Evidence for competition for target innervation in the medial prefrontal cortex

Peer reviewe

Isoflurane produces antidepressant effects and induces TrkB signaling in rodents

A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3 beta (GSK3 beta). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.Peer reviewe

WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas

Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described.We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas.To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization and organoid culture.We detected a heterozygous deletion at the cystic fibrosis locus (7q31.2) perfectly segregating with the intestinal tumor predisposition in the family. The deletion removes a topologically associating domain border between CFTR and WNT2, aberrantly activating WNT2 in the intestinal epithelium. These consequences suggest that the deletion predisposes to small intestinal neuroendocrine tumors and small and large intestinal adenocarcinomas, and reveals the broad tumorigenic effects of aberrant WNT activation in the human intestine.Peer reviewe

Synergistic HNO3_{3}–H2_{2}SO4_{4}–NH3_{3} upper tropospheric particle formation

New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN)$^{1,2,3,4}$. However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region5,6. Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particles—comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO$_{3}$–H$_{2}$SO$_{4}$–NH$_{3}$ nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere

Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine

Idiopathic pulmonary fibrosis (IPF) is characterized by activation and injury of epithelial cells, the accumulation of connective tissue and changes in the inflammatory microenvironment. The bone morphogenetic protein (BMP) inhibitor protein gremlin-1 is associated with the progression of fibrosis both in human and mouse lung. We generated a transgenic mouse model expressing gremlin-1 in type II lung epithelial cells using the surfactant protein C (SPC) promoter and the Cre-LoxP system. Gremlin-1 protein expression was detected specifically in the lung after birth and did not result in any signs of respiratory insufficiency. Exposure to silicon dioxide resulted in reduced amounts of lymphocyte aggregates in transgenic lungs while no alteration in the fibrotic response was observed. Microarray gene expression profiling and analyses of bronchoalveolar lavage fluid cytokines indicated a reduced lymphocytic response and a downregulation of interferon-induced gene program. Consistent with reduced Th1 response, there was a downregulation of the mRNA and protein expression of the anti-fibrotic chemokine CXCL10, which has been linked to IPF. In human IPF patient samples we also established a strong negative correlation in the mRNA expression levels of gremlin-1 and CXCL10. Our results suggest that in addition to regulation of epithelial-mesenchymal crosstalk during tissue injury, gremlin-1 modulates inflammatory cell recruitment and anti-fibrotic chemokine production in the lung.Peer reviewe

Context-Dependent Neural Activity in Mouse Motor Cortex

Movement is essential for an animal to interact with its environment. Furthermore, the better the animal learns the specific demands of the environment, the more fluent is the motor execution. The study of motor control, and how sensorimotor integration guides motor control, is important for understanding the function of neural networks. It is known that the primary motor areas are organized in a topographical manner, but the knowledge on how environmental demands are reflected and encoded in cortical neuronal activity and how this can be shaped by learning is still limited. In my thesis work I focused on how contextual information is encoded in the mouse motor cortex, using two-photon imaging combined with a regular vs. irregular rung ladder locomotion task and across learning. I found that context-depend activity in the primary motor area M1 develops during learning, especially for highly skilled grasping actions, but breaks apart upon silencing of projections from secondary motor cortex. Furthermore, neuronal populations in secondary motor cortex M2 enable adaptive motor behavior by refining context-specific activity patterns

SAIRAANHOITAJIEN KOKEMUKSIA SYÖPÄPOTILAIDEN LÄÄKKEELLISESTÄ KIVUNHOIDOSTA VUOSINA 1980-2013 : -Muistitietoa sairaanhoitajilta

Suomessa syöpätautien määrä on lisääntynyt viimeisten vuosikymmenien aikana. Syöpä aiheuttaa kipua monin eri tavoin, ja suurin osa syöpäpotilaista kärsii kivuista. Kipu heikentää potilaan elämänlaatua sekä toimintakykyä ja toisaalta se myös aiheuttaa pelkoa potilaiden keskuudessa. Kivunhoito koetaan lisäksi usein hyvin haasteelliseksi. Opinnäytetyön tutkimustehtävänä oli selvittää sairaanhoitajien kokemuksia syöpäpotilaiden lääkkeellisen kivunhoidon muuttumisesta vuosina 1980–2013. Tutkimus oli laadullinen ja menetelmänä käytettiin muistitietotutkimusta. Muistitieto kerättiin sairaanhoitajilta haastattelujen avulla ja aineisto analysoitiin käyttäen narratiivista analyysimenetelmää. Opinnäytetyön tarkoitus oli lisätä tietoa syöpäkivunhoidon kehittymisestä sekä saada aikaan keskustelua siitä. Opinnäytetyön tuloksista käy ilmi, että lääkkeellinen kivunhoito on muuttunut kolmenkymmen vuoden aikana merkittävästi. Uusien lääkkeenantoreittien, vahvojen kipulääkkeiden sekä lisääntyneiden konsultaatiomahdollisuuksien hyödyntäminen ovat tuoneet tehokkuutta kivunhoitotyöhön. Lisäksi syöpäkivunhoitoon liittyvä koulutus ja keskustelun lisääntyminen ovat muuttaneet sekä hoitajien että potilaiden asenteita. Tämän opinnäytetyön jatkotutkimusaiheena voi kerätä muistitietoa kivunhoidosta joltain tietyltä erikoisalalta tai aikakaudelta. Toisaalta keskittyä voi myös johonkin erityisen haastavaksi koettuun asiaan, esimerkiksi hoitotyöhön liittyvään teknologiaan.The number of cancer diagnoses has increased in Finland during the last decades. Cancer causes pain in many different ways and most of the cancer patients suffer from it. Pain weakens the quality of life and ability to function. In addition, it is the most feared symptom among cancer patients. Pain management is also experienced to be very challenging. The research task of this thesis was to collect data about how nurses have experienced the changes in pain management among cancer patients between 1980 and 2013. The study was qualitative and the research method was to study of oral history. The oral history was gathered from nurses through interviews. The material was analyzed using the narrative analysis. This study was aimed firstly at increasing the knowledge about history of cancer pain management and secondly at stimulating discussion about it. On the basis of the results of this research, it can be concluded that medical cancer pain management has changed significantly during the last decades. With the help of new medication routes, stronger pain medicines and increased possibilities of consultation it has successfully improved the efficiency of nursing the pain. Because of the education and increased discussion, the attitudes among nurses and patients have also changed. As a further study, oral history could be gathered from a specialized medical care unit or from a certain era of nursing

Vaikuttamisen rajoilla: Onko koetulla luonnolla sijaa kaupungin suunnittelussa ja päätöksenteossa?

To be able to support the opportunities of residentsto maintain their well-being and quality of life,information on the qualities of urban environmentas experienced by residents need to be consideredin planning and decision-making. The aim of thearticle is to discuss how residents’ values andmeanings related to urban nature areas can beas usable information as ecological and technicalinformation and be integrated in the informationbase for planning and decision-making concerningthese areas. First, we review values and meanings ofurban nature as experienced by residents. Second,practices in obtaining information from residentsare presented with examples from the HelsinkiMetropolitan Area. We sum up with a discussionon the challenges the experienced nature brings toplanning and decision-making