Focus: Sex and Gender Health: Theoretical Approaches to Lentiviral Mediated Neurotrophin Delivery in Potential Treatments of Parkinson’s Disease

Parkinson’s disease is a late-onset neurodegenerative disease, characterized by both motor and non-motor symptoms. Motor symptoms include postural instability, rigidity, and tremor, while non-motor symptoms include anxiety, dementia, and depression. In this integrative review, we discuss PD disease pathophysiology in detail and introduce how neurotrophic growth factor delivery via a retroviral-based system can be used as efficacious tools for targeted gene therapy.     

Role of Quantity of Additional Food to Predators as a Control in Predator–Prey Systems with Relevance to Pest Management and Biological Conservation

Necessity to understand the role of additional food as a tool in biological control programs is being increasingly felt, particularly due to its eco-friendly nature. A thorough mathematical analysis in this direction revealed the vital role of quality and quantity of the additional food in the controllability of the predator–prey systems. In this article controllability of the additional food—provided predator–prey system is studied from perspectives of pest eradication and biological conservation. Time optimal paths have been constructed to drive the state of the system to a desired terminal state by choosing quantity of the additional food as control variable. The theory developed in this article has been illustrated by solving problems related to pest eradication and biological conservation.     

Trends in antibiotic resistance in Prevotella species from patients of the University Hospital of Maxillofacial Surgery,Sofia, Bulgaria,in 2003–2009

Head-and-neck infections often involve anaerobes such as Prevotella species. Aim of the present study was to assess the evolution and the factors associated with resistance in Prevotella species to penicillin, clindamycin, metronidazole, tetracycline and β-lactams/β-lactamase inhibitors (BL/BLIs). In total, 192 Prevotella strains, isolated from patients with oral and head-and-neck infections, were evaluated. Common isolates were Prevotella intermedia and Prevotella melaninogenica within the pigmented species as well as Prevotella oris and Prevotella oralis group within the non-pigmented species. Overall resistance was 43.2% for penicillin, 10.9% for clindamycin, 0% for metronidazole. Nonsusceptibility to tetracycline was 29.1% without significant differences in resistance rates between pigmented and other species. Penicillin resistant strains were β-lactamase positive. From 2003–2004 to 2007–2009, penicillin resistance rates increased about four-fold (from 15.4% to 60.6%). Clindamycin resistance did not show evolution, whereas tetracycline nonsusceptibility decreased from 43.3% in 2003–2004 to 20.7% in 2007–2009. Except for one (0.5%) P. oralis strain with intermediate susceptibility to BL/BLIs, the other strains were susceptible to the agents. In conclusion, in Prevotella strains from patients with head-and-neck infections, the resistance rate to penicillin increased, that to clindamycin remained stable and the nonsusceptibility rate to tetracycline decreased during the period. Activity against >99% of Prevotella strains was observed with metronidazole and BL/BLIs. The penicillin resistance and tetracycline nonsusceptibility were associated with the year of study, national antibiotic consumption and possibly with previous treatment (for tetracycline). The evolution of penicillin resistance in Prevotella strains was highly dynamic.     

Causes of Aging Are Likely to be Many: Robin Holliday and Changing Molecular Approaches to Cell Aging, 1963–1988

Causal complexities involved in biological phenomena often generate ambiguous experimental results that may create epistemic niches for new approaches and interpretations. The exploration for new approaches may foment momentum of larger epistemological shifts, and thereby introduce the possibilities of adopting new technologies. This paper describes British molecular biologist Robin Holliday’s cell aging research from 1963 to the 1980s that transformed from simple hypothesis testing to working on various alternative and integrative approaches designed to deal with complex data. In the 1960s, hoping to use biochemical investigations of cells to settle a debate about whether DNA mutations or protein errors caused aging, Holliday carried out a series of experiments with fruit flies, fungi, and human fibroblast cells. The results seemed to demonstrate that cytoplasmic protein errors caused cell aging. However, other scientists obtained contradictory results and raised issues about potential flaws in Holliday’s experiments. In the 1970s, working as the director of the Genetics Division of the National Institute for Medical Research in Mill Hill, United Kingdom, Holliday relied on available talents of his associates, including computational expertise, to explore alternative hypotheses and approaches. By the early 1980s, they had worked out an epigenetic explanation and had established integrative, evolutionary models of cell aging that incorporated both DNA mutations and protein errors as critical factors. By delineating Holliday’s research path from simply testing hypotheses to integrating multiple factors involved in aging, this paper offers an account of the difficulties in targeting molecular cause in cell aging around the 1970s, whose failures nevertheless opened up an epistemic niche for integration.     

Prey Habitat Location by the Cassava Mealybug Predator Exochomus flaviventris: Olfactory Responses to Odor of Plant, Mealybug, Plant–Mealybug Complex, and Plant–Mealybug–Natural Enemy Complex

Exochomus flaviventris Mader is considered to be the most active predator of the cassava mealybug Phenacoccus manihoti Matile–Ferrero in Central Africa. The response of experienced gravid female coccinellids to the odor of cassava plant (var. Zanaga), unparasitized mealybugs, plant–mealybug complex with or without feeding prey (parasitized or not), and plant–mealybug complex with or without conspecific coccinellids was investigated in a Y-tube olfactometer. The odor of uninfested cassava plants was not more attractive than clean air. Dual-choice tests revealed that mealybug-infested plants were preferred to mealybugs alone and mealybug-damaged plants and were the major sources of volatiles that attract females coccinellids to the microhabitat of its prey. The emission of volatile chemicals did not appear to be limited to the infested parts of the plant but did occur systemically throughout the plant. The presence of conspecific coccinellid larvae or adult males did not modify the attractiveness of the mealybug-infested plants. However, when an infested plant with conspecific predator females (alone or with conspecific males) was compared to an infested plant or infested plant with conspecific males, E. flaviventris females showed a preference for the last two sources of odor. The uninfested plant with conspecific males was also preferred to the uninfested plant with conspecific females. In addition, the odor of conspecific males was preferred over that of conspecific females. Female predators preferred the plant infested with unparasitized mealybugs over the plant infested with mealybugs previously parasitized. These results showed that E. flaviventris females use herbivore-induced plant volatiles during foraging and can detect via olfaction the presence of conspecific gravid females and parasitized prey, thus assessing patch suitability from a distance.     

So Many Brands and Varieties to Choose from: Does This Compromise the Control of Food Intake in Humans?

The recent rise in obesity is widely attributed to changes in the dietary environment (e.g., increased availability of energy-dense foods and larger portion sizes). However, a critical feature of our “obesogenic environment” may have been overlooked - the dramatic increase in “dietary variability” (the tendency for specific mass-produced foods to be available in numerous varieties that differ in energy content). In this study we tested the hypothesis that dietary variability compromises the control of food intake in humans. Specifically, we examined the effects of dietary variability in pepperoni pizza on two key outcome variables; i) compensation for calories in pepperoni pizza and ii) expectations about the satiating properties of pepperoni pizza (expected satiation). We reasoned that dietary variability might generate uncertainty about the postingestive effects of a food. An internet-based questionnaire was completed by 199 adults. This revealed substantial variation in exposure to different varieties of pepperoni pizza. In a follow-up study (n= 66; 65% female), high pizza variability was associated with i) poorer compensation for calories in pepperoni pizza and ii) lower expected satiation for pepperoni pizza. Furthermore, the effect of uncertainty on caloric compensation was moderated by individual differences in decision making (loss aversion). For the first time, these findings highlight a process by which dietary variability may compromise food-intake control in humans. This is important because it exposes a new feature of Western diets (processed foods in particular) that might contribute to overeating and obesity.     

Functional polymorphisms in the interleukin-12 gene contribute to cancer risk: Evidence from a meta-analysis of 18 case–control studies

Background

Emerging evidence from preclinical and clinical studies has shown that interleukin-12 (IL-12) has some effectiveness against endogenously arising carcinogenesis. Several potentially functional polymorphisms of IL-12 gene have been implicated in cancer risk, but individually published studies showed inconclusive results. The aim of this study was to investigate the association between IL-12 polymorphisms and cancer risk.

Methods

The MEDLINE, EMBASE, Web of science and CBM databases were searched for all articles published up to June 10, 2012 that addressed IL-12 polymorphisms and cancer risk. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 softwares.

Results

Eighteen studies were included with a total of 6463 cancer cases and 7412 healthy controls. We found that the 3'UTR A > C (rs3212227) polymorphism of IL-12B gene was associated with significantly increased overall risk of cancers using random effects model (C vs A: odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.02-1.27; AC + CC vs AA: OR = 1.20, 95%CI: 1.01-1.43). However, the 3'UTR G > A (rs568408), IVS2 T > A (rs582054) and 5'UTR T > G (rs2243115) polymorphisms of IL-12A gene did not appear to have an influence on cancer susceptibility. Further subgroup analyses showed that the 3'UTR A > C (rs3212227) polymorphism was associated with increased cancer risks in the subgroups of Asians, cervical and nasopharyngeal cancers.

Conclusions

Results from the current meta-analysis indicates that the 3'UTR A > C (rs3212227) polymorphism of IL-12B gene might be a potential biomarker for cancer risk among Asians, especially for cervical and nasopharyngeal cancers.     

Food habits of sika deer in the Shiranuka Hills,eastern Hokkaido: a northern example from the north–south variations in food habits in sika deer

Seasonal changes in the composition of the diet of the sika deer population in the Shiranuka Hills, eastern Hokkaido, in 1998 were determined by fecal analyses. The deer were dependent on Sasa nipponica, a dwarf bamboo, throughout the year, particularly in winter when it accounted for as much as 77.7% of the diet. It accounted for 33.1% and 45.6% in spring and summer, respectively, and this decreased to 12.2% in autumn. Besides S. nipponica, all the graminoid categories accounted for large amounts (66–96.7%), while dicotyledonous plants accounted for little (3–8%) except in autumn when they accounted for 31%. The strong dependence of the Shiranuka population on graminoids was different from other Hokkaido deer populations, for example the population from Ashoro/Onbetsu and the extremely high density population on Nakanoshima Island. In spite of these differences, food for all Hokkaido sika deer was poor in winter. Along the north–south geographical cline in the food composition of sika deer along the Japanese archipelago, the Shiranuka population was positioned as a grazer type, in contrast to the southern populations. However, it is important to note that variations are great among local populations in Hokkaido.     

Conference Report from the 6th Trends in Medical Mycology Meeting,Copenhagen, 11–14 October 2013: Facing the Global Threat of Fungal Disease

Trends in Medical Mycology (TIMM) has become the essential leading meeting in the field of fungal infections, attracting clinicians and scientists from all over the world to attend state-of-the-art lectures, workshops and meet-the-expert sessions. TIMM-6, held in Copenhagen, Denmark, from 11 to 14 October 2013, was no exception, featuring presentations highlighting the potentially serious global threat presented by emerging fungal diseases and the continuing challenge of diagnosing and managing affected patients.     

Molecular Inferences Suggest Multiple Host Shifts of Rabies Viruses from Bats to Mesocarnivores in Arizona during 2001–2009

In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly during 2001–2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T₂₄₂ in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain. Roles of the amino acid changes, detected in our study, require additional investigations, using reverse genetics and other approaches.     

Evolution of New Disease Specificity at a Simple Resistance Locus in a Crop–Weed Complex: Reconstitution of the Lr21 Gene in Wheat

The wheat leaf-rust resistance gene Lr21 was first identified in an Iranian accession of goatgrass, Aegilops tauschii Coss., the D-genome donor of hexaploid bread wheat, and was introgressed into modern wheat cultivars by breeding. To elucidate the origin of the gene, we analyzed sequences of Lr21 and lr21 alleles from 24 wheat cultivars and 25 accessions of Ae. tauschii collected along the Caspian Sea in Iran and Azerbaijan. Three basic nonfunctional lr21 haplotypes, H1, H2, and H3, were identified. Lr21 was found to be a chimera of H1 and H2, which were found only in wheat. We attempted to reconstitute a functional Lr21 allele by crossing the cultivars Fielder (H1) and Wichita (H2). Rust inoculation of 5876 F₂ progeny revealed a single resistant plant that proved to carry the H1H2 haplotype, a result attributed to intragenic recombination. These findings reflect how plants balance the penalty and the necessity of a resistance gene and suggest that plants can reuse “dead” alleles to generate new disease-resistance specificity, leading to a “death–recycle” model of plant-resistance gene evolution at simple loci. We suggest that selection pressure in crop–weed complexes contributes to this process.PLANTS possess large numbers of resistance genes (R gene) as a part of an elaborate plant defense system. In different plants, an R-gene locus may consist of a single-copy (simple) or of multiple copies of R genes (complex) in clusters as a result of gene duplication events. This duplication is considered as the birth of an R gene. R genes are necessary for plants to respond to pathogen attacks and to survive when pathogens are in the environment. Mutations, gene conversion, and recombination were found to be the means to create new specificities for various pathogens (for review, Leister 2004). However, an R gene could bring a penalty when the pathogen is absent (Stahl et al. 1999). In such a case, plants have better fitness when they get rid of the R-gene function. In nature, the presence of different pathogens maintains the diversity of R-gene specificities. So far, there is no report on the fates of nonfunctional R genes.In native agricultural ecosystems, wild plants often grow as weeds intermixed with or adjacent to their crop relatives. Extensive gene flow occurs between wild and domesticated forms, spawning numerous crop landraces adapted to diverse environments and occasionally new species. Common (hexaploid or bread) wheat (Triticum aestivum L., 2n = 6x = 42, genome formula AABBDD) arose from such a process by hybridization of domesticated tetraploid wheat (T. turgidum L., 2n = 4x = 28, AABB) with goatgrass (Aegilops tauschii Coss., 2n = 2x = 14, DD) growing as a weed in farmers'' fields along the Caspian Sea in Iran ca. 8000 years ago (Kihara 1944; McFadden and Sears 1946; Nesbitt and Samuel 1998).Because of the pivotal importance of Ae. tauschii in wheat evolution and crop improvement, Kihara et al. (1965) gathered extensive collections from Iran, Afghanistan, and adjacent regions. They suggested that Caspian Iran was the center of the genetic diversity of Ae. tauschii, a proposition later confirmed by molecular-marker analysis (Lubbers et al. 1991), as well as of resistance to leaf rust. Nine named and 12 new leaf-rust resistance genes have been documented in Ae. tauschii, and many more remain to be identified (Gill et al. 2008). Leaf rust, a scourge of wheat since before Roman times, is caused by the fungus Puccinia triticina (Eriks). It attacks mainly the leaf blade, producing small, elliptical, orange-red pustules on the upper surface, causing premature defoliation that results in as much as a 40% yield loss (McIntosh et al. 1995).One Ae. tauschii accession, TA1599, collected in Caspian Iran, carries a gene named Lr21 that confers resistance to all known P. triticina races. Lr21, transferred to wheat in the 1970s (Rowland and Kerber 1974; McIntosh et al. 1995), was recently cloned (Huang et al. 2003) and shown to be a simple (single-copy) locus encoding a nucleotide-binding site–leucine-rich repeats (NBS–LRR) protein of 1080 amino acids. Here we report how a simple locus such as Lr21 evolved novel resistance specificities in a unique crop–weed system and how fragments of nonfunctional alleles could be reused in this process.     

Paths to last in mixed crop–livestock farming: lessons from an assessment of farm trajectories of change

Mixed crop–livestock systems, combining livestock and cash crops at farm level, are considered to be suitable for sustainable intensification of agriculture. Ensuring the survival of mixed crop–livestock systems is a challenge for European agriculture: the number of European mixed crop–livestock farms has been decreasing since 1970. Analysis of farming system dynamics may elucidate past changes and the forces driving this decline. The objectives of this study were (i) to identify the diversity of paths that allowed the survival of mixed crop–livestock farming and (ii) to elucidate the driving forces behind such survival. We analysed the variety of farm trajectories from 1950 to 2005. We studied the entire farm population of a case study site, located in the ‘Coteaux de Gascogne’ region. In this less favoured area of south-western France, farmers have limited specialisation. Currently, half of the farms use mixed crop–livestock systems. The data set of 20 variables for 50 farms on the basis of six 10-year time steps was collected through retrospective surveys. We used a two-step analysis including (i) a visual assessment of the whole population of individual farm trajectories and (ii) a computer-based typology of farm trajectories on the basis of a series of multivariate analyses followed by automatic clustering. The European Common Agricultural Policy, market globalisation and decreasing workforce availability were identified as drivers of change that favoured the specialisation process. Nevertheless, farmers’ choices and values have opposed against these driving forces, ensuring the survival of some mixed crop–livestock farming systems. The trajectories were clustered into five types, four of which were compatible with mixed crop–livestock systems. The first type was the maximisation of autonomy by combining crops and livestock. The second type was diversification of production to exploit economies of scope and protect the farm against market fluctuations. The other two types involved enlargement and progressive adaptation of the farm to the familial workforce. The survival of mixed crop–livestock systems in these two types is largely dependent on workforce availability. Only one type of trajectory, on the basis of enlargement and economies of scale, did not lead to mixed crop–livestock systems. In view of the current evolution of the driving forces, maximising autonomy and diversification appear to be suitable paths to deal with current challenges and maintain mixed crop–livestock systems in Europe.