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- Kipling, D, et al.
(författare)
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Telomere-dependent senescence
- 1999
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Ingår i: NATURE BIOTECHNOLOGY. - : NATURE AMERICA INC. ; 17:4
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Lindsay, Willow R, et al.
(författare)
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Endless forms of sexual selection
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The field of sexual selection has burgeoned with research into trait evolution in the context of ecology, sociality, phylogeny, natural selection, and sexual conflict. This paper is the product of a “stock-taking” workshop; our aim is to stimulate discussion, not to provide an exhaustive review. We identify outstanding questions organized into four thematic sections.1) Evolution of mate choice and mating systems. Variation in mate quality can generate mating competition and choice in either sex with implications for the evolution of mating systems. Limitations on mate choice may dictate the importance of direct vs. indirect benefits in mating decisions and consequently, mating systems. Specifically, polyandry evolves in response to the strength of pre- vs. post-copulatory selection. The evolution of polyandry may be related to diversity of pathogens and Major Histocompatibility Complex (MHC) genes. MHC genes are also potential cues of kinship in avoidance of inbreeding. The balance between inbreeding avoidance and inclusive fitness in mating decisions deserves greater attention.2) Sender and receiver mechanisms shaping signal design. Mediation of honest signal content likely depends on integration of temporally variable social and physiological costs that are a challenge to measure. The neuroethology of sensory and cognitive receiver biases is the main key to signal form and the ‘aesthetic sense’ proposed by Darwin. Since a receiver bias is sufficient to both start and drive ornament or armament exaggeration, without a genetically correlated or even coevolving receiver, this may be the appropriate ‘null model’ of sexual selection.3) Genetic architecture of sexual selection. Despite advances in modern molecular techniques, the number and identity of genes underlying performance remain largely unknown. A combination of genomic techniques and long-term field studies that reveal ecological correlates of reproductive success is warranted. In-depth investigations into the genetic basis of sexual dimorphism will reveal constraints and trajectories of sexually selected trait evolution.4) Sexual selection and conflict as drivers of speciation. Population divergence and speciation is often driven by an interplay between sexual and natural selection. To what extent sexual selection promotes or counteracts population divergence may differ depending on the genetic architecture of traits as well as covariance between mating competition and local adaptation, if traits have multiple functions and if sensory systems used in mate choice are locally adapted. Also, post-copulatory processes, e.g. selection against heterospecific sperm, may influence the importance of sexual selection. Sexual conflict can shape speciation processes, since mate choice selection on females can restrict gene flow whereas selection on males is permissive.We propose that efforts to resolve these four themes can catalyze conceptual progress in the field of sexual selection.
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| 3. |
- Lu, Lu, 1984-, et al.
(författare)
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MEPicides : α,β-Unsaturated Fosmidomycin N-acyl Analogsas inhibitors that selectively target DXR from Plasmodium falciparum, the deadliest causative parasite of human Malaria
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Fosmidomycin and FR-9000098 have been confirmed to show parasiticidal activity against Plasmodium falciparum, targeting DXR involved in the MEP pathway. We designed a construct of PfDXR that has successfully been overexpressed in E. coli BL21(DE3) C43, and purified by IMAC and SEC, with the final yield of 1.2 mg/ 8 L culture. PfDXR was concentrated to 20 mg/ml, and co-crystallized with previously tested inhibitors in the FR-9000098 scaffold in the presence of Mn2+. Three FR-9000098 analogues with double-bonded Ca-Cband/or a phenyl ring with various lengths to N1, showed inhibitory activities with IC50s roughly 50 nM. Three crystals were in triclinic P1space group, with similar dimensions in the unit cell (51Å, 56Å, 86Å, 103°, 103°, 101°). All four complex structures have been crystallographically determined at resolutions in the range 1.86 Å, 2.45 Å, 2.13Å, 2.05 Å. Given the high similarity in structures, the initial phases were determined by rigid body refinement with search model PfDXR-FN3 complex, followed by restrained refinement in refmac5. Subsequently, the ligands and surrounding amino acid residues were manually rebuilt with theqdstools in O. the Ca-Cbbonds of the three ligands were altered from a single to double bond based on the structure of FR9000098. In addition, two ligands were extended at the Cdwith a phenyl group, and with the benzyl group connected by two carbons. N-terminal NADPH binding domains from four complexes undergo minor rigid body movement, and more details of conformational changes in the flap region are discussed.
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| 6. |
- Van der Speeten, Kurt, et al.
(författare)
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Toxicity of a Uniform Combined Bidirectional Hyperthermic and Perioperative Intraperitoneal Chemotherapy Regimen after Cytoreductive Surgery in 147 Peritoneal Surface Malignancy Patients
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCurrently, the treatment of peritoneal surface malignancy is managed in selected patients by the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The chemotherapy agents utilized are selected from response rates in the treatment of gross disease and from pharmacologic studies. These agents are then subjected to morbidity/mortality studies to establish the safety of the treatment. The aim of this study was to analyze the morbidity and mortality of a new bidirectional hyperthermic and perioperative intraperitoneal chemotherapy regimen used after cytoreductive surgery.Materials and MethodsPatients (n=147) with peritoneal surface malignancy received a uniform treatment of cytoreductive surgery combined with intraoperative chemotherapy. HIPEC with mitomycin C and doxorubicin was supplemented with intravenous 5-fluorouracil and leucovorin. In 65 patients, additional early postoperative intraperitoneal (EPIC) 5-fluorouracil was added to the HIPEC for the first four postoperative days. The clinical factors were cataloged prospectively and any adverse events (AE) were tabulated. ResultsIn 85% of patients, complete cytoreduction was achieved. There was an increase in grade IV AE in patients with incomplete cytoreduction (p<0.04) and in patients receiving fresh frozen plasma (p<0.001). For both grades III and IV AE, a right colon resection increased morbidity (p<0.02) and chemotherapy treatment HIPEC plus EPIC increased morbidity, compared to HIPEC alone (p<0.05). The overall morbidity (grades I-IV) was 64% and mortality was 0.6%.ConclusionThe new bidirectional hyperthermic and perioperative intraperitoneal chemotherapy regimen used after CRS can be safely applied in peritoneal carcinomatosis patients.
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