The dual-specificity kinase DYRK1A modulates the levels of cyclin L2 to control HIV replication in macrophages

HIV replication in macrophages contributes to the latent viral reservoirs, which are considered the main barrier to HIV eradication. Few cellular factors that facilitate HIV replication in latently infected cells are known. We previously identified cyclin L2 as a critical factor required by HIV-1 and found that depletion of cyclin L2 attenuates HIV-1 replication in macrophages. Here we demonstrate that cyclin L2 promotes HIV-1 replication through interactions with the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Cyclin L2 and DYRK1A were colocalized in the nucleus and were found together in immunoprecipitation experiments. Knockdown or inhibition of DYRK1A increased HIV-1 replication in macrophages, while depletion of cyclin L2 decreased HIV-1 replication. Furthermore, depletion of DYRK1A increased expression levels of cyclin L2. DYRK1A is a proline-directed kinase that phosphorylates cyclin L2 at serine residues. Mutations of cyclin L2 at serine residues preceding proline significantly stabilized cyclin L2 and increased HIV-1 replication in macrophages. Thus, we propose that DYRK1A controls cyclin L2 expression, leading to restriction of HIV replication in macrophages

Association of interleukin-1 gene cluster polymorphisms and haplotypes with multiple sclerosis in an Iranian population

Multiple sclerosis (MS) is a multi-factorial autoimmune disease of the central nervous system. The exact etiology of MS is still unknown. Due to the important roles that cytokines play as mediators in immune and inflammatory responses, we have evaluated the association of IL-1 gene cluster polymorphisms and haplotypes with MS susceptibility in 306 unrelated MS patients and 312 healthy matched controls. A significant association was found for the IL-1β + 3953 T allele [OR = 1.43, 95% CI (1.14-1.79), P value = 0.002, Pc= 0.01] and for IL-1β + 3953 T/T genotype and MS risk [OR = 1.92, 95% CI (1.25-2.96), P value = 0.005, Pc= 0.01]. Interestingly, the genotypes of the polymorphisms remained significant under recessive, co-recessive and dominant models. However, no significant differences were found between MS patients and controls in the genotype and allele frequencies of the IL-1β - 511, - 31 and IL-1Ra polymorphisms. Haplotype analysis for IL-1β - 31 and IL-1β - 511, with moderate linkage disequilibrium (LD), using the EM algorithm revealed a significant global association of haplotype differences between the two groups. Lower presence of two haplotypes (H3: C-T and H4: T-C) was observed in the MS patients than healthy controls. However, after applying Bonferroni's correction the differences were not significant. To our knowledge, this is the first study reporting the association of the IL-1β + 3953 gene polymorphism and MS susceptibility. © 2015 Elsevier B.V

Empowering students with geospatial solutions through challenge-based learning

Today, the field of Geospatial Solutions primarily focuses on spatial and mapping data, analysis, and technologies that primarily revolve around place and space. It is considered more as a tool or means rather than the ultimate objective of various interdisciplinary activities, where minimal attention is given to theoretical aspects, equations, and underlying principles of the subject. Conversely, despite advancements in science and technology and a broader audience for geospatial subjects, it is predominantly taught conventionally, disregarding the diverse needs and expectations of students. In recent years, there has been an exploration of innovative educational methods to utilize new pedagogical frameworks and enhance academic performance among students. The present study aims to develop a framework and provide guidelines for the integration of Challenge Based Learning into Geomatics education. This framework consists of three interconnected phases: engage, investigate, and act. Subsequently, an educational pilot program is created and implemented to apply the designed framework to key topics such as food security and cultural heritage. Finally, the project refines the educational framework based on real pilot attempts and evaluation results, identifying potential issues and making necessary adjustments. The designed framework and the attained results are made publicly available for reference and utilization.</p

Assessing the impact of employing machine learning-based baseline load prediction pipelines with sliding-window training scheme on offered flexibility estimation for different building categories

The present study is focused on assessing the impact of the performance of baseline load prediction pipelines on the estimation (by the grid operator) accuracy of the flexibility offered by different categories of buildings. Accordingly, the corresponding impact of employing different machine learning (ML) algorithms, with sliding-window and offline training schemes, for hour-ahead baseline load prediction has been investigated and compared. Using a smart meter measurements dataset, training window sizes and the most promising pipeline for each building category are first identified. Next, the consumption profiles of five buildings (belonging to each category), with the regular operation (baseline load) and while offering flexibility, are physically simulated. Finally, the identified pipelines are used for predicting the baseline loads, and the resulting error in estimating the provided flexibility is determined. Obtained results demonstrate that the identified most promising prediction pipeline (extra trees algorithm with a sliding window of 5 weeks) offers a notably superior performance compared to that of offline training (average R2 score of 0.91 vs. 0.87). Employing these pipelines permits estimating the provided flexibility with acceptable accuracy (flexibility index's mean relative error between -2.45% to +2.79%), permitting the grid operator to guarantee fair compensation for buildings' offered flexibility

Enhancement of Kerr nonlinearity via multi-photon coherence

We propose a new method of resonant enhancement of optical Kerr nonlinearity using multi-level atomic coherence. The enhancement is accompanied by suppression of the other linear and nonlinear susceptibility terms of the medium. We show that the effect results in a modification of the nonlinear Faraday rotation of light propagating in an Rb87 vapor cell by changing the ellipticity of the light.Comment: 4 pages, 3 figures Submitted to Optics Letter

Velocity-selective resonance dips in the probe absorption spectra of Rb D2 transitions induced by a pump laser

We report experimental observation of velocity-selective resonances in the Doppler-broadened probe absorption spectra of 85Rb and 87Rb D2 transitions in the presence of a strong copropagating pump laser locked to a frequency within the Doppler profile of the transition. The set of three dips having the separation of allowed hyperfine transitions can be moved along the Doppler profile by tuning the pump laser frequency indicating a resonance between the pump laser frequency and the velocity shifted probe laser frequency.Comment: 7 pages, 4 figure

The Influence of Sex and Season on Conspecific Spatial Overlap in a Large, Actively-Foraging Colubrid Snake

Understanding the factors influencing the degree of spatial overlap among conspecifics is important for understanding multiple ecological processes. Compared to terrestrial carnivores, relatively little is known about the factors influencing conspecific spatial overlap in snakes, although across snake taxa there appears to be substantial variation in conspecific spatial overlap. In this study, we described conspecific spatial overlap of eastern indigo snakes (Drymarchon couperi) in peninsular Florida and examined how conspecific spatial overlap varied by sex and season (breeding season vs. non-breeding season). We calculated multiple indices of spatial overlap using 6- and 3-month utilization distributions (UD) of dyads of simultaneously adjacent telemetered snakes. We also measured conspecific UD density values at each telemetry fix and modeled the distribution of those values as a function of overlap type, sex, and season using generalized Pareto distributions. Home range overlap between males and females was significantly greater than overlap between individuals of the same sex and male home ranges often completely contained female home ranges. Male home ranges overlapped little during both seasons, whereas females had higher levels of overlap during the non-breeding season. The spatial patterns observed in our study are consistent with those seen in many mammalian carnivores, in which low male-male overlap and high inter-sexual overlap provides males with greater access to females. We encourage additional research on the influence of prey availability on conspecific spatial overlap in snakes as well as the behavioral mechanisms responsible for maintaining the low levels of overlap we observed

Incremental impact upon malaria transmission of supplementing pyrethroid-impregnated long-lasting insecticidal nets with indoor residual spraying using pyrethroids or the organophosphate, pirimiphos methyl

Background Long-lasting, insecticidal nets (LLINs) and indoor residual spraying (IRS) are the most widely accepted and applied malaria vector control methods. However, evidence that incremental impact is achieved when they are combined remains limited and inconsistent. Methods Fourteen population clusters of approximately 1000 residents each in Zambia’s Luangwa and Nyimba districts, which had high pre-existing usage rates (81.7 %) of pyrethroid-impregnated LLINs were quasi-randomly assigned to receive IRS with either of two pyrethroids, namely deltamethrin [Wetable granules (WG)] and lambdacyhalothrin [capsule suspension (CS)], with an emulsifiable concentrate (EC) or CS formulation of the organophosphate pirimiphos methyl (PM), or with no supplementary vector control measure. Diagnostic positivity of patients tested for malaria by community health workers in these clusters was surveyed longitudinally over pre- and post-treatment periods spanning 29 months, over which the treatments were allocated and re-allocated in advance of three sequential rainy seasons. Results Supplementation of LLINs with PM CS offered the greatest initial level of protection against malaria in the first 3 months of application (incremental protective efficacy (IPE) [95 % confidence interval (CI)] = 0.63 [CI 0.57, 0.69], P < 0.001), followed by lambdacyhalothrin (IPE [95 % CI] = 0.31 [0.10, 0.47], P = 0.006) and PM EC (IPE, 0.23 [CI 0.15, 0.31], P < 0.001) and then by deltamethrin (IPE [95 % CI] = 0.19 [−0.01, 0.35], P = 0.064). Neither pyrethroid formulation provided protection beyond 3 months after spraying, but the protection provided by both PM formulations persisted undiminished for longer periods: 6 months for CS and 12 months for EC. The CS formulation of PM provided greater protection than the combined pyrethroid IRS formulations throughout its effective life IPE [95 % CI] = 0.79 [0.75, 0.83] over 6 months. The EC formulation of PM provided incremental protection for the first 3 months (IPE [95 % CI] = 0.23 [0.15, 0.31]) that was approximately equivalent to the two pyrethroid formulations (lambdacyhalothrin, IPE [95 % CI] = 0.31 [0.10, 0.47] and deltamethrin, IPE [95 % CI] = 0.19 [−0.01, 0.35]) but the additional protection provided by the former, apparently lasted an entire year. Conclusion Where universal coverage targets for LLIN utilization has been achieved, supplementing LLINs with IRS using pyrethroids may reduce malaria transmission below levels achieved by LLIN use alone, even in settings where pyrethroid resistance occurs in the vector population. However, far greater reduction of transmission can be achieved under such conditions by supplementing LLINs with IRS using non-pyrethroid insecticide classes, such as organophosphates, so this is a viable approach to mitigating and managing pyrethroid resistance