CCCTC-binding factor locks premature IgH germline transcription and restrains class switch recombination

In response to antigenic stimulation B cells undergo class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) to replace the primary IgM/IgD isotypes by IgG, IgE, or IgA. CSR is initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues at the switch (S) regions of IgH. B cell stimulation promotes germline transcription (GLT) of specific S regions, a necessary event prior to CSR because it facilitates AID access to S regions. Here, we show that CCCTC-binding factor (CTCF)-deficient mice are severely impaired in the generation of germinal center B cells and plasma cells after immunization in vivo, most likely due to impaired cell survival. Importantly, we find that CTCF-deficient B cells have an increased rate of CSR under various stimulation conditions in vitro. This effect is not secondary to altered cell proliferation or AID expression in CTCF-deficient cells. Instead, we find that CTCF-deficient B cells harbor an increased mutation frequency at switch regions, probably reflecting an increased accessibility of AID to IgH in the absence of CTCF. Moreover, CTCF deficiency triggers premature GLT of S regions in naïve B cells. Our results indicate that CTCF restricts CSR by enforcing GLT silencing and limiting AID access to IgH

Rangeland Health Status and Condition Two Different Yet Complementary Concepts: National Reserve Pampa Galeras Barbara D´Achille Case

Pampa Galeras Barbara D´Achille National Reserve has an extension of 21,030 hectares constituted mainly by puna rangeland and has played a key role in the recovery of the vicuña (Vicugna vicugna) population from extinction. This reserve is divided into two zones, known as the Rigid zone with a total area of 6,500 ha, and the Buffer zone of 14,530 ha. The present study aimed to implement an Ecological Response Unit system (ERU) to create an evaluation and monitoring system of rangeland health and condition, that could serve as a model for the rest of the Protected National Areas destinated for the conservation of vicuña. A total of 29 ERUs were delimited combining fieldwork and spatial information analysis. The results revealed that rangeland health is still at risk due to domestic herbivorous pressure. This suggests the need to implement a Reference Area system (RA) to evaluate and monitor rangeland health and condition indicators and thus improve management and livestock grazing control systems. In this manner, the bases for the execution of an adaptative management plan will settle with the participation of Servicio Nacional de Áreas Naturales Protegidas (SERNANP) and the local rural communities, landowners, and usufructuaries of the economic value of the vicuña fiber

Decoherence of Einstein-Podolsky-Rosen steering

We consider two systems A and B that share Einstein-Podolsky-Rosen (EPR) steering correlations and study how these correlations will decay, when each of the systems are independently coupled to a reservoir. EPR steering is a directional form of entanglement, and the measure of steering can change depending on whether the system A is steered by B, or vice versa. First, we examine the decay of the steering correlations of the two-mode squeezed state. We find that if the system B is coupled to a reservoir, then the decoherence of the steering of A by B is particularly marked, to the extent that there is a sudden death of steering after a finite time. We find a different directional effect, if the reservoirs are thermally excited. Second, we study the decoherence of the steering of a Schr\"odinger cat state, modeled as the entangled state of a spin and harmonic oscillator, when the macroscopic system (the cat) is coupled to a reservoir

CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation

In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation