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31.
Good knowledge on the interactions between climatic variables and malaria can be very useful for predicting outbreaks and preparedness interventions. We investigated clinical malaria transmission patterns and its temporal relationship with climatic variables in Tubu village, Botswana. A 5-year retrospective time series data analysis was conducted to determine the transmission patterns of clinical malaria cases at Tubu Health Post and its relationship with rainfall, flood discharge, flood extent, mean minimum, maximum and average temperatures. Data was obtained from clinical records and respective institutions for the period July 2005 to June 2010, presented graphically and analysed using the Univariate ANOVA and Pearson cross-correlation coefficient tests. Peak malaria season occurred between October and May with the highest cumulative incidence of clinical malaria cases being recorded in February. Most of the cases were individuals aged >5 years. Associations between the incidence of clinical malaria cases and several factors were strong at lag periods of 1 month; rainfall (r = 0.417), mean minimum temperature (r = 0.537), mean average temperature (r = 0.493); and at lag period of 6 months for flood extent (r = 0.467) and zero month for flood discharge (r = 0.497). The effect of mean maximum temperature was strongest at 2-month lag period (r = 0.328). Although malaria transmission patterns varied from year to year the trends were similar to those observed in sub-Saharan Africa. Age group >5 years experienced the greatest burden of clinical malaria probably due to the effects of the national malaria elimination programme. Rainfall, flood discharge and extent, mean minimum and mean average temperatures showed some correlation with the incidence of clinical malaria cases. 相似文献
32.
Tumor suppressor Tsc1 is a new Hsp90 co‐chaperone that facilitates folding of kinase and non‐kinase clients
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Elijah Marris Diana M Dunn Adam R Blanden Ryan L Murphy Nicholas Rensing Oleg Shapiro Barry Panaretou Chrisostomos Prodromou Stewart N Loh David H Gutmann Dimitra Bourboulia Gennady Bratslavsky Michael Wong Mehdi Mollapour 《The EMBO journal》2017,36(24):3650-3665
The tumor suppressors Tsc1 and Tsc2 form the tuberous sclerosis complex (TSC), a regulator of mTOR activity. Tsc1 stabilizes Tsc2; however, the precise mechanism involved remains elusive. The molecular chaperone heat‐shock protein 90 (Hsp90) is an essential component of the cellular homeostatic machinery in eukaryotes. Here, we show that Tsc1 is a new co‐chaperone for Hsp90 that inhibits its ATPase activity. The C‐terminal domain of Tsc1 (998–1,164 aa) forms a homodimer and binds to both protomers of the Hsp90 middle domain. This ensures inhibition of both subunits of the Hsp90 dimer and prevents the activating co‐chaperone Aha1 from binding the middle domain of Hsp90. Conversely, phosphorylation of Aha1‐Y223 increases its affinity for Hsp90 and displaces Tsc1, thereby providing a mechanism for equilibrium between binding of these two co‐chaperones to Hsp90. Our findings establish an active role for Tsc1 as a facilitator of Hsp90‐mediated folding of kinase and non‐kinase clients—including Tsc2—thereby preventing their ubiquitination and proteasomal degradation. 相似文献
33.
Suppression of proliferative defects associated with processing-defective lamin A mutants by hTERT or inactivation of p53 总被引:1,自引:0,他引:1
Kudlow BA Stanfel MN Burtner CR Johnston ED Kennedy BK 《Molecular biology of the cell》2008,19(12):5238-5248
Hutchinson-Gilford progeria syndrome (HGPS) is a rare, debilitating disease with early mortality and rapid onset of aging-associated pathologies. It is linked to mutations in LMNA, which encodes A-type nuclear lamins. The most frequent HGPS-associated LMNA mutation results in a protein, termed progerin, with an internal 50 amino acid deletion and, unlike normal A-type lamins, stable farnesylation. The cellular consequences of progerin expression underlying the HGPS phenotype remain poorly understood. Here, we stably expressed lamin A mutants, including progerin, in otherwise identical primary human fibroblasts to compare the effects of different mutants on nuclear morphology and cell proliferation. We find that expression of progerin leads to inhibition of proliferation in a high percentage of cells and slightly premature senescence in the population. Expression of a stably farnesylated mutant of lamin A phenocopied the immediate proliferative defects but did not result in premature senescence. Either p53 inhibition or, more surprisingly, expression of the catalytic subunit of telomerase (hTERT) suppressed the early proliferative defects associated with progerin expression. These findings lead us to propose that progerin may interfere with telomere structure or metabolism in a manner suppressible by increased telomerase levels and possibly link mechanisms leading to progeroid phenotypes to those of cell immortalization. 相似文献
34.
Ceratium fusus (Ehrenb.) Dujardin was exposed to light of different wavelengths and photon flux densities (PFDs) to examine their effects on mechanically stimulable bioluminescence (MSL). Photoinhibition of MSL was proportional to the logarithm of PFD. Exposure to I μmol photons·m?2s?1 of broadband blue light (ca. 400–500 nm) produced near-complete photoinhibition (≥90% reduction in MSL) with a threshold at ca. 0.01 μmol photons·m?2·s?1. The threshold of photoinhibition was ca. an order of magnitude greater for both broadband green (ca. 500–580 nm) and red light (ca. 660–700 nm). Exposure to narrow spectral bands (ca. 10 nm half bandwidth) from 400 and 700 nm at a PFD of 0.1 μmol photons·m?2·s?1 produced a maximal response of photoinhibition in the blue wavelengths (peak ca. 490 nm). A photoinhibition response (≥ 10%) in the green (ca. 500–540 nm) and red wavelengths (ca. 680 nm) occurred only at higher PFDs (1 and 10 μmol photons·m?2·s?1). The spectral response is similar to that reported for Gonyaulax polyedra Stein and Pyrocystis lunula Schütt and unlike that of Alexandrium tamarense (Lebour) Balech et Tangen. The dinoflagellate's own bioluminescence is two orders of magnitude too low to result in self-photoinhibition. The quantitative relationships developed in the laboratory predict photoinhibition of bioluminescence in populations of C. fusus in the North Atlantic Ocean. 相似文献
35.
36.
Katherine R. Amato Rodolfo Martinez-Mota Nicoletta Righini Melissa Raguet-Schofield Fabiana Paola Corcione Elisabetta Marini Greg Humphrey Grant Gogul James Gaffney Elijah Lovelace LaShanda Williams Albert Luong Maria Gloria Dominguez-Bello Rebecca M. Stumpf Bryan White Karen E. Nelson Rob Knight Steven R. Leigh 《Oecologia》2016,180(3):717-733
37.
We have examined aspects of the bioluminescence of 5 clones of Dissodinium, 1 clone of Pyrocystis acuta, 4 clones of Pyrocystis fusiformis, and 5 clones of Pyrocystis noctiluca. All clones produced the same color bioluminescence with an intensity peak near 474 nm. The in vivo emission spectra of these clones agreed with those previously determined, for 4 other species of marine dinoflagellates. The amount of light emitted by the dinoflagellates in scotophase when mechanically stimulated to exhaustion was determined for most of the clones. The largest species, P. noctiluca and P. fusiformis, emitted 37–89 × 109 photons cell?1 and 23–62 × 109 photons cell?1, respectively, about a thousand, times as much light as Gonyaulax species. Pyrocystis acuta emitted 3–6 × 109 photons cell?1. Three of the 5 clones of Dissodinium were bioluminescent. The range for 3 clones was 5–13 × 109 photons cell?1. All 5 clones of Dissodinium are morphologically distinct. Both the clones of Dissodinium and Pyrocystis produced much higher numbers of photons per cell nitrogen (ca. 7–50 times) than Gonyaulax polyedra or Pyrodinium bahamense. The data suggested that enzyme turnover occurred in the reactions producing light during mechanical stimulation of Dissodinium and Pyrocystis species. 相似文献
38.
Elijah Swift 《Journal of phycology》1973,9(4):456-460
Living cells of the diatom Ethmodiscus rex (Rat-Iray) Wiseman & Hendey 1953 were found in the plankton of the southern Sargasso Sea. Apparently, this is the first report, of E rex from the plankton of the Atlantic Ocean. Scanning electron microscopy of peroxide-cleaned frustules revealed, some new morphological features for this species. When viewed, from inside the frustule, the puncta appear as rimmed pits. From outside the frustule, they appear to he shallow depressions with a small opening at the bottom. The so-called mucous tubules in the center of the valve were seen from the out side to be elongate slits and from the inside as obliquely directed flattened cylinders which cap the tubes. 相似文献
39.
Nathan Beutler Tossapol Pholcharee David Oyen Yevel Flores-Garcia Randall S. MacGill Elijah Garcia Jaeson Calla Mara Parren Linlin Yang Wayne Volkmuth Emily Locke Jason A. Regules Sheetij Dutta Daniel Emerling Angela M. Early Daniel E. Neafsey Elizabeth A. Winzeler C. Richter King Fidel Zavala Dennis R. Burton Ian A. Wilson Thomas F. Rogers 《PLoS pathogens》2022,18(3)
Potent and durable vaccine responses will be required for control of malaria caused by Plasmodium falciparum (Pf). RTS,S/AS01 is the first, and to date, the only vaccine that has demonstrated significant reduction of clinical and severe malaria in endemic cohorts in Phase 3 trials. Although the vaccine is protective, efficacy declines over time with kinetics paralleling the decline in antibody responses to the Pf circumsporozoite protein (PfCSP). Although most attention has focused on antibodies to repeat motifs on PfCSP, antibodies to other regions may play a role in protection. Here, we expressed and characterized seven monoclonal antibodies to the C-terminal domain of CSP (ctCSP) from volunteers immunized with RTS,S/AS01. Competition and crystal structure studies indicated that the antibodies target two different sites on opposite faces of ctCSP. One site contains a polymorphic region (denoted α-ctCSP) and has been previously characterized, whereas the second is a previously undescribed site on the conserved β-sheet face of the ctCSP (denoted β-ctCSP). Antibodies to the β-ctCSP site exhibited broad reactivity with a diverse panel of ctCSP peptides whose sequences were derived from field isolates of P. falciparum whereas antibodies to the α-ctCSP site showed very limited cross reactivity. Importantly, an antibody to the β-site demonstrated inhibition activity against malaria infection in a murine model. This study identifies a previously unidentified conserved epitope on CSP that could be targeted by prophylactic antibodies and exploited in structure-based vaccine design. 相似文献
40.
Photoinhibition of mechanically stimulable bioluminescence (MSL) in the heterotrophic dinoflagellate Protoperidinium depressum Bailey was investigated using samples collected from the Massachusetts and southern Texas coasts. The times for both photoinhibition of MSL (ca. 10 min) and dark recovery from photoinhibition of MSL (ca. 45 min) in this species were similar to those reported for autotrophic dinoflagellates. The degree of photoinhibition of MSL was a linear function of the logarithm of photon flux density (PFD). The threshold PFDs for the photoinhibition of MSL were 0.02, 0.6, and 21 μmol photons · m?2· s?1 for broad-band blue, green, and red light, respectively. These PFDs are lower than those required for photoinhibition of MSL by the autotrophic dinoflagellates Pyrocystis lunula and Ceratium fusus. We speculate that photosynthetic pigments in autotrophic dinoflagellates shield the photoreceptor that causes photoinhibition of MSL, thus lowering the sensitivity of these dinoflagellates to light. When field-collected P. depressum were kept in the laboratory without growth for a week, photoinhibition of MSL's sensitivity to light increased progressively along with 1) a decrease in its bioluminescence capacity (BCAP), 2) a decrease in the ratio of MSL to BCAP (MSL/BCAP), and 3) a decrease in the orange pigmentation (probably carotenoid) of the dinoflagellate. The action spectrum for photoinhibition of MSL in P. depressum was characterized primarily with a broad peak in the blue extending into the green. We suggest that carotenoid was not a photoreceptor for the photoinhibition of MSL in P. depressum because the peak of the action spectrum was too broad and extended too far into the green part of the spectrum, and because the orange pigment present decreased as photoinhibition of MSL became more sensitive to light. 相似文献