The conserved XPF:ERCC1-like Zip2:Spo16 complex controls meiotic crossover formation through structure-specific DNA binding.

In eukaryotic meiosis, generation of haploid gametes depends on the formation of inter-homolog crossovers, which enable the pairing, physical linkage, and eventual segregation of homologs in the meiosis I division. A class of conserved meiosis-specific proteins, collectively termed ZMMs, are required for formation and spatial control of crossovers throughout eukaryotes. Here, we show that three Saccharomyces cerevisiae ZMM proteins-Zip2, Zip4 and Spo16-interact with one another and form a DNA-binding complex critical for crossover formation and control. We determined the crystal structure of a Zip2:Spo16 subcomplex, revealing a heterodimer structurally related to the XPF:ERCC1 endonuclease complex. Zip2:Spo16 lacks an endonuclease active site, but binds specific DNA structures found in early meiotic recombination intermediates. Mutations in multiple DNA-binding surfaces on Zip2:Spo16 severely compromise DNA binding, supporting a model in which the complex's central and HhH domains cooperate to bind DNA. Overall, our data support a model in which the Zip2:Zip4:Spo16 complex binds and stabilizes early meiotic recombination intermediates, then coordinates additional factors to promote crossover formation and license downstream events including synaptonemal complex assembly

Submarine groundwater discharge: an unseen yet potentially important coastal phenomenon

In collaboration with researchers from Florida State University, Florida Sea Grant introduces an important but poorly known topic: submarine groundwater discharge. Although nearly invisible, submarine groundwater discharge influences coastal systems. This brochure helps explain this important phenomenon. (8pp.

Revising old child support orders: The Wisconsin experience

In an effort to make Wisconsin's child support cases more equitable and up-to-date, child support staff reviewed "old" child support orders in thirteen of the state's seventy-two counties. (Reviewing old child support orders is now mandatory under the provisions of the Family Support Act of 1988.) Of the reviewed cases, only 21 percent were revised. Primary reasons for non-revision were the economic circumstances of the noncustodial parent (among welfare cases) and a lack of permission by the custodial parent to proceed (among non-welfare cases). Revised orders increased substantially, an average of $116/month (77 percent). An alternative method of keeping orders current is to express them as a percentage of the noncustodial parent's income; these orders are kept up-to-date automatically and are associated with large increases in collections.

Adolescent and Adult Perceptions of Adolescent Diet, Physical Activity, Body Size, and Obesity Prevention in Botswana

Obesity is a worldwide health problem affecting developed and developing nations. Botswana is an upper-middle income nation experiencing rapid urbanization, economic, and nutritional change. The combined prevalence of adolescent overweight and obesity has now surpassed underweight. Little is known regarding the adolescent and adult perceptions of adolescent diet, physical activity, body size, the meaning of obesity, and obesity prevention interventions. This qualitative-descriptive study uses Ecological Systems Theory to analyze and interpret data from 15 focus groups (12 adolescent and 3 parent focus groups of unrelated participants) conducted in Gaborone, Botswana. The purpose of this study is to describe the factors that influence adolescent and adult perceptions and attitudes related to adolescent diet, physical activity, body size, obesity and potential obesity interventions. Prolonged data immersion, clustering of analogous data into themes, and direct reporting of participant voices were used to provide a rich description of the shared experiences and perceptions of the study participants. Results indicate that adolescents identify healthy versus unhealthy foods, yet choose unhealthy foods based on taste preferences, social pressures, and the perceived affordability of unhealthy foods. Parents prefer a healthy diet for their adolescent children, although they acknowledge purchasing unhealthy foods for their children based on adolescent taste preferences and social pressures. Adolescent and parent participants suggest a body size analogous to normal weight is most desirable for adolescents themselves and most attractive in the opposite sex. Obese body sizes are associated with perceived laziness, isolation, and negative social stigma. Additionally westernized preferences are replacing the historical notion that a large body size is consistent with wealth, strength, and prosperity. Participants also perceive thinness to be related to illness, specifically suspected HIV infection due to the relatively high prevalence of HIV infection in Botswana. Adolescents and parents of adolescents show a willingness to participate in obesity prevention programs. Participants suggest that any school-based program be voluntary, entertaining, informative, involve parents, take into consideration peer influence, and increase healthy food offerings while not eliminating individual choice. An ecological, school-based obesity prevention program with parent involvement should be developed for this adolescent population

Nivolumab-induced fulminant diabetic ketoacidosis followed by thyroiditis

Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy

A Chemical and Enzymatic Approach to Study Site-Specific Sumoylation.

A variety of cellular pathways are regulated by protein modifications with ubiquitin-family proteins. SUMO, the Small Ubiquitin-like MOdifier, is covalently attached to lysine on target proteins via a cascade reaction catalyzed by E1, E2, and E3 enzymes. A major barrier to understanding the diverse regulatory roles of SUMO has been a lack of suitable methods to identify protein sumoylation sites. Here we developed a mass-spectrometry (MS) based approach combining chemical and enzymatic modifications to identify sumoylation sites. We applied this method to analyze the auto-sumoylation of the E1 enzyme in vitro and compared it to the GG-remnant method using Smt3-I96R as a substrate. We further examined the effect of smt3-I96R mutation in vivo and performed a proteome-wide analysis of protein sumoylation sites in Saccharomyces cerevisiae. To validate these findings, we confirmed several sumoylation sites of Aos1 and Uba2 in vivo. Together, these results demonstrate that our chemical and enzymatic method for identifying protein sumoylation sites provides a useful tool and that a combination of methods allows a detailed analysis of protein sumoylation sites