TELSAM polymers accelerate crystallization of fused target proteins by stabilizing minimal crystal contacts and in the absence of direct inter-TELSAM contacts

We extend investigation into the usefulness of genetic fusion to TELSAM polymers as an effective protein crystallization strategy. We tested various numbers of the target protein fused per turn of the TELSAM helical polymer and various TELSAM–target connection strategies. We provide definitive evidence that: 1. A TELSAM–target protein fusion can crystallize more rapidly than the same target protein alone, 2. TELSAM–target protein fusions can form well-ordered, diffracting crystals using either flexible or rigid TELSAM–target linkers, 3. Well-ordered crystals can be obtained when either 2 or 6 copies of the target protein are presented per turn of the TELSAM helical polymer, 4. The TELSAM polymers themselves need not directly contact one another in the crystal lattice, and 5. Fusion to TELSAM polymer confers immense avidity to stabilize exquisitely weak inter-target protein crystal contacts. We report features of TELSAM-target protein crystals and outline future work needed to define the requirements for reliably obtaining optimal crystals of TELSAM–target protein fusions.

6D dynamic tractography visualizes the effective connectivity supporting specific linguistic stages in the developing brain

During a verbal conversation, as individuals listen and respond, the human brain moves through a series of complex linguistic processing stages: decoding of speech sounds, semantic comprehension, retrieval of semantically coherent words, and finally, overt production of speech outputs. Each process is thought to be supported by a cortical network consisting of local and long-range connections bridging between major cortical areas. Both temporal and extratemporal lobe regions are suggested to have functional compartments responsible for distinct language domains, including the perception and production of phonological and semantic components. This study provides quantitative evidence of how directly connected, inter-lobar neocortical networks support distinct linguistic stages of linguistic processing across brain development. A novel six-dimensional tractography animation technique was used to intuitively visualize the strength and temporal dynamics of direct inter-lobar effective connectivity between cortical areas activated during distinct linguistic processing stages. This study analyzed 3,401 non-epileptic intracranial electrode sites from 37 children with focal epilepsy (age: 5–20 years) who underwent extraoperative electrocorticography recording. We used a principal component analysis of high-gamma modulations during an auditory naming task to determine the relative involvement of each cortical area during each linguistic processing stage. To quantify direct effective connectivity, we delivered single-pulse electrical stimulation to 488 temporal lobe sites and 1,581 extratemporal lobe sites and measured the early cortico-cortical spectral responses at distant electrodes. Mixed model analyses determined the effects of naming-related high-gamma co-augmentation between connecting regions, age, and cerebral hemisphere on the strength of effective connectivity independent of epilepsy-related factors. Direct effective connectivity was strongest between temporal and extratemporal lobe site pairs which were simultaneously activated during the period between sentence offset and verbal response onset (i.e., semantic retrieval period); this connectivity was approximately twice more robust than that with temporal lobe sites activated during stimulus listening or overt response. Conversely, extratemporal lobe sites activated during overt response were equally connected with temporal lobe language sites. Older age was associated with the increased strength of inter-lobar effective connectivity between those activated during semantic retrieval. The arcuate fasciculus supported approximately two-thirds of the direct effective connectivity pathways from temporal to extratemporal auditory language-related areas but only up to half of those in the opposite direction. The uncinate fasciculus consisted of only less than 2% of those in the temporal-to-extratemporal direction and up to 6% of those in the opposite direction. Our multimodal study quantified and animated the direct inter-lobar networks toward and from temporal lobe regions supporting distinct stages of auditory language processing. Additionally, age-dependent strengthening of connectivity after age five may preferentially occur between language areas supporting semantic retrieval.

VARIETAL SPECIFICITY OF OPTO-BIOLOGICAL PROPERTIES AND PHYTOMETRIC PARAMETERS OF WINTER WHEAT CROPS

Identification of varietal specificity of opto-biological properties of field crops is necessary for adequate interpretation of satellite images, rapid determination of phytometric parameters of crops, indication of the level of their development and justification of corrective technological solutions. The aim of the research was to evaluate the opto-biological properties and phytometric parameters of diverse biological varieties of winter wheat; identify their relationship and inter-variety variability in high-tech reference crops based on satellite and ground monitoring. Field studies were conducted in 2019-2020 on the site of competitive ecological variety testing laid on the experimental field of the Orenburg State Agrarian University in the zone of the southern steppes of the Orenburg Cis-Urals (Preduralye). During the study, we found that agrocenoses of different winter wheat varieties differ markedly in opto-biological properties expressed in normalized difference vegetation index (NDVI) values. Varieties ‘Grom’, ‘Don 95’, ‘Bystritsa’, ‘Spartak’, ‘Stanichnaya’ and ‘Sintetik’ were characterized by the lowest average NDVI values during the growing season (0.57-0.59). Higher NDVI values (0.67) were observed in the crops of ‘Zhemchuzhina Povolzhya’, ‘Kolos Orenburzhya’, ‘Orenburgskaya 105’, ‘Rifey’ and ‘Pionerskaya 32’ varieties. The variability between the varieties according to the lowest (0.51 – ‘Grom’, 0.52 – ‘Don 95’) and the highest (0.69 – ‘Kolos Orenburzhya’, 0.70 – ‘Pionerskaya 32’, 0.69 – ‘Orenburgskaya 105’) NDVI values during the maximum assimilation apparatus development reached 0.17-0.19 units (phase of full spring tillering). By the heading, when NDVI was 0.78–0.79 and 0.85 units, respectively, this difference somewhat leveled but, in general, remained significant – at the level of 0.08-0.11 units (10.9–14.9 %). The largest leaf area (30 thousand m2/ha) was typical for the crops of ‘Saratovskaya 17’, ‘Kolos Orenburzhya’, ‘Orenburgskaya 105’, ‘Rifey’ and ‘Pionerskaya 32’. There was no direct inter-variety relationship between the leaf area and NDVI of winter wheat crops (R 2= 0.38).

Muslim Clergy vs. Authority in Contemporary Afghanistan: View from Uzbekistan

Significant geopolitical changes taking place in the modern world in recent decades urge us to take a fresh look at the role of Islam and the clergy in the political processes of a number of countries of the Muslim world. This perspective is especially relevant vis--vis Afghanistan where a fierce war is being waged under the slogans of Islam for more than four decades. The purpose of this research is an in-depth study of the relationship between the state and the Muslim clergy, Islamic institutions in the development of political processes in Afghanistan since the mid-70s of the last century. The article reflects shaping of the Islamic opposition and its efforts to stand up to innovations and reforms during attempts of the Soviet stile modernization in 1978-1992, and then the efforts to democratize Afghan society, undertaken in Afghanistan since the end of 2001 with the assistance of the international community. The work is based on the study of factual historical material, a chronicle of the events of the last decade and personal observations of the author during his work in Afghanistan during the mentioned period. Analytical materials published on the pages of English and Russian mass media were used. The methodological basis of this study is the comparative historical method; the article is based on the principles of historicism, reliability and scientific objectivity. The author concludes that the conflict is based on mistakes and underestimation by the state the role and influence of the Muslim clergy and Islamic institutions of the country. It has been noted that the recently reached US - Taliban agreements, as well as the assistance of such influential players as Russia, sparkle hope for the launch of a direct inter-Afghan negotiation process, which most likely will not be as simple but thorny.

Iran’s Syria Strategy: The Evolution of Deterrence

Iran has been a critical player in the Syrian war since 2011, crafting a complex foreign policy and military strategy to preserve its Syrian ally. What have been the drivers of Iranian decision-making in this conflict? And how has Iranian strategy evolved over the course of the war? This chapter argues that the logic of deterrence has been fundamental not just for shaping the contours of Iran–Syria relations since the Islamic Revolution of 1979, but also for determining the overall trajectory of Iranian strategy in the Syrian war. The authors outline Iran’s decision-making calculus and divide the country’s strategy on Syria after the Arab Spring into four primary phases: (1) a ‘Basij’ strategy to establish local militias in Syria; (2) a regionalization strategy to incorporate transnational fighters and militias in the war effort; (3) an internationalization strategy to incorporate Russia and balance the United States; and (4) a post-ISIS deterrence strategy to balance against the United States, Turkey and Israel. Iran’s Syria strategy progressively escalated in response to the possible defeat of its ally and the deterioration of its forward deterrence capacities against the United States and Israel. Today, the potential for direct inter-state conflict is rising as proxy warfare declines and Iran attempts to maintain the credibility of its forward deterrence.

Future proofing the principle of no significant harm

The principle of ‘no significant harm’ as a way of addressing transboundary environmental challenges is both inadequately researched and inadequately implemented in many parts of the world. This paper addresses the questions: What is the nature of transboundary harm in the Anthropocene? Is the principle of no significant harm able to address current and pre-empt future transboundary harm in the field of water and environmental law? This special issue has focused on this principle in the arena of water law. This article integrates the findings in the context of a broader understanding of global harm in the Anthropocene. We draw 4 conclusions. First, conceptually harm is moving beyond direct inter-state harm between neighbouring countries to a multi-directional, multi-actor/multi-level harm, which is increasingly creeping and cumulative, with growing spatial and temporal characteristics. It thus requires moving beyond quibbling over what is ‘significant’ harm to recognize the climate emergency, the sixth biodiversity extinction, the huge damage to water systems and to realize that the threshold of ecosystem and human tolerance of damage are reducing rapidly. Second, however, the no-harm principle tends to be better developed in qualifying sovereignty in relation to transboundary harm on rivers than in the broader environmental and development arena as demonstrated by agenda 2030 which reverts to full permanent sovereignty. Third, legal scholarship, however, does provide a wide range of instruments for addressing harm before it occurs, after it has happened, and considering the differentiated economic capacity of the actors. Finally, the larger problem is that it is not individual projects or programmes that cause problems as much as national prioritization of economic growth which has led to externalizing the environment. The no-harm principle will be ineffective if it cannot be used to question the content of ‘growth’-led policies. There is need to future proof the no-harm principle.

Pd(0)-Catalyzed Direct Inter- and Intramolecular C–H Functionalization of 4-Carboxyimidazoles

The palladium-catalyzed arylation and alkenylation of N-substituted methyl imidazole-4-carboxylates are described through inter- and intramolecular pathways. Both direct C2–H and C5–H arylation and alkenylation proceed under Pd(0)/Cu(I) cooperative catalysis and Pd(0) catalysis, respectively, in low-polarity 1,4-dioxane solvent. The methodology gives access to C2 (hetero)aryl or alkenyl imidazoles as well as innovative C2- and C5-arylated fused imidazoles tricycles with a five- to seven-membered middle ring.