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Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.
Hintergrund: Am Fachbereich Medizin der Universität Frankfurt werden jedes Jahr zwischen 15 und 20 neue Projekte zur Verbesserung der Lehre durch den Studienausschuss gefördert. Portfolios zur Skizzierung der Projekte werden von den Zentren und Instituten eingereicht. Diese Projekte haben u.a. die Neustrukturierung von Kursen und Praktika, die Implementierung und Evaluation von Prüfungen (z. B. objective structured clinical evaluation), die Förderung der didaktischen Aus- und Weiterbildung von Dozenten und Tutoren oder die curriculare Einbindung von elektronischen Medien in die Lehre zum Inhalt.
Um diese Projekte untereinander zu koordinieren, wurde im Juni 2006 das Frankfurter Ideenforum für Lehre und Unterricht – kurz FILU – geschaffen.
Ziele des Frankfurter Ideenforums für Lehre und Unterricht
1. Das Forum FILU bietet eine Informationsplattform für die Projektleiter der Lehrverbesserungsprojekte.
2. Das Forum übernimmt die Funktion eines Kondensators für thematisches und informationelles Vernetzungspotential der Projekte untereinander.
3. Übersteigt der Arbeits- und Koordinationsbedarf die Möglichkeiten des Forums, initiiert das FILU neue interdisziplinäre Arbeitsgruppen.
4. Der "Journal Club" innerhalb der Treffen des FILU läßt alle Teilnehmer an der aktuellen Studienlage in Ausbildungsforschung teilhaben.
5. Das Forum FILU engagiert sich dafür, die Aktivitäten zur Lehre innerhalb des Fachbereiches Medizin und darüber hinaus bekannt zu machen.
Methode: Koordination und Organisation des Forums übernimmt eine ärztliche wissenschaftliche Mitarbeiterin. Die Treffen finden in 4-Wochenrhythmen à 2 Stunden statt. Pflichtmitglieder sind die Initiatoren und Leiter der Lehrverbesserungsprojekte; weitere interessierte Akteure des Fachbereiches nehmen ebenfalls teil.
Pro Termin werden maximal zwei Lehrverbesserungsprojekte vorgestellt und diskutiert. In einem Journal Club wird eine aktuelle und für den Fachbereich relevante Studie aus den einschlägigen Journalen der Ausbildungsforschung und Medizindidaktik vorgestellt. Nach jedem Treffen erfolgt eine freiwillige Befragung der Mitglieder hinsichtlich Zielvorstellungen, Veranstaltungsankündigungen und Vortragswünschen. Halbjährig erfolgt ein Bericht an den Studienausschuss. [Ein Organigramm stellt bildhaft die Strukturen dar.]
Ergebnisse: Insgesamt haben bisher bei 9 Terminen 202 Personen teilgenommen. Aus der Befragung der Mitglieder initiierten sich ein interdisziplinäres Promotions- und Studienkolleg für Ausbildungsforschung und ein Lehrverbesserungsprojekt zur zentrumsübergreifenden Koordination von Simulationspatienten in OSCE.
Innerhalb des Forums entstand die Planung zur Präsentation der Lehre-Aktivitäten auf einer Veranstaltung der Frankfurter Medizinischen Gesellschaft. Der Fachbereich verfügt durch Anregung aus dem Gremium inzwischen über ein eigenes Online-Portal, einen virtuellen "Treffpunkt Lehre".
[Teilnehmerzahlen, Herkunftszentren der Teilnehmer, Themen der LV-Projekte über die letzten zwei Jahre]
Schlussfolgerung: Das "Frankfurter Ideenforum für Lehre und Unterricht", FILU, bietet seit seiner Implementierung eine lebendige Austausch- und Kommunikationsplattform für die Leiter der Lehrverbesserungsprojekte am Fachbereich. Über das Forum wird eine gemeinsame Nutzung der vorhandenen Ressourcen in der Lehre möglich. Die interdisziplinäre Zusammenarbeit der Akteure wird maßgeblich gefördert und bietet die Möglichkeit, sinnvolle thematische und personelle Synergien zu finden.
A morphological and molecular review of the genus Goniurosaurus, including an identification key
(2021)
The genus Goniurosaurus (tiger geckos) currently consists of 23 species distributed in China, Japan and Vietnam. Several species complexes and recent discoveries of cryptic species pose challenges to the species identification, which is crucial to effectively implement the recent listing of the species from China and Vietnam in CITES Appendix II and the species from Japan in CITES Appendix III. Based on the results of our field work in northern Vietnam and data compiled from literature, we herein provide a taxonomic review of the genus Goniurosaurus. Our phylogenetic analyses showed that all recorded populations of tiger geckos from Vietnam, which were found to be monophyletic with low intra-specific genetic divergences, are assigned to one of the four species: G. catbaensis, G. huuliensis, G. lichtenfelderi or G. luii. Both genetic and morphological analyses confirm that the species from China and Vietnam can be split into three major groups. Based on the newly collected data, we provide an extended morphological description of the Vietnamese species. In addition, we provide an identification key for all Goniurosaurus species from China, Japan and Vietnam in order to assist authorities in the enforcement of the recent CITES listing.
We describe a new species of Cyrtodactylus on the basis of two specimens collected from Ta Kou Nature Reserve, Binh Thuan Province, southern Vietnam. Cyrtodactylus chungi sp. nov. is distinguished from the remaining Indochinese bent-toed geckos by a combination of the following characters: relatively small body size (SVL up to 68.5 mm); a continuous neckband; 5 or 6 irregular transverse dorsal bands; 11 or 12 bands on original tail; keeled tubercles present on dorsum, posterior limbs and tail; 17 or 18 irregular dorsal tubercle rows; 30 or 31 ventral scale rows; ventrolateral skin folds indistinct; an angular series of seven precloacal pores in male and six pitted, enlarged precloacal scales in female, each series separated by a diastema of undifferentiated scales from 4–6 enlarged, poreless femoral scales; median subcaudals slightly enlarged; 17–20 subdigital lamellae under the fourth toe. Based on molecular analyses of the fragment of mitochondrial gene cytochrome c oxidase subunit I (COI), the new species is recovered as the sister taxon to Cyrtodactylus cattienensis s. str. with a genetic divergence of more than 9%. In phylogenetic analyses, the new species is recovered as a member of the Cyrtodactylus irregularis species group.
We describe a new species of Theloderma from northeastern Vietnam based on morphological differences and molecular divergence. Theloderma khoii sp. nov. is distinguishable from its congeners on the basis of a combination of the following characters: large size, SVL 52.1 mm in male, 59.4 mm in female; head length and width equal; vomerine teeth present; snout pointed and truncated, eye large, ED 4.7 mm in male, 5.6 mm in female, spinules on upper eyelid; tibiotarsal articulation reaches to the posterior border of the eye or the tip of the snout; dorsal skin very rough with large irregular gland ridges and warts, ventral surface of body granular; tips of all digits dilated but all considerably smaller than tympanum; dorsal surface mossy green or olive mottled with dark magenta. The distribution of the new species is unknown but probably extends into adjacent high elevation forested areas in Ha Giang Province, Vietnam and in Yunnan Province, China with an extent of occurrence of only < 1000 km2 and continuing decline in the quality of its habitat due to deforestation. Thus, we suggest the species should be considered Endangered following IUCN’s Red List categories.
We describe a new species of the genus Zhangixalus Li, Jiang, Ren & Jiang, 2019 from Ha Giang Province, Vietnam based on morphological and molecular data. In the molecular phylogenetic analyses, the new species is nested in the Zhangixalus duboisi (Ohler, Marquis, Swan & Grosjean, 2000) group, where it is sister to Z. duboisi with a genetic distance of 2.51%. The new species, Zhangixalus franki sp. nov., differs from its congeners by a combination of the following morphological characters: size large, SVL 77.9–85.8 mm in males; finger webbing formula I1-1II0-1III½-0IV; dorsal surface of head and body green with dark brown spots; ventral surface grey or dark grey, white stripe along edge of jaw, insertion of limbs, and along lateral ridges of fore and hind limbs and flank, separating upper green part from lower grey part. The new species occurs in evergreen montane tropical forests at an elevation of ca 1300 m a.s.l. The new discovery brings the total number of known species in the genus Zhangixalus to 38 and the species number reported from Vietnam to nine.
Mechanistic understanding of dynamic membrane proteins such as transporters, receptors, and channels requires accurate depictions of conformational ensembles, and the manner in which they interchange as a function of environmental factors including substrates, lipids, and inhibitors. Spectroscopic techniques such as electron spin resonance (ESR) pulsed electron–electron double resonance (PELDOR), also known as double electron–electron resonance (DEER), provide a complement to atomistic structures obtained from x-ray crystallography or cryo-EM, since spectroscopic data reflect an ensemble and can be measured in more native solvents, unperturbed by a crystal lattice. However, attempts to interpret DEER data are frequently stymied by discrepancies with the structural data, which may arise due to differences in conditions, the dynamics of the protein, or the flexibility of the attached paramagnetic spin labels. Recently, molecular simulation techniques such as EBMetaD have been developed that create a conformational ensemble matching an experimental distance distribution while applying the minimal possible bias. Moreover, it has been proposed that the work required during an EBMetaD simulation to match an experimentally determined distribution could be used as a metric with which to assign conformational states to a given measurement. Here, we demonstrate the application of this concept for a sodium-coupled transport protein, BetP. Because the probe, protein, and lipid bilayer are all represented in atomic detail, the different contributions to the work, such as the extent of protein backbone movements, can be separated. This work therefore illustrates how ranking simulations based on EBMetaD can help to bridge the gap between structural and biophysical data and thereby enhance our understanding of membrane protein conformational mechanisms.
We provide the first distribution pattern of the Microhyla heymonsi group based on available molecular and morphological data collected from East and Southeast Asia. Our analyses show a high level of genetic diversity in the M. heymonsi group with nine distinct lineages from China, Myanmar, Vietnam, Laos, Malaysia, Thailand, Cambodia, as well as Singapore, and Indonesia. The study also reveals the discovery of two new species in Vietnam, Microhyla hmongorum sp. nov. from Lai Chau Province and Microhyla xodangorum sp. nov. from Kon Tum Province. When comparing the 12S–16S rRNA gene, the genetic divergence between Microhyla xodangorum and other congeners of the Microhyla heymonsi group ranges from 7.5-- to 8.9% (M. cf. heymonsi) and approximately 8.4% between the new species and M. heymonsi s. str. from Taiwan, China. The genetic divergence between Microhyla hmongorum and its congeners ranges from 4.5–5.6% (M. cf. heymonsi) to 8.7% (Microhyla xodangorum). These new findings bring the total number of known species in the genus Microhyla to 48 and the recorded species of Microhyla from Vietnam to 14.
The Cyrtodactylus irregularis group, originally considered to consist of only one taxon, has been split into 26 species. We herein present the distribution of all species within the group in Cambodia, Laos and Vietnam and describe two new species based on integrative analyses. Cyrtodactylus chumuensis sp. nov. is discovered from Dak Lak Province and distinguished from the remaining taxa by more than 11.86% genetic divergence and by the following distinct morphological characters: size medium (SVL 67.5 mm); enlarged femoral scales on each thigh 4–5, femoral pores 0–2 in males; precloacal pores 6–7 in males; ventral scale rows 43–45; lamellae under toe IV 17–21. Cyrtodactylus arndti sp. nov. is described from Binh Dinh Province and genetically differentiated from its congeners by a minimum of 11.42% and by the following characters: adult size medium (SVL 73.4–80.8 mm); enlarged femoral scales on each thigh 5–11; femoral pores 0–2 in males; 6 precloacal pores in males, females with 6 pitted precloacal pores; ventral scale rows 26–38; lamellae under toe IV 17–22; subcaudal scales transversely enlarged. Additionally, we highlight the potential cryptic diversity with the taxon currently regarded as C. pseudoquadrivirgatus and understudied areas in Vietnam where new species will likely be discovered.
Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.