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991.
The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.  相似文献   
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993.

Introduction

The prevention and management of neurocognitive disorders (NCD) among older adults can be improved by early identification of risk factors such as walking speed. The objective of the study is to assess the association between gait speed and NCD onset in a population of Peruvian older adults.

Material and methods

Cohort conducted in older adults who attended the geriatrics service of Naval Medical Center (Callao, Peru). During the baseline assessment, participants’ gait speed was recorded. Subsequently, participants were followed-up annually for 5 years, with a mean of 21 months. NCD onset was defined as the occurrence of a score ≤ 24 points on the Mini Mental State Examination (screening test) during follow-up. The hazard ratios (HR) and their 95% confidence intervals (95% CI) were calculated using Cox regression.

Results

The study included 657 participants, with a mean age of 73.4 ± 9.2 (SD) years, of whom 47.0% were male, 47.8% had a gait speed < 0.8 m/s, and 20.1% developed NCD during the follow up. It was found that older adults who had gait speed < 0.8 m/s at baseline were more likely to develop NCD than those who had a gait speed ≥ 0.8 m/s (adjusted HR = 1.41, 95% CI = 1.34-1.47).

Conclusion

A longitudinal association was found between decreased gait speed and NCD onset, suggesting that gait speed could be useful to identify patients at risk of NCD onset.  相似文献   
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Coral Reefs - Both natural and anthropogenic factors are changing coral-reef structure and function worldwide. Long-term monitoring has revealed declines in the local composition and species...  相似文献   
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998.
Introgression can introduce novel genetic variation at a faster rate than mutation alone and result in adaptive introgression when adaptive alleles are maintained in the recipient genome over time by natural selection. A previous study from our group demonstrated adaptive introgression from Populus balsamifera into P. trichocarpa in a target genomic region. Here we expand our local ancestry analysis to the whole genome of both parents to provide a comprehensive view of introgression patterns and to identify additional candidate regions for adaptive introgression genomewide. Populus trichocarpa is a large, fast‐growing tree of mild coastal regions of the Pacific Northwest, whereas P. balsamifera is a smaller stature tree of continental and boreal regions with intense winter cold. The species hybridize where they are parapatric. We detected asymmetric patterns of introgression across the whole genome of these two poplar species adapted to contrasting environments, with stronger introgression from P. balsamifera to P. trichocarpa than vice versa. Admixed P. trichocarpa individuals contained more genomic regions with unusually high levels of introgression (19 regions) and also the largest introgressed genome fragment (1.02 Mb) compared with admixed P. balsamifera (nine regions). Our analysis also revealed numerous candidate regions for adaptive introgression with strong signals of selection, notably related to disease resistance, and enriched for genes that may play crucial roles in survival and adaptation. Furthermore, we detected a potential overrepresentation of subtelomeric regions in P. balsamifera introgressed into P. trichocarpa and possible protection of sex‐determining regions from interspecific gene flow.  相似文献   
999.
Deciphering the mechanism of functioning of DNA as the carrier of genetic information requires identifying inherent factors determining its structure and function. Following this path, our previous DFT studies attributed the origin of unique conformational characteristics of right-handed Watson-Crick duplexes (WCDs) to the conformational profile of deoxydinucleoside monophosphates (dDMPs) serving as the minimal repeating units of DNA strand. According to those findings, the directionality of the sugar-phosphate chain and the characteristic ranges of dihedral angles of energy minima combined with the geometric differences between purines and pyrimidines determine the dependence on base sequence of the three-dimensional (3D) structure of WCDs. This work extends our computational study to complementary deoxydinucleotide-monophosphates (cdDMPs) of non-standard conformation, including those of Z-family, Hoogsteen duplexes, parallel-stranded structures, and duplexes with mispaired bases. For most of these systems, except Z-conformation, computations closely reproduce experimental data within the tolerance of characteristic limits of dihedral parameters for each conformation family. Computation of cdDMPs with Z-conformation reveals that their experimental structures do not correspond to the internal energy minimum. This finding establishes the leading role of external factors in formation of the Z-conformation. Energy minima of cdDMPs of non-Watson-Crick duplexes demonstrate different sequence-dependence features than those known for WCDs. The obtained results provide evidence that the biologically important regularities of 3D structure distinguish WCDs from duplexes having non-Watson-Crick nucleotide pairing.  相似文献   
1000.
Annual row crops dominate agriculture around the world and have considerable negative environmental impacts, including significant greenhouse gas emissions. Transformative land‐use solutions are necessary to mitigate climate change and restore critical ecosystem services. Alley cropping (AC)—the integration of trees with crops—is an agroforestry practice that has been studied as a transformative, multifunctional land‐use solution. In the temperate zone, AC has strong potential for climate change mitigation through direct emissions reductions and increases in land‐use efficiency via overyielding compared to trees and crops grown separately. In addition, AC provides climate change adaptation potential and ecological benefits by buffering alley crops to weather extremes, diversifying income to hedge financial risk, increasing biodiversity, reducing soil erosion, and improving nutrient‐ and water‐use efficiency. The scope of temperate AC research and application has been largely limited to simple systems that combine one timber tree species with an annual grain. We propose two frontiers in temperate AC that expand this scope and could transform its climate‐related benefits: (i) diversification via woody polyculture and (ii) expanded use of tree crops for food and fodder. While AC is ready now for implementation on marginal lands, we discuss key considerations that could enhance the scalability of the two proposed frontiers and catalyze widespread adoption.  相似文献   
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