Conflict, cooperation or competition in the Caspian Sea region:A critical review of the New Great Game paradigm

This article critically reviews the New Great Game image of the Caspian Sea region and the assumptions, concepts, and mechanisms (revolving around actors, aims, and motivations) this image is based on. More specifically, this review essay answers the following questions: How does the academic literature interpret the impact of competition between great powers on social, political and economic developments in the Caspian Sea region? Which actors are presented as the dominant players? The essay also introduces the existing criticism of the New Great Game concept and alternatives to it that have already been put forward. By identifying the gaps and limits of existing scholarship, this article offers new avenues for alternative theoretical and empirical interpretations. More specifically, this article argues that the New Great Game literature promotes unsystematic and shallow discussion as it ignores and misunderstands historical, material, political, economic, and normative differences in the Caspian Sea region. Within this discussion, actors, interests, identities, social contexts, and principles are taken to be fixed, i.e. not prone to change or to any sort of adjustmen

HJURP Involvement in De Novo CenH3CENP-A and CENP-C Recruitment

Although our understanding of centromere maintenance, marked by the histone H3 variant CenH3CENP-A in most eukaryotes, has progressed, the mechanism underlying the de novo formation of centromeres remains unclear. We used a synthetic system to dissect how CenH3CENP-A contributes to the accumulation of CENP-C and CENP-T, two key components that are necessary for the formation of functional kinetochores. We find that de novo CENP-T accumulation depends on CENP-C and that recruitment of these factors requires two domains in CenH3CENP-A: the HJURP-binding region (CATD) and the CENP-C-binding region (CAC). Notably, HJURP interacts directly with CENP-C and is critical for de novo accumulation of CENP-C at synthetic centromeres. On the basis of our findings, we propose that HJURP serves a dual chaperone function in coordinating CenH3CENP-A and CENP-C recruitment

The Signal Transfer from the Receptor NpSRII to the Transducer NpHtrII Is Not Hampered by the D75N Mutation

Sensory rhodopsin II (NpSRII) is a phototaxis receptor of Natronomonas pharaonis that performs its function in complex with its cognate transducer (NpHtrII). Upon light activation NpSRII triggers by means of NpHtrII a signal transduction chain homologous to the two component system in eubacterial chemotaxis. The D75N mutant of NpSRII, which lacks the blue-shifted M intermediate and therefore exhibits a significantly faster photocycle compared to the wild-type, mediates normal phototaxis responses demonstrating that deprotonation of the Schiff base is not a prerequisite for transducer activation. Using site-directed spin labeling and time resolved electron paramagnetic-resonance spectroscopy, we show that the mechanism revealed for activation of the wild-type complex, namely an outward tilt motion of the cytoplasmic part of the receptor helix F and a concomitant rotation of the transmembrane transducer helix TM2, is also valid for the D75N variant. Apparently, the D75N mutation shifts the ground state conformation of NpSRII-D75N and its cognate transducer into the direction of the signaling state

Analysis of Light-Induced Conformational Changes of Natronomonas pharaonis Sensory Rhodopsin II by Time Resolved Electron Paramagnetic Resonance Spectroscopy†

The nature and kinetics of the conformational changes leading to the activated state of NpSRII ⁄ NpHtrII157 were investigated by time-resolved electron paramagnetic resonance (TR-EPR) spectroscopy in combination with site-directed spin labeling (SDSL) on a series of spin labeled mutants of NpSRII. A structural rearrangement of the cytoplasmic moiety of NpSRII upon light activation was detected (helices B, C, F and G). The increase in distance between helices C and F in the M-trapped state of the complex observed in one double mutant is in line with the notion that an outward movement of helix F occurs upon receptor activation. The data obtained from the NpSRII ⁄ NpH-trII157 complex reconstituted in purple membrane lipids are compared with those obtained from the X-ray structure of the late M-state of the complex which shows some discrepancies. The results are discussed in the context also of other biophysical and EPR experimental evidences.</p

Salt-driven Equilibrium between Two Conformations in the HAMP Domain from Natronomonas pharaonis: THE LANGUAGE OF SIGNAL TRANSFER?*

HAMP domains (conserved in histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis proteins, and phosphatases) perform their putative function as signal transducing units in diversified environments in a variety of protein families. Here the conformational changes induced by environmental agents, namely salt and temperature, on the structure and function of a HAMP domain of the phototransducer from Natronomonas pharaonis (NpHtrII) in complex with sensory rhodopsin II (NpSRII) were investigated by site-directed spin labeling electron paramagnetic resonance. A series of spin labeled mutants were engineered in NpHtrII157, a truncated analog containing only the first HAMP domain following the transmembrane helix 2. This truncated transducer is shown to be a valid model system for a signal transduction domain anchored to the transmembrane light sensor NpSRII. The HAMP domain is found to be engaged in a “two-state” equilibrium between a highly dynamic (dHAMP) and a more compact (cHAMP) conformation. The structural properties of the cHAMP as proven by mobility, accessibility, and intra-transducer-dimer distance data are in agreement with the four helical bundle NMR model of the HAMP domain from Archaeoglobus fulgidus

Increased Readiness for Water Splitting: NiO-Induced Weakening of Bonds in Water Molecules as Possible Cause of Ultra-Low Oxygen Evolution Potential

Bookholt T, Qin X, Lilli B, et al. Increased Readiness for Water Splitting: NiO-Induced Weakening of Bonds in Water Molecules as Possible Cause of Ultra-Low Oxygen Evolution Potential. Small . 2024: 2310665.The development of non-precious metal-based electrodes that actively and stably support the oxygen evolution reaction (OER) in water electrolysis systems remains a challenge, especially at low pH levels. The recently published study has conclusively shown that the addition of haematite to H2 SO4 is a highly effective method of significantly reducing oxygen evolution overpotential and extending anode life. The far superior result is achieved by concentrating oxygen evolution centres on the oxide particles rather than on the electrode. However, unsatisfactory Faradaic efficiencies of the OER and hydrogen evolution reaction (HER) parts as well as the required high haematite load impede applicability and upscaling of this process. Here it is shown that the same performance is achieved with three times less metal oxide powder if NiO/H2 SO4 suspensions are used along with stainless steel anodes. The reason for the enormous improvement in OER performance by adding NiO to the electrolyte is the weakening of the intramolecular O─H bond in the water molecules, which is under the direct influence of the nickel oxide suspended in the electrolyte. The manipulation of bonds in water molecules to increase the tendency of the water to split is a ground-breaking development, as shown in this first example. © 2024 The Authors. Small published by Wiley-VCH GmbH

Of elephants and men: politics and nature conservation in South Africa

South Africa's policy of destabilisation of neighbouring countries was closely associated with the rise of South Africa as a leading middleman in the international ivory trade. South African-based traders, acting in partnership or with protection from officers of the South African Military Intelligence Directorate, imported raw ivory from Angola, Mozambique and points further north and re-exported it to markets in the Far East. This was a source of income both for the South African secret services and for individuals associated with them. The same trade routes were also used for trade in other goods, including rhino horn, drugs, gems, currency and weapons. This was not only as a means of earning money but also a technique of destabilisation in itself. The extent of South Africa's involvement in this trade, although suspected by some conservationists, was difficult to prove and did not form the target of any concerted campaign by the leading conservation groups world-wide. In this respect, the strength of the South Africa lobby in the World-Wide Fund for Nature seems to have played a significant role. Since the ending of South Africa's military presence in Namibia and Angola in 1989, the Military Intelligence officers, Special Forces officers and others who conducted the wars for the defence of white South Africa have been intent on the struggle inside South Africa itself. There is evidence that such counter-insurgency specialists are now using Mozambique in particular as a base for operations inside South Africa. Moreover, they continue to have an interest in the ivory and rhino horn trades. Former officers of specialist counter-insurgency units have also found employment as game wardens in national parks. The bold proposals currently being implemented to create large new game parks along the South African-Mozambican border, using modern management techniques and involving local communities in their management, have important implications for politics and national security.ASC – Publicaties niet-programma gebonde

GAIN2 trial overall survival with intense versus tailored dose dense chemotherapy in early breast cancer

Abstract GAIN-2 trial evaluated the optimal intense dose-dense (idd) strategy for high-risk early breast cancer. This study reports the secondary endpoints pathological complete response (pCR) and overall survival (OS). Patients (n = 2887) were randomized 1:1 between idd epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) versus leukocyte nadir-based tailored regimen of dose-dense EC and docetaxel (dtEC-dtD) as adjuvant therapy, with neoadjuvant therapy allowed after amendment. At median follow-up of 6.5 years (overall cohort) and 5.7 years (neoadjuvant cohort, N = 593), both regimens showed comparable 5-year OS rates (iddEnPC 90.8%, dtEC-dtD 90.0%, p = 0.320). In the neoadjuvant setting, iddEnPC yielded a higher pCR rate than dtEC-dtD (51.2% vs. 42.6%, p = 0.045). Patients achieving pCR had significantly improved 5-year iDFS (88.7% vs. 70.1%, HR 0.33, p < 0.001) and OS rates (93.9% vs. 83.1%, HR 0.32, p < 0.001), but OS outcomes were comparable regardless of pCR status. Thus, iddEnPC demonstrates superior pCR rates compared to dtEC-dtD, yet with comparable survival outcomes