Anatomical Architectures Research Articles

Recent Advances of Emerging Spleen-Targeting Nanovaccines for Immunotherapy.

Vaccines provide a powerful tool to modulate the immune system for human disease prevention and treatment. Classical vaccines mainly initiate immune responses in the lymph nodes (LNs) after subcutaneous injection. However, some vaccines suffer from inefficient delivery of antigens to LNs, undesired inflammation, and slow immune induction when encountering the rapid proliferation of tumors. Alternatively, the spleen, as the largest secondary lymphoid organ with a high density of antigen-presenting cells (APCs) and lymphocytes, acts as an emerging target organ for vaccinations in the body. Upon intravenous administration, the rationally designed spleen-targeting nanovaccines can be internalized by the APCs in the spleen to induce selective antigen presentation to T and B cells in their specific sub-regions, thereby rapidly boosting durable cellular and humoral immunity. Herein, the recent advances of spleen-targeting nanovaccines for immunotherapy based on the anatomical architectures and functional zones of the spleen, as well as their limitations and perspectives for clinical applications are systematically summarized. The aim is to emphasize the design of innovative nanovaccines for enhanced immunotherapy of intractable diseases in the future.

Engineering Tridimensional Hydrogel Tissue and Organ Phantoms with Tunable Springiness

AbstractBiomimicking organ phantoms with vivid biological structures and soft and slippery features are essential for in vitro biomedical applications yet remain hither to unmet challenges in their fabrication such as balancing between spatial structural complexity and matchable mechanical properties. Herein, 3D printable tissue‐mimicking elastomeric double network hydrogels with tailorable stiffness are evolved to idiosyncratically match diverse biological soft tissues by regulating the compositions of hydrogel matrix and the density of metal coordination bonds. Relying on digital light processing 3D printing, various mechanically tunable biomimetic volumetric hydrogel organ constructs with structural complexity and fidelity, including kidney, brain, heart, liver, stomach, lung, trachea, intestine, and even the intricate vascularized tissues, are fabricated faultlessly. Proof‐of‐concept 3D printed hydrogel heart and liver phantoms provide sophisticated internal channels and cavity structures and external realistic anatomical architectures that more closely mimic native organs. For the in vitro application demonstration, a 3D printed hydrogel brain phantom with tortuous cerebral arteries and slippery characters serves as an effective neurosurgical training platform for realistic simulation of endovascular interventions. This platform offers a means to construct mechanically precisely tunable hydrogel‐based biomimetic organ phantoms that are expected to be used in surgical training, medical device testing, and organs‐on‐chips.

Ideas from Actions, Alternative Anatomical Architectures

In this curation of his work, performance artist Stelarc, explains the process of extending his body and his self while exploring movement, sound, and autonomy.

Phloem wedges in Malpighiaceae: origin, structure, diversification, and systematic relevance

BackgroundPhloem wedges furrowing the wood are one of the most notorious, widespread types of cambial variants in Angiosperms. Many lianas in Malpighiaceae show these variations in the arrangement of the secondary tissues. Here we explore their ontogeny, structure, and evolution in Malpighiaceae, where phloem wedges appeared multiple times, showing how they have contributed to the anatomical diversification of the family. Using a broad sampling with 143 species from 50 genera, covering all major lineages in Malpighiaceae, we crossed data from ontogeny, stem anatomy, and phylogenetic comparative methods to determine ontogenetic trajectories, final anatomical architectures, and evolution within the most recent phylogeny for the family.ResultsPhloem wedges appeared exclusively in lianas and disappeared in shrub lineages nested within liana lineages. At the onset of development, the vascular cambium is regular, producing secondary tissues homogeneously across its girth, but soon, portions of the cambium in between the leaf insertions switch their activity producing less wood and more phloem, initially generating phloem arcs, which progress into phloem wedges. In the formation of these wedges, two ontogenetic trajectories were found, one that maintains the continuity of the cambium, and another where the cambium gets dissected. Phloem wedges frequently remain as the main cambial variant in several lineages, while in others there are additional steps toward more complex cambial variants, such as fissured stems, or included phloem wedges, the latter a novel type of interxylary phloem first described for the family.ConclusionsPhloem wedges evolved exclusively in lianas, with two different ontogenies explaining the 10 independent origins of phloem wedges in Malpighiaceae. The presence of phloem wedges has favored the evolution of even more complex cambial variants such as fissured stems and interxylary phloem.

Interspecific anatomical differences result in similar highly flexible stems in Bignoniaceae lianas.

Lianas are intriguing forest components in the tropics worldwide. They are characterized by thin and flexible stems, which have been related to a unique stem anatomy. Here, we hypothesized that the anatomical diversity of lianas, varying in shapes, proportions, and dimensions of tissues and cell types, would result in different stem bending stiffnesses across species. To test this hypothesis, we chose four abundant liana species of central Amazonia belonging to the monophyletic tribe Bignonieae (Bignoniaceae) and compared their basal stems for their anatomical architectures and bending properties. Measurements of anatomical architecture and bending stiffness (structural Young's modulus) included light microscopy observations and three-point bending tests, which were performed on basal stems of eight individuals from four Bignonieae species. All analyses, including comparisons among species and relationships between stem stiffness and anatomical architecture, were performed using linear models. Although the anatomical architecture of each species consists of different qualitative and quantitative combinations of both tissues and cell types in basal stems, all species analyzed showed similarly lower bending stiffnesses. This similarity was shown to be directly related to high bark contribution to the second moment of area, vessel area and ray width. Similar values of stem bending stiffness were encountered in four liana species analyzed despite their variable anatomical architectures. This pattern provides new evidence of how different quantitative combinations of tissue and cell types in the basal stems of lianas can generate similarly low levels of stiffness in a group of closely related species.

The Anatomy of Inference: Generative Models and Brain Structure.

To infer the causes of its sensations, the brain must call on a generative (predictive) model. This necessitates passing local messages between populations of neurons to update beliefs about hidden variables in the world beyond its sensory samples. It also entails inferences about how we will act. Active inference is a principled framework that frames perception and action as approximate Bayesian inference. This has been successful in accounting for a wide range of physiological and behavioral phenomena. Recently, a process theory has emerged that attempts to relate inferences to their neurobiological substrates. In this paper, we review and develop the anatomical aspects of this process theory. We argue that the form of the generative models required for inference constrains the way in which brain regions connect to one another. Specifically, neuronal populations representing beliefs about a variable must receive input from populations representing the Markov blanket of that variable. We illustrate this idea in four different domains: perception, planning, attention, and movement. In doing so, we attempt to show how appealing to generative models enables us to account for anatomical brain architectures. Ultimately, committing to an anatomical theory of inference ensures we can form empirical hypotheses that can be tested using neuroimaging, neuropsychological, and electrophysiological experiments.

The anatomical scaffold underlying the functional centrality of known cortical hubs.

Cortical hubs play a fundamental role in the functional architecture of brain connectivity at rest. However, the anatomical scaffold underlying their centrality is still under debate. Certainly, the brain function and anatomy are significantly entwined through synaptogenesis and pruning mechanisms that continuously reshape structural and functional connections. Thus, if hubs are expected to exhibit a large number of direct anatomical connections with the rest of the brain, such a dense wiring is extremely inefficient in energetic terms. In this work, we investigate these aspects on fMRI and DTI data from a set of know resting-state networks, starting from the hypothesis that to promote integration, functional, and anatomical connections link different areas at different scales or hierarchies. Thus, we focused on the role of functional hubs in this hierarchical organization of functional and anatomical architectures. We found that these regions, from a structural point of view, are first linked to each other and successively to the rest of the brain. Thus, functionally central nodes seem to show few strong anatomical connections. These findings suggest an efficient strategy of the investigated cortical hubs in exploiting few direct anatomical connections to link functional hubs among each other that eventually reach the rest of the considered nodes through local indirect tracts. Hum Brain Mapp 38:5141-5160, 2017. © 2017 Wiley Periodicals, Inc.

From single cells and single columns to cortical networks: dendritic excitability, coincidence detection and synaptic transmission in brain slices and brains.

Although patch pipettes were initially designed to record extracellularly the elementary current events from muscle and neuron membranes, the whole‐cell and loose cell‐attached recording configurations proved to be useful tools for examination of signalling within and between nerve cells. In this Paton Prize Lecture, I will initially summarize work on electrical signalling within single neurons, describing communication between the dendritic compartments, soma and nerve terminals via forward‐ and backward‐propagating action potentials. The newly discovered dendritic excitability endows neurons with the capacity for coincidence detection of spatially separated subthreshold inputs. When these are occurring during a time window of tens of milliseconds, this information is broadcast to other cells by the initiation of bursts of action potentials (AP bursts). The occurrence of AP bursts critically impacts signalling between neurons that are controlled by target‐cell‐specific transmitter release mechanisms at downstream synapses even in different terminals of the same neuron. This can, in turn, induce mechanisms that underly synaptic plasticity when AP bursts occur within a short time window, both presynaptically in terminals and postsynaptically in dendrites. A fundamental question that arises from these findings is: ‘what are the possible functions of active dendritic excitability with respect to network dynamics in the intact cortex of behaving animals?’ To answer this question, I highlight in this review the functional and anatomical architectures of an average cortical column in the vibrissal (whisker) field of the somatosensory cortex (vS1), with an emphasis on the functions of layer 5 thick‐tufted cells (L5tt) embedded in this structure. Sensory‐evoked synaptic and action potential responses of these major cortical output neurons are compared with responses in the afferent pathway, viz. the neurons in primary somatosensory thalamus and in one of their efferent targets, the secondary somatosensory thalamus. Coincidence‐detection mechanisms appear to be implemented in vivo as judged from the occurrence of AP bursts. Three‐dimensional reconstructions of anatomical projections suggest that inputs of several combinations of thalamocortical projections and intra‐ and transcolumnar connections, specifically those from infragranular layers, could trigger active dendritic mechanisms that generate AP bursts. Finally, recordings from target cells of a column reveal the importance of AP bursts for signal transfer to these cells. The observations lead to the hypothesis that in vS1 cortex, the sensory afferent sensory code is transformed, at least in part, from a rate to an interval (burst) code that broadcasts the occurrence of whisker touch to different targets of L5tt cells. In addition, the occurrence of pre‐ and postsynaptic AP bursts may, in the long run, alter touch representation in cortex.

FIBER DIRECTION ESTIMATION, SMOOTHING AND TRACKING IN DIFFUSION MRI.

Diffusion magnetic resonance imaging is an imaging technology designed to probe anatomical architectures of biological samples in an in vivo and noninvasive manner through measuring water diffusion. The contribution of this paper is threefold. First, it proposes a new method to identify and estimate multiple diffusion directions within a voxel through a new and identifiable parametrization of the widely used multi-tensor model. Unlike many existing methods, this method focuses on the estimation of diffusion directions rather than the diffusion tensors. Second, this paper proposes a novel direction smoothing method which greatly improves direction estimation in regions with crossing fibers. This smoothing method is shown to have excellent theoretical and empirical properties. Last, this paper develops a fiber tracking algorithm that can handle multiple directions within a voxel. The overall methodology is illustrated with simulated data and a data set collected for the study of Alzheimer's disease by the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Healthy brain connectivity predicts atrophy progression in non-fluent variant of primary progressive aphasia.

Neurodegeneration has been hypothesized to follow predetermined large-scale networks through the trans-synaptic spread of toxic proteins from a syndrome-specific epicentre. To date, no longitudinal neuroimaging study has tested this hypothesis in vivo in frontotemporal dementia spectrum disorders. The aim of this study was to demonstrate that longitudinal progression of atrophy in non-fluent/agrammatic variant primary progressive aphasia spreads over time from a syndrome-specific epicentre to additional regions, based on their connectivity to the epicentre in healthy control subjects. The syndrome-specific epicentre of the non-fluent/agrammatic variant of primary progressive aphasia was derived in a group of 10 mildly affected patients (clinical dementia rating equal to 0) using voxel-based morphometry. From this region, the inferior frontal gyrus (pars opercularis), we derived functional and structural connectivity maps in healthy controls (n = 30) using functional magnetic resonance imaging at rest and diffusion-weighted imaging tractography. Graph theory analysis was applied to derive functional network features. Atrophy progression was calculated using voxel-based morphometry longitudinal analysis on 34 non-fluent/agrammatic patients. Correlation analyses were performed to compare volume changes in patients with connectivity measures of the healthy functional and structural speech/language network. The default mode network was used as a control network. From the epicentre, the healthy functional connectivity network included the left supplementary motor area and the prefrontal, inferior parietal and temporal regions, which were connected through the aslant, superior longitudinal and arcuate fasciculi. Longitudinal grey and white matter changes were found in the left language-related regions and in the right inferior frontal gyrus. Functional connectivity strength in the healthy speech/language network, but not in the default network, correlated with longitudinal grey matter changes in the non-fluent/agrammatic variant of primary progressive aphasia. Graph theoretical analysis of the speech/language network showed that regions with shorter functional paths to the epicentre exhibited greater longitudinal atrophy. The network contained three modules, including a left inferior frontal gyrus/supplementary motor area, which was most strongly connected with the epicentre. The aslant tract was the white matter pathway connecting these two regions and showed the most significant correlation between fractional anisotropy and white matter longitudinal atrophy changes. This study showed that the pattern of longitudinal atrophy progression in the non-fluent/agrammatic variant of primary progressive aphasia relates to the strength of connectivity in pre-determined functional and structural large-scale speech production networks. These findings support the hypothesis that the spread of neurodegeneration occurs by following specific anatomical and functional neuronal network architectures.

Persistence of chicken anemia virus antigen and inclusions in spontaneous cases of Marek’s disease visceral lymphomas in broiler chickens at slaughterhouses

The chicken anemia virus (CAV) and Marek’s disease virus (MDV) infect chickens worldwide; a single or dual infection by these viruses has a great impact on poultry production. In the present study, we examined the existence of CAV antigen and its inclusions in Marek’s disease (MD) lymphomas in chickens in the slaughterhouses of Iwate prefecture, Japan. Forty-nine spleens and 13 livers with different degrees of nodular lesions were histopathologically examined at our laboratory. Grossly, the tested organs showed various sizes and anatomical architectures. Based on the cellular morphology and the infiltrative nature of the neoplastic lymphocytes, MD was confirmed in 76% (37/49) of the spleens and 92% (12/13) of the livers. The lesions of MD, according to the pattern of lymphocytic accumulation in the affected organs, were divided into multifocal, coalesced and diffuse. CAV intranuclear inclusion bodies were detected within the small and the large bizarre lymphocytes of the MD lymphomas in 2 livers and 9 spleens, and the immunostaining test for CAV confirmed the persistence of CAV antigens and inclusions in the neoplastic cells. This study demonstrated the persistence of CAV infection within the neoplastic cells of naturally occurring MD lymphomas in chickens.

LCP distal ulna hook plate as alternative fixation for fifth metatarsal base fracture

Intramedullary screw fixation is the most common treatment for fifth metatarsal base fractures. Screw application does not achieve accurate reduction in fracture with small fragments, osteoporotic bone, or Lawrence zone 1 fractures, however. On the basis of similar anatomical architectures between the distal ulna and the fifth metatarsal base, the purpose of this study was to assess the results of a locking compression plate (LCP) distal ulna hook plate in stabilizing displaced zone 1 or 2 fifth metatarsal base fractures. Nineteen patients with Lawrence zone 1 (n=12) or 2 (n=7) fractures of the fifth metatarsal base were treated surgically with an LCP distal ulna hook plate. The patients were evaluated clinically and radiographically, and functional outcomes were graded by using the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot scoring system. Radiographic bony union was obtained in all patients, at an average of 7.4weeks. The mean AOFAS midfoot score improved from 26 (range, 0-45) preoperatively to 94 (range, 72-100) points at the final follow-up. There were three patients with post-traumatic cubometatarsal arthrosis and one patient with sural nerve neuropraxia. In our experience, the distal ulna hook plate achieves a high rate of bony consolidation and anatomically suitable fixation in zone 1 or 2 fifth metatarsal base fractures. We also suggest that the LCP distal ulna hook plate should be considered as an alternative treatment in multifragmentary, osteoporotic, and tuberosity avulsion (zone 1) fifth metatarsal base fractures.

Bioprinting Endothelial Cells With Alginate for 3D Tissue Constructs

Advanced solid freeform fabrication (SFF) techniques have been an interest for constructing tissue engineered polymeric scaffolds because of its repeatability and capability of high accuracy in fabrication resolution at the scaffold macro- and microscales. Among many important scaffold applications, hydrogel scaffolds have been utilized in tissue engineering as a technique to confide the desired proliferation of seeded cells in vitro and in vivo into its architecturally porous three-dimensional structures. Such fabrication techniques not only enable the reconstruction of scaffolds with accurate anatomical architectures but also enable the ability to incorporate bioactive species such as growth factors, proteins, and living cells. This paper presents a bioprinting system designed for the freeform fabrication of porous alginate scaffolds with encapsulated endothelial cells. The bioprinting fabrication system includes a multinozzle deposition system that utilizes SFF techniques and a computer-aided modeling system capable of creating heterogeneous tissue scaffolds. The manufacturing process is biologically compatible and is capable of functioning at room temperature and relatively low pressures to reduce the fluidic shear forces that could deteriorate biologically active species. The deposition system resolution is 10 microm in the three orthogonal directions XYZ and has minimum velocity of 100 microm/s. The ideal concentrations of sodium alginate and calcium chloride were investigated to determine a viable bioprinting process. The results indicated that the suitable fabrication parameters were 1.5% (w/v) sodium alginate and 0.5% (w/v) calcium chloride. Degradation studies via mechanical testing showed a decrease in the elastic modulus by 35% after 3 weeks. Cell viability studies were conducted on the cell encapsulated scaffolds for validating the bioprinting process and determining cell viability of 83%. This work exhibits the potential use of accurate cell placement for engineering complex tissue regeneration using computer-aided design systems.