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Abstract Prion diseases are fatal, infectious, and incurable neurodegenerative disorders caused by misfolding of the cellular prion protein (PrPC) into the infectious isoform (PrPSc). In humans, there are sporadic, genetic and infectious etiologies, with sporadic Creutzfeldt-Jakob disease (sCJD) being the most common form. Currently, no treatment is available for prion diseases. Cellular cholesterol is known to impact prion conversion, which in turn results in an accumulation of cholesterol in prion-infected neurons. The major elimination of brain cholesterol is achieved by the brain specific enzyme, cholesterol 24-hydroxylase (CYP46A1). Cyp46A1 converts cholesterol into 24(S)-hydroxycholesterol, a membrane-permeable molecule that exits the brain. We have demonstrated for the first time that Cyp46A1 levels are reduced in the brains of prion-infected mice at advanced disease stage, in prion-infected neuronal cells and in post-mortem brains of sCJD patients. We have employed the Cyp46A1 activator efavirenz (EFV) for treatment of prion-infected neuronal cells and mice. EFV is an FDA approved anti-HIV medication effectively crossing the blood brain barrier and has been used for decades to chronically treat HIV patients. EFV significantly mitigated PrPSc propagation in prion-infected cells while preserving physiological PrPC and lipid raft integrity. Notably, oral administration of EFV treatment chronically at very low dosage starting weeks to months after intracerebral prion inoculation of mice significantly prolonged the lifespan of animals. In summary, our results suggest that Cyp46A1 as a novel therapeutic target and that its activation through repurposing the anti-retroviral medication EFV might be valuable treatment approach for prion diseases.

Amyloid β (Aβ) peptides generated from the amyloid precursor protein (APP) play a critical role in the development of Alzheimer's disease (AD) pathology. Aβ-containing neuronal exosomes, which represent a novel form of intercellular communication, have been shown to influence the function/vulnerability of neurons in AD. Unlike neurons, the significance of exosomes derived from astrocytes remains unclear. In this study, we evaluated the significance of exosomes derived from U18666A-induced cholesterol-accumulated astrocytes in the development of AD pathology. Our results show that cholesterol accumulation decreases exosome secretion, whereas lowering cholesterol increases exosome secretion, from cultured astrocytes. Interestingly, exosomes secreted from U18666A-treated astrocytes contain higher levels of APP, APP-C-terminal fragments, soluble APP, APP secretases and Aβ1-40 than exosomes secreted from control astrocytes. Furthermore, we show that exosomes derived from U18666A-treated astrocytes can lead to neurodegeneration, which is attenuated by decreasing Aβ production or by neutralizing exosomal Aβ peptide with an anti-Aβ antibody. These results, taken together, suggest that exosomes derived from cholesterol-accumulated astrocytes can play an important role in trafficking APP/Aβ peptides and influencing neuronal viability in the affected regions of the AD brain.

Prion diseases are fatal, transmissible neurodegenerative disorders whose pathogenesis is driven by the misfolding, self-templating and cell-to-cell spread of the prion protein. Other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and Huntington’s disease, share some of these prion-like features, with different aggregation-prone proteins. Consequently, researchers have begun to apply prion-specific techniques, like the prion organotypic slice culture assay (POSCA), to these disorders. In this review we explore the ways in which the prion phenomenon has been used in organotypic cultures to study neurodegenerative diseases from the perspective of protein aggregation and spreading, strain propagation, the role of glia in pathogenesis, and efficacy of drug treatments. We also present an overview of the advantages and disadvantages of this culture system compared to in vivo and in vitro models and provide suggestions for new directions.

Abstract Introduction Stroke is a common cause of patient morbidity and mortality. Communicating its prognosis to family members, along with the establishment of goals of care, is a frequent task for neurologists and neurology residents. Given this, we felt it was an appropriate scenario from which to assess neurology resident medical expert and communication skills in an objective structured clinical examination (OSCE) setting. The OSCE station topic was created directly from objectives of training for neurology residents specified by the Royal College of Physicians and Surgeons of Canada. Methods This is a standardized case with an actor portraying a patient's relative. Residents are to give bad news of poor neurologic prognosis and establish goals of care for the patient. The case scenario, instructions to the examinee, and examiner marking sheet are included. Results The OSCE station was implemented with pediatric and adult senior neurology residents (PGY3-PGY5) from three universities. Of the 25 residents who experienced this case, 96% passed the station. Resident scores ranged from 60%-100%, with a mean of 86%. Discussion We consider the significance of the work to be the interpretation of a clinical scenario of poor neurologic prognosis of severe stroke and the communication of poor prognosis to a standardized family member with resultant establishment of code status, a task that is performed several times per week on the acute stroke service. This OSCE station is appropriate for neurology residents who participate in stroke care and will become neurologists who must communicate bad news on a daily basis.

Large-scale strandings of Sargassum spp. seaweeds occur annually on the beaches of the Caribbean islands and cause major environmental, health, and economic problems. In order to support an approach of valorisation of algae, an exhaustive characterisation of the composition of these seaweeds has been performed by analysing the contents in alginates, structural carbohydrates (fucans and glucans), minerals, proteins, lipids, mannitol, polyphenols, and heavy metals. Nine batches were collected at different harvesting sites over the years 2021 and 2022, to estimate the spatial and temporal variation in Sargassum composition. A batch of floats was harvested and analysed to estimate the differences in composition between floats and whole algae. Samples collected during the same year (floats or entire plant, freshly collected or stored) showed no significant differences in composition. However, slight differences were observed between batches collected in the two years. Some samples showed significant amounts of heavy metals, especially arsenic. A detailed structural carbohydrates analysis was carried out and discussed with literature data. As the nitrogen content of algae is an interesting parameter for food or agronomic uses, protein analysis enabled us to calculate a new nitrogen–protein conversion factor, specific to these algae species.

Wood-based panels are ubiquitous in our daily lives, both as building materials and as furnishing materials. Numerous studies have revealed that these materials emit volatile organic compounds, such as formaldehyde, into indoor air, which can be harmful to human health. These volatile organic compounds come both from the wood itself, more specifically cellulose, hemicellulose, and lignin, and from the resins used to bind the wood fibers or particles together. Today, new panels bonded with bio-based adhesives and binderless panels are emerging. The aim of this article is to highlight the importance of measuring VOC emissions from binderless wood-based panels, and more specifically, to identify the VOCs, originating from the wood and thermal transformation processes, likely to be emitted during the production of such panels, as well as how to sample them and measure their emissions. This work provides a useful approach to identifying and quantifying VOC emissions from these new materials. These methodologies should be applied more widely to gain knowledge about VOCs, which are relevant indicators for the development of environmentally friendly materials.

Since 2010, huge quantities of Sargassum spp. algae have been proliferating in the Atlantic Ocean and stranding on Caribbean beaches, causing major economic, environmental, and health problems. In this study, an innovative high-density binderless particleboard was developed using uniaxial thermo-compression coupled with a cooling system. The raw material consisted of ground Sargassum seaweeds pre-treated by twin-screw extrusion with water to remove sea salt. The raw material and the particleboards were produced by using various analytical techniques such as Dynamic Vapor Sorption (DVS), Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA), or Thermogravimetric Analysis (TGA). The experimental conditions for thermo-compression (temperature, pressure, time) were evaluated. The best thermo-compression conditions tested were 200 °C, 40 MPa pressure for 7.5 min. This resulted in a particleboard with high density (up to 1.63 ± 0.02 g/cm3) and high flexural strength/modulus (up to 32.3 ± 1.8 MPa/6.8 ± 0.2 GPa, respectively), but a low water contact angle of 38.9° ± 3.5°. Thermal analyses revealed the effect of alginates on the mechanical properties of particleboards. This work opens the door to a new way of adding value to Sargassum seaweed, using the whole algae with minimal pre-treatment.

Over the last decade, there have been renewed efforts into wine grape breeding within the research community. Quick characterisation by phenotyping of quality traits, including aroma composition, remains challenging. Selected Ion Flow Tube Mass Spectrometry (SIFT-MS), a high throughput soft ionisation technology first available in 2008, could be particularly useful for this purpose. In light of this, this technical article summarises recent results obtained with SIFT-MS.

Wine grape breeding for fungal resistance has been very dynamic worldwide over the last decade. The quick phenotyping of genotype quality traits, including aroma composition, remains challenging. Selected ion flow tube mass spectrometry (SIFT-MS) could be particularly valuable for this usage. Due to the high number of seedlings to phenotype and the low availability of berries, the sampling strategy can hardly rely on time-consuming destructive methods such as the measurement of classical maturity parameters (i.e., sugar concentration). To investigate the impact of the sampling time on the SIFT-MS fingerprint, berries from Vitis vinifera L. Syrah were collected in 2020, a season characterised by warm climatic conditions, at seven times during maturation and analysed by SIFT-MS using O2+ as reagent ion. This fingerprint has proved to be stable from 28 days after mid-veraison. This finding greatly simplifies the sampling procedure for future berry phenotyping, which can only rely on non-destructive data (lapse of time after mid-veraison date). For most m/z, a decrease in abundance was observed during the maturation, which could be the consequence of volatile emission or an increase in non-detectable bound compounds. Further studies would be necessary to assess the full grape aroma potential, to better understand the mechanisms involved, and to evaluate our approach over more than one season.

Abstract Background Hibernation is a physiological and behavioural adaptation that permits survival during periods of reduced food availability and extreme environmental temperatures. This is achieved through cycles of metabolic depression and reduced body temperature (torpor) and rewarming (arousal). Rewarming from torpor is achieved through the activation of brown adipose tissue (BAT) associated with a rapid increase in ventilation frequency. Here, we studied the rate of rewarming in the European hamster (Cricetus cricetus) by measuring both BAT temperature, core body temperature and ventilation frequency. Results Temperature was monitored in parallel in the BAT (IPTT tags) and peritoneal cavity (iButtons) during hibernation torpor-arousal cycling. We found that increases in brown fat temperature preceded core body temperature rises by approximately 48 min, with a maximum re-warming rate of 20.9℃*h-1. Re-warming was accompanied by a significant increase in ventilation frequency. The rate of rewarming was slowed by the presence of a spontaneous thoracic mass in one of our animals. Core body temperature re-warming was reduced by 6.2℃*h-1 and BAT rewarming by 12℃*h-1. Ventilation frequency was increased by 77% during re-warming in the affected animal compared to a healthy animal. Inspection of the position and size of the mass indicated it was obstructing the lungs and heart. Conclusions We have used a minimally invasive method to monitor BAT temperature during arousal from hibernation illustrating BAT re-warming significantly precedes core body temperature re-warming, informing future study design on arousal from hibernation. We also showed compromised re-warming from hibernation in an animal with a mass obstructing the lungs and heart, likely leading to inefficient ventilation and circulation.

Like other biological functions, food intake and energy metabolism display daily rhythms controlled by the circadian timing system that comprises a main circadian clock and numerous secondary clocks in the brain and peripheral tissues. Each secondary circadian clock delivers local temporal cues based on intracellular transcriptional and translational feedback loops that are tightly interconnected to intracellular nutrient-sensing pathways. Genetic impairment of molecular clocks and alteration in the rhythmic synchronizing cues, such as ambient light at night or mistimed meals, lead to circadian disruption that, in turn, negatively impacts metabolic health. Not all circadian clocks are sensitive to the same synchronizing signals. The master clock in the suprachiasmatic nuclei of the hypothalamus is mostly synchronized by ambient light and, to a lesser extent, by behavioral cues coupled to arousal and exercise. Secondary clocks are generally phase-shifted by timed metabolic cues associated with feeding, exercise, and changes in temperature. Furthermore, both the master and secondary clocks are modulated by calorie restriction and high-fat feeding. Taking into account the regularity of daily meals, the duration of eating periods, chronotype, and sex, chrononutritional strategies may be useful for improving the robustness of daily rhythmicity and maintaining or even restoring the appropriate energy balance.

The Atlas pistachio fruits are an important source of food due to their high fat content and medicinal interest in arid lands. For a better use, it is necessary to understand the diversity and distribution of lipids in their fruit. The purpose of the present study is to determine oil content, fatty acid, and phytosterol composition using gas chromatography of three ecotypes in Algeria during two consecutive years. The seed oil contents ranged from 32 to 47.8% depending on both year and ecotype. Unsaturated fatty acids (FA) represent at least 71% of total FA. The fruit contains a considerable level of phytosterols. The highest level of oil content and unsaturated FA were observed in the fruit of Bechar regardless of the part of the fruit. The study indicated that oil quality of the Atlas pistachio seed varies according to genotype and environmental conditions, and the findings could help breeders for diversity and selection program management.

Volatile organic compounds are species of concern for indoor air quality. They are emitted from a wide range of indoor sources and in particular from construction materials. Industrialized wood-based panels made from various types of wood bonded with thermosetting adhesive resins have been shown to emit volatile organic compounds over months or even years mostly due to the petrochemical binders. Some studies have been conducted on binderless panels, but they mainly focused on the pressing parameters to be applied to optimize the panel characteristics. The aim of this research is to document the emissions from binderless panels and to access the volatile composition of wood processing through the molding of materials. For this purpose, binderless boards were manufactured from hardwoods, known to emit less than softwoods with different thermopressing temperatures and times. Emissions were studied by placing the materials in microchambers. Volatile organic compounds were then sampled and analyzed by various chromatographic methods. On the other hand, materials were pyrolyzed and then analyzed by gas chromatography and mass spectrometry. The implemented protocols proved suitable for the determination of more than 40 organic compounds, among which are aldehydes, aromatics, furans and derivatives, and carboxylic acids.

Reflective functioning (RF), meaning the capacity to interpret mental states (intentions, emotions, thoughts, desires, and beliefs) underlying one’s own and others’ behaviors, may help understand the dysfunctional self-regulation associated with anxiety disorders. However, research on anxiety and RF in clinical samples is scarce. This study aimed to assess whether mothers’ and youths’ RF was associated with youths’ (a) anxiety disorders and symptoms and (b) internalizing symptoms. Another goal was to explore whether RF predicted anxiety and internalizing symptoms beyond the more commonly established effect of attachment. Canadian children and adolescents aged between 8 and 16years, and their mothers were recruited in an outpatient psychiatric clinic (clinical group with a diagnosed anxiety disorder, n=30, mean age=11.5±2.8years) and in the general population (non-clinical group, n=23, mean age=11.5±2.1years). The Child Attachment Interview was used to assess youths’ attachment along with three dimensions of RF (global, regarding self, regarding others). Mothers’ attachment and RF were assessed with the Adult Attachment Interview. Children’s and adolescents’ anxiety and internalizing symptoms were measured with the Behavior Assessment Scale for Children, second version. The clinical and non-clinical groups did not differ in mothers’ or youths’ RF. However, in the overall sample, youths’ RF regarding themselves and maternal attachment preoccupation were associated with internalizing symptoms. Sequential regression analyses revealed that higher RF regarding self predicted a higher level of self-reported internalizing symptoms, beyond the effect of maternal attachment (β=0.43, p

Female reproductive success relies on proper integration of circadian- and ovarian- signals to the hypothalamic-pituitary-gonadal axis in order to synchronize the preovulatory LH surge at the end of the ovarian follicular stage with the onset of the main active period. In this study, we used a combination of neuroanatomical and electrophysiological approaches to assess whether the hypothalamic neurons expressing Arg-Phe amiderelated peptide (RFRP-3), a gonadotropin inhibitory peptide, exhibit daily and estrous stage dependent variations in female mice. Furthermore, we investigated whether arginine vasopressin (AVP), a circadian peptide produced by the suprachiamatic nucleus regulates RFRP-3 neurons. The number of c-Fos–positive RFRP-3 immunoreactive neurons is significantly reduced at the day-to-night transition with no difference between diestrus and proestrus. Contrastingly, RFRP neuron firing rate is higher in proestrus as compared to diestrus, independently of the time of the day. AVP immunoreactive fibers contact RFRP neurons with the highest density observed during the late afternoon of diestrus and proestrus. Application of AVP increases RFRP neurons firing in the afternoon (ZT6-10) of diestrus, but not at the same time point of proestrus, indicating that AVP signaling on RFRP neurons may depend on circulating ovarian steroids. Together, these studies show that RFRP neurons integrate both daily and estrogenic signals, which downstream may help to properly time the preovulatory LH surge.

The PEAK family pseudokinases are essential components of tyrosine kinase (TK) pathways that regulate cell growth and adhesion; however, their role in human cancer remains unclear. Here, we report an oncogenic activity of the pseudokinase PEAK2 in colorectal cancer (CRC). Notably, high PRAG1 expression, which encodes PEAK2, was associated with a bad prognosis in CRC patients. Functionally, PEAK2 depletion reduced CRC cell growth and invasion in vitro, while its overexpression increased these transforming effects. PEAK2 depletion also reduced CRC development in nude mice. Mechanistically, PEAK2 expression induced cellular protein tyrosine phosphorylation, despite its catalytic inactivity. Phosphoproteomic analysis identified regulators of cell adhesion and F-actin dynamics as PEAK2 targets. Additionally, PEAK2 was identified as a novel ABL TK activator. In line with this, PEAK2 expression localized at focal adhesions of CRC cells and induced ABL-dependent formation of actin-rich plasma membrane protrusions filopodia that function to drive cell invasion. Interestingly, all these PEAK2 transforming activities were regulated by its main phosphorylation site, Tyr413, which implicates the SRC oncogene. Thus, our results uncover a protumoural function of PEAK2 in CRC and suggest that its deregulation affects adhesive properties of CRC cells to enable cancer progression.

Summary: The central circadian pacemaker, the suprachiasmatic nucleus (SCN), encodes day length information by mechanisms that are not well understood. Here, we report that genetic ablation of miR-132/212 alters entrainment to different day lengths and non-24 hr day-night cycles, as well as photoperiodic regulation of Period2 expression in the SCN. SCN neurons from miR-132/212-deficient mice have significantly reduced dendritic spine density, along with altered methyl CpG-binding protein (MeCP2) rhythms. In Syrian hamsters, a model seasonal rodent, day length regulates spine density on SCN neurons in a melatonin-independent manner, as well as expression of miR-132, miR-212, and their direct target, MeCP2. Genetic disruption of Mecp2 fully restores the level of dendritic spines of miR-132/212-deficient SCN neurons. Our results reveal that, by regulating the dendritic structure of SCN neurons through a MeCP2-dependent mechanism, miR-132/212 affects the capacity of the SCN to encode seasonal time. : Seasonal adaptation is believed to require plasticity in the SCN, although the mechanisms are unclear. Mendoza-Viveros et al. report that miR-132/212 modulates dendritic protrusion density and photoperiodic adaptation in mice and hamsters, by regulating the expression of MeCP2, and downstream BDNF and mTOR signaling. Keywords: circadian rhythms, seasonal timekeeping, suprachiasmatic nucleus, microRNA, miR-132/212, entrainment, MeCP2, dendritic morphology, structural plasticity, spinogenesis

Adaptation of reproductive activity to environmental changes is essential for breeding success and offspring survival. In mammals, the reproductive system displays regular cycles of activation and inactivation which are synchronized with seasonal and/or daily rhythms in environmental factors, notably light intensity and duration. Thus, most species adapt their breeding activity along the year to ensure that birth and weaning of the offspring occur at a time when resources are optimal. Additionally, female reproductive activity is highest at the beginning of the active phase during the period of full oocyte maturation, in order to improve breeding success. In reproductive physiology, it is therefore fundamental to delineate how geophysical signals are integrated in the hypothalamo-pituitary-gonadal axis, notably by the neurons expressing gonadotropin releasing hormone (GnRH). Several neurochemicals have been reported to regulate GnRH neuronal activity, but recently two hypothalamic neuropeptides belonging to the superfamily of (Arg)(Phe)-amide peptides, RFRP-3 and kisspeptin, have emerged as critical for the integration of environmental cues within the reproductive axis. The goal of this review is to survey the current understanding of the role played by RFRP-3 in the temporal regulation of reproduction, and consider how its effect might combine with that of kisspeptin to improve the synchronization of reproduction to environmental challenges.

ERBB2 overexpression in human breast cancer leads to invasion and metastasis. Here the authors report that ERBB2 induces indirect phosphorylation of TOM1L1 that promotes trafficking of the metalloprotease MT1-MMP to invadopodia, which leads to tumour cell invasion.

Most container–content interaction studies are carried out through migration tests on end products or simulants involving generally toxic solvents. This study was conducted with the aim of identifying potential leachables from materials used in cosmetic plastic packaging by using two approaches based on solvent-free extraction, i.e., solid-phase microextraction sampling and pyrolyzer/thermal desorption coupled with gas chromatography mass spectrometry. Volatile and semi-volatile intentionally and non-intentionally added substances were detected in seven packaging samples made of polypropylene, polyethylene, and styrene-acrylonitrile copolymer. Thirty-five compounds related to the polymers industry or packaging industry were identified, among them phthalates, alkanes, styrene, and cyanide derivates including degradation products, impurities, additives, plasticizers, and monomers. All except eight belong to the Cramer class I. These thermodesorption techniques are complementary to those used for migration tests.

Cerebrospinal fluid (CSF) is a fluidic part of the brain’s microenvironment that isolates the brain from the rest of the body. CSF dilutes metabolites from neuronal activities and removes them from the brain. Its production and resorption are regulated dynamically and are central to maintaining brain homeostasis. We discovered that the major CSF source, the choroid plexus (CP), harbors the brain’s strongest circadian clock. Here, we consider some implications of the CP circadian clock for metabolite clearance in the brain. If the circadian clock contributes to timed production of the CSF, its synchronization with sleep timing can maximize clearance efficiency and help prevent neurodegenerative diseases such as Alzheimer’s disease.

Abstract The clinical management of metastatic colorectal cancer (mCRC) faces major challenges. Here, we show that nilotinib, a clinically approved drug for chronic myeloid leukaemia, strongly inhibits human CRC cell invasion in vitro and reduces their metastatic potential in intrasplenic tumour mouse models. Nilotinib acts by inhibiting the kinase activity of DDR1, a receptor tyrosine kinase for collagens, which we identified as a RAS‐independent inducer of CRC metastasis. Using quantitative phosphoproteomics, we identified BCR as a new DDR1 substrate and demonstrated that nilotinib prevents DDR1‐mediated BCR phosphorylation on Tyr177, which is important for maintaining β‐catenin transcriptional activity necessary for tumour cell invasion. DDR1 kinase inhibition also reduced the invasion of patient‐derived metastatic and circulating CRC cell lines. Collectively, our results indicate that the targeting DDR1 kinase activity with nilotinib may be beneficial for patients with mCRC.

Melatonin is a neurohormone produced in both animals and plants. It binds at least three G-protein-coupled receptors: MT1 and MT2, and Mel1cGPR. Mammalian GPR50 evolved from the reptilian/avian Mel1c and lost its capacity to bind melatonin in all the therian mammal species that have been tested. In order to determine if binding is lost in the oldest surviving mammalian lineage of monotremes we investigated whether the melatonin receptor has the ability to bind melatonin in the platypus (Ornithorhynchus anatinus), and evaluated its pharmacological profile. Sequence and phylogenetic analysis showed that platypus has in fact retained the ancestral Mel1c and has the capacity to bind melatonin similar to other mammalian melatonin receptors (MT1 and MT2), with an affinity in the 1 nM range. We also investigated the binding of a set of melatoninergic ligands used previously to characterize the molecular pharmacology of the melatonin receptors from sheep, rats, mice, and humans and found that the general profiles of these compounds make Mel1c resemble human MT1 more than MT2. This work shows that the loss of GPR50 binding evolved after the divergence of monotremes less than 190MYA in therian mammals.

Female mammals are classified into spontaneous and induced ovulators based on the mechanism eliciting ovulation. Ovulation in spontaneous species (e.g., human, sheep, cattle, horse, pigs, and most rodents) occurs at regular intervals and depends upon the circulating estradiol. However, in induced ovulators (e.g., rabbits, ferrets, cats, and camelids), ovulation is associated with coitus. In the later, various factors have been proposed to trigger ovulation, including auditory, visual, olfactory, and mechanic stimuli. However, other studies have identified a biochemical component in the semen of induced ovulators responsible for the induction of ovulation and named accordingly ovulation-inducing factor (OIF). In camelids, intramuscular or intrauterine administration of seminal plasma (SP) was shown to induce the preovulatory luteinizing hormone (LH) surge followed by ovulation and subsequent formation of corpus luteum. Recently, this OIF has been identified from SP as a neurotrophin, the β subunit of nerve growth factor (β-NGF). β-NGF is well known as promoting neuron survival and growth, but in this case, it appears to induce ovulation through an endocrine mode of action. Indeed, β-NGF may be absorbed through the endometrium to be conveyed, via the blood stream, to the central structures regulating the LH preovulatory surge. In this review, we provide a summary of the most relevant results obtained in the field, and we propose a working hypothesis for the central action of β-NGF based on our recent demonstration of the presence of neurons expressing kisspeptin, a potent stimulator of GnRH/LH, in the camel hypothalamus.

Pistacia atlantica, which belongs to the Anacardiaceae family, is an important species for rural people in arid and semi-arid areas. The fruit, rich in oil, is used in traditional medicine for the treatment of various diseases. The oil extracted from this species growing in a northern area of Algeria and its fatty acid composition were previously studied. However, the largest areas where this species is present (traditional cultivation) is located in southern Algeria. Moreover, studies on oil fatty acid composition and essential oil were always conducted separately. This study was performed in order to assess the fatty acid and volatile organic compound composition of P. atlantica vegetable oil. The seeds were collected randomly from Djelfa (300 km South of Algiers, Algeria). Oil content and fatty acid composition were determined by Soxhlet extraction. The seeds contained high concentrations of oil (32−67%). The major fatty acids were oleic (39−49%), linoleic (23.6−31%), and palmitic (21.3−26.6%) acids. The ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA) indicated that the content of unsaturated fatty acids was approximately three times higher than that of SFA. This ratio is widely used in epidemiological studies and research on cardiovascular diseases, diabetes, and metabolic syndrome. The ratios of ω-acids, i.e., ω-9/ω-6 and ω-6/ω-3, were 1.3−2 and 18.5−38.3, respectively. Crushed seeds were analyzed by headspace solid-phase microextraction (SPME) coupled with gas chromatography−mass spectrometry. More than 40 compounds were identified, mainly monoterpenes (C10H16), such as α-terpinene and terpinolene, but also sesquiterpenes (C15H24) at lower levels. The value of this species as a source of healthy oil rich in ω-3 acid and its effects on cardiovascular disease risk are discussed.

For many years, it was of interest to identify the sequences encoding the two melatonin receptors (MT1 and MT2) from various species. After publishing the basic molecular characterization of the human, rat, mouse, sheep, and platypus MT1, MT2, or Mel1c receptors, we began cloning the genes from other animals, such as birds, bats, and vipers. The goal was to advance the receptor crystallization, which could greatly contribute the understanding of the sequence/stability relationship. European hamster MT1 receptor was cloned for the first time from this gender, was expressed in stable form in cells, and its binding characterized with a sample of 19 melatonin ligands. Siberian hamster (Phodopus sungorus) expresses a non-functional MT2. We observed that unlike this hamster, the European hamster (Cricetus cricetus) does not have a stop codon in the MT2 sequence. Thus, we undertook the tedious task of cloning the MT2 receptor. We partially succeeded, sequencing the complete exon 2 and a fragment of exon 1 (from putative amino acids 12 to 38 and 77 to 323), after several years of efforts. In order to show that the protein parts we cloned were capable to sustain some binding capacities, we designed a chimeric MT2 receptor using a consensus sequence to replace the unknown amino acids, based on other small rodent MT2 sequences. This chimeric construct could bind melatonin in the nanomolar range. This work is meant to be the basis for attempts from other laboratories of the community to determine the complete natural sequence of the European hamster MT2 receptor. The present work is the first to show that, among the hamsters, if the Siberian is a natural knockout for MT2, the European one is not.

The nematode Caenorhabditis elegans provides a unique opportunity to interrogate the neural basis of behavior at single neuron resolution. In C. elegans, neural circuits that control behaviors can be formulated based on its complete neural connection map, and easily assessed by applying advanced genetic tools that allow for modulation in the activity of specific neurons. Importantly, C. elegans exhibits several elaborate behaviors that can be empirically quantified and analyzed, thus providing a means to assess the contribution of specific neural circuits to behavioral output. Particularly, locomotory behavior can be recorded and analyzed with computational and mathematical tools. Here, we describe a robust single worm-tracking system, which is based on the open-source Python programming language, and an analysis system, which implements path-related algorithms. Our tracking system was designed to accommodate worms that explore a large area with frequent turns and reversals at high speeds. As a proof of principle, we used our tracker to record the movements of wild-type animals that were freshly removed from abundant bacterial food, and determined how wild-type animals change locomotory behavior over a long period of time. Consistent with previous findings, we observed that wild-type animals show a transition from area-restricted local search to global search over time. Intriguingly, we found that wild-type animals initially exhibit short, random movements interrupted by infrequent long trajectories. This movement pattern often coincides with local/global search behavior, and visually resembles Lévy flight search, a search behavior conserved across species. Our mathematical analysis showed that while most of the animals exhibited Brownian walks, approximately 20% of the animals exhibited Lévy flights, indicating that C. elegans can use Lévy flights for efficient food search. In summary, our tracker and analysis software will help analyze the neural basis of the alteration and transition of C. elegans locomotory behavior in a food-deprived condition.

When food availability is restricted, animals adjust their behavior according to the timing of food access. Most rodents, such as rats and mice, and a wide number of other animals express before timed food access a bout of activity, defined as food-anticipatory activity (FAA). One notable exception amongst rodents is the Syrian hamster, a photoperiodic species that is not prone to express FAA. The present study was designed to understand the reasons for the low FAA in that species. First, we used both wheel-running activity and general cage activity to assess locomotor behavior. Second, the possible effects of photoperiod was tested by challenging hamsters with restricted feeding under long (LP) or short (SP) photoperiods. Third, because daytime light may inhibit voluntary activity, hamsters were also exposed to successive steps of full and skeleton photoperiods (two 1-h light pulses simulating dawn and dusk). When hamsters were exposed to skeleton photoperiods, not full photoperiod, they expressed FAA in the wheel independently of daylength, indicating that FAA in the wheel is masked by daytime light under full photoperiods. During FAA under skeleton photoperiods, c-Fos expression was increased in the arcuate nuclei independently of the photoperiod, but differentially increased in the ventromedial and dorsomedial hypothalamic nuclei according to the photoperiod. FAA in general activity was hardly modulated by daytime light, but was reduced under SP. Together, these findings show that food-restricted Syrian hamsters are not prone to display FAA under common laboratory conditions, because of the presence of light during daytime that suppresses FAA expression in the wheel.

Understanding how pollinator behavior may influence pollen transmission across floral types is a major challenge, as pollinator decision depends on a complex range of environmental cues and prior experience. Here we report an experiment using the plant Antirrhinum majus and the bumblebee Bombus terrestris to investigate how prior learning experience may affect pollinator preferences between floral types when these are presented together. We trained naive bumblebees to forage freely on flowering individuals of either A. majus pseudomajus (magenta flowers) or A. majus striatum (yellow flowers) in a flight cage. We then used a Y-maze device to expose trained bumblebees to a dual choice between the floral types. We tested the influence of training on their choice, depending on the type of plant signals available (visual signals, olfactory signals, or both). Bumblebees had no innate preference for either subspecies. Bumblebees trained on the yellow-flowered subspecies later preferred the yellow type, even when only visual or only olfactory signals were available, and their preference was not reinforced when both signal types were available. In contrast, bumblebees trained on the magenta-flowered subspecies showed no further preference between floral types and took slightly more time to make their choice. Since pollinator constancy has been observed in wild populations of A. majus with mixed floral types, we suggest that such constancy likely relies on short-term memory rather than acquired preference through long-term memory induced by prior learning.

The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN) breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity in vitro. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of ABL expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.