Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging

The amyloid cascade hypothesis provides an economical mechanistic explanation for Alzheimer's disease (AD) dementia and correlated neuropathology. However, some nonagenarian individuals (high pathology controls, HPC) remain cognitively intact while enduring high amyloid plaque loads for decades. If amyloid accumulation is the prime instigator of neurotoxicity and dementia, specific protective mechanisms must enable these HPC to evade cognitive decline. We evaluated the neuropathological and biochemical differences existing between non-demented (ND)-HPC and an age-matched cohort with AD dementia. The ND-HPC selected for our study were clinically assessed as ND and possessed high amyloid plaque burdens. ELISA and Western blot analyses were used to quantify a group of proteins related to APP/Aβ/tau metabolism and other neurotrophic and inflammation-related molecules that have been found to be altered in neurodegenerative disorders and are pivotal to brain homeostasis and mental health. The molecules assumed to be critical in AD dementia, such as soluble or insoluble Aβ40, Aβ42 and tau were quantified by ELISA. Interestingly, only Aβ42 demonstrated a significant increase in ND-HPC when compared to the AD group. The vascular amyloid load which was not used in the selection of cases, was on the average almost 2-fold greater in AD than the ND-HPC, suggesting that a higher degree of microvascular dysfunction and perfusion compromise was present in the demented cohort. Neurofibrillary tangles were less frequent in the frontal cortices of ND-HPC. Biochemical findings included elevated vascular endothelial growth factor, apolipoprotein E and the neuroprotective factor S100B in ND-HPC, while anti-angiogenic pigment epithelium derived factor levels were lower. The lack of clear Aβ-related pathological/biochemical demarcation between AD and ND-HPC suggests that in addition to amyloid plaques other factors, such as neurofibrillary tangle density and vascular integrity, must play important roles in cognitive failure.     

Spatial but not temporal co-divergence of a virus and its mammalian host

Co-divergence between host and parasites suggests that evolutionary processes act across similar spatial and temporal scales. Although there has been considerable work on the extent and correlates of co-divergence of RNA viruses and their mammalian hosts, relatively little is known about the extent to which virus evolution is determined by the phylogeographic history of host species. To test hypotheses related to co-divergence across a variety of spatial and temporal scales, we explored phylogenetic signatures in Andes virus (ANDV) sampled from Chile and its host rodent, Oligoryzomys longicaudatus. ANDV showed strong spatial subdivision, a phylogeographic pattern also recovered in the host using both spatial and genealogical approaches, and despite incomplete lineage sorting. Lineage structure in the virus seemed to be a response to current population dynamics in the host at the spatial scale of ecoregions. However, finer scale analyses revealed contrasting patterns of genetic structure across a latitudinal gradient. As predicted by their higher substitution rates, ANDV showed greater genealogical resolution than the rodent, with topological congruence influenced by the degree of lineage sorting within the host. However, despite these major differences in evolutionary dynamics, the geographic structure of host and virus converged across large spatial scales.     

Overcoming seed dormancy in ex situ plant germplasm conservation programmes; an example in the endemic Argyranthemum (Asteraceae: Anthemideae) species from the Canary Islands

Germplasm of 21 diverse Argyranthemum taxa was collected from contrasting ecological zones in the Canary Islands. Seed dormancy was considerable in the majority of taxa. Extensive investigations, based on a germination test procedure algorithm for Asteraceae, with achenes from ray and disc florets of five contrasting taxa identified a procedure to promote full (85%) germination of the seeds from both ray and disc florets of all five taxa; viz, excision of the seeds from the achenes, followed by testing at 15°C with 2.6×10^-3 m GA₃ co-applied. Subsequent tests showed that this regime was effective in promoting full germination in seeds from both ray and disc florets of the remaining 16 taxa. The results are discussed in the context of ex situ plant germplasm conservation.     

Selection for higher yields and heat resistance in Pima cotton has caused genetically determined changes in stomatal conductances

Gas exchange analysis was used to characterize photosynthetic and stomatal responses to key environmental stimuli in five commercial lines of Pima cotton ( Gossypium barbadense L.) which represent a gradient of selection for higher yields and heat resistance, and a primitive, uncultivated G. barbadense. At constant light and vapor pressure deficit, stomatal conductance increased linearly with air temperature in the 23 to 36$C range in all five commercial lines, and conductance at each temperature increased as a function of selection. In contrast, photosynthetic rates had a low sensitivity to temperature in the 23 to 36$C range, particularly in the advanced lines. In a segregating F₂ population from a cross between the advanced line, Pima S-6, and the primitive cotton, B368, the slope of the stomatal response to temperature in each F₂ plant was positively correlated with the stomatal conductance measured at 40$C. An analysis of the frequency distribution of stomatal conductance in F₁ and F₂ progeny of the cross showed that the differences in stomatal conductance between lines were genetically determined. These data indicate that selection for higher yield and heat resistance in Pima cotton has caused genetically determined changes in stomatal properties. Characterization of the relationship between the altered stomatal properties and the attained increases in heat resistance and yields could make it possible to use these physiological traits as selection criteria in future breeding programs.     

Oviposition and development of Drosophila modified by magnetic fields

Drosophila flies placed in a habitat with two lateral boxes demonstrated sensitivity to magnetic fields: Oviposition decreased by exposure to pulsated extremely low frequency (ELF) (100)Hz, 1.76 miliTesla (mT) and sinusosidal fields (50 Hz, 1 mT), while there was no initial effect of exposure to a static magnetic field (4.5 mT). Drosophila eggs treated for 48 h with the above described fields showed that (1) mortality of eggs was lower in controls than in eggs exposed to all tested magnetic fields; (2) mortality of larvae increased when a permanent magnet was used; (3) mortality of pupae was highest when a permanent magnet was used; and (4) general adult viability was highest in controls (67%) and diminished progressively when eggs were exposed to pulsated (55%), sinusoidal (45%), and static (35%) magnetic fields.     

Dung Beetle and Terrestrial Mammal Diversity in Forests, Indigenous Agroforestry Systems and Plantain Monocultures in Talamanca, Costa Rica

In order to explore the importance of indigenous agroforestry systems for biodiversity conservation, we compared the abundance, species richness and diversity of dung beetles and terrestrial mammals across a gradient of different land use types from agricultural monocultures (plantains) to agroforestry systems (cocoa and banana) and forests in the BriBri and Cabécar indigenous reserves in Talamanca, Costa Rica. A total of 132,460 dung beetles of 52 species and 913 tracks of 27 terrestrial mammal species were registered. Dung beetle species richness and diversity were greatest in the forests, intermediate in the agroforestry systems and lowest in the plantain monocultures, while dung beetle abundance was greatest in the plantain monocultures. The number of mammal tracks per plot was significantly higher in forests than in plantain monocultures, whereas mammal species richness was higher in forests than in either cocoa agroforestry systems or plantain monocultures. Species composition of both terrestrial mammals and dung beetles also varied across the different land use types. Our study indicates that indigenous cocoa and banana agroforestry systems maintain an intermediate level of biodiversity (which is less than that of the original forest but significantly greater than that of plantain monocultures) and provide suitable habitat for a number of forest-dependent species. Although the agroforestry systems appear to serve as favorable habitats for many terrestrial mammal species, their potential positive contribution to mammal conservation is being offset by heavy hunting pressure in the reserves. As in other agricultural landscapes, the conservation of biodiversity in Talamanca will depend not only on maintaining the existing forest patches and reducing the conversion of traditional agroforestry systems to monocultures, but also on reducing hunting pressure.     

Comparable Long-Term Efficacy of Lopinavir/Ritonavir and Similar Drug-Resistance Profiles in Different HIV-1 Subtypes

Background

Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment.

Methods

Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS.

Results

607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16).

Conclusions

Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment.     

Risk of symptomatic dengue for foreign visitors to the 2014 FIFA World Cup in Brazil

Brazil will host the FIFA World Cup™, the biggest single-event competition in the world, from June 12-July 13 2014 in 12 cities. This event will draw an estimated 600,000 international visitors. Brazil is endemic for dengue. Hence, attendees of the 2014 event are theoretically at risk for dengue. We calculated the risk of dengue acquisition to non-immune international travellers to Brazil, depending on the football match schedules, considering locations and dates of such matches for June and July 2014. We estimated the average per-capita risk and expected number of dengue cases for each host-city and each game schedule chosen based on reported dengue cases to the Brazilian Ministry of Health for the period between 2010-2013. On the average, the expected number of cases among the 600,000 foreigner tourists during the World Cup is 33, varying from 3-59. Such risk estimates will not only benefit individual travellers for adequate pre-travel preparations, but also provide valuable information for public health professionals and policy makers worldwide. Furthermore, estimates of dengue cases in international travellers during the World Cup can help to anticipate the theoretical risk for exportation of dengue into currently non-infected areas.