Genetic burden of TNNI3K in diagnostic testing of patients with dilated cardiomyopathy and supraventricular arrhythmias

BACKGROUND:Genetic variants in TNNI3K (troponin-I interacting kinase) have previously been associated with dilated cardiomyopathy (DCM), cardiac conduction disease, and supraventricular tachycardias. However, the link between TNNI3K variants and these cardiac phenotypes shows a lack of consensus concerning phenotype and protein function. METHODS:We describe a systematic retrospective study of a cohort of patients undergoing genetic testing for cardiac arrhythmias and cardiomyopathy including TNNI3K. We further performed burden testing of TNNI3K in the UK Biobank. For 2 novel TNNI3K variants, we tested cosegregation. TNNI3K kinase function was estimated by TNNI3K autophosphorylation assays. RESULTS:We demonstrate enrichment of rare coding TNNI3K variants in DCM patients in the Amsterdam cohort. In the UK Biobank, we observed an association between TNNI3K missense (but not loss-of-function) variants and DCM and atrial fibrillation. Furthermore, we demonstrate genetic segregation for 2 rare variants, TNNI3K-p.Ile512Thr and TNNI3K-p.His592Tyr, with phenotypes consisting of DCM, cardiac conduction disease, and supraventricular tachycardia, together with increased autophosphorylation. In contrast, TNNI3K-p.Arg556_Asn590del, a likely benign variant, demonstrated depleted autophosphorylation. CONCLUSIONS:Our findings demonstrate an increased burden of rare coding TNNI3K variants in cardiac patients with DCM. Furthermore, we present 2 novel likely pathogenic TNNI3K variants with increased autophosphorylation, suggesting that enhanced autophosphorylation is likely to drive pathogenicity.Genetics of disease, diagnosis and treatmen

Silvicultural planning in spruce mire forests by the means of the BDq method

This paper addresses problems associated with the silvicultural planning in the Norway spruce mire forests (Sphagno girgensohnii−Piceetum Polak. 1962) that are characterized by an uneven−aged structure and a high degree of irregularity at small scale. Based on detailed inventory using 30 permanent circular sample plots in two control units located in the Augustów Forest (NE Poland), the BDq method was employed for determining future silvicultural activities of the current forest management cycle. The equilibrium models are based on diameter distributions and have the following parameters, depending on site conditions: B=28 m²/ha; q−factor=1.32 and D=51 cm in the case of poorer forest site type (S.−P. typicum) and 55 cm more fertile one (S.−P. thelypteridetosum)

Structure and dynamics of uneven−aged Scots pine−dominated old−growth stands in Kaliszki and Sieraków strict protection areas in the Kampinos National Park. Part 1. Species composition, tree density and basal area

The paper describes changes, which took place over the last 30 years in old−growth forest stands occupying two permanent research plots, established in the Kaliszki and Sieraków strict protection areas in the Kampinos National Park (central Poland). Both plots have a form of ecological transects. The Kaliszki plot is 20 m wide and 700 m long (1.40 ha), while the Sieraków plot (total area of 2.56 ha) consists of two parts: main (40×460 m) and side (40×180 m) transect. In the Kaliszki plot, the stand measurements were conducted in 1993, 2007, and 2017, while in the Sieraków plot – in 1989, 1994, 2006, and 2017. For every tree with breast height diameter (DBH) 5 cm, species identity, DBH and spatial coordinates were determined. Starting from the second census, all trees which had died (‘losses’), as well as trees which exceeded the DBH threshold (‘gains’) since the previous record were noted, as well. The major tree species occurring on sample plots are Scots pine (Pinus sylvestris), pedunculate oak (Quercus robur), silver and downy birch (Betula sp.), and black alder (Alnus glutinosa). During the study period, the overall tree density declined by ca. 50%. The diminishing trends occurred for all dominant tree species. In contrast to major, dominant tree species, the demographic status of a group of minor tree species (lime, hornbeam and maple) was much more stable. One may even speak about some expansion in this case. Particularly, hornbeam density increased rapidly in the period 2006−2017 in some areas of the main transect located in the Sieraków plot. The future studies will show if this tendency will be maintained and will include other regions of sample plots. Assuming a lack of significant disturbances, one may expect that the stands growing on research plots will rather slowly change in the nearest future. Most dynamics will have a quantitative and not qualitative character. One may anticipate, for example, a growing role of pedunculate oak at the expense of Scots pine, however, considering that the two species are rather long−living, they will probably for a long time keep their dominant roles in the stand canopies

Structure and dynamics of uneven−aged, Scots pine−dominated, old−growth stands in Kaliszki and Sieraków strict reserves in Kampinos National Park. Part 2. Tree mortality and recruitment processes and their effects on tree diameter distributions

Two fundamental demographic processes (tree recruitment and mortality) are analyzed for forest stands growing on permanent study plots located in strictly protected Scots pine−dominated, old−growth stands of Kampinos National Park (central Poland). The major implications of the observed demographic trends for the general shape of tree size distributions are determined, as well. During the past ca 30 years, in the stands sampled, there was a pronounced lack of balance between mortality and recruitment processes. Mortality rate was eight times higher than recruitment rate. Eventually, there was a net significant decline in population density, observed for all major tree species, including Scots pine, pedunculate oak, silver and downy birch, and black alder. As mortality processes affected mainly smaller trees, there was also a significant deterioration of the general demographic status of most important tree species. This effect was shown by the change of the overall shape of diameter distributions over the study period: from reverse J−shaped to flat curves running nearly parallel to X−axis. The values of recruitment rates were markedly lower, and the values of mortality rates – significantly higher, than analogous values characterizing comparable forests (e.g., those obtained for the natural stands of Białowieża National Park). Low recruitment rates, as obtained for Kampinos stands, suggest that presently, in the local, Scots pine−dominated, old−growth stands, the general conditions for forest regeneration and for maintaining a long−term demographic stability are unfavorable. Most probably, the regeneration of this type of forest has an episodic, ‘wave−like’ character and corresponds to the ‘catastrophic’ model, according to which the successful regeneration of current dominants (especially Scots pine, silver and downy birch, black alder) must be preceded by a stand−initiating (stand−replacing) disturbance, leading to total or partial, but heavy, destruction of the currently existing stand. At the moment, it would be difficult to predict, however, if and when such a disturbance will affect the stands under investigation. Thus, we predict that in the nearest future at least, the state of overall demographic unbalance will continue or even increase