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Trafficking protein particle (TRAPP) complexes, which include the TRAPPC4 protein, regulate membrane trafficking between lipid organelles in a process termed vesicular tethering. TRAPPC4 was recently implicated in a recessive neurodevelopmental condition in four unrelated families due to a shared c.454+3A>G splice variant. Here, we report 23 patients from 17 independent families with an early-infantile-onset neurodegenerative presentation, where we also identified the homozygous variant hg38:11:119020256 A>G (NM_016146.5:c.454+3A>G) in TRAPPC4 through exome or genome sequencing. No other clinically relevant TRAPPC4 variants were identified among any of over 10,000 patients with neurodevelopmental conditions. We found the carrier frequency of TRAPPC4 c.454+3A>G was 2.4-5.4 per 10,000 healthy individuals. Affected individuals with the homozygous TRAPPC4 c.454+3A>G variant showed profound psychomotor delay, developmental regression, early-onset epilepsy, microcephaly and progressive spastic tetraplegia. Based upon RNA sequencing, the variant resulted in partial exon 3 skipping and generation of an aberrant transcript owing to use of a downstream cryptic splice donor site, predicting a premature stop codon and nonsense mediated decay. These data confirm the pathogenicity of the TRAPPC4 c.454+3A>G variant, and refine the clinical presentation of TRAPPC4-related encephalopathy.

Talking Circles are safe spaces where relationships are built, nurtured, reinforced, and sometimes healed; where norms and values are established; and where people connect intellectually, spiritually, and emotionally with other members of the Circle. The Circle can also be an evaluation method that increases voice, decreases invisibility, and does not privilege one worldview or version of reality over another. The purpose of this article is to describe how the Circle can be a culturally responsive evaluation practice for those evaluators wishing to build relationships, share power, elicit stakeholder voice, solve problems, and increase participants' capacity for program design, implementation, and evaluation. Circles can be used by both Indigenous and non-Indigenous evaluators. By offering the global evaluation community this concrete, practical, and culturally responsive approach, we open the door so that others can build on this work and offer additional insights as this practice is used, refined, and documented.

This brief summary provides an overview of the Apprenticeship in Ecological Horticulture's alumni survey methods and results. The survey was administered to graduates of the six-month training program in organic farming, gardening and food systems that takes place each year at the University of California, Santa Cruz, and is administered by the Center for Agroecology and Sustainable Food Systems through UCSC Extension.

Developed by the UCSC Center for Agroecology & Sustainable Food Systems, this series of case studies focuses on the social and environmental efforts of innovative U.S. food system businesses across different geographies, scales, legal structures, and points along the food supply chain.While these represent only a handful of the thousands of socially and environmentally responsible food businesses across the nation, they have many features that others can learn from in developing sustainable businesses that incorporate the triple bottom line of people, planet, and profits.

Developed by the UCSC Center for Agroecology & Sustainable Food Systems, this series of case studies focuses on the social and environmental efforts of innovative U.S. food system businesses across different geographies, scales, legal structures, and points along the food supply chain. While these represent only a handful of the thousands of socially and environmentally responsible food businesses across the nation, they have many features that others can learn from in developing sustainable businesses that incorporate the triple bottom line of people, planet, and profits.

Feature articles:Apprenticeship Graduates Put Skills to Work in Local Food, Farming EffortsStudy Examines Factors in Farming Conservation PracticesCover Crops Offer Soil, Pest Management OptionsFarm-to-College Efforts Help "Green" Campus Food SystemsStrawberry Study Shows Value of Crop Rotations

This research brief examines the livelihoods of small-scale coffee growing households in Nicaragua, comparing those that are selling to certified "specialty" coffee markets with those selling to conventional markets. The study uses the Millennium Development Goals as established by the United Nations in 2000 as a framework for analyzing the current status of 177 Nicaraguan households involved in small-scale coffee production. The authors conclude that, despite some recent gains in terms of coffee price increases), small-scale growers—no matter whether they sell to certified or conventional markets—are in fact losing economic ground due to declining real prices and the rising costs of sustainable production, a situation that needs to be addressed by the coffee industry, certification groups, producer organizations, and governments.

Offers ideas for water-conserving irrigation techniques, including a brief overview of drip irrigation.

Introduces the technique of worm composting, an effective compost method that can be used to produce a nutrient-rich soil amendment in a limited space

Describes how to make sowing and potting mixes, as well as compost tea, for seed starting.

Information on how to control snails and slugs with methods that meet organic standards

This research brief explores the apparent conflict between new food safety rules designed to minimize the presence of wildlife around farm fields, and environmental protection efforts designed to decrease the impacts of pesticides, fertilizers, and sediments on the environment.Using information from existing research, the brief examines the effectiveness of measures being used by Central Coast growers to address environmental problems. We then summarize the history of food safety issues on the Central Coast, and outline potential sources of crop contamination in the field. Finally, we discuss the ways that food safety guidelines conflict with environmental protection methods, proposing the idea that such methods could in fact be designed to reduce contamination sources and improve food safety.

This article provides a framework to assist evaluators, teaching artists, and program managers in working together.

Feature Articles:Serving the Public in a Public UniversityCommunity-Based ResearchOn-Line Sustainable Agriculture Curriculum Resource DevelopedCenter Plans National Sustainable Agriculture Educators ConferenceOrganic Rose Care: Selecting, Siting, and Planting

This research brief describes the process of participatory action research using examples from work on shade coffee landscapes and community development in Nicaragua and El Salvador.

Feature articles:Trap Crops in Organic Strawberry ProductionInternational Meeting on Community Supported AgricultureBlueberry Variety Trial at the UCSC FarmImpacts of GM Plants on Wild Relatives of California CropsGopher Control on Organic Farms

The 2001-2003 Activity Report/Research Summary reports on the research, education, and public outreach work of the Center for Agroecology and Sustainable Food Systems from July 1, 2001 through June 30, 2003.

Feature articles:Community Agroecology NetworkStrawberry Ecosystem StudyPolitics of Methyl BromideGrowing Beans in the Home Garden

This Research Brief details the experiences of Community Supported Agriculture (CSA) members in the California central coast's 5-county region: who and why they joined a CSA, their connection to farmers, reasons for staying with or leaving the CSA project, and the impact of the CSA on their eating habits and on their awareness of agricultural and enviornmental issues.

The 1999–2001 Activity Report/Research Summary reports on the research, education, and public outreach work of the Center for Agroecology and Sustainable Food Systems from July 1, 1999 through June 30, 2001.

Correctional educators, recognizing that the majority of inmates lack the math, reading, and language skills required to be successful in today's workplace, strive to equip offenders with the skills and abilities needed to find and maintain work on their release. However, most adult literacy programs in prisons fail to raise the gradelevel equivalency scores of low-performing students high enough to qualify inmates for General Education Development preparation courses, and many do not equip inmates with the basic computer skills needed to apply for most jobs. This pre-/posttest, single-group study on Florida Ready to Work (FLRTW), a computer-based workplace credentialing program, is the first of its kind in a correctional environment. The purpose of this study is to determine the impact of FLRTW on learning gains in reading, language, and math as measured by the Test of Adult Basic Education. Fifty-three male inmates residing in a private, therapeutic work-release center who were required to complete FLRTW voluntarily agreed to participate in this study. Findings indicate much larger than average grade-level increases ranging from 3.1 to 3.5, with no moderating impact by the independent variables of race, age, sentence length, and prior incarcerations. The study fills a knowledge gap related to the effectiveness of workplace credentialing programs in correctional institutions, and provides recommendations related to policy, practice, and research in this challenging environment.

Reports a correlational study to determine whether teacher's mathematics anxiety might inhibit the introduction of more problem solving and abstraction in elementary schools to enable more ninth graders to enroll in algebra. Correlations on 19 variables for 116 teachers indicated that anxiety decreased with increased mathematics content studied and age. (MDH)

Abstract Background Human papillomavirus (HPV) vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections. The yeast-derived recombinant quadrivalent HPV L1 vaccine, GARDASIL(R), has played an important role in reducing cancer and genital warts since its introduction in 2006. The L1 proteins self-assemble into virus-like particles (VLPs). Results VLPs were subjected to post-purification disassembly and reassembly (D/R) treatment during bioprocessing to improve VLP immunoreactivity and stability. The post-D/R HPV16 VLPs and their complex with H16.V5 neutralizing antibody Fab fragments were visualized by cryo electron microscopy, showing VLPs densely decorated with antibody. Along with structural improvements, post-D/R VLPs showed markedly higher antigenicity to conformational and neutralizing monoclonal antibodies (mAbs) H16.V5, H16.E70 and H263.A2, whereas binding to mAbs recognizing linear epitopes (H16.J4, H16.O7, and H16.H5) was greatly reduced. Strikingly, post-D/R VLPs showed no detectable binding to H16.H5, indicating that the H16.H5 epitope is not accessible in fully assembled VLPs. An atomic homology model of the entire HPV16 VLP was generated based on previously determined high-resolution structures of bovine papillomavirus and HPV16 L1 pentameric capsomeres. Conclusions D/R treatment of HPV16 L1 VLPs produces more homogeneous VLPs with more virion-like antibody reactivity. These effects can be attributed to a combination of more complete and regular assembly of the VLPs, better folding of L1, reduced non-specific disulfide-mediated aggregation and increased stability of the VLPs. Markedly different antigenicity of HPV16 VLPs was observed upon D/R treatment with a panel of monoclonal antibodies targeting neutralization sensitive epitopes. Multiple epitope-specific assays with a panel of mAbs with different properties and epitopes are required to gain a better understanding of the immunochemical properties of VLPs and to correlate the observed changes at the molecular level. Mapping of known antibody epitopes to the homology model explains the changes in antibody reactivity upon D/R. In particular, the H16.H5 epitope is partially occluded by intercapsomeric interactions involving the L1 C-terminal arm. The homology model allows a more precise mapping of antibody epitopes. This work provides a better understanding of VLPs in current vaccines and could guide the design of improved vaccines or therapeutics.

Research is reviewed on the characteristics of highly gifted children, notably nonintellective factors such as creative/productive behavior cited by J. Renzulli and the traits of child prodigies in studies by D. Feldman. (CL)

The research reported did not generally support the assumption that subordinates will be more satisfied with their jobs if their values are similar to those of their superiors. (Author/IRT)

Fulvestrant is a dose dependent selective estrogen receptor (ER) down-regulator (SERD) used in ER-positive metastatic breast cancer (MBC). Nearly all patients develop resistance. We performed molecular analysis of circulating tumor cells (CTC) to gain insight into fulvestrant resistance. Preclinical studies were performed with cultured breast cancer cells spiked into human blood and analyzed on the CellSearch ® system. Clinical data are limited to a subset of patients with ER-positive MBC from a previously reported pilot trial whose disease was progressing on fulvestrant (N = 7) or aromatase inhibitors (AIs) (N = 10). CTCs were enumerated and phenotyped for ER and B-cell lymphoma (BCL2) using the CellSearch ® CXC kit. In preclinical modeling, tamoxifen and AIs resulted in stabilized ER expression, whereas fulvestrant eliminated it. Five of seven patients progressing on fulvestrant had ≥5CTC/7.5 ml WB. Two of these five, treated with 500 mg/month fulvestrant, had no detectable CTC-expression of ER and BCL2 (an ER regulated gene). Three patients had heterogeneous CTC-ER and BCL2 expression indicating incomplete degradation of the ER target by fulvestrant. Two of these patients received 250 mg/month whereas the third patient received 500 mg/month fulvestrant. Her cancer harbored a mutation (Y537S) in the estrogen receptor alpha gene ( ESR1 ). All seven ER positive patients progressing on AIs had heterogeneous CTC-ER expression. These results suggest heterogeneous mechanisms of resistance to fulvestrant, including insufficient dosage, ESR1 mutation, or conversion to dependence on non-ER pathways. CTC enumeration, phenotyping, and genotyping might identify patients who would benefit from fulvestrant dose escalation versus switching to alternative therapies. [ABSTRACT FROM AUTHOR]

The article discusses the dining habits of early colonists in the New England region of the U.S. The foods eaten by Colonists includes: eagle, pumpkin pie, clam chowder, cod, corn, Indian pudding, baked beans, and chicken pies. Foods that were avoided include tomatoes, quahogs, hard-shell clams, and lobsters. The article also mentions New England restaurants that offer traditional New England dishes and includes two traditional recipes.