Mounting evidence implicates dysfunctional GABA
R-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). ...The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABA
R positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.
Patients with Parkinson's disease (PD) manifest nonmotor and motor symptoms. Autonomic cardiovascular dysregulation is a common nonmotor manifestation associated with increased morbimortality. ...Conventional clinical treatment alleviates motor signs but does not change disease progression and fails in handling nonmotor features. Nutrition is a key modifiable determinant of chronic disease. This study aimed to assess the effects of propolis on cardiological features, heart rate (HR) and heart rate variability (HRV) and on nigrostriatal dopaminergic damage, detected by tyrosine hydroxylase (TH) immunoreactivity, in the 6-hydroxydopamine (6-OHDA) rat model of PD. Male Wistar rats were injected bilaterally with 6-OHDA or saline into the striatum and were treated with propolis or water for 40 days. Autonomic function was assessed by time domain parameters (standard deviation of all normal-to-normal intervals (SDNN) and square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD)) of HRV calculated from electrocardiogram recordings. Reductions in HR (
= 1.47×10
), SDNN (
= 3.42×10
) and RMSSD (
= 8.2×10
) detected in parkinsonian rats were reverted by propolis. Propolis attenuated neuronal loss in the substantia nigra (
= 5.66×10
) and reduced striatal fiber degeneration (
= 7.4×10
) in 6-OHDA-injured rats, which also showed significant weight gain (
= 1.07×10
) in comparison to 6-OHDA-lesioned counterparts. Propolis confers cardioprotection and neuroprotection in the 6-OHDA rat model of PD.
Lentibulariaceae is the richest family of carnivorous plants spanning three genera including Pinguicula, Genlisea, and Utricularia. Utricularia is globally distributed, and, unlike Pinguicula and ...Genlisea, has both aquatic and terrestrial forms. In this study we present the analysis of the chloroplast (cp) genome of the terrestrial Utricularia reniformis. U. reniformis has a standard cp genome of 139,725bp, encoding a gene repertoire similar to essentially all photosynthetic organisms. However, an exclusive combination of losses and pseudogenization of the plastid NAD(P)H-dehydrogenase (ndh) gene complex were observed. Comparisons among aquatic and terrestrial forms of Pinguicula, Genlisea, and Utricularia indicate that, whereas the aquatic forms retained functional copies of the eleven ndh genes, these have been lost or truncated in terrestrial forms, suggesting that the ndh function may be dispensable in terrestrial Lentibulariaceae. Phylogenetic scenarios of the ndh gene loss and recovery among Pinguicula, Genlisea, and Utricularia to the ancestral Lentibulariaceae cladeare proposed. Interestingly, RNAseq analysis evidenced that U. reniformis cp genes are transcribed, including the truncated ndh genes, suggesting that these are not completely inactivated. In addition, potential novel RNA-editing sites were identified in at least six U. reniformis cp genes, while none were identified in the truncated ndh genes. Moreover, phylogenomic analyses support that Lentibulariaceae is monophyletic, belonging to the higher core Lamiales clade, corroborating the hypothesis that the first Utricularia lineage emerged in terrestrial habitats and then evolved to epiphytic and aquatic forms. Furthermore, several truncated cp genes were found interspersed with U. reniformis mitochondrial and nuclear genome scaffolds, indicating that as observed in other smaller plant genomes, such as Arabidopsis thaliana, and the related and carnivorous Genlisea nigrocaulis and G. hispidula, the endosymbiotic gene transfer may also shape the U. reniformis genome in a similar fashion. Overall the comparative analysis of the U. reniformis cp genome provides new insight into the ndh genes and cp genome evolution of carnivorous plants from Lentibulariaceae family.
Cross-frequency coupling (CFC) mechanisms play a central role in brain activity. Pathophysiological mechanisms leading to many brain disorders, such as Alzheimer's disease (AD), may produce unique ...patterns of brain activity detectable by electroencephalography (EEG). Identifying biomarkers for AD diagnosis is also an ambition among research teams working in Down syndrome (DS), given the increased susceptibility of people with DS to develop early-onset AD (DS-AD). Here, we review accumulating evidence that altered theta-gamma phase-amplitude coupling (PAC) may be one of the earliest EEG signatures of AD, and therefore may serve as an adjuvant tool for detecting cognitive decline in DS-AD. We suggest that this field of research could potentially provide clues to the biophysical mechanisms underlying cognitive dysfunction in DS-AD and generate opportunities for identifying EEG-based biomarkers with diagnostic and prognostic utility in DS-AD.
Hypercalcemic crisis is a rare endocrine emergency that occurs in a small percentage of patients with primary hyperparathyroidism. Although modern diagnostic capabilities allow timely diagnosis and ...intervention, hypercalcemic crisis still has a high potential for morbidity and mortality. We report an adult patient with a history of kidney stones who presented with heart palpitations, shortness of breath, fatigue, nausea, and 20-pound weight loss over 2 months. Workup revealed hypercalcemia, elevated parathyroid hormone (PTH), and a mediastinal mass on computed tomography angiography. This patient’s hypercalcemic crisis was treated with intravenous hydration using normal saline, zoledronate, and furosemide. After medical optimization, the patient underwent definitive treatment with surgical parathyroidectomy via a transcervical approach. At operation, a large parathyroid adenoma was removed from a posterior–superior mediastinal location dorsal to the recurrent laryngeal nerve with subsequent normalization of calcium and PTH. We discuss the timing of parathyroidectomy in cases of hypercalcemic crisis and the surgical approach to ectopic parathyroid glands in the mediastinum.
The carnivorous plants of the family Lentibulariaceae have attained recent attention not only because of their interesting lifestyle, but also because of their dynamic nuclear genome size. ...Lentibulariaceae genomes span an order of magnitude and include species with the smallest genomes in angiosperms, making them a powerful system to study the mechanisms of genome expansion and contraction. However, little is known about mitochondrial DNA (mtDNA) sequences of this family, and the evolutionary forces that shape this organellar genome. Here we report the sequencing and assembly of the complete mtDNA from the endemic terrestrial Brazilian species Utricularia reniformis. The 857,234bp master circle mitochondrial genome encodes 70 transcriptionaly active genes (42 protein-coding, 25 tRNAs and 3 rRNAs), covering up to 7% of the mtDNA. A ltrA-like protein related to splicing and mobility and a LAGLIDADG homing endonuclease have been identified in intronic regions, suggesting particular mechanisms of genome maintenance. RNA-seq analysis identified properties with putative diverse and important roles in genome regulation and evolution: 1) 672kbp (78%) of the mtDNA is covered by full-length reads; 2) most of the 243kbp intergenic regions exhibit transcripts; and 3) at least 69 novel RNA editing sites in the protein-coding genes. Additional genomic features are hypothetical ORFs (48%), chloroplast insertions, including truncated plastid genes that have been lost from the chloroplast DNA (5%), repeats (5%), relics of transposable elements mostly related to LTR retrotransposons (5%), and truncated mitovirus sequences (0.4%). Phylogenetic analysis based on 32 different Lamiales mitochondrial genomes corroborate that Lentibulariaceae is a monophyletic group. In summary, the U. reniformis mtDNA represents the eighth largest plant mtDNA described to date, shedding light on the genomic trends and evolutionary characteristics and phylogenetic history of the family Lentibulariaceae.
In the carnivorous plant family Lentibulariaceae, all three genome compartments (nuclear, chloroplast, and mitochondria) have some of the highest rates of nucleotide substitutions across angiosperms. ...While the genera Genlisea and Utricularia have the smallest known flowering plant nuclear genomes, the chloroplast genomes (cpDNA) are mostly structurally conserved except for deletion and/or pseudogenization of the NAD(P)H-dehydrogenase complex (ndh) genes known to be involved in stress conditions of low light or CO2 concentrations. In order to determine how the cpDNA are changing, and to better understand the evolutionary history within the Genlisea genus, we sequenced, assembled and analyzed complete cpDNA from six species (G. aurea, G. filiformis, G. pygmaea, G. repens, G. tuberosa and G. violacea) together with the publicly available G. margaretae cpDNA. In general, the cpDNA structure among the analyzed Genlisea species is highly similar. However, we found that the plastidial ndh genes underwent a progressive process of degradation similar to the other terrestrial Lentibulariaceae cpDNA analyzed to date, but in contrast to the aquatic species. Contrary to current thinking that the terrestrial environment is a more stressful environment and thus requiring the ndh genes, we provide evidence that in the Lentibulariaceae the terrestrial forms have progressive loss while the aquatic forms have the eleven plastidial ndh genes intact. Therefore, the Lentibulariaceae system provides an important opportunity to understand the evolutionary forces that govern the transition to an aquatic environment and may provide insight into how plants manage water stress at a genome scale.
Human-machine interfaces (HMIs) can be used to decode a user's motor intention to control an external device. People that suffer from motor disabilities, such as spinal cord injury, can benefit from ...the uses of these interfaces. While many solutions can be found in this direction, there is still room for improvement both from a decoding, hardware, and subject-motor learning perspective. Here we show, in a series of experiments with non-disabled participants, a novel decoding and training paradigm allowing naïve participants to use their auricular muscles (AM) to control two degrees of freedom with a virtual cursor. AMs are particularly interesting because they are vestigial muscles and are often preserved after neurological diseases. Our method relies on the use of surface electromyographic records and the use of contraction levels of both AMs to modulate the velocity and direction of a cursor in a two-dimensional paradigm. We used a locking mechanism to fix the current position of each axis separately to enable the user to stop the cursor at a certain location. A five-session training procedure (20-30 min per session) with a 2D center-out task was performed by five volunteers. All participants increased their success rate (Initial: 52.78 ± 5.56%; Final: 72.22 ± 6.67%; median ± median absolute deviation) and their trajectory performances throughout the training. We implemented a dual task with visual distractors to assess the mental challenge of controlling while executing another task; our results suggest that the participants could perform the task in cognitively demanding conditions (success rate of 66.67 ± 5.56%). Finally, using the Nasa Task Load Index questionnaire, we found that participants reported lower mental demand and effort in the last two sessions. To summarize, all subjects could learn to control the movement of a cursor with two degrees of freedom using their AM, with a low impact on the cognitive load. Our study is a first step in developing AM-based decoders for HMIs for people with motor disabilities, such as spinal cord injury.
Plants have evolved elaborate surveillance systems that allow them to perceive the attack by pests and pathogens and activate the appropriate defenses. Mechanical stimulation, such as mechanical ...wounding, represents one of the most reliable cues for the perception of potential herbivore aggressors. Here we demonstrate that mechanical wounding disturbs the growth versus defense balance in tomato, a physiological condition where growth reduction arises as a pleiotropic consequence of the activation of defense responses (or vice-versa). We observed that multiple lesions on tomato leaves impairs the formation of several growth-related traits, including shoot elongation, leaf expansion and time for flowering, while concomitantly activating the production of defense responses such as trichome formation and the upregulation of defense-related genes. We also provide genetic evidence that this wound-induced growth repression is possibly a consequence of tomato plants sensing the injuries via jasmonates (JAs), a class of plant hormones known to be master regulators of the plant growth versus defense balance. Besides providing a mechanistic explanation on how the growth and defense balance is shifted when plants are subjected to a specific type of mechanical stimulus, our results may offer a practical explanation for why tomato productivity is so negatively impacted by herbivore attack.
•Growth versus defense antagonism is affected by mechanical wounding in tomato.•Mechanical wounding hinders tomato growth and flowering.•Growth responses to lesions are dependent on the jasmonate signaling pathway.•Mechanical wounding induces the formation of defense traits in tomato.
Modulation of brain activity is one of the main mechanisms capable of demonstrating the synchronization dynamics of neural oscillations. In epilepsy, modulation is a key concept since seizures ...essentially result from neural hypersynchronization and hyperexcitability. In this study, we have introduced a time-dependent index based on the Kullback-Leibler divergence to quantify the effects of phase and frequency modulations of neural oscillations in neonatal mice exhibiting epileptiform activity induced by Zika virus (ZIKV) infection. Through this index, we demonstrate that fast oscillations (gamma and beta 2) are the more susceptible modulated rhythms in terms of phase, during seizures, whereas slow waves (delta and theta) mainly undergo changes in frequency. The index also allowed detection of specific patterns associated with the interdependent modulation of phase and frequency in neural activity. Furthermore, by comparing ZIKV modulations with the general computational model Epileptors, we verify different signatures related to the brain rhythms modulation in phase and frequency. These findings instigate new studies on the effects of ZIKV infection on neuronal networks from electrophysiological activities, and how different mechanisms can trigger epilepsy.
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