A dual function of the CRISPR-Cas system in bacterial antivirus immunity and DNA repair

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR-associated protein that is common to all CRISPR-containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single-stranded and branched DNAs including Holliday junctions, replication forks and 5'-flaps. The crystal structure of YgbT and site-directed mutagenesis have revealed the potential active site. Genome-wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR-Cas system have a function in DNA repair.     

Specific and Selective Bacteriophages in the Fight against Multidrug-resistant Acinetobacter baumannii

Acinetobacter baumannii causes serious infections especially in immunocompromised and/or hospitalized patients. Several A. baumannii strains are multidrug resistant and infect wounds, bones, and the respiratory tract. Current studies are focused on finding new effective agents against A. baumannii. Phage therapy is a promising means to fight this bacterium and many studies on procuring and applying new phages against A. baumannii are currently being conducted. As shown in animal models, phages against multidrug-resistant A. baumannii may control bacterial infections caused by this pathogen and may be a real hope to solve this dangerous health problem.     

Continual assembly of desmosomes within stable intercellular contacts of epithelial A-431 cells

Subclones of human carcinoma-derived A-431 cell line stably producing fusion proteins consisting of the enhanced green fluorescent protein and either human desmoglein 2 (Dsg-GFP) or human plakoglobin (GFP-Pg) were used to examine the behavior of desmosomes in living cells. Immunofluorescence microscopy of the fixed cells showed that both fusion proteins, which were expressed in significantly lower levels relative to their endogenous counterparts, were efficiently recruited into desmosomes. Time-lapse confocal imaging of these cells reveals that such GFP-labeled desmosomes (GFP desmosomes) are stable structures which exhibit various dynamic and motile activities. The most notable are independent lateral mobility and fusion. Furthermore, the continual assembly of new nascent desmosomes is observed within stable contacts located at the middle of the epithelial sheet. A new GFP desmosome appears as a closely apposed group of fine patches which after a few minutes aggregate into a single structure. These three dynamic processes resulted in constant changes of desmosome distribution, numbers, and sizes. In addition, fluorescence recovery after photobleaching experiments showed that fine patches of desmosomal proteins may participate in desmosome maintenance. Such a diverse range of dynamic activities of desmosomes apparently produces flexible but tight cell-cell adhesion required for different morphogenetic events in epithelial structures.This work was supported by grant AR44016-04 from the National Institutes of Health     

Autonomy,productiveness, and community: the rise of inequality in an Amazonian society

In Amazonian societies, autonomy is said to be a core value motivating egalitarian politics. This article shows how the quest for autonomy and productiveness presently sets in motion processes that encroach upon these very values. Among the Shuar of Amazonian Ecuador, the realization of autonomy and productiveness increasingly depends on the capture of state resources. Shuar interact with the local state as members of relatively recent sedentary communities and through the mediation of elected leaders. In these processes, ‘community’ itself is transformed: being a channel to regenerate domestic livelihoods, it also becomes an end in itself, giving rise to new economistic attitudes while legitimizing inequalities between commoners and leaders. The article suggests that the pursuit of autonomy and productiveness within a process of village formation is central to the transformation of egalitarianism that occurs when small-scale Amazonian polities engage with nation-state politics.     

Are offspring begging levels exaggerated beyond the parental optimum? Evidence from a bidirectional selection experiment

Parental care involves elaborate behavioural interactions between parents and their offspring, with offspring stimulating their parents via begging to provision resources. Thus, begging has direct fitness benefits as it enhances offspring growth and survival. It is nevertheless subject to a complex evolutionary trajectory, because begging may serve as a means for the offspring to manipulate parents in the context of evolutionary conflicts of interest. Furthermore, it has been hypothesized that begging is coadapted and potentially genetically correlated with parental care traits as a result of social selection. Further experiments on the causal processes that shape the evolution of begging are therefore essential. We applied bidirectional artificial selection on begging behaviour, using canaries (Serinus canaria) as a model species. We measured the response to selection, the consequences for offspring development, changes in parental care traits, here the rate of parental provisioning, as well as the effects on reproductive success. After three generations of selection, offspring differed in begging behaviour according to our artificial selection regime: nestlings of the high begging line begged significantly more than nestlings of the low begging line. Intriguingly, begging less benefitted the nestlings, as reflected by on average significantly higher growth rates, and increased reproductive success in terms of a higher number of fledglings in the low selected line. Begging could thus represent an exaggerated trait, possibly because parent–offspring conflict enhanced the selection on begging. We did not find evidence that we co‐selected on parental provisioning, which may be due to the lack of power, but may also suggest that the evolution of begging is probably not constrained by a genetic correlation between parental provisioning and offspring begging.     

Nasal Priming with Lactobacillus rhamnosus CRL1505 Stimulates Mononuclear Phagocytes of Immunocompromised Malnourished Mice: Improvement of Respiratory Immune Response

The effect of Lactobacillus rhamnosus CRL1505 (Lr) on macrophages (Ma) and dendritic cells (DC) in the orchestration of anti-pneumococcal immunity was stud     

Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV‐2

Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS‐CoVs and Middle East Respiratory Syndrome coronavirus (MERS‐CoVs), the detailed information about SARS‐CoV‐2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high‐throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS‐CoV‐2 proteins and structures. Here we report two high‐resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.