在体大鼠海马区侧枝联合纤维通路和TA通路的不同空间整合特性

在麻醉Wistar大鼠上,结合脑室给药,应用双电极刺激技术刺激海马独立的两条侧枝／联合纤维通 路、TA通路,并在CAl区放射层记录兴奋性突触后电位(EPSP),对海马CAl区锥体细胞近、远端树突EPSP 的空间整合进行了初步探讨。结果表明,海马CAl区锥体细胞近、远端树突的空间整合都是亚线性的;近端树 突的空间整合不受期望值大小的影响,但远端树突的空间整合随期望值增加而减小(更趋于亚线性)。此外, 荷包牡丹碱没有影响EPSP的空间整合;但瞬时A型钾通道(IAK+)的拮抗剂氨基吡啶-4却使得近端树突的 空间整合趋于线性发展。本研究表明,海马CAl锥体细胞近、远端树突不同的被动、主动特征使它们具有了不 同的空间整合特性。由于近端树突接受海马内部侧枝／联合纤维投射的信息,远端树突通过TA通路接受内嗅皮 层投射的信息,由此提示,CAl区锥体细胞对来自海马内部和直接来自皮层的信息输入采用了不同的整合方 式。

PLCß介导的钙调腺苷酸环化酶在突触可塑性相关基因转录中的作用和FE65对海马依赖学习及LTP的调节

Gene regulation is required for activity-dependent changes in synaptic plasticity and remodeling. The metabotropic glutamate receptors (mGluRs) contribute to different brain functions, including learning/memory, mental disorders, drug addiction, and persistent pain in the CNS. We found that Gp I mGluRs activate PLCß through Gq and then lead to activation of several calcium-dependent signaling pathways, including ERK, which play an important role in gene transcription. These findings support a calcium-dependent role for Gq in release of Calcium and activation of calcium-stimulated adenylyl cyclases I in activity-dependent transcription in response to application of group I metabotropic glutamate receptors agonist and may provide insights into group I mGluRs-dependent synaptic plasticity through MAP kinases signaling. Moreover, the present study investigated the transcription-dependent changes of Arc in response to the activation of group I mGluRs and suggested the central role of ERK1/2 in group I mGluR-mediated Arc transcription. Further, we selected APP-interaction protein FE65 to investigate the mechanism of transcription-related process in synaptic plasticity. FE65 is expressed predominantly in the brain, and interacts with the C-terminal domain of β-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with the isoform-specific FE65 knock-out (p97FE65-/-) mice. p97FE65 knock-out mice showed impaired short-term memory for both TDPA and CFC when tested 10min after training, which is transcription-independent. Consistently, at the Schaffer collateral-CA1 synapses, p97FE65 knock-out mice showed defective early phase LTP. These results demonstrate novel roles of FE65 in synaptic plasticity, acquisition, and retention for certain forms of memory formation.

Islamic corporate financing : does it promote profit and loss sharing?

Islamic financing instruments can be categorised into profit and loss/risk sharing and non-participatory instruments. Although profit and loss sharing instruments such as musharakah are widely accepted as the ideal form of Islamic financing, prior studies suggest that alternative instruments such as murabahah are preferred by Islamic banks. Nevertheless, prior studies did not explore factors that influence the use of Islamic financing among non-financial firms. Our study fills this gap and contributes new knowledge in several ways. First, we find no evidence of widespread use of Islamic financing instruments across non-financial firms. This is because the instruments are mostly used by less profitable firms with higher leverage (i.e., risky firms). Second, we find that profit and loss sharing instruments are hardly used, whilst the use of murabahah is dominant. Consistent with the prediction of moral-hazard-risk avoidance theory, further analysis suggests that users with a lower asset base (to serve as collateral) are associated with murabahah financing. Third, we present a critical discourse on the contentious nature of murabahah as practised. The economic significance and ethical issues associated with murabahah as practised should trigger serious efforts to steer Islamic corporate financing towards risk-sharing more than the controversial rent-seeking practice.

Konspiracja i podziemie zbrojne w Wielkopolsce 1945-1949. Powstanie, rozwój i rozbicie przez aparat bezpieczeństwa

Wydział Historyczny

Entorhinal cortex volume in older adults: reliability and validity considerations for three published measurement protocols.

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

Financing of SME's: an asset side story

The main sources of financing for small and medium sized enterprises (SMEs) are equity (internally generated cash), trade credit paid on time, long and short term bank credits, delayed payment on trade credit and other debt. The marginal costs of each financing instrument are driven by asymmetric information (cost of gathering and analysing information) and transactions costs associated with non-payment (costs of collecting and selling collateral). According to the Pecking Order Theory, firms will choose the cheapest source in terms of cost. In the case of the static trade-off theory, firms choose finance so that the marginal costs across financing sources are all equal, thus an additional Euro of financing is obtained from all the sources whereas under the Pecking Order Theory the source is determined by how far down the Pecking Order the firm is presently located. In this paper, we argue that both of these theories miss the point that the marginal costs are dependent of the use of the funds, and the asset side of the balance sheet primarily determines the financing source for an additional Euro. An empirical analysis on a unique dataset of Portuguese SME's confirms that the composition of the asset side of the balance sheet has an impact of the type of financing used and the Pecking Order Theory and the traditional Static Trade-off theory are rejected.

Second Metatarsophalangeal joint Synovitis: Update

In podiatric clinics is very common to find inflamatory process in metatarsophalangeal joint capsule , plantar plate and collateral ligaments damage, but it is not clearly recognized. Many authors hipotetized with joint instability of multiple aetiology and his concomitant evolution in different stages with own joint disease. This pathology has more incidence in second metatarsophalangeal joint than third and others and it is a common etiology of metatarsal pain. Bad biomechanics alters forefoot function and can produce overload in capsular joint, decreasing mobility and getting worse the pathology.

Recent Innovations in Antibody-Mediated, Targeted Particulate Nanotechnology and Implications for Advanced Visualisation and Drug Delivery

Research into the targeting of drug substances to a specific disease site has enjoyed sustained activity for many decades. The reason for such fervent activity is the considerable clinical advantages that can be gained when the delivery system plays a pivotal role in determining where the drug is deposited. When compared to conventional formulations where no such control exists, such as parenteral and oral systems, the sophisticated targeting device can reduce side effects and limit collateral damage to surrounding normal tissue. No more so is this important than in the area of oncology when dose-limiting side effects are often encountered as an ever present difficulty. In this review, the types of colloidal carrier commonly used in targeted drug delivery are discussed, such as gold and polymeric colloids. In particular, the process of attaching targeting capabilities is considered, with reference to antibody technologies used as the targeting motifs. Nanotechnology has brought together a means to carry both a drug and targeting ligand in self-contained constructs and their applications to both clinical therapy and diagnosis are discussed.

mGluR5 Positive Allosteric Modulators Facilitate both Hippocampal LTP and LTD and Enhance Spatial Learning

Highly selective positive allosteric modulators (PAMs) of metabotropic glutamate receptor subtype 5 (mGluR5) have emerged as a potential approach to treat positive symptoms associated with schizophrenia. mGluR5 plays an important role in both long-term potentiation (LTP) and long-term depression (LTD), suggesting that mGluR5 PAMs may also have utility in improving impaired cognitive function. However, if mGluR5 PAMs shift the balance of LTP and LTD or induce a state in which afferent activity induces lasting changes in synaptic function that are not appropriate for a given pattern of activity, this could disrupt rather than enhance cognitive function. We determined the effect of selective mGluR5 PAMs on the induction of LTP and LTD at the Schaffer collateral-CA1 synapse in the hippocampus. mGluR5-selective PAMs significantly enhanced threshold theta-burst stimulation (TBS)-induced LTP. In addition, mGluR5 PAMs enhanced both DHPG-induced LTD and LTD induced by the delivery of paired-pulse low-frequency stimulation. Selective potentiation of mGluR5 had no effect on LTP induced by suprathreshold TBS or saturated LTP. The finding that potentiation of mGluR5-mediated responses to stimulation of glutamatergic afferents enhances both LTP and LTD and supports the hypothesis that the activation of mGluR5 by endogenous glutamate contributes to both forms of plasticity. Furthermore, two systemically active mGluR5 PAMs enhanced performance in the Morris water maze, a measure of hippocampus-dependent spatial learning. Discovery of small molecules that enhance both LTP and LTD in an activity-appropriate manner shows a unique action on synaptic plasticity that may provide a novel approach for the treatment of impaired cognitive function. Neuropsychopharmacology (2009) 34, 2057-2071; doi:10.1038/npp.2009.30; published online 18 March 2009

Context-Dependent Pharmacology Exhibited by Negative Allosteric Modulators of Metabotropic Glutamate Receptor 7

Phenotypic studies of mice lacking metabotropic glutamate receptor subtype 7 (mGluR7) suggest that antagonists of this receptor may be promising for the treatment of central nervous system disorders such as anxiety and depression. Suzuki et al. (J Pharmacol Exp Ther 323: 147-156, 2007) recently reported the in vitro characterization of a novel mGluR7 antagonist called 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), which noncompetitively inhibited the activity of orthosteric and allosteric agonists at mGluR7. We describe that MMPIP acts as a noncompetitive antagonist in calcium mobilization assays in cells coexpressing mGluR7 and the promiscuous G protein G alpha(15). Assessment of the activity of a small library of MMPIP-derived compounds using this assay reveals that, despite similar potencies, compounds exhibit differences in negative co-operativity for agonist-mediated calcium mobilization. Examination of the inhibitory activity of MMPIP and analogs using endogenous G(i/o)-coupled assay readouts indicates that the pharmacology of these ligands seems to be context-dependent, and MMPIP exhibits differences in negative cooperativity in certain cellular backgrounds. Electrophysiological studies reveal that, in contrast to the orthosteric antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxyclycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), MMPIP is unable to block agonist-mediated responses at the Schaffer collateral-CA1 synapse, a location at which neurotransmission has been shown to be modulated by mGluR7 activity. Thus, MMPIP and related compounds differentially inhibit coupling of mGluR7 in different cellular backgrounds and may not antagonize the coupling of this receptor to native G(i/o) signaling pathways in all cellular contexts. The pharmacology of this compound represents a striking example of the potential for context-dependent blockade of receptor responses by negative allosteric modulators.

Good news-bad news:the Yin and Yang of immune privilege in the eye

The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialized function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because its natural defenses are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood-ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics, and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumor-related IP can combine to permit extensive tumor growth and increased risk of metastasis thus threatening the survival of the host.

Community asset transfer in Northern Ireland

Community Asset Transfer (CAT), introduced by the New Labour administration and strengthened by the Coalition, aims to provide local groups with the opportunity to own public sector facilities and related services. It is a contested concept, with critics seeing it as another strategy in welfare displacement and state disinvestment, while for others it offers communities an opportunity to acquire collateral and take control over services affecting their lives. This paper explores CAT in Northern Ireland and suggests that while there are important practices, the region lacks the policies, legislative framework and skills to develop it in more progressive and inclusive ways.

The Impact of Extension and Ecosystem Services on Smallholders’ Credit Constraint.

On formal credit markets, access to formal credit and reasonable credit terms of smallholder farmers
in rural sub-Saharan Africa is limited due to adverse selection. Financial institutions operating in
rural areas often cannot distinguish between borrowers (farmers) that are creditworthy and those that
are not, thus, allocate limited resource to agriculture to reduce credit risk. In the presence of limited business quality signaling by smallholder farmers, financial institutions shall demand for collateral and/or offer unfavorable contract terms. Moreover, agricultural productivity of rural sub-Saharan
Africa, dominated by subsistence or small-scale farmers, is also negatively impacted by the adverse
effect of climate change. A strategy that may make the farming practices of smallholder farmer’s
climate resilient and profitable may also improve smallholder farmer's access to formal credit. This
study investigates to what extent participating in ecosystem and extension services (EES) programs
signals business quality of smallholders, thus granting them credit accessibility. We collected data
on 210 smallholder farmers in 2013, comprising farmers that receive payments for ecosystem
services (PES) and farm management training from the International Small Group Tree Planting
Program (TIST) Kenya to test the aforementioned theory empirically. We use game theory,
particularly a screening and sorting model, to illustrate the prospects for farmers with EES to access
formal credit and to improve their credit terms given that they receive PES and banking services
training. Furthermore, the PES’ long term duration (10 – 30 years) generates stable cash-flow which
may be perceived as collateral substitute. Results suggest that smallholder farmers in the TIST
program were less likely to be credit constraint compared to non-TIST farmers. Distance to market,
education, livestock and farm income are factors that determine access to credit from microfinance
institutions in rural Kenya. Amongst farmers that have obtained loans, those keeping business records
enjoy more favorable formal credit conditions. These farmers were observed to pay ca. 5 percent less
interest rate in microfinance charges. For TIST farmers, this type of farm management practices may
be attributed to the banking services and other training they receive within the program. While the
availability of classical collateral (farmlands) and PES may reduce interest rate, the latter was found
to be statistically insignificant. This research underlines the importance of an effective extension
services in rural areas of developing countries and the need to improve gains from conservation
agriculture and ensuing PES. The benefits associated with EES and PES may encompass agricultural
financing.

Evolução da qualidade de cebola armazenada, variedades "Pandero" e "Legend", em função da temperatura e aplicação de hidrazida maleica

A cebola representa no Ribatejo um dos produtos hortícolas de maior peso na economia agrícola regional. Os mercados dos produtos agrícolas são caracterizados por uma oferta contínua ao longo dos doze meses do ano. Actualmente é possível, garantir o fornecimento de cebola num apreciável período de tempo; no entanto, torna-se necessário proceder à sua conservação como forma de garantia de escoamento e regularização do abastecimento ao mercado. O material experimental constou de bolbos das variedades “Pandero” e “Legend” provenientes das plantações dos associados da Agromais e aplicação de um anti-abrolhante (hidrazida maleica), para que se tenha cebola não espigada com 6 meses de armazenamento, mantendo um equilíbrio no mercado durante o ano inteiro. As cebolas foram armazenadas em oito combinações; dois grupos da variedade “Pandero” um tratado outro não com HM, conservados a 4º C. Outros dois grupos da mesma variedade um tratado outro não com HM, conservados a 2,5ºC, repetindo a mesma forma na variedade “Legend”, com uma humidade relativa cerca de 75% (recomendada na conservação da cebola). Foram observadas as seguintes variáveis: podridão; espigamento; defeitos menores; defeitos maiores; defeitos totais e perda de peso. As observações foram realizadas em períodos de 15 em 15 dias, com os seguintes dias de conservação; 0; 16; 30; 46 e 59. O objectivo deste trabalho foi perceber os efeitos da hidrazida maleica e diferentes temperaturas (4 e 2,5ºC) sobre os parâmetros fisiológicos dos bolbos de cebola armazenados. Verificou-se uma menor podridão na temperatura a 2,5ºC, a HM reduziu o espigamento na variedade “Pandero” à temperatura de 4ºC, já sem HM o espigamento foi maior na “Pandero” à temperatura de 4ºC; com o abaixamento da temperatura de 4 para 2,5ºC houve uma redução de 5% no espigamento; os defeitos totais não foram afectados pela temperatura,

Aplicação da terapia fotodinâmica no processo de esterilização de sangue

A importância médica do sangue associada ao risco de doenças infeciosas levou a um melhoramento das técnicas de rastreio de patogénicos no sangue doado. No entanto, devido aos períodos de "janela", durante o qual os agentes infeciosos não podem ser detetados, a desinfeção de sangue e seus derivados assume uma importância vital. Considerando que as técnicas convencionais de desinfeção (tratamento com solvente-detergente ou irradiação com UV ou radiação gama) pode ser empregue em concentrados de plasma ou de proteínas, o efeito colateral associado aos respetivos tratamentos não permite a sua utilização em frações celulares. Consequentemente, é necessário o desenvolvimento de uma nova alternativa eficaz para inativar microrganismos em sangue. Uma boa estratégia que merece ser considerada baseia-se na terapia fotodinâmica antimicrobiana (aPDT). aPDT envolve a interação entre a luz e um fotossensibilizador (PS) na presença de oxigénio molecular. Esta interação produz espécies reativas de oxigénio (ROS), que causam danos oxidativos às moléculas microbianas necessárias à sobrevivência do microrganismo. Em alguns países, esta metodologia já está aprovada para descontaminação de plasma, utilizando azul de metileno ou psoraleno como PSs. O objetivo deste estudo foi avaliar a adequação de de estrutura do tipo ftalocianina (Pc) e porfirina (Por) para desinfeção fotodinâmica de hemoderivados. Plasma e sangue total foram infetados com 108 unidades formadoras de colónias (CFU) / mL de Escherichia coli e após incubação com os derivados Pc e Por em estudo, expostos respetivamente a luz vermelha ou a luz branca com uma irradiância de 150 W/m2durante 270 min. As concentrações de E. coli viáveis foram determinadas a 0, 30, 60, 90, 180 e 270 min e comparadas com as obtidas nos controlos claro (amostras irradiadas na ausência de PS) e controlos escuro (amostras incubadas com PS mas não irradiadas). O efeito do tratamento aPDT nas células do sangue (glóbulos vermelhos e brancos) também foi avaliado. Os resultados obtidos mostram que, em todos os componentes do sangue, a Por em estudo é mais eficaz na inativação de E. coli que o derivado Pc. Após o tratamento aPDT, o número de células vermelhas e brancas no sangue é semelhante aos valores observados nas amostras de controlo. A eficiente inativação de células de E. coli e a ausência de efeito sobre as células de sangue transformam os derivados porfirínicos e ftalocianinas potenciais candidatos a serem utilizados com fotossensibilizadores na desinfeção fotodinâmica de produtos derivados do sangue.