Pelagic seabirds reduce risk by flying into the eye of the storm.

Cyclones can cause mass mortality of seabirds, sometimes wrecking thousands of individuals. The few studies to track pelagic seabirds during cyclones show they tend to circumnavigate the strongest winds. We tracked adult shearwaters in the Sea of Japan over 11 y and found that the response to cyclones varied according to the wind speed and direction. In strong winds, birds that were sandwiched between the storm and mainland Japan flew away from land and toward the eye of the storm, flying within ≤30 km of the eye and tracking it for up to 8 h. This exposed shearwaters to some of the highest wind speeds near the eye wall (≤21 m s-1) but enabled them to avoid strong onshore winds in the storm's wake. Extreme winds may therefore become a threat when an inability to compensate for drift could lead to forced landings and collisions. Birds may need to know where land is in order to avoid it. This provides additional selective pressure for a map sense and could explain why juvenile shearwaters, which lack a map sense, instead navigating using a compass heading, are susceptible to being wrecked. We suggest that the ability to respond to storms is influenced by both flight and navigational capacities. This may become increasingly pertinent due to changes in extreme weather patterns.

Functional Cooperation of α-Synuclein and Tau Is Essential for Proper Corticogenesis.

Alpha-synuclein (αSyn) and tau are abundant multifunctional neuronal proteins, and their intracellular deposits have been linked to many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Despite the disease relevance, their physiological roles remain elusive, as mice with knock-out of either of these genes do not exhibit overt phenotypes. To reveal functional cooperation, we generated αSyn-/-tau-/- double-knock-out mice and characterized the functional cross talk between these proteins during brain development. Intriguingly, deletion of αSyn and tau reduced Notch signaling and accelerated interkinetic nuclear migration of G2 phase at early embryonic stage. This significantly altered the balance between the proliferative and neurogenic divisions of progenitor cells, resulting in an overproduction of early born neurons and enhanced neurogenesis, by which the brain size was enlarged during the embryonic stage in both sexes. On the other hand, a reduction in the number of neural progenitor cells in the middle stage of corticogenesis diminished subsequent gliogenesis in the αSyn-/-tau-/- cortex. Additionally, the expansion and maturation of macroglial cells (astrocytes and oligodendrocytes) were suppressed in the αSyn-/-tau-/- postnatal brain, which in turn reduced the male αSyn-/-tau-/- brain size and cortical thickness to less than the control values. Our study identifies important functional cooperation of αSyn and tau during corticogenesis.SIGNIFICANCE STATEMENT Correct understanding of the physiological functions of αSyn and tau in CNS is critical to elucidate pathogenesis involved in the etiology of neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. We show here that αSyn and tau are cooperatively involved in brain development via maintenance of progenitor cells. αSyn and tau double-knock-out mice exhibited an overproduction of early born neurons and accelerated neurogenesis at early corticogenesis. Furthermore, loss of αSyn and tau also perturbed gliogenesis at later embryonic stage, as well as the subsequent glial expansion and maturation at postnatal brain. Our findings provide new mechanistic insights and extend therapeutic opportunities for neurodegenerative diseases caused by aberrant αSyn and tau.

Core-Shell-Corona Micelles from a Polyether-Based Triblock Terpolymer: Investigation of the pH-Dependent Micellar Structure.

Core-shell-corona micelles featuring a pH-responsive shell have been characterized in dilute aqueous solution at different pH values (4-8) by using dynamic light scattering (DLS), field-flow fractionation coupled with multiangle light scattering detector (FFF-MALS), steady-state fluorescence, small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). The micelles are formed by self-assembly of a polyether-based triblock terpolymer consisting of a hydrophobic poly( tert-butyl glycidyl ether) block (P tBGE), a pH-responsive modified poly(allyl glycidyl ether) segment (PAGECOOH), and a neutral hydrophilic poly(ethylene oxide) block (PEO). Because of the side-chain carboxylic acids in the middle block, the micellar structure and size depends on the solution pH. Hereby, we show that an increase in pH induces a decrease in the aggregation number ( Nagg). In addition, the combination of the above measurements revealed an unexpected morphological change from spherical to ellipsoidal micelles by increasing pH.

Motor Nerve Arborization Requires Proteolytic Domain of Damage-Induced Neuronal Endopeptidase (DINE) during Development.

UNLABELLED: Damage-induced neuronal endopeptidase (DINE)/endothelin-converting enzyme-like 1 (ECEL1) is a membrane-bound metalloprotease, which we originally identified as a nerve regeneration-associated molecule. Abundant expression of DINE is observed in regenerating neurons, as well as in developing spinal motor neurons. In line with this, DINE-deficient (DINE KO) embryos fail to arborize phrenic motor nerves in the diaphragm and to form proper neuromuscular junctions (NMJ), which lead to death shortly after birth. However, it is unclear whether protease activity of DINE is involved in motor nerve terminal arborization and how DINE participates in the process. To address these issues, we performed an in vivo rescue experiment in which three types of motor-neuron specific DINE transgenic mice were crossed with DINE KO mice. The DINE KO mice, which overexpressed wild-type DINE in motor neurons, succeeded in rescuing the aberrant nerve terminal arborization and lethality after birth, while those overexpressing two types of protease domain-mutated DINE failed. Further histochemical analysis showed abnormal behavior of immature Schwann cells along the DINE-deficient axons. Coculture experiments of motor neurons and Schwann cells ensured that the protease domain of neuronal DINE was required for proper alignment of immature Schwann cells along the axon. These findings suggest that protease activity of DINE is crucial for intramuscular innervation of motor nerves and subsequent NMJ formation, as well as proper control of interactions between axons and immature Schwann cells. SIGNIFICANCE STATEMENT: Damage-induced neuronal endopeptidase (DINE) is a membrane-bound metalloprotease; expression is abundant in developing spinal motor neurons, as well as in nerve-injured neurons. DINE-deficient (KO) embryos fail to arborize phrenic motor nerves in the diaphragm and to form a neuromuscular junction, leading to death immediately after birth. To address whether proteolytic activity of DINE is involved in this process, we performed in vivo rescue experiments with DINE KO mice. Transgenic rescue of DINE KO mice was accomplished by overexpression of wild-type DINE, but not by protease domain-mutated DINE. Immature Schwann cells were abnormally aligned along the DINE protease-deficient axons. Thus, the protease activity of DINE is crucial for motor axon arborization, as well as the interaction between axons and immature Schwann cells.

Self-Assembly of Calix[4]arene-Based Amphiphiles Bearing Polyethylene Glycols: Another Example of "Platonic Micelles".

The aggregation number of classical micelles exhibits a certain distribution, which is a recognizable feature of conventional micelles. However, we recently identified perfectly monodisperse calix[4]arene-based micelles whose aggregation numbers agree with the vertex numbers of regular polyhedra, that is, Platonic solids, and thus they are named "Platonic micelles". Regarding our hypothesis of the formation mechanism of Platonic micelles, both repulsive interactions including steric hindrance and electrostatic repulsions among the headgroups are important for determining their aggregation number; however, neither of these is necessarily needed to consider. In this study, we employed polyethylene glycols (PEGs) as the nonionic headgroup of calix[4]arene-based amphiphiles to study the effects of only repulsive interactions caused by steric hindrance on the formation of Platonic micelles. The amphiphiles containing relatively low-molecular-weight PEGs (550 or 1000 g mol-1) form dodecamer or octamer micelles, respectively, with no variation in the aggregation number. However, relatively high-molecular-weight PEGs (2000 g mol-1) produce polydispersed micelles with a range of aggregation number. PEG 2000 exhibits a greater affinity for water than PEG 550 and 1000, resulting in fewer hydrophobic interactions in micelle formation, as indicated by the drastic increase of the critical micelle concentration (CMC) value in the PEG 2000 system. The instability of the structure of PEG2kCaL5 micelles might contribute to the higher mobility of PEG in the micellar shell, resulting in a non-Platonic aggregation number with polydispersity.

Monitoring the Discontinuous Dodecamer-Icosamer Transition of a Calix[4]arene-Derived Surfactant by Time-Resolved Small-Angle X-ray Scattering.

Calix[4]arene-derived surfactants form monodisperse micelles with a well-defined aggregation number (Nagg ) of 4, 6, 8, 12, or 20, corresponding to the Platonic solids. This feature is in strong contrast to conventional micelles. In this study, a transition from a dodecamer (Nagg =12) to an icosamer (Nagg =20) was induced by a rapid increase in the NaCl concentration (CNaCl ) using a stopped-flow device and directly observed by time-resolved small-angle X-ray scattering. The Nagg remained unchanged during the first 60 s after the increase in CNaCl , and then abruptly increased to 20. This feature resembles phase transitions in supersaturated or supercooled states, or highly cooperative phenomena. We surmise that this finding may be due to the fact that only a few Nagg values are thermodynamically allowed when Nagg is sufficiently small. This is the first observation of such an induction time in micellar aggregation.

N-terminal cleaved pancreatitis-associated protein-III (PAP-III) serves as a scaffold for neurites and promotes neurite outgrowth.

Pancreatitis-associated protein (PAP)-III, also known as regenerating gene/regenerating islet-derived (Reg)-IIIγ, is a small secretory protein whose expression is substantially induced in injured nerves. Here, we found that PAP-III protein underwent proteolytic N-terminal processing by trypsin-like protease(s) in injured sciatic nerves after axotomy. In vitro studies demonstrated that the N terminus-truncated PAP-III (ΔN-PAP-III) polymerized into a filament with a relatively uniform diameter of 10-20 nm, and the filaments formed higher order structures in a Na(+) concentration-dependent manner. When the ΔN-PAP-III fibers were added to the culture media, the ΔN-PAP-III fibers were tightly attached to neurites and somata of primary cortical neurons in vitro. In contrast, little association with glial cells was observed. When dense matrices of ΔN-PAP-III fibers were sheeted on a culture dish, neurites preferentially adhered to the fibers, and neurite extension was enhanced. This neurite outgrowth activity was significantly suppressed by preincubation with antibodies against PAP-III. These results imply that the released PAP-III might be cleaved and forms ΔN-PAP-III fibers at the nerve injury sites. Consequently, these resulting fibers would provide regenerating axons with a platform for extension.

Head direction cells in a migratory bird prefer north.

Animals exhibit remarkable navigation abilities as if they have an internal compass. Head direction (HD) cells encoding the animal's heading azimuth are found in the brain of several animal species; the HD cell signals are dependent on the vestibular nuclei, where magnetic responsive cells are present in birds. However, it is difficult to determine whether HD cell signals drive the compass orientation in animals, as they do not necessarily rely on the magnetic compass under all circumstances. Recording of HD cell activities from the medial pallium of shearwater chicks (Calonectris leucomelas) just before their first migration, during which they strongly rely on compass orientation, revealed that shearwater HD cells prefer a north orientation. The preference remained stable regardless of geolocations and environmental cues, suggesting the existence of a magnetic compass regulated by internally generated HD signals. Our findings provide insight into the integration of the direction and magnetoreception senses.

DOPAnization of tyrosine in α-synuclein by tyrosine hydroxylase leads to the formation of oligomers.

Parkinson's disease is a progressive neurodegenerative disorder characterized by the preferential loss of tyrosine hydroxylase (TH)-expressing dopaminergic neurons in the substantia nigra. Although the abnormal accumulation and aggregation of α-synuclein have been implicated in the pathogenesis of Parkinson's disease, the underlying mechanisms remain largely elusive. Here, we found that TH converts Tyr136 in α-synuclein into dihydroxyphenylalanine (DOPA; Y136DOPA) through mass spectrometric analysis. Y136DOPA modification was clearly detected by a specific antibody in the dopaminergic neurons of α-synuclein-overexpressing mice as well as human α-synucleinopathies. Furthermore, dopanized α-synuclein tended to form oligomers rather than large fibril aggregates and significantly enhanced neurotoxicity. Our findings suggest that the dopanization of α-synuclein by TH may contribute to oligomer and/or seed formation causing neurodegeneration with the potential to shed light on the pathogenesis of Parkinson's disease.

Continuous stress-induced dopamine dysregulation augments PAP-I and PAP-II expression in melanotrophs of the pituitary gland.

Under continuous stress (CS) in rats, melanotrophs, the predominant cell-type in the intermediate lobe (IL) of the pituitary, are hyperactivated to secrete α-melanocyte-stimulating hormone and thereafter degenerate. Although these phenomena are drastic, the molecular mechanisms underlying the cellular changes are mostly unknown. In this study, we focused on the pancreatitis-associated protein (PAP) family members of the secretory lectins and characterized their expression in the IL of CS model rats because we had identified two members of this family as up-regulated genes in our previous microarray analysis. RT-PCR and histological studies demonstrated that prominent PAP-I and PAP-II expression was induced in melanotrophs in the early stages of CS, while another family member, PAP-III, was not expressed. We further examined the regulatory mechanisms of PAP-I and PAP-II expression and revealed that both were induced by the decreased dopamine levels in the IL under CS. Because the PAP family members are implicated in cell survival and proliferation, PAP-I and PAP-II secreted from melanotrophs may function to sustain homeostasis of the IL under CS conditions in an autocrine or a paracrine manner.

Correction: Damage-induced neuronal endopeptidase (DINE) enhances axonal regeneration potential of retinal ganglion cells after optic nerve injury.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Machine learning enables improved runtime and precision for bio-loggers on seabirds.

Unravelling the secrets of wild animals is one of the biggest challenges in ecology, with bio-logging (i.e., the use of animal-borne loggers or bio-loggers) playing a pivotal role in tackling this challenge. Bio-logging allows us to observe many aspects of animals' lives, including their behaviours, physiology, social interactions, and external environment. However, bio-loggers have short runtimes when collecting data from resource-intensive (high-cost) sensors. This study proposes using AI on board video-loggers in order to use low-cost sensors (e.g., accelerometers) to automatically detect and record complex target behaviours that are of interest, reserving their devices' limited resources for just those moments. We demonstrate our method on bio-loggers attached to seabirds including gulls and shearwaters, where it captured target videos with 15 times the precision of a baseline periodic-sampling method. Our work will provide motivation for more widespread adoption of AI in bio-loggers, helping us to shed light onto until now hidden aspects of animals' lives.

Deep learning-assisted comparative analysis of animal trajectories with DeepHL.

A comparative analysis of animal behavior (e.g., male vs. female groups) has been widely used to elucidate behavior specific to one group since pre-Darwinian times. However, big data generated by new sensing technologies, e.g., GPS, makes it difficult for them to contrast group differences manually. This study introduces DeepHL, a deep learning-assisted platform for the comparative analysis of animal movement data, i.e., trajectories. This software uses a deep neural network based on an attention mechanism to automatically detect segments in trajectories that are characteristic of one group. It then highlights these segments in visualized trajectories, enabling biologists to focus on these segments, and helps them reveal the underlying meaning of the highlighted segments to facilitate formulating new hypotheses. We tested the platform on a variety of trajectories of worms, insects, mice, bears, and seabirds across a scale from millimeters to hundreds of kilometers, revealing new movement features of these animals.

Publisher Correction: Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Damage-induced neuronal endopeptidase (DINE) enhances axonal regeneration potential of retinal ganglion cells after optic nerve injury.

Damage-induced neuronal endopeptidase (DINE)/endothelin-converting enzyme-like 1 (ECEL1) is a membrane-bound metalloprotease that we identified as a nerve regeneration-associated molecule. The expression of DINE is upregulated in response to nerve injury in both the peripheral and central nervous systems, while its transcription is regulated by the activating transcription factor 3 (ATF3), a potent hub-transcription factor for nerve regeneration. Despite its unique hallmark of injury-induced upregulation, the physiological relevance of DINE in injured neurons has been unclear. In this study, we have demonstrated that the expression of DINE is upregulated in injured retinal ganglion cells (RGCs) in a coordinated manner with that of ATF3 after optic nerve injury, whereas DINE and ATF3 are not observed in any normal retinal cells. Recently, we have generated a mature DINE-deficient (KOTg) mouse, in which exogenous DINE is overexpressed specifically in embryonic motor neurons to avoid aberrant arborization of motor nerves and lethality after birth that occurs in the conventional DINE KO mouse. The DINE KOTg mice did not show any difference in retinal structure and the projection to brain from that of wild-type (wild type) mice under normal conditions. However, injured RGCs of DINE KOTg mice failed to regenerate even after the zymosan treatment, which is a well-known regeneration-promoting reagent. Furthermore, a DINE KOTg mouse crossed with a Atf3:BAC Tg mouse, in which green fluorescent protein (GFP) is visualized specifically in injured RGCs and optic nerves, has verified that DINE deficiency leads to regeneration failure. These findings suggest that injury-induced DINE is a crucial endopeptidase for injured RGCs to promote axonal regeneration after optic nerve injury. Thus, a DINE-mediated proteolytic mechanism would provide us with a new therapeutic strategy for nerve regeneration.

Compass orientation drives naïve pelagic seabirds to cross mountain ranges.

Wildlife migration is a spectacular phenomenon [1]. Studies using telemetry - tracking devices attached on free-living animals - have shown that large topographic barriers and obstacles, such as oceans and deserts, elicit extreme feats of migration [2]. Overcoming the challenges of these obstacles might require experience and skill that young individuals lack [2-5]. Further, younger, inexperienced animals might determine their migration routes using navigation strategies different from those of older animals [6-9], but our knowledge of how orientation mechanisms and experience drive migration strategy is limited. We have studied how experienced (adults) and inexperienced (first-time migrating fledglings) streaked shearwaters (Calonectris leucomelas) approach the challenge of migration using animal-borne tracking devices. The study birds migrate from a colony on the north of a large topographic barrier, Honshu Island, Japan. Shearwaters use a wind- and wave-based flight pattern-dynamic soaring-to extract energy for highly efficient travel over oceans [10]. We therefore expected that shearwaters migrating southward from the colony would make substantial detours to avoid any landmasses. We found that migrating adults followed one of two paths that detour around landmasses that hinder direct southerly migration. In contrast, inexperienced fledglings followed a straight course in a south-oriented direction that forced them to complete a trans-mountain journey, suggesting that the birds rely on an innate compass. Thus, we suggest that fledglings would eventually override the simple compass navigation, which appears to be the primary driver for their extreme migration, before being able to interact appropriately with the marine environment.

Platonic Micelles: Monodisperse Micelles with Discrete Aggregation Numbers Corresponding to Regular Polyhedra.

The concept of micelles was first proposed in 1913 by McBain and has rationalized numerous experimental results of the self-aggregation of surfactants. It is generally agreed that the aggregation number (Nagg) for spherical micelles has no exact value and a certain distribution. However, our studies of calix[4]arene surfactants showed that they were monodisperse with a defined Nagg whose values are chosen from 6, 8, 12, 20, and 32. Interestingly, some of these numbers coincide with the face numbers of Platonic solids, thus we named them "Platonic micelles". The preferred Nagg values were explained in relation to the mathematical Tammes problem: how to obtain the best coverage of a sphere surface with multiple identical circles. The coverage ratio D(N) can be calculated and produces maxima at N = 6, 12, 20, and 32, coinciding with the observed Nagg values. We presume that this "Platonic nature" may hold for any spherical micelles when Nagg is sufficiently small.

Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport.

Although α-synuclein (αSyn) has been linked to Parkinson's disease (PD), the mechanisms underlying the causative role in PD remain unclear. We previously proposed a model for a transportable microtubule (tMT), in which dynein is anchored to a short tMT by LIS1 followed by the kinesin-dependent anterograde transport; however the mechanisms that produce tMTs have not been determined. Our in vitro investigations of microtubule (MT) dynamics revealed that αSyn facilitates the formation of short MTs and preferentially binds to MTs carrying 14 protofilaments (pfs). Live-cell imaging showed that αSyn co-transported with dynein and mobile ßIII-tubulin fragments in the anterograde transport. Furthermore, bi-directional axonal transports are severely affected in αSyn and γSyn depleted dorsal root ganglion neurons. SR-PALM analyses further revealed the fibrous co-localization of αSyn, dynein and ßIII-tubulin in axons. More importantly, 14-pfs MTs have been found in rat femoral nerve tissue, and they increased approximately 19 fold the control in quantify upon nerve ligation, indicating the unconventional MTs are mobile. Our findings indicate that αSyn facilitates to form short, mobile tMTs that play an important role in the axonal transport. This unexpected and intriguing discovery related to axonal transport provides new insight on the pathogenesis of PD.

Expression analysis of the regenerating gene (Reg) family members Reg-IIIß and Reg-IIIγ in the mouse during development.

The regenerating gene/regenerating islet-derived (Reg) family is a group of small secretory proteins. Within this family, Reg type-III (Reg-III) consists of: Reg-IIIα, -ß, -γ, and -δ. To elucidate the physiological relevance of Reg-III, we examined the localization and ontogeny of Reg-IIIß and Reg-IIIγ in mice at different time points spanning from embryonic day 13.5 to 7 weeks old, using in situ hybridization and immunohistochemistry. Our results showed that Reg-IIIß was expressed in specific subsets of primary sensory neurons and motor neurons, and that expression was transient during the embryonic and perinatal periods. Reg-IIIß expression was also observed in absorptive epithelial cells of the intestine. In contrast, Reg-IIIγ expression was mainly observed in epithelial cells of the airways and intestine, but not in the nervous system, and expression levels showed a gradually increasing pattern along with development. In the airways Reg-IIIγ was expressed in goblet and Clara-like cells, whereas in the intestine Reg-IIIγ was expressed in the absorptive epithelial cells and Paneth cells, and was found to be expressed in development before these organs had been exposed to the outside world. The present findings imply that Reg-IIIß and Reg-IIIγ expression is regulated along divergent pathways. Furthermore, we also suggest that expression of Reg-IIIγ in the airway and intestinal epithelia may occur to protect these organs from exposure to antigens or other factors (e.g., microbes) in the outer world, whereas the transient expression of Reg-IIIß in the nervous system may be associated with the development of the peripheral nervous system including such processes as myelination.