Leptotene/zygotene chromosome movement via the SUN/KASH protein bridge in Caenorhabditis elegans

The Caenorhabditis elegans inner nuclear envelope protein matefin/SUN-1 plays a conserved, pivotal role in the process of genome haploidization. CHK-2-dependent phosphorylation of SUN-1 regulates homologous chromosome pairing and interhomolog recombination in Caenorhabditis elegans. Using time-lapse microscopy, we characterized the movement of matefin/SUN-1::GFP aggregates (the equivalent of chromosomal attachment plaques) and showed that the dynamics of matefin/SUN-1 aggregates remained unchanged throughout leptonene/zygotene, despite the progression of pairing. Movement of SUN-1 aggregates correlated with chromatin polarization. We also analyzed the requirements for the formation of movement-competent matefin/SUN-1 aggregates in the context of chromosome structure and found that chromosome axes were required to produce wild-type numbers of attachment plaques. Abrogation of synapsis led to a deceleration of SUN-1 aggregate movement. Analysis of matefin/SUN-1 in a double-strand break deficient mutant revealed that repair intermediates influenced matefin/SUN-1 aggregate dynamics. Investigation of movement in meiotic regulator mutants substantiated that proper orchestration of the meiotic program and effective repair of DNA double-strand breaks were necessary for the wild-type behavior of matefin/SUN-1 aggregates.     

Are Biological Effects of Desert Shrubs More Important than Physical Effects on Soil Microorganisms?

Vegetation cover plays a major role in providing organic matter and in acting as a physical barrier, with both together contributing to the formation of “fertile islands,” which play an active role in prolonging biological activity in desert ecosystems. By undertaking this study, a long-term research, we designed an experiment to separate the two components—the physical and biotic parts of the perennial plants—and to identify the factor that contributes the most to the ecosystem. The study site was located in the northern Negev Desert, Israel, where 50 Hammada scoparia shrubs and 50 artificial plants were randomly marked. Soil samples were collected monthly over 3 years of research at three locations: under the canopy of H. scoparia shrubs, in the vicinity of the artificial plants, and between the shrubs (control). The contribution to microbial activity was measured by evaluation of the microbial community functions in soil. The functional aspects of the microbial community that were measured were CO₂ evolution, microbial biomass, microbial functional diversity, and the physiological profile of the community. The results of this study are presented in two ways: (1) according to the three locations/treatments; and (2) according to the phenological situation of the vegetation (annual and perennial plants) in the research field: the growing phase, the drying process, and the absence of annual plants. The only parameters that were found to affect microbial activity were the contribution of the organic matter of perennial shrubs and the growth of vegetation (annual and perennial) during the growing seasons. The physical component was found to have no effect on soil microbial functional diversity, which elucidates the important contribution of the desert shrub in enhancing biological multiplicity and activity.     

Bim and Bcl-2 mutually affect the expression of the other in T cells

The life and death of T cells is controlled to a large extent by the relative amounts of Bcl-2-related proteins they contain. The antiapoptotic protein Bcl-2 and the proapoptotic protein Bim are particularly important in this process with the amount of Bcl-2 per cell dropping by about one-half when T cells prepare to die. In this study we show that Bcl-2 and Bim each control the expression of the other. Absence of Bim leads to a drop in the amount of intracellular Bcl-2 protein, while having no effect on the amounts of mRNA for Bcl-2. Conversely, high amounts of Bcl-2 per cell allow high amounts of Bim, although in this case the effect involves increases in Bim mRNA. These mutual effects occur even if Bcl-2 is induced acutely. Thus these two proteins control the expression of the other, at either the protein or mRNA level.     

The COP9 signalosome is vital for timely repair of DNA double-strand breaks

The DNA damage response is vigorously activated by DNA double-strand breaks (DSBs). The chief mobilizer of the DSB response is the ATM protein kinase. We discovered that the COP9 signalosome (CSN) is a crucial player in the DSB response and an ATM target. CSN is a protein complex that regulates the activity of cullin ring ubiquitin ligase (CRL) complexes by removing the ubiquitin-like protein, NEDD8, from their cullin scaffold. We find that the CSN is physically recruited to DSB sites in a neddylation-dependent manner, and is required for timely repair of DSBs, affecting the balance between the two major DSB repair pathways—nonhomologous end-joining and homologous recombination repair (HRR). The CSN is essential for the processivity of deep end-resection—the initial step in HRR. Cullin 4a (CUL4A) is recruited to DSB sites in a CSN- and neddylation-dependent manner, suggesting that CSN partners with CRL4 in this pathway. Furthermore, we found that ATM-mediated phosphorylation of CSN subunit 3 on S410 is critical for proper DSB repair, and that loss of this phosphorylation site alone is sufficient to cause a DDR deficiency phenotype in the mouse. This novel branch of the DSB response thus significantly affects genome stability.     

The Tyrosine Kinase c-Abl Promotes Homeodomain-interacting Protein Kinase 2 (HIPK2) Accumulation and Activation in Response to DNA Damage

The non-receptor tyrosine kinase c-Abl is activated in response to DNA damage and induces p73-dependent apoptosis. Here, we investigated c-Abl regulation of the homeodomain-interacting protein kinase 2 (HIPK2), an important regulator of p53-dependent apoptosis. c-Abl phosphorylated HIPK2 at several sites, and phosphorylation by c-Abl protected HIPK2 from degradation mediated by the ubiquitin E3 ligase Siah-1. c-Abl and HIPK2 synergized in activating p53 on apoptotic promoters in a reporter assay, and c-Abl was required for endogenous HIPK2 accumulation and phosphorylation of p53 at Ser⁴⁶ in response to DNA damage by γ- and UV radiation. Accumulation of HIPK2 in nuclear speckles and association with promyelocytic leukemia protein (PML) in response to DNA damage were also dependent on c-Abl activity. At high cell density, the Hippo pathway inhibits DNA damage-induced c-Abl activation. Under this condition, DNA damage-induced HIPK2 accumulation, phosphorylation of p53 at Ser⁴⁶, and apoptosis were attenuated. These data demonstrate a new mechanism for the induction of DNA damage-induced apoptosis by c-Abl and illustrate network interactions between serine/threonine and tyrosine kinases that dictate cell fate.     

Biometry and phenology of two sibling Phylloscopus warblers on their circum-Mediterranean migrations

The Mediterranean Sea is known as an ecological barrier for numerous migratory birds flying from European breeding grounds to African wintering sites. Birds generally avoid migration over open sea and fly over land. In the Mediterranean Basin, few land bridges or bottlenecks for migratory birds exist. The narrowest are at the western and eastern extremes: the Strait of Gibraltar and Israel. Comparative studies between these locations are extremely rare to date. Therefore, in order to elucidate the differences between the two flyways, we compared data collected simultaneously for two sister leaf warbler species, the Bonelli’s Warbler complex, Phylloscopus bonelli and Phylloscopus orientalis, at ringing stations in the western Mediterranean Basin Gibraltar, and the eastern Eilat, Israel. Data on biometrics and passage dates of individuals trapped at Gibraltar and Eilat were used, and it was found that mean arrival date of Western Bonelli’s Warblers at Gibraltar was 15 days later than Eastern Bonelli’s Warblers at Eilat. Furthermore, Western Bonelli’s Warblers had shorter wings than Eastern Bonelli’s Warblers. On the other hand, birds in Eilat were in poorer body condition than individuals in Gibraltar. The comparison between geographically distant stop-over sites contributes to furthering our understanding of the development of migration strategies across ecological barriers in sibling species. Our study showed that populations that breed in southwestern Europe migrate through Gibraltar and winter in West Africa are able to accomplish migration in comparatively good body condition. This is in contrast to those that winter in East Africa, migrate through Israel and have to endure the combined challenge of crossing the Sahel, Sahara and Sinai deserts before reaching their breeding grounds across southeast Europe and southwest Asia. Hence, the discrepancies described between the western and the eastern flyway suggest that individuals in the west, in general, migrate shorter distances, have a physiologically less demanding crossing of the North African deserts and appear to stage before their crossing the Strait of Gibraltar, a privilege unavailable to the migrants of the eastern flyway.     

Mechanisms of magnetic stimulation of central nervous system neurons

Transcranial magnetic stimulation (TMS) is a stimulation method in which a magnetic coil generates a magnetic field in an area of interest in the brain. This magnetic field induces an electric field that modulates neuronal activity. The spatial distribution of the induced electric field is determined by the geometry and location of the coil relative to the brain. Although TMS has been used for several decades, the biophysical basis underlying the stimulation of neurons in the central nervous system (CNS) is still unknown. To address this problem we developed a numerical scheme enabling us to combine realistic magnetic stimulation (MS) with compartmental modeling of neurons with arbitrary morphology. The induced electric field for each location in space was combined with standard compartmental modeling software to calculate the membrane current generated by the electromagnetic field for each segment of the neuron. In agreement with previous studies, the simulations suggested that peripheral axons were excited by the spatial gradients of the induced electric field. In both peripheral and central neurons, MS amplitude required for action potential generation was inversely proportional to the square of the diameter of the stimulated compartment. Due to the importance of the fiber's diameter, magnetic stimulation of CNS neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. Passive dendrites affect this process primarily as current sinks, not sources. The simulations predict that neurons with low current threshold are more susceptible to magnetic stimulation. Moreover, they suggest that MS does not directly trigger dendritic regenerative mechanisms. These insights into the mechanism of MS may be relevant for the design of multi-intensity TMS protocols, may facilitate the construction of magnetic stimulators, and may aid the interpretation of results of TMS of the CNS.