Electro-energetics of Biventricular, Septal and Conduction System Pacing

Abnormal electrical activation of the ventricles creates abnormalities in cardiac mechanics. Local contraction patterns, as reflected by strain, are not only out of phase, but also show opposing length changes in early and late activated regions. Consequently, the efficiency of cardiac pump function (the amount of stroke work generated by a unit of oxygen consumed), is approximately 30% lower in dyssynchronous than in synchronous hearts. Maintaining good cardiac efficiency appears important for long-term outcomes. Biventricular, left ventricular septal, His bundle and left bundle branch pacing may minimise the amount of pacing-induced dyssynchrony and efficiency loss when compared to conventional right ventricular pacing. An extensive animal study indicates maintenance of mechanical synchrony and efficiency during left ventricular septal pacing and data from a few clinical studies support the idea that this is also the case for left bundle branch pacing and His bundle pacing. This review discusses electro-mechanics and mechano-energetics under the various paced conditions and provides suggestions for future research.

Distribution map of peristaltic waves in the chicken embryonic gut reveals importance of ENS and inter-region cross talks along the gut axis

Gut peristaltic movements recognized as the wave-like propagation of a local contraction are crucial for effective transportation and digestion/absorption of ingested materials. Although the physiology of gut peristalsis has been well studied in adults, it remains largely unexplored how the cellular functions underlying these coordinated tissue movements are established along the rostral-caudal gut axis during development. The chicken embryonic gut serves as an excellent experimental model for elucidating the endogenous potential and regulation of these cells since peristalsis occurs even though no ingested material is present in the moving gut. By combining video-recordings and kymography, we provide a spatial map of peristaltic movements along the entire gut posterior to the duodenum: midgut (jejunum and ileum), hindgut, caecum, and cloaca. Since the majority of waves propagate bidirectionally at least until embryonic day 12 (E12), the sites of origin of peristaltic waves (OPWs) can unambiguously be detected in the kymograph. The spatial distribution map of OPWs has revealed that OPWs become progressively confined to specific regions/zones along the gut axis during development by E12, and that such specific zones are largely conserved between different individuals implying genetic regulation for OPW determination. We have also found that the enteric nervous system (ENS) is essential for the OPW patterning since an ablation of ENS or blocking neural activity by tetrodotoxin disrupts the confined pattern of OPWs, resulting in a failure of transportation of inter-luminally injected ink. Finally, we have discovered a functional coupling of the endpoint of hindgut with the cloaca. When surgically separated, the cloaca ceases its acute contractions that would normally occur concomitantly with the peristaltic rhythm of the hindgut. Our findings shed light on the intrinsic regulations of gut peristalsis, including unprecedented ENS contribution and inter-region cross talk along the gut axis.

The Effect of Multisite Phosphorylation on the Conformational Properties of Intrinsically Disordered Proteins

Intrinsically disordered proteins are involved in many biological processes such as signaling, regulation, and recognition. A common strategy to regulate their function is through phosphorylation, as it can induce changes in conformation, dynamics, and interactions with binding partners. Although phosphorylated intrinsically disordered proteins have received increased attention in recent years, a full understanding of the conformational and structural implications of phosphorylation has not yet been achieved. Here, we present all-atom molecular dynamics simulations of five disordered peptides originated from tau, statherin, and β-casein, in both phosphorylated and non-phosphorylated state, to compare changes in global dimensions and structural elements, in an attempt to gain more insight into the controlling factors. The changes are in qualitative agreement with experimental data, and we observe that the net charge is not enough to predict the impact of phosphorylation on the global dimensions. Instead, the distribution of phosphorylated and positively charged residues throughout the sequence has great impact due to the formation of salt bridges. In statherin, a preference for arginine–phosphoserine interaction over arginine–tyrosine accounts for a global expansion, despite a local contraction of the phosphorylated region, which implies that also non-charged residues can influence the effect of phosphorylation.

Functional calculus on non-homogeneous operators on nilpotent groups

We study the functional calculus associated with a hypoelliptic left-invariant differential operator $$\mathcal {L}$$ L on a connected and simply connected nilpotent Lie group G with the aid of the corresponding Rockland operator $$\mathcal {L}_0$$ L 0 on the ‘local’ contraction $$G_0$$ G 0 of G, as well as of the corresponding Rockland operator $$\mathcal {L}_\infty $$ L ∞ on the ‘global’ contraction $$G_\infty $$ G ∞ of G. We provide asymptotic estimates of the Riesz potentials associated with $$\mathcal {L}$$ L at 0 and at $$\infty $$ ∞ , as well as of the kernels associated with functions of $$\mathcal {L}$$ L satisfying Mihlin conditions of every order. We also prove some Mihlin–Hörmander multiplier theorems for $$\mathcal {L}$$ L which generalize analogous results to the non-homogeneous case. Finally, we extend the asymptotic study of the density of the ‘Plancherel measure’ associated with $$\mathcal {L}$$ L from the case of a quasi-homogeneous sub-Laplacian to the case of a quasi-homogeneous sum of even powers.

Dynamic organization of cortical actin filaments during the ooplasmic segregation of ascidian Ciona eggs

Spatial reorganization of cytoplasm in zygotic cells is critically important for establishing the body plans of many animal species. In ascidian zygotes, maternal determinants (mRNAs) are first transported to the vegetal pole a few minutes after the fertilization, and then to the future posterior side of the zygotes in later phase of the cytoplasmic reorganization, before the first cell division. Here, by using a novel fluorescence polarization microscope that reports the position and the orientation of fluorescently labeled proteins in living cells, we mapped the local alignments and the time-dependent changes of cortical actin networks in Ciona eggs. The initial cytoplasmic reorganization started with the contraction of vegetal hemisphere approximately 20 s after the fertilization induced [Ca2+] increase. Timing of the vegetal contraction was consistent with the emergence of highly aligned actin filaments at the cell cortex of vegetal hemisphere which ran perpendicular to the animal-vegetal axis. We propose that the cytoplasmic reorganization is initiated by the local contraction of laterally aligned cortical actomyosin in the vegetal hemisphere, which in turn generates the directional movement of cytoplasm within whole egg. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

Cyclic b -Multiplicative A , B -Hardy–Rogers-Type Local Contraction and Related Results in b -Multiplicative and b -Metric Spaces

The aim of this paper is to define cyclic b -multiplicative Hardy–Rogers-type local contraction in the context of generalized spaces named as b -multiplicative spaces to extend various results of the literature including the main results of Yamaod et al. In this way, we apply a new generalized contractive condition only on a closed set instead of a whole set and by using b -multiplicative space instead of multiplicative metric space. We apply our results to obtain new results in b -metric spaces. Examples are given to show the usability of our results, when others cannot.

Control and mechanisms of pulsatile flows in epithelial monolayers

Epithelial cells flows are observed both in vivo and in vitro and are essential for morphogenesis. Here, we show that pulsatile flows involving local contraction and expansion of a tissue can arise in vitro in an epithelial monolayer of Madine Darby Canine Kidney (MDCK) cells. The strength of pulsation can be modulated through friction heterogeneity by observing the monolayer dynamics on micro-contact printed fibronectin grids with dimensions matching the length-scale of spontaneous oscillations. We also report pulsations by inducing wound closure in domains of similar size with micro-fabricated pillars. In contrast, strongly coherent flows can be induced by adding and washing out acto-myosin cytoskeleton inhibitors. To gain insight into the associated cellular mechanisms, we fluorescently label actin and myosin. We find that lamellipodia align with the direction of the flow, and tissue-scale myosin gradients arise during pulsations in wound-healing experiments. Pulsations and flows are recapitulated in silico by a vertex model with cell motility and polarisation dynamics. The nature of collective movements depends on the interplay between velocity alignment and random diffusion of cell polarisation. When they are comparable, a significant pulsatile flow emerges, whereas the tissue undergoes long-range flows when alignment dominates. We conjecture that the interplay between lamellipodial motile activity and cell polarization, with a possible additional role for tissue-scale myosin gradients, is at the origin of the pulsatile nature of the collective flow. Altogether, our study reveals that monolayer dynamics is dictated by simple rules of interaction at cellular levels which could be involved in morphogenesis.

Base-salt Relief Controls Salt-related Contractional Styles in the Translational Domain of the Outer Kwanza Basin, offshore Angola

<p>Salt-bearing passive margins are typically characterized by thin-skinned, gravity-driven deformation above a salt detachment, resulting in kinematically-linked domains of updip extension and downdip contraction. These domains are commonly connected by a mid-slope translational domain in which salt-related structures accommodate local extensional and contractional strains associated with salt flow across base-salt relief. Despite a general understanding of these salt-tectonic processes and products, little is still known about the detailed geometric and kinematic evolution of mid-slope contractional structures.</p><p>We use a high-quality, depth-migrated three-dimensional seismic reflection dataset located in the mid-slope translational domain of the Outer Kwanza Basin, offshore Angola. We analysed the seismic-stratigraphic architecture of the Aptian salt and its immediate Albian overburden to reveal the distribution of local, salt-related contractional structures above varying geometries of base-salt relief.</p><p>Our analysis reveals two types of salt-related contractional structures, variably distributed in terms of their trend relative to underlying ramps that trend NW or N. The first type is represented by salt-cored anticlines, the limbs of which may be dissected by salt-detached thrusts. The folds trend parallel to the NW- or N-trending ramps, being located either updip or directly above the underlying ramp. These folds increase in amplitude and decrease in wavelength basinward, and are also locally polyharmonic; showing an upwards increase in wavelength, but a decrease in amplitude. The second type of structure is represented by two sub-types of salt walls: (i) reactive salt walls, and (ii) squeezed salt walls. These salt walls trend broadly parallel to, and are located above or downdip of NW-trending, basinward- and landward-facing ramps. The salt-cored anticlines are formed by local contraction associated with salt flow deceleration above ramp-updip. This process of local contraction also locally induces active rise and overburden piercement as salt walls translate over local base-salt structural highs. Still, other salt walls are locally contracted on the basinward-facing ramp during salt flow seaward, resulting in the squeezed salt wall.</p><p>We show that careful seismic-stratigraphic analysis of salt and overburden deformation, in the context of the underlying base-salt geometry, reveals complex patterns of salt structure evolution during seaward translation across the midslope translational domain. The results are applicable along salt-bearing passive margin worldwide and may provide an important insight in identifying potential plays along the midslope translational domain, where major deepwater oilfields reside.</p>