Biology subjects

Devlin, J.

Publications and source records attributed to Devlin, J..

6 recordsLinked to original sources

bioRxiv2026

Subtype-specific differences in susceptibility to monoclonal antibodies and vaccines among contemporary RSV-A and RSV-B isolates

Respiratory syncytial virus (RSV) continues to circulate at high levels despite the introduction of new monoclonal antibodies (mAbs) and vaccines targeting the prefusion F (pre-F) protein. We analyzed the viral genome sequences of 133 RSV clinical samples collected during the 2022-2023 and 2023-2024 seasons, and selected representative isolates for phenotypic testing. We selected four RSV A and four RSV B replication-competent, sequence-verified stocks that were assessed for replication kinetics in vitro and neutralization sensitivity by a panel of F-targeting mAbs and polyclonal sera using a rabbit vaccination model. Isolates retained sensitivity to all mAbs tested. We detected no mutations in mAb binding sites in the isolates tested. RSV-A isolates were slightly less susceptible to multiple mAbs than RSV-B isolates. Antigenic cartography revealed a separation of antibody responses by subtype: RSV-A isolates clustered together and aligned with lower neutralization by antibodies such as MPE8 and 101F, whereas RSV-B isolates formed a distinct cluster associated with higher mAb susceptibility. In a rabbit vaccination model, RSV-A-only sera efficiently neutralized all RSV-A isolates and the RSV-B1 reference strain but showed diminished activity against contemporary RSV-B isolates. RSV-B-only sera displayed balanced neutralization across both subtypes. Combined RSV-A+B immunization produced uniformly strong responses to all isolates, suggesting that multivalent exposure may overcome subtype-specific antibody polarization. Collectively, our results demonstrate consistent antigenic divergence of RSV subtypes and underscore the importance of considering genetic and phenotypic divergence for F-directed immunoprophylaxis. ImportanceRSV remains a major cause of lower respiratory tract infections. Although new mAbs and vaccines have been approved in recent years, the impact of circulating genetic diversity on these therapeutics is incompletely understood. In this study, we demonstrate how recent RSV isolates respond to a panel of mAbs and whether sera from rabbits vaccinated with mRNA vaccines effectively neutralize these isolates. We reveal that RSV-A isolates are more resistant to neutralization by mAbs than RSV-B isolates, and the bivalent vaccine elicits broader neutralizing responses than the monovalent vaccine. This study provides insights into how viral diversity may influence antibody-mediated protection and suggests that recent RSV-B isolates may respond differently from the laboratory-adapted strains commonly used in research.

microbiology↗

bioRxiv2025

BeeSAM2: detecting bees in cherry flowers using timelapse images and foundational models

Bees perform important pollination services in fruit crops such as cherry. Growers will often bring in bees to supplement natural pollinators. Monitoring the performance of these pollinators is important to understand the impact of augmenting pollinators on fruit yield particularly in relation to June drop which is a major cause of yield instability in the cherry industry. Timelapse imaging plus automated image analysis methods is a valuable tool in studying the role of bee pollination in fruit set. Timelapse cameras allow for continuous monitoring of the flowers, but manual analysis of the generated footage is very time consuming. We have developed a novel method of detecting bees in time lapse images, called BeeSAM2. This exploits both the zero shot detector Grounding Dino and the foundational model Segment Anything 2. Promising results are achieved with the method able to detect the bumblebee Bombus terrestris in images with a recall of 0.959 and precision of 0.991. These results are accurate enough to deploy our method to quantify bee activity in cherry plantations, advancing the ability of researchers to monitor bee interactions with flowers with a significant time saving over manual analysis of timelapse footage.

ecology↗

bioRxiv2024

Onset of Mismatch Repair by the Human Mismatch Repair Protein, MutSbeta for a Biosensing Device

Deficiency of MutSbeta protein has been proven to be a cause of Lynch Syndrome, which leads to hereditary colorectal cancer. In the absence of MutSbeta, or the energy source to initiate the conformational change of MutSbeta, the DNA repair pathway would not detect the DNA base pairing errors resulting in a failure to proceed. To examine the essential role of MutSbeta and the interface between MutSbeta and a mismatched DNA strand, 500ns of molecular dynamics simulations were performed and the results were compared with the controls. It is found that during the first 100ns, the outermost domain of MutSbeta (chain BP4) gets hold of the DNA, and the inner domains (AP1 and BP1) prepare to scan the DNA strand. An RMSD of 5-7[A] for the control MutSbeta compared to 3-6.5[A] in the presence of a mismatched DNA indicate that starting [~]75ns, MutSbeta stabilizes and initiates the scanning of the mismatched DNA. The reduction of the distance between the two biomolecules by [~]16[A], increase of Van der Waals energies by [~]75 kCal/mol and a crucial role played by the interfacial water molecules and their hydrogen bonds during the next 100ns also supports the manipulative nature and initiation of scanning by MutSbeta. Author SummaryAbout 1 and 23 men and 1 and 26 women have the chances of developing colorectal cancer and the chances only increase with old age. Cancer typically develops from mutated DNA, which emphasizes the importance of understanding how proteins a part of the DNA repair pathway process interact with a mutated strand of DNA. One such protein, MutSbeta, is the first protein that initiates the repair pathway process and scans DNA for any mutations. As the initiator, a deficiency of MutSbeta leads to higher chances of mutated DNA going undetected, and therefore forming cancerous cells. Using 3D simulations, we analyzed the interactions between MutSbeta and a mutated DNA strand. We found that the two outer domains, AP4 and BP4 grab hold of the DNA strand while the inner clamps, AP1 and BP1 scan the DNA strand. It was also discovered that Van der Waals play a more dominant role compared to electrostatics in terms of the driving force behind the interactions between DNA and MutSbeta. Overall, our data supported the attractive nature of MutSbeta towards DNA and its stability as it initiates the scanning process. Furthermore, this data was used to verify the presence of MutSbeta for a biosensor that was built previously; owing to the significance and applicatory effects of this work.

biophysics↗

bioRxiv2022

Gut Microbiome of Helminth Infected Indigenous Malaysians Is Context Dependent

While microbiomes in industrialized societies are well characterized, indigenous populations with traditional lifestyles have microbiomes that are more akin to those of ancient humans. However, metagenomic data in these populations remains scarce and the association with soil-transmitted helminth infection status is unclear. Here, we sequenced 650 metagenomes of indigenous Malaysians from 5 villages with different prevalence of helminth infections. Individuals from villages with higher prevalence of helminth infections have more unmapped reads and greater microbial diversity. Microbial community diversity and composition were most strongly associated with different villages and the effects of helminth infection status on the microbiome varies by village. Longitudinal changes in the microbiome in response to albendazole anthelmintic treatment was observed in both helminth infected and uninfected individuals. Inference of bacterial population replication rates from origin of replication analysis identified specific replicating taxa associated with helminth infection. Our results indicated that helminth effects on the microbiota was highly dependent on context and effects of albendazole on the microbiota can be confounding for the interpretation of deworming studies. Furthermore, a substantial quantity of the microbiome remains undescribed and this large dataset from indigenous populations associated with helminth infections should facilitate characterization of the disappearing microbiome from developed industrialized societies.

microbiology↗

bioRxiv2019

Transcranial magnetic stimulation during British Sign Language production reveals monitoring of discrete linguistic units in left superior parietal lobule

Successful human hand and arm movements are typically carried out by combining visual, motoric, and proprioceptive information in planning, initiation, prediction, and control. The superior parietal lobule (SPL) has been argued to play a key role in integrating visual and motoric information particularly during grasping of objects and other such tasks which prioritise visual information. However, sign language production also engages SPL even though fluent signers do not visually track their hands or fixate on target locations. Does sign language production simply rely on the motoric/ proprioceptive processes engaged in visually guided action, or do the unique characteristics of signed languages change these processes? Fifteen fluent British Sign Language users named pictures while we administered transcranial magnetic stimulation (TMS) to left SPL, a control site, or no TMS. TMS to SPL had very specific effects: an increased rate of (sign-based) phonological substitution errors for complex two-handed signs (those requiring hand contact), but TMS did not slow or otherwise impair performance. Thus, TMS decreased the likelihood of detecting or correcting phonological errors during otherwise successful bimanual coordination, but it did not noticeably alter fine movement control. These findings confirm that for fluent signers SPL has adapted to monitor motor plans for discrete hand configurations retrieved from memory as well as more fine-grained aspects of visually guided actions.

neuroscience↗

bioRxiv2017

Variation in the microbiome of the urogenital tract of koalas (Phascolarctos cinereus) with and without "wet bottom"

Koalas (Phascolarctos cinereus) are iconic Australian marsupials currently threatened by several processes. Infectious reproductive tract disease, caused by Chlamydia pecorum, and koala retrovirus infection are considered key drivers of population decline. The clinical sign of wet bottom, a staining of the rump associated with urinary incontinence, is often caused by chlamydial urogenital tract infections. However, wet bottom has been recorded in koalas free of C. pecorum, suggesting other causative agents in those individuals. Current understanding of the bacterial community of the koala urogenital tract is limited. We used 16S rRNA diversity profiling to investigate the microbiome of the urogenital tract of ten female koalas. This was to produce baseline data on the female koala urogenital tract microbiome, and to undertake preliminary investigations of potential causative agents of wet bottom, other than C. pecorum. Five urogenital samples were processed from koalas presenting with wet bottom and five were clinically normal. We detected thirteen phyla across the ten samples, with Firmicutes occurring at the highest relative abundance (77.6%). The order Lactobacillales, within the Firmicutes, comprised 70.3% of the reads from all samples. After normalising reads using DESeq2 and testing for significant differences (P < 0.05), there were 25 operational taxonomic units (OTUs) more commonly found in one group over the other. The families Aerococcaceae and Tissierellaceae both had four significantly differentially abundant OTUs. These four Tissierellaceae OTUs were all significantly more abundant in koalas with wet bottom.\n\nImportanceThis study provides an essential foundation for future investigations of both the normal microflora of the koala urogenital tract, and better understanding of the causes of koala urogenital tract disease. Koalas in the states of Queensland and New South Wales are currently undergoing decline, and have been classified as vulnerable populations. Urogenital tract disease is a leading cause of hospital admissions in these states, yet previously little was known of the normal flora of this site. Wet bottom is a clinical sign of urogenital tract disease, which is often assumed to be caused by C. pecorum and treated accordingly. Our research highlights that other organisms may be causing wet bottom, and these potential aetiological agents need to be further investigated to fully address the problems this species faces.

microbiology↗