Alternative Splicing Diversifies the Transcriptome during Early Photomorphogenesis and Responds to Metabolic Signals in Arabidopsis

Light is an important source of both information and energy for plants. Diurnal rhythms and seasonal changes, as well as surrounding competition are detected by the available light quality and quantity. Sensing changing light conditions to adjust metabolism and control development is cruicial for survival. Here, we analyse transcriptome-wide changes in gene expression and alternative splicing (AS) in dark-grown (etiolated) seedlings as they transition to growth in white, blue, or red light, undergoing photomorphogenesis. We find changes in expression levels for about 20 % of all genes and changes in splicing patterns in hundreds of transcripts. In more than 60 % of the light-regulated splicing events involving an assumed non-coding variant, production of a presumably protein-coding variant is increased in light, while levels of the other variant carrying Nonsense-mediated decay (NMD)-triggering features decline. Following this pattern, AS of the red light signalling component and putative splicing regulator REDUCED RED-LIGHT RESPONSES IN CRY1CRY2 BACKGROUND 1 (RRC1) shifts in favour of the functional variant upon light exposure. While AS of splicing regulator Ser/Arg-rich protein (SR) 30 also favours the protein-coding variant in light, the alternative variant is not degraded by NMD, and we explore potential other biological functions of this AS event. Furthermore, aiming to elucidate upstream signalling components, we find light-dependent AS to be unaffected in the photoreceptor mutant phyA phyB exposed to white light, indicating that photoreceptor signalling only plays a minor role upstream of AS in white light. Interestingly, sucrose supply and light alter the AS output similarly, suggesting that the changes in AS correlate with the plant energy status.Pflanzen nutzen Licht als Energiequelle und Informationsträger um den Tag/Nacht Zyklus, die Jahreszeiten sowie konkurrierende Pflanzen in ihrer unmittelbaren Umgebung zu detektieren. Das Erkennen veränderter Lichtbedingungen ist für Pflanzen essentiell um ihren Metabolismus den äußeren Bedingungen anzupassen und ihre Entwicklungsprozesse zu steuern. In dieser Arbeit haben wir transkriptomweite Änderungen der Genexpression und des Alternativen Spleißens (AS) in dunkel gezogenen (etiolierten) Keimlingen untersucht, die sich unter blauem, rotem oder weißem Licht morphologisch den veränderten Lichtbedingungen anpassen, d. h. den Prozess der Photomorphogenese durchlaufen. Unsere Analyse zeigt, dass sich hierbei die Expressionslevel nahezu 20 % aller Gene, sowie die Spleißmuster hunderter Vorläufer-mRNAs (prä-mRNAs) ändern. Licht führt in mehr als 60 % der lichtregulierten Fälle mit AS zu einer vermutlich nicht-proteinbildenden Spleißvariante zur verstärkten Bildung der wahrscheinlich proteinkodierenden Spleißform. Die Varianten, von denen hierbei im Ausgleich weniger gebildet wird, tragen Merkmale, die voraussichtlich zum Abbau dieser mRNAs durch den RNA-Qualitätskontrollmechanismus Nonsense-mediated decay (NMD) führen. Entsprechend zeigen wir für den mutmaßlichen Spleißfaktor REDUCED RED-LIGHT RESPONSES IN CRY1CRY2 BACKGROUND 1 (RRC1), dessen Rolle in der Lichtsignalgebung in einer früheren Arbeit beschrieben wurde, dass in Licht das AS der prä-mRNA zugunsten der funktionellen Variante verschoben wird. Außerdem untersuchen wir die biologische Funktion des lichtabhängigen AS von dem Spleißfaktor Ser/Arg-rich protein (SR) 30, dessen alternative Variante trotz vorhandener NMD Merkmale nicht durch NMD abgebaut zu werden scheint. Um die für lichtabhängiges AS notwendige Signalgebung besser zu verstehen haben wir Bedeutung von Photorezeptoren in diesem Zusammenhang untersucht. Die Analysen zeigen, dass die Reaktion auf Weißlicht in der Rotlichtrezeptormutante phyA phyB unverändert ist. Dies deutet auf eine untergeordnete Rolle von Photorezeptoren für die Regulation von lichtabhängigem AS hin. Zudem führen interessanterweise die Gabe von Saccharose zu sehr ähnlichen Änderungen im AS wie Licht, was auf eine Kopplung des AS mit dem Energiestatus der Pflanze hinweist

Propensity-Score-Matching Sleeve Gastrektomie vs. Magenbypass nach 3 Jahren

Die Prävalenz der Adipositas ist in den letzten Jahren erheblich gestiegen. Durch zahlreiche Komorbiditäten und Folgeerkrankungen, die damit einhergehen, kommt es zur eingeschränkten Lebensqualität der Betroffenen sowie zu einer gesteigerten Morbidität und Mortalität. Um diesem Problem entgegenzuwirken, haben sich in den letzten Jahren verschiedene chirurgische Therapieverfahren etabliert. Die vorliegende Arbeit vergleicht perioperative Daten von Patienten nach Sleeve Gastrektomie und Magenbypass. Grundlage dafür war die „Qualitätssicherungsstudie für operative Therapie der Adipositas“ aus dem Zeitraum von 2005 bis 2017. Besonderer Fokus lag auf der Morbidität und Mortalität sowie den Komorbiditäten. Neben allgemeinen demografischen Parametern wurden ebenso Komorbiditäten und Komplikationen verglichen. Damit sollte ein Beitrag zur Qualitätssicherung in der Adipositas- und metabolischen Chirurgie geleistet werden. Statistisch signifikante Unterschiede ließen sich bei der BMI-Reduktion und der Komorbidität Reflux feststellen. Keine Unterschiede bestanden bei den Komplikationen

Reading books in the second half of life: What correlations are there with aspects of quality of life and health?

This DZA Aktuell is intended to provide an initial contribution on book reading and possible positive correlations with health-related aspects in the second half of life. In addition to differentiations according to age, gender and educational status, correlations between the volume of reading and emotional well-being (positive affect), subjective health and cognitive performance are presented. Key messages: The average number of books read has remained largely stable over the last 20 years. People between the ages of 46 and 85 read an average of eight to nine books a year between 2008 and 2021, compared to just seven in 2002. Around two-fifths of people in the second half of life are avid readers, reading at least 6 books a year. A good quarter of all respondents, on the other hand, do not read at all. A differentiation by education and gender clearly shows that highly educated people and women are particularly likely to be avid readers. In 2021, around half belonged to the group of avid readers, but also a good quarter of respondents with a low level of education. However, reading has nothing to do with age. All age groups read roughly the same amount. Over 85 per cent of avid readers reported positive feelings. Among non-readers, this proportion was significantly lower at 72 per cent to 79 per cent. Almost two thirds of avid readers rate their health as good or very good. Among non-readers, on the other hand, there are roughly as many people with poor as good subjective health. In the cognition test conducted in 2017, 96 per cent of avid readers scored well. This was only the case for around 89 per cent of non-reader

Bioprospecting the Regional Diversity of Australian Wine Microbiota

Like all plants, grapevines are host to a plethora of microorganisms. During the winemaking process, the microflora of the grape surface can be transferred into the fermentation environment. While the yeast Saccharomyces cerevisiae is the main driver of alcoholic fermentation during wine production, it has become apparent that other grape and cellarderived microbes can have a significant impact on fermentation and the resulting wine. This impact is manifested in the sensorial differences between wines resulting from inoculated fermentations and spontaneous ‘wild’ fermentations and is attributed to the various secondary metabolites and enzymes these microorganisms produce. Carbohydrate active enzymes can affect the composition of grape juice by altering the extractability and organoleptic properties of many wine compounds. Of these enzymes, glycoside hydrolases mediate hydrolysis of glycosides and are found ubiquitously through nature. Micro-organisms, especially those associated with plants, use glycoside hydrolases to afford access to plant resources by degrading the plant cell wall and similarly soil microbes utilise these enzymes during degradation and composting of plant material. During winemaking, glycoside hydrolases have the potential to affect the breakdown of complex sugars in plant cell walls, which can aid in juice extraction and clarification. Glycoside hydrolases can also mediate the release of volatile flavour and aroma compounds from glycosyl-linked, non-volatile precursors. These enzymes therefore represent an attractive target for biotechnological applications. A combination of metagenomics and synthetic biology were used to explore the enzymatic potential of two grapevine derived environments, an Chardonnay grape must (CGM) and a mixed varietal grape marc (MVGM), with the aim of identifying novel enzymes with potential applications as winemaking adjuncts. The CGM was specifically selected as a source of fungal microbiota native to the grapevine, whilst the grape marc was chosen as a source of plant decomposing microorganisms from a glucose-limited environment. Whole genome sequencing and bioinformatic techniques were used to probe the genomic landscape of these two environments, identify enzymes of interest, assess the types of microbiota present in the microbial communities and where possible assemble microbial genomes. The two environments contained very distinct microbial communities. As expected, the Chardonnay must community comprised a high portion of fungal genomes whereas the MVGM was dominated almost exclusively by bacteria. Five candidate polygalacturonases, with potential applications in wine clarification, and seven β-glucosidases, with potential applications in wine aroma and flavour, were chosen for heterologous expression in Pichia pastoris and Saccharomyces cerevisiae. Two of the selected polygalacturonases exhibited significant levels of activity at wine pH and were tested for in-wine activity, using recombinant S. cerevisiae strains in fermentation experiments with synthetic grape must. With future testing in real grape juice, these enzymes and S. cerevisiae strains could be leveraged to improve juice extraction and clarification during winemaking.Thesis (Ph.D.) -- University of Adelaide, School of Biological Sciences, 202

Der Proteinkomplex von NPHP15/CEP164 in humanen Nierenzellen

In dieser Arbeit wurde eine HEK 293T-Zelllinie etabliert, die das NPH-Protein NPHP15 (CEP164) gekoppelt an ein Flag-Tag exprimiert. Mittels Co-Immunpräzipitation und nachfolgender Massenspektrometrie wurde eine Interaktomanalyse von NPHP15 erstellt. Hier zeigten sich 31 signifikant angereicherte Proteine, welche teilweise bekannte Funktionen von NPHP15 stützen. Diese Daten wurden mit Proteomdaten anderer zentrosomaler Proteine sowie proximity labeling Daten anderer NPH-Proteine verglichen

An inconspicuous, conspicuous new species of Asian pipesnake, genus Cylindrophis (Reptilia: Squamata: Cylindrophiidae), from the south coast of Jawa Tengah, Java, Indonesia, and an overview of the tangled taxonomic history of C. ruffus (Laurenti, 1768)

We describe a new species of Cylindrophis currently known only from Grabag, Purworejo Regency, Jawa Tengah Province (Central Java), Java, Indonesia. Cylindrophis subocularis sp. nov. can be distinguished from all congeners by the presence of a single, eponymous subocular scale between the 3rd and 4th or 4th and 5th supralabial, preventing contact between the 4th or 5th supralabial and the orbit, and by having the prefrontal in narrow contact with or separated from the orbit. We preface our description with a detailed account of the tangled taxonomic history of the similar and putatively wide-ranging species C. ruffus, which leads us to (1) remove the name Scytale scheuchzeri from the synonymy of C. ruffus, (2) list the taxon C. rufa var. javanica as species inquirenda, and (3) synonymize C. mirzae with C. ruffus. We provide additional evidence to confirm that the type locality of C. ruffus is Java. Cylindrophis subocularis sp. nov. is the second species of Asian pipesnake from Java

Self-monitoring blood pressure in hypertension, patient and provider perspectives: A systematic review and thematic synthesis.

OBJECTIVE: To systematically review the qualitative evidence for patient and clinician perspectives on self-measurement of blood pressure (SMBP) in the management of hypertension focussing on: how SMBP was discussed in consultations; the motivation for patients to start self-monitoring; how both patients and clinicians used SMBP to promote behaviour change; perceived barriers and facilitators to SMBP use by patients and clinicians. METHODS: Medline, Embase, PsycINFO, Cinahl, Web of Science, SocAbs were searched for empirical qualitative studies that met the review objectives. Reporting of included studies was assessed using the COREQ framework. All relevant data from results/findings sections of included reports were extracted, coded inductively using thematic analysis, and overarching themes across studies were abstracted. RESULTS: Twelve studies were included in the synthesis involving 358 patients and 91 clinicians. Three major themes are presented: interpretation, attribution and action; convenience and reassurance v anxiety and uncertainty; and patient autonomy and empowerment improve patient-clinician alliance. CONCLUSIONS: SMBP was successful facilitating the interaction in consultations about hypertension, bridging a potential gap in the traditional patient-clinician relationship. PRACTICE IMPLICATIONS: Uncertainty could be reduced by providing information specifically about how to interpret SMBP, what variation is acceptable, adjustment for home-clinic difference, and for patients what they should be concerned about and how to act

Bücherlesen in der zweiten Lebenshälfte: Welche Zusammenhänge gibt es mit Aspekten von Lebensqualität und Gesundheit?

Dieses DZA Aktuell liefert einen Beitrag zum Bücherlesen und möglichen positiven Zusammenhängen mit gesundheitsrelevanten Aspekten in der zweiten Lebenshälfte in Deutschland. Neben Differenzierungen nach Alter, Geschlecht und Bildungsstatus, werden Zusammenhänge des Lesevolumens zu emotionalem Wohlbefinden (positiver Affekt), subjektiver Gesundheit und kognitiver Leistung dargestellt. Mit Daten des Deutschen Alterssurveys wurde untersucht, wie viele Bücher die 46- bis 85-Jährigen in den vorangegangenen zwölf Monaten gelesen haben. Es zeigte sich, dass mehr als zwei Fünftel (41,7 Prozent) 6 Bücher und mehr gelesen hatte. Auch konnte festgestellt werden, dass die durchschnittlich gelesene Zahl der Bücher in den letzten 20 Jahren nicht abgenommen hat. Von einer Krise des Lesens kann in dieser Altersgruppe also keine Rede sein. Zudem zeigte sich, dass Menschen, die vergleichsweise viele Bücher gelesen haben, eher von häufigen positiven Emotionen berichteten und ihre Gesundheit besser einschätzten als Menschen, die gar nicht lasen. So gaben fast 86 Prozent der "Viel-Leser*innen" an, häufige positive Gefühle zu erleben und über 63 Prozent in dieser Gruppe schätzten ihre Gesundheit gut oder sehr gut ein. Diese Ergebnisse sind mit Vorsicht zu betrachten, da die Wirkrichtung hier nicht abgebildet werden konnte, das heißt, dass nicht zwingend das Bücherlesen Emotionen und Gesundheitsempfinden positiv beeinflusst, sondern es auch sein könnte, dass Menschen, die sich wohl und gesund fühlen, mehr lesen. Studien aus anderen Ländern legen jedoch nahe, dass das Lesen von Büchern sich sehr wohl positiv auf verschiedene Aspekte eines guten Alterns auswirken kann. Dabei spielt scheinbar das "vertiefte Lesen", auch "Deep Reading" genannt, eine entscheidende Rolle, bei dem sich die/der Leser*in empathisch und emotional auf das Gelesene einlässt - im Gegensatz zu dem oft flüchtigen Lesen in digitalen Medien. Wenn sich der Befund erhärtet, dass das Lesen von Büchern für die Lebensqualität in der zweiten Lebenshälfte förderlich ist, sollte es Interventionen geben, um Lesen auch in dieser Lebensphase besser zu fördern und zu ermöglichen: Durch Aufrechterhaltung bzw. Förderung von Bibliotheksangeboten sowie von Bücherbussen und Onlineangeboten, oder durch Lesepatenschaften, bei denen ältere Menschen Kinder und Jugendliche beim Lesenlernen unterstützen und durch ihr Engagement selbst sozial eingebunden werden

Predictive value of synaptic plasticity for functional decline in patients with multiple sclerosis.

BACKGROUND Previous research suggested that quadripulse (QPS)-induced synaptic plasticity is associated with both cognitive and motor function in patients with multiple sclerosis (MS) and does not appear to be reduced compared to healthy controls (HCs). OBJECTIVE This study aimed to explore the relationship between the degree of QPS-induced plasticity and clinically significant decline in motor and cognitive functions over time. We hypothesized that MS patients experiencing functional decline would exhibit lower levels of baseline plasticity compared to those without decline. METHODS QPS-induced plasticity was evaluated in 80 MS patients (56 with relapsing-remitting MS and 24 with progressive MS), and 69 age-, sex-, and education-matched HCs. Cognitive and motor functions, as well as overall disability status were evaluated annually over a median follow-up period of 2 years. Clinically meaningful change thresholds were predefined for each outcome measure. Linear mixed-effects models, Cox proportional hazard models, logistic regression, and receiver-operating characteristic analysis were applied to analyse the relationship between baseline plasticity and clinical progression in the symbol digit modalities test, brief visuospatial memory test revised (BVMT-R), nine-hole peg test (NHPT), timed 25-foot walk test, and expanded disability status scale. RESULTS Overall, the patient cohort showed no clinically relevant change in any functional outcome over time. Variability in performance was observed across time points in both patients and HCs. MS patients who experienced clinically relevant decline in manual dexterity and/or visuospatial learning and memory had significantly lower levels of synaptic plasticity at baseline compared to those without such decline (NHPT: β = -0.25, p = 0.02; BVMT-R: β = -0.50, p = 0.005). Receiver-operating characteristic analysis underscored the predictive utility of baseline synaptic plasticity in discerning between patients experiencing functional decline and those maintaining stability only for visuospatial learning and memory (area under the curve = 0.85). CONCLUSION Our study suggests that QPS-induced plasticity could be linked to clinically relevant functional decline in patients with MS. However, to solidify these findings, longer follow-up periods are warranted, especially in cohorts with higher prevalences of functional decline. Additionally, the variability in cognitive performance in both patients with MS and HCs underscores the importance of conducting further research on reliable change based on neuropsychological tests