Crystal nucleation and growth of spherulites demonstrated by coral skeletons and phase-field simulations

Spherulites are radial distributions of acicular crystals, common in biogenic, geologic, and synthetic systems, yet exactly how spherulitic crystals nucleate and grow is still poorly understood. To investigate these processes in more detail, we chose scleractinian corals as a model system, because they are well known to form their skeletons from aragonite (CaCO3) spherulites, and because a comparative study of crystal structures across coral species has not been performed previously. We observed that all 12 diverse coral species analyzed here exhibit plumose spherulites in their skeletons, with well-defined centers of calcification (CoCs), and crystalline fibers radiating from them. In 7 of the 12 species, we observed a skeletal structural motif not observed previously: randomly oriented, equant crystals, which we termed “sprinkles”. In Acropora pharaonis, these sprinkles are localized at the CoCs, while in 6 other species, sprinkles are either layered at the growth front (GF) of the spherulites, or randomly distributed. At the nano- and micro-scale, coral skeletons fill space as much as single crystals of aragonite. Based on these observations, we tentatively propose a spherulite formation mechanism in which growth front nucleation (GFN) of randomly oriented sprinkles, competition for space, and coarsening produce spherulites, rather than the previously assumed slightly misoriented nucleations termed “non-crystallographic branching”. Phase-field simulations support this mechanism, and, using a minimal set of thermodynamic parameters, are able to reproduce all of the microstructural variation observed experimentally in all of the investigated coral skeletons. Beyond coral skeletons, other spherulitic systems, from aspirin to semicrystalline polymers and chocolate, may also form according to the mechanism for spherulite formation proposed here. Statement of Significance: Understanding the fundamental mechanisms of spherulite nucleation and growth has broad ranging applications in the fields of metallurgy, polymers, food science, and pharmaceutical production. Using the skeletons of reef-building corals as a model system for investigating these processes, we propose a new spherulite growth mechanism that can not only explain the micro-structural diversity observed in distantly related coral species, but may point to a universal growth mechanism in a wide range of biologically and technologically relevant spherulitic materials systems

CMV Immunoglobulins for the Treatment of CMV Infections in Thoracic Transplant Recipients

Intravenous ganciclovir and, increasingly, oral valganciclovir are now considered the mainstay of treatment for cytomegalovirus (CMV) infection or CMV disease. Under certain circumstances, CMV immunoglobulin (CMVIG) may be an appropriate addition or, indeed, alternative. Data on monotherapy with CMVIG are limited, but encouraging, for example in cases of ganciclovir intolerance. In cases of recurrent CMV in thoracic transplant patients after a disease- and drug-free period, adjunctive CMVIG can be considered in patients with hypogammaglobulinemia. Antiviral-resistant CMV, which is more common among thoracic organ recipients than in other types of transplant, can be an indication for introduction of CMVIG, particularly in view of the toxicity associated with other options, such as foscarnet. Due to a lack of controlled trials, decision-making is based on clinical experience. In the absence of a robust evidence base, it seems reasonable to consider the use of CMVIG to treat CMV in adult or pediatric thoracic transplant patients with ganciclovir-resistant infection, or in serious or complicated cases. The latter can potentially include (i) treatment of severe clinical manifestations, such as pneumonitis or eye complications; (ii) patients with a positive biopsy in end organs, such as the lung or stomach; (iii) symptomatic cases with rising polymerase chain reaction values (for example, higher than 5.0 log10) despite antiviral treatment; (iv) CMV disease or CMV infection or risk factors, such as CMV-IgG-negative serostatus; (vi) ganciclovir intolerance; (vii) patients with hypogammaglobulinemia

Precise Doppler shift compensation in the hipposiderid bat, Hipposideros armiger

Abstract Bats of the Rhinolophidae and Hipposideridae families, and Pteronotus parnellii, compensate for Doppler shifts generated by their own flight movement. They adjust their call frequency such that the frequency of echoes coming from ahead fall in a specialized frequency range of the hearing system, the auditory fovea, to evaluate amplitude and frequency modulations in echoes from fluttering prey. Some studies in hipposiderids have suggested a less sophisticated or incomplete Doppler shift compensation. To investigate the precision of Doppler shift compensation in Hipposideros armiger, we recorded the echolocation and flight behaviour of bats flying to a grid, reconstructed the flight path, measured the flight speed, calculated the echo frequency, and compared it with the resting frequency prior to each flight. Within each flight, the average echo frequency was kept constant with a standard deviation of 110 Hz, independent of the flight speed. The resting and reference frequency were coupled with an offset of 80 Hz; however, they varied slightly from flight to flight. The precision of Doppler shift compensation and the offset were similar to that seen in Rhinolophidae and P. parnellii. The described frequency variations may explain why it has been assumed that Doppler shift compensation in hipposiderids is incomplete

The resting frequency of echolocation signals changes with body temperature in the hipposiderid bat Hipposideros armiger

Doppler shift (DS) compensating bats adjust in flight the second harmonic of the constant-frequency component (CF(2)) of their echolocation signals so that the frequency of the Doppler-shifted echoes returning from ahead is kept constant with high precision (0.1–0.2%) at the so-called reference frequency (f(ref)). This feedback adjustment is mediated by an audio–vocal control system that correlates with a maximal activation of the foveal resonance area in the cochlea. Stationary bats adjust the average CF(2) with similar precision at the resting frequency (f(rest)), which is slightly below the f(ref). Over a range of time periods (from minutes up to years), variations of the coupled f(ref) and f(rest) have been observed, and were attributed to age, social influences and behavioural situations in rhinolophids and hipposiderids, and to body temperature effects and flight activity in Pteronotus parnellii. We assume that, for all DS-compensating bats, a change in body temperature has a strong effect on the activation state of the foveal resonance area in the cochlea, which leads to a concomitant change in emission frequency. We tested our hypothesis in a hipposiderid bat, Hipposideros armiger, and measured how the circadian variation of body temperature at activation phases affected f(rest). With a miniature temperature logger, we recorded the skin temperature on the back of the bats simultaneously with echolocation signals produced. During warm-up from torpor, strong temperature increases were accompanied by an increase in f(rest), of up to 1.44 kHz. We discuss the implications of our results for the organization and function of the audio–vocal control systems of all DS-compensating bats