Marmosets as model systems for the study of Alzheimer's disease and related dementias: substantiation of physiological Tau 3R and 4R isoform expression and phosphorylation.

INTRODUCTION: Marmosets have been shown to spontaneously develop pathological hallmarks of Alzheimer's disease (AD) during advanced age, including amyloid-beta plaques, positioning them as a model system to overcome the rodent-to-human translational gap for AD. However, Tau expression in the marmoset brain has been understudied. METHODS: To comprehensively investigate Tau isoform expression in marmosets, brain tissue from eight unrelated marmosets across various ages was evaluated and compared to human postmortem AD tissue. Microtubule-associated protein tau ( MAPT ) mRNA expression and splicing were confirmed by RT-PCR. Tau isoforms in the marmoset brain were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining. Synaptic Tau expression was analyzed from crude synaptosome extractions. RESULTS: 3R and 4R Tau isoforms are expressed in marmoset brains at both transcript and protein levels across ages. Results from western blot analysis were confirmed by mass spectrometry, which revealed that Tau peptides in marmoset corresponded to the 3R and 4R peptides in the human AD brain. 3R Tau was primarily enriched in neonate brains, and 4R enhanced in adult and aged brains. Tau was widely distributed in neurons with localization in the soma and synaptic regions. Phosphorylation residues were observed on Thr-181, Thr-217, and Thr-231, Ser202/Thr205, Ser396/Ser404. Paired helical filament (PHF)-like aggregates were also detected in aged marmosets. DISCUSSION: Our results confirm the expression of both 3R and 4R Tau isoforms and important phosphorylation residues in the marmoset brain. These data emphasize the significance of marmosets with natural expression of AD-related hallmarks as important translational models for the study of AD.

Biochemical and molecular biomarkers and their association with anthropogenic chemicals in wintering Manx shearwaters (Puffinus puffinus).

Anthropogenic pollution poses a threat to marine conservation by causing chronic toxic effects. Seabirds have contact throughout their lives with pollutants like plastic, metals, polychlorinated biphenyls (PCBs), and organochlorine pesticides such as hexachlorocyclohexanes (HCHs). We assessed 155 Manx shearwaters (Puffinus puffinus) stranded along the Brazilian coast, analyzing associations between organic pollutants, plastic ingestion, biomarkers (transcript levels of aryl hydrocarbon receptor, cytochrome P450-1A-5 [CYP1A5], UDP-glucuronosyl-transferase [UGT1], estrogen receptor alpha-1 [ESR1], and heat shock protein-70 genes) and enzymes activity (ethoxy-resorufin O-deethylase and glutathione S-transferase [GST]). Plastic debris was found in 29 % of the birds. The transcription of UGT1 and CYP1A5 was significantly associated with hexachlorobenzene (HCB) and PCBs levels. ESR1 was associated with HCB and Mirex, and GST was associated with Drins and Mirex. While organic pollutants affected shearwaters more than plastic ingestion, reducing plastic availability remains relevant as xenobiotics are also potentially adsorbed onto plastics.

Transcriptomic investigation and biomarker discovery for zinc response in oysters Crassostrea gasar.

In an era of unprecedented industrial and agricultural growth, metal contamination in marine environments is a pressing concern. Sentinel organisms such as the mangrove oyster Crassostrea gasar provide valuable insights into these environments' health. However, a comprehensive understanding of the molecular mechanisms underlying their response to metal exposure remains elusive. To address this gap, we reanalyzed the 454-sequencing data of C. gasar, utilizing an array of bioinformatics workflow of CDTA (Combined De Novo Transcriptome Assembly) to generate a more representative assembly. In parallel, C. gasar individuals were exposed to two concentrations of zinc (850 and 4500 µg L-1 Zn) for 48 h to understand their molecular responses. We utilized Trinotate workflow for the 11,684-CDTA unigenes annotation, with most transcripts aligning with the genus Crassostrea. Our analysis indicated that 67.3% of transcript sequences showed homology with Pfam, while 51.4% and 54.5%, respectively had GO and KO terms annotated. We identified potential metal pollution biomarkers, focusing on metal-related genes, such as those related to the GSH biosynthesis (CHAC1 and GCLC-like), to zinc transporters (ZNT2-like), and metallothionein (MT-like). The evolutionary conservation of these genes within the Crassostrea genus was assessed through phylogenetic analysis. Further, these genes were evaluated by qPCR in the laboratory exposed oysters. All target genes exhibited significant upregulation upon exposure to Zn at both 850 and 4500 µg L-1, except for GCLC-like, which showed upregulation only at the higher concentration of 4500 µg L-1. This result suggests distinct activation thresholds and complex interactions among these genes in response to varying Zn concentrations. Our study provides insights into the molecular responses of C. gasar to Zn, adding valuable tools for monitoring metal pollution in marine ecosystems using the mangrove oyster as a sentinel organism.

Early molecular events of autosomal-dominant Alzheimer's disease in marmosets with PSEN1 mutations.

INTRODUCTION: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan. METHODS: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1. Founders and their germline offspring are comprehensively studied longitudinally using non-invasive measures including behavior, biomarkers, neuroimaging, and multiomics signatures. RESULTS: Prior to adulthood, increases in plasma amyloid beta were observed in PSEN1 mutation carriers relative to non-carriers. Analysis of brain revealed alterations in several enzyme-substrate interactions within the gamma secretase complex prior to adulthood. DISCUSSION: Marmosets carrying KI point mutations in PSEN1 provide the opportunity to study the earliest primate-specific mechanisms that contribute to the molecular and cellular root causes of AD onset and progression. HIGHLIGHTS: We report the successful generation of genetically engineered marmosets harboring knock-in point mutations in the PSEN1 gene. PSEN1 marmosets and their germline offspring recapitulate the early emergence of AD-related biomarkers. Studies as early in life as possible in PSEN1 marmosets will enable the identification of primate-specific mechanisms that drive disease progression.

Emerging and legacy contaminants on the Brazilian southern coast (Santa Catarina): A multi-biomarker approach in oysters Crassostrea gasar (Adanson, 1757).

Coastal environments, such as those in the Santa Catarina State (SC, Brazil), are considered the primary receptors of anthropogenic pollutants. In this study, our objective was to evaluate the levels of emerging contaminants (ECs) and persistent organic pollutants (POPs) in indigenous Crassostrea gasar oysters from different regions of SC coast in the summer season (March 2022). Field collections were conducted in the São Francisco do Sul, Itajaí, Florianópolis and Laguna coastal zones. We analyzed the bioaccumulation levels of 75 compounds, including antibiotics (AB), endocrine disruptors (ED), non-steroidal anti-inflammatory drugs (NSAIDs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and pesticides. Furthermore, we assessed biomarker responses related to biotransformation, antioxidant defense, heat shock protection and oxidative damage in oysters' gills. Prevalence of ECs was observed in the central and southern regions, while the highest concentrations of POPs were detected in the central-northern regions of SC. Oysters exhibited an induction in biotransformation systems (cyp2au1 and cyp356a1, sult and GST activity) and antioxidant enzymes activities (SOD, CAT and GPx). Higher susceptibility to lipid peroxidation was observed in the animals from Florianópolis compared to other regions. Correlation analyses indicated possible associations between contaminants and environmental variables in the biomarker responses, serving as a warning related to climate change. Our results highlight the influence of anthropogenic activities on SC, serving as baseline of ECs and POPs levels in the coastal areas of Santa Catarina, indicating more critical zones for extensive monitoring, aiming to conserve coastal regions.

Improving preclinical to clinical translation of cognitive function for aging-related disorders: the utility of comprehensive touchscreen testing batteries in common marmosets.

Concerns about poor animal to human translation have come increasingly to the fore, in particular with regards to cognitive improvements in rodent models, which have failed to translate to meaningful clinical benefit in humans. This problem has been widely acknowledged, most recently in the field of Alzheimer's disease, although this issue pervades the spectrum of central nervous system (CNS) disorders, including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. Consequently, recent efforts have focused on improving preclinical to clinical translation by incorporating more clinically analogous outcome measures of cognition, such as touchscreen-based assays, which can be employed across species, and have great potential to minimize the translational gap. For aging-related research, it also is important to incorporate model systems that facilitate the study of the long prodromal phase in which cognitive decline begins to emerge and which is a major limitation of short-lived species, such as laboratory rodents. We posit that to improve translation of cognitive function and dysfunction, nonhuman primate models, which have conserved anatomical and functional organization of the primate brain, are necessary to move the field of translational research forward and to bridge the translational gaps. The present studies describe the establishment of a comprehensive battery of touchscreen-based tasks that capture a spectrum of domains sensitive to detecting aging-related cognitive decline, which will provide the greatest benefit through longitudinal evaluation throughout the prolonged lifespan of the marmoset.

Direct interhemispheric cortical communication via thalamic commissures: a new white matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as a vital fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Lumbosacral pain in a patient with psoriatic arthritis: when the rheumatic disease is innocent.

Lumbar pain is a very common symptom that derives from benign musculoskeletal conditions, rheumatic inflammatory diseases, neoplasms, and referred and/or nociplastic pain. A 70-year-old man with psoriatic arthritis presented with early-onset lumbosacral pain without evident red flags. Symptomatic treatment was unhelpful. Radiographic imaging showed subtle signs of a disease that could easily be missed. Magnetic resonance imaging revealed a massive prostatic malignancy with bone (sacral and iliopubic) metastasis. Awareness must be given not to disregard every lumbar pain as part of the preexisting rheumatic inflammatory disease (spondyloarthropathy in this case) or a common muscle/ligament/articular disarrangement. Persistence of pain, albeit not inflam-matory nor sharp in nature, despite adequate treatment might be just as important as an acute red flag and requires proper follow-up.

Exploring the impact of sodium salts on hydrotropic solubilization.

Some ionic liquids (ILs) were shown to display a strong ability to enhance the solubility of phenolic compounds through hydrotropy. However, evidence shows that salt ions in hydrotropic aqueous solutions may change the behavior of molecules by promoting possible interactions between the components of the system, thus causing changes in solubility. Herein, we study the impact of sodium salt anions on the hydrotropic dissolution of syringic acid using 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) as a hydrotrope, with a focus on dicyanamide Na[N(CN)2] and thiocyanate Na[SCN] salts. Dynamic light scattering, Raman spectroscopy, and nuclear magnetic resonance spectroscopy were used to investigate how the mixture of IL-salts affects the solvation. The results obtained show that [C4mim]Cl is able to increase the solubility of syringic acid 80-fold. Despite their structural similarities, the presence of Na[N(CN)2] or Na[SCN] in an aqueous solution of [C4mim]Cl induced opposite solubility trends. The addition of Na[N(CN)2] promotes a higher ability to solubilize syringic acid than in the corresponding IL system due to a pH buffering effect, resulting in the deprotonation of the solute. The addition of Na[SCN], on the other hand, induces a relative decrease in syringic acid solubilization at higher concentrations of ILs due to the negative contribution of the NaCl formed by anion-exchange. These results emphasise the often overlooked pH contribution provided by ILs for biomolecule solubilisation whilst providing experimental insights into the structure of aqueous solutions of ionic liquids and the role it plays in the formation of IL-salt aggregates.

Bridging the rodent to human translational gap: Marmosets as model systems for the study of Alzheimer's disease.

Introduction: Our limited understanding of the mechanisms that trigger the emergence of Alzheimer's disease (AD) has contributed to the lack of interventions that stop, prevent, or fully treat this disease. We believe that the development of a non-human primate model of AD will be an essential step toward overcoming limitations of other model systems and is crucial for investigating primate-specific mechanisms underlying the cellular and molecular root causes of the pathogenesis and progression of AD. Methods: A new consortium has been established with funding support from the National Institute on Aging aimed at the generation, characterization, and validation of Marmosets As Research Models of AD (MARMO-AD). This consortium will study gene-edited marmoset models carrying genetic risk for AD and wild-type genetically diverse aging marmosets from birth throughout their lifespan, using non-invasive longitudinal assessments. These include characterizing the genetic, molecular, functional, behavioral, cognitive, and pathological features of aging and AD. Results: The consortium successfully generated viable founders carrying PSEN1 mutations in C410Y and A426P using CRISPR/Cas9 approaches, with germline transmission demonstrated in the C410Y line. Longitudinal characterization of these models, their germline offspring, and normal aging outbred marmosets is ongoing. All data and resources from this consortium will be shared with the greater AD research community. Discussion: By establishing marmoset models of AD, we will be able to investigate primate-specific cellular and molecular root causes that underlie the pathogenesis and progression of AD, overcome limitations of other model organisms, and support future translational studies to accelerate the pace of bringing therapies to patients.

Noninvasive disruption of the blood-brain barrier in the marmoset monkey.

The common marmoset monkey (Callithrix jacchus) is a species of rising prominence in the neurosciences due to its small size, ease of handling, fast breeding, and its shared functional and structural brain characteristics with Old World primates. With increasing attention on modeling human brain diseases in marmosets, understanding how to deliver therapeutic or neurotropic agents to the marmoset brain noninvasively is of great preclinical importance. In other species, including humans, transcranial focused ultrasound (tFUS) aided by intravenously injected microbubbles has proven to be a transient, reliable, and safe method for disrupting the blood-brain barrier (BBB), allowing the focal passage of therapeutic agents that do not otherwise readily traverse the tight endothelial junctions of the BBB. The critical gap that we address here is to document parameters to disrupt the BBB reliably and safely in marmosets using tFUS. By integrating our marmoset brain atlases and the use of a marmoset-specific stereotactic targeting system, we conduct a series of systematic transcranial sonication experiments in nine marmosets. We demonstrate the effects of center frequency, acoustic pressure, burst period, and duration, establish a minimum microbubble dose, estimate microbubble clearance time, and estimate the duration that the BBB remains open to passage. Successful BBB disruption is reported in vivo with MRI-based contrast agents, as well as Evans blue staining assessed ex vivo. Histology (Hematoxylin and Eosin staining) and immunohistochemistry indicate that the BBB can be safely and reliably opened with the parameters derived from these experiments. The series of experiments presented here establish methods for safely, reproducibly, and focally perturbing the BBB using tFUS in the common marmoset monkey that can serve as a basis for noninvasive delivery of therapeutic or neurotropic agents.

Direct interhemispheric cortical communication via thalamic commissures: a new white-matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Heterotopic connectivity of callosal dysgenesis in mice and humans.

The corpus callosum (CC), the largest brain commissure and the primary white matter pathway for interhemispheric cortical connectivity, was traditionally viewed as a predominantly homotopic structure, connecting mirror areas of the cortex. However, new studies verified that most callosal commissural fibers are heterotopic. Recently, we reported that ~75% of the callosal connections in the brains of mice, marmosets, and humans are heterotopic, having an essential role in determining the global properties of brain networks. In the present study, we leveraged high-resolution diffusion-weighted imaging and graph network modeling to investigate the relationship between heterotopic and homotopic callosal fibers in human subjects and in a spontaneous mouse model of Corpus Callosum Dysgenesis (CCD), a congenital developmental CC malformation that leads to widespread whole-brain reorganization. Our results show that the CCD brain is more heterotopic than the normotypical brain, with both mouse and human CCD subjects displaying highly variable heterotopicity maps. CCD mice have a clear heterotopicity cluster in the anterior CC, while hypoplasic humans have strongly variable patterns. Graph network-based connectivity profile showed a direct impact of heterotopic connections on CCD brains altering several network-based statistics. Our collective results show that CCD directly alters heterotopic connections and brain connectivity.

Field study of metal concentrations and biomarker responses in resident oysters of an estuarine system in southern Brazil.

Pollutant exposure is considered an important factor responsible for the decline in marine biodiversity of Latin American coastal ecosystems. This threat has been detected in an estuarine system in southern Brazil, which prompted an investigation into the long-term biological effects of a chronic metal contamination on resident oysters from the Laguna Estuarine System (LES). Here, we present the species- and size-specific variations of biomarker responses (catalase, glucose-6-phosphate dehydrogenase, glutathione S-transferase, and protein carbonylation) in the gills and digestive gland of Crassostrea gigas and Crassostrea gasar. In parallel, concentrations of eight metals (Al, Cd, Cr, Cu, Fe, Mn, Pb, Zn) in soft tissues were measured. Our analyses revealed that the metal levels exhibited decreasing order in both species: Zn > Fe > Al > Cu > Mn > Cd. Except for Cu and Al, metal concentrations did not differ between oyster species. Biomarker results highlighted that C. gasar presented higher antioxidant responses, whereas C. gigas showed increased biotransformation upon exposure to LES pollutants, which varied according to the tissue. However, C. gasar showed a significant higher content of protein carbonylation but was not related to metals. In our research approach, the observation of metals presence and biomarkers-related responses are considered biologically relevant from an ecotoxicological perspective and serve as a baseline for future pollution studies in estuaries of Latin America. Finally, we recommend adopting a suite of biomarkers in both C. gasar and C. gigas, regardless their size and weight, as sentinel organisms in future regional biomonitoring studies in southern Brazil.

Comparative biochemical and molecular responses of biotransformation and antioxidant systems in three species of Crassostrea (Sacco, 1897) oysters exposed to chrysene.

Chrysene (CHR) is among the most persistent polycyclic aromatic hydrocarbons (PAH) in water and a priority compound for pollutants monitoring, due to its carcinogenic, mutagenic and genotoxic potential. Aquatic animals exposed to CHR may present alterations of biomarkers involved in the biotransformation and oxidative stress-related parameters. The aim of this study was to investigate differences in antioxidant and biotransformation (phase I and II) systems of Crassostrea gigas, C. gasar and C. rhizophorae and its effects resulting from CHR exposure. Adult oysters of these species were exposed to 10 µg L-1 of CHR for 24 h and 96 h. In gills, the transcripts CYP1-like, CYP2-like, CYP2AU1-like, GSTO-like, MGST-like, SULT-like were evaluated after 24 h of exposure. The activity of SOD, CAT, GPx, GR and G6PDH were analyzed in gills and digestive glands after 96 h of exposure. CHR bioaccumulated in tissues. Differences in the remaining levels of CHR in water after 96 h were observed in aquaria containing C. gigas or C. gasar oysters and may be associated to the different filtration rates between these species. Downregulate of biotransformation genes were observed in gills of C. gasar (CYP2AU1-like and GSTO-like) and C. rhizophorae (CYP1-like1, CYP2-like, MGST-like and SULT-like), suggesting that biotransformation responses may be species-specific. Differential activity of antioxidant enzymes were observed in gills and digestive gland of oysters exposed to CHR. Biochemical responses suggested that C. gigas and C. gasar are more responsive to CHR. Differential responses observed among the three Crassostrea species can be related to evolutionary differences, ecological niches and adaptation to environment.

Effects of cadmium and zinc on gene expression of novel molecular biomarkers in the mangrove oyster Crassostrea gasar.

Metal contamination impacts various aquatic species, and mollusk bivalves are appropriate sentinel organisms in coastal pollution assessment. Metal exposure can disrupt homeostasis, alter gene expression, and harm cellular processes. However, organisms have evolved mechanisms to regulate metal ions and counteract their toxicity. This study examined the effect of acute cadmium (Cd) and zinc (Zn) on metal-related gene expression in gills of Crassostrea gasar following 24 and 48 h of laboratory exposure. We focused on Zn transport, metallothionein (MT), glutathione (GSH) biosynthesis, and calcium (Ca) transporter genes to understand the underlying Cd and Zn-accumulating mechanisms that prevent metal toxicity. Our findings revealed increased Cd and Zn levels in oyster gills, with significantly higher accumulation after 48 h. C. gasar accumulated high Cd concentrations even in scarce conditions and increased Zn levels, suggesting a strategy to cope with toxicity. While no significant gene expression differences were observed after 24 h, the increased metal accumulation after 48 h led to upregulation of CHAC1, GCLC, ZnT2, and MT-like genes in oysters exposed to Cd, and increased ZnT2-like expression following exposure to higher Cd/Zn mixtures. We found evidence of oysters may mobilize metal-related genes to mitigate Cd-induced toxicity by both chelating metals and/or reducing their intracellular concentrations. The observed genes upregulation also indicates their sensitivity to changes in metal bioavailability. Overall, this study offers insights into oyster mechanisms for coping with metal toxicity and suggests ZnT2, MT, CHAC1, and GCLC-like as molecular biomarkers for monitoring aquatic metal pollution using C. gasar as sentinel species.

In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis.

Remyelination is crucial to recover from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral inflammatory demyelinating lesions, we investigated whether MRI is sensitive to, and can characterize, remyelination. In six animals followed with multisequence 7 T MRI, 31 focal lesions, predicted to be demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in four of six marmosets and 45% of lesions. Radiological-pathological comparison showed that MRI had high statistical sensitivity (100%) and specificity (90%) for detecting remyelination. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents.

How does habitat influence metabolism? Clues from biomarker response and contaminant profile in Tursiops truncatus (Montagu, 1821) subspecies living in parapatry.

In western South America (WSA) two subspecies of bottlenose dolphin are recognized: Tursiops truncatus gephyreus, predominantly found in estuaries and river mouths, and Tursiops truncatus truncatus, occurring along the continental shelf. Despite a partial spatial overlap, both subspecies are considered to occupy different habitats and ecological niches. In the present study, chemical analyzes as well as biochemical and molecular biomarkers were used to investigate the influence of niche partitioning over metabolic pathways associated with the detoxification of persistent organic pollutants (POPs), antioxidant metabolism, immune activity and lipid metabolism in Tursiops truncatus subspecies living in parapatry. Overall, the profile and levels of bioaccumulated PCBs, pesticides and PBDEs were similar between groups, with a greater variety of pesticides, such as γ-HCHs, heptachlor, oxychlordane and o,p'DDT, detected in T. truncatus gephyreus. Multivariate analysis of variance (MANOVA) and non-metric multidimensional scaling (NMDS) results indicated that glutathione reductase (GR) and superoxide dismutase (SOD) enzymatic activities were higher in coastal dolphins, as were the mRNA levels of metallothionein 2A (MT2A), interleukin-1α (IL-1α), ceramide synthase 3 (CERS3) and fatty acid elongase (ELOVL4). In parallel, mRNA levels of fatty acid synthase complex 1 (FASN 1) were higher in oceanic dolphins. These findings suggest that, due to their occurrence in coastal habitats, T. truncatus gephyreus is more exposed to environmental pollutants and pathogenic microorganisms. Likewise, niche partitioning may influence lipid biosynthesis, possibly due to differences on feeding habits, reflecting in an enhanced long chain ceramides biosynthesis in T. truncatus gephyreus. Collectively, these data reinforce the need to address habitat specificities in conservation efforts, since distinct groups can be facing different anthropogenic pressures in WSA.

Fipronil impairs the GABAergic brain responses of Nile Tilapia during the transition from normoxia to acute hypoxia.

γ-aminobutyric acid (GABA) is one of the main neurotransmitters involved in the adaptation processes against the damage that hypoxia can cause to the brain. Due to its antagonist action on GABA receptors, the insecticide fipronil can turn the fish more susceptible to the negative effects of hypoxia. This study aimed to understand better if fipronil affects these GABAergic responses of Tilapia ahead to hypoxia. Oreochromis Niloticus (Nile Tilapia) were exposed for 3 and 8 h to fipronil (0.0, 0.1, and 0.5 µg.L-1 ) under normoxia (dissolved O2 > 6 mg.L-1 ) and moderate hypoxia (dissolved O2 < 2 mg.L-1 ) conditions. Briefly, hypoxia caused opposite effects on the gene transcription of the evaluated ionotropic and metabotropic GABA receptors. Unexpectedly, we obtained reduced HIF1A mRNA and brain GABA levels, mostly in the first 3 h of the experiment, for the hypoxic group compared with the normoxia one. Besides that, we also demonstrated that the insecticide fipronil impairs the brain GABAergic signaling of a hypoxia-tolerant fish during the transition from a normoxic to an acute hypoxic state. Thus, these results predict the relevant impact on the brain metabolic adaptations of fishes exposed to such stressful conditions in an aquatic environment, as well as the effects of fipronil in the GABAergic responses to hypoxia, which in turn may have ecological and physiological significance to hypoxia-tolerant fishes exposed to this insecticide.

Effects of a physiotherapeutic protocol in cardiorespiratory, muscle strength, aerobic capacity and quality of life after hematopoietic stem cell transplantation.

OBJECTIVE: To analyze the effects of hospital cardiorespiratory physical therapy protocol on the functional capacity and quality of life of patients submitted to hematopoietic stem cell transplantation (HSCT). METHODS: From January to December 2019, bilateral dynamometry, Manovacuometry and Ventilometry, peak expiratory flow "Peak Flow", 6-min walk test (6MWT), SF-36 Quality of Life Questionnaire and Visual Analog Scale (VAS) were applied in patients who have undergone an allogeneic or autologous hematopoietic stem cell transplantation (HSCT), pre-conditioning (initial evaluation) and pre-discharge (final evaluation). The patients were submitted to an intervention protocol, consisting of aerobic training, muscle strengthening and respiratory muscle training, between the two assessments. RESULTS: 29 patients were enrolled in the study and 24 (83%) completed all procedure. Myeloablative and reduced intensity conditioning were performed in 89.6% and 10.4%, respectively; 17 (58%) patients have undergone an autologous HSCT; 10 (35%) identical related allogeneic HSCT, and 2 (7%) haploidentical allogeneic HSCT. The median number of interventions per patient was 3 (1-9). A decreasing in the right and left dynamometry (p  ≤ 0.0001 and 0.002, respectively) and, also in the distance covered in the 6MWT (p  = 0.004), was observed after HSCT. There was no significant difference in respiratory muscle strength, quality of life and fatigue sensation. CONCLUSION: Cardiorespiratory rehabilitation can preserve functional capacity and quality of life.