Dorsal Section Research Articles

Endoscopic evaluation of the feline tympanic bulla is feasible for detection of epithelial remnants following ventral bulla osteotomy in a cadaveric model.

To evaluate endoscopy for detection of epithelial remnants within the feline tympanic bulla following ventral bulla osteotomy (VBO) and to report the most likely locations within the bulla for epithelial remnants to occur. This was a single-center experimental cadaveric study. 10 VBO procedures were performed by 5 board-certified surgeons in 5 feline cadavers. Following completion, a 1.9-mm, 30° rigid endoscope was inserted into the rostral, caudal, dorsal, lateral, and medial section, and images were acquired. A blinded observer evaluated the endoscopic images for epithelial remnants, and the percentage of the section containing epithelial remnants was measured. The mean and SD of distribution of epithelial remnants were calculated for each section. Remnant epithelium was noted in at least 1 section in each cadaver. The dorsal section was the most common to have epithelial remnants identified (10 of 10), whereas the lateral (5 of 10) and medial (5 of 10) were the least common. The lateral section contained the most epithelial remnants (6.9 ± 11.42%), whereas the caudal section contained the least (1.2 ± 1.42%). The use of a 1.9-mm, 30° endoscope was feasible for evaluation and identification of epithelial remnants in a feline tympanic bulla following VBO. Epithelial remnants were consistently identified in all sections with endoscopic assistance. Endoscopy following completion of a VBO may be considered to ensure complete removal of epithelium.

Description of six new species forming the sumbana species group of the genus Nemophora Hoffmannsegg (Lepidoptera, Adelidae) from the Lesser Sunda Islands in Indonesia.

In this study six new species of the genus Nemophora Hoffmannsegg, 1798, are described from the Lesser Sunda Islands (Bali, Sumbawa, Sumba, and Timor) in Indonesia. These species (N. sumbana Kozlov, sp. nov., N. timorella Kozlov, sp. nov., N. umbronitidella Kozlov, sp. nov., N. wegneri Kozlov, sp. nov., N. longipeniculella Kozlov, sp. nov., and N. brevipeniculella Kozlov, sp. nov.) constitute a monophyletic group, characterized by a Λ-shaped yellow marking on the forewing, with the dorsal section of the distal leg of this marking extending along the outer wing margin.

The role of carcass processing (hot vs. cold boning) on pork belly morphological and mechanical characteristics

This study assessed the effect of boning processing method (hot vs. cold) on pork belly morphological and mechanical traits and the evolution of these traits during refrigerated storage postmortem (PM). A total of 14 crossbred pigs were slaughtered and their carcasses and bellies processed under two conditions: hot boning (n = 14, right sides of carcasses cut immediately after slaughter) and cold boning (n = 14, left sides of carcasses cut 24 h PM). Morphological and mechanical evaluations were made at 1-, 5-, 24- and 48-h PM on the hot-boned bellies, and at 24 and 48 h on the cold-boned ones. Compared to the cold-boned bellies, the hot-boned ones were shorter, wider and thicker (P < 0.01), with greater firmness (flop distance and angle) (P < 0.001) and cohesiveness (skin-fat separation) (P < 0.05 in the dorsal and central sections). At 48 h PM, hot-boned bellies had a thicker skin (P < 0.001) and softer subcutaneous fat in the dorsal-cranial and central sections (finger scores and compression textural test) (P < 0.05). Morphological and mechanical traits for hot-boned bellies confirmed an intense shortening and hardening (increased firmness and cohesiveness), and a slight yield loss from 1 to 24 h PM. From 24 to 48 h PM, there was a certain flattening in hot-boned bellies that was associated with a slight softening (reduced firmness). Although a larger sample may be needed to corroborate these findings, they demonstrate the impact of carcass processing method and refrigerated storage time on belly quality. This may be useful for the pork industry for obtaining the desired type of belly.

Determination of Morphometric Characteristics of Glandula Lacrimalis in Siirt-Colored Mohair Goat (Capra hircus) and Romanov Sheep (Ovis aries) by Computed Tomography Images

This study was carried out to determine the morphometric characteristics of the glandula lacrimalis in Siirt-colored Mohair goats and Romanov sheep using computed tomography (CT) images and to analyze the differences between sexes and species. CT images of the glandula lacrimalis of ten male and ten female Siirt-colored Mohair goats and ten male and ten female Romanov sheep were used in the study. Morphometric measurements were taken from transversal, sagittal and dorsal sections of the right and left glandula lacrimalis in both male and female animals. Morphometric values were statistically analyzed. As a result of the study, there was no sex-related difference in morphometric measurement parameters in the Romanov sheep breed. In Siirt-colored mohair goats, statistical differences were observed in terms of TY and DU values depending on sex. Statistical similarities and differences were determined between the two species in terms of morphometric parameters. In conclusion, statistical differences in the measurement parameters of glandula lacrimalis of adult Siirt-colored Mohair goats and Romanov sheep between sexes and species were determined using computed tomography images.

New localities and sexual dichromatism in Blue-green eyed Spotted Cuscus Spilocuscus wilsoni Helgen et Flannery, 2004 (Mammalia: Marsupialia: Phalangeridae) from Biak Island, Indonesia

Spotted cuscuses are medium-sized tree-dwelling mammals native to tropical forests of Australo-Papua that primarily feed on fruits and leaves. They belong to the phalangerid genus Spilocuscus (Gray, 1862). The difference in pelage color between male and female Spilocuscus wilsoni has not yet been well described morphologically. In the present study, we describe the coat color of four S. wilsoni individuals: a male adult, a sub-adult male, a sub-adult female, and a juvenile female. Dorsal, lateral, and ventral body section images were captured on camera, and body weight &amp; length, tail &amp; ear length were measured. The adult male S. wilsoni had brown spot and blotch patterns on the dorsal and lateral regions, and the ventral region was plain beige. The sub-adult male had distinct spot patterns without blotches on the dorsal and lateral regions, while the ventral region was plain with a cream base color. The sub-adult female had a mottled pattern that blended with the base color, making a silvery appearance. The female juvenile was spotless throughout, with a foundation hue ranging from creamy to somewhat yellow.

Diagnostic strategies for Sparicotyle chrysophrii detection based on size-variability and site-location

Routine monitoring of monogenean loads is a crucial step for infection management in aquaculture facilities. This analysis is usually performed from partial gill analyses and thus, knowledge of parasite distribution and size can be helpful to optimise diagnosis, estimate infection levels and improve management procedures. Gill location preferences and intraspecific size variations relative to parasite age, host factors and parasite abundance are herein determined for the monogenean Sparicotyle chrysophrii, one of the most challenging pathogens in gilthead sea bream aquaculture. Present findings on parasite location show that the life-history stages of S. chrysophrii have distinct location preferences. Analysis of intraspecific size variations of adult stages of S. chrysophrii revealed that the size of most morphological features of S. chrysophrii increased significantly with parasite age and host size. Positive and significant relationships between the size of the posteriormost clamp and host size pointed out the adaptation of the parasite to the gilthead sea bream size from the initial settlement. Host size also seems to restrict the development of parasites after maturity as the oldest specimens were exclusively found in mid-large fish (>18 cm). By contrast, no clear patterns were observed for the relationship between parasite size and location or abundance. Post-maturity size variations of S. chrysophrii should be considered for parasite identification and the clamp pair number should be fixed for accurate taxonomic diagnosis. Based on the site location of S. chrysophrii, the dorsal sections or the outermost holobranches would be suitable for adult detection while the analysis of the central and dorsal sections of the outermost holobranches may be a better option for finding most of the adult, juvenile or post-larval stages.

Ultra Sonographic Study of Kidney Changes Following Experimental Cryogenic Partial Nephrectomy in a Rabbit Model

Background and Objective: Treatment of some limited kidney neoplasms is a partial kidney resection called a partial nephrectomy. One of the concerns in partial nephrectomy is severe and uncontrolled hemorrhage that sometimes results in kidney removal. Cryosurgery is one of the less invasive methods for the management of small kidney lesions, during which the controlled freezing of unwanted tissues will eventually lead to necrosis and gradual destruction of the lesion.The advantages of the cryosurgery method are easy implementation, no thermal ischemia damage during the operation, and no need to cut and suture the kidney parenchyma. Materials and Methods: In this experimental intervention research, the caudal pole of the left kidney of 9 adult female rabbits was subjected to cryogenic partial nephrectomy through a lateral laparotomy. Rabbits were evaluated by ultrasound on 1, 3, 7, 14, 21, and 28 days after surgery to record and observe the extent of kidney damage and healing in the Sagittal and Dorsal sections. Several parameters, such as kidney length dimensions, size of the caudal cortex, and cranial cortex of the kidney, were measured and recorded. Results: Kidney length on days 1, 21, and 28 was significantly less than day 0. On the 7th day after surgery, 2 separate areas, damaged and frozen necrotic tissue (caudal cortex) and healthy and normal kidney tissue were visible. The size of the caudal cortex from day 14 onwards was significantly less than day 0. The process of significant changes in the caudal cortex of the kidney started from day 14 of surgery and the border between dead and living tissue (Line of Demarcation) was distinguishable as a transition zone. On the 21st day after surgery, both the length of the kidney and the caudal cortex decreased significantly compared to day 0. Gradual loss of the caudal pole of the kidney (caudal cortex, the place where cryosurgery was performed directly) showed the applicability of cryosurgery in surgeries during which the tumor was removed (tumor ablation). On the 28th day after surgery, due to gradual necrosis and the loss of the caudal pole of the kidney, the kidney looked like a bitten apple, and the results of changes in the dimensions of the kidney (caudal cortex and length of the kidney) indicated necrosis of the caudal pole of the kidney, which finally led to the shrinking of the kidney. Conclusion: Ultrasonographic study of kidney injury and healing showed that cryosurgery, in addition to tumor ablation, would also have the ability to remove peripheral tissues (partial nephrectomy).

Human umbilical cord mesenchymal stem cell treatment alleviates symptoms in an atopic dermatitis-like mouse model

BackgroundAtopic dermatitis (AD) is one of the most common immune and inflammatory skin disorders, leading to insufferable itching and skin abnormalities that seriously affect life quality of patients. There are still huge unmet needs for long-term and effective disease control, despite currently available therapies. Evidenced by some preclinical and clinical studies of AD treatment with stem cells, stem cell treatment could significantly and effectively ameliorate AD symptoms.ObjectivesTo elucidate underlying mechanisms of how stem cells therapy alleviates AD-like symptoms.MethodsAn AD-like mouse model was constructed and treated with mesenchymal stem cells (MSCs) subcutaneously or subcutaneously combined with intravenously. The differentially expressed genes were sorted out from RNA sequencing results of dorsal skin and blood.ResultsTwo injection routes of MSCs could alleviate AD-like symptoms and pathologic changes of the skin and immune organs. RNA sequencing of dorsal skin sections and blood provided gene expression signatures for amelioration of skin defects, inflammatory and immune modulation by MSCs, as well as common AD molecular markers for the skin and blood, which may benefit for clinical diagnosis. IL-1β and its signaling pathway were specifically found to be associated with the development of AD-like dermatitis lesions. MSC treatment effectively inhibited the JAK-STAT pathway and receptors of IL-4, IL-13, IL-17, and IgE.ConclusionsMSC therapy could regulate abnormal immune and inflammatory status in AD. Mechanistic exploration will contribute to the development of personalized AD treatment based on MSCs.

Fibromyalgia patients with elevated levels of anti-satellite glia cell immunoglobulin G antibodies present with more severe symptoms.

Transferring fibromyalgia patient immunoglobulin G (IgG) to mice induces pain-like behaviour, and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. However, it is unknown how frequently fibromyalgia patients have anti-SGC antibodies and how anti-SGC antibodies associate with disease severity. Here, we quantified serum or plasma anti-SGC IgG levels in 2 fibromyalgia cohorts from Sweden and Canada using an indirect immunofluorescence murine cell culture assay. Fibromyalgia serum IgG binding to human SGCs in human dorsal root ganglia tissue sections was also assessed by immunofluorescence. In the cell culture assay, anti-SGC IgG levels were increased in both fibromyalgia cohorts compared with control group. Elevated anti-SGC IgG was associated with higher levels of self-reported pain in both cohorts, and higher fibromyalgia impact questionnaire scores and increased pressure sensitivity in the Swedish cohort. Anti-SGC IgG levels were not associated with fibromyalgia duration. Swedish fibromyalgia (FM) patients were clustered into FM-severe and FM-mild groups, and the FM-severe group had elevated anti-SGC IgG compared with the FM-mild group and control group. Anti-SGC IgG levels detected in culture positively correlated with increased binding to human SGCs. Moreover, the FM-severe group had elevated IgG binding to human SGCs compared with the FM-mild and control groups. These results demonstrate that a subset of fibromyalgia patients have elevated levels of anti-SGC antibodies, and the antibodies are associated with more severe fibromyalgia symptoms. Screening fibromyalgia patients for anti-SGC antibodies could provide a path to personalized treatment options that target autoantibodies and autoantibody production.

A new perspective on the corneo‐scleral junction with three types of microscopy techniques

The conjunctions of the cornea and sclera in the eyes of donkeys, cattle, dogs, sheep, pigs and rabbits, regardless of gender, were examined in this study. No animals were specifically sacrificed for this investigation. Scanning electron microscopy, light microscopy, and dissecting microscopy were used in this research. In the limbus of all the animals investigated, the cornea and sclera fused in accordance with a pattern. At the corneo-scleral junction, the sclera was situated anteriorly and the cornea posteriorly in the dorsal and ventral sections of the bulbus oculi. In the medial and lateral parts of the eyeball, the cornea and sclera were facing each other and interlaced. Pigmentation and the sulcus scleralis externus could be used to identify the macro-and micro-anatomical boundaries of the limbus. In addition, the cytoplasm of basal epithelial cells shrank, signaling the end of the corneal epithelium and the start of the conjunctival epithelium. The presence of Bowman's membrane in cattle and sheep eyes was definitely determined in histological examinations. Bowman's membrane in these animals came to an end at the limbus, which is where the conjunctival epithelium starts and the corneal epithelium ends. In all areas of the cornea, Bowman's membrane revealed irregular, abrupt thickening and thinning. The corneal epithelium was thick in the vertex and thinner towards the limbus, whereas Descemet's membrane was thin in the center (vertex) and thick in the periphery (near the limbus). In this study, pictures and diagrams were used to illustrate the general anatomical, histological, and morphometric characteristics of the limbus in the species under investigation. The data from our study showed that the limbus region of the bulbus oculi was narrow in the lateral and medial parts and wide in the dorsal and ventral parts. This was confirmed in the studied animals as a general rule. The width value will undoubtedly affect the number of cells covered by the regions. It is conceivable that these cells will play a significant role in the decision of where to perform surgical procedures in order to promote wound healing, giving doctors an advantage. In this circumstances, we think that the limbus should be studied in terms of clinical methods because it has different shapes depending on the species and the position of the bulbus.

Proposal of the colour pattern reconstruction of basal cervids

ABSTRACTMethodologies that analyse the colouration and external appearance of extant species are very useful tools when facing one of the greatest challenges in the palaeoartistic reconstructions of extinct fauna: inferring the colour patterns. Earlier works have applied this methodology, for example, in the reconstruction of the Miocene bovid Tethytragus, proving that the maximum likelihood (ML) analysis to infer ancestral states has promising potential. This study offers a proposal for the reconstruction of the external appearance of Heteroprox moralesi Azanza 1989, an early cervid of the Middle Miocene present in several fossil sites of Central Spain. For the reconstruction of the external appearance, the colour patterns of all the extant species of the family Cervidae were studied with the method of ML analysis, as well as recent works about their phylogeny. The results show the most probable basal colour pattern of the cervids: dark shades on the limbs, dorsal section, and head of the animal, and, in contrast, lighter colours on the neck and perianal region. This basal pattern can be used as a basis for reconstructing colouration and to hypothesise about the external appearance of extinct taxa. Furthermore, the inferred forest habitat of H. moralesi has been taken into consideration in order to adjust the colour pattern, comparing the final results of the analysis performed in this study with that of the pattern observed in extant forest deer as well as with previous works employing this methodology.

A single dose of cocaine raises SV2A density in hippocampus of adolescent rats.

Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a single dose of cocaine suffices to affect pre-synaptic SV2A density, especially during adolescence when synapses undergo intense maturation. Here, we explored potential changes of pre-synaptic SV2A density in target brain areas associated with the cocaine-induced boost of dopaminergic neurotransmission, specifically testing if the effects would last after the return of dopamine levels to baseline. We administered cocaine (20 mg/kg i.p.) or saline to rats in early adolescence, tested their activity levels and removed the brains 1 hour and 7 days after injection. To evaluate immediate and lasting effects, we did autoradiography with [3H]UCB-J, a specific tracer for SV2A, in medial prefrontal cortex, striatum, nucleus accumbens, amygdala, and dorsal and ventral areas of hippocampus. We also measured the striatal binding of [3H]GBR-12935 to test cocaine's occupancy of the dopamine transporter at both times of study. We found a significant increase of [3H]UCB-J binding in the dorsal and ventral sections of hippocampus 7 days after the cocaine administration compared to saline-injected rats, but no differences 1 hour after the injection. The [3H]GBR-12935 binding remained unchanged at both times. Cocaine provoked lasting changes of hippocampal synaptic SV2A density after a single exposure during adolescence.

Fabrication and characterization of PVA@PLA electrospinning nanofibers embedded with Bletilla striata polysaccharide and Rosmarinic acid to promote wound healing

In this study, a novel nanofiber material with Polylactic acid (PLA), natural plant polysaccharides-Bletilla striata polysaccharide (BSP) and Rosmarinic acid (RA) as the raw materials to facilitate wound healing was well prepared through coaxial electrospinning. The morphology of RA-BSP-PVA@PLA nanofibers was characterized through scanning electron microscopy (SEM), and the successful formation of core-shell structure was verified under confocal laser microscopy (CLSM) and Fourier transform infrared spectroscopy (FTIR). RA-BSP-PVA@PLA exhibited suitable air permeability for wound healing, as indicated by the result of the water vapor permeability (WVTR) study. The results of tension test results indicated the RA-BSP-PVA@PLA nanofiber exhibited excellent flexibility and better accommodates wounds. Moreover, the biocompatibility of RA-BSP-PVA@PLA was examined through MTT assay. Lastly, RA-BSP-PVA@PLA nanofibers can induce wound tissue growth, as verified by the rat dorsal skin wound models and tissue sections. Furthermore, RA-BSP-PVA@PLA can facilitate the proliferation and transformation of early wound macrophages, and down-regulate MPO+ expression of on the wound, thus facilitating wound healing, as confirmed by the result of immunohistochemical. Thus, RA-BSP-PVA@PLA nanofibers show great potential as wound dressings in wound healing.

Validation of Spinal Cord Injury Sensory Deficit Model with Head-Fixed Rat

Background/Objective: Numerous studies have reported restoring motor function through spinal cord stimulation in a rodent spinal cord injury model; however, replicating sensory information through spinal cord stimulation has not been thoroughly tested.We have previously trained rats to detect artificial sensations which lead to the question if this can be generated in a spinal cord injured rat. Our study begins to address this question by first validating a spinal cord injury model to test. Our hypothesis is if a decrease in the percent correct response compared to pre-procedure is observed, then this will verify sensory loss in this dorsal column lesion model of spinal cord injury. Methods: We use sensory detection in a head-fixed rat to verify a spinal cord injury sensory deficit model. We begin by placing a water-deprived rat into a custom-made head-fix set up where two water spouts are placed in front of the rat. Vibration stimuli is applied to the hind paw via a vibration motor set at 200 hz ± 50 hz. The rat is trained to associate stimulus with left spout and no stimulus with right spout. Correct percent response is recorded and once rat demonstrates detection, the rat undergoes a dorsal column hemi-section procedure. Post procedure, the rat will be placed back in the head-fix set up to repeat the behavioral experiment. Results: Thus far, only habituation training has been completed with the rat. The following steps include detection training, dorsal column hemi section, and re doing the detection training to measure a difference in correct response rate. Conclusion and Potential Impact:This is a crucial step for spinal cord injury research as this confirms sensory loss and will allow further testing to restore sensation. After validation, we can begin testing to restore sensation using stimulation of the spinal cord.

Minoxidil and Dexamethasone Eluting Nanofiber Dressing for Cutaneous Wound Healing in Rat

Background: Minoxidil is an antihypertensive agent and vasodilator which may help to promote local blood flow thus hastening the closure of excisional skin wounds. Corticosteroids may down-regulate wound healing. This work aims to develop and characterize nanofiber-eluting dexamethasone and minoxidil and investigate their effect on wound healing in a rat model. Methods: Minoxidil and dexamethasone-loaded wound dressings were developed and characterized with scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). In vitro, drug release studies were performed for 12 days. To model the wound-healing activity of the developed formulations, excisional wounds were created on the dorsal section of male rats. Results: All the electrospun wound dressing nanofibers displayed smooth structures and surfaces without drug crystals. Histological results of Hematoxylin &amp; Eosin and Masson’s trichrome staining indicate wound healing suppression in the dexamethasone-treated group and good healing activity in the minoxidil-treated group. Here we identified that the application of topical minoxidil can be effective for wound healing probably driven by the anagen hair growth while dexamethasone suppresses collagen production and prevents scar formation. Conclusion: The findings suggest that this minoxidil and dexamethasone wound dressing can potentially be developed as a new treatment modality in the clinic to accelerate wound healing while preventing scar formation.

Analysis of a cell niche with proliferative potential at the roof of the aqueduct of Sylvius

The aqueduct of Sylvius connects the third with the fourth ventricle and is surrounded by the Periaqueductal Grey. Here, we report a novel niche of cells in the dorsal section of the aqueduct, hereby named dorsal aqueduct niche or DAN, by applying a battery of selective markers and transgenic mouse lines. The somata of DAN cells are located toward the lumen of the ventricle forming multiple layers in close association with the cerebrospinal fluid (CSF). A single process emerges from the soma and run with the blood vessels. Cells of the DAN express radial glia/stem cell markers such as GFAP, vimentin and nestin, and the glutamate transporter GLAST or the oligodendrocyte precursor/pericyte marker NG2, thereby suggesting their potential for the generation of new cells. Morphologically, DAN cells resemble tanycytes of the third ventricle, which transfer biochemical signals from the CSF to the central nervous system and display proliferative capacity. The aqueduct ependymal lining can proliferate as observed by the integration of BrdU and expression of Ki67. Thus, the dorsal section of the aqueduct of Sylvius possesses cells that may act a niche of new glial cells in the adult mouse brain.

Genetic parameter estimates for intermuscular bone trait in grass carp (Ctenopharyngodon idella)

Intermuscular bones (IBs) are ossified myoseptal tendons, occurring only in teleosts among recent vertebrates. Most aquaculture species in the world contain a certain number of IBs, especially cyprinid fishes. The large number of IBs that are not easy to separate have seriously affected the edible and processability of fish and reduced the economic value of freshwater cultured fish. Grass carp (Ctenopharyngodon idella) is one of the major aquaculture species in the world with the certain number of IBs. In order to explore the possibility of reducing the number of IBs in C. idella by selective breeding, the genetic parameters for IBs trait of C. idella were evaluated in this study. The high polymorphic microsatellite loci were used to genotype 136 parents (66 males and 70 females) and their 538 offspring from cross breeding. After counting the IBs number and estimating the genetic parameters, animal models were used to evaluate the heritability of tested traits. The results showed that the IBs number of whole fish body was ranged from 102 to 127 with the average of 117, coefficient of variation (CV) being 3.23%. The CV of epipleural bones number in the ventral section (5.53%) was significantly higher than that of epineural bones in the dorsal section (2.52%). The heritability of IBs number in C. idella showed low level (0.137) for whole body, and epipleural bones had the lower heritability (0.068) compared to that of epinleural bones (0.132), which indicated the difficulty of traditional selective breeding for reducing IBs. However, the results found a high and significant genetic correlation between body height and whole body IBs number (0.918, p < 0.05), especially between body height and ventral IBs number, which may provide a new reference index for future breeding research on IBs number trait. The study reported the genetic parameters of IBs trait in C. idella for the first time, the low level heritability, but high genetic correlation between body height and IBs number, providing a reference of family-based breeding to obtain grass carp with less IBs.

Investigating Peripheral Regional Anesthesia Using Induced Pluripotent Stem Cell Technology: Exploring Novel Terrain.

Investigating Peripheral Regional Anesthesia Using Induced Pluripotent Stem Cell Technology: Exploring Novel Terrain.

Skin wrinkles and folds enable asymmetric stretch in the elephant trunk

The elephant's trunk is multifunctional: It must be flexible to wrap around vegetation, but tough to knock down trees and resist attack. How can one appendage satisfy both constraints? In this combined experimental and theoretical study, we challenged African elephants to reach far-away objects with only horizontal extensions of their trunk. Surprisingly, the trunk does not extend uniformly, but instead exhibits a dorsal "joint" that stretches 15% more than the corresponding ventral section. Using material testing with the skin of a deceased elephant, we show that the asymmetry is due in part to patterns of the skin. The dorsal skin is folded and 15% more pliable than the wrinkled ventral skin. Skin folds protect the dorsal section and stretch to facilitate downward wrapping, the most common gripping style when picking up items. The elephant's skin is also sufficiently stiff to influence its mechanics: At the joint, the skin requires 13 times more energy to stretch than the corresponding length of muscle. The use of wrinkles and folds to modulate stiffness may provide a valuable concept for both biology and soft robotics.

Innate Immune Responses and P. falciparum CS Repeat-Specific Neutralizing Antibodies Following Vaccination by Skin Scarification.

The skin is the site of host invasion by the mosquito-borne Plasmodium parasite, which caused an estimated 229 million infections and 409,000 deaths in 2019 according to WHO World Malaria report 2020. In our previous studies, we have shown that skin scarification (SS) with a P. falciparum circumsporozoite (CS) peptide in the oil-in-water adjuvant AddaVax containing a combination of TLR 7/8 and TLR 9 agonists can elicit sporozoite neutralizing antibodies. SS with AddaVax + TLR agonists, but not AddaVax alone, elicited CD4+ Th1 cells and IgG2a/c anti-repeat antibody. To explore the innate immune responses that may contribute to development of adaptive immunity following SS, we examined the skin at 4h and 24h post priming with CS peptide in AddaVax with or without TLR agonists. H&E stained and IHC-labeled dorsal skin sections obtained 24h post SS demonstrated a marked difference in the pattern of infiltration with F4/80+, CD11b+ and Ly6G+ cells at the immunization site, with the lowest intensity noted following SS with AddaVax + TLR agonists. Serum collected at 4h post SS, had reproducible increases in IL-6, MIP-3α, IL-22 and IP-10 (CXCL10) following SS with AddaVax + TLR agonists, but not with AddaVax alone. To begin to decipher the complex roles of these pro-inflammatory cytokines/chemokines, we utilized IP-10 deficient (IP-10 -/-) mice to examine the role of this chemokine in the development of anti-repeat antibody response following SS. In the absence of IP-10, the levels of Th1-type IgG2a/c antibody and kinetics of the primary anti-repeat antibody response were reduced following prime and boost. The IP-10 chemokine, present as early as 4h post prime, may provide an early serological marker for rapid screening of adjuvant formulations and delivery platforms to optimize SS-induced humoral immunity to CS repeats as well as other pathogens.