This is a summary of the 1st Academic Model Providing Access to Healthcare (AMPATH) Oncology Institute research grant writing workshop organized in collaboration with the Kenya Medical Research Institute (KEMRI) and held in Kisumu, Kenya from January 16th to 18th, 2013. The goal of this meeting was to mentor future Kenyan scientists and prioritize research topics that would lead to improved cancer care and survival for the citizens of Kenya.
BACKGROUND: Most motile cilia and flagella have nine outer doublet and two central pair (CP) microtubules. Outer doublet microtubules are continuous with the triplet microtubules of the basal body, are templated by the basal body microtubules, and grow by addition of new subunits to their distal ("plus") ends. In contrast, CP microtubules are not continuous with basal body microtubules, raising the question of how these microtubules are assembled and how their polarity is established.
METHODS: CP assembly in Chlamydomonas reinhardtii was analyzed by electron microscopy and wide-field and super-resolution immunofluorescence microscopy. To analyze CP assembly independently from flagellar assembly, the CP-deficient katanin mutants pf15 or pf19 were mated to wild-type cells. HA-tagged tubulin and the CP-specific protein hydin were used as markers to analyze de novo CP assembly inside the formerly mutant flagella.
RESULTS: In regenerating flagella, the CP and its projections assemble near the transition zone soon after the onset of outer doublet elongation. During de novo CP assembly in full-length flagella, the nascent CP was first apparent in a subdistal region of the flagellum. The developing CP replaces a fibrous core that fills the axonemal lumen of CP-deficient flagella. The fibrous core contains proteins normally associated with the C1 CP microtubule and proteins involved in intraflagellar transport (IFT). In flagella of the radial spoke-deficient mutant pf14, two pairs of CPs are frequently present with identical correct polarities.
CONCLUSIONS: The temporal separation of flagellar and CP assembly in dikaryons formed by mating CP-deficient gametes to wild-type gametes revealed that the formation of the CP does not require proximity to the basal body or transition zone, or to the flagellar tip. The observations on pf14 provide further support that the CP self-assembles without a template and eliminate the possibility that CP polarity is established by interaction with axonemal radial spokes. Polarity of the developing CP may be determined by the proximal-to-distal gradient of precursor molecules. IFT proteins accumulate in flagella of CP mutants; the abnormal distribution of IFT proteins may explain why these flagella are often shorter than normal.
In malaria holoendemic settings, decreased parasitemia and clinical disease is associated with age and cumulative exposure. The relative contribution of acquired immunity against various stages of the parasite life cycle is not well understood. In particular, it is not known whether changes in infection dynamics can be best explained by decreasing rates of infection, or by decreased growth rates of parasites in blood. Here, we analyze the dynamics of Plasmodium falciparum infection after treatment in a cohort of 197 healthy study participants of different ages. We use both polymerase chain reaction (PCR) and microscopy detection of parasitemia in order to understand parasite growth rates and infection rates over time. The more sensitive PCR assay detects parasites earlier than microscopy, and demonstrates a higher overall prevalence of infection than microscopy alone. The delay between PCR and microscopy detection is significantly longer in adults compared with children, consistent with slower parasite growth with age. We estimated the parasite multiplication rate from delay to PCR and microscopy detections of parasitemia. We find that both the delay between PCR and microscopy infection as well as the differing reinfection dynamics in different age groups are best explained by a slowing of parasite growth with age.
Challenges in sodium intake reduction and meal consumption patterns among participants with metabolic syndrome in a dietary trial
BACKGROUND: Dietary guidelines suggest limiting daily sodium intake to
METHODS: Two hundred forty participants with metabolic syndrome enrolled in a dietary intervention trial to lose weight and improve dietary quality. Three 24-hour dietary recalls were collected at each visit which provided meal patterns and nutrient data, including sodium intake. A secondary data analysis was conducted to examine sodium consumption patterns at baseline and at one-year study visits. Sodium consumption patterns over time were examined using linear mixed models.
RESULTS: The percentage of meals reported eaten in the home at both baseline and one-year follow-up was approximately 69%. Follow-up for the one-year dietary intervention revealed that the participants who consumed sodium greater than 2,300 mg/d declined from 75% (at baseline) to 59%, and those that consumed higher than 1,500 mg/d declined from 96% (at baseline) to 85%. Average sodium intake decreased from 2,994 mg at baseline to 2,558 mg at one-year (P < 0.001), and the sodium potassium ratio also decreased from 1.211 to 1.047 (P < 0.001). Sodium intake per meal varied significantly by meal type, location, and weekday, with higher intake at dinner, in restaurants, and on weekends. At-home lunch and dinner sodium intake decreased (P < 0.05), while dinner sodium intake at restaurant/fast food chains increased from baseline to one-year (P < 0.05).
CONCLUSION: Sodium intake for the majority of participants exceeded the recommended dietary guidelines. Findings support actions that encourage low-sodium food preparation at home and encourage public health policies that decrease sodium in restaurants and prepared foods.
This Issue Brief details important facts about intimate partner violence within the Deaf community and provides specific recommendations for providers about best practices for working with Deaf clients.