Mind over chatter: plastic up-regulation of the fMRI alertness network by EEG neurofeedback

EEG neurofeedback (NFB) is a brain-computer interface (BCI) approach used to shape brain oscillations by means of real-time feedback from the electroencephalogram (EEG), which is known to reflect neural activity across cortical networks. Although NFB is being evaluated as a novel tool for treating brain disorders, evidence is scarce on the mechanism of its impact on brain function. In this study with 34 healthy participants, we examined whether, during the performance of an attentional auditory oddball task, the functional connectivity strength of distinct fMRI networks would be plastically altered after a 30-min NFB session of alpha-band reduction (n=17) versus a sham-feedback condition (n=17). Our results reveal that compared to sham, NFB induced a specific increase of functional connectivity within the alertness/salience network (dorsal anterior and mid cingulate), which was detectable 30 minutes after termination of training. Crucially, these effects were significantly correlated with reduced mind-wandering 'on-task' and were coupled to NFB-mediated resting state reductions in the alpha-band (8-12 Hz). No such relationships were evident for the sham condition. Although group default-mode network (DMN) connectivity was not significantly altered following NFB, we observed a positive association between modulations of resting alpha amplitude and precuneal connectivity, both correlating positively with frequency of mind-wandering. Our findings demonstrate a temporally direct, plastic impact of NFB on large-scale brain functional networks, and provide promising neurobehavioral evidence supporting its use as a noninvasive tool to modulate brain function in health and disease

Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations

Sirenomelia is a severe congenital malformation of the lower body characterized by the fusion of the legs into a single lower limb. This striking external phenotype consistently associates severe visceral abnormalities, most commonly of the kidneys, intestine, and genitalia that generally make the condition lethal. Although the causes of sirenomelia remain unknown, clinical studies have yielded two major hypotheses: i) a primary defect in the generation of caudal mesoderm, ii) a primary vascular defect that leaves the caudal part of the embryo hypoperfused. Interestingly, Sirenomelia has been shown to have a genetic basis in mice, and although it has been considered a sporadic condition in humans, recently some possible familial cases have been reported. Here, we report that the removal of one or both functional alleles of Shh from the Bmp7-null background leads to a sirenomelia phenotype that faithfully replicates the constellation of external and internal malformations, typical of the human condition. These mutants represent an invaluable model in which we have analyzed the pathogenesis of sirenomelia. We show that the signaling defect predominantly impacts the morphogenesis of the hindgut and the development of the caudal end of the dorsal aortas. The deficient formation of ventral midline structures, including the interlimb mesoderm caudal to the umbilicus, leads to the approximation and merging of the hindlimb fields. Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia

Sonic hedgehog specifies flight feather positional information in avian wings

Classical tissue recombination experiments performed in the chick embryo provide evidence that signals operating during early limb development specify the position and identity of feathers. Here, we show that Sonic hedgehog (Shh) signalling in the embryonic chick wing bud specifies positional information required for the formation of adult flight feathers in a defined spatial and temporal sequence that reflects their different identities. We also reveal that Shh signalling is interpreted into specific patterns of Sim1 and Zic transcription factor expression, providing evidence of a putative gene regulatory network operating in flight feather patterning. Our data suggest that flight feather specification involved the co-option of the pre-existing digit patterning mechanism and therefore uncovers an embryonic process that played a fundamental step in the evolution of avian flight

CathepsinKCre mediated deletion of βcatenin results in dramatic loss of bone mass by targeting both osteoclasts and osteoblastic cells

It is well established that activation of Wnt/βcatenin signaling in the osteoblast lineage leads to an increase in bone mass through a dual mechanism: increased osteoblastogenesis and decreased osteoclastogenesis. However, the effect of this pathway on the osteoclast lineage has been less explored. Here, we aimed to examine the effects of Wnt/βcatenin signaling in mature osteoclasts by generating mice lacking βcatenin in CathepsinK-expressing cells (Ctnnb1;CtsKCre mice). These mice developed a severe low-bone-mass phenotype with onset in the second month and in correlation with an excessive number of osteoclasts, detected by TRAP staining and histomorphometric quantification. We found that WNT3A, through the canonical pathway, promoted osteoclast apoptosis and therefore attenuated the number of M-CSF and RANKL-derived osteoclasts in vitro. This reveals a cell-autonomous effect of Wnt/βcatenin signaling in controlling the life span of mature osteoclasts. Furthermore, bone Opg expression in Ctnnb1;CtsKCre mice was dramatically decreased pointing to an additional external activation of osteoclasts. Accordingly, expression of CathepsinK was detected in TRAP-negative cells of the inner periosteal layer also expressing Col1. Our results indicate that the bone phenotype of Ctnnb1;CtsKCre animals combines a cell-autonomous effect in the mature osteoclast with indirect effects due to the additional targeting of osteoblastic cells.This work was supported by grant ISCIII PI12/01405 to JGM and grant BFU2014-57216-P to MAR from the Spanish Government and R01AR056679 from NIAMS/NIH to MA.Peer Reviewe

The tyrosine kinase FER is responsible for the capacitation-associated increase in tyrosine phosphorylation in murine sperm

Sperm capacitation is required for fertilization. At the molecular level, this process is associated with fast activation of protein kinase A. Downstream of this event, capacitating conditions lead to an increase in tyrosine phosphorylation. The identity of the tyrosine kinase(s) mediating this process has not been conclusively demonstrated. Recent experiments using stallion and human sperm have suggested a role for PYK2 based on the use of small molecule inhibitors directed against this kinase. However, crucially, loss-of-function experiments have not been reported. Here, we used both pharmacological inhibitors and genetically modified mice models to investigate the identity of the tyrosine kinase(s) mediating the increase in tyrosine phosphorylation in mouse sperm. Similar to stallion and human, PF431396 blocks the capacitation-associated increase in tyrosine phosphorylation. Yet, sperm from Pyk2(-/-) mice displayed a normal increase in tyrosine phosphorylation, implying that PYK2 is not responsible for this phosphorylation process. Here, we show that PF431396 can also inhibit FER, a tyrosine kinase known to be present in sperm. Sperm from mice targeted with a kinase-inactivating mutation in Fer failed to undergo capacitation-associated increases in tyrosine phosphorylation. Although these mice are fertile, their sperm displayed a reduced ability to fertilize metaphase II-arrested eggs in vitro.Fil: Alvau, Antonio. University of Massachussets; Estados UnidosFil: Battistone, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gervasi, Maria Gracia. University of Massachussets; Estados UnidosFil: Navarrete, Felipe A.. University of Massachussets; Estados UnidosFil: Xu, Xinran. State University of Colorado - Fort Collins; Estados UnidosFil: Sánchez Cárdenas, Claudia. Universidad Nacional Autónoma de México. Instituto de Biotecnología; MéxicoFil: De la Vega Beltran, José Luis. Universidad Nacional Autónoma de México. Instituto de Biotecnología; MéxicoFil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Greer, Peter. Queens University; CanadáFil: Darszon, Alberto. Universidad Nacional Autónoma de México. Instituto de Biotecnología; MéxicoFil: Krapf, Diego. State University of Colorado - Fort Collins; Estados UnidosFil: Salicioni, Ana María. University of Massachussets; Estados UnidosFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Visconti, Pablo E.. University of Massachussets; Estados Unido

Functional human sperm capacitation requires both bicarbonate dependent-PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases

In all mammalian species studied so far, sperm capacitation correlates with an increase in protein tyrosine (Tyr) phosphorylation mediated by a bicarbonate-dependent cAMP/PKA pathway. Recent studies in mice revealed however that a Src Family Kinase (SFK) induced inactivation of serine/threonine (Ser/Thr) phosphatases is also involved in the signaling pathways leading to Tyr phosphorylation. In view of these observations and with the aim of getting a better understanding of the signaling pathways involved in human sperm capacitation, in the present work we investigated the involvement of both the cAMP/PKA and SFK/phosphatase pathways in relation to the capacitation state of the cells. For this purpose, different signaling events and sperm functional parameters were analyzed as a function of capacitation time. Results revealed a very early bicarbonate-dependent activation of PKA indicated by the rapid (1 min) increase in both phospho-PKA substrates and cAMP levels (p<0.05). However, a complete pattern of Tyr phosphorylation was detected only after 6 h-incubation at which time sperm exhibited the ability to undergo the acrosome reaction (AR) and to penetrate zona-free hamster eggs. Sperm capacitated in the presence of the SFK inhibitor SKI606 showed a decrease in both PKA substrate and Tyr phosphorylation levels which was overcome by exposure of sperm to the Ser/Thr phosphatase inhibitor okadaic acid (OA). However, OA was unable to induce phosphorylation when sperm were incubated under PKA-inhibitory conditions (i.e. in the absence of bicarbonate or presence of PKA inhibitor). Moreover, the increase in PKA activity by exposure to a cAMP analogue and a phosphodiesterase inhibitor did not overcome the inhibition produced by SKI606. Whereas the presence of SKI606 during capacitation produced a negative effect (p<0.05) on sperm motility, progesterone-induced AR and fertilizing ability, none of these inhibitions were observed when sperm were exposed to SKI606 and OA. Interestingly, different concentrations of inhibitors were required to modulate human and mouse capacitation revealing the species-specificity of the molecular mechanisms underlying this process. In conclusion, our results describe for the first time the involvement of both PKA activation and Ser/Thr phosphatase down-regulation in functional human sperm capacitation and provide convincing evidence that early PKA-dependent phosphorylation is the convergent regulatory point between these two signaling pathways.Fil: Battistone, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas -conicet. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas -conicet. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Salicioni, A.. University Of Massachussets; Estados UnidosFil: Navarrete, F.. University Of Massachussets; Estados UnidosFil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Visconti, P. E.. University Of Massachussets;Fil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas -conicet. Instituto de Biología y Medicina Experimental (i); Argentin

SLAM Project - Long Term Ecological Study of the Impacts of Climate Change in the Natural Forest of Azores: III - Testing the impact of edge effects in a native forest of Terceira Island

BACKGROUND: The data we present are part of the long-term project “SLAM Project - Long Term Ecological Study of the Impacts of Climate Change in the Natural Forest of Azores” that started in 2012, aiming to understand the impact of biodiversity erosion drivers on Azorean native forests (Azores, Macaronesia, Portugal). The data for the current study consist in an inventory of arthropods collected in three locations of a native forest fragment at Terra-Brava protected area (Terceira, Azores, Portugal) aiming to test the impact of edge effects on Azorean arthropod communities. The three locations were: (i) the edge of the forest, closer to the pastures; (ii) an intermediate area (100 m from edge); and (iii) the deepest part of the native forest fragment (more than 300 m from edge). The study was carried out between June 2014 and December 2015. A total of nine passive flight interception SLAM (Sea, Land and Air Malaise) traps were deployed (three in each of the studied locations), during 18 consecutive months. This study provides the raw data to investigate temporal and edge effect variation for the Azorean arthropod communities. NEW INFORMATION: The collected arthropods belong to a wide diversity of taxonomic groups of Arachnida, Diplopoda, Chilopoda and Insecta classes. We collected a total of 13,516 specimens from which it was possible to identify to species level almost all specimens (13,504). These identified specimens belong to 15 orders, 58 families (plus three with only genus or family level identification) and 97 species of arthropods. A total of 35 species are considered introduced, 34 native non-endemic and 28 endemic. Additionally, a total of 10 taxa (12 specimens) were recorded at genus, family or order level. This dataset will allow researchers to test the impact of edge effect on arthropod biodiversity and to investigate seasonal changes in Azorean arthropod native forest communities.Trap acquisition and fieldwork were funded by the project Portuguese National Funds, through FCT - Fundação para a Ciência e a Tecnologia, within the project UID/BIA/00329/2013-2023. The database management and Open Access was funded by the project "MACRISK-Trait-based prediction of extinction risk and invasiveness for Northern Macaronesian arthropods" Fundacao para a Ciencia e a Tecnologia (FCT) -PTDC/BIA-CBI/0625/2021 (2022-2024). MB was supported by FCT - DL57/2016/CP1375/CT0001. NT and MTF were supported by the project LIFE-BETTLES (LIFE18 NAT/PT/000864). PAVB and RG were additionally supported by FCT-UIDP/00329/2020-2024 (Thematic Line 1-Integrated ecological assessment of environmental change on biodiversity) and MACRISK - PTDC/BIA-CBI/0625/2021, through the FCT - Fundacao para a Ciencia e a Tecnologia.info:eu-repo/semantics/publishedVersio

Pitx2 Expression Defines a Left Cardiac Lineage of Cells: Evidence for Atrial and Ventricular Molecular Isomerism in the iv/iv Mice

AbstractThe homeobox gene Pitx2 has been characterized as a mediator of left-right signaling in heart, gut, and lung morphogenesis. However, the relationship between the developmental role of Pitx2 and its expression pattern at the organ level has not been explored. In this study we focus on the role of Pitx2 in heart morphogenesis. Chicken Pitx2 transcripts are present in the left portion of the cardiac crescent and in the left side of the heart tube. Through looping Pitx2 is present in the left atrium, in the ventral portion of the ventricles and in the left-ventral part of the outflow tract. Mouse Pitx2 shows a similar developmental profile of expression. To test whether Pitx2 represents a lineage marker we have tagged the left portion of the chicken cardiac tube with fluorescent DiD. Labeled cells were found at HH16 in the left atrium and in the ventral region of the ventricles and the outflow tract. In the iv/iv mouse model of cardiac heterotaxia Pitx2 was abnormally expressed in the atrial and in the ventricular chambers. Furthermore, altered Pitx2 expression correlated with the occurrence of DORV. Our data reveal the existence of molecular isomerism not only in the atrial, but also in the ventricular compartment of the heart

SLAM Project - Long Term Ecological Study of the Impacts of Climate Change in the Natural Forest of Azores: II - A survey of exotic arthropods in disturbed forest habitats

BACKGROUND: The data we present consist of an inventory of exotic arthropods, potentially invasive, collected in exotic and mixed forests and disturbed native forest patches of the Azores Archipelago. The study was carried out between 2019 and 2020 in four islands: Corvo, Flores, Terceira and Santa Maria, where a total of 45 passive flight interception SLAM traps were deployed, during three to six consecutive months. This manuscript is the second contribution of the “SLAM Project - Long Term Ecological Study of the Impacts of Climate Change in the Natural Forest of Azores”. NEW INFORMATION: We provide an inventory of terrestrial arthropods belonging to Arachnida, Diplopoda, Chilopoda and Insecta classes from four Azorean islands. We identified a total of 21,175 specimens, belonging to 20 orders, 93 families and 249 species of arthropods. A total of 125 species are considered introduced, 89 native non-endemic and 35 endemic. We registered 34 new records (nine for Corvo, three for Flores, six for Terceira and 16 for Santa Maria), of which five are new for Azores, being all exotic possibly recently introduced: Dieckmanniellus nitidulus (Gyllenhal, 1838), Gronops fasciatus Küster, 1851, Hadroplontus trimaculatus (Fabricius, 1775), Hypurus bertrandi (Perris, 1852) (all Coleoptera, Curculionidae) and Cardiocondyla mauritanica Forel, 1890 (Hymenoptera, Formicidae). This publication highlights the importance of planted forests and disturbed native forest patches as reservoirs of potentially invasive arthropods and refuges for some rare relict endemic arthropod species.Trap acquisition and fieldwork were funded by the projects: Portuguese National Funds, through FCT – Fundação para a Ciência e a Tecnologia, within the project UID/BIA/ 00329/2013-2023; Direcção Regional do Ambiente - PRIBES (LIFE17 IPE/PT/000010) (2019-2020); Direcção Regional do Ambiente – LIFE-BETTLES (LIFE18 NAT_PT_000864) (2020-2024); AZORESBIOPORTAL – PORBIOTA (ACORES-01-0145-FEDER-000072) (2019-2022). The database management and Open Access was funded by the project “MACRISK-Traitbased prediction of extinction risk and invasiveness for Northern Macaronesian arthropods” Fundação para a Ciência e a Tecnologia (FCT) - PTDC/BIA-CBI/0625/2021 (2022-2024). MB was supported by FCT - DL57/2016/CP1375/CT0001. NT and MTF were supported by the project LIFE-BETTLES (LIFE18 NAT_PT_000864).info:eu-repo/semantics/publishedVersio