The Role of Cholinergic Midbrain Neurons in Startle and Prepulse Inhibition

One of the two major cholinergic centers of the mammalian brain is located in the midbrain, i.e., the pedunculopontine tegmentum (PPTg) and the adjacent laterodorsal tegmentum. These cholinergic neurons have been shown to be important for e.g., arousal, reward associations, and sleep. They also have been suggested to mediate sensorimotor gating, measured as prepulse inhibition of startle (PPI). PPI disruptions are a hallmark of schizophrenia and are observed in various other psychiatric disorders, where they are associated with, and often predictive of, other cognitive symptoms. PPI has been proposed to be mediated by a short midbrain circuitry including inhibitory cholinergic projections from PPTg to the startle pathway. Although the data indicating the involvement of the PPTg is very robust, some more recent evidence challenges that there is a cholinergic contribution to PPI. We here use transient optogenetic activation of specifically the cholinergic PPTg neurons in male and female rats to address their role in startle modulation in general, and in PPI specifically. Although we could confirm the crucial role of PPTg cholinergic neurons in associative reward learning, validating our experimental approach, we found that activation of cholinergic PPTg neurons did not inhibit startle responses. In contrast, activation of cholinergic PPTg neurons enhanced startle, which is in accordance with their general role in arousal and indicate a potential involvement in sensitization of startle. We conclude that noncholinergic PPTg neurons mediate PPI in contrast to the longstanding hypothetical view that PPI is mediated by cholinergic PPTg neurons

Use of a Novel Polymer-Coated Steel as an Alternative to Traditional Can Manufacturing in the Food Industry

[EN] Metal containers (both food and beverage cans) are made from huge steel or aluminum coils that are transformed into two- or three-piece products. During the manufacturing process, the metal is sprayed on both sides and the aerosol acts as insulation, but unfortunately produces volatile organic compounds (VOCs). The present work presents a different way to manufacture these containers using a novel prelaminated two-layer polymer steel. It was experimentally possible to verify that the material survives all the involved manufacturing processes. Thus tests were carried out in an ironing simulator to measure roughness, friction coefficient and surface quality. In addition, two theoretical ironing models were developed: upper bound model and artificial neural network. These models are useful for packaging designers and manufacturers.Sellés, M.; Schmid, SR.; Sanchez-Caballero, S.; Ramezani, M.; Pérez Bernabeu, E. (2021). Use of a Novel Polymer-Coated Steel as an Alternative to Traditional Can Manufacturing in the Food Industry. Polymers. 13(2):1-15. https://doi.org/10.3390/polym13020222S11513

An Economical and Environmental Alternative to Traditional Can Manufacturing Using a New Pre-Laminated Steel

[EN] Metal containers are the most commonly used packaging worldwide in both the food and beverage industry. Some manufacturing processes in the canning industry include multi-step transformations that take large aluminum or steel coils and make them into two or three-piece cans. During this process, the containers are sprayed to obtain a better surface for the contents; however, this spray produces volatile organic compounds (VOC). This paper presents a new and environmentally friendly can manufacturing method, which uses a novel pre-laminated two-layer polymer steel. As experimentally proven, this innovative polymer-coated steel successfully withstands every manufacturing requirement. The specimens were tested in an ironing simulator, measuring roughness and friction coefficients. The development of an upper bound ironing model, along with a supporting neural network, allows an insight into the design of new materials for can manufacturing.Sellés Cantó, MÁ.; Schmid, SR.; Sanchez-Caballero, S.; Ramezani, M.; Pérez Bernabeu, E. (2020). An Economical and Environmental Alternative to Traditional Can Manufacturing Using a New Pre-Laminated Steel. Materials Proceedings. 2(21):1-10. https://doi.org/10.3390/CIWC2020-06841S11022

Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State and Associated Molecular Adaptations in the Prefrontal Cortex.

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. Furthermore, we observed profound alterations in several prefrontal cortical molecular pathways consistent with sub-cortical DAergic dysregulation. Our findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to THC in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology

Digital multiplex ligation assay for highly multiplexed screening of β-lactamase-encoding genes in bacterial isolates

Increasing incidence of antibiotic resistance in clinical and environmental settings calls for increased scalability in their surveillance. Current screening technologies are limited by the number of samples and genes that can easily be screened. We demonstrate here digital multiplex ligation assay (dMLA) as a low-cost targeted genomic detection workflow capable of highly-parallel screening of bacterial isolates for multiple target gene regions simultaneously. Here, dMLA is used for simultaneous detection of 1187 β-lactamase-encoding genes, including extended spectrum β-lactamase (ESBL) genes, in 74 bacterial isolates. We demonstrate dMLA as a light-weight and cost-efficient workflow which provides a highly scalable tool for antimicrobial resistance surveillance and is also adaptable to genetic screening applications beyond antibiotic resistance

Cannabidiol counteracts amphetamine-induced neuronal and behavioral sensitization of the mesolimbic dopamine pathway through a novel mTOR/p70S6 kinase signaling pathway

Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that blockDAreceptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes. Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses. However, the neuronal and molecular mechanisms through which CBD may exert these effects are entirely unknown. We used amphetamine (AMPH)-induced sensitization and sensorimotor gating in rats, two preclinical procedures relevant to schizophrenia-related psychopathology, combined with in vivo single-unit neuronal electrophysiology recordings in the ventral tegmental area, and molecular analyses to characterize the actions ofCBDdirectly in the nucleus accumbens shell (NASh), a brain region that is the current target of most effective antipsychotics. We demonstrate that Intra-NASh CBD attenuates AMPH-induced sensitization, both in terms of DAergic neuronal activity measured in the ventral tegmental area and psychotomimetic behavioral analyses. We further report that CBD controls downstream phosphorylation of the mTOR/p70S6 kinase signaling pathways directly within the NASh. Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology

L-theanine prevents long-term affective and cognitive side effects of adolescent Δ-9-tetrahydrocannabinol exposure and blocks associated molecular and neuronal abnormalities in the mesocorticolimbic circuitry

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. L-Theanine is an amino acid analog of L-glutamate and L-glutamine derived from various plant sources, including green tea leaves. L-Theanine has previously been shown to modulate levels of GABA, DA, and glutamate in various neural regions and to possess neuroprotective properties. Using a preclinical model of adolescent THC exposure in male rats, we report that L-theanine pretreatment before adolescent THC exposure is capable of preventing long-term, THC-induced dysregulation of both PFC and VTA DAergic activity states, a neuroprotective effect that persists into adulthood. In addition, pretreatment with L-theanine blocked THC-induced downregulation of local GSK-3 (glycogen synthase kinase 3) and Akt signaling pathways directly in the PFC, two biomarkers previously associated with cannabis-related psychiatric risk and subcortical DAergic dysregulation. Finally, L-theanine powerfully blocked the development of both affective and cognitive abnormalities commonly associated with adolescent THC exposure, further demonstrating functional and long-term neuroprotective effects of L-theanine in the mesocorticolimbic system

Labor-associated gene expression in the human uterine fundus, lower segment, and cervix

Background Preterm labor, failure to progress, and postpartum hemorrhage are the common causes of maternal and neonatal mortality or morbidity. All result from defects in the complex mechanisms controlling labor, which coordinate changes in the uterine fundus, lower segment, and cervix. We aimed to assess labor-associated gene expression profiles in these functionally distinct areas of the human uterus by using microarrays. Methods and Findings Samples of uterine fundus, lower segment, and cervix were obtained from patients at term (mean +/- 6 SD = 39.1 +/- 0.5 wk) prior to the onset of labor (n = 6), or in active phase of labor with spontaneous onset (n = 7). Expression of 12,626 genes was evaluated using microarrays ( Human Genome U95A; Affymetrix) and compared between labor and non-labor samples. Genes with the largest labor-associated change and the lowest variability in expression are likely to be fundamental for parturition, so gene expression was ranked accordingly. From 500 genes with the highest rank we identified genes with similar expression profiles using two independent clustering techniques. Sets of genes with a probability of chance grouping by both techniques less than 0.01 represented 71.2%, 81.8%, and 79.8% of the 500 genes in the fundus, lower segment, and cervix, respectively. We identified 14, 14, and 12 those sets of genes in the fundus, lower segment, and cervix, respectively. This enabled networks of coregulated and co-expressed genes to be discovered. Many genes within the same cluster shared similar functions or had functions pertinent to the process of labor. Conclusions Our results provide support for many of the established processes of parturition and also describe novel-to-labor genes not previously associated with this process. The elucidation of these mechanisms likely to be fundamental for controlling labor is an important prerequisite to the development of effective treatments for major obstetric problems - including prematurity, with its long-term consequences to the health of mother and offspring

The hand of Australopithecus sediba

Here we describe the functional morphology of the Australopithecus sediba hand, including the almost complete hand of the presumed female Malapa Hominin (MH) 2 skeleton and a single, juvenile metacarpal from the presumed male MH1 skeleton. Qualitative and quantitative comparisons with extant hominids and fossil hominins, ranging from Ardipithecus to early Homo sapiens, reveal that Au. sediba presents a unique suite of morphological features that have not been found in any other known hominin. Analyses of intrinsic hand proportions show that the MH2 hand has a thumb that is longer relative to its fingers than recent humans and any other known hominin. Furthermore, the morphology of the hamatometacarpal articulation suggests that the robust fifth metacarpal was positioned in a slightly more flexed and adducted posture than is typical of Neandertals and humans. Together, this morphology would have facilitated opposition of the thumb to the fingers and pad-to-pad precision gripping that is typical of later Homo. However, the remarkably gracile morphology of the first ray and the morphology of the lateral carpometacarpal region suggest limited force production by the thumb. The distinct scaphoid-lunatecapitate morphology in MH2 suggests a greater range of abduction at the radiocarpal joint and perhaps less central-axis loading of the radiocarpal and midcarpal joints than is interpreted for other fossil hominins, while the morphology of the hamatotriquetrum articulation suggests enhanced stability of the medial midcarpal joint in extended and/or adducted wrist postures. The MH2 proximal phalanges show moderate curvature and, unusually, both the proximal and intermediate phalanges have well-developed flexor sheath ridges that, in combination with a palmarly-projecting hamate hamulus, suggest powerful flexion and that some degree of arboreality may have been a functionally important part of the Au. sediba locomotor repertoire. Finally, the MH1 and MH2 third metacarpals differ remarkably in their size and degree of robusticity, but this variation fits comfortably within the sexual dimorphism documented in recent humans and other fossil hominins, and does not necessarily reflect differences in function or hand use. Overall, the morphology of the current Au. sediba hand bones suggests the capability for use of the hands both for powerful gripping during locomotion and precision manipulation that is required for tool-related behaviors, but likely with more limited force production by the thumb than is inferred in humans, Neandertals, and potentially Homo naledi

Teaching Hands-Only CPR in Schools: A Program Evaluation in San José, Costa Rica

Background: Hands-only bystander CPR increases survival from out-of-hospital cardiac arrest. Video-based CPR instruction in schools has been proposed as a means to mass-educate laypersons in Hands-only CPR™ (HOCPR), in developed as well as developing countries. Objectives: The purpose of this study is to determine whether a brief video- and mannequin-based instructional program, developed by the American Heart Association (AHA), is an effective strategy for teaching Costa Rican middle- and high-school age children to learn the steps of HOCPR. Methods: This study took place in four educational centers that spanned the entire socioeconomic spectrum within the Grand Metropolitan Area of Costa Rica. Three hundred and eight students from the sixth to eleventh grades participated. The intervention included exposure to the AHA “CPR Anytime” video and practice with CPR mannequins. Before and after the intervention, students took a four-question, multiple-choice quiz that measured their knowledge of the correct steps and proper techniques of HOCPR; a separate question assessed their level of comfort “doing CPR on someone with a cardiac arrest.” Pre- and post-intervention “percent correct” scores were compared and tested for statistical significance using paired t-tests or the McNemar test as appropriate. Improvement in knowledge and comfort levels were also compared across the different educational centers and compared with similar programs implemented in the United States. Results: The students’ overall scores (mean percent correct) on the multiple choice questions more than doubled after training (40.9% ± 1.4% before training vs. 92.5% ± 0.9% after training, p < 0.00001). Improvements were observed in each school, regardless of geographic location or socioeconomic status. Knowledge of the appropriate steps of HOCPR doubled after training (42.2% before training vs. 92.5% after training, p < 0.000001). Post-intervention, a majority (73%) of children reported comfort with performing CPR on an individual who had suffered a cardiac arrest. Conclusion: This study demonstrates the effectiveness of the AHA “CPR Anytime” program in teaching HOCPR to school-age children within the Grand Metropolitan Area of Costa Rica. Additional studies are needed to measure longer-term knowledge retention and students’ ability to perform CPR in simulated cardiac arrest settings