Prefrontal Cortex HCN1 Channels Enable Intrinsic Persistent Neural Firing and Executive Memory Function

In many cortical neurons, HCN1 channels are the major contributors to I(h), the hyperpolarization-activated current, which regulates the intrinsic properties of neurons and shapes their integration of synaptic inputs, paces rhythmic activity, and regulates synaptic plasticity. Here, we examine the physiological role of I(h) in deep layer pyramidal neurons in mouse prefrontal cortex (PFC), focusing on persistent activity, a form of sustained firing thought to be important for the behavioral function of the PFC during working memory tasks. We find that HCN1 contributes to the intrinsic persistent firing that is induced by a brief depolarizing current stimulus in the presence of muscarinic agonists. Deletion of HCN1 or acute pharmacological blockade of I(h) decreases the fraction of neurons capable of generating persistent firing. The reduction in persistent firing is caused by the membrane hyperpolarization that results from the deletion of HCN1 or I(h) blockade, rather than a specific role of the hyperpolarization-activated current in generating persistent activity. In vivo recordings show that deletion of HCN1 has no effect on up states, periods of enhanced synaptic network activity. Parallel behavioral studies demonstrate that HCN1 contributes to the PFC-dependent resolution of proactive interference during working memory. These results thus provide genetic evidence demonstrating the importance of HCN1 to intrinsic persistent firing and the behavioral output of the PFC. The causal role of intrinsic persistent firing in PFC-mediated behavior remains an open question

PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells.

mTORC1 (mammalian target of rapamycin complex 1) controls transcriptional programs that determine CD8+ cytolytic T cell (CTL) fate. In some cell systems, mTORC1 couples phosphatidylinositol-3 kinase (PI3K) and Akt to the control of glucose uptake and glycolysis. However, PI3K-Akt-independent mechanisms control glucose metabolism in CD8+ T cells, and the role of mTORC1 has not been explored. The present study now demonstrates that mTORC1 activity in CD8+ T cells is not dependent on PI3K or Akt but is critical to sustain glucose uptake and glycolysis in CD8+ T cells. We also show that PI3K- and Akt-independent pathways mediated by mTORC1 regulate the expression of HIF1 (hypoxia-inducible factor 1) transcription factor complex. This mTORC1-HIF1 pathway is required to sustain glucose metabolism and glycolysis in effector CTLs and strikingly functions to couple mTORC1 to a diverse transcriptional program that controls expression of glucose transporters, multiple rate-limiting glycolytic enzymes, cytolytic effector molecules, and essential chemokine and adhesion receptors that regulate T cell trafficking. These data reveal a fundamental mechanism linking nutrient and oxygen sensing to transcriptional control of CD8+ T cell differentiation

Un petit oiseau de souche galliforme (Aves : Paraorygidae) de l’Éocène de l’Ouzbékistan

Les gallinacés (ordre des Galliformes) sont parmi les oiseaux les plus caractéristiques des faunes d’oiseaux modernes), mais leur histoire évolutive précoce est insuffisamment connue. La diversité des galliformes éocènes décrits jusqu’à présent implique un grand rôle de la diversification à l’Éocène dans l’évolution précoce de ce groupe. Cependant, presque rien n’est connu quant à la diversité éocène des galliformes en Asie, bien que ce vaste continent, avec une grande variété d’habitats, puisse avoir joué un rôle significatif dans leur évolution précoce. Dans cet article est décrit un coracoïde partiel du Lutétien–Bartonien d’Ouzbékistan, qui est le plus ancien oiseau de type galliforme qu’on puisse diagnostiquer et, en outre, le premier qui soit connu dans cette zone géographique. Le spécimen présente une morphologie unique, avec plusieurs autapomorphies et une combinaison inattendue de similarités avec les genres africain Scopelortyx et eurasien Paraortyx, d’où sa description en tant que Xorasmortyx turkestanensis gen. et sp. nov. au sein de la famille éteinte des Paraortygidae, tout en étant le premier représentant asiatique de ce clade. Des similarités avec le genre africain Scpelortyx et eurasien Paraortyx indiquent une connexion de faunes d’oiseaux entre l’Afrique du Nord/Arabie et l’Asie à l’Éocène moyen. De meilleures aptitudes à la dispersion des galliformes précoces Paraortyugidae sont déduites de l’ostéologie de leur ceinture pectorale et de l’humérus, qui ne montrent pas d’adaptation à un puissant élan d’envol (vol de fuite), caractéristique des Phasianidae les plus modernes.Landfowl (order Galliformes) are among the most characteristic birds of the modern avian faunas, but their early evolutionary history is insufficiently known. The diversity of previously described Eocene galliforms implies a great role of Eocene diversification in the early evolution of this group. However, almost nothing is known about the Eocene diversity of galliforms in Asia, even though this large continent with a variety of habitats might have played a significant role in their early evolution. Here we describe a partial coracoid from the Lutetian–Bartonian of Uzbekistan, which is the oldest diagnosable galliform bird in Asia, and is further the first landbird known from this geographical area. The specimen displays a unique morphology with few autapomorphies and an unexpected combination of similarities with the African genus Scopelortyx and Eurasian Paraortyx, and hence is described as a new taxon, Xorazmortyx turkestanensis gen. et sp. nov., within the extinct family Paraortygidae, being the first Asian representative of this clade. Similarities with the African genus Scopelortyx indicate a connection of land bird faunas between northern Africa/Arabia and Asia in the middle Eocene. Better dispersal abilities of the early galliforms Paraortygidae are inferred from the osteology of their pectoral girdle and the humerus, which do not show adaptations to the powerful burst take off (escape flight), characteristic of most modern Phasianidae.</p

BASIC PRINCIPLES IN THE CORRECTION OF SEVERE SCOLIOTIC DEFORMITIES USING PEDICLE SCREW FIXATION

ABSTRACT Objective: To determine the effectiveness of surgical treatment of patients with idiopathic scoliosis who have severe spinal deformity, using either all pedicle screw or hybrid constructs. Methods: A retrospective analysis of the results of treatment of 34 patients aged 15 to 27 years with severe scoliosis, operated on using pedicle screws. A comparison group consisted of 22 patients who were operated on using hybrid constructs. Patients from both groups were compared according to the following parameters: pre/postoperative Cobb angle, mobility according to the traction test, global sagittal/frontal balance, apical vertebral rotation, operative time, intraoperative blood loss, number of instrumented vertebrae, and loss of correction within 24 months. Results: In group A (pedicle screw fixation) compared to group B (hybrid spinal fixation), patients had better results in the following parameters: postoperative correction was 48% and 41%, apical vertebral rotation decreased from 78° to 55° (30%) and from 74° to 59° (21%), correction of global frontal/sagittal balance from 39/25 mm to 14/12 mm (64%/52%) and 35/26 mm to 16/15 mm (55%/43%) between treatment groups, respectively. These results suggest a better trunk balance and greater postoperative correction in patients submitted to the all pedicle screw fixation. Smaller values were found for loss of correction of the major curve, and there was a slight increase in thoracic kyphosis in the postoperative period (24 months) 3.8%/4.3% in group A vs. 6.2%/7.5% in group B, indicating greater reliability and stability of the metal with the «all screw» fixation. This was a Level III retrospective comparative study. Conclusion: All the pedicle screw constructs enabled better postoperative correction, derotation, global sagittal and frontal balance, as well as a shorter fixation, compared to hybrid fixation of the spine. Level of Evidence III, Retrospective comparative study

DEVELOPING NEW METHODS OF SPINAL CORD INJURY TREATMENT USING MAGNETIC NANOPARTICLES IN COMBINATION WITH ELECTROMAGNETIC FIELD

ABSTRACT Objective: To determine the amount of loss of function after spinal cord transection of varying extents, and whether magnetic iron oxide nanoparticles, in combination with an external magnetic field, improve the rate of subsequent functional recovery in rats. Methods: The animals were divided into groups with 50%, 80% and complete spinal cord transection. The animals of all three study groups were administered magnetic iron oxide nanoparticle suspension to the area of injury. The three control groups were not administered magnetic nanoparticles, but had corresponding transection levels. All animals were exposed to a magnetic field for 4 weeks. Loss of postoperative function and subsequent recovery were assessed using the BBB motor function scale and somatosensory evoked potential monitoring on the first day after surgery, and then weekly. Terminal histological analysis was also conducted in all the groups. Results: The animals in the control or complete transection groups did not demonstrate statistically significant improvement in either the BBB scores or evoked potential amplitude over the four-week period. In the group with 50% transection, however, a statistically significant increase in evoked potential amplitude and BBB scores was observed four weeks after surgery, with the highest increase during the second week of the study. In the group with 80% transection, only improvement in evoked potential amplitude was statistically significant, although less pronounced than in the 50% transection group. Conclusion: The use of magnetic iron oxide nanoparticles in combination with a magnetic field leads to higher rates of functional recovery after spinal cord injury in laboratory animals. The mechanism of this functional improvement needs further investigation