| 1. |
- Block, Keith I., et al.
(författare)
-
Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
-
Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
-
Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
|
|
| 2. |
|
|
| 3. |
- Vanegas, Hernan, et al.
(författare)
-
Zika RNA and Flavivirus-Like Antigens in the Sperm Cells of Symptomatic and Asymptomatic Subjects
- 2021
-
Ingår i: Viruses. - : MDPI. - 1999-4915. ; 13:2
-
Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) RNA has been found to remain in human semen for up to one year after infection, but the presence of Flavivirus antigens in the different compartments of semen has been largely unexplored. Following the introduction of ZIKV in Nicaragua (2016), a prospective study of patients with clinical symptoms consistent with ZIKV was conducted in Leon to investigate virus shedding in different fluids. ZIKV infection was confirmed in 16 male subjects (>= 18 years of age) by RT-qPCR in either blood, saliva or urine. Of these, three provided semen samples at 7, 14, 21, 28, 60 and 180 days postsymptom onset (DPSO) for Flavivirus antigens and RNA studies. These cases were compared with 19 asymptomatic controls. Flavivirus antigens were examined by immunofluorescence (IF) using the 4G2 Mabs, and confocal microscopy was used to explore fluorescence patterns. The three (100%) symptomatic subjects and 3 (16%) of the 19 asymptomatic subjects had Flavivirus antigens and viral RNA in the spermatozoa fraction. The percentage of IF Flavivirus-positive spermatozoa cells ranged from 1.9% to 25% in specimens from symptomatic subjects, as compared with 0.8% to 3.8% in specimens from asymptomatic controls. A marked IF-pattern in the cytoplasmic droplets and tail of the spermatozoa was observed. The sperm concentrations (45 x 10(6)/mL vs. 63.5 x 10(6)/mL, p = 0.041) and the total motility percentage (54% vs. 75%, p = 0.009) were significantly lower in specimens from ZIKV-positive than in those of ZIKV-negative. In conclusion, this study demonstrated the presence of Flavivirus antigens and RNA within a time frame of 28 DPSO in sperm cells of symptomatic and asymptomatic subjects during the ZIKV epidemic. These findings have implications for public health, in terms of nonarthropod-born, silent transmission facilitated by sperm cells and potential transmission from asymptomatic males to pregnant women, with consequences to the fetus.
|
|
| 4. |
- Bowman, Natalie M., et al.
(författare)
-
Clinical and Epidemiological Features of Acute Zika Virus Infections in Leon, Nicaragua
- 2021
-
Ingår i: American Journal of Tropical Medicine and Hygiene. - : AMER SOC TROP MED & HYGIENE. - 0002-9637 .- 1476-1645. ; 105:4, s. 924-930
-
Tidskriftsartikel (refereegranskat)abstract
- The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in Leon, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory datamay help clinicians suspect ZIKV infection during future outbreaks.
|
|
| 5. |
- Collins, Matthew D., et al.
(författare)
-
Arsenicicoccus bolidensis gen. nov., sp nov., a novel actinomycete isolated from contaminated lake sediment
- 2004
-
Ingår i: INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 54, s. 605-608
-
Tidskriftsartikel (refereegranskat)abstract
- An unknown Gram-positive, catalase-positive, facultatively anaerobic, non-spore-forming, coccus-shaped bacterium originating from sediment was characterized using phenotypic, molecular chemical and molecular phylogenetic methods. Chemical studies revealed the presence of a cell-wall murein based on ll-diaminopimelic acid (type ll-Dpm-glycine1), a complex mixture of saturated, monounsaturated and iso- and anteiso-methyl-branched, non-hydroxylated, long-chain cellular fatty acids and tetrahydrogenated menaquinones with eight isoprene units [MK-8(H4)] as the major respiratory lipoquinone. This combination of characteristics somewhat resembled members of the suborder Micrococcineae, but did not correspond to any currently described species. Comparative 16S rRNA gene sequencing confirmed that the unidentified coccus-shaped organism is a member of the Actinobacteria and represents a hitherto-unknown subline related to, albeit different from, a number of taxa including Intrasporangium, Janibacter, Terrabacter, Terracoccus and Ornithinicoccus. Based on phenotypic and phylogenetic considerations, it is proposed that the unknown bacterium originating from lake sediment be classified as a new genus and species, Arsenicicoccus bolidensis gen. nov., sp. nov. (type strain CCUG 47306T=DSM 15745T).
|
|
| 6. |
- Lakens, Daniel, et al.
(författare)
-
Justify your alpha
- 2018
-
Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
-
Tidskriftsartikel (refereegranskat)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
|
|
| 7. |
- Palmer, Elizabeth E., et al.
(författare)
-
Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition
- 2023
-
Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 28:2, s. 668-697
-
Tidskriftsartikel (refereegranskat)abstract
- Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.
|
|
| 8. |
- Routh, Joyanto, 1968-, et al.
(författare)
-
Arsenicicoccus bolidensis a novel arsenic reducing actinomycete in contaminated sediments near the Adak mine (northern Sweden): Impact on water chemistry
- 2007
-
Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 379:2-3, s. 216-225
-
Tidskriftsartikel (refereegranskat)abstract
- Weathering of mine tailings in Adak results in high As concentrations in surface and ground water, sediments, and soil. In spite of the oxic conditions, As-rich surface and ground water samples indicate As(III) species predominantly (up to 83%). Several microorganisms were isolated from the enrichment cultures that were involved in As cycling. Amongst them was Arsenicicoccus bolidensis — a novel gram-positive, facultatively anaerobic, coccus-shaped actinomycete, which actively reduced As(V) to As(III) in aqueous media. A. bolidensis reduced 0.06–0.20 mM day− 1 As(V). As(V) reduction displays a direct correlation between the initial As(V) concentration, growth rate, and biomass yield.
|
|
