| 1. |
- Blicharska, Malgorzata, 1979-, et al.
(författare)
-
Between biodiversity conservation and sustainable forest management - A multidisciplinary assessment of the emblematic Bialowieza Forest case
- 2020
-
Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 248
-
Tidskriftsartikel (refereegranskat)abstract
- The tension between biodiversity conservation and multipurpose forest management may lead to conflicts. An internationally prominent example is the Bialowieza Forest Massif (BFM), an extensive forest complex with high levels of naturalness. We apply a systematic, multidisciplinary assessment process to review empirical evidence on different dimensions of the BFM conflict. While there is broad consensus that this forest massif is an exceptional place worth conserving and that a way forward is a zonation system combining conservation with management, exactly how this should be done has yet to be agreed upon. Our assessment shows that the key reasons for the BFM controversy go beyond the availability of knowledge on the ecological status of the BFM and include: 1) evidence stemming from different sources, which is often contradictory and prone to different interpretations; 2) knowledge gaps, particularly with regard to socio-economic drivers and beneficiaries as well as uncertainties about future trends; 3) fundamentally different values and priorities among stakeholder groups, resulting in power struggles, and an overall lack of trust. We conclude that evidence-based knowledge alone is insufficient to cope with complex conservation conflicts. While more evidence may help assess the consequences of decisions, the actual management decisions depend on different actors' worldviews, which are rooted in their professional identities and power, and their political and legal realities. This calls for conflict management through a well-organized participatory process organized and supervised by a body deemed legitimate by the groups involved.
|
|
| 2. |
- Truelsen, Sigurd Friis, et al.
(författare)
-
The role of water coordination in the pH-dependent gating of hAQP10
- 2022
-
Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736. ; 1864:1
-
Tidskriftsartikel (refereegranskat)abstract
- Human aquaporin 10 (hAQP10) is an aquaglyceroporin that assists in maintaining glycerol flux in adipocytes during lipolysis at low pH. Hence, a molecular understanding of the pH-sensitive glycerol conductance may open up for drug development in obesity and metabolically related disorders. Control of hAQP10-mediated glycerol flux has been linked to the cytoplasmic end of the channel, where a unique loop is regulated by the protonation status of histidine 80 (H80). Here, we performed unbiased molecular dynamics simulations of three protonation states of H80 to unravel channel gating. Strikingly, at neutral pH, we identified a water coordination pattern with an inverted orientation of the water molecules in vicinity of the loop. Protonation of H80 results in a more hydrophobic loop conformation, causing loss of water coordination and leaving the pore often dehydrated. Our results indicate that the loss of such water interaction network may be integral for the destabilization of the loop in the closed configuration at low pH. Additionally, a residue unique to hAQP10 (F85) reveals structural importance by flipping into the channel in correlation with loop movements, indicating a loop-stabilizing role in the closed configuration. Taken together, our simulations suggest a unique gating mechanism combining complex interaction networks between water molecules and protein residues at the loop interface. Considering the role of hAQP10 in adipocytes, the detailed molecular insights of pH-regulation presented here will help to understand glycerol pathways in these cells and may assist in drug discovery for better management of human adiposity and obesity.
|
|
| 3. |
- Wang, Kaituo, et al.
(författare)
-
Structure of the human ClC-1 chloride channel
- 2019
-
Ingår i: PLoS biology. - : Public Library Science. - 1544-9173 .- 1545-7885. ; 17:4
-
Tidskriftsartikel (refereegranskat)abstract
- ClC-1 protein channels facilitate rapid passage of chloride ions across cellular membranes, thereby orchestrating skeletal muscle excitability. Malfunction of ClC-1 is associated with myotonia congenita, a disease impairing muscle relaxation. Here, we present the cryo-electron microscopy (cryo-EM) structure of human ClC-1, uncovering an architecture reminiscent of that of bovine ClC-K and CLC transporters. The chloride conducting pathway exhibits distinct features, including a central glutamate residue ("fast gate") known to confer voltage-dependence (a mechanistic feature not present in ClC-K), linked to a somewhat rearranged central tyrosine and a narrower aperture of the pore toward the extracellular vestibule. These characteristics agree with the lower chloride flux of ClC-1 compared with ClC-K and enable us to propose a model for chloride passage in voltage-dependent CLC channels. Comparison of structures derived from protein studied in different experimental conditions supports the notion that pH and adenine nucleotides regulate ClC-1 through interactions between the so-called cystathionine-β-synthase (CBS) domains and the intracellular vestibule ("slow gating"). The structure also provides a framework for analysis of mutations causing myotonia congenita and reveals a striking correlation between mutated residues and the phenotypic effect on voltage gating, opening avenues for rational design of therapies against ClC-1-related diseases.
|
|
