Female patients outnumbered males by a ratio of more than 2 : 1. The mean time from referral to be seen in clinic was 25 days, 28 days, and 13 days respectively. Hb and MCV were checked in all patients and ferritin in 98%–100%. Among patients referred, IDA was confirmed in 86%, 79%, and 90% respectively. EMA was checked in 89%, 100%, and 97% respectively. Of patients found to have IDA, the proportion sent for both upper and lower GI investigation was 72%, 95%, and 99% (90% attended and completed investigations). In the 2004 audit, a further 17% underwent gastroscopy only and 12% had colonoscopy only. Conclusion: The nurse led

clinic for anaemia has proved to be an effective way to manage the large number of referrals for investigation of IDA. Significant pathology is identified early as a result http://www.selleckchem.com/products/CP-690550.html of the requested investigations (up to 9% colorectal cancers and up to 6% coeliac disease). Notable improvements in the service since 2004 are reduced waiting times and increased compliance with investigation recommendations.

The proportion of patients referred who are confirmed to have IDA has also increased. PLX4032 Key Word(s): 1. Anaemia; 2. Iron deficiency; Presenting Author: LIFANG ZHAO Additional Authors: JIANHONG WANG Corresponding Author: JIANHONG WANG Affiliations: xijing hospital of digestive disease Objective: To analyze the clinical features of upper gastrointestinal bleeding (UGB) in elderly patients. Methods: The clinical features of 365 elderly patients with UGB treated in our hospital from January 2009 to December 2012 were retrospectively analyzed, and compared with those of 410 younger patients

during the same period. Results: Incidence of UGB caused by peptic ulcer, acute gastric mucosal lesion and digestive tract cancer is significantly higher in older age-group than in younger group (P < 0.01 or 0.05), while the incidence by esophageal-gastric varices bleeding (EGVB) is significantly lower in older age-group than in younger group (P < 0.01). UGB caused by gastric ulcer is mainly in older age-group, Progesterone while that by duodenal ulcer is mainly in younger group. Compared with the younger patients, aged patients had fewer known contributing causes for UGB (P < 0.05). However, incidence of UGB in aged patients used non-steroids or glucocorticoid is significantly higher than that in younger patients, and incidence of UGB in aged patients of excessive drinking is significantly lower than that in younger patients (P < 0.01). Incidence of hypo-perfusion of peripheral circulation is significantly higher in older age-group than in younger group, while that of upper abdominal pain is significantly lower in older age-group than in younger group (P < 0.01). incidence of haematemesis is significantly lower in older age-group than in younger group, while incidence of tarry stool is significantly higher in older age-group than in younger group (P < 0.05).

Future work should evaluate more broad-spectrum miRNA profiling on larger sample sizes. Clinical questions for future study include how well miR-20a and miR-92a discriminate HCV liver disease from liver disease by other factors, including hepatitis B virus, alcohol, and nonalcoholic fatty liver disease. Questions for basic researchers will be to determine how acute HCV infection leads to changes in serum miRNA levels. What are the cellular pathways that generate circulating miRNAs? Are cellular pathogen recognition receptors, CP-673451 purchase such as retinoic acid inducible gene I and Toll-like receptor (TLR)3, known sensors of HCV infection in hepatocytes,[14,

15] or TLRs 2, 7, and 8, which appear to sense HCV RNA or proteins in immune cells,[16] or C1q complement receptor, a sensor of HCV core protein,[17] involved in miRNA induction? Furthermore, what cellular mRNAs are being regulated by these HCV-induced miRNAs? Which host cell types are being targeted, and importantly, how do host miRNA responses influence HCV infection and contribute to pathogenesis of HCV liver disease? Studies of this nature will undoubtedly keep miRs in scientific Selleck GSK-3 inhibitor and clinical orbit for years to come as scientists continue to define the mechanisms for miRNA-associated liver disease as well as prognostic values of circulating miRNAs. The author thanks Peter Sarnow and Joyce Wilson for reviewing the manuscript.

Stephen J. Polyak, Ph.D. “
“Aim:  Several host and viral factors have been reported to influence the effectiveness of pegylated interferon plus ribavirin combination therapy for chronic hepatitis C. In Japan, where the age of treated patients is comparatively high, recent studies have reported poor response to treatment in older female patients, but little is known about the relationship between advanced age in women and previously reported factors. Methods:  Using a database of 1167 patients chronically infected

with hepatitis C virus (HCV) genotype 1b, we analyzed the amino acid sequences of the HCV core protein and interferon sensitivity determining region (ISDR) and examined the relationships among predictive Thiamine-diphosphate kinase factors. Results:  The proportion of patients with substitutions at core 70, which is associated with poor response to pegylated interferon plus ribavirin therapy, increased with age only in female patients. A similar trend was observed for ISDR wild type (wt). We also found that core 70 wt is associated with core 91 wt (P = 5.4 × 10−9) as well as ISDR wt (P = 0.025). HCV RNA levels were higher in patients with core and ISDR wt (P < 0.001). Furthermore, core amino acid mutations were associated with advanced fibrosis and higher inflammatory activity (P = 0.028 and 0.048, respectively) as well as higher gamma-glutamyltranspeptidase, alanine aminotransferase and low-density lipoprotein cholesterol levels (P < 0.001, 0.006 and 0.001, respectively).

3A,B). In this regard, D-UCMSCs resembled PHHs serving as positive controls. ASGPR has been suggested to play a role in HBV binding and uptake.8-10 HBV uptake by D-UCMSCs was directly correlated with ASGPR mRNA expression see more (R2 = 0.924, P < 0.01; Fig. 3C). In Fig. 3D we show that HBV binding

to D-UCMSCs may be partially inhibited by Ca2+ chelation (21.1 ± 2.5% inhibition) and thyroglobulin addition (77.8 ± 1%), the latter being one known ASGPR-specific ligand. Suramin, which is known to block HBV attachment,22, 23 inhibited 87.4 ± 1% of HBV binding to D-UCMSCs. The addition of increasing concentrations of D-galactose (0.03-100 μM), before and during inoculation of D-UCMSCs, resulted in a dose-dependent inhibition of HBV uptake (up to 79.3 ± 0.7%, P < 0.0001; Fig. 3E). The median effective concentration (EC50) = 0.2 μM (95% confidence interval [CI], 0.17-0.23) was calculated for D-galactose by dose-response analysis (Supporting Fig. 4F). Total HBV DNA was quantified BMN 673 clinical trial by qPCR at 3 and

7 days postinfection and compared to the amount of viral DNA present inside the cells at 24 hours postincubation (Fig. 4A). Intracellular HBV DNA levels decreased along time in UD-UCMSCs (P < 0.0001), whereas they increased in PHHs (P = ns) and D-UCMSCs (P = 0.016) at day 3 and 7, suggesting productive viral replication. At 7 days postinfection, intracellular HBV DNA levels did not differ between D-UCMSCs and PHHs, but were significantly higher in D-UCMSCs than in UD-UCMSCs (P < 0.01). A further increase of HBV DNA levels was seen at 10 days postinfection in D-UCMSCs (P = 0.029; Fig. 4B). PHHs were not tested beyond 7 days postinfection to avoid biases due to dedifferentiation.11 In D-UCMSCs, an MOI of at least 100 was needed to yield detectable viral replication (Fig. 4C). Increase of HBV DNA replication intermediates along time was confirmed at Southern blotting

on the same samples used for qPCR (Supporting Fig. 5C). We subsequently measured cccDNA by qPCR (Fig. 4D). In D-UCMSCs, cccDNA levels increased along time up to 0.03 ± 0.04 copies/cell at 7 days postinfection, corresponding Bcl-w to approximately every 30th cell containing at least one copy of cccDNA. By contrast, 0.7 ± 0.8 copies/per cell were found in PHHs, and no cccDNA was detected in UD-UCMSCs. Controls to prove specificity of cccDNA detection by qPCR are shown in the Supporting Data. To further confirm the effect of differentiation on cellular susceptibility to viral replication, we infected UD-UCMSCs as described above and induced differentiation after 24 hours. For this postinfection differentiation we used a serum-free medium corresponding to the final step of the differentiation protocol described above. HBV DNA levels in UCMSCs undergoing postinfection differentiation increased along time as compared to UD-UCMSCs (P = 0.018), suggesting replication of the small quantity of HBV (0.22 ± 0.32 vge/cell) internalized by undifferentiated cells (Fig. 4E).

Our results showed that successful sexual reproduction can only be achieved when crossing parental strains in the exponential growth phase. Evidence was provided for the fact that sexual reproduction is a density-dependent 3-deazaneplanocin A price event and requires a threshold cell concentration to start, although this might vary considerably amongst strains. Moreover, the onset of the sexual phase was coupled to a marked reduction in growth of the vegetative parental cells. The crosses carried out in physically mixed conditions produced a significantly reduced number of sexual stages as compared to crosses in still conditions, showing that mixing

impairs sexualization. The results of our experiments suggest that the signaling that triggers the sexual phase is favored when cells can accumulate, reducing the PD0325901 distance between them and facilitating contacts and/or the perception of chemical cues. Information on the progression of the sexual phase in laboratory conditions

help understanding the conditions at which sex occurs in the natural environment. “
“Bulk segregant analysis, random amplified polymorphic DNA (RAPD), and sequence characterized amplified region (SCAR) methods were used to identify sex-linked molecular markers in the haploid-diploid rhodophyte Gracilaria chilensis C. J. Bird, McLachlan et E. C. Oliveira. One hundred and eighty 10 bp primers were tested on three bulks of DNA: haploid males, haploid females, and diploid tetrasporophytes. (-)-p-Bromotetramisole Oxalate Three RAPD primers (OPD15, OPG16, and OPN20) produced male-specific bands; and one RAPD primer (OPD12), a female-specific band. The sequences of the cloned putative sex-specific PCR fragments were used to design specific primers for the female marker SCAR-D12-386 and the male marker SCAR-G16-486. Both SCAR markers gave unequivocal band patterns that allowed sex and phase to be determined in G. chilensis. Thus, all the females presented only the female band, and all the males only the male band, while all the tetrasporophytes amplified both male and female bands.

Despite this sex-specific association, we were able to amplify SCAR-D12-386 and SCAR-G16-486 in both sexes at low melting temperature. The differences between male and female sequences were of 8%–9% nucleotide divergence for SCAR-D12-386 and SCAR-G16-486, respectively. SCAR-D12-386 and SCAR-G16-486 could represent degenerated or diverged sequences located in the nonrecombining region of incipient sex chromosomes or heteromorphic sex chromosomes with sequence differences at the DNA level such that PCR primers amplify only one allele and not the other in highly specific PCR conditions. Seven gametic progenies composed of 19 males, 19 females, and the seven parental tetrasporophytes were analyzed. In all of them, the two SCAR markers segregated perfectly with sexual phenotypes. “
“The cell-cycle progression of Ulva compressa is diurnally gated at the G1 phase in accordance with light–dark cycles.

Interestingly, the CD4+/CD8+ ratio changed after splenectomy without other treatment. However, many confounding factors may be implicated in this change. It is likely that patients

with a high fibrotic area in their liver specimens had a high CD4+/CD8+ ratio; Estrogen antagonist therefore, we may expect a decrease in the CD4+/CD8+ ratio after splenectomy. A decrease in Treg cells that stimulate TGF-β1 may lead to alleviation of fibrosis. Because the immune function of CD4+ CTL, CD8+ CTL and the CD4+/CD8+ ratio is affected by a wide variety of factors including recent exercise, poor nutrition and coincident acute viral infections, it is difficult to evaluate immune function using only CD4+ CTL, CD8+ CTL and the CD4+/CD8+ ratio. However, in our study, the ratio of CD4+ T cells to all lymphocytes in PB was significantly decreased in cirrhotic patients after splenectomy, while the ratio of CD8+ T cells FK506 ic50 to all lymphocytes slightly increased, resulting in a significant decrease in the CD4+/CD8+ ratio. The CD4+/CD8+ ratios in PB, spleens and livers were significantly higher in patients

with hypersplenism and in those in whom liver fibrosis had progressed than in the controls. As a positive correlation was observed between the CD4+/CD8+ ratios in the spleens, livers and PB, it is possible to expect to predict the immunological state of the liver and spleen from the immunological state of PB. In addition, carcinogenesis was significantly lower in groups in which a large difference in the CD4+/CD8+ ratio was observed between before and after splenectomy or in those with a high CD4+/CD8+ ratio before

splenectomy though there were few cases that we could observe. The CD4+/CD8+ ratio is likely find more to be a key parameter for appropriate tumor-infiltrating lymphocyte function, and was shown to be different in different types of cancer.[2, 31-35] Host immune responses to cancer were reported to depend on T lymphocytes, particularly CD8+ lymphocytes.[18, 19, 24, 36-39] An increase in their ratio after splenectomy and the consequent decrease in the CD4+/CD8+ ratio observed in this study may be a positive change in terms of immunology against HCC. Such a change was particularly marked in patients with a high CD4+/CD8+ ratio before splenectomy. In our study, the CD4+/CD8+ ratio also significantly increased as the fibrosis of non-tumor areas in the liver tissue progressed. These significant differences were observed regardless of the HCC status. Although the cause of these differences is unknown, it appears to depend on the background of histological factors in the liver such as fibrosis. Many studies have investigated the relationship between tumors, Treg and TGF-β.[20-22, 25, 40] Guo-He et al. showed that the expression of TGF-β appeared to be positively correlated with Treg in HCC tissue. The 5-year survival rate was significantly lower in patients with HCC tissues with high Treg cell infiltration than in those with low infiltration.

For example, deletion and homologous overproduction experiments have shown that red light absorption by the RsbP protein can activate a stress response in Bacillus subtilis (Avila-Perez et al., 2010). Blue light, either sensed by a photoreceptor or initiating photosynthetic electron transport, has the opposite effect on the transcription of photosynthesis-related genes in Rhodobacter sphaeroides (Happ et al., 2005). Furthermore, a blue light–activated histidine kinase (HK), frequently used for environmental sensing by bacterial two-component transduction systems (TCSTS), has been shown to regulate Brucella abortus virulence (Swartz et al.,

2007). Blue light photoreceptors are of the utmost importance for some organisms, allowing the development of DNA-repair Selleck NVP-BEZ235 systems in light illumination (Weber, 2005), the formation of protective (shielding) substances or for allowing MAPK inhibitor motile organisms to escape from regions with a high UV/blue light intensity (Armitage & Hellingwerf, 2003). Per-ARNT-Sim (PAS) domains are important signalling modules that monitor changes in light, oxygen, voltage (LOV), small ligands and the overall

energy level of a cell (Taylor & Zhulin, 1999). Prokaryotic genome analysis with bioinformatics methods has revealed the presence of PAS-domain-containing proteins (thereafter PAS proteins) in approximately 15% of all sequenced genomes, and 81.36% of the more than 22 000 identified PAS domains were found in bacteria (Letunic et al., 2006). Increasing experimental evidence suggests

that many PAS domains act as photoreceptors. Although sequence identity is low in the PAS superfamily (Taylor & Zhulin, 1999), the three-dimensional structures of PAS domains are highly conserved (Zhong et al., 2003), suggesting that common mechanisms may be used for signalling. The revealed general secondary structure of a PAS domain is ββααααβββ, and cofactors frequently interact with α helixes (Möglich et al., 2009; Jaiswal et al., 2010). Light promotes the detachment of the Jα helix from the central beta-sheet AZD9291 purchase (Harper et al., 2003) and its subsequent unfolding of the second PAS domain in oat phototropin (Hoersch et al., 2010). Therefore, the secondary structure topology (SST) of the PAS domain is valuable to reveal the activation sites of PAS domains and further to analyse functions of PAS proteins. The integration of SST analysis and determining the sequence of PAS domains will be an effective and promising methodology. Xanthomonas campestris pv. campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield worldwide (Swings et al., 1993). This organism generally invades and multiplies in cruciferous plant vascular tissues, resulting in the characteristic ‘black rot’ symptoms of blackened veins and V-shaped necrotic lesions at the foliar margin (Alvarez, 2000).

Glick et al. (1998) proposed that ACC deaminase-containing bacteria attach to plant tissues and degrade ACC, Belinostat cell line the direct precursor of ethylene biosynthesis in plants that is exuded from the plant cell, and as a result, provide a sink for ACC and reduce plant ethylene biosynthesis.

Thus, the application of ACC deaminase may be used as a strategy to reduce ethylene levels during the transformation process and to increase A. tumefaciens-mediated transformation efficiency. Most recently, it has been reported that the introduction of ACC deaminase into A. tumefaciens increased the transient gene delivery efficiency of melon cotyledon explants when tested 3 days after infection (Nonaka et al., 2008a). However, the effect of ACC deaminase on A. tumefaciens-mediated stable transformation efficiency was not evaluated in that study. Canola is an

important source of vegetable oil, ranking second only to soybeans worldwide (Halfhill et al., 2002). In PF-01367338 concentration recent years, researches started to genetically modify canola to make it tolerant to heavy metals and other toxic compounds and use it for phytoremediation (Basu et al., 2001; Stearns et al., 2005), to produce pharmaceutically active proteins and edible vaccines (Giddings et al., 2000), and to improve it for producing biofuel (http://www.canolacouncil. org/biodiesel/). A considerable amount of work has been reported previously in an effort to improve A. tumefaciens-mediated transformation efficiency of canola, including choosing the best plant material for the transformation and optimization of the infection and regeneration protocols (Cardoza & Stewart, 2003; Zhang & Bhalla, 2004; Zhang et al., 2005; Bhalla & Singh, 2008). However, most of the studies used the model cultivar Brassica napus cv. Westar, which is an old spring cultivar

and is no longer grown in the fields due to some agronomic deficiencies. Because Cobimetinib clinical trial the transformation and regeneration of canola is genotype dependent, it is therefore important to evaluate and optimize the transformation protocols for commercialized cultivars. Both cultivars B. napus cv. Hyola 401 and cv. 4414RR are top canola spring hybrids and there are no reports to date regarding their transformation. In this study, an ACC deaminase-encoding gene was introduced into A. tumefaciens GV3101∷pMP90, and using the protocol established by Cardoza & Stewart (2003), transformation efficiency assays were performed using the canola model cultivar Westar and the two commercial cultivars Hyola 401 and 4414RR. These experiments allowed determination of the effect of ACC deaminase on A. tumefaciens-mediated transformation efficiency. The plasmid pPZP-eGFP (provided by Dr Barbara Moffatt, Department of Biology, University of Waterloo), a pPZP-RCS2 (Tzfira et al.

Escherichia coli strains were grown in Luria–Bertani (LB) medium at 37 °C with either shaking at 180 r.p.m. or statically. Yersinia pseudotuberculosis YpIII and the isogenic mutant strains were grown in YLB medium (Yersinia LB, LB with half the concentration of NaCl) at 28 °C unless otherwise stated. Antibiotics (where appropriate) were applied at the following concentrations: www.selleckchem.com/products/AZD0530.html 30 μg mL−1 chloramphenicol, 15 μg mL−1 nalidixic acid and 100 μg mL−1 ampicillin. ΔsraG was constructed using the suicide plasmid pDM4 (O’Toole et al., 1996). The +1 site and terminator of SraG was

determined by annotation in the NCBI database. To delete the +1 to +184 region of the sraG gene, a 510-bp fragment upstream of the +1 of sraG with SalI and EcoRI and a 505-bp fragment downstream of the +184 of sraG with EcoRI and BglII were amplified by PCR (all primers are listed in Supporting Information, Table S1). The fragments were digested with specific restriction enzymes and inserted into the pDM4 plasmid by T4 DNA ligase. The recombinant plasmid was transformed into E. coli S17-1 λ-pir. Transconjugation was performed as described previously

(Hu et al., 2009). WT YpIII was used as the parental strain to obtain ΔsraG in which nucleotides +1 to 184 of the sraG gene were replaced by the EcoRI site. Mutants were verified by both PCR and sequencing. To construct the SraG complementing plasmid, a plasmid named pRO-SraG was constructed based on the pMD 18-T Vector (TaKaRa). First, the DNA fragment was amplified PtdIns(3,4)P2 AZD2281 molecular weight by PCR to obtain the plasmid backbone containing the

lac promoter, ampicillin resistance cassette, pUC replicon and lacZ terminator. The sraG gene was amplified using primers psraGoverlapF and psraG-ER (Table S1). The sense primer anneals to the +1 site of sraG and carries a short overlapping fragment with plasmid backbone. The antisense primer binds to the region ~100 nt downstream of the SraG terminator and adds an EcoRI site to the PCR product. Overlapping PCR and EcoRI digestion were used to ligate the plasmid backbone and sraG to construct pRO-SraG, which was then electrotransformed into the ΔsraG strain. To construct the translational gene::lacZ fusion, the antisense primer was designed to pair with the exact 3′-end of the coding sequence (CDS), omitting the stop codon with the SpeI site, and the sense primer was designed to pair with the region about 500 nt upstream of the stop codon with the SalI site. The PCR fragment was digested with SpeI and SalI and ligated into the pDM4-lacZ plasmid (Hu et al., 2009). The single-copy lacZ fusion was obtained by transconjugation as described previously (Hu et al., 2009).

Data abstraction was completed by VL and checked by RR. Included studies were then examined by all three members of the research team. The most appropriate set of guidelines to apply to this review was considered to be the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). As the guidelines did not fully match the subject matter, the most relevant parts of PRISMA were used in the formulation of this review, excluding points 5, 11–14, 16 and 19–23 on

the checklist. The literature search identified a total of 13 papers which related to the UK. Papers employed both qualitative and quantitative research methods; postal questionnaires, semi-structured interviews (face-to-face and telephone), observations, work-study logs and work sampling were all used in the research identified. No appropriate review papers were found. Table 3 PF 2341066 provides a summary of the papers identified, in chronological order.[36–48] A number of studies looked at community pharmacists’ workload within AZD3965 manufacturer the UK, employing a variety of research methods. There was some evidence found which investigated both what pharmacists do

during the day (categorisation of activities) and their general workload. These are summarised below. Several studies employed observational methods to research pharmacists’ work.[36,37,39,41] Rutter et al. reported that pharmacists spent the majority of time on dispensing, and that little time is dedicated to patient contact or pharmaceutical care. This was seen to be independent of prescription

workload or staffing levels.[41] Pharmacists appeared to be Carbohydrate placed inappropriately, completing the same tasks as dispensers. Comparisons were also made between a subjective work-study and an observational study, looking at the differences between the workload pharmacists perceived themselves to be subject to, and what they actually did.[38,39] Interestingly, pharmacists overestimated the time spent on NHS work (70% estimated versus 57% actual) and significantly (P = 0.042) underestimated the time spent on breaks/personal time and non-health communication (P = 0.002).[39] Specific limitations of one the studies conducted by Rutter et al. relate to the fact that when pharmacists were performing more than one task at once, this was recorded in its own category.[39] It would have been useful to know which tasks they were combining. It would also have been helpful to how the total time identified as waiting or personal was allocated; was this a discrete period/s, or split throughout the day? Savage also used direct observations in two studies to investigate time for pharmacist contact with patients in several community pharmacies.[36,37] Mean data from customer workload in 18 community pharmacies was recorded as 23 events per hour (prescription and OTC events).

The lack of sequence-specific learning despite the same amount of practice as the 1 Hz group suggests a state-dependent element where current activity in PMd, the activity producing the interference effect,

is not enhanced by stimulating PMd. The net result is that offline consolidation and implicit sequence-specific motor learning are similar to those seen in the control group in the absence of stimulation, where any learning is PD0325901 concentration associated with gains in sensorimotor efficiency rather than sequence-specific elements. This further supports a competitive model of declarative/procedural consolidation where competition is biased towards the developing declarative memories. Interestingly, the enhancement associated with cumulative 1 Hz rTMS over the PMd appeared to reflect retained improvement in spatial accuracy rather than a reduction EGFR tumor in response lag. While these two variables are not completely independent of each other our results suggest that consolidation of spatial aspects of a motor sequence may be mediated by PMd and M1 networks but that procedural elements

of these representations are stored in M1 (Muellbacher et al., 2002). The relative insensitivity of temporal aspects to 1 Hz rTMS during early offline consolidation highlights the importance of other cortical areas for implicit sequence-specific learning, such as the supplementary motor area (Mushiake et al., 1991) and cerebellum (Boyd & Winstein, 2004a). In particular,

the changes in spatial tracking error may relate to the role of the PMd in preparing aspects of spatial working memory during externally guided movements (Mushiake et al., 1991). Traditionally, 1 Hz rTMS has been associated with inhibitory effects that persist beyond cessation of stimulation (Wassermann et al., 1996; Chen et al., 2003; Vidoni et al., 2010). Our interpretation of our results is based upon this assumption, but an alternative Methamphetamine explanation may be that enhanced implicit sequence-specific learning observed following 1 Hz rTMS post-practice is linked to state-dependent effects present during application of the 1 Hz rTMS. Silvanto et al. (2007a,b) and Silvanto & Pascual-Leone (2008) demonstrated similar state-dependent effects in the visual cortex using adaptation paradigms. Therefore, it cannot be ruled out that resonant activity within the PMd, tied to online learning that persisted into the early period of offline consolidation, may have caused 1 Hz rTMS to enhance the PMd contributions to early offline consolidation.