Evolutionary Biology - Among closely related species, larger mammals tend to have a longer face and proportionally smaller braincase. This putative ‘rule’ in mammalian macroevolution... 相似文献
Mutations in the catalytic Roc‐COR and kinase domains of leucine‐rich repeat kinase 2 (LRRK2) are a common cause of familial Parkinson's disease (PD). LRRK2 mutations cause PD with age‐related penetrance and clinical features identical to late‐onset sporadic PD. Biochemical studies support an increase in LRRK2 kinase activity and a decrease in GTPase activity for kinase domain and Roc‐COR mutations, respectively. Strong evidence exists that LRRK2 toxicity is kinase dependent leading to extensive efforts to identify selective and brain‐permeable LRRK2 kinase inhibitors for clinical development. Cell and animal models of PD indicate that LRRK2 mutations affect vesicular trafficking, autophagy, protein synthesis, and cytoskeletal function. Although some of these biological functions are affected consistently by most disease‐linked mutations, others are not and it remains currently unclear how mutations that produce variable effects on LRRK2 biochemistry and function all commonly result in the degeneration and death of dopamine neurons. LRRK2 is typically present in Lewy bodies and its toxicity in mammalian models appears to be dependent on the presence of α‐synuclein, which is elevated in human iPS‐derived dopamine neurons from patients harboring LRRK2 mutations. Here, we summarize biochemical and functional studies of LRRK2 and its mutations and focus on aberrant vesicular trafficking and protein synthesis as two leading mechanisms underlying LRRK2‐linked disease.
The furs of mammals have varied and complex functions. Other than for thermoregulation, fur is involved in physical protection, sensory input, waterproofing and colouration, the latter being important for crypsis or camouflage. Some of these diverse functions potentially conflict. We have investigated how variation in cryptic colouration and thermal features may interact in the coats of mammals and influence potential heat inflows from solar radiation, much of which is outside the visible spectral range. The coats of the polar bear (Ursus maritimus) and the marsupial koala (Phascolarctus cinereus) have insulative similarities but, while they feature cryptic colouration, they are of contrasting colour, i.e. whitish and dark grey. The reflectance of solar radiation by coats was measured across the full solar spectrum using a spectroradiometer. The modulation of incident solar radiation and resultant heat flows in these coats were determined at a range of wind speeds by mounting them on a heat flux transducer/temperature-controlled plate apparatus in a wind tunnel. A lamp with a spectral distribution of radiation similar to the solar spectrum was used as a proxy for the sun. Crypsis by colour matching was apparent within the visible spectrum for the two species, U. maritimus being matched against snow and P. cinereus against Eucalyptus forest foliage. While reflectances across the full solar spectrum differed markedly, that of U. maritimus being 66 % as opposed to 10 % for P. cinereus, the heat influxes from solar radiation reaching the skin were similar. For both coats at low wind speed (1 m s?1), 19 % of incident solar radiation impacted as heat at the skin surface; at higher wind speed (10 m s?1) this decreased to approximately 10 %. Ursus maritimus and P. cinereus have high and comparable levels of fur insulation and although the patterns of reflectance and depths of penetrance of solar radiation differ for the coats, the considerable insulation limited the radiant heat reaching the skin. These data suggest that generally, if mammal coats have high insulation then heat flow from solar radiation into an animal is much restricted and the impact of coat colour is negligible. However, comparisons with published data from other species suggest that as fur insulation decreases, colour increasingly influences the heat inflow associated with solar radiation. 相似文献
Since tools of modern biotechnology have become available, the most commonly applied and often discussed genetically modified organisms are genetically modified crop plants, although genetic engineering is also being used successfully in organisms other than plants, including bacteria, fungi, insects, and viruses. Many of these organisms, as with crop plants, are being engineered for applications in agriculture, to control plant insect pests or diseases. This paper reviews the genetically modified non-plant organisms that have been the subject of permit approvals for environmental release by the United States Department of Agriculture/Animal and Plant Health Inspection Service since the US began regulating genetically modified organisms. This is an indication of the breadth and progress of research in the area of non-plant genetically modified organisms. This review includes three examples of promising research on non-plant genetically modified organisms for application in agriculture: (1) insects for insect pest control using improved vector systems; (2) fungal pathogens of insects to control insect pests; and (3) virus for use as transient-expression vectors for disease control in plants. 相似文献
Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD.
Methods and Findings
In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds-ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control.
Conclusions
An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention.
Several ethical considerations emerge when conducting research with memory-impaired individuals, including the individuals' ability to comprehend and accurately respond to survey questions. However, little empirical research exists on how to format surveys to decrease cognitive demands, thereby allowing researchers to more accurately survey this population. The current study presents data from structured interviews with 125 community-residing, memory-impaired older adults about their illness experience. The interview contained 14 scales varying in subjectivity, directionality, and response choice content. While objectivity did not affect participants' ability to use the full range of responses, participants with greater cognitive impairment tended to use simpler, dichotomous response categories, especially when questions had bidirectional response choices. Results suggest that memory-impaired individuals can participate in survey research, that such surveys should contain unidirectional frequency/amount items when possible, and that not all memory-impaired individuals will have difficulty completing surveys. 相似文献