Dissertação (mestrado)—Universidade de Brasília, Instituto de Física, Programa de Pós-Graduação em Física, 2016. / A alternância dos comprimentos de ligação (Bond Length Alternation, BLA) em cadeias moleculares conjugadas longas tem sido tópico de discussões por muitas décadas, tanto experimental quanto teoricamente. O BLA é um parâmetro estrutural que vem da diferença entre o comprimento de ligações duplas e simples ao longo da cadeia conjugada. Neste trabalho nós utilizamos um método estatístico muito utilizado em várias áreas do conhecimento, a Análise dos Componentes Principais (do inglês Principal Components Analysis - PCA), criado por Karl Pearson em 1901, para redefinir o parâmetro BLA. Com esta técnica calculamos um parâmetro estrutural, comparável ao BLA, de um grupo de 17 moléculas derivadas de tertiofeno e, a partir disto, fizemos comparações com a forma mais comum de calcular o BLA, o que nos forneceu uma forma alternativa de calcular este parâmetro. Com a PCA podemos ir mais além ao cálculo do parâmetro estrutural e, por exemplo, podemos identificar quais ligações têm maior relevância para o valor do BLA. Outro ponto desta análise que merece destaque, foi mostrar a evolução dos coeficientes gerados por esta técnica, chamados de PC1, assim como, a evolução dos valores do BLA com o aumento do número de moléculas presentes no grupo inicial para o cálculo e a diferença em relação a aromaticidade de tais moléculas, mostrando qual o número mínimo para que esta técnica possa ser aplicada. / The Bond Length Alternation (BLA) in long conjugated molecular chains have been the topic of discussion for many decades, both experimentally and theoretically. The BLA is a structural parameter that comes from the difference between the length of double and single bonds along the conjugated chain. In this work we have used a statistical method widely used in many fields of knowledge, the Principal Component Analysis, created by Karl Pearson in 1901, to redefine the parameter BLA. With this technique we calculated the BLA of a group of 17 molecules derived from terthiophene and made comparisons with the most common way to calculate the BLA, which provided us with an alternative way to calculate the parameter. With the PCA we can go further the BLA and we can also identify which bonds are more relevant to its value. Another point that is worth mentioning, was showing the evolution of the coefficients generated by this technique, as well as the evolution of BLA values, along with the increasing number of molecules present in the initial group for the calculation and the differences between the aromaticity of such molecules, resulting in the minimum number to apply this technique.

La résistance aux antibiotiques est un problème majeur de santé publique. Les éléments génétiques mobiles, comme les séquences d’insertion (IS), jouent un rôle important dans la dissémination des gènes de résistance, notamment chez les entérobactéries, pathogènes majeurs chez l’Homme. Nous avons identifié une IS atypique, l’IS1294b (1713 pb) en amont du gène de la céphalosporinase blaCMY-2 présent sur le plasmide conjugatif (p2735) d’une souche d’origine clinique de Klebsiella pneumoniae résistante à haut niveau à la ceftazidime (céphalosporine de 3ième génération). L’IS1294b appartient à la famille des IS91-like qui transpose probablement selon le mode de la réplication du cercle roulant. Nous avons montré expérimentalement que l’IS1294b était capable de mobiliser le gène blaCMY-2 d'un plasmide à un autre, via le mécanisme de "one-ended transposition". Cette transposition, se produisant avec une fréquence comprise entre 1,7 et 14,0%, et implique la non-reconnaissance de l’une de ses extrémités (terIS). Nous avons développé un test chez Escherichia coli et étudié l’effet des mutations introduites dans l’IS1294b sur la fréquence de transposition in vivo. Nous avons identifié 8 nucléotides critiques à l’extrémité oriIS, et un motif de liaison à l’ADN probable (6 cystéines et 1 histidine importantes) dans le domaine N-terminal de la transposase. La délétion de la région 1 à 24 de l’extrémité terIS pourrait favoriser efficacement le mécanisme de « one-ended transposition ». Des résidus tyrosines (Y254 et Y258) et histidines (H164, H166 et H153) sont indispensables à l’activité de cette transposase Y2 et conforte son appartenance à la superfamille des protéines HUH. La purification, en cours, de la transposase (fusionnée à la thioredoxine pour la solubiliser) permettra l’étude ultérieure de son activité in vitro. Notre étude constitue une première description expérimentale de la mobilisation d'un gène d’une ß-lactamase par un élément appartenant à la famille des IS91 et ouvre des voies dans la compréhension du mécanisme de transposition de ces éléments génétiques mobiles. / Antibiotic resistance is a major public health issue. Mobile genetic elements, such as the insertion sequences (IS), play an important role in the dissemination of antibiotic resistance genes mainly in enterobacteria, major human pathogens. We identified an atypical IS, IS1294b (1713 bp), upstream the cephalosporinase gene, blaCMY-2. They were located on the conjugative plasmid (p2735) from a clinical strain of Klebsiella pneumoniae, highly resistant to ceftazidime (third generation cephalosporin). IS1294b belongs to the IS91-like family which probably transposes according to the mode of rolling circle replication. We have shown experimentally that IS1294b was able to mobilize the blaCMY-2 gene from a plasmid to another, through the mechanism of "one-ended transposition". This mobilization involving the non-recognition of the terIS end occurred with a percentage ranging between 1.7 and 14%. We developed a transposition test in Escherichia coli and studied the effect of mutations introduced into the IS1294b on in vivo transposition frequency. We identified 8 critical nucleotides at the oriIS end, and a probable DNA binding motif (6 cysteines and one histidine are essential) in the N-terminal domain of the transposase. The deletion of the region 1-24 at the terIS end could enhance effectively the mechanism of "one-ended transposition." Tyrosines residues (Y254 and Y258) and histidines (H164, H166 and H153) are essential to the activity of the transposase Y2 and reinforce its belonging to the HUH protein superfamily. Purification of the transposase (fused to the thiroredoxine for solubilization) is in progress and will allow further study of its in vitro activity. Our study is the first experimental description of the mobilization of a beta-lactamase gene by an element belonging to the IS91 family, and could initiate the understanding of the mechanism of transposition of these mobile genetic elements.

Extended-spectrum β-lactamases (ESBLs) are plasmid-mediated bacterial enzymes that confer resistance for most β-lactams antibiotics. These enzymes are widespread in microorganisms in hospital settings worldwide. This study estimated the distribution and prevalence of the main ESBLs families among samples of Escherichia coli and Klebsiella spp. in the university hospital of Santa Maria (HUSM), Rio Grande do Sul. During a period of 14 months 90 microorganisms were selected as probable ESBL producers according to the recommendations of Clinical and Laboratory Standards Institute (CLSI). The isolated microorganisms were submitted to phenotypic confirmatory tests for the presence of ESBL. Samples that showed negative results were tested against their susceptibility to cefoxitin. The ESBLs types found in each organism were determined by the research of the genes bla TEM, bla SHV e bla CTX-M by polymerase chain reaction (PCR). Fifty-five (61.1%) samples were confirmed as ESBL positive by the combined disc method and fifty-seven (63.3%) by the double disc method. In the cefoxitin susceptibility test 16 of the 39 samples presented resistance to this agent. Based on PCR, 74 (82,2%) samples harbored TEM-type ESBL gens, 61 (67,8%) SHV-type and 19 (21,1%) CTX-M-type. Only one Escherichia coli isolate appeared harboring genes for the CTX-M family of ESBLs. The distribution of TEM, SHV and CTX-M ESBL families from HUSM presented some similarities and differences compared with ESBLs of other hospital settings. / As β-lactamases de Espectro Estendido (ESBLs) são enzimas bacterianas mediadas por plasmídeos que conferem resistência à maioria dos antibióticos β-lactâmicos. Estas enzimas estão amplamente disseminadas em microrganismos nos ambientes hospitalares do mundo. Este estudo estimou a distribuição e prevalência das principais famílias de ESBLs entre amostras de Escherichia coli e Klebsiella spp. no Hospital Universitário de Santa Maria (HUSM), Rio Grande do Sul. Durante um período de 14 meses, 90 microrganismos foram selecionados como prováveis produtores de ESBLs de acordo com os critérios estabelecidos pelo Clinical and Laboratory Standards Institute (CLSI). Os microrganismos isolados foram submetidos a testes fenotípicos confirmatórios para a presença de ESBL. As amostras que apresentaram resultado negativo nestes testes tiveram sua susceptibilidade testada frente à cefoxitina. Os tipos de ESBLs presentes em cada microrganismo foram determinados pela pesquisa dos genes bla TEM, bla SHV e bla CTX-M através da reação em cadeia da polimerase (PCR). Empregando-se o método do disco combinado, a presença de ESBLs foi confirmada em 55 (61,1%) amostras; quando o método do duplo disco foi utilizado, 57 (63,3%) amostras foram confirmadas. No teste de susceptibilidade à cefoxitina, 16 das 39 amostras testadas apresentaram resistência a este substrato. Com base na PCR, 74 (82,2%) amostras possuíam genes para a família TEM de ESBLs, 61 (67,8%) para a família SHV e 19 (21,1%) para a família CTX-M. Apenas um isolado de Escherichia coli demonstrou possuir genes para a família CTX-M de ESBLs. A distribuição de ESBLs das famílias TEM, SHV e CTX-M no HUSM apresentou semelhanças e diferenças em comparação com ESBLs de outros ambientes hospitalares.

The experiments reported in this thesis studied the contributions of opioid and NMDA receptors to predictive fear learning, as measured by freezing in the rat. The first series of experiments (Chapter 2) used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct action of predictive error on Pavlovian association formation. Systemic administrations of the opioid receptor antagonist naloxone or intra-vlPAG administrations of the selective μ-opioid receptor antagonist CTAP prior to Stage II training prevented one-trial blocking. These results show for the first time that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation. The second series of experiments (Chapter 3) then studied temporal-difference prediction errors during Pavlovian fear conditioning. In Stage I rats received CSA ?? shock pairings. In Stage II they received CSA/CSB ?? shock pairings that blocked learning to CSB. In Stage III, a serial overlapping compound, CSB → CSA, was followed by shock. The change in intra-trial durations supported fear learning to CSB but reduced fear of CSA, revealing the selective operation of temporal-difference prediction errors. This bi-directional change in responding was prevented by systemic NMDA receptor antagonism prior to Stage III training. In contrast opioid receptor antagonism differentially affected the learning taking place during Stage III, enhancing learning to CSB while impairing the loss of fear to CSA. The final series of experiments (Chapter 4) then examined potential neuroanatomical loci for the systemic effects reported in Chapter 3. It was observed that intra-BLA infusion of ifenprodil, an antagonist of NMDA receptors containing the NR2B subunit, prevented all learning during Stage III, whereas intra-vlPAG infusion of the μ-opioid receptor antagonist CTAP facilitated learning to CSB but impaired learning to CSA. These results are consistent with the suggestion that opioid receptors in the vlPAG provide an important contribution to learning. Importantly, this contribution of the vlPAG is over and above its role in producing the freezing conditioned response. Furthermore, the findings of this thesis identify complementary but dissociable roles for amygdala NMDA receptors and vlPAG μ-opioid receptors in predictive fear learning.

The experiments reported in this thesis studied the contributions of opioid and NMDA receptors to predictive fear learning, as measured by freezing in the rat. The first series of experiments (Chapter 2) used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct action of predictive error on Pavlovian association formation. Systemic administrations of the opioid receptor antagonist naloxone or intra-vlPAG administrations of the selective μ-opioid receptor antagonist CTAP prior to Stage II training prevented one-trial blocking. These results show for the first time that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation. The second series of experiments (Chapter 3) then studied temporal-difference prediction errors during Pavlovian fear conditioning. In Stage I rats received CSA ?? shock pairings. In Stage II they received CSA/CSB ?? shock pairings that blocked learning to CSB. In Stage III, a serial overlapping compound, CSB → CSA, was followed by shock. The change in intra-trial durations supported fear learning to CSB but reduced fear of CSA, revealing the selective operation of temporal-difference prediction errors. This bi-directional change in responding was prevented by systemic NMDA receptor antagonism prior to Stage III training. In contrast opioid receptor antagonism differentially affected the learning taking place during Stage III, enhancing learning to CSB while impairing the loss of fear to CSA. The final series of experiments (Chapter 4) then examined potential neuroanatomical loci for the systemic effects reported in Chapter 3. It was observed that intra-BLA infusion of ifenprodil, an antagonist of NMDA receptors containing the NR2B subunit, prevented all learning during Stage III, whereas intra-vlPAG infusion of the μ-opioid receptor antagonist CTAP facilitated learning to CSB but impaired learning to CSA. These results are consistent with the suggestion that opioid receptors in the vlPAG provide an important contribution to learning. Importantly, this contribution of the vlPAG is over and above its role in producing the freezing conditioned response. Furthermore, the findings of this thesis identify complementary but dissociable roles for amygdala NMDA receptors and vlPAG μ-opioid receptors in predictive fear learning.

Identifying the dynamical processes that are active in tropical cirrus clouds is important for understanding the role of cirrus in the tropical atmosphere. This study focuses on analyzing turbulent motions inside tropical anvil cirrus with the use of a Cloud Resolving Model. Convection in the transition from shallow to deep convection has been simulated with Colorado State University Large Eddy Simulator/Cloud Resolving Model System for Atmospheric Model (SAM 6.3) in a high resolution three-dimensional simulation and anvil cirrus formed in the end of this simulation has been analyzed. For model set up, data gathered during the Tropical Rainfall Measuring Mission Large-Scale Biosphere-Atmosphere (TRMM LBA) field experiment in Amazonas, Brazil have been used as large scale forcing. 31 anvil clouds have been localized from a single time step of the simulation, “a snapshot”, of the entire simulated cloud field consisting of convective clouds of different scales and subsequently divided into three categories that represent different stages of the anvil lifetime; growing, mature and dissipating anvil stages. The classification is based on in-cloud properties such as cloud condensate content and vertical velocities. The simulated anvils have been analyzed both individually and as groups to examine the transition from isotropic three-dimensional turbulence in the convective core of the thunderstorm to stratified two-dimensional turbulence in the anvil outflow. A dimensionless number F is derived and used as a measure of the “isotropic” behavior of the turbulence inside the cloud. F is expressed as the ratio between the horizontal part of TKE and the total (horizontal + vertical) Experiments show that SAM 6.3 clearly can resolve turbulent structures and that the transition from isotropic three-dimensional turbulence to stratified two-dimensional turbulence occurs in the middle layers of the mature and dissipating anvil stages. / Sammanfattning av ”Studier av turbulenta rörelser i städmoln med hjälp av numeriska simuleringar av tropisk konvektion”  Städmoln i tropikerna har stor inverkan på strålningsballansen på grund av de är så vanligt förekommande och att de ligger på hög höjd i atmosfären. Att förstå de drivande krafterna som är aktiva i skapandet och underhållandet av städmoln är viktiga för att få en bra bild av rollen städmoln spelar i den tropiska atmosfären. Den här uppsatsen fokuserar på att studera turbulenta rörelser inuti tropiska städmoln med hjälp av en molnmodell. Tropisk konvektion har simulerats med Colorado State University’s molnmodell SAM 6.3 i en högupplöst tredimensionell simulering. Data från en ”ögonblicksbild” av det simulerade molnfältet har analyserats och 31 städmoln har valts ut och studerats vidare. De simulerade städmolnen indelades i tre olika kategorier baserat på utvecklingsstadier; växande städmoln, moget städmoln och skingrade städmoln. Stadieklassificeringen bestämdes beroende på isvatteninnehåll och vertikalhastigheter i molnet. Städmolnen har därefter analyserats både individuellt och som grupper för att lokalisera och analysera övergången från tredimensionell isotropisk turbulens i kärnan av Cb-molnet till tvådimensionell stratifierad turbulens i städmolnet. För att initiera simuleringen användes mätdata insamlade under fältexperimentet TRMM LBA (Tropical Rainfall Measuring Mission Large-Scale Biosphere-Atmosphere) i Amazonas, Brasilien. För att beskriva turbulenta rörelser i molnen togs det dimensionslösa talet 𝐹 fram som ett mått på isotropin. 𝐹 uttrycks som kvoten mellan den horisontella delen av TKE och den totala (horisontell och vertikal). Den här studien visar att den undersökta molnmodellen SAM 6.3 klart kan simulera turbulenta i rörelser i övergången mellan isotropisk till horisontell turbulens i olika stadier av städmolnens livscykel. Mina analyser visar att övergången sker främst i de mellersta skikten av de mogna och skingrade stadierna av städmolnets utveckling.

Made available in DSpace on 2014-06-11T19:32:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-05-20Bitstream added on 2014-06-13T20:23:54Z : No. of bitstreams: 1 dutra_i_dr_botfca.pdf: 443501 bytes, checksum: 619fba74818591e1f2862d5ce54ae329 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Universidade Estadual Paulista (UNESP) / Este trabalho foi desenvolvido na região do Agropólo Assu-Mossoró com objetivo de estudar os efeitos de três lâminas de irrigação, três doses de potássio e três doses de nitrogênio, aplicadas via fertirrigação por gotejamento, na produtividade e qualidade de frutos de melão Pele de Sapo. O estudo foi desenvolvido no período de setembro a dezembro de 2004 e constou de três experimentos realizados simultaneamente, sendo representados pelas lâminas de irrigação L1= 0,7.NTI, L2= 0,9.NTI e L3 = 1,1.NTI, que corresponderam a 281, 349 e 423 mm, respectivamente. Foi utilizado o delineamento experimental em blocos casualizados com três repetições, em esquema fatorial 3 x 3 + 2. Os onze tratamentos resultaram da combinação fatorial entre três doses de N e três doses de K, mais dois tratamentos adicionais (N0K2 e N2K0). As doses de N estudadas na pesquisa foram: N0 = 0 kg.ha-1, N1.= 91 kg.ha-1, N2 = 140 kg.ha-1 e N = 184 kg.ha-1; e as de K2O foram: K0 = 0 kg.ha-1, K1 = 174 kg.ha-1, K2 = 270 e K3 = 352 kg.ha-1. A fertirrigação foi realizada diariamente mediante curva de absorção utilizando-se injetores tipo venture. Para comparação dos tratamentos, foram avaliados os aspectos quantitativos (produção total, produção mercado externo e interno) e os qualitativos (teor de sólidos solúveis, firmeza e espessura de polpa e o índice de formato). O monitoramento da umidade no solo foi feita com tensiômetros instalados em torno das plantas. Pelos valores de tensão de água do solo, a lâmina de irrigação L3 manteve o perfil de distribuição de água mais constante do que os de L1 e L2. As produções comerciável e total foram influenciadas pelos níveis de irrigação e doses de nitrogênio, sendo as maiores produções de 30,97 e 37,40 Mg ha-1, obtidas com as combinações de 141 kg de N ha-1 e 381 mm e 149 kg de N ha-1 e 397 mm, respectivamente. Os níveis... / This work was developed region of Assu and Mossoró the objective to study the effects of three irrigations depths, and three potassium and nitrogen levels applied by drip fertirrigation, on yield and quality of pele de sapo melon fruits. The study, carried out between September and December 2004, was constituted by three simultaneous trials represented by irrigation depths: L1= 1,1.NTI, L2= 0,9.NTI e L3 = 0,7.NTI corresponding to 464, 385 e 308 mm, respectively. The experimental design was an entirely randomized block with three replications in a 3 x 3 + 2 factorial scheme. Eleven treatments resulted from the combination of three N doses, three K doses and two additional treatments (N0K2 e N2K0). Doses of N were: N0 = 0 kg.ha-1, N1.= 91 kg.ha-1, N2 = 140 kg.ha-1 and N3 = 184 kg.ha-1; and doses of K2O were: K0 = 0 kg.ha-1, K1 = 174 kg.ha-1, K2 = 270 and K3 = 352 kg.ha-1. The fertirrigation was applied daily based on nutrient absorption curves used injector type venture. Treatments were compared by quantitative (total yield, foreign market and national type yield) and qualitative aspects (soluble solids contents, pulp firmness, pulp thickness and shape index). Soil moisture monitoring was made by tensiometers installed around the plants. From the water soil tension values, the irrigation depht L3 maintained the water distribution pattern more constant than the L1 and L2.The marketable and total yields were modified by the irrigation dephts and nitrogen levels, with the higher yields of 30,97 and 37,40 Mg ha-1, obtained with the combinations of 141 kg N ha-1 and 381 mm and 149 kg N ha-1 and 397 mm, respectively. The irrigation levels affected the parameters of quality significantly evaluate the day of harvest, except the value of soluble solids contents that was also influenced by the other factors, with obtained the value of 12,2% with irrigation depht... (Complete abstract, click electronic access below)

Extended Spectrum β-Lactamases (ESBLs) are produced by the Enterobacteriaceae bacterial family, mainly by E. coli and K. pneumoniae. As these species are some of the main causes of urinary tract infections and sepsis, ESBL-production is of major concern. Occurrence of ESBLs also gives rise to concern as it is increasing epidemically. This because the genes coding for ESBLs (i.e. bla-genes) are located on plasmids replicating and spreading the replicated copies independently. Plasmids replicate by replicons. Plasmids with the same replicon variant are grouped into the same plasmid family. The aim of this study was to detect plasmid families carrying bla-genes in E. coli and K. pneumoniae from clinical (n = 6) and environmental water (n = 22) isolates. Plasmid family prevalence was examined. Association between plasmid families and bla-genes was also examined. Plasmid families were detected by a PBRT kit (PCR Based Replicon Typing), a multiplex PCR kit that detected 30 replicons, whereof 27 replicons representing the 27 plasmid families in Enterobacteriaceae, and three novel replicons. The IncF plasmid family was the most prevalent for both species in both clinical and environmental isolates. IncF seemed to be prevalent for all examined ESBLs, but it was difficult to associate one bla-gene with one plasmid family as most isolates carried several bla-genes and several plasmid families. / Extended Spectrum β-Lactamases (ESBLs) produceras av bakteriefamiljen Enterobacteriaceae, främst av E. coli och K. pneumoniae. Eftersom dessa arter är bland de vanligaste orsakerna till urinvägsinfektioner och sepsis är ESBL-produktion ett allvarligt problem. ESBL är också oroande eftersom det sprids epidemiskt. Detta möjliggörs av att generna som kodar för ESBLs (s.k. bla-gener) ligger på plasmider, som replikerar och sprider de replikerade plasmidkopiorna självständigt. Plasmider replikeras som s.k. replikon. Plasmider med samma replikonvariant tillhör samma plasmidfamilj. Syftet med detta arbete var att detektera plasmidfamiljer som bär bla-gener i E. coli och K. pneumoniae isolerade från kliniska prov (n = 6) och miljöprov (n = 22) från Helge Å. Plasmidfamiljernas prevalens undersöktes, liksom sambandet mellan plasmidfamiljer och bla-gener. Plasmidfamiljerna detekterades med ett PBRT-kit (PCR Based Replicon Typing), ett multiplext PCR-kit som detekterade 30 replikon varav 27 replikon som representerar de 27 plasmidfamiljer som finns i Enterobacteriaceae och tre nya replikon. Plasmidfamiljen IncF var vanligast förekommande i båda arter i både kliniska isolat och miljöisolat. IncF verkade förekomma för alla undersökta typer av ESBL, men det var generellt svårt att förknippa en bla-gen med en plasmidfamilj, eftersom de flesta isolaten bar flera bla-gener och flera plasmidfamiljer.

Ciliary neurotrophic factor (CNTF) is produced by astrocytes which have been implicated in regulating stress responses. We found that CNTF in the medial amygdala (MeA) promotes despair or passive coping, i.e., immobility in an acute forced swim stress, in female mice, while having no effect in males. Neutralizing CNTF antibody injected into the MeA of wildtype females reduced activation of downstream STAT3 (Y705) 24 and 48 h later. In concert, the antibody reduced immobility in the swim test in females and only after MeA injection, but not when injected in the central or basolateral amygdala. Antibody injected into the male MeA did not affect immobility. These data reveal a unique role of CNTF in female MeA in promoting despair or passive coping behavior. Moreover, 4 weeks of chronic unpredictable stress (CUS) increased immobility in the swim test and reduced sucrose preference in wildtype CNTF+/+, but not CNTF-/- littermate, females. Following CUS, 10 min of restraint stress increased plasma corticosterone levels only in CNTF+/+ females. In males, the CUS effects were present in both genotypes. Further, CUS increased CNTF expression in the MeA of female, but not male, mice. CUS did not alter CNTF in the female hippocampus, hypothalamus and bed nucleus of stria terminalis. This suggests that MeA CNTF has a female-specific role in promoting CUS-induced despair or passive coping, behavioral anhedonia and neuroendocrine responses. Compared to CNTF+/+ mice, CNTF-/- mice did not show differences in CUS-induced anxiety-like behavior and sensorimotor gating function as measured by elevated T-Maze, open field and pre-pulse inhibition of the acoustic startle response. Together, this study reveals a novel CNTF-mediated female-specific mechanism in stress responses and points to opportunities for developing treatments for stress-related disorders in women.