Ventral Tissue Research Articles

Disease and Stem Cell-Based Analysis of the 2013 ASNTR Meeting.

A wide diversity of subjects are presented at the annual American Society of Neural Therapy and Repair meeting every year, and 2013 was no exception. An insight into the current research trends in regenerative medicine was provided, including studies to elucidate disease mechanisms and the means to treat them. Different methods featured in 2013 included stem cell and tissue transplantation, gene therapy, dietary supplementation, and hydrogels as scaffold systems for the growth of stem cells. Diseases ranged from Parkinson's disease, spinal cord injury, and stroke to traumatic brain injury, pain, and epilepsy. Traumatic brain injury was an increasingly popular topic, highlighting the concerns of soldiers returning from duty overseas. A number of studies looked at ways to treat or elucidate mechanisms for more than one disorder. The studies including stem cells predominantly involved human-derived cells being transplanted, and the most common recipient of stem cells were rodents. Only one autologous transplant study, which featured mouse bone marrow cells being transplanted into mice for the treatment of stroke, was presented this year. The most popular stem cell studied was the neural stem cell, which in some instances was predifferentiated from induced pluripotent stem cells or embryonic stem cells. Other stem cells included the mesenchymal stem cell and adipose, amniotic fluid, and umbilical cord blood-derived cells. Many studies also looked at more than one stem cell type. Combinational studies, such as gene therapy and transplantation, were also commonly explored as well as studies using fetal ventral mesencephalon or spinal cord tissue rather than stem cells. Numerous studies also featured the use of "drugs"-some naturally derived or naturally occurring as well as drug cocktails. A number of possible treatments, including physical therapy and socialization, were explored for a number of different diseases, as well as reports on the current status of four gene therapy clinical trials for the treatment of Parkinson's disease. Other studies assessed possible causes of specific disorders. In this way, the ASNTR provides an important snapshot of developments in the field of regenerative medicine.

A comparison of microscopic ink characteristics of 35 commercially available surgical margin inks

To compare microscopic characteristics of commercially available surgical margin inks used for surgical pathology specimens. Prospective in vitro study. Thirty-five different surgical margin inks (black, blue, green, orange, red, violet, and yellow from 5 different manufacturers). Inks were applied to uniform, single-source, canine cadaveric full-thickness ventral abdominal tissue blocks. Tissue blocks and ink manufacturers were randomly paired and each color was applied to a length of the cut tissue margin. After drying, tissues were fixed in formalin, and 3 radial slices were obtained from each color section and processed for routine histologic evaluation, yielding 105 randomly numbered slides with each manufacturer's color represented in triplicate. Slides were evaluated by 5 blinded, board-certified veterinary anatomic pathologists using a standardized scoring scheme. Statistical analyses were performed to evaluate for ink manufacturer effects on scores, correlation among different subjective variables, and pathologist agreement. Black and blue had the most consistently high scores whereas red and violet had the most consistently low overall scores, across all manufacturers. All colors tested, except yellow, had statistically significant differences in overall scores among individual manufacturers. Overall score was significantly correlated to all other subjective microscopic scores evaluated. The average Spearman correlation coefficient among the 10 pairwise pathologists overall ink scores was 0.60. There are statistically significant differences in microscopic ink characteristics among manufacturers, with a notable degree of inter-pathologist agreement.

Development: Scaling to Size by Protease Inhibition

The dorsal half of bisected Xenopus laevis embryos can regenerate a well-proportioned organism on a smaller scale. A new study indicates that the removal of ventral tissue generates a steeper Chordin gradient by reducing Sizzled, a secreted inhibitor of Tolloid chordinases.

Expression of the decapentaplegic ortholog in embryos of the onychophoran Euperipatoides rowelli

The gene decapentaplegic (dpp) and its homologs are essential for establishing the dorsoventral body axis in arthropods and vertebrates. However, the expression of dpp is not uniform among different arthropod groups. While this gene is expressed along the dorsal body region in insects, its expression occurs in a mesenchymal group of cells called cumulus in the early spider embryo. A cumulus-like structure has also been reported from centipedes, suggesting that it might be either an ancestral feature of arthropods or a derived feature (=synapomorphy) uniting the chelicerates and myriapods. To decide between these two alternatives, we analysed the expression patterns of a dpp ortholog in a representative of one of the closest arthropod relatives, the onychophoran Euperipatoides rowelli. Our data revealed unique expression patterns in the early mesoderm anlagen of the antennal segment and in the dorsal and ventral extra-embryonic tissue, suggesting a divergent role of dpp in these tissues in Onychophora. In contrast, the expression of dpp in the dorsal limb portions resembles that in arthropods, except that it occurs in the mesoderm rather than in the ectoderm of the onychophoran limbs. A careful inspection of embryos of E. rowelli revealed no cumulus-like accumulation of dpp expressing cells at any developmental stage, suggesting that this feature is either a derived feature of chelicerates or a synapomorphy uniting the chelicerates and myriapods.

Survival and Functional Restoration of Human Fetal Ventral Mesencephalon following Transplantation in a Rat Model of Parkinson's Disease

Cell replacement therapy by intracerebral transplantation of fetal dopaminergic neurons has become a promising therapeutic option for patients suffering from Parkinson's disease during the last decades. However, limited availability of human fetal tissue as well as ethical issues, lack of alternative nonfetal donor cells, and the absence of standardized transplantation protocols have prevented neurorestorative therapies from becoming a routine procedure in patients suffering from neurodegenerative diseases. Improvement of graft survival, surgery techniques, and identification of the optimal target area are imperative for further optimization of this novel treatment. In the present study, human primary fetal ventral mesencephalon-derived tissue from 7- to 9-week-old human fetuses was transplanted into 6-hydroxydopamine-lesioned adult Sprague-Dawley rats. Graft survival, fiber outgrowth, and drug-induced rotational behavior up to 14 weeks posttransplantation were compared between different intrastriatal transplantation techniques (full single cell suspension vs. partial tissue pieces suspension injected by glass capillary or metal cannula) and the intranigral glass capillary injection of a full (single cell) suspension. The results demonstrate a higher survival rate of dopamine neurons, a greater reduction in amphetamine-induced rotations (overcompensation), and more extensive fiber outgrowth for the intrastriatally transplanted partial (tissue pieces) suspension compared to all other groups. Apomorphine-induced rotational bias was significantly reduced in all groups including the intranigral group. The data confirm that human ventral mesencephalon-derived cells serve as a viable cell source, survive in a xenografting paradigm, and functionally integrate into the host tissue. In contrast to rat donor cells, keeping the original (fetal) neuronal network by preparing only a partial suspension containing tissue pieces seems to be beneficial for human cells, although a metal cannula that causes greater tissue trauma to the host is required for injection. In addition, homotopic intranigral grafts may represent a complimentary grafting approach to the "classical" ectopic intrastriatal target site in PD.

US AND DOPPLER-GUIDED SURGICAL TREATMENT BASED ON IMMUNOHISTOCHEMICAL FINDINGS IN MIDPORTION ACHILLES TENDINOPATHY SHOWS GOOD CLINICAL RESULTS AND FAST RETURN TO ACTIVITY

IntroductionTreatment of midportion Achilles tendinopathy has been known to be difficult. Recent ultrasound(US) and Doppler(CD) findings (high blood flow outside ventral tendon), together with results of immunohistochemical analyses (marked presence...

A curious abnormally developed embryo of the pill millipede Glomeris marginata (Villers, 1789)

This paper reports on an abnormally developed embryo (ADE) of the common pill millipede Glomeris marginata. This ADE represents a modified case of Duplicitas posterior, in which two posterior ends are present, but only one anterior end. While the major posterior germ band of the embryo appears almost normally developed, the minor posterior germ band is heavily malformed, has no clear correlation to the single head, little or no ventral tissue, and a minute amount of yolk. The anterior end of the minor germ band is fused to the ventral side of the major germ band between the first and second trunk segment. At least one appendage of the second trunk segment appears to be shared by the two germ bands. Morphology and position of the minor germ band suggest that the ADE may be the result of an incorrectly established single cumulus [the later posterior segment addition zone (SAZ)]. This differs from earlier reports on Duplicitas posterior type ADEs in Glomeris marginata that are likely the result of the early formation of two separate cumuli.

Heteropterys tomentosa (A. Juss.) infusion counteracts Cyclosporin a side effects on the ventral prostate

BackgroundCyclosporin A (CsA) is an immunosuppressive drug widely used in treatment of auto-immune diseases or after organ transplants. However, several side effects are commonly associated with CsA long term intake, some regarding to loss of reproductive organ function due to oxidative damage. Considering that phytotherapy is an important tool often used against oxidative stress, we would like to describe the beneficial effects of Heteropterys tomentosa intake to minimize the damage caused by CsA to the ventral prostate tissue of Wistar rats under laboratorial conditions.MethodsThirty adult Wistar rats (Rattus norvegicus albinus) were divided into: control group (water); CsA group (Cyclosporin A); Ht group (H. tomentosa infusion) and CsA + Ht group (CsA and H. tomentosa infusion). Plasmic levels of hepatotoxicity markers, triglycerides, cholesterol and glucose were quantified. The ventral prostate tissue was analyzed under light microscopy, using stereological, morphometrical and immunohistochemical techniques.ResultsH. tomentosa did not cause any alterations either of the plasmic parameters or of the ventral prostate structure. CsA caused alterations of GOT, total and indirect bilirubin, cholesterol, triglycerides and glucose levels in the plasma; CsA-treated rats showed alterations of the ventral prostate tissue. There were no alterations regarding the plasma levels of GOT, triglycerides and glucose of CsA + Ht animals. The same group also showed normalization of most of the parameters analyzed on the ventral prostate tissue when compared to the CsA group. The treatments did not alter the pattern of AR expression or the apoptotic index of the ventral prostate epithelium.ConclusionsThe results suggest a protective action of the H. tomentosa infusion against the side effects of CsA on the ventral prostate tissue, which could also be observed with plasmic biochemical parameters.

Study of the ventral prostate of Wistar rats treated with Heteropterys tomentosa (A. Juss.)

Heteropterys tomentosa is a Brazilian plant traditionally used as an aphrodisiac and stimulant. Previous studies suggested possible androgenic and antioxidant effects after long term administration of H. tomentosa infusion. The aim of the present study was to evaluate the effects of this plant infusion on the rat ventral prostate: an androgen responsive organ. Wistar rats were treated, by gavage, with H. tomentosa roots infusion (treated group, n=6) or water (control group, n=6) for 56 days. Morphological, morphometrical and stereological analyses were employed to study the ventral prostate tissue, as well as androgen receptor and apoptotic cell staining. The ultrastructure of the prostatic epithelium was also analyzed. No alteration was observed in the stereological and morphometrical analyses. The pattern of androgen receptor expression and the apoptotic index were identical in the control and treated group. Ultrastructural analysis showed no alterations caused by H. tomentosa. These results suggested that treatment with H. tomentosa infusion, although considered a strong aphrodisiac, did not cause any major damage nor benefit to the prostate tissue.

Neuregulin-1 receptor tyrosine kinase ErbB4 is upregulated in midbrain dopaminergic neurons in Parkinson disease

Previously we demonstrated that systemically administered neuregulin-1-β1, a nerve growth and differentiation factor, passed the blood–brain barrier and accumulated in brain areas with expression of its receptor ErbB4. In substantia nigra (SN), neuregulin-1-β1 phosphorylated ErbB4 and protected dopaminergic neurons in a toxin-based mouse model of Parkinson disease (PD). We studied ErbB4 in the context of human midbrain dopaminergic degeneration in vivo and in vitro. Post-mortem ventral midbrain tissue sections of neuropsychiatric healthy individuals and PD patients (matched for age, gender and post-mortem delay) were immunostained for ErbB4. Cultured Lund human mesencephalic (LUHMES) post-mitotic dopaminergic neurons were treated with dopaminergic toxins and analyzed for ErbB4 expression. In control individuals, 85.0±5.0% of dopaminergic neurons, containing cytoplasmic neuromelanin, expressed ErbB4 in the SN. In PD cases, the percentage of ErbB4-positive nigral dopaminergic neurons was increased to 94.9±2.5%. The mean ErbB4 immunoreactivity of melanized neurons was higher in PD than controls. LUHMES neurons upregulated ErbB4 when exposed to toxins 1-methyl-4-phenylpyridinium and 6-hydroxydopamine. Increased rate of ErbB4-positive dopaminergic neurons in PD may either reflect a better survival of ErbB4-positive neurons or an increased expression of ErbB4 by remaining neurons to seek trophic support. Enhanced ErbB4 expression in human in vitro toxin-based PD models supports the latter interpretation. Thus, dopaminergic neurons in SN might be susceptible to neuregulin-1 treatment in PD.

Cyclosporin A causes impairment of the ventral prostate tissue structure of Wistar rats

Cyclosporin A (CsA) is an immunosuppressive drug widely used in medicine to reduce the immune system activity and, therefore, the risk of organ rejection after transplantation. However, many side effects can be related to its use, such as, reduction in serum testosterone levels due to damage of the testis structure and, consequently, male infertility. The present study aims to evaluate the effects of chronic CsA administration on the ventral prostate tissue (15 mg/kg per d, for 56 days). Stereological, morphometrical, morphological and ultrastructural observations were employed. The plasmatic testosterone and glucose levels were measured. An androgen receptor (AR) immunohistochemical method was applied on ventral prostate sections. Apoptosis was detected with the terminal deoxynucleotidyl transferase dUTP nick end labeling technique. CsA treatment caused reduction in plasmatic testosterone levels and an increase in glycemia. The volume of all ventral prostate tissue components (lumen, epithelium and muscular and nonmuscular stroma) and ventral prostate weight were reduced in the CsA-treated group. Light and transmission electron microscopy confirmed epithelium atrophy of treated animals. There was no alteration of AR expression or apoptotic index. CsA chronic treatment in the therapeutic doses caused damage to prostate tissue of adult Wistar rats, probably due to increase in the glucose levels and reduction in the plasmatic testosterone levels.

Birth dating of midbrain dopamine neurons identifies A9 enriched tissue for transplantation into Parkinsonian mice

Clinical trials have provided proof of principle that new dopamine neurons isolated from the developing ventral midbrain and transplanted into the denervated striatum can functionally integrate and alleviate symptoms in Parkinson's disease patients. However, extensive variability across patients has been observed, ranging from long-term motor improvement to the absence of symptomatic relief and development of dyskinesias. Heterogeneity of the donor tissue is likely to be a contributing factor in the variable outcomes. Dissections of ventral midbrain used for transplantation will variously contain progenitors for different dopamine neuron subtypes as well as different neurotransmitter phenotypes. The overall impact of the resulting graft will be determined by the functional contribution from these different cell types. The A9 substantia nigra pars compacta dopamine neurons, for example, are known to be particularly important for motor recovery in animal models. Serotonergic neurons, on the other hand, have been implicated in unwanted dyskinesias. Currently little knowledge exists on how variables such as donor age, which have not been controlled for in clinical trials, will impact on the final neuronal composition of fetal grafts. Here we performed a birth dating study to identify the time-course of neurogenesis within the various ventral midbrain dopamine subpopulations in an effort to identify A9-enriched donor tissue for transplantation. The results show that A9 neurons precede the birth of A10 ventral tegmental area dopamine neurons. Subsequent grafting of younger ventral midbrain donor tissue revealed significantly larger grafts containing more mitotic dopamine neuroblasts compared to older donor grafts. These grafts were enriched with A9 neurons and showed significantly greater innervation of the target dorso-lateral striatum and DA release. Younger donor grafts also contained significantly less serotonergic neurons. These findings demonstrate the importance of standardized methods to improve cell therapy for Parkinson's disease and have significant implications for the generation and selectivity of dopamine neurons from stem cell based sources.

Amphetamine-induced rotation in the transplanted hemi-parkinsonian rat – Response to pharmacological modulation

The transplantation of dopamine rich foetal tissue into Parkinson's disease patients holds much promise as a therapeutic strategy. The functional efficiency of transplantation is often tested experimentally, by grafting rat derived embryonic ventral mesencephalon tissue suspensions into the denervated striatum of hemi-parkinsonian rats that were previously rendered dyskinetic with l-DOPA. The survival and integration of the grafts in rats can be assessed by a variety of behavioural tests, however amphetamine-induced rotations remain one of the most widely used and robust measures. In this test, dopamine released from the transplant typically drives net rotation in the contralateral direction, in contrast to the ipsilateral rotational bias seen post-lesion. It is unknown what contribution other neurotransmitter systems may make to this response. In this study we monitored amphetamine-induced rotation in transplanted rats that were co-administered a second pharmacological challenge with agents known to affect dopamine-mediated behavioural responses in this model. Both D1 and D2 receptor antagonism (by SCH23390 and raclopride respectively) reduced the rotational response. However the cannabinoid CB1 agonist WIN55,212-2 and α1 and α2 adrenergic receptor antagonist yohimbine had no effect on rotation. Interestingly, glutamatergic antagonists reduced (MTEP) or even reversed (MK-801) total net rotations. The serotoninergic 5-HT1A and 5-HT1B agonists (8-OH-DPAT and CP94253 respectively) altered the temporal profile of the rotational behaviour supporting a regulatory role. Although dopamine clearly drives the motor response, this data implicates both 5-HT and glutamate systems in its regulation.

Mercury and cadmium concentrations in farmed bluefin tuna (Thunnus orientalis) and the suitability of using the caudal peduncle muscle tissue as a monitoring tool.

Three regions (cephalic, central, and caudal) of the dorsal and ventral muscle tissue (R1 through R6) and the caudal peduncle muscle tissue (CPMT) of 20 farmed bluefin tuna (Thunnus orientalis) were analyzed for mercury (Hg) and cadmium (Cd) concentrations. Region 1 (cephalic-ventral) had significantly lower concentrations of Hg but significantly higher concentrations of Cd than did the other regions. However, average metal concentrations of all regions (R1 through R6) were only 6% lower for Hg and were not significantly different for Cd from those in the CPMT. Therefore, the CPMT was used to monitor the concentrations of these two metals in more than 100 farmed tuna collected from July 2004 to January 2009 under the assumption that the Cd concentrations in the CPMT would be representative of the Cd concentration in the whole body and that the Hg concentrations would be, in the worst case, overestimated by approximately 6%. The Hg and Cd concentrations in these tuna were inversely related to the condition index, i.e., the tuna in better condition had the lowest concentrations of these metals. The mean concentrations in the CPMT of all fish analyzed were 0.31 ± 0.17 μg/g wet weight for Hg and 0.007 ± 0.006 μg/g wet weight for Cd. These concentrations were below the limits established by Mexican regulations for seafood (1.0 and 0.5 μg/g for Hg and Cd, respectively) and Japan (0.4 μg/g for Hg).

Evidence for a rhodopsin-retinochrome photosensitive system in chromatophores of the squid, Loligo pealeii

Event Abstract Back to Event Evidence for a rhodopsin-retinochrome photosensitive system in chromatophores of the squid, Loligo pealeii Alexandra Kingston1*, George Bell2, Alan M. Kuzirian2, Roger T. Hanlon2 and Thomas W. Cronin1 1 University of Maryland Baltimore County, Biological Sciences, United States 2 Marine Biological Laboratory, Marine Resources Center, United States Cephalopods, including squid, cuttlefish, and octopus, are hypothesized to have extraocular photoreceptors located in their skin. These putative photoreceptors are thought to detect light using an opsin-based photoreception system. In photoreceptors of the retina, an opsin protein is bound to a retinal chromophore to form a functional photopigment, and retinochrome acts as a photoisomerase, recycling the chromophore. The presence of opsin and retinochrome in close proximity suggests the presence of a functional photoreceptor. My work focuses on detecting opsin and retinochrome in putative extraocular photoreceptors in the skin of the longfin squid, Loligo pealeii. We searched for opsin and retinochrome in the skin and retinas of L. pealeii using RT-PCR. Opsin was detected in the retina, ventral mantle, ventral fin surface, 1st arm, 2nd arm, 3rd arm, 4th arm, tentacle and muscle tissue of L. pealeii. Retinochrome was detected in all these locations as well as the dorsal mantle and dorsal fin surface. Identical opsin and retinochrome transcripts were also detected in dissociated chromatophores from several locations. Future work will include in situ hybridization and immunohistochemistry to determine in what cells opsin and retinochrome transcripts and proteins are expressed. Keywords: chromatophore, retinochrome, Rhodopsin Conference: Tenth International Congress of Neuroethology, College Park. Maryland USA, United States, 5 Aug - 10 Aug, 2012. Presentation Type: Poster (but consider for participant symposium and student poster award) Topic: Sensory: Vision Citation: Kingston A, Bell G, Kuzirian AM, Hanlon RT and Cronin TW (2012). Evidence for a rhodopsin-retinochrome photosensitive system in chromatophores of the squid, Loligo pealeii. Conference Abstract: Tenth International Congress of Neuroethology. doi: 10.3389/conf.fnbeh.2012.27.00169 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Apr 2012; Published Online: 07 Jul 2012. * Correspondence: Ms. Alexandra Kingston, University of Maryland Baltimore County, Biological Sciences, Baltimore, MD, 21250, United States, acnahm@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Alexandra Kingston George Bell Alan M Kuzirian Roger T Hanlon Thomas W Cronin Google Alexandra Kingston George Bell Alan M Kuzirian Roger T Hanlon Thomas W Cronin Google Scholar Alexandra Kingston George Bell Alan M Kuzirian Roger T Hanlon Thomas W Cronin PubMed Alexandra Kingston George Bell Alan M Kuzirian Roger T Hanlon Thomas W Cronin Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Sleep Deprivation Alters Rat Ventral Prostate Morphology, Leading to Glandular Atrophy: A Microscopic Study Contrasted with the Hormonal Assays

We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR.

An abnormally developed embryo of the pill millipede Glomeris marginata that lacks dorsal segmental derivatives

The body of arthropods is subdivided in serially homologous units, the so-called segments. In many arthropods, ventral and dorsal segmental tissue typically is aligned in parallel, but is dependent on different genetic inputs. In the pill millipede Glomeris marginata (Myriapoda: Diplopoda), ventral and dorsal segmental patterning is clearly decoupled providing an excellent model for the investigation of ventral versus dorsal segmentation mechanisms. This paper reports on the finding of a single embryo that lacks dorsal segmental and extraembryonic tissue. Ventral derivatives, however, are widely developed normally. This suggests that ventral and dorsal tissue is not only patterned differently, as shown previously, but also that ventral tissue can develop (or at least persist) independently from dorsal tissue. It also suggests a correlation of dorsal segmentation and function of the extraembryonic tissue. This assumed correlation may involve the guidance of the two dorsal hemispheres of the developing embryo dorsally, or that formation and/or maintenance of extraembryonic tissue depends on the input of dorsal segmental tissue. Whether the observed abnormalities are caused by mutation or are the result of otherwise disturbed early development is unclear.

Commentary to “A standardized classification of hypospadias”

It has been accepted, by the majority of hypospadias surgeons, for a long time that a classification of hypospadias based simply on the position of the external urethral meatus was both inaccurate and misleading. Professor P.D.E. Mouriquand has argued that the division of the corpus spongiosus is a more accurate criterion of the severity of hypospadias and the degree of hypoplasia of the ventral penile tissue. This paper supports that hypothesis with some excellent and well presented data. It describes how the division of the corpus spongiosus can be assessed preoperatively and, in addition to that, it introduces a novel assessment that can be performed per-operatively, relating the division of the spongiosus to the upper margin of the pubic symphysis. This will provide a more rigid classification system enabling a more accurate comparison of the outcomes of different operative techniques. At international meetings many surgeons still state that they will correct distal hypospadias but not the more severe proximal forms! This paper will be a useful tool in putting an end to this unacceptable practice. It convincingly shows that the position of the external meatus is not a true reflection of the severity of hypospadias, and on many occasions the actual severity can only be accurately assessed perioperatively. No surgeon should undertake any hypospadias repair unless they can correct all degrees of severity.

Metamorphic Remodeling of a Planktotrophic Larva to Produce the Predatory Feeding System of a Cone Snail (Mollusca, Neogastropoda)

I used histological sections and 3D reconstructions to document development through metamorphosis of the foregut and proboscis in the conoidean neogastropod Conus lividus. A goal was to determine how highly derived features of the post-metamorphic feeding system of this gastropod predator develop without interfering with larval structures for microherbivory. A second goal was to compare foregut development in this conoidean with previous observations on foregut development in the buccinoidean neogastropod Nassarius mendicus. These two neogastropods both have a feeding larval stage, but they show major differences in post-metamorphic foregut morphology. Basic events in development of the proboscis and proboscis sheath in C. lividus and N. mendicus were similar. However, the elongate buccal tube of C. lividus forms during metamorphosis as a composite of apical epidermal tissue that grows inward and ventral foregut tissue that extends outward. The larval mouth is not carried through metamorphosis. Comparative observations on foregut development in caenogastropods, which now include data on C. lividus, suggest that the foregut incorporates dorsal and ventral modules having different ontogenetic and functional fates. This developmental modularity may have facilitated evolutionary diversification of the post-metamorphic foregut. Foregut diversification in predatory gastropods may have been further fast-tracked by developmental uncoupling of larval and post-metamorphic mouths.

Stem cell-based therapies in Parkinson’s disease: future hope or current treatment option?

Parkinson's disease (PD) is one of the most frequent neurodegenerative diseases and represents a major therapeutic challenge because of the so far missing therapeutic means to influence the ongoing loss of dopaminergic innervation to the striatum. Cell replacement has raised hope to offer the first restorative treatment option. Clinical trials have provided "proof of principle" that transplantation of dopamine-producing neurons into the striatum of PD patients can achieve symptomatic relief given that the striatum is sufficiently re-innervated. Various cell sources have been tested, including fetal ventral midbrain tissue, embryonic stem cells, fetal and adult neural stem cells and, after a ground-breaking discovery, induced pluripotent stem cells. Although embryonic and induced pluripotent stem cells have emerged as the most promising candidates to overcome most of the obstacles to clinical successful cell replacement, each cell source has its unique drawbacks. This review does not only provide a comprehensive overview of the different cellular candidates, including their assets and drawbacks, but also of the various additional issues that need to be addressed in order to convert cellular replacement therapies from an experimental to a clinically relevant therapeutic alternative.