Smad2条件基因剔除载体的构建及LoxP位点有效性鉴定

Smads家族是最新发现的TGF－β信号转导途径中一个重要的新基因家族,SMAD2属于受体激活的SMADs。Smad2在某些肿瘤中发生突变,是一种可能的肿瘤抑制基因。Smad2基因完全剔除小鼠在胚胎期E6．5天死亡,为了研究Smad2在成体各组织器官及肿瘤发生中的可能作用,构建了Smad2条件基因剔除载体,将LoxP置于Smad2基因组序列C末端功能域两侧,并在组成型表达Cre重组酶的大肠杆菌中检测了LoxP位点的功能,该载体的构建为进行Smad2组织特异性基因剔除研究了奠定了基础。     

Partial migration in inexperienced pied avocets Recurvirostra avosetta: distribution pattern and correlates

Birds exhibit a range of wintering behaviour from strictly migrant to strictly resident species. In partially migrating ones, some birds overwinter within their breeding region (resident birds) while others, although breeding in the same area, winter far away (migrant birds). Accordingly, choosing a wintering region is a key stage in the annual life cycle of birds, notably for inexperienced first‐year individuals. The present study aimed to investigate this issue, and more specifically to study the distribution pattern during winter and factors influencing the wintering behaviour of first‐year pied avocets Recurvirostra avosetta. Based on a 10‐yr ringing study carried out on five of the major French breeding colonies distributed along the Atlantic coast, we showed the coexistence of different wintering tactics. The resident tactic was predominant (approximately 86% of the 575 birds re‐sighted), while the other birds adopted migration. Among resident individuals, two different tactics occurred: 43% of birds overwintered within their natal colony, whereas the others wintered in another site located at relatively close proximity along the French Atlantic coast. Hatching date was a consistent predictor of all wintering tactics. More specifically, the probability of migrating was the highest for early‐hatched birds, and for resident ones, the probability of wintering within their natal colony rather than in another French site was the highest for both median‐ and late‐hatched individuals. In addition, a colony effect was demonstrated for resident birds. Several biological interpretations, including social system, variations in both individual body condition and habitat quality, were put forward to explain these correlates.     

Juvenile bimodal length distribution and sea-run migration of the lower modal group in the Pacific Ocean form of three-spined stickleback

Juvenile three-spined stickleback Gasterosteus aculeatus in their nursery pond had a bimodal length distribution after October in their first year of life. A sea-run migration of all individuals belonging to the lower modal group was observed, with a peak in early November. These data suggest that partial migration based on the early status of individual juveniles occurs in the Pacific Ocean form of three-spined stickleback.     

Post-natal heart adaptation in a knock-in mouse model of calsequestrin 2-linked recessive catecholaminergic polymorphic ventricular tachycardia

Cardiac calsequestrin (CASQ2) contributes to intracellular Ca²⁺ homeostasis by virtue of its low-affinity/high-capacity Ca²⁺ binding properties, maintains sarcoplasmic reticulum (SR) architecture and regulates excitation–contraction coupling, especially or exclusively upon β-adrenergic stimulation. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease associated with cardiac arrest in children or young adults. Recessive CPVT variants are due to mutations in the CASQ2 gene. Molecular and ultra-structural properties were studied in hearts of CASQ2^R33Q/R33Q and of CASQ2^−/− mice from post-natal day 2 to week 8. The drastic reduction of CASQ2-R33Q is an early developmental event and is accompanied by down-regulation of triadin and junctin, and morphological changes of jSR and of SR-transverse-tubule junctions. Although endoplasmic reticulum stress is activated, no signs of either apoptosis or autophagy are detected. The other model of recessive CPVT, the CASQ2^−/− mouse, does not display the same adaptive pattern. Expression of CASQ2-R33Q influences molecular and ultra-structural heart development; post-natal, adaptive changes appear capable of ensuring until adulthood a new pathophysiological equilibrium.     

条件性基因敲除:骨髓细胞特异性敲除Ncol2基因小鼠的建立和基因型鉴定

Ncol2是新发现的参与免疫调节的重要因子,Ncol2基因骨髓细胞特异性敲除小鼠的建立,能够有针对性的研究Ncol2基因缺失后对免疫系统的影响。根据条件性基因敲除的原理,本文利用loxp转基因小鼠和在骨髓细胞特异性表达Cre重组酶的LysMcre小鼠,繁殖建立了骨髓细胞特异性敲除Ncol2基因的小鼠,并提供了用鼠尾做基因型鉴定的简便方法。     

Third‐way neoliberalism and conditional cash transfers: The paradoxes of empowerment,participation and self‐help among poor Uruguayan women

The Latin American literature on Conditional Cash Transfer (CCT) welfare programs has typically involved the quantitative evaluation of social and economic impact, with fewer studies addressing the qualitative and gendered impacts of CCTs. Drawing from ethnographic fieldwork in poor squatter settlement communities in Uruguay, this article explores the everyday social realities of poor single mothers who have been disconnected from their kinship networks and must rely on CCT payments for survival. I locate these women's experiences within the third‐way neoliberal discourses of ‘empowerment’, ‘participation’ and ‘self‐help’ espoused by the state, and the various structural conditions, including crime, violence and unequal gender relations, that impact negatively on women's abilities to comply with their social and civic duties. I argue that rather than producing responsible and empowered subjects, Uruguay's recent CCT welfare program has paradoxically limited some women's participation in civic and public life and reproduced their dependent relations with men.     

On the limitations of standard statistical modeling in biological systems: A full Bayesian approach for biology

One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist.     

Selective inactivation of LGI1 in neuronal precursor cells leads to cortical dysplasia in mice

Constitutional mutations in Leucine‐rich glioma inactivated 1 (LGI1) predispose to an autosomal dominant epilepsy syndrome in humans and germline inactivation of LGI1 in mice leads to early onset seizures. LGI1 is highly expressed in the regions involved in neuronal stem cell generation and migration and detailed analysis of the brains in these mice reveals a subtle cortical dysplasia characterized by hypercellularity in the outer cortical layers. To investigate the cellular origin for this cortical dysplasia, we created mice that allow cell‐specific, conditional inactivation of LGI1. Exons 3–4, which contain critical motifs for LGI1 function, were targeted for deletion and, using a CMV‐cre mouse strain, global inactivation of LGI1 led to early onset seizures and the same cortical dysplasia seen in the constitutionally null mice. Similarly, inactivation of LGI1 in cells expressing Nestin, expressed primarily in neuronal precursor cells, led to early onset seizures and cortical dysplasia. In contrast, targeting inactivation of LGI1 in cells expressing Gfap, Camk2a, and parvalbumin, did not lead to cortical dysplasia. This strain of mouse, therefore, allows for a more refined investigation of the cell types involved in the cortical dysplasia seen following inactivation of LGI1 and potentially a better understanding of the molecular mechanisms behind LGI1‐induced epilepsy.