Publications by authors named "LATHAM M"

Background: Global progress toward malaria elimination and eradication goals has stagnated in recent years, with many African countries reporting increases in malaria morbidity and mortality. Insecticide-treated nets and indoor residual spraying are effective, but the emergence and increased intensity of insecticide resistance and the challenge of outdoor transmission are undermining their impact. New tools are needed to get back on track towards global targets.

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Cultured pluripotent stem cells are unique in being the only fully diploid immortal human cell lines. However, during continued culture, they acquire significant chromosome abnormalities. Chromosome 12 trisomy is the most common whole-chromosome abnormality found during culture of human induced pluripotent stem cells (iPSCs).

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The RNA recognition motif (RRM) is a conserved and ubiquitous RNA-binding domain that plays essential roles in mRNA splicing, polyadenylation, transport, and stability. RRM domains exhibit remarkable diversity in binding partners, interacting with various sequences of single- and double-stranded RNA, despite their small size and compact fold. During pre-mRNA cleavage and polyadenylation, the RRM domain from CSTF2 recognizes U- or G/U-rich RNA sequences downstream from the cleavage and polyadenylation site to regulate the process.

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  • Biorational larvicides are essential for managing mosquito populations and mosquito-borne diseases, but effective and safe options are scarce, leading to a push for innovative formulations using existing active ingredients.
  • A comparison study between OmniPrene® G and Altosid® Pellets, both containing S-methoprene, showed that while both were effective, OmniPrene G initially outperformed Altosid Pellets at lower doses.
  • Over time, Altosid Pellets began to show better efficacy, particularly at higher doses, but both products demonstrated similar mortality patterns, with the majority of mosquito deaths occurring before they could emerge.
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  • Gerresheimer and Midas Pharma created a new autoinjector design that uses a cartridge kept under constant pressure, and analyzed the primary packaging materials for performance over time.
  • The study involved testing materials from three glass manufacturers and two rubber manufacturers, focusing on how they behave under long-term pressure regarding septum stability, piercing ability, glide and break-loose forces, and the integrity of a marketed antibody drug.
  • Results showed that while the cartridge septum initially bulged, it stabilized after 14 days, and no significant issues such as septum rupture or degradation of the drug were observed, indicating the design is safe and effective even under prolonged pressure.
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Radiofrequency ablation (RFA) is a relatively novel, increasingly popular treatment option for leiomyomas. We studied medical device-related reports of leiomyoma RFA devices to determine whether there are emerging device-related issues. The Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database was queried from 2012 through November 2022.

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Rapid urbanisation in the Asia-Pacific region is associated with complex changes to urban food environments. The impact of changing food environments on food purchasing and consumption and the diets and nutritional status of vulnerable groups, especially women and young children, is not well researched in low- and middle-income country cities. This paper aimed to examine: the risks and opportunities for healthy diets for low income populations offered by modernising urban centres; the concept of food deserts in relation to urban food environments in the Asia-Pacific region and how these could be mitigated; and measures to strengthen the resilience of food environments in the region using a case study of the impact of COVID-19 on informal food vendors.

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  • Charged residues on proteins are essential for stability and binding, but high net-charge regions can destabilize proteins while helping them interact with oppositely charged targets.
  • Researchers studied the folding of a specific yeast protein domain (SH3) and found that increased salt concentrations surprisingly stabilize its structure by mimicking interactions that occur during target binding.
  • The study revealed that while the protein experiences both hydrophobic collapse and electrostatic repulsion during folding, the formation of favorable interactions like salt-bridges and hydrogen bonds allows it to maintain a functional, folded state after overcoming initial challenges.
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  • Charged residues on proteins are crucial for stability and interactions, often creating regions that might destabilize proteins but are necessary for binding to oppositely charged targets.
  • The study found that increasing salt concentrations stabilizes the folding of the yeast SH3 domain by reducing electrostatic repulsion, thanks to effects like Debye-Huckel screening.
  • Experiments revealed that while the addition of urea or salt affects folding rates, the key folding events happen in the transition state, allowing the protein domain to efficiently fold and prepare for binding despite its high charge.
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NMR spectroscopy is an excellent tool for studying protein structure and dynamics which provides a deeper understanding of biological function. As the size of the biomolecule of interest increases, it can become advantageous to dilute the number of observed signals in the NMR spectrum to decrease spectral overlap and increase resolution. One way to limit the number of resonances in the NMR data is by selectively labeling a smaller domain within the larger macromolecule, a process called segmental isotopic labeling.

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Effective mitigation of the impacts of invasive ship rats (Rattus rattus) requires a good understanding of their ecology, but this knowledge is very sparse for urban and peri-urban areas. We radiomarked ship rats in Wellington, New Zealand, to estimate detection parameters (σ, ε, θ, and g) that describe the process of an animal encountering a device (bait stations, chew cards and WaxTags) from a distance, and then approaching it and deciding whether to interact with it. We used this information in simulation models to estimate optimal device spacing for eradicating ship rats from Wellington, and for confirming eradication.

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Autoimmunity develops when extracellular DNA released from dying cells is not cleared from serum. While serum DNA is primarily digested by Dnase1 and Dnase1L3, Dnase1 cannot rescue autoimmunity arising from Dnase1L3 deficiencies. Dnase1L3 uniquely degrades antigenic forms of cell-free DNA, including DNA complexed with lipids and proteins.

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Outdoor biting constitutes a major limitation of current vector control based primarily on long-lasting insecticidal nets and indoor residual spraying, both of which are indoor interventions. Consequently, malaria elimination will not be achieved unless additional tools are found to deal with the residual malaria transmission and the associated vector dynamics. In this study we tested a new vector control approach for rapidly crashing mosquito populations and disrupting malaria transmission in Africa.

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Nascent pre-mRNA 3'-end cleavage and polyadenylation (C/P) involves numerous proteins that recognize multiple RNA elements. Human CSTF2 binds to a downstream U- or G/U-rich sequence through its RNA recognition motif (RRM) regulating C/P. We previously reported the only known disease-related CSTF2 RRM mutant (CSTF2) and showed that it changed the on-rate of RNA binding, leading to alternative polyadenylation in brains of mice carrying the same mutation.

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The Mre11-Rad50-Nbs1 protein complex is one of the first responders to DNA double-strand breaks. Studies have shown that the catalytic activities of the evolutionarily conserved Mre11-Rad50 (MR) core complex depend on an ATP-dependent global conformational change that takes the macromolecule from an open, extended structure in the absence of ATP to a closed, globular structure when ATP is bound. We have previously identified an additional 'partially open' conformation using luminescence resonance energy transfer (LRET) experiments.

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The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a significant demand on healthcare providers (HCPs) to provide respiratory support for patients with moderate to severe symptoms. Continuous Positive Airway Pressure (CPAP) non-invasive ventilation can help patients with moderate symptoms to avoid the need for invasive ventilation in intensive care. However, existing CPAP systems can be complex (and thus expensive) or require high levels of oxygen, limiting their use in resource-stretched environments.

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Aedes aegypti is the predominant vector of dengue, chikungunya, and Zika viruses. This mosquito is difficult to control with conventional methods due to its container-inhabiting behavior and resistance to insecticides. Autodissemination of pyriproxyfen (PPF), a potent larvicide, has shown promise as an additional tool to control Aedes species in small-scale field trials.

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Objective: Determine whether automated changes in electronic screen color temperature of personal electronic devices is associated with changes in objective and self-reported indices of sleep and mental health in young adults, as well as determine feasibility and acceptability of the experimental manipulation.

Participants: A single-blind randomized controlled trial was conducted at a large public university in the Pacific Northwest region of the United States. Fifty-five participants (female=78%, mean age=19.

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The MRE11-RAD50-NBS1 (MRN) protein complex plays a vital role in DNA double strand break sensing, signaling, and repair. Mutation in any component of this complex may lead to disease as disrupting DNA double strand break repair has the potential to cause translocations and loss of genomic information. Here, we have investigated an MRE11 mutation, F237C, identified in a breast cancer tumor.

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Efficient decision-making integrates previous experience with new information. Tactical use of misinformation can alter choice in humans. Whether misinformation affects decision-making in other free-living species, including problem species, is unknown.

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The Mre11-Rad50-Nbs1/Xrs2 protein complex plays a pivotal role in the detection and repair of DNA double strand breaks. Through traditional and emerging structural biology techniques, various functional structural states of this complex have been visualized; however, relatively little is known about the transitions between these states. Indeed, it is these structural transitions that are important for Mre11-Rad50-mediated DNA unwinding at a break and the activation of downstream repair signaling events.

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CSTF2 encodes an RNA-binding protein that is essential for mRNA cleavage and polyadenylation (C/P). No disease-associated mutations have been described for this gene. Here, we report a mutation in the RNA recognition motif (RRM) of CSTF2 that changes an aspartic acid at position 50 to alanine (p.

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The MRE11-RAD50-NBS1 (MRN) protein complex is one of the primary vehicles for repairing DNA double strand breaks and maintaining the genomic stability within the cell. The role of the MRN complex to recognize and process DNA double-strand breaks as well as signal other damage response factors is critical for maintaining proper cellular function. Mutations in any one of the components of the MRN complex that effect function or expression of the repair machinery could be detrimental to the cell and may initiate and/or propagate disease.

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  • The study investigates the assembly of functional amyloids in the epididymal lumen, focusing on a cystatin-rich matrix that aids in sperm maturation and protection.
  • Researchers developed a purification protocol for a mouse protein called CRES, using advanced techniques like X-ray crystallography and NMR to observe its transition from a single protein unit to a complex amyloid structure.
  • Findings reveal that CRES monomers have a distinct structural fold and can assemble through two mechanisms, providing insights into how functional amyloids form and emphasizing their diverse assembly processes.
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