Circadian rhythm of atrioventricular conduction predicts long-term survival in patients with chronic atrial fibrillation

The R-R interval of the electrocardiogram during atrial fibrillation (AF) appears absolutely irregular. However, the Poincaré plot of the R-R interval reveals a sector shape of distribution that is unique to AF. Furthermore, the height of lower envelope (LE1.0) of the distribution and the degree of scatter above the envelope (scattering index) may reflect the refractoriness and concealment of atrioventricular (AV) conduction, respectively. We previously observed that both the LE1.0 and scattering index show clear circadian rhythms in patients with chronic AF and that the rhythms are blunted in those with congestive heart failure and chronic AF. In the present study, we examined if the blunted circadian rhythm of the AV conduction has prognostic value in patients with chronic AF. We studied a retrospective cohort of 120 patients who underwent 24h Holter monitoring at baseline. During an observation period of 33 +/- 16 mon, there were 25 deaths (21%) including 13 cardiac and 8 stroke deaths. All patients showed significant circadian rhythms in both LE1.0 and scattering index with acrophases occurring at night; however, patients dying subsequently from cardiac causes, but not those from fatal stroke were blunted in the circadian rhythms (the amplitudes were < 55% of those in surviving patients). Furthermore, the reduced circadian amplitude of scattering index was an increased risk for cardiac death even after adjustment of coexisting cardiovascular risks [adjusted relative risk (95% confidence interval) per 1-SD decrement, 4.24 (1.54-11.6)]. When patients were divided by the circadian amplitude of the scattering index of 36.5 msec (mean minus 1-SD), the 5yr cardiac mortality below and above the cutoff was 57 and 6%, respectively (log-rank test, p < 0.001). We conclude that the blunted circadian rhythm of AV conduction is an independent risk for cardiac death in patients with chronic AF.     

The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.     

Implications of seasonal variation in nitrate export from forested ecosystems: a review from the hydrological perspective of ecosystem dynamics

In recent decades, the seasonal variation in NO₃ ^? discharge from forest ecosystems has been used increasingly by ecologists and hydrologists as a diagnostic indicator of the nutrient status of ecosystems. Major factors underlying the seasonal patterns of stream NO₃ ^? concentration include seasonal variations in (1) ecosystem nutrient demand, (2) solute transport capability of the hydrological condition, and (3) in-stream nutrient usage and supply. In this article I show how case studies have helped elucidate the dominant controlling factors by comparing data from Japanese catchments with previously compiled data from studies in North America and Europe. Moreover, I explain the different influences that hydrological and biogeochemical controls exert in regions with rainy (Japan) and dry (northeastern United States and Europe) summers. The seasonal variation in hydrological conditions is the predominant controlling factor in Japanese forests, whereas nutrient demand may predominate in the northeastern United States and Europe. I emphasize the importance of comparing seasonal patterns among regions with differing climates to obtain more universal explanations of seasonal variations in NO₃ ^?-related biogeochemical and hydrological dynamics in a forest ecosystem. In addition, multi-scale investigations will be needed to provide insight into the relative contributions of hillslope biogeochemical effects and in-stream biological activities.     

Roosting ecology of endangered plant‐roosting bats on Okinawa Island: Implications for bat‐friendly forestry practices

Roosting information is crucial to guiding bat conservation and bat‐friendly forestry practices. The Ryukyu tube‐nosed bat Murina ryukyuana (Endangered) and Yanbaru whiskered bat Myotis yanbarensis (Critically Endangered) are forest‐dwelling bats endemic to the central Ryukyu Archipelago, Japan. Despite their threatened status, little is known about the roosting ecology of these species and the characteristics of natural maternity roosts are unknown. To inform sustainable forestry practices and conservation management, we radio‐tracked day roosts of both species in the subtropical forests of Okinawa''s Kunigami Village District. We compared roost and roost site characteristics statistically between M. ryukyuana nonmaternity roosts (males or nonreproductive females), maternity roosts, and all M. yanbarensis roosts. Generalized linear models were used to investigate roost site selection by M. ryukyuana irrespective of sex and age class. Lastly, we compiled data on phenology from this and prior studies. Nonreproductive M. ryukyuana roosted alone and primarily in understory foliage. Murina ryukyuana maternity roosts were limited to stands >50 years old, and ~60% were in foliage. Myotis yanbarensis roosted almost entirely in cavities along gulch bottoms and only in stands >70 years old (~1/3 of Kunigami''s total forest area). Murina ryukyuana maternity roosts were higher (4.3 ± 0.6 m) than conspecific nonmaternity roosts (2.3 ± 0.5 m; p < .001) and M. yanbarensis roosts (2.7 ± 0.5 m; not significant). Model results were inconclusive. Both species appear to be obligate plant roosters throughout their life cycle, but the less flexible roosting preferences of M. yanbarensis may explain its striking rarity. To conserve these threatened bats, we recommend the following forestry practices: (a) reduce clearing of understory vegetation, (b) refrain from removing trees along streams, (c) promote greater tree cavity densities by protecting old‐growth forests and retaining snags, and (d) refrain from removing trees or understory between April and July, while bats are pupping.     

A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H

Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-Rβ or Akt, it did inhibit the phosphorylation of Erk1/2 and PLCγ1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G₀/G₁ phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLCγ inhibitor, increased the proportion of cells in the G₀/G₁ phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G₀/G₁ phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation.     

Using food network unfolding to evaluate food–web complexity in terms of biodiversity: theory and applications

Food–web complexity often hinders disentangling functionally relevant aspects of food–web structure and its relationships to biodiversity. Here, we present a theoretical framework to evaluate food–web complexity in terms of biodiversity. Food network unfolding is a theoretical method to transform a complex food web into a linear food chain based on ecosystem processes. Based on this method, we can define three biodiversity indices, horizontal diversity (D_H), vertical diversity (D_V) and range diversity (D_R), which are associated with the species diversity within each trophic level, diversity of trophic levels, and diversity in resource use, respectively. These indices are related to Shannon's diversity index (H′), where H′ = D_H + D_V ? D_R. Application of the framework to three riverine macroinvertebrate communities revealed that D indices, calculated from biomass and stable isotope features, captured well the anthropogenic, seasonal, or other within‐site changes in food–web structures that could not be captured with H′ alone.     

Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3β-dependent and β-catenin-independent mechanism

Both BMPs and Wnts play important roles in the regulation of bone formation. We examined the molecular mechanism regulating cross-talk between BMPs and Wnts in the osteoblastic differentiation of C2C12 cells. Canonical Wnts (Wnt1 and Wnt3a) but not non-canonical Wnts (Wnt5a and Wnt11) synergistically stimulated ALP activity in the presence of BMP-4. Wnt3a and BMP-4 synergistically stimulated the expression of type I collagen and osteonectin. However, Wnt3a did not stimulate ALP activity that was induced by a constitutively active BMP receptor or Smad1. Noggin and Dkk-1 suppressed the synergistic effect of BMP-4 and Wnt3a, but Smad7 did not. Overexpression of β-catenin did not affect BMP-4-induced ALP activity. By contrast, inhibition or stimulation of GSK3β activity resulted in either stimulation or suppression of ALP activity, respectively, in the presence of BMP-4. Taken together, these findings suggest that BMPs and canonical Wnts may regulate osteoblastic differentiation, especially at the early stages, through a GSK3β-dependent but β-catenin-independent mechanism.     

Nematomorph parasites indirectly alter the food web and ecosystem function of streams through behavioural manipulation of their cricket hosts

Nematomorph parasites manipulate crickets to enter streams where the parasites reproduce. These manipulated crickets become a substantial food subsidy for stream fishes. We used a field experiment to investigate how this subsidy affects the stream community and ecosystem function. When crickets were available, predatory fish ate fewer benthic invertebrates. The resulting release of the benthic invertebrate community from fish predation indirectly decreased the biomass of benthic algae and slightly increased leaf break-down rate. This is the first experimental demonstration that host manipulation by a parasite can reorganise a community and alter ecosystem function. Nematomorphs are common, and many other parasites have dramatic effects on host phenotypes, suggesting that similar effects of parasites on ecosystems might be widespread.