Round Table Interview with Mike Hastings, Anita Jensen, Estelle Lavoie, and Mary McAleney by Andrea L’Hommedieu

Biographical NoteMichael M. Hastings, a native of Morrill, Maine, graduated from Tilton School (NH) in 1968 and Bowdoin College in 1972. Following a year of graduate study in Public & International Affairs at George Washington University, he worked for seven years as a foreign and defense policy aide to Senator William S. Cohen (1973-1980) and for four years for Senator George J. Mitchell (1980-1984). In October, 1984, he joined the international staff of Catholic Relief Services (CRS) and moved to Africa. Over a span of eight years, he worked as a CRS development administrator in Kenya, Tanzania, Togo and The Gambia. During the same period, he assisted in the provision of emergency food for people displaced by civil wars in the Southern Sudan and Liberia. In 1992, he returned to Maine to direct a “center for excellence,” focusing on aquaculture and economic development. Since 2004, he has worked for the University of Maine as its Director of Research and Sponsored Programs. Between 1992 and 2008, he also served on several civic boards and institutions including the Maine Fishermen’s Forum, The Maine Oil Spill Advisory Committee (which he chaired), the Maine Indian Tribal State Commission, the Down East Institute, and the Maine Sea Grant Policy Advisory Committee. Between 1996 and 2001 he was elected three times to be a member of the Town Council of Hampden, ME, where he resides with his wife, a middle school teacher. Anita Holst-Jensen was born in Karl-Marx-Stadt (Chemnitz), East Germany, on March 16, 1945, to Rasma Rasmanis and Arvids Lusis. Her mother emigrated from Latvia in September of 1944, and Jensen was born in a displaced persons camp, where she lived until she was four years old. Her family eventually emigrated to Australia in 1949, settling in Victoria. Jensen received all of her schooling in Australia and went to university in Melbourne. She married Henning Holst-Jensen, and in 1966 they moved to Perth. When immigration into the United States became possible in 1968, they relocated to the Washington, D.C. area, and Jensen took a job with Investors Overseas Services, later Equity Funding. In 1970, she went to work in Senator Ed Muskie’s office, where she continued until he became secretary of state. She transitioned to George Mitchell’s staff when he was appointed to Muskie’s vacated Senate seat and remained for his fourteen years of Senate service, becoming increasingly involved with speech writing and research. Estelle Lavoie was born in Lewiston, Maine, on November 23, 1949, and grew up there, the youngest of three children. Her father worked as a building contractor until his death in 1964, after which her mother worked part-time as a bank teller. She attended Lewiston public schools and was graduated from Bates College (class of 1971), spending her junior year studying in Switzerland. At the end of 1972, she went to work for Governor Ken Curtis. By September of 1973, she had been hired as part of Senator Ed Muskie’s staff, working first as a caseworker and eventually as his legislative assistant. She attended law school at American University from 1978 to 1981 and transitioned to Senator Mitchell’s staff when he assumed Muskie’s Senate seat. She left Mitchell’s staff in the fall of 1983 and joined the law firm of Preti, Flaherty, Beliveau & Pachios the following June. Her practice has evolved from health law to other political practice issues. She served on the Democratic State Committee from 1986 to 1990 and was a delegate to the 1988 National Convention. Mary Elizabeth McAleney was born on March 18, 1945, in Tuscaloosa, Alabama. Her mother, Helen Irene (Twombly) McAleney, was a Works Progress Administration worker, and her father, William McAleney, was a U.S. Customs officer. Mary came from a strongly Democratic Maine family and was politically active from a young age. She was sent from her home near Vanceboro, Maine, to St. Joseph’s boarding school in South Portland, and from there she went to Merrimac College. After her graduation, she taught high school in Maine, first at St. Joseph’s and then at Catherine McAuley High School. After eight years of teaching, she went into political work. She quickly rose through the ranks during Senator Muskie’s ‘76 campaign and worked for state Senator Jim Tierney. She served in George Mitchell’s U.S. Senate office for ten years (1984-1994), focusing on Maine issues. SummaryInterview includes discussion of: how Mary McAleney became Mitchell’s scheduler; the transition from Muskie to Mitchell; how Mitchell’s briefcase would be searched entering the office because initially no one knew who he was; the Elizabeth Taylor story; the cow joke; the 1982 U.S. Senate campaign; anecdotes about when Mitchell accidentally sat in a canoe backwards and when David Emery’s float sank in the Kennebec River; the relationship between Cohen and Mitchell; Mitchell’s gaining the support of one of Estelle Lavoie’s friends because he knew the name spelling; Mitchell’s work ethic; Mitchell’s complimenting Byrd on his history of the Senate; Mitchell eye glasses and the striped belt; visiting Talmadge Plantation after Mitchell’s reelection in 1988; Mitchell’s ability to learn and adapt; Anita Jensen’s experience driving Mitchell to work; Mitchell’s lifestyle in D.C.; Sally Mitchell’s decision to stay in Maine and not become involved in politics; the women’s restroom situation in the Capitol; the machine-gun ban and how Feinstein did not want to come to the Senate floor the day after it passed; Mitchell’s process for examining different points of view; an anecdote about Mitchell’s changing his mind and explaining it to the press; Jensen’s lively discussions with Mitchell; the Rehnquist nomination; the role of the staff in Mitchell’s office; Gayle Cory and her influence in the office and with Mitchell; Buzz Fitzgerald; the dynamics of the Mitchell Senate office and the office organization’s lack of hierarchy; the longevity of the staff; Anita Jensen’s role as the speechwriter; writing updates about China; Larry Benoit’s and David Lemoine’s traveling around Maine to update the voter lists; Larry Benoit; Mitchell’s making sure that there were Mainers working for him; the interns; and the Mitchell Institute

Wetenschap met de ramen wijd open: tien lessen voor wie impact wil maken

In tien lessen geven door de wol geverfde sociale en geesteswetenschappers handvatten aan collega’s die impact willen maken met hun onderzoek. In een nieuwe brochure, een uitgave van de Sociaal-Wetenschappelijke Raad van de KNAW, pleiten ze voor meer waardering voor impact en geven ze praktische handvatten om aan de slag te gaan. Wetenschap met de ramen wijd open, tien lessen voor wie impact wil maken is een uitgave van de Sociaal-Wetenschappelijke Raad van de Koninklijke Nederlandse Akademie voor Wetenschappen (KNAW). De brochure is geschreven door Godfried Engbersen, Andrea Evers, Beatrice de Graaf, Paul ’t Hart, Anita Jansen, Lotte Jensen, Leo Lucassen en Maarten Prak, allen hoogleraar in de sociale of geesteswetenschappen. De gedrukte brochure wordt in het Nederlands verspreid over alle faculteiten

Role of Soil, Crop Debris, and a Plant Pathogen in Salmonella enterica Contamination of Tomato Plants

Background: In the U.S., tomatoes have become the most implicated vehicle for produce-associated Salmonellosis with 12 outbreaks since 1998. Although unconfirmed, trace backs suggest pre-harvest contamination with Salmonella enterica. Routes of tomato crop contamination by S. enterica in the absence of direct artificial inoculation have not been investigated. Methodology/Principal Findings: This work examined the role of contaminated soil, the potential for crop debris to act as inoculum from one crop to the next, and any interaction between the seedbourne plant pathogen Xanthomonas campestris pv. vesicatoria and S. enterica on tomato plants. Our results show S. enterica can survive for up to six weeks in fallow soil with the ability to contaminate tomato plants. We found S. enterica can contaminate a subsequent crop via crop debris; however a fallow period between crop incorporation and subsequent seeding can affect contamination patterns. Throughout these studies, populations of S. enterica declined over time and there was no bacterial growth in either the phyllosphere or rhizoplane. The presence of X. campestris pv. vesicatoria on co-colonized tomato plants had no effect on the incidence of S. enterica tomato phyllosphere contamination. However, growth of S. enterica in the tomato phyllosphere occurred on co-colonized plants in the absence of plant disease. Conclusions/Significance: S. enterica contaminated soil can lead to contamination of the tomato phyllosphere. A six week lag period between soil contamination and tomato seeding did not deter subsequent crop contamination. In the absence o

ISSCR standards for the use of human stem cells in basic research.

The laboratory culture of human stem cells seeks to capture a cellular state as an in vitro surrogate of a biological system. For the results and outputs from this research to be accurate, meaningful, and durable, standards that ensure reproducibility and reliability of the data should be applied. Although such standards have been previously proposed for repositories and distribution centers, no widely accepted best practices exist for laboratory research with human pluripotent and tissue stem cells. To fill that void, the International Society for Stem Cell Research has developed a set of recommendations, including reporting criteria, for scientists in basic research laboratories. These criteria are designed to be technically and financially feasible and, when implemented, enhance the reproducibility and rigor of stem cell research

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Risk of Parkinson's disease after tamoxifen treatment

<p>Abstract</p> <p>Background</p> <p>Women have a reduced risk of developing Parkinson's disease (PD) compared with age-matched men. Neuro-protective effects of estrogen potentially explain this difference. Tamoxifen, commonly used in breast cancer treatment, may interfere with the protective effects of estrogen and increase risk of PD. We compared the rate of PD in Danish breast cancer patients treated with tamoxifen to the rate among those not treated with tamoxifen.</p> <p>Methods</p> <p>A cohort of 15,419 breast cancer patients identified from the Danish Breast Cancer Collaborative Group database was linked to the National Registry of Patients to identify PD diagnoses. Overall risk and rate of PD following identification into the study was compared between patients treated with tamoxifen as adjuvant hormonal therapy and patients not receiving tamoxifen. Time-dependent effects of tamoxifen treatment on PD rate were examined to estimate the likely induction period for tamoxifen.</p> <p>Results</p> <p>In total, 35 cases of PD were identified among the 15,419 breast cancer patients. No overall effect of tamoxifen on rate of PD was observed (HR = 1.3, 95% CI: 0.64-2.5), but a PD hazard ratio of 5.1 (95% CI: 1.0-25) was seen four to six years following initiation of tamoxifen treatment.</p> <p>Conclusions</p> <p>These results provide evidence that the neuro-protective properties of estrogen against PD occurrence may be disrupted by tamoxifen therapy. Tamoxifen treatments may be associated with an increased rate of PD; however these effects act after four years, are of limited duration, and the adverse effect is overwhelmed by the protection against breast recurrence conferred by tamoxifen therapy.</p

Effects of low birth weight, maternal smoking in pregnancy and social class on the phenotypic manifestation of Attention Deficit Hyperactivity Disorder and associated antisocial behaviour: investigation in a clinical sample

<p>Abstract</p> <p>Background</p> <p>Attention Deficit Hyperactivity Disorder (ADHD) is a genetically influenced condition although indicators of environmental risk including maternal smoking during pregnancy, low birth weight and low social class have also been found to be associated with the disorder.</p> <p>ADHD is a phenotypically heterogeneous disorder in terms of the predominant symptom types (inattention, hyperactive-impulsivity), their severity and comorbidity, notably Conduct Disorder. It is possible that these different clinical manifestations of the disorder may arise because of the differing effects of the environmental indicators of environmental risk. We set out to test this hypothesis.</p> <p>Methods</p> <p>In a sample of 356 children diagnosed with ADHD, we sought to investigate possible effects of three indicators of environmental risk – maternal smoking during pregnancy, birth weight and social class – on comorbid Conduct Disorder, conduct disorder symptoms and inattentive and hyperactive-impulsive symptom severity.</p> <p>Results</p> <p>Multiple regression analysis revealed that, after controlling for significant covariates, greater hyperactive-impulsive symptom severity was significantly associated with maternal smoking during pregnancy (r²= 0.02, Beta = 0.11, t = 1.96, p = 0.05) and social class (r²= 0.02, Beta = 0.12, t = 2.19, p = 0.03) whilst none of the environmental risk indicators significantly predicted number of inattentive symptoms. Conduct Disorder symptoms were positively predicted by maternal smoking in pregnancy (r²= 0.04, Beta = 0.18, t = 3.34, p = 0.001) whilst both maternal smoking during pregnancy and social class significantly predicted a diagnosis of Conduct Disorder (OR = 3.14, 95% CI: 1.54, 6.41, Wald = 9.95, p = 0.002) and (OR = 1.95 95% CI: 1.18, 3.23 Wald = 6.78, p = 0.009) respectively.</p> <p>Conclusion</p> <p>These findings suggest that indicators of environmental risk, in this instance maternal smoking in pregnancy and environmental adversity indexed by lower social class, independently influence the clinical presentation of the ADHD phenotype. Other types of study design are needed to investigate whether these associations between indicators of environmental risk factors and ADHD clinical heterogeneity are attributable to causal risk effects and to further establish the magnitude of these effects. These findings have implications, not only for our understanding of the aetiology of ADHD, but may also be of clinical value, enabling the identification of individuals who are at higher risk of problematic behaviours in ADHD, notably conduct disorder, to enable earlier, targeted risk reduction strategies.</p

Solonamide B Inhibits Quorum Sensing and Reduces Staphylococcus aureus Mediated Killing of Human Neutrophils

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a serious human pathogen, and particularly the spread of community associated (CA)-MRSA strains such as USA300 is a concern, as these strains can cause severe infections in otherwise healthy adults. Recently, we reported that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs) to sensor histidine kinase, AgrC, of the agr two-component system. The hypervirulence of USA300 has been linked to increased expression of central virulence factors like α-hemolysin and the phenol soluble modulins (PSMs). Importantly, in strain USA300 Solonamide B dramatically reduced the activity of α-hemolysin and the transcription of psma encoding PSMs with an 80% reduction in toxicity of supernatants towards human neutrophils and rabbit erythrocytes. To our knowledge this is the first report of a compound produced naturally by a Gram-negative marine bacterium that interferes with agr and affects both RNAIII and AgrA controlled virulence gene expression in S. aureus

Non-Invasive Quantification of White and Brown Adipose Tissues and Liver Fat Content by Computed Tomography in Mice

OBJECTIVES: Obesity and its distribution pattern are important factors for the prediction of the onset of diabetes in humans. Since several mouse models are suitable to study the pathophysiology of type 2 diabetes the aim was to validate a novel computed tomograph model (Aloka-Hitachi LCT-200) for the quantification of visceral, subcutaneous, brown and intrahepatic fat depots in mice. METHODS: Different lean and obese mouse models (C57BL/6, B6.V-Lep(ob), NZO) were used to determine the most adequate scanning parameters for the detection of the different fat depots. The data were compared with those obtained after preparation and weighing the fat depots. Liver fat content was determined by biochemical analysis. RESULTS: The correlations between weights of fat tissues on scale and weights determined by CT were significant for subcutaneous (r(2) = 0.995), visceral (r(2) = 0.990) and total white adipose tissue (r(2) = 0.992). Moreover, scans in the abdominal region, between lumbar vertebrae L4 to L5 correlated with whole-body fat distribution allowing experimenters to reduce scanning time and animal exposure to radiation and anesthesia. Test-retest reliability and measurements conducted by different experimenters showed a high reproducibility in the obtained results. Intrahepatic fat content estimated by CT was linearly related to biochemical analysis (r(2) = 0.915). Furthermore, brown fat mass correlated well with weighted brown fat depots (r(2) = 0.952). In addition, short-term cold-expose (4 °C, 4 hours) led to alterations in brown adipose tissue attributed to a reduction in triglyceride content that can be visualized as an increase in Hounsfield units by CT imaging. CONCLUSION: The 3D imaging of fat by CT provides reliable results in the quantification of total, visceral, subcutaneous, brown and intrahepatic fat in mice. This non-invasive method allows the conduction of longitudinal studies of obesity in mice and therefore enables experimenters to investigate the onset of complex diseases such as diabetes and obesity

Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory gd T cell subsets

Two distinct subsets of γδ T cells that produce interleukin 17 (IL-17) (CD27(-) γδ T cells) or interferon-γ (IFN-γ) (CD27(+) γδ T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-γ-producing or IL-17-producing γδ T cell subsets in vivo. We found that CD27(+) γδ T cells were committed to the expression of Ifng but not Il17, whereas CD27(-) γδ T cells displayed permissive chromatin configurations at loci encoding both cytokines and their regulatory transcription factors and differentiated into cells that produced both IL-17 and IFN-γ in a tumor microenvironment