-rich conotoxins and conopeptides in a compartmentalized venom gland. The pharmacology of cone snail venom has been increasingly investigated over more than half a century. The rising interest in cone snails was initiated by the surprising high human lethality rate caused by the defensive stings of some species. Although a vast amount of information has been uncovered on their venom composition, pharmacological targets, and mode of action of conotoxins, the venom-ecology relationships are still poorly understood for many lineages. This is especially important given the relatively recent discovery that some species can use different venoms to achieve rapid prey capture and efficient deterrence of aggressors. Indeed, via an unknown mechanism, only a selected subset of conotoxins is injected depending on the intended purpose. Some of these remarkable venom variations have been characterized, often using a combination of mass spectrometry and transcriptomic methods. In this review, we present the current knowledge on such specific predatory and defensive venoms gathered from sixteen different cone snail species that belong to eight subgenera: Pionoconus, Chelyconus, Gastridium, Cylinder, Conus, Stephanoconus, Rhizoconus, and Vituliconus. Further studies are needed to help close the gap in our understanding of the evolved ecological roles of many cone snail venom peptides.

Evaluation of the sexual function of female partners of men with erectile dysfunction receiving different treatment modalities: An observational study.

OBJECTIVE: To evaluate sexual functions of patients with erectile dysfunction (ED) and their female partners. METHODS: A total of 90 consecutive ED patients who received different ED therapies and their partners and 90 consecutive controls and their partners were divided into four groups. All participants were evaluated by the 15-item international index of erectile function and the Arabic version of female sexual function index (Ar-FSFI). RESULTS: All ED patients who received sildenafil demonstrated significant improvements of their erectile function compared to baseline. Their partners did not demonstrate improvements in frequency of pain during vaginal penetration (3.86 ± 0.58, 3.93 ± 0.45, p = 0.477), confidence of becoming aroused (3.86 ± 0.58, 3.93 ± 0.45, p 0.477), frequency of satisfaction with arousal (3.07 ± 0.37, 3.03 ± 0.49, p 0.712), and maintenance of lubrication (4.37 ± 0.49, 4.23 ± 0.73, p 0.354). All ED patients who received quadmix demonstrated significant improvements of their erectile function compared to baseline. Their partners did not demonstrate improvements in desire level (2.6 ± 0.67, 2.63 ± 0.85, p = 0.869) and lubrication maintenance (3.53 ± 0.82, 3.47 ± 0.82, p = 0.423). Finally, All ED patients who underwent semi rigid penile implant demonstrated significant improvements of their erectile function compared to baseline. Their female partners demonstrated significant improvements in all items of FSFI-19 compared to baseline except the frequency of pain during vaginal penetration (3.86 ± 0.58, 3.93 ± 0.45, p = 0.477), confidence of becoming aroused (3.86 ± 0.58, 3.93 ± 0.45, p = 0.477), frequency of satisfaction with arousal (3.07 ± 0.37, 3.03 ± 0.49, p = 0.712), and maintenance of lubrication (4.37 ± 0.49, 4.23 ± 0.73, p = 0.354). CONCLUSIONS: Sexual functions of ED males significantly improved after ED therapies. Nevertheless, some sexual functions of their partners were not positively impacted.

Reborn Three-Dimensional Graphene with Ultrahigh Volumetric Desalination Capacity.

The constructing of 3D materials with optimal performance is urgently needed to meet the growing demand of advanced materials in the high-tech sector. A distinctive 3D graphene (3DG) is designed based on a repeated rebirth strategy to obtain a better body and performance after each round of rebirth, as if it is Phoenix Nirvana. The properties of reborn graphene, namely 3DG after Nirvana (NvG), has been dramatically upgraded compared to 3DG, including high density (3.36 times) together with high porosity, as well as better electrical conductivity (1.41 times), mechanical strength (32.4 times), and ultrafast infiltration behavior. These advantages of NvG make it a strong intrinsic motivation for application in capacitive deionization (CDI). Using NvG directly as the CDI electrode, it has an extremely high volumetric capacity of 220 F cm-3 at 1 A cm-3 and a maximum salt absorption capacity of 8.02~9.2 mg cm-3 (8.9-10.2 times), while the power consumption for adsorption of the same mass of salt is less than a quarter of 3DG. The "Phoenix Nirvana"-like strategy of manufacturing 3D structures will undoubtedly become the new engine to kick-start the development of innovative carbon materials through an overall performance upgrade.

Repetition and the compulsion to repeat, a French perspective.

The discovery of a compulsion to repeat and its involvement in the elaboration of the second drive theory of the libido and the death drive was fundamental in the evolution of Freud's thought: psychic functioning was no longer governed by the pleasure principle alone, and this changed analytic technique. This led in 1923 to a change of topography in order to take into consideration the existence of destructiveness within the mind that Freud had hitherto underestimated.

Virtual Reality Based Cognitive Rehabilitation in Minimally Conscious State: A Case Report with EEG Findings and Systematic Literature Review.

Chronic disorders of consciousness cause a total or partial and fluctuating unawareness of the surrounding environment. Virtual reality (VR) can be useful as a diagnostic and/or a neurorehabilitation tool, and its effects can be monitored by means of both clinical and electroencephalography (EEG) data recording of brain activity. We reported on the case of a 17-year-old patient with a disorder of consciousness (DoC) who was provided with VR training to improve her cognitive-behavioral outcomes, which were assessed using clinical scales (the Coma Recovery Scale-Revised, the Disability Rating Scale, and the Rancho Los Amigos Levels of Cognitive Functioning), as well as EEG recording, during VR training sessions. At the end of the training, significant improvements in both clinical and neurophysiological outcomes were achieved. Then, we carried out a systematic review of the literature to investigate the role of EEG and VR in the management of patients with DoC. A search on PubMed, Web of Science, Scopus, and Google Scholar databases was performed, using the keywords: "disorders of consciousness" and "virtual reality", or "EEG". The results of the literature review suggest that neurophysiological data in combination with VR could be useful in evaluating the reactions induced by different paradigms in DoC patients, helping in the differential diagnosis. In conclusion, the EEG plus VR approach used with our patient could be promising to define the most appropriate stimulation protocol, so as to promote a better personalization of the rehabilitation program. However, further clinical trials, as well as meta-analysis of the literature, are needed to be affirmative on the role of VR in patients with DoC.

Use of virtual reality in improving poststroke neglect: Promising neuropsychological and neurophysiological findings from a case study.

After experiencing a stroke in the right hemisphere, almost 50% of patients show unilateral spatial neglect (USN). Virtual Reality technologies offer impressive opportunities for both the rehabilitation and assessment of different cognitive deficits, including USN. A 57-year-old woman, affected by subarachnoid hemorrhage presented a severe left hemiparesis with severe cognitive and behavioral alterations, including temporal and spatial disorientation, reduction of attention and memory process, slowing ideation, USN, and depression of mood. She underwent two different rehabilitation trainings, including standard cognitive training (SCT) in addition to semi-immersive virtual training with her shadow (S-IVT_s) and SCT in addition to a Semi- immersive virtual training, without her shadow (S-IVT). The patient was assessed before and after each of the two different trainings, by using a specific psychometric battery and the event related potential, P300. Only at the end of the use of the S-IVT, we observed a significant improvement in the motor and cognitive function, with regard to USN. SCT in addition to S-IVT with Bts-Nirvana System may be a promising approach in improving attention process, spatial cognition, and mood in patients with post stroke USN, as also demonstrated by the electrophysiological parameters.

Leafhopper genus Nirvana Kirkaldy (Hemiptera: Cicadellidae: Evacanthinae) newly recorded from Pakistan with description of a new species.

The leafhopper genus Nirvana is reported for the first time from Pakistan based on one new species described here in: Nirvana spinosa sp. nov. Habitus and genital photographic illustrations are provided for the new species.

Improving post-stroke cognitive and behavioral abnormalities by using virtual reality: A case report on a novel use of nirvana.

Cognitive impairment, as well as mood and anxiety disorders, occur frequently in patients following stroke. Aim of this study was to evaluate the effects of a combined rehabilitative treatment using conventional relaxation and respiratory techniques, in a specific rehabilitative virtual environment (by using Bts-Nirvana). A 58-year-old woman, affected by hemorrhagic stroke, underwent two different rehabilitation trainings, including either standard relaxation techniques alone in a common clinical setting or the same psychological approach in a semi-immersive virtual environment with an augmented sensorial (audio-video) and motor feedback (sensory motor-interaction). We evaluated the patient's cognitive and psychological profile before and after the two different trainings, by using a specific psychometric battery, aimed to assess cognitive status, attention processes and to estimate the presence of mood alterations, anxiety and coping strategies. Only at the end of the combined approach, we observed a significant improvement in attention and memory functions, with a nearly complete relief of anxiety symptoms and an improvement in coping strategies. Relaxation and respiratory techniques in a semi-immersive virtual reality environment, using Bts-Nirvana, may be a promising tool in improving attention process, coping strategies, and anxiety in individuals with neurological disorders, including stroke.

Reflexões sobre os dois princípios do acontecer psíquico e algumas relações com o projeto de psicologia e trabalhos posteriores / Reflexiones sobre los dos principios del acaecer psiquico y algunas relaciones con el proyecto de psicologia y trabajos posteriores / Reflecting upon the two principles of psychic events and some correlations with the psychology project and latter publications

O autor parte da definição do conceito de princípio valendo-se das contribuições de alguns filósofos. Logo após, detendo-se mais no Projeto para uma psicolocia científica de Freud (1895[1950]), relaciona os vários princípios freudianos alinhando-os com os juízos de condenação ou atribuição e o juízo de realidade. E assim retomado o constante diálogo entre os referidos juízos durante os inúmeros fenômenos vitais. O texto de Freud, A negativa de 1925, é tomado como parâmetro comparativo e relacionado com o complexo do semelhante descrito em 1895. Finalmente, através do conceito de espaço transicional de Winnicott, é reexaminado o texto de Freud de 1924, A perda da realidade na neurose e psicose, comparando criatividade e saúde como algo entre a neurose e a psicose.

The author begins his work with the definition of principle making use of the contributions of a number of philosophers. He goes on analyzing Freud's A project for scientific psychology (1895[1950]), correlating the many Freudian principles, aligning them with the judgments of condemnation or attribution and the judgment of reality. Therefore, the constant dialogue between the mentioned judgments is reestablished during the innumerous vital phenomena. The author uses Freud's text, Negation (1925), as a comparative parameter and relates it to the similarity complex described in 1895. Finally, using Winnicott's transitional space concept, Freud's (1924) text, The loss of reality in neurosis and psychosis, is reexamined, comparing creativity and health as something in between neurosis and psychosis.

El autor parte de la definición del concepto de principio valiéndose de lãs contribuciones de algunos filósofos. Luego, deteniéndose más en el Proyecto para una psicologia científica de Freud (1895[1950]), relaciona los varios princípios freudianos estableciendo una línea entre los mismos y los juicios de condenación o atribución y el juicio de realidad. Así se retoma el constante diálogo entre los referidos juicios durante los innumerables fenómenos vitales. El texto de Freud, La negativa de 1925, es tomado como parámetro comparativo y relacionado con el complejo del semejante descripto en 1895. Finalmente, a través del concepto de espacio transicional de Winnicott, se vuelve a analizar el texto de Freud de 1924, La pérdida de la realidad en la neurosis y la psicosis, comparando creatividad y salud a algo entre la neurosis y la psicosis.