Zeitschriftenartikel zum Thema „E178.1 .p4 2001“

Abstract Progesterone (P4) plays a central role in normal uterine function, from embryo implantation in endometrium to establishment and maintenance of uterine quiescence during pregnancy in the myometrium. Considering its diverse physiological effects on female reproductive function, rather little is known about downstream events of P4 action. Recent progress in differential screening technologies facilitated identification of such inducible genes. We used uteri of wild-type and progesterone receptor null mutant mice as a starting material and screened for differentially expressed genes by medium-density cDNA expression array. Here, we report that the expression of the morphogen, Indian hedgehog (Ihh), is rapidly stimulated by P4 in the mouse uterus. The level of Ihh mRNA is induced within 3 h, after a single administration of P4 to ovariectomized mice. The induced Ihh mRNA and protein were localized to the luminal and glandular epithelial compartment of the endometrium. During pseudopregnancy, the Ihh mRNA level was transiently increased in the preimplantation period and d 3 and d 4 post coitum and then decreased rapidly at d 5 post coitum. Furthermore, the expression profile of patched-1, hedgehog interacting protein-1, and chicken ovalbumin upstream promoter-transcription factor II, genes known to be in the hedgehog signaling pathway in other tissues, followed the expression pattern of Ihh during the periimplantation period. Our results suggested that Ihh is regulated by P4, and the Ihh signaling axis may play a role in the preparation of the uterus for implantation during the periimplantation period.

Among inositol phosphate kinases, Ins(3,4,5,6)P4 1-kinase has been considered to be an outsider with disparate sequence, a proclaimed capacity to also phosphorylate proteins and apparent 1-phosphatase activity. Such multifunctionality, coupled with ignorance of its operational domains, complicates any mechanistic rationale behind literature reports that Ins(3,4,5,6)P4 1-kinase regulates apoptosis, salt and fluid secretion, and transcription. We have expressed poly(His)-tagged human Ins(3,4,5,6)P4 1-kinase in Sf9 insect cells and purified the enzyme using Ni–agarose chromatography. Protein kinase activity was eluted from the Ni–agarose column, but this did not co-elute with the Ins(3,4,5,6)P4 1-kinase, indicating that the protein kinase and inositol kinase activities belong to separate proteins. To pursue this conclusion, we prepared catalytically inactive mutants of the Ins(3,4,5,6)P4 1-kinase by identifying and targeting the ATP-binding site. Our strategy was based on sequence alignments suggesting homology of the Ins(3,4,5,6)P4 1-kinase with ATP-grasp metabolic enzymes. Individual mutation of four candidate MgATP-binding participants, Lys157, Asp281, Asp295 and Asn297, severely compromised Ins(3,4,5,6)P4 1-kinase activity. Yet, these mutations did not affect the protein kinase activity. We conclude that the Ins(3,4,5,6)P4 1-kinase is not a protein kinase, contrary to earlier reports [e.g. Wilson, Sun, Cao and Majerus (2001) J. Biol. Chem. 276, 40998–41004]. Elimination of protein kinase activity from the enzyme's repertoire and recognition of its ATP-grasp homology together indicate that structural, functional and catalytic relationships between Ins(3,4,5,6)P4 1-kinase and other inositol phosphate kinases are closer than previously thought [Gonzalez, Schell, Letcher, Veprintsev, Irvine and Williams (2004) Mol. Cell 15, 689–701].

8078 Background: Treatment of metastatic non-small cell lung cancer (NSCLC) has evolved over the last decade with the increased use of third-generation chemotherapy agents, established benefits from second-line chemotherapy, and the development of targeted agents. We conducted a study to evaluate whether these treatment advances translated into improved survival in a large registry database. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with NSCLC stage IV, aged 21 or older, and diagnosed between 1990 and 2005. Overall Survival (OS) rates were estimated by the Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was fitted to evaluate whether the diagnostic period is an independent predictor for OS. Demographic variables included period of diagnosis (1990–1993 or P1, 1994–1997 or P2, 1998–2001 or P3, and 2002–2005 or P4), age, gender, race, and histology. Results: There were 127,816 patients meeting eligibility criteria. Median age at presentation was 67 and most patients were male (58%), white (81%), and had adenocarcinoma (39%). Although there was no significant differences in OS between periods 1 and 2 (p = 0.18), there was a significant improvement from periods 2 to 3 (p < 0.001) and 3 to 4 (p < 0.001). 1-y and 2-y OS increased from 13.2% and 4.5% respectively in P1 to 19.4% and 7.8% respectively in P4. Predictive factors for improved survival in multivariate analyses included diagnostic period (p < 0.001), younger age (p < 0.0001), female gender (p < 0.0001), and non-black race (p < 0.0001). After adjusting for demographic factors, there were no significant differences in OS between adenocarcinoma and squamous cell from P1 to P3 (1990–2001). However, P4 showed a significant increase in OS for adenocarcinoma compared with squamous cell (p = 0.02). Conclusions: There has been a significant improvement in OS for stage IV NSCLC over the last 8 years. The recent differences in outcomes based on histology observed in P4 may reflect the increased activity of newer therapies in adenocarcinoma compared with squamous cell, including gefitinib and erlotinib. No significant financial relationships to disclose.

In beef cattle, 20 to 44% embryonic loss occurs during the early stages of pregnancy (Humblot et al. 2001). However, the mechanism of early and late embryonic death is not clear. We investigated occurrence of embryonic death by monitoring ovarian hormones dynamics and checking for the presence of the conceptus after artificial insemination or embryo transfer in beef cattle. Twenty Japanese black females were inseminated (AI) and 12 females were transferred with 1 embryo (ET). Blood samples were collected on Days 21, 24, 28, 38, 48, 58, and 68 post-oestrus (oestrus = Day 0) and then stored at –30°C. Progesterone (P4) and oestradiol (E2) plasma concentrations were analysed using a chemiluminescent immunoassay. On each day of blood sampling, ovaries and presence of a conceptus in the uterus were monitored by ultrasonography. At Day 24 post-oestrus, the presence of the fetus was detected in 8 females (AI, n = 6; ET, n = 2), whereas only 3 females were confirmed to be pregnant at Day 28 and Day 38 post-oestrus. No embryo loss was seen at later stages of pregnancy (Days 48, 58, and 68 post-oestrus). At Day 21 post-oestrus, the conceptus could not be detected by ultrasonography but the E2/P4 ratio provided indication on the pregnancy status of the females that were classified as pregnant (n = 8) or not pregnant (n = 24) at day 24 post-oestrus (1.7 ± 2.2 versus 28.0 ± 34.2 respectively; mean ± s.d.). In the nonpregnant females compared with the pregnant ones at Day 24 post-oestrus, P4 declined below 1 ng mL–1 (0.6 ± 0.2 ng mL–1 v. 8.6 ± 3.9 ng mL–1), whereas E2 blood level remained stable (15.7 ± 21.9 v. 18.1 ± 1.1 pg mL–1). The decrease in P4 levels led to an increase in E2/P4 ratio (1.3 to 37.3 on Day 24). Our study suggests that a large proportion of embryo loss (75%) occurs before Day 24, whereas an additional 16% loss was seen between Day 24 and Day 28 post-oestrus. This embryo loss was shown to be associated with the altered balance of ovarian hormones.

The importance of serum progesterone (P4) during the first weeks of pregnancy to reduce the embryo mortality in cattle herds has been demonstrated (Mann and Lamming 2001 Reproduction 121, 175-180). Studies show that a P4 peak at the beginning of pregnancy (about 5 days after the natural breeding or AI) helps development of the concept via secretion of interferon-τ (Mann 2002 XXII World Buiatrics Congress 18-23, 300-306). Studies have shown that the administration of gonadotropin-releasing hormone (GnRH) or its agonists after AI may stimulate corpus luteum function, induce the formation of an accessory corpus luteum, or increase of P4 serum concentrations and, therefore, improve embryonic survival (Bartolome et al. 2005 Theriogenology 63, 1026-1037). This work aims to evaluate the effect of GnRH injection 12 d after fixed-time AI(FTAI) on P4 serum levels and pregnancy rate of beef crossbred cows. The cows (Bos taurus indicus × Bos taurus taurus, n = 59), range in body condition (BCS) from 2.5 to 3.5 (scale of 1 to 5), were not previously pregnant. The animals were allocated to 2 treatments: TEB treatment (n = 30) consisted of Day 0 insertion of progesterone intravaginal device (ID) plus 2 mg of estradiol benzoate (EB), i.m. followed on Day 8 by removal of the ID and 300 IU of eCG and 0.15 mg of PGF2α, i.m. on Day 9, 1 mg injection of EB (i.m.) was given, followed by FTAI at 48 to 56 h after the withdrawal of ID. The TEBGnRH12 treatment (n = 29) protocol was similar to TEB, but with administration of 25 μg of GnRH analogue (Lecirelina) 12 d after the FTAI. Transrectal ultrasound was used for pregnancy diagnosis on Day 35 after AI. Blood samples for P4 serum assay were collected from 30% of animals in each treatment, at the time of AI and on Days 5, 12, and 20 after FTAI. For all statistical analysis, we used the program SAS 9.0 (2002; SAS Institute Inc., Cary, NC, USA) at 5% probability. The pregnancy rate was analyzed by logistic regression. The effects of treatment and day in P4 concentration were analyzed in a split plot, with the effect of day in plot, in mixed model, considering the error and repetition as a random effect, and comparison of means by Tukey-Kramer. Pregnancy rate and the concentration of serum P4 on different days was analyzed by Spearman correlation. The pregnancy rate for TEB cows was 53.33% (16/30) for the first service compared with 37.93% (11/29) for TEBGnRH12 cows. The protocol used did not affect the pregnancy rate of crossbred cows (P > 0.05). There were no treatment differences (P > 0.05) between the concentrations of P4 (TEB = 3.88 ng mL-1; TEBGnRH12 = 3.12 ng mL-1). In conclusion, the administration of the analogue of GnRH 12 days after FTAI does not affect the rates of pregnancy or the concentration of P4. Supported by grants from CNPq, FAPEMIG and DZO-UFV.

The title compounds were prepared by arc-melting cold-pressed pellets of the elemental components. They crystallize with a tetragonal structure already reported for CeCr2Si2C. It was refined from single-crystal X-ray data of PrCr2S2C: P4/mmm, a - 402.2( 1) pm, c = 535.2(1) pm, Z = 1, R = 0.012 for 252 structure factors and 10 variable parameters. Magnetic susceptibility measurements with a SQUID magnetometer indicate Pauli paramagnetism for YCr2Si2C, while CeC2Si2C shows mixed valent behavior. The carbon atoms in the structure of these compounds are isolated from each other. The silicon atoms form pairs with a Si-Si distance of 245.3 pm, somewhat greater than the single-bond distance of 235.2 pm in elemental silicon. Together with the chromium atoms, the silicon pairs and carbon atoms form a three-dimensionally infinite polyanion, which has some similarity with the polyanions found in several related tetragonal structures, e.g., the structures of ThCr2Si2 and LuNi2B2C.

New intermetallic cadmium compounds RE2Rh2Cd (RE= La, Ce, Pr, Nd, Sm) were synthesized from the elements in sealed tantalum tubes in a high-frequency furnace. They were characterized through X-ray powder data: Mo2FeB2 type, space group P4/mbm, Z = 2. Single crystal data of the cerium compound (a = 762.8(1), c = 377.8(1) pm, wR2 = 0.0662, 199 F2 values, and 13 variable parameters) revealed small defects on the rhodium position leading to the composition Ce2Rh186(3)Cd for the investigated crystal. According to the course of the cell volumes Ce2Rh2Cd may be classified as a mixedvalent compound. The Ce2Rh2Cd structure is an intergrowth of slightly distorted AlB2 and CsCl related slabs of compositions CeRh2 and CeCd. Within the CeRh2 slab short Ce-Rh contacts (284-300 pm) are indicative of strong Ce-Rh bonding. The Rh-Rh distance within the AlB2 related slab is 289 pm.

Purpose In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision. Methods To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data. Twenty-seven separate analyses, one for each different age cutoff (adjusting for MYCN and stage), tested age influence on outcome. The cutoff that maximized outcome difference between younger and older patients was selected. Results Thirty-seven percent of patients were younger than 365 days, and 64% were ≥ 365 days old (4-year event-free survival [EFS] rate ± SE: 83% ± 1% [n = 1,339] and 45% ± 1% [n = 2,327], respectively; P < .0001). Graphical analyses revealed the continuous nature of the prognostic contribution of age to outcome. The optimal 460-day cutoff we selected maximized the outcome difference between younger and older patients. Forty-three percent were younger than 460 days, and 57% were ≥ 460 days old (4-year EFS rate ± SE: 82% ± 1% [n = 1,589] and 42% ± 1% [n = 2,077], respectively; P < .0001). Using a 460-day cutoff (assuming stage 4, MYCN-amplified patients remain high-risk), 5% of patients (365 to 460 days: 4-year EFS 92% ± 3%; n = 135) fell into a lower risk group. Conclusion The prognostic contribution of age to outcome is continuous in nature. Within clinically relevant risk stratification, statistical support exists for an age cutoff of 460 days.

Two new species of Dorsiceratus Drzycimski, 1967 (Copepoda, Harpacticoida, Ancorabolidae), Dorsiceratus wilhelminae sp. nov. and D. dinah sp. nov. are described from Sedlo and Seine Seamounts, respectively (both northeast Atlantic). These are the first records of Dorsiceratus species from seamount summits. Both new species resemble the described species D. octocornis Drzycimski, 1967, D. triarticulatus Coull, 1973, and D. ursulae George, 2006, with respect to most morphological features. On the other hand, D. wilhelminae sp. nov. has long spinules at the inner margin of the A2 enp, while D. dinah sp. nov. bears two, rather than one, tubepores dorsally on third abdominal somite, and a geniculate first outer seta on P1 exp2. These characters are considered as apomorphic relative to the described Dorsiceratus species. As discussed in the present paper, the maintenance of a genus Dorsiceratus appears to be problematic. Although specimens may be assigned without difficulty to a group “Dorsiceratus”, such assignments are based on diagnostic features only; no clear-cut apomorphies have been detected so far to characterize the monophyly of Dorsiceratus. Just two apomorphic characters appear to be synapomorphies for all of the described Dorsiceratus species: 1) P2 enp2 with one rather than two setae and 2) P4 exp sexually dimorphic. Unfortunately, these features are relatively widespread within the Ceratonotus-group sensu Conroy-Dalton (2001) and therefore of rather low value. The authors decided, however, to retain the genus Dorsiceratus until new insights provide more information to support or disprove that hypothesis.

Abstract &lt;Background&gt;In the latest updated ASCO/CAP guideline, a new category, ER low-positive was introduced, which are determined by the 1% to10 % of positive staining of the tumor nuclei for ER. However clinical meaning of ER-low positive was unclear compared with ER- positive or ER-negative in HER2 negative breast cancer. &lt;Purpose&gt; In order to clarify the clinicopathological features of ER-low positive breast cancer, we compared the clinicopathological factors and prognosis among three groups, ER negative, ER-low positive, and ER-positive groups in the patients with HER2 negative breast cancer. &lt;Patients and Method&gt; A total of 1,882 patients with HER2 negative breast cancer who underwent surgery between 2001 and 2018 were included in this study. We divided them into three groups, ER negative (&lt;1%), ER-low positive (1-10%), and ER positive (10%≦). The relationships between ER status and clinicopathological characteristics and prognosis were evaluated. &lt;Result&gt;According to ER status, 553(29.4%), 183(9.7%), 1146(60.9%) patients were divided into ER negative, low-positive and positive groups. Compared with ER-positive group, patients in the ER negative and low-positive groups were of higher age (p&lt;.0001), and those tumors were significantly associated with the larger tumor size (p&lt;.0001), higher histological grade (p&lt;.0001) and more administration of adjuvant chemotherapy (p&lt;0.0001). Most of the patients with ER low-positive and ER-positive tumors had received the adjuvant endocrine therapy. The prognosis of the patients with ER low-positive tumors were poorer than that of those with ER positive tumors in terms of relapse-free survival (RFS p&lt;.0001), distant metastasis-free survival (DMFS p&lt;.0001) and overall survival (OS p&lt;.0001).In the node negative patients, the prognosis of the ER-negative and ER low-positive groups were equivalent, and poorer than that of the ER-positive group (RFS; p=0.0068, DMFS; p=0.0013, OS: p=0.0032). In addition, in pStage III patients, prognosis of the ER-negative and ER low-positive groups were also equivalent, and poorer than that of the ER-positive group (RFS; p=0.008, DMFS; p=0.0021, OS: p=0.0010). &lt;Conclusion&gt; This study showed that the prognosis of the patients with ER negative and ER low-positive were similar, and poorer than that of those with ER positive tumors. Therefore, the new category of ER-low positive is clinically especially important in order to determine the appropriate adjuvant therapy. Citation Format: Tajiri Wakako. The clinical importance of the new category, ER low-positive in the ER expression HER2 negative early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-11.

Central Mexico is considered a center of genetic diversity for Phytophthora infestans on the basis of a range of genotypic and phenotypic characteristics (3). Surprisingly, while mitochondrial DNA (mtDNA) haplotypes I-a, II-a, and II-b have been reported from central Mexico, haplotype I-b has not been found in central Mexico (1). Therefore, a more extensive search for haplotypes was conducted in areas where sexual reproduction occurs. During the summer of 2003, leaflets of cvs. Rosita and Tollocan with a single lesion of late blight were collected in the area of Villarreal, located in Terrenate County in Tlaxcala, Mexico (170 km northeast of Mexico City). Fourteen P. infestans isolates were characterized for mtDNA haplotype, isozyme genotype (glucose 6- phosphate isomerase [Gpi] and peptidase [Pep]), and mating type. Isolation, mating type, and isozyme genotype were characterized following reported protocols (1,4). MtDNA haplotype was determined by amplifying and digesting the P2 and P4 regions and comparing amplicons to those of reference strains of known haplotype (1,2). Twelve isolates were mtDNA haplotype I-a and two were I-b. While the mtDNA I-b has been associated with the US-1 lineage (mating type: A1, Gpi: 86/100, Pep: 92/100), the genotypes for the Mexican isolates were A2, 86/100 Gpi, 100/100 Pep from cv. Rosita and A2, 86/100 Gpi, 92/100 Pep from cv. Tollocan. To our knowledge, this is the first report of the I-b mtDNA haplotype of P. infestans from central Mexico and it is now clear that all four haplotypes exist in Mexico. This finding therefore, stresses the importance of including a representative regional sampling of Mexican and Andean isolates in studies inferring the origin of this species. References: (1) W. G. Flier et al. Phytopathology 93:382, 2003. (2) G. W. Griffith and D. S. Shaw. Appl. Environ. Microbiol. 64:4007, 1998. (3) N. J. Grünwald and W. G. Flier. Ann. Rev. Phytopathol. 43:171, 2005. (4) N. J. Grünwald et al. Phytopathology 91:882, 2001.

Abstract Introduction and objectives Up to 30% of early breast cancer (BC) patients treated with neoadjuvant chemotherapy will have systemic relapse during the follow-up. The integration of clinical, analytical and molecular parameters associated to tumor biology or host immune response could help to better stratify the prognosis of these patients. The aim of this study was to analyze the prognostic ability of immune-related and proliferation markers in combination with clinical parameters in patients with early BC treated with neoadjuvant chemotherapy. Methods and materials Retrospective and single-center cohort of BC patients treated with neoadjuvant chemotherapy between 2001 and 2010. We analyzed the following pre-treatment biological markers: neutrophil-to-lymphocyte ratio (NLR) in peripheral blood and CD3+-tumor-infiltrating lymphocytes (TIL), interferon-gamma and interleukin-10 in tumor samples by using a tissue microarray. Gene expression of AURKA, MYBL2, MKI67 and CTNNB1 in RNA from tumor samples was also evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Survival analysis was performed using Cox regression. The predictive capacity of the regression models was evaluated using AIC (Akaike Information Criterion) index, ROC curves and Harrell's C statistics. Results A total of 121 patients were included. Median age: 56 years. Cancer stage at diagnosis: 16% IIA, 28% IIB, 33% IIIA, 7% IIIB and 16% IIIC. Molecular subtype: 64% hormone receptor-positive (12% HER2-positive), 11% HER2-positive and 22% triple-negative. Pathological complete response (pCR): 16.5%. Median follow-up: 12 years. In the univariate analysis, NLR (HR 1.23, 95% CI 1.11-1.36; p&lt;0.001), TIL (HR 0.89, CI95% 0.81-0.98; p=0, 02), AURKA (HR 1.02, 95% CI 1.01-1.04; p&lt;0.001) and MYBL2 (HR 1.10, 95% CI 1.03-1.19; p=0.007) showed prognostic value for overall survival (OS). In the multivariate analysis, including staging after neoadjuvant therapy (HR 6.54, 95% CI 1.36-31.49; p=0.02), NLR (HR 1.33, 95% CI 1.08-1.64; p=0.008), TIL (HR 0.84, 95% CI 0.73-0.97; p=0.21), AURKA (HR 1.05, 95% CI 0.99-1.10; p=0.055) and MYBL2 (HR 1.14, 95% CI 1.00-1.31; p=0.04) remained as independent predictive variables in a regression analysis. Consecutive addition of these biomarkers to a regression model based on staging after neoadjuvant treatment progressively increased the discrimination accuracy of the models. These differences were more marked for the predictive model that included the four biological parameters identified in the multivariate analysis: NLR, TIL, AURKA and MYBL2 (Table 1). Conclusion In our cohort, the creation of a prognostic model integrated by clinical factors together with proliferation and both tissue and circulating immune biomarkers demonstrated high predictive capacity for OS. The validation of these findings in independent cohorts could impact in patient’s management. Table 1.Analysis of prognostic capacity with the consecutive addition of biomarkersAICAUC ROC (95% CI)pHarrell's C-index (95% CI)pModel 1: ypTN2740,76 (0,58-0,94)Ref*0,74 (0,57-0,91)Ref*Model 2: ypTN + NLR1870,78 (0,61-0,95)0,830,80 (0,67-0,93)0,53Model 3: ypTN + NLR + TIL850,85 (0,73-0,98)0,300,83 (0,73-0,94)0,30Model 4: ypTN + NLR + TIL + + AURKA + MYBL2570,91 (0,80-1)0,110,89 (0,81-0,97)0,13*Ref: model 1 was the reference category that was used for comparison of AUC and C-index.AIC: Akaike Information Criterion. AUC ROC: Area Under the ROC Curve. ROC: Receiver Operating Characteristic. Citation Format: Esmeralda Garcia-Torralba, Beatriz Álvarez-Abril, Carlos Bravo-Pérez, Esther Navarro Manzano, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elisa García-Garre, Gema Marín Zafra, Francisco Ayala de la Peña, Elena García-Martínez. Development of prognostic models based on clinical, immune-related and proliferation factors in early breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-03.

The objective of the present study was to characterise follicular dynamics in Santa Ines (SI) during a 9-day protocol for oestrous synchronization and to evaluate the efficiency of the vaginal progesterone-releasing device Primer-PR® (Tecnopec, Brazil). Cyclic females were used (n = 10) at the ruminant sector of the veterinary hospital of the FMVZ–USP, in March 2009. The animals had body scores between 2.5 and 3 and were of proven fertility. Ultrasound examinations were performed using an ALOKA SSD-500 Scanner (Berger, Brazil) with a linear 5.0-MHz transducer, attached to a handle to allow safe intrarectal manipulation. Examinations were performed daily from 3 days (D-3) before the day of device placement (D0) until the day of device removal (D9), and twice daily from device removal until ovulation. All ewes received 0.03 mg of prostaglandin (D-cloprostenol, Prolise®, Tecnopec, Brazil) on D9. Ovulation was assessed by the disappearance of the growing larger follicle or follicles present in the previous examinations. Oestrous detection was performed using an intact male 3 times a day (at 10:00 a.m., 6:00 p.m., and 12:00 p.m.) from D9 until the last acceptant ewe, and blood samples were taken by jugular puncture for progesterone (P4) measurement by radioimmunoassay on solid phase (COAT-A-COUNT, Siemens, USA) from D-3 until the day of ovulation. Data were analysed by Shapiro–Wilk (PROC UNIVARIATE) using the SAS program (SAS Institute Inc., Cary, NC, USA, 2001) and shown as mean ± standard deviation. Plasma P4 concentrations between D0 and D9 were 6.56 ± 2.32 ng mL–1, peaking between D3 and D5 (8.07 ± 2.31 ng mL–1). Oestrous behaviour was shown 45.6 ± 12.71 h after Primer-PR® removal. The first and the last ewe that showed oestrous behaviour was at 30 h and 66 h after Primer-PR® removal, respectively, and the majority of ewes (50%) at 42 h. Oestrous lasted 26.40 ± 9.47 h, and the majority of ewes (70%) showed oestrous behaviour during 24 h. Ovulation occurred 73 ± 14.38 h after Primer–PR® removal and 1.3 ± 0.48 ovulations per animal were observed. From all growing presumptively dominant follicles observed, 92.3% of them ovulated. When double ovulations occurred (n = 3), the interval between first and second ovulation was 16 ± 6.93 h. Emergence of the ovulatory follicular wave occurred at 8.5 days + 16 h after Primer–PR® insertion. The follicles observed to continue growing had a diameter of 3.48 ± 0.28 mm when they were first detected and reached 5.63 ± 0.66 mm, with a growth rate of 0.73 ± 0.43 mm per day. A standard follicle wave within the 9-day protocol was not possible to determine, and the follicles receded in up to 4 days. In conclusion, placement of a Primer-PR® device for 9 days resulted in synchronous oestrus and ovulation in Santa Inês ewes. FAPESP, CAPES, Tecnopec.

A completely defined medium for in vitro maturation (IVM) of equine oocytes has not yet been developed, since most of the media used for IVM are supplemented with serum or BSA. Furthermore, in this species there is no report about the influence of progesterone on maturation, although it has already been used as supplement (500ngmL−1) in EMMI (Maclellan LJ et al., 2001, Theriogenolgy 55, 310 abst). The aims of this study were to develop a completely defined medium for equine oocyte maturation and to investigate the effect of progesterone on nuclear maturation. Equine oocytes were collected by follicular scraping of abattoir-derived ovaries between April and June. The basal medium for maturation was SOFaa supplemented with pFSH-LH 0.1IUmL−1 (Pluset, Laboratorios Calier, Barcelona, Spain), EGF* 50ngmL−1, ITS (Insulin, Transferrin, Sodium selenite), L-cysteine 1.2mM, Maturation SOF (MSOF). Compact cumulus-oocyte complexes were selected, washed three times in H-SOF and matured in one of the following media (15–20 oocytesmL−1): (1) MSOF+FCS 10% (MSOF-FCS), (2) MSOF+progesterone 100ngmL−1 (MSOF-P4), (3) MSOF. After 24h of culture in 5% CO2 in air at 38.5°C, the oocytes were denuded by gently pipetting in a 0.25% trypsin solution, washed and stained with Hoechst 33258 (10μgmL−1 in PBS) for 30min at room temperature. Oocytes were examined under a fluorescent microscope to assess nuclear maturation. Only oocytes with an evident polar body and metaphase II plate (MII) were considered mature. The experiment was done in 6 replicates. Chi Square test was used for statistical analysis (Statistica for Windows – Stat Soft Inc., Tusla, OK, USA). Significance was assessed for P&lt;0.05. The results of this study show that MSOF can be considered a suitable completely defined medium for IVM of equine oocytes. Adding progesterone significantly (P&lt;0.05) increases the nuclear maturation rate at 24h of culture. It can be speculated that although cumuls cells produce this hormone, supplementation is useful to reach progesterone concentrations similar to those present in follicular fluid (early dominant 63.4±19.3ngmL−1, healthy preovulatory follicle 1094.3±170.9ngmL−1; Gerard N et al., 2002, Reproduction 124, 241–248). Further studies are needed to investigate the influence of progesterone on cytoplasmic maturation and to test the effect of different progesterone concentrations and time of maturation in a completely defined system.*All chemicals were purchased from Sigma, St. Louis, MO, USA, unless otherwise stated. Table 1 Maturation of equine oocytes in different media

Abstract Introduction. There are still 30-40% of patients with early breast cancer (BC) that relapse after neoadjuvant chemotherapy (NAC). New prognostic biomarkers are needed. Current evidence shows that both markers of antitumor local and systemic immune response, such as tumor infiltrating lymphocytes (TIL) and neutrophil-to-lymphocyte ratio (NLR) have prognostic value in early BC. Most works have evaluated baseline levels, but their variation after NAC might be related to treatment resistance and should be explored.The aim of this study was to simultaneously investigate the prognostic significance of the pre-post-NAC variation of TIL and NLR in patients with early BC.Methods. Retrospective, single-center cohort of 121 patients with early BC treated with NAC between 2001 and 2010. Pre- and post-NAC TIL (CD3+) were assessed by tumor tissue microarrays performed in both diagnostic core-needle biopsy and surgical excision specimens, respectively. Pre- and post-NAC NLR were calculated based on blood tests collected within 1 month of cancer diagnosis and at the moment of surgery, respectively. The change on TIL and NLR after NAC was estimated by calculating the absolute difference of post- and pre- values of these parameters (Δpost-pre). We examined the association between the absolute difference of TIL and NLR (both divided into deciles) and survival outcomes by Cox regression. To represent in Kaplan-Meier curves the combined effect of the change of TIL and NLR in OS, we divided patients into 4 groups, depending on the sign of Δpost-pre values of TIL and NLR: 1) no TIL nor NLR increment after NAC (ΔTIL & ΔNRLpost-pre≤0); 2) no TIL but NLR increment (ΔTILpost-pre≤0, ΔNRLpost-pre&gt;0); 3) TIL but no NLR increment (ΔTILpost-pre&gt;0, ΔNRLpost-pre≤0); and 4) TIL and NLR increment following NAC (ΔTIL & ΔNRLpost-pre&gt;0).Results. 47 (40%) out of 121 patients had pre- and post-NAC values of both NLR and TIL. Patients’ baseline characteristics are shown in Table 1. The median follow-up of this group was 11.5 years (IQR: 10.5 - 12.5 years). At the final follow-up date, overall survival (OS) was 87.2 %. In the univariable analysis, the increase in TIL and NLR after NAC among deciles showed a negative prognostic value for OS (TIL: HR 1.54, 95%CI 1.05-2.26, p=0.026; HR 1.32 95%CI 0.98-1.79, p=0.070). In the multivariable analysis, adjusted by cancer staging after NAC, both the increase of TIL and NLR after NAC among deciles add independent predictive value (TIL: HR 1.53, 95%CI 1.00-2.34, p=0.049; RNL: HR 1.42 95%CI 0.95-2.12, p=0.09).The subpopulation of patients with no TIL increment after NAC (Groups 1&2, N=23) showed the best prognosis, with no deaths at 10 years. Among patients with TIL increment (Groups 3&4, N=22), those with no NLR increment (Group 3, N=5) showed an intermediate prognosis (20% deaths at 10 years), whereas patients with concurrent NLR increment (Group 4, N=17) had the lowest OS (29.4% deaths at 10 years). Differences observed between groups were statistically significant (Log Rank p=0.042).Conclusion. The integrated characterization of TIL and NLR variations after NAC identifies different prognostic subgroups in early BC patients. In our cohort, both the increment of TIL and/or NLR after NAC are associated to a worse prognosis. Future validation of these findings in large, multicenter cohorts might allow treatment optimization by means of new strategies such as immunotherapy. Table 1.Patients’ baseline characteristicsN=47Age (median, range)56 (21, 78)Menstrual statusPostmenopausal25 (53,2%)Premenopausal22 (46,8%)Histologic subtypeInvasive ductal carcinoma42 (91,5%)Other subtypes4 (8,5%)Histologic gradeGrade 12 (4,3%)Grade 218 (38,3%)Grade 323 (48,9%)Unknown4 (8,6%)cTcT221 (44,7%)cT324 (51,1%)cT4a-d2 (4,2%)cNcN018 (38,3%)cN114 (29,8%)cN26 (12,8%)cN39 (19,1%)Molecular subtypeHR+ HER2-22 (46,8%)HER2+ HR+8 (17,0%)HER2+ HR-6 (12,8%)Triple negative10 (21,3%)Breast surgeryConservative26 (55,3%)Mastectomy21 (44,7%)Axillary surgerySentinel lymph node biopsy12 (25,5%)Axillary lymph node dissection35 (74,5%)Relapse typeMetastasis7 (14,9%)Local/contralateral1 (0,83%)Deaths6 (12,8%) Citation Format: Esmeralda Garcia-Torralba, Beatriz Álvarez-Abril, Carlos Bravo-Pérez, Esther Navarro Manzano, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elisa García-Garre, Gema Marín Zafra, Francisco Ayala de la Peña, Elena García-Martínez. Prognostic significance of changes in tumor infiltrating lymphocytes and neutrophil-to-lymphocyte ratio after neoadjuvant chemotherapy in early breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-11.

Births of the first cloned equids were reported in 2003 (Woods et al. 2003 Science 301(5636), 1063; Galli et al. 2003 Nature 424 (6949), 635) but no equine clones have been reported in Latin America. The aim of this work was to inform the birth of the first equine clone in Argentina as a result of interdisciplinary teamwork. Equine oocytes were obtained from slaughterhouse ovaries and were transported at 38°C for 15 h in TCM-199 buffered with 20 mM HEPES and supplemented with 1 mM glutamine, 0.19 mM sodium pyruvate, 2 μg mL–1 LH, 5 μg mL–1 FSH, 100 ng mL–1 EGF, 100 ng mL–1 IGF-I, and 10% FCS. After 16 to 18 h of maturation, oocytes were denuded and enucleated. Frozen–thawed somatic cells from 1 of 2 aged (23 and 20 years old) Polo Argentino breed donor mares were inserted into the perivitelline space of each enucleated oocyte and fusion was induced. Activation was performed by exposure to Ionomycin (5 μM) for 4 min, followed by 4 h culture in a combination of 6-DMAP and cycloheximide in SOFaas culture media (Choi et al. 2001 Reproduction 122, 177–183). Embryos were cultured in 50 μL SOFm droplets for 7 to 8 days and then were transferred non-surgically to anovulatory recipient mares treated with 1.5 mg oestrogen, followed by long acting progesterone (BioRelease P4 300 LA, BET Pharm, KY). The production rates of the first cell line were: fusion 301/553 (54.4%), cleavage 163/218 (53.4%), blastocysts produced 20/163 (12.2%), blastocysts transferred 18/20 (90%), pregnancies 1/18 (5.5%) and no foal born. The production rates of the second cell line were: fusion 252/553 (45.6%), cleavage 55/252 (21.8%), blastocysts produced 8/55 (14.5%), blastocysts transferred 7/8 (87.5%), pregnancies 4/7 (57%) and 1 filly was born. DNA microsatellite analysis confirmed that the filly was a clone from the original donor cell line. The filly, born naturally on Day 329 of gestation, suffered premature placental separation and weighed 12 kg. Despite the intensive care provided, the filly’s respiratory, nervous, and cardiovascular functions deteriorated rapidly and she died 14 h postpartum. Fetal membranes weighed 5.7 kg (47.5% of the filly’s weight) and showed marked oedema of the chorioalantois and umbilical cord (which also showed a torsion of 9 twists). Histopathologically, the chorioalantois showed scant and poorly developed villi and also connective tissue oedema. Death could have been due to marked immaturity, as a consequence of placental insufficiency and umbilical cord torsion.

Abstract BACKGROUND: Breast cancer (BC) is the most common cancer diagnosed in premenopausal women with an increasing incidence for age 35 or less. Although proportionally less frequent, hormone receptor (HR)–positive BC still remains the main subtype for this group, but given tumor characteristics and suboptimal adjuvant endocrine therapy (ET), present inferior long-term outcomes when compared to HR-positive BC in older women. Both Tamoxifen and Exemestane Trial (TEXT) and Suppression of Ovarian Function Trial (SOFT) have helped to optimize ET strategies for premenopausal women, identifying which patients benefit from ovarian function suppression (OFS). In Chile, we have scarce data on very young BC patients and limited access to proper OFS treatment specially in our public health system. Thus we aim to characterize a cohort of very young women regarding treatment strategies and survival, plus as an exploratory analysis evaluate Regan Score in our cohort. METHODS We conducted a retrospective population-cohort study involving women under 36 years of age, with early HR-positive/human epidermal growth factor receptor 2 (HER2)–negative BC, treated both at a community hospital and at an academic private hospital between 2001 and 2021. We did a descriptive analysis including stage distribution and treatment strategies (chemotherapy (CT), ET of choice and OFS use). We evaluated prognosis for the entire population. Survival analysis was carried out using the Kaplan-Meier method. RESULTS A total of 143 patients were included. Median age at diagnosis was 33 (19 - 36); 15.4% percent of patients were diagnosed in stage I, 51.4% stage II and 30.1% stage III. Eighty six percent received CT, 35.0% neoadjuvant. Ninety three percent received endocrine adjuvant treatment: 81.2% TAM alone, 6.8% TAM/OFS and 10.5% IA/OFS. Regarding OFS strategies only 38.5% received gonadotropin-releasing hormone (GnRH) agonists while the rest were oophorectomized. Regan median composite score was 2.77 (2.61 - 2.93) for the entire cohort. Rising to 2.95 (2.79 - 3.11) for patients treated with CT plus ET compared to 1.91 (1.55 - 2.27) for those treated with ET exclusively (p=0.0001). Patients that received TAM alone had a median Regan Score of 2.72 (0.77-4) compared to 3.14 (2.07-4.0) for patients that had OFS added (p=0.04). With a median follow-up of 59 months, 5-year Disease Free Survival (DFS), Distant DFS and Overall Survival (OS) for the entire cohort were 63.5%, 66.9% and 88.7%, respectively. CONCLUSION. To our knowledge this is one of the largest cohorts considering very young women BC in Latinamerica. We confirm their elevated overall risk with markedly higher Regan scores compared to SOFT and TEXT populations for both CT and ET exclusively treated patients. Due to access difficulties very few patients received OFS and when used, surgical oophorectomy was the main strategy of choice, with all the potential long term consequences it conveys. Thus OFS use was restricted to very high risk women, meaning that a large group of only TAM users were undertreated according to nowadays standards. This could explain the elevated recurrence risk observed in our population when compared to other under 35 years of age cohorts. Table 1. Cohort characteristics Table 2. Regan risk score Citation Format: Ana Heredia, Benjamin Walbaum, Francisco Acevedo, Cesar Sánchez. Real world data of adjuvant endocrine therapy for breast cancer in very young women. A Chilean 20-year experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-05.

“Candidatus phytoplasma asteris” and related strains (i.e., aster yellows group 16SrI) have been associated with diseases of numerous plant species worldwide. Symptoms of aster yellows (AY) have been reported on rapeseed/canola (Brassica napus and B. rapa) crops in Saskatchewan (SK) and Manitoba, Canada since 1953 (2). Symptoms generally include stunting, virescence, leaf yellowing or purpling, phyllody, and formation of bladder-like siliques. A total of 120 mature B. rapa cv. AC Sunbeam plants exhibiting AY symptoms were collected in commercial fields near Medstead, SK during 2003 and 2004 (one field per year). As described previously (4), total genomic DNA was extracted from leaf, stem, roots, and seeds collected from the 120 plants, from seeds from the seed lots sown in 2003 and 2004, and from leaf and stem tissue of 20 greenhouse-grown plants from each seed lot. The latter DNA samples were assayed for phytoplasma DNA by a nested polymerase chain reaction (PCR) assay incorporating phytoplasma universal 16S rRNA primer pairs P1/P6 (1) followed by R16R2/R16F2 (4). Seed samples analyzed from the 2003 and 2004 seed lots and tissues of the 40 greenhouse-grown plants all tested negative for phytoplasma DNA using this assay. Leaf, stem, and/or root tissues of all plants collected in the field in 2003 (60 plants) and 2004 (60 plants) and 71.1% (315 of 443) of seed samples (five seeds per sample) tested positive for the presence of phytoplasma DNA, as evidenced by the presence of an expected band of 1.2 kb on the gels after the second amplification with primers R16R2/R16F2. Nested PCR products from plant samples collected in 2003 were cloned, sequenced, and compared with phytoplasma sequences archived in the GenBank nucleotide database. On this basis, phytoplasmas detected in plants or their seeds collected in 2003 were found to be most similar (98.8%) to CHRY (Accession No. AY180956), a 16SrI-A subgroup strain, or were most similar (98.9%) to isolate 99UW89 (Accession no. AF268407), a known 16SrI-B subgroup strain. Sequences of phytoplasmas detected in plants or their seeds in 2004 were obtained by direct sequencing of rRNA products amplified from samples using PCR incorporating primer pairs P1/P6 and P4/P7 (3). Analysis of sequence data revealed that phytoplasmas in these plants were all most similar (99.5%) to AY-WB (Accession no. AY389828), a 16SrI-A subgroup member. The nucleotide sequences have been deposited with GenBank under Accession nos. DQ404346, DQ404347, and DQ411470. To our knowledge, this is the first report of 16SrI-A and 16SrI-B subgroup phytoplasmas infecting plants and seed of B. rapa in Saskatchewan. References: (1) I.-M. Lee et al. Phytopathology, 83:834, 1993. (2) W. E. Sackston. Can. Plant Dis. Surv. 33:41, 1953. (3) L. B. Sharmila et al. J. Plant Biochem. Biotech. 13:1, 2004. (4) E. Tanne et al. Phytopathology, 91:741, 2001.

Brain size may not matter, but proportions sure do. Haller's Rule, which holds that brains of smaller animals must take up more room to function, has been a landmark principle for all who have considered brain size. Since, the brain is part of the body, it is important to know the relationships of brain size to body size. To date, there has not been a method that assesses brain size using functional magnetic resonance imaging (fMRI). all other methods described in literature are based on autopsy and MRI [Filipek et al. (1994), Caviness et al. (1996), Courchesne et al. (2000), Dekaban and Sadowsky (1978), Dobbing and Sands (1973), Giedd et al. (1996), Kretschmann et al. (1979)].We reviewed literature comparing brain size to body height and body size. An equation commonly found in literate states that brain size can be computed based on the total amount of energy available to sustain it. This basis is used to derive the equation BM (e) = 1.77 * (W0.76) where BM (e) predicts brain mass, in grams, and W = body mass, in grams [Martin 1981]. The most recent equation in literature characterizing brain size is based on an adjustment to equations proposed by Birch [Birch 1999] and another proposed by Riddle [Riddle et al. (2010)] is Y = y1 * (1 + P4*X+P5*X2) where Y is the brain size in the modified equation, X is age, y1 is the brain size for the original unmodified Birch equation, P1–5 are parameters. The equations demonstrate that the size of the human brain at different development stages can be predicted both gender and age.The aforementioned equations chosen from literature, and the equation developed by us were fit to the subset of data obtained from volunteers in the study examining cognitive fatigue in Gulf War Illness using fMRI. These participants included 9 healthy male volunteer subjects, between the age of 42 and 64 years old, average age of 49 years old. Brain tissue volume, normalized for subject head size, was estimated with SIENAX [Smith 2001, Smith 2002], part of FSL [Smith 2004]. The conversion of volume in cubic millimeter to Kilogram (kg) was computed by multiplying the volume by the human brain density of 1.01 × 10^‐6 Kg/cubic millimeter (Brain size range: 1.42Kg – 1.56 Kg), average: 1.48 Kg, Standard deviation: 0.041, SEM: 0.013). The average body mass is 99.38 Kg, average height is 1.79 m. We calculated the percent difference between the models and the percent difference between the brain sizes computed using the models and the actual brain size obtained from fMRI. The estimated brain sizes from both models were vastly different. We calculated over 100% error using Martins equation, whereas we calculated a 4.1% error using the equation proposed by Riddle. Martins use of an allometric exponent value a = 0.76 as suggested for placental mammals vastly overestimates brain sizes for humans. This is directly relevant to accurately determining brain size based not just on body weight but taking into consideration age and height. Furthermore, this finding suggests the need for a new empirical formula predicting brain size using a modern method such as fMRI. fMRI would serve as a better model to empirically derive an accurate equation since it would take into account deviations in regional brain size in clinical samples, which is often the limitation of other methods utilizing autopsy and MRI.

<h1 align="left"><span style="font-family: Times New Roman;"><span style="font-size: medium;">1. Introduction.</span><span style="font-size: medium;"> </span><span style="font-size: medium;">Research using the event-related potential (ERP) technique has provided many important insights into the neural mechanisms associated with language comprehension. The integration of lexico-semantic information is associated with an increased centro-parietal negativity between 300-500 ms known as the N400 (Kutas &amp; Federmeier, 2011; Kutas &amp; Hillyard 1980). Morphosyntactic integration is associated with an early left anterior negativity (LAN) maximal around 200-500 ms, followed by a late posterior positivity (P600) maximal between 500 and 800 ms (see Kutas, Van Petten &amp; Kluender (2005) for review). The P600, in absence of early negativity, is also elicited by well-formed sentences that present increased difficulty due to temporary ambiguity (i.e. garden-paths; Gouvea, Phillips, Kazanina &amp; Poeppel, 2010; Osterhout, Holcomb &amp; Swinney, 1994). The use of ERP as a means of indexing the different neural mechanisms associated with language processing is contingent on the assumption that all neurologically normal, native speakers show consistent responses to sentence stimuli such that the grand averaged ERPs reflect effects that are manifest uniformly across individuals. This notion was recently challenged by Tanner and Van Hell (2014). In their innovative study, they showed that, although in the grand mean syntactic violations elicited a classic biphasic LAN/P600 response, most participants either showed an N400 or a P600 rather than a biphasic response. Given the topographical distribution of the effects for each group, they concluded that the LAN often found for syntactic violations in grand mean analyses is the result of the distributed negativity in some subjects being neutralized or minimized by the right lateralized positivity in the others such that only the left anterior negativity remains. Response dominance did not, however, predict acceptability judgment accuracy, nor did it correlate with measures of working memory (WM) and executive control. </span></span></h1><p align="left"><span style="font-family: Times New Roman;">The individual differences in N400/P600 response dominance observed by Tanner and Van Hell (2014) lead to interesting questions regarding other contexts which tend to elicit these potentials. Garden-path sentences are known to elicit P600 effects in absence of early effects but there is some variability (Friederici, Mecklinger, Spencer, Steinhauer &amp; Donchin, 2001; Gouvea et al., 2010; Horberg, Koptjevskaja-Tamm &amp; Kallionen, 2013; Matzke, Mai, Nager, Russeler &amp; Munte, 2002; Vos, Gunter, Schriefers &amp; Friederici, 2001). This variablity could suggest the possibility of individual differences in response profiles, as Tanner and Van Hell (2014) found for syntactic violations. </span></p><p align="left"><span style="font-family: Times New Roman;">One known source of variability in garden-path effects for both P600s and comprehension accuracy is working memory capacity (WMC). High WMC individuals show greater P600 effects for garden-path sentences compared to low WMC individuals (Friederici, Steinhauer, Mecklinger, &amp; Meyer, 1998). High WMC individuals also show reduced garden-path effects in comprehension accuracy such that they have better comprehension accuracy for garden-paths (Just &amp; Carpenter, 1992). Lower comprehension accuracy in low WMC individuals indicates they are more likely to arrive at “Good Enough” interpretations (Ferreira, Bailey &amp; Ferraro, 2002) in which the faithful interpretation of the sentence is not adopted. </span></p><p align="left"><span style="font-family: Times New Roman;">In the current study we applied the RDI analysis to the ERPs associated with garden-path sentences in order to determine (1) if participants’ N400/P600 dominance for garden-path sentences will fall into a continuum such that there will be a continuous distribution of N400 and P600 effect magnitudes with negative correlations between them, (2) if response dominance will predict comprehension accuracy, and (3), if so, is that effect reducible to individual differences in WMC.</span></p><p align="left"><span style="font-family: Times New Roman; font-size: small;"> </span></p><p align="left"><span style="font-family: Times New Roman; font-size: small;"> </span></p><p align="left"><strong><span style="font-family: Times New Roman;">2. Methods.</span></strong></p><p align="left"><span style="font-family: Times New Roman;">2.1. Participants.<strong> </strong>Data were collected from 62 right handed participants, 25 of which were excluded due to eligibility issues, technical issues, noncompliance, or excessive artifacts. As a result, 37 participants (20 female) between the ages of 18 and 35 (<em>M</em> = 21.6, <em>SD</em> = 3.21) were included in the analysis. All participants were right-handed, neurologically normal, native speakers of English with normal or corrected-to-normal vision, and none had had started learning a second language before age 12.</span></p><p align="left"><span style="font-family: Times New Roman;">2.2. Sentence Stimuli<strong> </strong>This experiment used the same control and garden-path sentences as O’Rourke &amp; Colflesh (2014) (based on Gouvea et al., 2010). See sentences (1) and (2) for examples of garden-path and control sentences, respectively.</span></p><ol><li><p>The patient met the doctor and the nurse with the white dress <span style="text-decoration: underline;">showed</span> the chart during the meeting.</p></li><li><p>The patient met the doctor while the nurse with the white dress <span style="text-decoration: underline;">showed</span> the chart during the meeting.</p></li></ol><p align="left"><span style="font-family: Times New Roman;">There were 36 sentences per condition and an additional 288 sentences including fillers and conditions not presented herein. Fifty percent of the sentences were followed by a yes/no comprehension question. </span></p><p align="left"><span style="font-family: Times New Roman;">2.3. Complex Span Tasks. As indices of WMC, three complex span tasks were used in the current study: reading span (Daneman &amp; Carpenter, 1980; Unsworth, Heitz, Schrock &amp; Engle, 2005), operation span (Unsworth, et al., 2005), and symmetry span (Unsworth, Redick, Heitz, Broadway, &amp; Engle, 2009). In the reading span task participants were presented with a series of sentences and asked to indicate, via button press, if the sentence they read made sense. After each sentence they were then presented with a letter that they were to remember for later recall. At the end of the sequence, they had to recall the letters in serial order. Their score reflects the total number of letters recalled in the correct serial position out of a total of 75 items. Operation span was identical to reading span as described above except instead of making sense judgments on sentences, participants had to read math problems involving two operations, one addition/subtraction and one multiplication/division, and verify if the solution provided was correct. Symmetry Span (Engle, 2005) is a complex span task like the aforementioned tasks, but it uses visuospatial stimuli. Participants were presented with a series of 8x8 black and white grids and asked to indicate, via button press, whether the design was vertically symmetrical. After each symmetry judgment they were presented with a 4x4 grid with a square filled in red that they were asked to remember for later recall. At the end of the sequence, participants had to recall the position of the red squares, in the order in which they appeared. The maximum score was 42.</span></p><p align="left"><span style="font-family: Times New Roman;">2.5. Procedure.<strong> </strong>Electroencephalographic (EEG) data was recorded using the Electrical Geodesics Inc. (EGI) Hydrocel 256 channel system while participants performed the sentence processing task. Sentences were presented word-by-word and participants responded to the comprehension questions with a button press. Data was collected over two sessions. Upon completion of the sentence processing task, participants performed the working memory assessments.</span></p><p align="left"><span style="font-family: Times New Roman;">2.6. Data Analysis. Upon completion of pre-processing and averaging, ERPs were computed for each individual for each experimental condition for a 1500 ms interval time-locked to the presentation of the critical verb (“showed” in the examples above) relative to a 200 ms pre-stimulus baseline. The following time windows were considered in the analysis of P600 effects: 300-500, 500-700 and 700-900 ms. The analyses were performed on midline and dorsal and electrodes. The midline electrodes were divided into anterior (FPZ, AFZ, FZ, FCZ, CZ) and posterior (CPZ, 90, PZ, POZ, OZ) sections. The dorsal electrodes were grouped by anterior-posterior (AP) location and hemisphere: Left anterior (FP1, AF3, F1, F3, FC3, C3), right anterior (FP2, AF4, F2, F4, FC4, C3), left posterior (CP3, CP1, P1, P3, P1, PO3, O1) and right posterior (CP4, CP1, P4, P2, PO4, O2). Sentence type effects in the ERP data were assessed in the dorsal regions with multiple three-way analysis of variance (ANOVA) (Sentence Type x AP x Hemisphere) and in the midline electrodes with a two-way ANOVA (Sentence Type x AP). RDI was then calculated using Tanner &amp; Van Hell (2014)’s formula, using the same centro-parietal region of interest and time windows. Participants were divided into groups according to response dominance (N400 or P600). An analysis of covariance (ANCOVA) was run with garden-path comprehension accuracy as the dependent variable, RDI group as the independent variable and average, standardized WM score (average z-score for the three measures) as the covariate.</span></p><p align="left"><strong><span style="font-family: Times New Roman;">3. Results. </span></strong></p><p align="left"><span style="font-family: Times New Roman;">3.1. Sentence Type Effects.<strong> </strong>Accuracy for garden-path sentences (<em>M</em> = 68.3%, <em>SD</em> = 14.4) was significantly lower than control sentences (<em>M</em> = 73.6%, <em>SD</em> = 11.4; <em>F</em>(1,36) = 6.13, <em>p</em> &lt; .05, <em>η_p²</em> = .15). In the ERP data, garden-path sentences (compared to controls) showed a significant interaction of Type and AP over midline sites in the 500-700 and 700-900 ms time windows (<em>F</em>(1,36) = 4.18, <em>p</em> &lt; .05, <em>η_p²</em> = .10 and <em>F</em>(1,36) = 6.02, <em>p</em> &lt; .05, <em>η_p²</em> = .14, respectively) such that garden-paths elicited greater positivity than control sentences over posterior sites. Simple comparisons showed significant effects of type in posterior areas in both the 500-700 (<em>F</em>(1,36) = 4.14, <em>p</em> &lt; .05, <em>η_p²</em> = .10) and 700-900 time windows (<em>F</em>(1,36) = 4.93, <em>p</em> &lt; .05, <em>η_p²</em> = .12). There were no effects in the anterior sites. </span></p><p align="left"><span style="font-family: Times New Roman;">3.2. RDI Analysis.<strong> </strong>Analysis of N400 and P600 effect magnitudes for garden path sentences showed a strong negative correlation (<em>r</em>(32) = -.90; <em>p</em> &lt; .001). The data suggest a continuum between strong N400 and P600 dominance. Participants were divided into groups based on RDI values (negative values indicating N400 dominance and positive indicating P600 dominance). A total of 18 participants were N400 dominant and 19 were P600 dominant. </span></p><p align="left"><span style="font-family: Times New Roman;">Prior to running the ANCOVA, it was necessary to determine that the covariates affected the dependent variable equally across the two groups. In the entire sample, there was a significant correlation between average complex span score and garden-path comprehension accuracy (<em>r</em>(32) = .52, p &lt; .01). Each RDI group showed positive correlations (N400 dominant, <em>r</em>(14) = .63; P600 dominant, <em>r</em>(16) = .48). Using a Fisher transformation (Fisher, 1915), the difference between the group correlations was not significant (<em>z</em> = .6, <em>p</em> &gt; .50). </span></p><p align="left"><span style="font-family: Times New Roman;">The ANCOVA showed that there was a significant effect of Response Dominance on GP Comprehension Accuracy after controlling for WMC, F(1,31) = 4.45, p &lt; .05, <em>η_p²</em> =.13) such that P600 dominant individuals had greater accuracy. Complex span performance accounted for a significant amount of variance (F(1,31) = 13.8, p &lt; .005, <em>η_p²</em> = .31).</span></p><p align="left"><span style="font-family: Times New Roman;"><strong>4. Discussion. </strong>The current study found evidence of distinct neural response profiles which were not apparent in the grand averaged data in neurologically normal, native English speakers during the processing of garden-path sentences and this individual differences measure predicted comprehension performance. The key finding of the current study is the effect of response dominance on behavioral performance. Response dominance emerged as an effective predictor of comprehension accuracy such that P600 dominant participants had better comprehension accuracy for garden-path sentences. The results of the ANCOVA show that response dominance is not a proxy for WMC but rather a distinct individual difference measure. This suggests that cognitive capacity alone does not limit the individual’s ability to resolve garden-paths. Response dominance may, instead, indicate the engagement of specific parsing strategies. The results of the current study extend the utility of Tanner and Van Hell (2014)’s RDI as an individual difference to the processing of the garden-path sentences showing that individuals in the sample exhibited distinct response profiles (either N400 or P600 dominant). While future research will reveal the neurocognitive underpinnings of response dominance, the findings of the current study establish this individual difference measure as a means of predicting behavior from neural activity. </span></p>