Sequential Sparsening by Successive Adaptation in Neural Populations

In the principal cells of the insect mushroom body, the Kenyon cells (KC), olfactory information is represented by a spatially and temporally sparse code. Each odor stimulus will activate only a small portion of neurons and each stimulus leads to only a short phasic response following stimulus onset irrespective of the actual duration of a constant stimulus. The mechanisms responsible for the sparse code in the KCs are yet unresolved. Here, we explore the role of the neuron-intrinsic mechanism of spike-frequency adaptation (SFA) in producing temporally sparse responses to sensory stimulation in higher processing stages. Our single neuron model is defined through a conductance-based integrate-and-fire neuron with spike-frequency adaptation [1]. We study a fully connected feed-forward network architecture in coarse analogy to the insect olfactory pathway. A first layer of ten neurons represents the projection neurons (PNs) of the antenna lobe. All PNs receive a step-like input from the olfactory receptor neurons, which was realized by independent Poisson processes. The second layer represents 100 KCs which converge onto ten neurons in the output layer which represents the population of mushroom body extrinsic neurons (ENs). Our simulation result matches with the experimental observations. In particular, intracellular recordings of PNs show a clear phasic-tonic response that outlasts the stimulus [2] while extracellular recordings from KCs in the locust express sharp transient responses [3]. We conclude that the neuron-intrinsic mechanism is can explain a progressive temporal response sparsening in the insect olfactory system. Further experimental work is needed to test this hypothesis empirically. [1] Muller et. al., Neural Comput, 19(11):2958-3010, 2007. [2] Assisi et. al., Nat Neurosci, 10(9):1176-1184, 2007. [3] Krofczik et. al. Front. Comput. Neurosci., 2(9), 2009.Comment: 5 pages, 2 figures, This manuscript was submitted for review to the Eighteenth Annual Computational Neuroscience Meeting CNS*2009 in Berlin and accepted for oral presentation at the meetin

Endogenous testicular D-aspartic acid regulates gonadal aromatase activity in boar testis.

D-aspartic acid (D-Asp), aromatase enzyme activity and the putative D-Asp involvement on aromatase induction have been studied in the testis of mature boars. The peroxidase-antiperoxidase and the indirect immunofluorescence methods, applied to cryostat and paraffin sections, were used to evaluate D-Asp and aromatase distributions. D-Asp level was dosed by an enzymatic method performed on boar testis extracts. Biochemical aromatase activity was determined by in vitro experiments carried out on testis extracts. D-Asp immunoreactivity was found in Leydig cells, and, to a lesser extent, in germ cells. Analogously, aromatase immunoreactivity was present in Leydig cells, but absent from seminiferous tubule elements. In vitro experiments showed that the addition of D-Asp to testicular tissue acetone powder induced a significant increase of aromatase activity, as assessed by testosterone conversion to 17beta-estradiol. Enzyme Km was not affected by D-Asp (about 25 nM in control and D-Asp added tests). These findings suggest that D-Asp could be involved in the local regulation of aromatase in boar Leydig cells and intervenes in this organ's production of estrogens

Effects of orexins on 17β-estradiol synthesis and P450 aromatase modulation in the testis of alpaca (Vicugna pacos).

The steroidogenic enzyme P450 aromatase (ARO) has a key role in the conversion of testosterone (T) into estrogens (E), expressed as 17β-estradiol. The presence and localization of this key enzyme have not been described before in the South American camelid alpaca (Vicugna pacos). In our previous studies of the expression and biological effects of orexin A (OxA) and OxB on the alpaca testis demonstrated that OxA, via its specific receptor 1 (OX1R), stimulated T synthesis. In order to extend these findings, we presently explored the presence and localization of ARO in the alpaca male gonad, and the possible correlation between ARO and the orexinergic complex. Western blotting and immunohistochemistry demonstrated the presence of ARO in tissue homogenates and its localization in the tubular and interstitial compartments of the alpaca testis, respectively. The addition of OxA to fresh testicular slices decreased the 17β-estradiol E levels. This effect was annulled by the sequential addition of the selective OX1R antagonist, SB-408124. OxB incubation did not have any effect on the biosynthesis of E. Furthermore, the OxA-mediated down-regulation of E secretion could be ascribed to ARO inhibition by exogenous OxA, as indicated by measurement of ARO activity in tissue slices incubated with OxA. Overall, our findings suggest that locally secreted OxA interacting with OX1R could indirectly inhibit ARO activity, disabling the conversion of T to E, and consequently lowering E biosynthesis and increasing the production of T in mammalian testis

Potential role of orexin A binding the receptor 1 for orexins in normal and cryptorchid dogs.

Background: Cryptorchidism is one of the most common birth disorders of the male reproductive system identified in dogs and other mammals. This condition is characterised by the absence of one (unilateral) or both (bilateral) gonads from the scrotum. The peptides orexin A (OxA) and B (OxB) were obtained by post-transcriptional proteolytic cleavage of a precursor molecule, called prepro-orexin. These substances bind two types of G-coupled receptors called receptor 1 (OX1R) and 2 (OX2R) for orexins. OX1R is specific to OxA while OX2R binds the two peptides with equal affinity. Orexins modulate a great variety of body functions, such as the reproductive mechanism. The purpose of the present research was to study the presence of OxA and its receptor 1 and their possible involvement in the canine testis under healthy and pathological conditions. Methods: This study was performed using adult male normal dogs and male dogs affected by unilateral cryptorchidism. Tissue samples were collected from testes and were divided into three groups: normal, contralateral and cryptic. The samples were used for immunohistochemistry, Western blot and in vitro tests for testosterone evaluation in normal and pathological conditions. Results: OxA-immunoreactivity (IR) was described in interstitial Leydig cells of the normal gonad, and Leydig, Sertoli cells and gonocytes in the cryptic gonad. In the normal testis, OX1R-IR was described in Leydig cells, in pachytene and second spermatocytes and in immature and mature spermatids throughout the stages of the germ developing cycle of the male gonad. In the cryptic testis OX1R-IR was distributed in Leydig and Sertoli cells. The presence of prepro-orexin and OX1R was demonstrated by Western blot analysis. The incubation of fresh testis slices with OxA caused the stimulation of testosterone synthesis in the normal and cryptic gonad while the steroidogenic OxA-induced effect was cancelled by adding the selective OX1R antagonist SB-408124. Conclusions: These results led us to hypothesise that OxA binding OX1R might be involved in the modulation of spermatogenesis and steroidogenesis in canine testis in healthy and pathological conditions

Isoforms of Nitric Oxide Synthase in the Pig Testis

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Localization of orexin B and receptor 2 for orexins in testicular cytotypes of the camelid alpaca (Vicugna pacos).

The orexins A (OxA) and B (OxB) are two hypothalamic peptides involved in many physiological functions of the mammalian body. They act through the binding of two G-coupled receptors named receptor 1 (OX1 ) and receptor 2 (OX2 ) for orexins. The first receptor is specific for OxA, while the second binds both the substances with equal affinity. The orexins and the relative receptors have been traced by means of different techniques also at the periphery of the body and particularly in the adrenals, and in gastrointestinal and genital organs. Aim of this work was to investigate the presence of OxB and OX2 by means of immunohistochemistry and Western blotting analysis in the testis of the South American camelid alpaca, a species primarily breed in Chile and Ecuador and recently diffused in Europe where the quality of its wool is particularly appreciated. OxB immunoreactivity (IR) was found in the tubular compartment of the testis where spermatogonia (resting), zygotene and pachytene spermatocytes, and spermatids clearly showed differently sized and shaped cytoplasmic positive structures. OX2 -IR was found both in the interstitial and tubular compartments of the testis and particularly in Leydig cells and round and elongated spermatids. Western blotting analysis of testis lysates showed the presence of a protein band whose molecular weight corresponded to that currently assigned to OX2 . Such findings easily translate the hypothesis that OxB and its receptor 2 play a functional role both in the interstitial and tubular compartments of the alpaca testis

Climate Change and Reproductive Biocomplexity in Fishes: Innovative Management Approaches towards Sustainability of Fisheries and Aquaculture

The ongoing rapid climate change, combined with the disturbance of fish breeding grounds, may impact reproduction by endangering successful breeding and survival, and thus affect the viable sustainability in aquaculture systems as well as in the sea. In this study we focus on the biocomplexity of fish reproduction in response to climate change. Further, we propose adaptive strategies, including technological advancements, using a noninvasive and non-lethal approach, and we outline an assisted reproduction and nutrigenomics approach to mitigating fish reproductive risks posed by climate change. This was done in an effort to monitor fish aquaculture and ensure that, as a livelihood, it may provide a useful source of nutrition for our society

FCR (Fludarabine, Cyclophosphamide, Rituximab) regimen followed by 90yttrium ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma: a report of 9 cases

<p>Abstract</p> <p>Background</p> <p>This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin^®in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR.</p> <p>Methods</p> <p>The median age was 63 yrs (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m²x 3 days), C (1 gr/m²day 1) and R (375 mg/m²day 4) for 4 cycles. Who achieved at least a partial remission, with < 25% bone marrow involvement, was treated with ⁹⁰Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after ⁹⁰Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy.</p> <p>Results</p> <p>Nine patients have completed the treatment: FCR followed by ⁹⁰Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after ⁹⁰Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 34 months (range 13-50) the current analysis has shown that overall survival (OS) is 89% at 2 years, 76% at 3 years and 61% at 4 years. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection.</p> <p>Conclusions</p> <p>Our experience indicate feasibility, tolerability and efficacy of FCR regimen followed by ⁹⁰Y-RIT in patients relapsed with grades 1 and 2 FL with no unexpected toxicities. A longer follow up and a larger number of patients with relapsed grades 1 and 2 FL are required to determine the impact of this regimen on long-term duration of response and PFS.</p

The Emergence of Miller's Magic Number on a Sparse Distributed Memory

Human memory is limited in the number of items held in one's mind—a limit known as “Miller's magic number”. We study the emergence of such limits as a result of the statistics of large bitvectors used to represent items in memory, given two postulates: i) the Sparse Distributed Memory; and ii) chunking through averaging. Potential implications for theoretical neuroscience are discussed