Blastocyst development and pregnancies after IVF of mature oocytes retrieved from unstimulated patients with PCOS after in-vivo HCG priming.

A major side-effect of controlled ovarian stimulation (COS) in patients with polycystic ovarian syndrome (PCOS) is the risk of ovarian hyperstimulation syndrome (OHSS). In-vitro maturation (IVM) of immature oocytes represents a potential alternative for the fertility treatment of these patients. Two patients at high risk of OHSS were primed with 10,000 IU HCG 36 h before oocyte retrieval. After retrieval, oocyte maturity was evaluated. Oocytes considered to be mature at the time of collection were inseminated by IVF or ICSI, and the resulting embryos were cultured to blastocysts. Transfer of these blastocysts resulted in pregnancy in both patients. Immature oocytes were cultured in YS medium supplemented with 30% human follicular fluid, 1 IU/ml rFSH, 10 IU/ml HCG and 10 ng/ml epidermal growth factor (rhEGF). After in-vitro maturation of the oocytes, ICSI was performed. Two and five expanded blastocysts were obtained after 5 day culture and were cryopreserved. This report indicates that mature oocytes can be collected at the time of retrieval using only in-vivo HCG priming in women with PCOS, and clinical pregnancy can be established by transfer of blastocysts derived from the mature oocytes. This approach opens a potential for a new dimension in the management of patients with PCOS.     

Direct and indirect T cell priming by dendritic cell vaccines

The mechanisms by which dendritic cell (DC) vaccines prime host T cells in vivo was analyzed. Mice were immunized with syngeneic bone marrow-derived DC and as surrogate antigen β-galactosidase (β-gal) was used. DC either pulsed with peptide, loaded with β-gal antigen or gene-modified induced β-gal-specific cytotoxic T lymphocytes (CTL) and moderate rejection of an in vivo challenge with β-gal expressing tumors. In addition, β-gal-specific CTL lysed the syngeneic DC that were used as vaccines. Using SCID mice reconstituted with F1 lymphocytes, direct priming by gene-modified DC vaccines was demonstrated by the presence of β-gal-specific CTL of the haplotype exclusively expressed by DC while indirect priming by host antigen-presenting cells (APC) was shown by the detection of CTL of the haplo type exclusively present on host APC and absent on DC vaccines. Since DC immunization in syngeneic mice was associated with an increase in NK1.1⁺/Ly49C⁻ cells and detectable lysis of DC in vitro by lymphokine-activated killer cells, DC vaccines appear to interact with host natural killer cells as well as with antigen-specific T cells. These effector cells in turn may lyse DC vaccines thereby leading to the release of antigens that can be taken up by host APC.     

Default polyfunctional T helper 1 response to ample signal 1 alone

CD4⁺ T cells integrate well-defined signals from the T-cell receptor (TCR) (signal 1) and a host of costimulatory molecules (signal 2) to initiate clonal expansion and differentiation into diverse functional T helper (Th) subsets. However, our ability to guide the expansion of context-appropriate Th subsets by deploying these signals in vaccination remains limited. Using cell-based vaccines, we selectively amplified signal 1 by exclusive presentation of an optimized peptide:MHC II (pMHC II) complex in the absence of classic costimulation. Contrary to expectations, amplified signal 1 alone was strongly immunogenic and selectively expanded high-affinity TCR clonotypes, despite delivering intense TCR signals. In contrast to natural infection or standard vaccines, amplified signal 1, presented by a variety of professional and nonprofessional antigen-presenting cells (APCs), induced exclusively polyfunctional Th1 effector and memory cells, which protected against retroviral infection and tumor challenge, and expanded tumor-reactive CD4⁺ T cells otherwise rendered unresponsive in tumor-bearing hosts. Together, our findings uncover a default Th1 response to ample signal 1 and offer a means to selectively prime such protective responses by vaccination.     

Effects of repetition priming on electrophysiological and behavioral indices of conflict adaptation and cognitive control

We investigated the effects of repetition priming on indices of conflict adaptation. Event-related potentials (ERPs) were obtained while 210 healthy individuals (111 female, 99 male) completed an Eriksen flanker task. Error rates, response times (RTs), and N2 and P3 amplitudes showed significant conflict adaptation (i.e., previous-trial congruencies influenced current-trial measures). After omitting trials with stimulus-response repetitions, RTs did not index conflict adaptation, but did show switching effects; error rates and N2 and P3 amplitudes remained sensitive to conflict adaptation. P3 amplitudes positively correlated with RTs. N2 amplitudes correlated with RTs only on incongruent trials following congruent trials after excluding repetitions. Results indicate that neural indices of conflict monitoring remain reliably associated with conflict adaptation effects in the absence of RT adjustments upon omission of repetition priming effects.     

A mid-central N450 component of the ERP distinguishes trial-by-trial effects of target familiarity and context strength

N400-like components in the ERP are commonly understood as being inversely related to the degree at which contextual factors have prepared the brain for the processing of meaningful stimuli. Here we show independent and systematic effects of familiarity and context on mid-central N450 in a simple visual priming task. Participants selected a target digit defined by color while ignoring a distractor digit. Pairs of two subsequent displays (prime, probe) were considered. Probe target familiarity could be high (prime-probe target repetition), low (novel probe target), or very low (probe target = prime distractor). Context strength depended on history of the probe distractor and could be high (prime-probe distractor repetition), low (novel probe distractor), or very low (probe distractor = prime target). The seven priming conditions showed exactly the predicted order of N450 amplitude, with largest N450 for strong context/low target familiarity and smallest N450 for weak context/high target familiarity. Results significantly broaden the view of N400, as a universal marker of stimulus familiarity and context strength also in basic, non-linguistic settings.     

Testing asymmetries in noncognate translation priming: Evidence from RTs and ERPs

In this study, English–French bilinguals performed a lexical decision task while reaction times (RTs) and event related potentials (ERPs) were measured to L2 targets, preceded by noncognate L1 translation primes versus L1 unrelated primes (Experiment 1a) and vice versa (Experiment 1b). The prime–target stimulus onset asynchrony was 120 ms. Significant masked translation priming was observed, indicated by faster reaction times and a decreased N400 for translation pairs as opposed to unrelated pairs, both from L1 to L2 (Experiment 1a) and from L2 to L1 (Experiment 1b), with the latter effect being weaker (RTs) and less longer lasting (ERPs). A translation priming effect was also found in the N250 ERP component, and this effect was stronger and earlier in the L2 to L1 priming direction than the reverse. The results are discussed with respect to possible mechanisms at the basis of asymmetric translation priming effects in bilinguals.     

Response priming in the Simon paradigm

The Simon effect refers to the finding of faster responses when stimulus and response locations correspond than when they do not, although a nonspatial stimulus feature is task-relevant. These performance differences are usually accounted for by response priming processes directly induced by the task-irrelevant stimulus location. The present study investigated neural mechanisms of response priming in a Simon task at the level of the motor cortex with the help of transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) in both arms. A single TMS was applied contralateral or ipsilateral to the requested response at the time point where response priming was at a maximum. The MEP effects depended on the stimulated hemisphere. Over the left hemisphere, MEP areas were larger when TMS was applied over the primed motor cortex. However, reduced MEPs for the nonprimed hemisphere fell short of significance. Over the right hemisphere, only a MEP reduction for nonprimed left-hand responses was present. Therefore, we conclude that mainly excitatory activation underlies response priming in a Simon task, whereas the role of inhibitory processes is tentative.     

Prenatal immune priming with helminth infections: parasite-specific cellular reactivity and Th1 and Th2 cytokine responses in neonates

The present investigation aimed to determine to what extent maternal helminth infection primes parasite-specific cellular responsiveness in neonates. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood mononuclear cells (PBMC) from mothers proliferated in response to mitogenic stimulation with concanavalin A, as well as to bacterial Streptococcus pyogenes-derived (streptolysin O) and helminth-specific antigens of Necator americanus and Onchocerca volvulus. Cellular responses to Echinococcus multilocularis (Em) and Oesophagostomum bifurcum (Oes), helminth parasites not endemic in the study area, were absent (for Em) or very low (for Oes due to antigenic cross-reactivity). Cellular responsiveness to mitogen and antigens was higher in mothers than in their neonates. Several Th1-type (IL-2, IL-12, and IFN-gamma) and Th2-type (IL-5 and IL-10) cytokines were produced by UCBC from neonates and PBMC from mothers. Low levels of IFN-gamma were elicited by UCBC in response to helminth and bacterial antigens, while secretion of IL-2 was pronounced and similarly high in neonates and their mothers. Amounts of IL-5 produced by UCBC in response to bacterial SL-O and mitogenic stimulation (PHA) were low, but equivalent levels of IL-5 were induced by intestinal helminth and filaria-derived antigens in neonates and mothers. A pronounced production of IL-10 and IL-12 by UCBC was observed--spontaneous IL-10 and IL-12 secretion by UCBC was higher in neonates than by PBMC from mothers. Net amounts of IL-10 elicited by helminth antigens were similar, while net IL-12 in response to mitogen, and bacterial and helminth antigens was significantly higher in mothers than their offspring. Our results indicate that human maternal helminth infection does sensitize in utero for parasite-specific cellular responsiveness in offspring, and also activates specific production of several cytokines, and such children do not present a dominant expression of immunity of either Th1 or Th2.     

Missed prime words within the attentional blink evoke an N400 semantic priming effect

When subjects identified a target among distractors in a rapid serial visual presentation task, the detection of a subsequent target is impaired (attentional blink). By measuring event-related potentials (ERPs) we investigated if the processing of an unidentified prime word elicits the N400 semantic priming effect. Subjects (N = 12) had to identify three target words among distractors in a rapid serial visual presentation task. We varied the association strength between a prime (second target) and a probe (third target). The detection of the prime was impaired. Missed primes did not elicit a P300, indicating that they were not explicitly recognized. Despite this difference between recognized and missed primes, the N400 effect was present in both cases. This result suggests that automatic spread of activation (ASA) can be evoked by missed primes within the attentional blink. It furthermore demonstrates that ASA is sufficient to evoke the N400 effect.     

Selective breeding for acoustic priming

Data on eight generations of selective breeding for acoustic priming efficacy are reported. The realized heritability of this trait is approximately 0.2–0.3, indicating that the trait is determined in part by genetic factors. Animals selectively bred for acoustic priming do not differ in terms of first-trial (i.e., non-priming-induced) audiogenic seizures. These data suggest that acoustic priming and first-trial audiogenic seizures are controlled by different genetic mechanisms.This research was supported by Research Grant MH 13026 from the National Institute of Mental Health.