g., fictive eupnea and sighs)? (3) How is preBotC activity affected by surrounding structures? Using newborn rat slices with systematically varied dimensions in physiological [K+] (3 mM), we found that a 175 mu m thickness is sufficient for generating inspiratory-related rhythms. In 700-mu m-thick slices with unilaterally exposed preBotC, a kernel <100 mu m thick, centered 0.5 mm caudal to the facial nucleus, is necessary for rhythm AZD1208 manufacturer generation. Slices containing this kernel plus caudal structures produced eupneic bursts of

regular amplitude, whereas this kernel plus rostral tissue generated sighs, intermingled with eupneic bursts of variable amplitude (“eupnea-sighpattern”). After spontaneous arrest of rhythm, substance-P or neurokinin-1 MCC950 manufacturer (NK1) receptor agonist induced the eupnea-sigh burst pattern in >= 250-mu m-thick slices, whereas thyrotropin-releasing hormone or phosphodiesterase-4 blockers evoked the eupnea burst pattern. Endogenous rhythm was depressed by NK1 receptor antagonism. Multineuronal Ca2+ imaging revealed that preBotC neurons reconfigure between eupnea and eupnea-sigh burst patterns. We hypothesize a (gradient-like) spatio-chemical organization of regions adjacent to the preBotC, such

that a small preBotC inspiratory-related oscillator generates eupnea under the dominant influence of caudal structures or thyrotropin-releasing hormone-like transmitters but eupnea-sigh activity when the influence of rostral structures or substance-P-like transmitters predominates.”
“The purpose of the present study was to evaluate the effectiveness of a 3-carboranyl thymidine analogue (3CTA), 3-[5-2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-ylpentan-1-yl]

thymidine, designated N5-2OH, for boron neutron capture therapy (BNCT) of brain tumors using the RG2 rat glioma Epacadostat cell line model. Target validation was established using the thymidine kinase (TK) 1(+) wild-type, murine L929 cell line and its TK1(-) mutant counterpart, which were implanted s.c. (s.c.) into nude mice. Two intratumoral (i.t.) injections of B-10-enriched N5-20H were administered to tumor-bearing mice at 2-hour intervals, after which BNCT was carried out at the Massachusetts Institute of Technology (MIT) Research Reactor. Thirty days after BNCT, mice bearing TK1(+) L929 tumors had a 15x reduction in tumor volume compared with TK1(-) controls. Based on these favorable results, BINICT studies were then initiated in rats bearing intracerebral (i.c.) RG2 gliomas, after i.c. administration of N5-20H by Alzet osmotic pumps, either alone or in combination with i.v. (i.v.) boronophenylalanine (BIPA), a drug that has been used clinically. The mean survival times (MSTs) of RG2 glioma bearing rats were 45.6 +/- 7.2 days, 35.0 +/- 3.3 days, and 52.9 +/- 8.9 days, respectively, for animals that received N5-20H, BIPA, or both.

Mechanistic studies revealed that upon cellular uptake

and lysosomal delivery, GemC18 in the acid-sensitive micelles was released and hydrolyzed more efficiently. Furthermore, GemC18 loaded in the highly acid-sensitive PHC-2 micelles inhibited the expression of RRM1 and increased the level of gemcitabine triphosphate (dFdCTP) in gemcitabine resistant tumor cells. The strategy of delivering lipophilized nucleoside analogs using highly acid-sensitive micelles may represent a new platform technology to increase the antitumor activity of nucleoside analogs and to overcome tumor cell resistance to them. (C) 2012 Elsevier Ltd. All rights reserved.”
“The loci of the 5S and 45S rRNA genes were localized on chromosomes in five species of Capsicum, namely, an-nuum, chacoense, frutescens, baccatum, and chinense by MLN2238 nmr FISH. The 5S rDNA was localized to the distal region of one chromosome in all species observed. The number of 45S rDNA

loci varied among species; one in annuum, two in chacoense, frutescens, and chinense, and four in baccatum, with the exceptions that ‘CM334′ of annuum had three loci and ‘tabasco’ of frutescens had one locus. ‘CM334′-derived BAC clones, 384B09 and 365P05, were screened with 5S rDNA as a probe, and BACs 278M03 and 262A23 were screened with 25S rDNA as a probe. Both ends of these BAC clones were sequenced. FISH with these BAC probes on pachytenes from ‘CM334′ plant showed one 5S rDNA locus and three 45S rDNA

loci, consistent with the patterns on the somatic chromosomes. The 5S rDNA probe was also applied on extended DNA fibers to reveal that PCI-34051 its coverage measured as long as 0.439 Mb in the pepper genome. FISH techniques applied on somatic and meiotic chromosomes and fibers have been established for chili to provide valuable information about the copy Ferroptosis inhibitor review number variation of 45S rDNA and the actual physical size of the 5S rDNA in chili.”
“The transport of excitatory amino acids (EAA) in CNS is performed by a family of high affinity, sodium dependent carriers. One of these transporters, excitatory amino acid carrier 1 (EAAC1), is known to be regulated by several mechanisms that modify carrier abundance on the plasma membrane. Much less is known on EAAC1 regulation at the level of gene expression. Here we report that, in C6 rat glioma cells, a line recently described to contain neural stem-like cells, EAAC1 is markedly induced by all trans-retinoic acid (ATRA), a well known differentiating agent. Consistently, ATRA stimulates EAA transport, with the maximal effect observed at concentrations >= 1 mu M. After 4 days of treatment with 10 mu M ATRA, the transport V-max is fivefold enhanced, SIc1a1 mRNA is increased by 400% compared with control, EAAC1 carrier is sixfold overexpressed and the C6 culture is greatly enriched of cells with bipolar morphology strongly positive for EAAC1 immunoreactivity.

In the present study, we found that GADM effectively PCI-32765 inhibited cell proliferation and colony formation in MCF-7 human breast cancer cells, which was much stronger than that of MDA-MB-231 breast cancer cells. GADM both concentration- and time-dependently mediated G1 cell

cycle arrest and significantly decreased the protein level of CDK2, CDK6, cycle D1, p-Rb and c-Myc in MCF-7 cells. Moreover, GADM obviously induced DNA fragmentation and cleavage of PARP which are the characteristics of apoptosis and decreased the mitochondrial membrane potential in MCF-7 cells. Besides, we also showed that GADM elicited DNA damage as measured by comet assay which is a sensitive method for DNA damage detection. gamma-H2AX, a marker of DNA damage, was also slightly up-regulated after treated with GADM for 6 h, suggesting that the G1 cell cycle arrest and apoptosis induced by GADM may be partially resulted from GADM-induced DNA damage. These results have advanced our current understandings

of the anti-cancer mechanisms of GADM. (C) 2011 Elsevier B.V. All rights reserved.”
“The aim of the study was to analyse the status of the genetic structure of two autochthonous Croatian Podolian breeds (Istrian cattle and Slavonian Syrmian Podolians). The study comprised 20 randomly selected blood samples of each cattle breed. The genotyping was performed on 11 microsatellites (TGLA227, BM2113, TGLA53, ETH10, SPS115, TGLA126, TGLA122, INRA23, ETH3, ETH225, BM1824) as recommended by International Society of Animal S63845 nmr Genetics buy Cyclopamine and Food and Agriculture Organization. The procedure enabled the identification of 423 (96.14%) genotypes, indicating the validity of DNA analyses in blood samples and adequacy of the selected microsatellite markers. Likewise, there was the total number of 203 alleles with minimal differences among the studied groups. The differences (p > 0.05) were observed within the genotypes of the studied groups regarding the microsatellite

loci. The distribution of the genetic relationship was presented by Wright F coefficients. The F-IS had negative values for the TGLA 227 locus in both studied groups and for ETH3, ETH225 and BM1834 loci in the Slavonian Syrmian Podolians. This obtained data with relative high values of heterozygosity also shows a genetical influence of other breeds. Almost all F-IT values were appropriate (0.31905) as a result of excessive selection effects. The mean value of F-ST (0.07336) indicates that the average degree of genetic variability of the studied breeds was not significantly different despite certain differences in individual loci. The observed specific polymorphism of loci shows that the Istrian cattle and the Slavonian Syrmian Podolians have similar genetic characteristics, but also that there are certain differences between the breeds and even inter-breed differences.

All rights reserved.”
“Background: Nephrolithiasis is more frequent and severe in obese patients from different western nations. This may be supported by higher calcium, urate, oxalate excretion in obese stone formers. Except these parameters, clinical characteristics of obese stone formers were not extensively explored. Aims: In the present paper we studied the relationship between obesity and its metabolic check details correlates and nephrolithiasis.

Materials and methods: We studied 478 Caucasian subjects having BMI bigger than = 25 kg/m(2). The presence of nephrolithiasis, hypertension, diabetes mellitus and metabolic syndrome were noted. They underwent measurements of anthropometry (BMI and waist circumference, body composition), serum variables (fasting glucose, serum lipids and serum enzymes) and Mediterranean

diet (MedDiet) nutritional questionnaire. Results: 45 (9.4%) participants were stone formers. Subjects with high serum concentrations of triglycerides ( bigger than = 150 mg/dl), fasting glucose ( bigger than 100 mg/dl) and AST ( bigger than 30 U/I in F or bigger than 40 U/I in M) were more frequent among stone formers than non-stone formers. Multinomial logistic regression confirmed that kidney stone production was associated with high fasting glucose (OR = 2.6, 95% CI 1.2-5.2, P = 0.011), AST (OR = 4.3, 95% CI 1.1-16.7, P = 0.033) and triglycerides (OR = 2.7, 95% CI 1.3-5.7, P = 0.01). MedDiet score was not different in stone formers and non-stone formers. However, stone formers had a lower selleck inhibitor consumption frequency of olive oil and nuts, and higher consumption frequency of wine compared with non-stone formers. Conclusions: Overweight and obese stone SBE-β-CD cost formers may have a defect in glucose metabolism and a potential liver damage. Some foods typical of Mediterranean diet may protect against nephrolithiasis.”
“Rationale The risk of developing active tuberculosis in persons with latent Mycobacterium tuberculosis

infection is substantially increased shortly after HIV-1 seroconversion. Immune responses in the lung are important to restrict the growth of M. tuberculosis to prevent the development of disease.\n\nObjectives: To investigate innate and adaptive immune responses to M. tuberculosis in bronchoalveolar lavage from HIV-1-infected persons without active tuberculosis.\n\nMethods: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, HIV-1-uninfected (n = 21) and HIV-1-infected (n = 15) adults. Growth of M. tuberculosis was assessed in monocytes and alveolar macrophages. Cytokine expression by mycobacteria-specific CD4 and CD8 T cells was measured by intracellular cytokine staining or IFN-gamma ELISpot.\n\nMeasurements and Main Results: Mycobacterial growth in monocytes or alveolar macrophages from HIV-1-infected and -uninfected persons did not differ. Total CD4 T-cell frequencies in BAL were lower in HIV-1-infected than in HIV-1-uninfected persons (P < 0.001).

This study identified

24 differentially expressed genes in HBMECs upon A beta treatment. Among these genes, we found that the gene for a well-characterized calcium-regulating hormone, stanniocalcin-1 (STC1) was specifically up-regulated by A beta treatment in a time and dose-dependent manner. Moreover, using overexpression and knock-down strategies, we found that overexpression AMN-107 datasheet of STC1 decreased transmigration of monocytes induced by A beta and prevented A beta-induced apoptosis of HBMECs. in addition, we explored the possible mechanisms underlying the effects of STC1, showing that overexpression of STC1 attenuated the effect of A beta on up-regulating early growth response-1 (Egr-1), macrophage inflammatory SB273005 supplier Protein-1 beta (MIP-1 beta), or cleaved caspase-8. Our data thus indicate a key role of STC1 in the response of HBMECs to A beta exposure. (C) 2008 Elsevier Inc. All rights reserved.”
“The neural pathways through which substance P (SP) influences fear and

anxiety are poorly understood. However, the amygdala, a brain area repeatedly implicated in fear and anxiety processes, is known to contain large numbers of SP-containing neurons and SP receptors. Several studies have implicated SP neurotransmission within the amygdala in anxiety processes. In the present study, we evaluated the effects of site-specific infusions of an SP receptor antagonist, GR 82334, on conditioned fear responses using the fear-potentiated startle paradigm. GR 82334 infusion into the basolateral (BLA) or the medial (MeA) nuclei of the amygdala, but not into the central nucleus of the amygdala (CeA), dose dependently reduced fear-potentiated startle. Similar effects were obtained with GR 82334 infusion into the ventromedial nucleus of the hypothalamus (VMH), to which the MeA projects, and into the rostral dorsolateral periaqueductal gray (PAG), to which the VMH projects, but not into the deep layers of the superior colliculus/deep mesencephalic nucleus (dSC/DpMe), an output of the CeA previously shown to be important for fear-potentiated startle. Consistent with previous findings, infusion of the AMPA receptor DNA Damage inhibitor antagonist, NBQX, into the dSC/DpMe, but

not into the PAG, did disrupt fear-potentiated startle. These findings suggest that multiple outputs from the amygdala play a critical role in fear-potentiated startle and that SP plays a critical, probably modulatory role, in the MeA to VMH to PAG to the startle pathway based on these and data from others.”
“Global warming is currently of great concern. Yet the ecological effects of low-frequency climate variations remain largely unknown. Recent analyses of interdecadal variability in population abundance of the Oriental migratory locust (Locusta migratoria manilensis) in China have revealed negative associations with temperature and positive associations with Yangtze drought and flood frequencies during the past millennium (AD 957-1956).

This research demonstrated that the elevation of reactive RG-7112 supplier oxygen species is sufficient to induce the apoptosis of chicken embryonic fibroblasts, whereas the administration of Vitamin C does not necessarily have certain antiapoptotic effects, especially when the stimulus is not directly linked

with redox state.”
“Background: Previous studies on the association between the distribution of left ventricle hypertrophy and the clinical features of hypertrophic cardiomyopathy (HCM) have yielded unclear results. The aim of this study was to investigate the differences in the prevalence, clinical features, management strategies, and long-term outcomes between patients with midventricular hypertrophic obstructive cardiomyopathy (MVHOCM) and patients with apical check details HCM (ApHCM).\n\nMethods: A retrospective study of 60 patients with MVHOCM and 263 patients with ApHCM identified in a consecutive single-centre cohort consisting of 2068 patients with HCM was performed. The prevalence, clinical features, and natural history of the patients in these 2 groups were compared.\n\nResults: Compared

with ApHCM patients, patients with MVHOCM tended to be much younger and more symptomatic during their initial evaluation. Over a mean follow-up of 7 years, the probability of cardiovascular mortality and that of morbidity was significantly greater in MVHOCM patients compared with ApHCM patients (log-rank, P < 0.001).\n\nConclusions: Our results suggest that, compared with ApHCM, MVHOCM represents an uncommon presentation of the clinical spectrum of HCM that is characterized by progressive clinical deterioration leading to increased cardiovascular mortality and morbidity. Our results also underscore the importance of the timely recognition of MVHOCM for the prediction of prognosis and the early consideration of appropriate management strategies.”
“Epstein-Barr selleck virus (EBV) is a ubiquitous virus that infects about 90-95% of the adult population. EBV establishes life-long latent persistence. The virus is found to be the major cause of infectious mononucleosis but

it has also been associated with development of endemic Burkitt’s lymphoma. Result of EBV infection is the most common complication in patients after transplantation which is a post-transplant lymphoproliferative disease. Strong associations between EBV infection and Hodgkin’s lymphoma, nasopharyngeal carcinoma, gastric carcinoma and carcinomas derived from smooth muscle tissue also exist. There is a hypothesis that there is an association between EBV infection and autoimmune and allergic diseases. EBV is a Herpesvirus family member; its genetic material has dsDNA form. There are two strains of EBV: A and B. The only host for EBV is human with target cells: B cells and epithelial cells. The life cycle of EBV consists of lytic and latent phases. In the latent phase three different patterns of gene expression are possible.

The efficiency of luciferase gene transfection of lipoplexes 1-3 was compared with that of commercial dioleoyl-trimethylammonium propane (DOTAP) and polyethyleneimine (PEI) in 293T cells and Epoxomicin cost HepG2 cells with or without poly(ethylene glycol) PEG stabilizer. The

complexation and protection of DNA of liposome 3 was the strongest among the three liposomes. The efficiency of gene transfection of liposomes 1-3 was two-to threefold higher than that of PEI and/or DOTAP in 293T cells. Liposomes 1 and 3 in PEG as stabilizer showed sixfold higher transfection efficiency than that of PEI and/or DOTAP, whereas liposome 2 showed very low transfection efficiency. In HepG2 cells, the transfection efficiency of all the cationic liposomes was much lower than that of DOTAP. In conclusion, lipids 1-3 were efficient and non-toxic gene vectors; the headgroup of cationic lipids and the stabilizer of liposome formulation had an important influence on gene transfection.”
“The abortive properties and the clinical and pathological features https://www.selleckchem.com/products/dinaciclib-sch727965.html of poisoning by the pods of Stryphnodendron fissuratum were studied in 8 pregnant goats. Two goats that ingested 3.25 g/kg body weight daily doses for 2 days, and 2 that ingested 2.5 g/kg daily doses for 3 days showed digestive clinical signs and aborted, but the animals that ingested 3 daily doses of 2.5 g/kg died. Lesions of the digestive system

and liver were observed at necropsy. Two goats that ingested a single dose of 5.5 g/kg showed mild clinical signs and recovered without abortion. Another 2 goats that ingested single doses of 5 g/kg showed no clinical signs. These results demonstrate that Stryphnodendron fisuratum pods cause digestive disorders, liver disease, abortion Kinase Inhibitor Library supplier and death. (C) 2011 Elsevier Ltd. All rights reserved.”
“Hypocalcaemia is a rare complication of calcium channel blocker overdose, having been reported only once previously (J Toxicol Clin Toxicol, 1992, 30, 309). In this article,

we report a case of a 37-year-old woman who developed hypocalcaemia after a verapamil overdose, review the literature and propose a mechanism for this rare finding.”
“BACKGROUND: Breast-associated morphea (BAM) can mimic benign and malignant inflammatory breast disorders. The aim of the current study was to document our experience with this rare sclerosing dermatologic disorder.\n\nMETHOD: We conducted a retrospective study at a single institution of all patients who had pathological diagnosis of morphea between January 1995 and October 2007.\n\nRESULTS: We identified 15 patients with pathological evidence of morphea involving the breast. Two thirds of these patients were initially misdiagnosed with inflammatory breast cancer or breast infections. While 2 patients had previous exposure to external beam radiation, the remaining patients had no identifiable predisposing risk factors.

Muscle stretching (sinusoidal half-waves of different amplitudes and combinations of such waves) allowed us to obtain well-reproducible

successions of impulses with no significant changes in the resting MP of the studied motoneurons. In 14 of such cells, we found BI 6727 significant correlation between normalized variations of the instantaneous frequency (in a sequence of preceding and subsequent action potentials, APs), indicative of a considerable probability of alternation of high and low values of this parameter. The same trend (toward alternation of high and low values) was observed in successive magnitudes of afterhyperpolarization (AH) that followed APs. Between the values of the extrema of AH trajectories and values of the instantaneous frequency of impulsation, we observed significant negative correlation. The mechanisms underlying the formation of

AH in spinal motoneurons and also the effects of this hyperpolarization on the characteristics of impulse activity generated by these cells are discussed.”
“Pyomyositis, a subacute bacterial infection of muscles, is uncommon in children. Three children with pyomyositis and multiple abscesses caused by Staphylococcus aureus are reported. The intercostal muscles were involved in one case, the paraspinal muscles in another and in the third there was associated septic arthritis.”
“An emotional version of Sapir-Whorf hypothesis suggests that differences in language emotionalities influence differences among CCI-779 cultures no less than conceptual differences. Conceptual contents of languages and Cultures to significant extent are determined by words and their semantic differences; these could be borrowed among languages and exchanged among cultures. Emotional

differences, as suggested in the paper, are related to grammar and mostly cannot be borrowed. The paper considers conceptual https://www.selleckchem.com/products/carfilzomib-pr-171.html and emotional mechanisms of language along with their role in the mind and Cultural evolution. Language evolution from primordial undifferentiated animal cries is discussed: while conceptual contents increase, emotional reduced. Neural mechanisms of these processes are suggested as well as their mathematical models: the knowledge instinct, the dual model connecting language and cognition, neural modeling fields, Mathematical results are related to cognitive science, linguistics, and psychology. Experimental evidence and theoretical arguments are discussed. Dynamics of the hierarchy-heterarchy Of human minds and cultures is formulated using mean-field approach and approximate equations are obtained. The knowledge instinct operating in the mind heterarchy leads to mechanisms of differentiation and synthesis determining ontological development and cultural evolution.

\n\nConclusion: This study reveals an alarmingly high prevalence of STH among Orang Asli children and clearly brings out an urgent need to implement school-based de-worming programmes and other control measures like providing Sapitinib clinical trial a proper sanitation, as well as a treated drinking water supply and proper health education regarding good personal hygiene practices. Such an integrated control program will help significantly in reducing the prevalence

and intensity of STH in Orang Asli communities.”
“Bacterial lipopolysaccharide (LPS) is widely used to study immune influences on the CNS, and cerebrovascular prostaglandin (PG) synthesis is implicated in mediating LPS influences on some acute phase responses. Other bacterial products, such as staphylococcal enterotoxin B (SEB), impact target tissues differently

in that their effects are T-lymphocyte-dependent, yet both LPS and SEB recruit a partially overlapping set of subcortical central autonomic cell groups. We sought to compare neurovascular responses to the two pathogens, and the mechanisms by which they may access the brain. Rats received iv injections BB-94 Proteases inhibitor of LPS (2 mu g/kg), SEB (1 mg/kg) or vehicle and were sacrificed 0.5-3 h later. Both challenges engaged vascular cells as early 0.5 h, as evidenced by induced expression of the vascular early response gene (Verge), and the immediate-early gene, NGFI-B. Cyclooxygenase-2 (COX-2) expression was detected in both endothelial and perivascular cells (PVCs) in response to LPS, but only in PVCs of SEB-challenged animals. The non-selective COX inhibitor, indomethacin LY3023414 in vivo (1 mg/kg, iv), blocked LPS-induced activation

in a subset of central autonomic structures, but failed to alter SEB-driven responses. Liposome mediated ablation of PVCs modulated the CNS response to LPS, did not affect the SEB-induced activational profile. By contrast, disruptions of interoceptive signaling by area postrema lesions or vagotomy (complete or hepatic) markedly attenuated SEB-, but not LPS-, stimulated central activational responses. Despite partial overlap in their neuronal and vascular response profiles, LPS and SEB appear to use distinct mechanisms to access the brain. (C) 2009 Elsevier Inc. All rights reserved.”
“Bladder cancer is the second most common cancer of the urinary tract, however the invasive cystoscopy is still the standard technique for diagnosis and surveillance of bladder cancer. Herein, we radiolabel bladder cancer specific peptide with radioactive iodine (I-131/124) and evaluate its potential as a new radiopharmaceutical for the non-invasive diagnosis of bladder cancer.

The overall yield of the purified Al-BMP was about 15% as related to the initial amount of the hemeprotein. Al-BMP possesses extensive fluorescence

in the 550650 nm region with excitation in the porphyrin absorbance bands. The protein was shown to bind substrates of P450BM-3 (palmitic, arachidonic, and cis-parinaric acids) with affinities similar to those of the native enzyme (36 mu M). However, the substrate-induced changes in fluorescence SN-38 of Al-PP reveal the existence of a second, low-affinity substrate-binding site, which cannot be detected by the spin shift in the native, heme-containing BMP. Using fluorescence resonance energy transfer, we have demonstrated that Al-BMP forms a complex with the flavoprotein domain of P450BM-3 labeled with

7-ethylamino-3-(4′-maleimidylphenyl)-4-methylcoumarin maleimide, revealing the affinity similar to that of native BMP (Kd = 5 mu M at 0.06 M ionic strength). Therefore, aluminum-substituted BMP may serve as a valuable tool in studies on the mechanisms of interactions of P450s with their substrates and protein partners.”
“Novel geldanamycin derivative, 4,5-dihydro-thiazino-geldanamycin (3), was characterized from the gdmP mutant in Streptomyces hygroscopicus 17997, besides expected 4,5-dihydro-geldanamycin (2). The presence of this compound would suggest an unknown post-PKS modification in geldanamycin biosynthesis. Compound BTSA1 3 exhibited moderate anti-HSV-1-virus activity and higher water solubility than geldanamycin (1). Cysteine served as a precursor to synthesize 3, whose formation required obligatory enzymatic assistance.”
“Sleep deprivation impairs contextual but not cued learned fear, and it has been suggested that this SRT2104 chemical structure pattern reflects an insensitivity of the amygdala to sleep loss. The lack of effect of sleep deprivation on cued conditioning, however, might simply be due to the strong

attention drawn by the typically loud cue tone. We reduced tone volume from our standard 80 dB to either 70 or 60 dB, to test if reduced cue volume allowed effects of sleep deprivation to be detected. Using the platform-over-water method, male C57BL/6 mice were sleep-deprived for 24 h: control mice were moved to novel cages for 24 h. Mice then underwent fear conditioning with a standard “delay” protocol, and were tested for contextual and cued learning the next day. A control group received no footshock during conditioning. In the cue test, and for both cue volumes, SD had no effect on freezing to the tone, which was very robust in conditioned mice regardless of sleep treatment. As expected, freezing to the tone in the no-shock groups was essentially absent. Also, freezing prior to the tone was low in all mice. At the lowest volume, the tone was only similar to 10 dB above background noise. 24 h sleep deprivation, however, blocked contextual fear in the same mice.