פרסומים

Author summary Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. The basic level of regulation is mediated by different types of DNA-binding proteins, where each type regulates particular gene(s). We distinguish between two basic forms of regulation: positive—if a gene is activated by the binding of its regulatory protein, and negative—if it is active unless bound by its regulatory protein. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. How does the form of regulation, positive or negative, affect the extent of regulatory crosstalk? To address this question, we used a mathematical model integrating many genes and many regulators. As intuition suggests, we found that in most of the parameter space, crosstalk increased with the availability of regulators. We propose, that crosstalk is usually reduced when networks are designed such that minimal regulation is needed, which we call the ‘idle’ design. In other words: a frequently needed gene will use negative regulation and conversely, a scarcely needed gene will employ positive regulation. In both cases, the requirement for the regulators is minimized. In addition, we demonstrate how crosstalk can be calculated from available datasets and discuss the technical challenges in such calculation, specifically data incompleteness.

Measuring root properties, the ``hidden half'' of the plant, is challenging due to their heterogeneous and dynamic nature. A promising method for noninvasive mapping of roots and their activity, spectral induced polarization (SIP), has been introduced. However, measurements of root properties together with their SIP responses are missing, limiting the interpretation of a root's SIP signature. In this study, we coupled SIP measurements of roots in hydroponic solution with measurements of root biomass, surface area, and diameter. Furthermore, we monitored the SIP response of roots poisoned by cyanide, which results in depolarization of the root's cell membrane potential. We found a linear correlation between root biomass and surface area, and the low-frequency electrical polarization. In addition, we demonstrate the relationship between root cell membrane potential and root polarization. Based on the results, we suggest that in comparison with the stem-based approach used by other researchers, the polarization in the contact-free method used in this study is related to the external surface area of the root and external architectural structures such as root diameter and root hair. Overall, a direct link between root properties and their electrical signature was established.

Intracellular protein inclusions are diverse cellular entities with distinct biological properties. They vary in their protein content, sequestration sites, physiological function, conditions for their generation, and turnover rates. Major distinctions have been recognized between stationary amyloids and dynamic, misfolded protein deposits. The former being a dead end for irreversibly misfolded proteins, hence, cleared predominantly by autophagy, while the latter consists of a protein-quality control mechanism, important for cell endurance, where proteins are sequestered during proteotoxic stress and resolved upon its relief. Accordingly, the disaggregation of transient inclusions is a regulated process consisting of protein solubilization, followed by a triage step to either refolding or to ubiquitin-mediated degradation. Recent studies have demonstrated an indispensable role in disaggregation for components of the chaperone and the ubiquitin-proteasome systems. These include heat-shock chaperones of the 40/70/100 kDa families, the proteasome, proteasome substrate shuttling factors, and deubiquitylating enzymes. Thus, a functional link has been established between the chaperone machinery that extracts proteins from transient deposits and 26S proteasome-dependent disaggregation, indicative of a coordinated process. In this review, we discuss data emanating from these important studies and subsequently consolidate the information in the form of a working model for the disaggregation mechanism.

We assessed how religiosity is related to desired emotions. We tested two competing hypotheses. First, religiosity could be associated with a stronger desire for emotions that strengthen foundational religious beliefs (i.e., more awe and gratitude and less pride). Second, religiosity could be associated with a stronger desire for emotions that promote prosocial engagement (e.g., more love and empathy and less anger and jealousy). Two cross-cultural studies supported the first hypothesis. Religiosity was related to desire for emotions that strengthen religious beliefs, but not to desire for socially engaging or socially disengaging emotions. These findings held across countries and across several different religions. A third study investigating the mechanisms of both hypotheses using structural equation modeling supported only the first hypothesis. This research extends prior work on desired emotions to the domain of religiosity. It demonstrates that the emotions religious people desir

This introduction to the special section of South Asia: Journal of South Asian Studies, titled ‘Religious Minorities in Pakistan’, reviews the existing scholarship on this topic, points out gaps in the research, and discusses problematic notions and assumptions in both popular and academic discourses on minorities. Furthermore, it attempts a definition of the term ‘religious minority’, demonstrates its extensive entanglement with the question of caste—a characteristic specific to the South Asian case—and situates this discourse within broader debates about post-colonial state-building, the history of sectarianism in the region, contestations over religious authority, and the striving for a coherent political and cultural identity in Pakistan, the second-largest Muslim nation in the world.

Plants transmit their experiences of environmental conditions to their progeny through epigenetic inheritance, improving their progeny’s fitness under prevailing conditions. Though ABA is known to regulate epigenetic-modification genes, no strong phenotypic link between those genes and intergenerational “memory” has been shown. Previously, we demonstrated that mesophyll insensitivity to ABA (FBPase::abi1-1{fa} transgenic plants) results in a range of developmental phenotypes, including early growth vigor and early flowering (i.e., stress-escape behavior). Here, we show that null plants, used as controls (segregates of FBPase::abi1 that are homozygote descendants of a heterozygous transgenic plant, but do not contain the transformed abi1-1 gene) phenotypically resembled their FBPase::abi1-1 parents. However, in germination and early seedling development assays, null segregants resembled WT plants. These FBPase::abi1-1 null segregants mesophyll-related phenotypes were reproducible and stable for at least three generations. These results suggest that the heritability of stress response is linked to ABA’s epigenetic regulatory effect through ABI1 and mesophyll-related traits. The discrepancy between the epigenetic heritability of seed and mesophyll-related traits is an example of the complexity of epigenetic regulation, which is both gene and process-specific, and may be attributed to the fine-tuning of tradeoffs between flowering time, growth rate and levels of risk that allow annual plants to optimize their fitness in uncertain environments.

Remote sensing of night light emissions in the visible band offers a unique opportunity to directly observe human activity from space. This has allowed a host of applications including mapping urban areas, estimating population and GDP, monitoring disasters and conflicts. More recently, remotely sensed night lights data have found use in understanding the environmental impacts of light emissions (light pollution), including their impacts on human health. In this review, we outline the historical development of night-time optical sensors up to the current state of the art sensors, highlight various applications of night light data, discuss the special challenges associated with remote sensing of night lights with a focus on the limitations of current sensors, and provide an outlook for the future of remote sensing of night lights. While the paper mainly focuses on space borne remote sensing, ground based sensing of night-time brightness for studies on astronomical and ecological light pollution, as well as for calibration and validation of space borne data, are also discussed. Although the development of night light sensors lags behind day-time sensors, we demonstrate that the field is in a stage of rapid development. The worldwide transition to LED lights poses a particular challenge for remote sensing of night lights, and strongly highlights the need for a new generation of space borne night lights instruments. This work shows that future sensors are needed to monitor temporal changes during the night (for example from a geostationary platform or constellation of satellites), and to better understand the angular patterns of light emission (roughly analogous to the BRDF in daylight sensing). Perhaps most importantly, we make the case that higher spatial resolution and multispectral sensors covering the range from blue to NIR are needed to more effectively identify lighting technologies, map urban functions, and monitor energy use.

Neuronal loss can considerably diminish neural circuit function, impairing normal behavior by disrupting information flow in the circuit. We reasoned that by rerouting the flow of information in the damaged circuit it may be possible to offset these negative outcomes. We examined this possibility using the well-characterized chemosensory circuit of the nematode worm C. elegans . In this circuit, a main sensory neuron class sends parallel outputs to several interneuron classes. We found that the removal of one of these interneuron classes impairs chemotaxis to attractive odors, revealing a prominent path for information flow in the circuit. To alleviate these deficiencies, we sought to reinforce a remaining neural pathway. We used genetically engineered electrical synapses for this purpose, and observed the successful recovery of chemotaxis performance. However, we were surprised to find that the recovery was largely mediated by inadvertently formed left-right lateral electrical connections within individual neuron classes. Our analysis suggests that these additional electrical synapses help restore circuit function by amplifying weakened neuronal signals in the damaged circuit. These results demonstrate the power of genetically engineered synapses to regulate information flow and signal intensity in damaged neural circuits. \#\#\# Competing Interest Statement The authors have declared no competing interest.

DOI

The unfolded protein response (UPR) is a cellular homeostatic circuit regulating protein synthesis and processing in the ER by three ER-to-nucleus signaling pathways. One pathway is triggered by the inositol-requiring enzyme 1 (IRE1), which splices the X-box binding protein 1 (Xbp1) mRNA, thereby enabling expression of XBP1s. Another UPR pathway activates the activating transcription factor 6 (ATF6). Here we show that murine cytomegalovirus (MCMV), a prototypic $\beta$-herpesvirus, harnesses the UPR to regulate its own life cycle. MCMV activates the IRE1-XBP1 pathway early post infection to relieve repression by XBP1u, the product of the unspliced Xbp1 mRNA. XBP1u inhibits viral gene expression and replication by blocking the activation of the viral major immediate-early promoter by XBP1s and ATF6. These findings reveal a redundant function of XBP1s and ATF6 as activators of the viral life cycle, and an unexpected role of XBP1u as a potent repressor of both XBP1s and ATF6-mediated activation.

The effects of environmental heat-stress on production and reproduction in dairy cows have been intensively studied throughout the past few decades. In light of climate changes and global warming, this issue has gained attention worldwide. So far, most of the documentations are related to warmer-climate regions, however, environmental thermal stress has recently been reported in cooler regions, such as Europe. The review attempts to present the experiences from the past years and lessons for the present. The review highlights some of the environmental characterizations and provides some practical approaches to estimate the level of heat load on farms. For instance, the intensity of heat stress can be evaluated by the temperature humidity index (THI). Other environmental parameters, such as the increased number of consecutive hot days or the increased frequency of extremely hot days, can be also used to estimate the level of heat load on farms. Exposure of dairy cows to environmental thermal stress results in multiple behavioral changes, physiological responses and endocrinological alterations, which in sequence, lead to reduced reproductive performance. Multiple in-vitro studies have been performed for better understanding the mechanism by which heat stress impairs reproductive processes. However, the current review focuses mainly on animal reactions and on the limitations of physiological and behavioral responses in main-taining normothermia, without human intervention. The review provides evidence that thermal stress induces alterations in the hypothalamus-pituitary-ovarian axis. For instance, impaired gonadotropin secretion, attenuation of follicular development, reduced steroid production and progesterone concen-tration in the plasma. These were found to be associated with impaired estrus behavior, reduced oocyte developmental competence and embryo survival. Heat stress also has direct and indirect effects on the preimplantation embryo. The review summarizes the thermo-sensitivity of the embryo and the acqui-sition of its thermotolerance through early developmental stages. Understanding the effects of environmentally elevated temperature on the reproductive physiology of lactating cows is extremely important for the development of new strategies in order to mitigate the effects of heat stress on farms. The review also provides various types of management and practical tools, in order to alleviate the effects of thermal stress. It introduces some approaches that have been developed during recent years, ones that have been practically used to alleviate the effect of the environmental heat load and suggested to be implanted. Cooling is the predominant strategy used nowadays in order to alleviate the effects of heat stress. It includes indirect cooling of the environment surrounding the animal, by providing shed and ventilation (with or without water) or direct evaporative cooling of the cow with water and fans. Using an efficient cooling system can improve milk production during the hot season, but it cannot eliminate the decline in reproduction. The review also discusses some additional approaches such as timed artificial insemination, hormonal treatment and embryo transfer, which have already been developed. These are suggested to be examined, adapted and implemented in dairy farms located in new regions that have recently suffered from environmental heat stress. The review also discusses unclear points and open questions some of which might lead new research directions. (C) 2020 Elsevier Inc. All rights reserved.

This chapter reviews the research on the effects of EPV and on the intervention programs contained in this volume, and discusses the theoretical, methodological and ethical issues relating to these reports. In addition, building on the implications of the research for prevention of EPV, the chapter reviews the enforcement gap between international humanitarian and human rights law designed to protect children from EPV and the reality of increasing EPV in the world. It also discusses factors that have led to the enforcement gap, including weaknesses in enforcement mechanisms and psychosocial processes that lead individuals and groups to discount the rights of children. Finally, a we suggest approaches that researchers and practioners in the social sciences and international law could take for protecting children and families from EPV in armed conflict.

 Scholars have long sensed that Shakespeare distances himself from the ideology of perfect friendship, so dominant in his culture. This essay participates in this conversation by advancing two explanations for Shakespeare’s distrust of friendship. First, friends limit selves to what they were, preventing some transformations (examples discussed involve the love versus friendship tension played out in some of the comedies). Second, opening one’s heart to a friend requires abandoning self-love when recognizing the varied excellences which friends exhibit (a pattern of friendship resisted suggested by Timon of Athens).