Toxicity of cockroach gel baits to the oothecal parasitoid Aprostocetus hagenowii (Hymenoptera: Eulophidae) and implications for cockroach integrated pest management.

Aprostocetus hagenowii (Ratzeburg) is a parasitoid wasp that parasitizes the oothecae of peridomestic pest cockroaches. A. hagenowii has been used in integrated pest management (IPM) programs for cockroach control but little is known about how this parasitoid responds to the insecticides commonly used for cockroach management. Five insecticidal gel bait products containing indoxacarb, clothianidin, fipronil, dinotefuran, or abamectin B1 were tested for their toxicity towards A. hagenowii and the American cockroach, Periplaneta americana (L.; Blattodea: Blattidae), a host of A. hagenowii and a common pest. All baits were tested as fresh and 1-d aged deposits. Indoxacarb was the only active ingredient that did not cause significant (P < 0.05) A. hagenowii mortality compared to the control in both the fresh and aged gel experiments (Median survival time [MST]s: 168 h fresh, 72 h aged). Clothianidin caused the lowest A. hagenowii MSTs across experiments (24 h, fresh and aged). All baits caused significant P. americana mortality as fresh and 1-d aged deposits (P < 0.05). Indoxacarb appears most compatible with A. hagenowii in cockroach IPM.

The human Shu complex promotes RAD51 activity by modulating RPA dynamics on ssDNA.

Templated DNA repair that occurs during homologous recombination and replication stress relies on RAD51. RAD51 activity is positively regulated by BRCA2 and the RAD51 paralogs. The Shu complex is a RAD51 paralog-containing complex consisting of SWSAP1 and SWS1. We demonstrate that SWSAP1-SWS1 binds RAD51, maintains RAD51 filament stability, and enables strand exchange. Using single molecule confocal fluorescence microscopy combined with optical tweezers, we show that SWSAP1-SWS1 decorates RAD51 filaments proficient for homologous recombination. We also find SWSAP1-SWS1 enhances RPA diffusion on ssDNA. Importantly, we show human sgSWSAP1 and sgSWS1 knockout cells are sensitive to pharmacological inhibition of PARP and APE1. Lastly, we identify cancer variants in SWSAP1 that alter SWS1 complex formation. Together, we show that SWSAP1-SWS1 stimulates RAD51-dependent high-fidelity repair and may be an important new cancer therapeutic target.

Therapeutic Delivery of Soluble Fractalkine Ameliorates Vascular Dysfunction in the Diabetic Retina.

Diabetic retinopathy (DR)-associated vision loss is a devastating disease affecting the working-age population. Retinal pathology is due to leakage of serum components into retinal tissues, activation of resident phagocytes (microglia), and vascular and neuronal damage. While short-term interventions are available, they do not revert visual function or halt disease progression. The impact of microglial inflammatory responses on the neurovascular unit remains unknown. In this study, we characterized microglia-vascular interactions in an experimental model of DR. Early diabetes presents activated retinal microglia, vascular permeability, and vascular abnormalities coupled with vascular tortuosity and diminished astrocyte and endothelial cell-associated tight-junction (TJ) and gap-junction (GJ) proteins. Microglia exclusively bind to the neuronal-derived chemokine fractalkine (FKN) via the CX3CR1 receptor to ameliorate microglial activation. Using neuron-specific recombinant adeno-associated viruses (rAAVs), we therapeutically overexpressed soluble (sFKN) or membrane-bound (mFKN) FKN using intra-vitreal delivery at the onset of diabetes. This study highlights the neuroprotective role of rAAV-sFKN, reducing microglial activation, vascular tortuosity, fibrin(ogen) deposition, and astrogliosis and supporting the maintenance of the GJ connexin-43 (Cx43) and TJ zonula occludens-1 (ZO-1) molecules. The results also show that microglia-vascular interactions influence the vascular width upon administration of rAAV-sFKN and rAAV-mFKN. Administration of rAAV-sFKN improved visual function without affecting peripheral immune responses. These findings suggest that overexpression of rAAV-sFKN can mitigate vascular abnormalities by promoting glia-neural signaling. sFKN gene therapy is a promising translational approach to reverse vision loss driven by vascular dysfunction.

Changes in inundation drive carbon dioxide and methane fluxes in a temperate wetland.

Wetlands cycle carbon by being net sinks for carbon dioxide (CO2) and net sources of methane (CH4). Daily and seasonal temporal patterns, dissolved oxygen (DO) availability, inundation status (flooded or dry/partially flooded), water depth, and vegetation can affect the magnitude of carbon uptake or emissions, but the extent and interactive effects of these variables on carbon gas fluxes are poorly understood. We characterized the linkages between carbon fluxes and these environmental and temporal drivers at the Old Woman Creek National Estuarine Research Reserve (OWC), OH. We measured diurnal gas flux patterns in an upstream side channel (called the cove) using chamber measurements at six sites (three vegetated and three non-vegetated). We sampled hourly from 7 AM to 7 PM and monthly from July to October 2022. DO concentrations and water levels were measured monthly. Water inundation status had the most influential effect on carbon fluxes with flooded conditions supporting higher CH4 fluxes (0.39 µmol CH4 m-2 s-1; -1.23 µmol CO2 m-2 s-1) and drier conditions supporting higher CO2 fluxes (0.03 µmol CH4 m-2 s-1; 0.86 µmol CO2 m-2 s-1). When flooded, the wetland was a net CO2 sink; however, it became a source for both CH4 and CO2 when water levels were low. We compared chamber-based gas fluxes from the cove in flooded (July) and dry (August) months to fluxes measured with an eddy covariance tower whose footprint covers flooded portions of the wetland. The diurnal pattern of carbon fluxes at the tower did not vary with changing water levels but remained a CO2 sink and a CH4 source even when the cove where we performed the chamber measurements dried out. These results emphasize the role of inundation status on wetland carbon cycling and highlight the importance of fluctuating hydrologic patterns, especially hydrologic drawdowns, under changing climatic conditions.

Discovery of a 53BP1 Small Molecule Antagonist Using a Focused DNA-Encoded Library Screen.

Methyl-lysine reader p53 binding protein 1 (53BP1) is a central mediator of DNA break repair and is associated with various human diseases, including cancer. Thus, high-quality 53BP1 chemical probes can aid in further understanding the role of 53BP1 in genome repair pathways. Herein, we utilized focused DNA-encoded library screening to identify the novel hit compound UNC8531, which binds the 53BP1 tandem Tudor domain (TTD) with an IC50 of 0.47 ± 0.09 µM in a TR-FRET assay and Kd values of 0.85 ± 0.17 and 0.79 ± 0.52 µM in ITC and SPR, respectively. UNC8531 was cocrystallized with the 53BP1 TTD to guide further optimization efforts, leading to UNC9512. NanoBRET and 53BP1-dependent foci formation experiments confirmed cellular target engagement. These results show that UNC9512 is a best-in-class small molecule 53BP1 antagonist that can aid further studies investigating the role of 53BP1 in DNA repair, gene editing, and oncogenesis.

Team science: A syllabus for success on big projects.

Interdisciplinary teams are on the rise as scientists attempt to address complex environmental issues. While the benefits of team science approaches are clear, researchers often struggle with its implementation, particularly for new team members. The challenges of large projects often weigh on the most vulnerable members of a team: trainees, including undergraduate students, graduate students, and post-doctoral researchers. Trainees on big projects have to navigate their role on the team, with learning project policies, procedures, and goals, all while also training in key scientific tasks such as co-authoring papers. To address these challenges, we created and participated in a project-specific, graduate-level team science course. The purposes of this course were to: (1) introduce students to the goals of the project, (2) build trainees' understanding of how big projects operate, and (3) allow trainees to explore how their research interests dovetailed with the overall project. Additionally, trainees received training regarding: (1) diversity, equity & inclusion, (2) giving and receiving feedback, and (3) effective communication. Onboarding through the team science course cultivated psychological safety and a collaborative student community across disciplines and institutions. Thus, we recommend a team science course for onboarding students to big projects to help students establish the skills necessary for collaborative research. Project-based team science classes can benefit student advancement, enhance the productivity of the project, and accelerate the discovery of solutions to ecological issues by building community, establishing a shared project vocabulary, and building a workforce with collaborative skills to better answer ecological research questions.

Polymerase θ inhibition steps on the cGAS pedal.

Deficiencies in homologous recombination (HR) repair lead to an accumulation of DNA damage and can predispose individuals to cancer. Polymerase theta (Pol θ, encoded by POLQ) is overexpressed by HR-deficient cancers and promotes cancer cell survival by mediating error-prone double-stranded break (DSB) repair and facilitating resistance against poly-ADP ribose polymerase inhibitor treatment. In this issue of the JCI, Oh, Wang, et al. report on the impact of Pol θ inhibition on activation of antitumor immunity. The authors used pancreatic ductal adenocarcinoma (PDAC) cell and mouse models characterized by HR-associated gene alterations and POLQ overexpression. POLQ knockdown showed synthetic lethality in combination with gene mutations involving DNA repair, including BRCA1, BRCA2, and ATM. Notably, Pol θ deficiency or inhibition suppressed tumor growth, increased the accumulation of unrepaired DNA damage, and enhanced T cell infiltration via the cGAS/STING pathway. These findings suggest a broader scope for Pol θ inhibition in HR-deficient cancers.

Potential of the oothecal parasitoid Aprostocetus hagenowii (Hymenoptera: Eulophidae) as a biological control agent for the Turkestan cockroach (Blattodea: Blattidae).

The Turkestan cockroach, Blatta lateralis (Walker), is a peridomestic pest of growing concern in the US Southwest. The parasitoid Aprostocetus hagenowii (Ratzburg) is used in IPM programs targeting other blattid cockroach species and may aid in B. lateralis suppression. Information about the ability of A. hagenowii to parasitize B. lateralis is lacking. A no-choice host-switching experiment was used to test A. hagenowii acceptance of B. lateralis oothecae, and a multigenerational no-choice experiment was used to determine the suitability of B. lateralis as a host for A. hagenowii over several months of rearing. Periplaneta americana (L.) (Blattodea: Blattidae), the preferred host of A. hagenowii, and Blatta orientalis L., a known host and relative of B. lateralis, were used for comparison. Development time was similar among hosts and generations (P > 0.05). Parasitism success and proportion of female progeny declined significantly with subsequent generations on both Blatta spp. (parasitism success: χ2 = 14.916; df = 2; P = 0.001; proportion female: H = 6.364; df = 2; P = 0.041). These results suggest that A. hagenowii may initially aid in suppression of B. lateralis, but an overall decline in fitness will require repeated releases or provisioning of P. americana oothecae. Development of a strain more suitable for B. lateralis control may be possible via selection from laboratory strains or through use of wild A. hagenowii from areas where B. lateralis is present.

Water availability and seasonality shape elemental stoichiometry across space and time.

The interaction of climate change and increasing anthropogenic water withdrawals is anticipated to alter surface water availability and the transport of carbon (C), nitrogen (N), and phosphorus (P) in river networks. But how changes to river flow will alter the balance, or stoichiometry, of these fluxes is unknown. The Lower Flint River Basin (LFRB) is part of an interstate watershed relied upon by several million people for diverse ecosystem services, including seasonal crop irrigation, municipal drinking water access, and public recreation. Recently, increased water demand compounded with intensified droughts have caused historically perennial streams in the LFRB to cease flowing, increasing ecosystem vulnerability. Our objectives were to quantify how riverine dissolved C:N:P varies spatially and seasonally and determine how monthly stoichiometric fluxes varied with overall water availability in a major tributary of LFRB. We used a long-term record (21-29 years) of solute water chemistry (dissolved organic carbon, nitrate/nitrite, ammonia, and soluble reactive phosphorus) paired with long-term stream discharge data across six sites within a single LFRB watershed. We found spatial and seasonal differences in soluble nutrient concentrations and stoichiometry attributable to groundwater connections, the presence of a major floodplain wetland, and flow conditions. Further, we showed that water availability, as indicated by the Palmer Drought Severity Index (PDSI), strongly predicted stoichiometry with generally lower C:N and C:P and higher N:P fluxes during periods of low water availability (PDSI < -4). These patterns suggest there may be long-term and significant changes to stream ecosystem function as water availability is being dramatically altered by human demand with consequential impacts on solute transport, in-stream processing, and stoichiometric ratios.

Impact of a 5-Week Individualised Training Program on Physical Performance and Measures Associated with Musculoskeletal Injury Risk in Army Personnel: A Pilot Study.

OBJECTIVE: To examine the feasibility and effect of an individualised and force-plate guided training program on physical performance and musculoskeletal injury risk factors in army personnel. DESIGN: Pre-post, randomised control. METHODS: Fourteen male and five female Australian Army soldiers were randomised into two groups and performed 5-weeks of physical training. The control group (n = 9) completed standard, group-designed, physical training whilst the experimental group (n = 8) completed an individualised training program. Physical (push-ups, multi-stage fitness test, three repetition maximum (3RM) for squat, strict press, deadlift and floor press), occupational (weight-loaded march time), and technological assessments (two-leg and one-leg countermovement jumps (CMJ), one-leg balance, one-arm plank) were conducted prior to and following the training period. Comparisons between groups and changes within groups were conducted via Mann-Whitney U tests. RESULTS: Compared to the control group, the experimental group exhibited a significantly smaller improvement for weight-loaded march time (-0.7% ± 4.0% vs. -5.1% ± 3.0%, p = 0.03) and a greater improvement for deadlift-3RM (20.6% ± 11.9% vs. 8.4% ± 6.8%, p = 0.056). All other outcomes were similar between groups. Visually favourable alterations in the two-leg CMJ profile with no reports of injuries were noted for the experimental group. CONCLUSIONS: Individualised physical training was feasible within an army setting and, for the most part, produced similar physical, occupational and technological performances to that of standard, group-designed physical training. These preliminary results provide a foundation for future research to expand upon and clarify the benefits of individualised training programs on long-term physical performance and injury risk/incidence in active combat army personnel.

Exploring experiences of loneliness among Canadian long-term care residents during the COVID-19 pandemic: A qualitative study.

BACKGROUND: The COVID-19 pandemic has significant impact on long-term care (LTC) residents' health and well-being. OBJECTIVES: This study investigated resident experiences of loneliness during the COVID-19 pandemic in Canadian LTC homes to offer lessons learned and implications. METHODS: 15 residents and 16 staff members were recruited from two large urban Canadian LTC homes with large outbreaks and fatalities. We used a telepresence robot to conduct one-on-one semi-structured interviews with participants remotely. We applied the Collaborative Action Research (CAR) methodology and report the early phase of CAR focused on collecting data and reporting findings to inform actions for change. Thematic analysis was performed to identify themes. RESULTS: Four themes were identified. The first two themes characterise what commonly generated feelings of loneliness amongst residents, including (1) social isolation and missing their family and friends and (2) feeling hopeless and grieving for lives lost. The second two themes describe what helped residents alleviate loneliness, including (3) social support and (4) creating opportunities for recreation and promoting positivity. CONCLUSIONS: Residents living in LTC experienced significant social isolation and grief during the pandemic that resulted in loneliness and other negative health consequences. IMPLICATIONS FOR PRACTICE: Promoting meaningful connection, safe recreational activities and a positive atmosphere in LTC homes during the pandemic may help mitigate residents' experiences of loneliness due to social isolation and/or grief and enhance their quality of life.

Reliability of Force Plate Metrics During Standard Jump, Balance, and Plank Assessments in Military Personnel.

INTRODUCTION: Prevention of musculoskeletal injury is vital to the readiness, performance, and health of military personnel with the use of specialized systems (e.g., force plates) to assess risk and/or physical performance of interest. This study aimed to identify the reliability of one specialized system during standard assessments in military personnel. METHODS: Sixty-two male and ten female Australian Army soldiers performed a two-leg countermovement jump (CMJ), one-leg CMJ, one-leg balance, and one-arm plank assessments using a Sparta Science force plate system across three testing sessions. Sparta Science (e.g., total Sparta, balance and plank scores, jump height, and injury risk) and biomechanical (e.g., average eccentric rate of contraction, average concentric force, and sway velocity) variables were recorded for all sessions. Mean ± SD, intraclass correlation coefficients (ICCs), coefficient of variation, and bias and limits of agreement were calculated for all variables. RESULTS: Mean results were similar between sessions 2 and 3 (P > .05). The relative reliability for the Sparta Science (ICC = 0.28-0.91) and biomechanical variables (ICC = 0.03-0.85) was poor to excellent. The mean absolute reliability (coefficient of variation) for Sparta Science variables was similar to or lower than that of the biomechanical variables during the CMJ (1-10% vs. 3-7%), one-leg balance (4-6% vs. 9-14%), and one-arm plank (5-7% vs. 12-17%) assessments. The mean bias for most variables was small (<5% of the mean), while the limits of agreement varied with most unacceptable (±6-87% of the mean). CONCLUSIONS: The reliability of most Sparta Science and biomechanical variables during standard assessments was moderate to good. The typical variability in metrics documented will assist practitioners with the use of emerging technology to monitor and assess injury risk and/or training interventions in military personnel.

Kudzu Bug (Megacopta cribraria) and Associated Egg Parasitoids Emergence Rates in Alabama are Predicted by Weather Indices.

The kudzu bug, Megacopta cribraria (Fabricius) (Hemiptera: Plataspidae), is a major economic pest of soybean in the southeastern United States. With climate warming, this pest is expected to move northward and cause additional crop damage. Parasitoid biocontrol is a potential method of integrated pest management for kudzu bug. Two species of egg parasitoid wasps have been observed emerging from kudzu bug egg masses in the southeastern United States: Paratelenomus saccharalis (Dodd) (Hymenoptera: Platygastridae) and Ooencyrtus nezarae (Ishii) (Hymenoptera: Encyrtidae). This paper used egg mass emergence data collected between 2018 and 2020 in Alabama soybean fields and compared the data to weather indices. Indices included the number of days with minimum temperatures below zero, accumulated rainfall (mm m-2), as well as species specific metrics of accumulated growing degree days, accumulated daily minimum temperature (°C), and accumulated daily maximum temperature (°C). Emergence of the generalist parasitoid, O. nezarae, was highly correlated with kudzu bug nymph abundance, accumulated degree day, accumulated daily temperatures, and precipitation. Ooencyrtus nezarae emergence was predicted in a stepwise regression equation by aggregated degree day and date of collection, which indicates that seasonality may be a predictor of its presence. In contrast, collections of the specialist parasitoid, P. saccharalis, were near-zero throughout the collection period, suggesting that this species may no longer be a usable biocontrol agent in the southeastern United States as a result of external limiting factors.

Fitness of evolving bacterial populations is contingent on deep and shallow history but only shallow history creates predictable patterns.

Long-term evolution experiments have tested the importance of genetic and environmental factors in influencing evolutionary outcomes. Differences in phylogenetic history, recent adaptation to distinct environments and chance events, all influence the fitness of a population. However, the interplay of these factors on a population's evolutionary potential remains relatively unexplored. We tracked the outcome of 2000 generations of evolution of four natural isolates of Escherichia coli bacteria that were engineered to also create differences in shallow history by adding previously identified mutations selected in a separate long-term experiment. Replicate populations started from each progenitor evolved in four environments. We found that deep and shallow phylogenetic histories both contributed significantly to differences in evolved fitness, though by different amounts in different selection environments. With one exception, chance effects were not significant. Whereas the effect of deep history did not follow any detectable pattern, effects of shallow history followed a pattern of diminishing returns whereby fitter ancestors had smaller fitness increases. These results are consistent with adaptive evolution being contingent on the interaction of several evolutionary forces but demonstrate that the nature of these interactions is not fixed and may not be predictable even when the role of chance is small.

Ventrolateral Prefrontal Cortex Contributes to Human Motor Learning.

This study assesses the involvement in human motor learning, of the ventrolateral prefrontal cortex (BA 9/46v), a somatic region in the middle frontal gyrus. The potential involvement of this cortical area in motor learning is suggested by studies in nonhuman primates which have found anatomic connections between this area and sensorimotor regions in frontal and parietal cortex, and also with basal ganglia output zones. It is likewise suggested by electrophysiological studies which have shown that activity in this region is implicated in somatic sensory memory and is also influenced by reward. We directly tested the hypothesis that area 9/46v is involved in reinforcement-based motor learning in humans. Participants performed reaching movements to a hidden target and received positive feedback when successful. Before the learning task, we applied continuous theta burst stimulation (cTBS) to disrupt activity in 9/46v in the left or right hemisphere. A control group received sham cTBS. The data showed that cTBS to left 9/46v almost entirely eliminated motor learning, whereas learning was not different from sham stimulation when cTBS was applied to the same zone in the right hemisphere. Additional analyses showed that the basic reward-history-dependent pattern of movements was preserved but more variable following left hemisphere stimulation, which suggests an overall deficit in somatic memory for target location or target directed movement rather than reward processing per se. The results indicate that area 9/46v is part of the human motor learning circuit.

Unusual presentation of a small cell lung cancer with bilateral breast metastases: Case report and a brief review of the literature.

Small cell lung cancer (SCLC) is a smoker's disease and occurs almost exclusively in smokers. SCLC is a high-grade neuroendocrine tumor and commonly presents as a central tumor with bulky mediastinal adenopathy. It is notorious for causing widespread disease and paraneoplastic syndromes. The usual sites of metastasis include the liver, brain, bone, and adrenals. SCLC presenting with breast metastasis is unusual; however, there are reports of unilateral and bilateral breast metastases. SCLC with bilateral breast metastases is extremely rare, with only five previously reported cases available in the literature. We are taking this opportunity to report and add to the growing literature on the unusual presentation of a small cell lung cancer with bilateral breast metastases.

Effect of Exercise Training Programs on Physical Fitness Domains in Military Personnel: A Systematic Review and Meta-Analysis.

INTRODUCTION: Physical training is important to prepare soldiers for the intense occupational demands in the military. However, current physical training may not address all fitness domains crucial for optimizing physical readiness and reducing musculoskeletal injury. The effects of nontraditional military physical training on fitness domains have been inconsistently reported, which limits the design of the ideal training program for performance optimization and injury prevention in the military. The aim of this systematic review was to identify the effects of exercise training on various fitness domains (i.e., aerobic fitness, flexibility, muscular endurance, muscular power, muscular strength, and occupationally specific physical performance) that contribute to occupational performance and musculoskeletal injury risk in military personnel. METHODS: An extensive literature search was conducted in January 2021 and was subsequently updated in July 2021 and December 2021. Included studies consisted of comparative groups of healthy military personnel performing traditional and nontraditional military physical training with at least one assessment representative of a fitness domain. Study appraisal was conducted using the PEDro scale. Meta-analysis was conducted via forest plots, standard mean difference (SMD, effect size), and intertrial heterogeneity (I2). RESULTS: From a total of 7,350 records, 15 studies were identified as eligible for inclusion in this review, with a total of 1,613 participants. The average study quality via the PEDro score was good (5.3/10; range 4/10 to 6/10). Nontraditional military physical training resulted in greater posttraining values for muscular endurance (SMD = 0.46; P = .004; I2 = 68%), power (SMD = 1.57; P < .0001; I2 = 90%), strength via repetition maximum testing (SMD = 1.95; P < .00001; I2 = 91%), and occupationally specific physical performance (SMD = 0.54; P = .007; I2 = 66%) compared to the traditional group. There was no significant difference for aerobic fitness (SMD = -0.31; P = .23; I2 = 86%), flexibility (SMD = 0.58; P = .16; I2 = 76%), and muscular strength via maximal voluntary contraction (SMD = 0.18; P = .28; I2 = 66%) between training groups. CONCLUSIONS: The current systematic review identified that nontraditional military physical training had a greater posttraining effect on muscular endurance, power, strength measured via repetition maximum, and occupationally specific physical performance compared to traditional military physical training. Overall, these findings suggest that nontraditional military physical training may be beneficial in optimizing occupational performance while potentially reducing musculoskeletal injury risk.

Upper airway hematoma: An unusual presentation of acute upper airway obstruction.

Acute upper airway obstruction secondary to supraglottic hematoma is a rare but life-threatening complication of oral anticoagulants, particularly with warfarin. Symptoms include sore throat, dysphagia, odynophagia, dysphonia, neck swelling, and dyspnea. We are reporting a case of an elderly male on warfarin therapy who developed acute upper airway obstruction due to spontaneous supraglottic hemorrhage. Commonly reported sites of spontaneous bleeding are the sublingual and retropharyngeal spaces.