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Emch, M.

Publications and source records attributed to Emch, M..

4 recordsLinked to original sources

Crop-specific agricultural land use and Rift Valley fever outbreaks in Uganda: a longitudinal compositional analysis

Rift Valley fever (RVF) is a mosquito-borne disease that can cause severe illness and death in both humans and livestock. Since 2016, Uganda has experienced recurrent but localized RVF outbreaks concentrated in the countrys southwestern region. The ecological drivers of this emergence remain unclear, as outbreaks have occurred throughout the year and show little association with meteorological patterns. We evaluated whether crop cultivation, particularly banana cultivation, is associated with RVF outbreak occurrence after controlling for likely confounders. We conducted a longitudinal study of human-inhabited 5 x 5 km grid cells across southwestern Uganda from 2016-2024. Annual Sentinel-2 satellite imagery composites were used to classify land cover into banana, coffee, ground crops, and non-crop categories, and the proportion of each land type was calculated for every grid-cell year. Because land cover proportions are compositional, isometric log-ratio transformations were used to estimate the independent effects of each land type. Confounding was addressed through propensity weighting, and crop substitution effects were estimated using g-computation. Banana land cover was the only land type consistently associated with increased RVF outbreak likelihood. In grid-cell years with low baseline banana cover, a 10-percentage point substitution from other land classes into banana was associated with a 1.64-fold increase in the odds of an RVF outbreak (95% CI: 1.17-2.29). In a simplified banana-only model, each 10-percentage point increase in banana cover was associated with a 1.21-fold increase in outbreak odds (95% CI: 1.02-1.43). Holding banana cover constant, substitutions among coffee, ground crop, and non-crop land showed weak or null associations. These findings suggest that banana cultivation may be an important ecological feature influencing RVF transmission dynamics and outbreak risk in southwestern Uganda. Author SummaryRift Valley fever (RVF) is a mosquito-borne disease that affects both humans and livestock and has caused repeated outbreaks in southwestern Uganda since 2016. While rainfall and flooding are often linked to RVF outbreaks elsewhere, Ugandas recent outbreaks have occurred across seasons and are not well explained by weather patterns alone. We investigated whether agricultural land use could help explain where outbreaks occur. Using satellite imagery from 2016-2024, we measured the amount of banana cultivation, coffee cultivation, ground crops, and non-crop land across southwestern Uganda and evaluated their association with RVF outbreak occurrence. We found that areas with greater banana cultivation were consistently more likely to experience RVF outbreaks, even after accounting for environmental and demographic factors. In contrast, coffee, ground crops, and non-crop land showed little evidence of an independent association with outbreak risk. These findings suggest that banana cultivation may create ecological conditions that favor RVF transmission. Rather than indicating that bananas themselves cause disease, the results point to banana-growing landscapes as potential environments where interactions among mosquitoes, livestock, and humans may increase transmission opportunities. Understanding these local ecological drivers could help improve surveillance, risk assessment, and prevention strategies for RVF in Uganda and other endemic regions.

ecology↗

Malaria entomological surveillance in Kinshasa Province: A longitudinal study

BackgroundMalaria remains a major public health challenge in the Democratic Republic of Congo. To address the lack of contemporary entomological data, particularly in Kinshasa Province, this four-year study characterized key entomological parameters, including mosquito species composition, abundance, biting behavior, and insecticide resistance. MethodsWe conducted a prospective observational cohort study (2018-2022) in three health areas representing rural, peri-urban, and urban settings in Kinshasa Province. Adult Anopheles mosquitoes were sampled using CDC miniature light traps and pyrethrum spray catches. Insecticide susceptibility of adult females was assessed using WHO tube tests, and a generalized estimating equations model evaluated the effects of year, season, site, sampling location, and collection time on mosquito abundance. ResultsA total of 1,449 Anopheles mosquitoes were collected: 50% in the rural health area of Bu, 49% in peri-urban Kimpoko, and 1% in urban La Voix du Peuple. The species captured were An. gambiae s.l. (85%), An. paludis (11%), and An. funestus (4%). An. gambiae s.l. was significantly more abundant indoors and after 10 PM. The overall entomological inoculation rate (EIR) was 4.6 infective bites per person per year, with An. gambiae s.l. contributing the highest rate. An. paludis showed a localized transmission peak in Impuru during the rainy season (EIR = 8.87). Resistance to DDT and pyrethroids was widespread, with an estimated 0.94 frequency of the kdr L1014F mutation. Bendiocarb and pirimiphos-methyl remained effective. ConclusionsThis study confirms that An. gambiae s.l. remains the predominant malaria vector and plays a central role in transmission in Kinshasa. However, an emerging role of An. paludis in rural settings was observed. These findings underscore the need for vector control strategies tailored to diverse ecological settings. Continued entomological surveillance will be essential to track biting behavior and resistance patterns and ensure that interventions remain effective over time. Author summaryMalaria remains a major health problem in the Democratic Republic of the Congo, but very little recent information is available about the mosquitoes that spread the disease, especially in Kinshasa Province. To help fill this gap, we spent four years studying mosquitoes in rural, peri-urban, and urban communities. We focused on how many mosquitoes were present, which species they were, when and where they bite, and whether they were resistant to the insecticides commonly used in malaria control. We found that most mosquitoes belonged to Anopheles gambiae, the main malaria-transmitting species in Africa. These mosquitoes mostly bit indoors and late at night, when bed nets can offer good protection. However, we also observed mosquitoes biting earlier in the evening and outside, which may reduce the impact of bed nets. Another species, Anopheles paludis, played an important role in malaria transmission in some rural areas, showing that different environments can shape which mosquitoes spread the disease. We also found that many mosquitoes were resistant to widely used insecticides, although some alternative insecticides were still effective. Our findings show why it is important to monitor mosquito behavior and insecticide resistance regularly and to adapt malaria prevention strategies to local conditions.

ecology↗

Unbiased CRISPR Synthetic Lethal Screening for Genetic Vulnerabilities in Succinate Dehydrogenase (SDH)-loss Model of Paraganglioma

Succinate dehydrogenase (SDH)-deficient paraganglioma and pheochromocytoma (PPGL) are rare neuroendocrine tumors for which no effective targeted therapies currently exist. To uncover new potential therapeutic targets, we performed an unbiased CRISPR-Cas9 genetic screen in immortalized mouse chromaffin cells (imCCs) with and without Sdhb loss. Our screen identified genes that differentially affect cell proliferation in Sdhb-deficient versus normal imCCs. Notably, several subunits of the transcriptional Mediator complex emerged as potential tumor suppressors, as their loss selectively promoted growth of Sdhb-deficient cells. Most strikingly, we found that the neddylation pathway--required for ubiquitin-mediated selective protein degradation--plays a critical role in controlling cell growth and survival in Sdhb-deficient imCCs. Specifically, loss of the neddylation regulator Ube2m led to increased proliferation, while loss of Ube2f suppressed growth of Sdhb-deficient imCCs. Consequently, global neddylation inhibitor MLN4924 (Pevonedistat) and UBE2F-CRL5 axis inhibitor HA-9104 were shown to downregulate neddylation, suppressing UBE2F activity and selectively inhibiting growth of Sdhb-deficient imCCs. This unexpected result highlights the neddylation pathway as a promising druggable vulnerability in this cell culture model of SDH-deficient PPGL.

biochemistry↗

RanGTP induces an effector gradient of XCTK2 and importin α/β for spindle microtubule cross-linking

High RanGTP around chromatin is important for governing spindle assembly during meiosis and mitosis by releasing the inhibitory effects of importin /{beta}. Here we examine how the Ran gradient regulates Kinesin-14 function to control spindle organization. We show that Xenopus Kinesin-14, XCTK2, and importin /{beta} form an effector gradient, which is highest at the poles that diminishes toward the chromatin and is inverse of the RanGTP gradient. Importin /{beta} preferentially inhibit XCTK2 anti-parallel microtubule cross-linking and sliding by decreasing the microtubule affinity of the XCTK2 tail domain. This change in microtubule affinity enables RanGTP to target endogenous XCTK2 to the spindle. We propose that these combined actions of the Ran pathway are critical to promote Kinesin-14 parallel microtubule cross-linking at the spindle poles to cluster centrosomes in cancer cells. Furthermore, our work illustrates that RanGTP regulation in the spindle is not simply a switch, but rather generates effector gradients where RanGTP gradually tunes the activities of spindle assembly factors.\n\nSummaryEms-McClung et al. visualize a RanGTP effector gradient of association between XCTK2 and importin /{beta} in the spindle. The importins preferentially inhibit XCTK2-mediate anti-parallel microtubule cross-linking and sliding, which allows XCTK2 to cross-link parallel microtubules and help focus spindle poles.

cell biology↗