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Pistachio (Pistacia vera L.) forests support livelihoods in communities within Afghanistan's Pistachio Belt, a region characterized by extreme poverty and chronic insecurity. In this study, we used ecological data, as well as survey data to characterize standing attributes and resource user perceptions about local pistachio forests and their management. The survey questionnaire was verbally administered to 507 household representatives in remote communities that were chosen from eight districts in northern and northwestern Afghanistan based on accessibility and their location within the Pistachio Belt. Stand density and tree form varied widely between sites and as a function of elevation. Partial harvesting for fuelwood collection was positively correlated with stand density. The survey data also showed that pistachio forests support a variety of livelihood activities among respondents and their households. However, suboptimal nut collection timing and use of damaging nut harvesting methods were widespread with little effort to accommodate natural regeneration. Forest users typically recognized the degraded condition of the pistachio forest and the negative impacts of grazing and fuelwood collection on forest density. Respondents also recognized the impacts of nut collection practices, fuelwood collection, and grazing on forest regeneration status. These results suggest that efforts to sustainably manage pistachio forests must recognize considerable variation within and between communities regarding forest physical condition, accustomed uses by associated communities, and existing or potential mechanisms regulating forest uses. All of these necessitate context-specific forest management planning. We discuss challenges inherent to collecting baseline data needed for planning multiple-use community-based natural resources management in highly insecure environments. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) is a universal second messenger that plays a key role in cellular signaling. However, Ca2+ signals are transduced with the help of Ca2+-binding proteins, which serve as sensors, transducers, and elicitors. Among the collection of these Ca2+-binding proteins, calmodulin (CaM) emerged as the prototypical model in eukaryotic cells. This is a small protein that binds four Ca2+ ions and whose functions are multiple, controlling many essential aspects of cell physiology. CaM is universally distributed in eukaryotes, from multicellular organisms, such as human and land plants, to unicellular microorganisms, such as yeasts and ciliates. Here, we review most of the information gathered on CaM in Paramecium, a group of ciliates. We condense the information here by mentioning that mature Paramecium CaM is a 148 amino acid-long protein codified by a single gene, as in other eukaryotic microorganisms. In these ciliates, the protein is notoriously localized and regulates cilia function and can stimulate the activity of some enzymes. When Paramecium CaM is mutated, cells show flawed locomotion and/or exocytosis. We further widen this and additional information in the text, focusing on genomic data. [ABSTRACT FROM AUTHOR]

Background: Calmodulin (CaM) is an evolutionarily conserved eukaryotic multifunctional protein that functions as the major sensor of intracellular calcium signaling. Its calcium-modulated function regulates the activity of numerous effector proteins involved in a variety of physiological processes in diverse organs, from proliferation and apoptosis, to memory and immune responses. Due to the pleiotropic roles of CaM in normal and pathological cell functions, CaM antagonists are needed for fundamental studies as well as for potential therapeutic applications. Calmidazolium (CDZ) is a potent small molecule antagonist of CaM and one the most widely used inhibitors of CaM in cell biology. Yet, CDZ, as all other CaM antagonists described thus far, also affects additional cellular targets and its lack of selectivity hinders its application for dissecting calcium/CaM signaling. A better understanding of CaM:CDZ interaction is key to design analogs with improved selectivity. Here, we report a molecular characterization of CaM:CDZ complexes using an integrative structural biology approach combining SEC-SAXS, X-ray crystallography, HDX-MS, and NMR. Results: We provide evidence that binding of a single molecule of CDZ induces an open-to-closed conformational reorientation of the two domains of CaM and results in a strong stabilization of its structural elements associated with a reduction of protein dynamics over a large time range. These CDZ-triggered CaM changes mimic those induced by CaM-binding peptides derived from physiological protein targets, despite their distinct chemical natures. CaM residues in close contact with CDZ and involved in the stabilization of the CaM:CDZ complex have been identified. Conclusion: Our results provide molecular insights into CDZ-induced dynamics and structural changes of CaM leading to its inhibition and open the way to the rational design of more selective CaM antagonists. Calmidazolium is a potent and widely used inhibitor of calmodulin, a major mediator of calcium-signaling in eukaryotic cells. Structural characterization of calmidazolium-binding to calmodulin reveals that it triggers open-to-closed conformational changes similar to those induced by calmodulin-binding peptides derived from enzyme targets. These results provide molecular insights into CDZ-induced dynamics and structural changes of CaM leading to its inhibition and open the way to the rational design of more selective CaM antagonists. [ABSTRACT FROM AUTHOR]

Although three‐dimensional (3D) seismic surveys have improved the success rate of exploratory drilling for oil and gas, the impacts have received little scientific scrutiny, despite affecting more area than any other oil and gas activity. To aid policy‐makers and scientists, we reviewed studies of the landscape impacts of 3D‐seismic surveys in the Arctic. We analyzed a proposed 3D‐seismic program in northeast Alaska, in the northern Arctic National Wildlife Refuge, which includes a grid 63,000 km of seismic trails and additional camp‐move trails. Current regulations are not adequate to eliminate impacts from these activities. We address issues related to the high‐density of 3D trails compared to 2D methods, with larger crews, more camps, and more vehicles. We focus on consequences to the hilly landscapes, including microtopography, snow, vegetation, hydrology, active layers, and permafrost. Based on studies of 2D‐seismic trails created in 1984–1985 in the same area by similar types of vehicles, under similar regulations, approximately 122 km2 would likely sustain direct medium‐ to high‐level disturbance from the proposed exploration, with possibly expanded impacts through permafrost degradation and hydrological connectivity. Strong winds are common, and snow cover necessary to minimize impacts from vehicles is windblown and inadequate to protect much of the area. Studies of 2D‐seismic impacts have shown that moist vegetation types, which dominate the area, sustain longer‐lasting damage than wet or dry types, and that the heavy vehicles used for mobile camps caused the most damage. The permafrost is ice rich, which combined with the hilly topography, makes it especially susceptible to thermokarst and erosion triggered by winter vehicle traffic. The effects of climate warming will exacerbate the impacts of winter travel due to warmer permafrost and a shift of precipitation from snow to rain. The cumulative impacts of 3D‐seismic traffic in tundra areas need to be better assessed, together with the effects of climate change and the industrial development that would likely follow. Current data needs include studies of the impacts of 3D‐seismic exploration, better climate records for the Arctic National Wildlife Refuge, especially for wind and snow; and high‐resolution maps of topography, ground ice, hydrology, and vegetation. [ABSTRACT FROM AUTHOR]

Furthermore, Beaudry alludes to a central aspect of US visions of the ice sheet as a terrain, namely the ambition to not only transcend the material complexities of the landscape, but to simultaneously draw on the unique operational potentialities of the ice sheet as a vertical and voluminous sub-terrain (DUPI [34]). Standing out as the longest trek of its kind, the 1955 glaciological expedition, Project Jello, offers a telling example of how US desires to enlist the ice sheet as a terrain inspired them to reach into the very fabric of the ice sheet[5] - even when terrain was envisioned as surface. The subterranean geopolitics of the ice sheet terrain rested somewhere between its physicality and what the scientists, engineers, and military planners made of it; how they interpreted and framed matter and its inherent vibrancy, how they negotiated the temporality and liveliness of ice, and how they subsequently (re)assembled the ice sheet as a coherent territorial whole. The US scientific insertions in Greenland, of which Jello and the experiments at Camp Fistclench represented two minor factions, cast Greenland as part of its vast territorial network stretching across the Arctic and beyond.[12] Since SIPRE helped the US military gain epistemological access to the ice sheet and its deep structures, their calculative enactments of terrain were arguably key to establishing Greenland as a territory of US control. [Extracted from the article]

Tendon disease constitutes an unmet clinical need and remains a critical challenge in the field of orthopaedic surgery. Innovative solutions are required to overcome the limitations of current tendon grafting approaches, and bioelectronic therapies show promise in treating musculoskeletal diseases, accelerating functional recovery through the activation of tissue regeneration-specific signaling pathways. Self-powered bioelectronic devices, particularly piezoelectric materials, represent a paradigm shift in biomedicine, negating the need for battery or external powering and complementing existing mechanotherapy to accelerate the repair processes. Here, the dynamic response of tendon cells to a piezoelectric collagen-analogue scaffold comprised of aligned nanoscale fibers made of the ferroelectric material poly(vinylidene fluoride-co-trifluoroethylene) is shown. It is demonstrated that motion-powered electromechanical stimulation of tendon tissue through piezo-bioelectric device results in ion channel modulation in vitro and regulates specific tissue regeneration signaling pathways. Finally, the potential of the piezo-bioelectronic device in modulating the progression of tendinopathy-associated processes in vivo, using a rat Achilles acute injury model is shown. This study indicates that electromechanical stimulation regulates mechanosensitive ion channel sensitivity and promotes tendon-specific over non-tenogenic tissue repair processes., (© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Background: Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient's chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies. Methods: A literature search was conducted using the University of Manitoba search engine. Using this search engine allowed access to a greater variety of journals/articles that would have otherwise been restricted for general use. In order to be considered for discussion for this review, all articles must have been published later than 2009. Results: The alternative pre-approved antibiotics demonstrated high efficacy against B. anthracis both in vitro and in vivo. In addition, the safety profile and clinical pharmacology of these drugs were already known. Compounds that targeted underexploited bacterial processes (DNA replication, RNA synthesis, and cell division) were also very effective in combatting B. anthracis. In addition, these novel compounds prevented bacterial resistance. Targeting B. anthracis virulence, more specifically the anthrax toxins, increased the length of which treatment could be administered. Conclusions: Several novel and pre-existing antibiotics, as well as toxin inhibitors, have shown increasing promise. A combination treatment that targets both bacterial growth and toxin production would be ideal and probably necessary for effectively combatting this armed bacterium. [ABSTRACT FROM AUTHOR]

Nuristan province, in north-east Afghanistan, holds a significant portion of the country's remaining forests, but because of the inaccessible terrain and the recent history of poor security little is known about the wildlife inhabiting these forests. We conducted transect surveys in central Nuristan and confirmed the presence of musk deer Moschus cupreus > 60 years after the last documented observation of the species in Afghanistan. We found that, in summer, musk deer inhabit remote alpine scrub on scattered rock outcrops and in upper fringes of closed coniferous forests at c. 3,000–3,500 m. They invariably use steep slopes (≥ 20°), which makes them difficult to approach. We built a data-driven geographical model, which predicted that suitable habitat for musk deer in Afghanistan extends over c. 1,300 km2 in the contiguous provinces of Nuristan (75.5%), Kunar (14.4%) and Laghman (10.1%). Although relatively vast, the area of habitat potentially available to musk deer in Afghanistan appears to be highly fragmented. Despite indications of unsustainable hunting, this Endangered species persists in Afghanistan and targeted conservation programmes are required to protect it and its forest habitat. [ABSTRACT FROM AUTHOR]

The covalent transfer of the AMP portion of ATP onto a target protein—termed adenylylation or AMPylation—by the human Fic protein HYPE/FICD has recently garnered attention as a key regulatory mechanism in endoplasmic reticulum homeostasis, neurodegeneration, and neurogenesis. As a central player in such critical cellular events, high-throughput screening (HTS) efforts targeting HYPE-mediated AMPylation warrant investigation. Herein, we present a dual HTS assay for the simultaneous identification of small-molecule activators and inhibitors of HYPE AMPylation. Employing the fluorescence polarization of an ATP analog fluorophore—Fl-ATP—we developed and optimized an efficient, robust assay that monitors HYPE autoAMPylation and is amenable to automated, high-throughput processing of diverse chemical libraries. Challenging our pilot screen with compounds from the LOPAC, Spectrum, MEGx, and NATx libraries yielded 0.3% and 1% hit rates for HYPE activators and inhibitors, respectively. Further, these hits were assessed for dose-dependency and validated via orthogonal biochemical AMPylation assays. We thus present a high-quality HTS assay suitable for tracking HYPE's enzymatic activity, and the resultant first small-molecule manipulators of HYPE-promoted autoAMPylation. [ABSTRACT FROM AUTHOR]