A segmentation clock patterns cellular differentiation in a bacterial biofilm.

Contrary to multicellular organisms that display segmentation during development, communities of unicellular organisms are believed to be devoid of such sophisticated patterning. Unexpectedly, we find that the gene expression underlying the nitrogen stress response of a developing Bacillus subtilis biofilm becomes organized into a ring-like pattern. Mathematical modeling and genetic probing of the underlying circuit indicate that this patterning is generated by a clock and wavefront mechanism, similar to that driving vertebrate somitogenesis. We experimentally validated this hypothesis by showing that predicted nutrient conditions can even lead to multiple concentric rings, resembling segments. We additionally confirmed that this patterning mechanism is driven by cell-autonomous oscillations. Importantly, we show that the clock and wavefront process also spatially patterns sporulation within the biofilm. Together, these findings reveal a biofilm segmentation clock that organizes cellular differentiation in space and time, thereby challenging the paradigm that such patterning mechanisms are exclusive to plant and animal development.

Magnesium Flux Modulates Ribosomes to Increase Bacterial Survival.

Bacteria exhibit cell-to-cell variability in their resilience to stress, for example, following antibiotic exposure. Higher resilience is typically ascribed to "dormant" non-growing cellular states. Here, by measuring membrane potential dynamics of Bacillus subtilis cells, we show that actively growing bacteria can cope with ribosome-targeting antibiotics through an alternative mechanism based on ion flux modulation. Specifically, we observed two types of cellular behavior: growth-defective cells exhibited a mathematically predicted transient increase in membrane potential (hyperpolarization), followed by cell death, whereas growing cells lacked hyperpolarization events and showed elevated survival. Using structural perturbations of the ribosome and proteomic analysis, we uncovered that stress resilience arises from magnesium influx, which prevents hyperpolarization. Thus, ion flux modulation provides a distinct mechanism to cope with ribosomal stress. These results suggest new approaches to increase the effectiveness of ribosome-targeting antibiotics and reveal an intriguing connection between ribosomes and the membrane potential, two fundamental properties of cells.

SnapShot: Electrochemical Communication in Biofilms.

The role of electricity in biological systems was first appreciated through electrical stimulation experiments performed by Luigi Galvani in the 18th century. These pioneering experiments demonstrated that the behavior of living tissues is governed by the flow of electrochemical species-an insight that gave rise to the modern field of electrophysiology. Since then, electrophysiology has largely remained a bastion of neuroscience. However, exciting recent developments have demonstrated that even simple bacteria residing in communities use electrochemical communication to coordinate population-level behaviors. These recent works are defining the emerging field of bacterial biofilm electrophysiology. To view this SnapShot, open or download the PDF.

Chromosomal Arrangement of Phosphorelay Genes Couples Sporulation and DNA Replication.

Genes encoding proteins in a common regulatory network are frequently located close to one another on the chromosome to facilitate co-regulation or couple gene expression to growth rate. Contrasting with these observations, here, we demonstrate a functional role for the arrangement of Bacillus subtilis sporulation network genes on opposite sides of the chromosome. We show that the arrangement of two sporulation network genes, one located close to the origin and the other close to the terminus, leads to a transient gene dosage imbalance during chromosome replication. This imbalance is detected by the sporulation network to produce cell-cycle coordinated pulses of the sporulation master regulator Spo0A∼P. This pulsed response allows cells to decide between sporulation and continued vegetative growth during each cell cycle spent in starvation. The simplicity of this coordination mechanism suggests that it may be widely applicable in a variety of gene regulatory and stress-response settings. VIDEO ABSTRACT.

Natural course of talar avascular necrosis during short-term follow-up and factors associated with Disease progression.

BACKGROUND: This retrospective cohort study aimed to investigate the natural history of talar avascular necrosis (AVN) during short-term outpatient follow-up and to identify the risk factors for progression to collapse and arthritic changes. METHODS: Thirty-four cases of talar AVN from 34 patients (15 males, 19 females) were included. The mean age of the patients was 48.9 years (SD 16.0 years) and the mean follow-up period was 39.5 months (SD 42.0 months). The patients were divided into two groups i.e., progression and non-progression groups. The progression group consisted of those who showed aggravation of the Ficat stage during the follow-up period or advanced arthritis of the ankle joint (Ficat stage 4) at presentation. Demographic data and information regarding BMI, medical comorbidities, trauma history, bilaterality, and location of the lesion (shoulder vs. non-shoulder lesions) were collected. Following the univariate analysis, a binary logistic regression analysis was performed. RESULTS: The location of the talar AVN was the only significant factor (p = 0.047) associated with disease progression. A total of 14.3% (2 of 14) of the central (non-shoulder) talar AVN lesions showed progression, while 50% (10 of 20) of shoulder lesions aggravated during follow-up. Age, sex, bilaterality, medical comorbidities, and trauma history were not associated with progressive talar collapse or subsequent arthritic changes in talar AVN. CONCLUSIONS: Conservative treatment should be considered for a central lesion of the talar AVN because it tends to remain stable without progression. A more comprehensive study with a larger study population is required to establish the surgical indications for talar AVN. LEVEL OF EVIDENCE: Prognostic level III.

Clinical outcomes following tibiotalocalcaneal arthrodesis with intramedullary nailing combined with partial fibulectomy and onlay bone graft.

INTRODUCTION: Although intramedullary nailing is a popular method for tibiotalocalcaneal arthrodesis, nonunion is one of the most commonly reported complications. This study aimed to evaluate the fusion rate, improvement in functional outcomes, and occurrence of complications in tibiotalocalcaneal arthrodesis using retrograde intramedullary nailing with partial fibulectomy and onlay bone graft technique. MATERIALS AND METHODS: Twenty-six consecutive patients using the proposed technique were retrospectively reviewed. For radiographic outcomes, the union rate, alignment, and any related complications were assessed. Functional outcomes were evaluated using the American Orthopedic Foot and Ankle Society hindfoot scale, Foot and Ankle Outcome Score, and visual analog scale, preoperatively and at the final follow-up. RESULTS: The mean follow-up period was 38.2 months. The tibiotalar joint achieved complete union in 80.8% at six months postoperatively, while all the cases achieved complete union at 12 months postoperatively. However, the subtalar joint achieved complete union in 26.9% at six months postoperatively, which gradually increased to 73.1% at 12 months postoperatively, and 80.8% at the final follow-up without revision surgery. A subgroup analysis showed there was a trend of higher subtalar fusion rate when an additional screw for the subtalar joint fixation was placed (86.7% vs. 54.5%). The functional outcomes significantly improved at the final follow-up. A few minor complications occurred, including surgical site infection, irritational symptoms, and metal failure; however, they eventually resolved. CONCLUSIONS: Our technique of tibiotalocalcaneal arthrodesis with partial fibulectomy and onlay bone grafting could be a good option where both the tibiotalar and subtalar joints need to be fused.

Fabrication of InVO4/SnWO4 heterostructured photocatalyst for efficient photocatalytic degradation of tetracycline under visible light.

In the present study, novel InVO4/SnWO4 nanocomposites with different concentrations of SnWO4 were successfully prepared using a facile hydrothermal technique and investigated employing a wide range of analytical methods for efficient photocatalytic degradation of tetracycline (TC). X-ray diffraction analysis showed the presence of the orthorhombic phases of both InVO4 and SnWO4 in the composite catalyst. Dispersion of SnWO4 nanoplates over the InVO4 nanosheets enhanced the synergistic interactions, improving the separation of charge carriers and their transfer. Furthermore, the formation of heterostructure expanded the absorption range and promoted visible light harvesting. The TC degradation efficiency of InVO4/SnWO4 nanocomposite (5 mg loading of SnWO4) reached 97.13% in 80 min under visible light, with the kinetic rate constants 5.51 and 7.63 times greater than those of pure InVO4 and SnWO4, respectively. Additionally, the scavenger results proved that hydroxyl radicals and holes played a significant role in the photodegradation of TC. Furthermore, the electrochemical impedance spectroscopy (EIS) and transient photocurrent response analysis showed enhanced e-/h+ partition efficiency. Thus, the formation of heterostructure with strong synergistic interactions can effectively transfer the excited charge carriers and shorten the reunion rate. Accordingly, the InVO4/SnWO4 nanocomposites exhibited remarkable photocatalytic performance due to the increased number of charge carriers on the surface.

Ankle dorsiflexion assistance of patients with foot drop using a powered ankle-foot orthosis to improve the gait asymmetry.

BACKGROUND: Foot drop is a neuromuscular disorder that causes abnormal gait patterns. This study developed a pneumatically powered ankle-foot orthosis (AFO) to improve the gait patterns of patients with foot drop. We hypothesized that providing unilateral ankle dorsiflexion assistance during the swing phase would improve the kinematics and spatiotemporal gait parameters of such patients. Accordingly, this study aims to examine the efficacy of the proposed assistance system using a strategy for joint kinematics and spatiotemporal gait parameters (stride length, swing velocity, and stance phase ratio). The analysis results are expected to provide knowledge for better design and control of AFOs in patients with foot drop. METHOD: Ten foot drop patients with hemiparesis (54.8 y ± 14.1 y) were fitted with a custom AFO with an adjustable calf brace and portable air compressor for ankle dorsiflexion assistance in the gait cycle during the swing phase. All subjects walked under two different conditions without extensive practice: (1) barefoot and (2) wearing a powered AFO. Under each condition, the patients walked back and forth on a 9-m track with ten laps of level ground under the supervision of licensed physical therapists. The lower-limb joint and trunk kinematics were acquired using 12 motion-capture cameras. RESULTS: We found that kinematic asymmetry decreased in the three lower-limb joints after ankle dorsiflexion assistance during the swing phase. The average ankle-joint angle increased after using the AFO during the entire gait cycle. Similarly, the knee-joint angle showed a slight increase while using the AFO, leading to a significantly decreased standard deviation within patients. Conversely, the hip-joint angle showed no significant improvements with assistance. While several patients exhibited noticeably lower levels of asymmetry, no significant changes were observed in the average asymmetry of the swing velocity difference between the affected and unaffected sides while using the AFO. CONCLUSION: We experimentally validated that ankle dorsiflexion assistance during the swing phase temporarily improves gait asymmetry in foot-drop patients. The experimental results also prove the efficacy of the developed AFO for gait assistance in foot-drop patients.

Computed tomography arthrography versus magnetic resonance imaging for diagnosis of osteochondral lesions of the talus.

INTRODUCTION: Osteochondral lesions of the talus (OLT) usually have non-specific clinical symptoms, and radiographs have a low sensitivity for detecting OLT. The purpose of this study is to compare the diagnostic value of CT arthrography (CTa) with that of MRI using arthroscopy as the reference standard for grading OLT. MATERIALS AND METHODS: We retrospectively reviewed patients who had OLT between 2015 and 2020. Patients with symptomatic OLT as a surgical indication, who were treated arthroscopically, and underwent both CTa and MRI before surgery were included. OLT was evaluated by both CTa and MRI using arthroscopy as the standard. We graded CTa, MRI, arthroscopic findings using Mintz classification. RESULTS: Thirty-five patients were included. Accuracy rates of MRI and CTa for grading OLT, compared to those of arthroscopy, were 57.1% and 88.6%, respectively. Among 15 mismatched cases in MRI, 12 lesions (80%) were matched in CTa and arthroscopy. CTa had significantly higher diagnostic performance than MRI for the detection of grade III lesions (p = 0.041). Using the receiver operating characteristics curves, the area under the curve values for lesion grading were 0.893 for CTa and 0.762 for MRI. CONCLUSION: CTa was statistically significantly better in detecting chondral flapping or subchondral exposure lesions for OLT than MRI on using arthroscopy as the reference standard. Because the stability of the OLT is essential in determining the treatment method, if an OLT is observed on MRI and is suspected to cause ankle pain, we recommend additional CTa examination to determine the more correct treatment strategies for OLT. LEVEL OF EVIDENCE: Diagnostic Level III.

Efficacy of Far Cortical Locking Screws in Treating Distal Tibia Fractures in Comparison With That of Standard Locking Screws.

There are no clinical studies about treatment of distal tibia fractures using far cortical locking (FCL) screws, even though it has been shown to be superior to standard locking screws in biomechanical studies. We compared the efficacy of FCL screws to that of traditional locking screws. Twenty-five distal tibia fractures were treated with minimally invasive plate osteosynthesis using traditional locking screws, whereas 20 were treated using FCL screws. We retrospectively compared time taken for callus formation and radiographic bone union between 2 groups. The effect of age, sex, diabetes, and smoking history on bone healing was analyzed. Complications were also noted. As a result, there was no significant difference in age (p = .292), sex (p = 1.0), diabetes (p = 1.0), or smoking history (p = .704) between 2 groups. Time to callus formation was 77.5 days in the FCL group, and 96 days in the traditional group (p = .023). Average time to bone union was 134.8 days, and 163.1 days in the FCL group and the traditional group, respectively (p = .017). There was one case of screw loosening in the FCL group, and one case of screw breakage in the traditional group. This study suggests that FCL screws promote quicker healing of distal tibia fractures than traditional locking screws.

Preoperative incongruent subtalar joint predicts less favorable clinical outcome in total ankle arthroplasty.

BACKGROUND: This study aimed to determine the clinical effect of incongruent subtalar joint space on total ankle arthroplasty (TAA). METHODS: Thirty-four consecutive patients who underwent TAA were grouped according to the status of subtalar joint incongruency. A comparison of clinical and radiographic parameters between groups as well as multiple regression analysis was performed to identify contributing factors to the final functional outcome. RESULTS: The final American Orthopaedic Foot and Ankle Society (AOFAS) score was significantly higher in the congruent group compared to that of the incongruent group (p = 0.007). There were no significant differences between the two groups in measured radiographic angles. In multiple regression analysis, the female sex (p = 0.006) and incongruency of the subtalar joint (p = 0.013) were found to be significant contributing factors to the final AOFAS score. CONCLUSIONS: A thorough preoperative investigation should be taken into the state of the subtalar joint for TAA.

Chemoresistive Sensor Readout Circuit Design for Detecting Gases with Slow Response Time Characteristics.

Based on an analysis of the signal characteristics of gas sensors, this work presents a chemoresistive sensor readout circuit design for detecting gases with slow response time characteristics. The proposed readout circuit directly generates a reference voltage corresponding to the initial value of the gas sensor and extracts only the amount of gas concentration change in the sensor. Because the proposed readout circuit can adaptively regenerate the suitable reference voltage under various changing ambient conditions, it can alleviate the variation in output values at the same gas concentration caused by non-uniformities among gas sensors. Furthermore, this readout circuit effectively eliminates the initial value shifts due to the poor reproducibility of the gas sensor itself without requiring complex digital signal calibrations. This work focuses on a commercially viable readout circuit structure that can effectively obtain slow response gas information without requiring a large capacitor. The proposed readout circuit operation was verified by simulations using spectre in cadence simulation software. It was then implemented on a printed circuit board with discrete components to confirm the effectiveness with existing gas sensor systems and its commercial viability.

Engineering chloroplast development in rice through cell-specific control of endogenous genetic circuits.

The engineering of C4 photosynthetic activity into the C3 plant rice has the potential to nearly double rice yields. To engineer a two-cell photosynthetic system in rice, the rice bundle sheath (BS) must be rewired to enhance photosynthetic capacity. Here, we show that BS chloroplast biogenesis is enhanced when the transcriptional activator, Oryza sativa Cytokinin GATA transcription factor 1 (OsCGA1), is driven by a vascular specific promoter. Ectopic expression of OsCGA1 resulted in increased BS chloroplast planar area and increased expression of photosynthesis-associated nuclear genes (PhANG), required for the biogenesis of photosynthetically active chloroplasts in BS cells of rice. A further refinement using a DNAse dead Cas9 (dCas9) activation module driven by the same cell-type specific promoter, directed enhanced chloroplast development of the BS cells when gRNA sequences were delivered by the dCas9 module to the promoter of the endogenous OsCGA1 gene. Single gRNA expression was sufficient to mediate the transactivation of both the endogenous gene and a transgenic GUS reporter fused with OsCGA1 promoter. Our results illustrate the potential for tissue-specific dCas9-activation and the co-regulation of genes needed for multistep engineering of C4 rice.

Lactobacillus rhamnosus HDB1258 modulates gut microbiota-mediated immune response in mice with or without lipopolysaccharide-induced systemic inflammation.

BACKGROUND: Gut microbiota closely communicate in the immune system to maintain a balanced immune homeostasis in the gastrointestinal tract of the host. Oral administration of probiotics modulates gut microbiota composition. In the present study, we isolated Lactobacillus rhamnosus HDB1258, which induced tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression in macrophages, from the feces of breastfeeding infants and examined how HDB1258 could regulate the homeostatic immune response in mice with or without lipopolysaccharide (LPS)-induced systemic inflammation. RESULTS: Oral administration of HDB1258 significantly increased splenic NK cell cytotoxicity, peritoneal macrophage phagocytosis, splenic and colonic TNF-α expression, TNF-α to IL-10 expression ratio, and fecal IgA level in control mice, while Th1 and Treg cell differentiation was not affected in the spleen. However, HDB1258 treatment significantly suppressed peritoneal macrophage phagocytosis and blood prostaglandin E2 level in mice with LPS-induced systemic inflammation. Its treatment increased LPS-suppressed ratios of Treg to Th1 cell population, Foxp3 to T-bet expression, and IL-10 to TNF-α expression. Oral administration of HDB1258 significantly decreased LPS-induced colon shortening, myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon, while the ratio of IL-10 to TNF-α expression increased. Moreover, HDB1258 treatment shifted gut microbiota composition in mice with and without LPS-induced systemic inflammation: it increased the Cyanobacteria and PAC000664_g (belonging to Bacteroidetes) populations and reduced Deferribacteres and EU622763_s group (belonging to Bacteroidetes) populations. In particular, PAC001066_g and PAC001072_s populations were negatively correlated with the ratio of IL-10 to TNF-α expression in the colon, while the PAC001070_s group population was positively correlated. CONCLUSIONS: Oral administered HDB1258 may enhance the immune response by activating innate immunity including to macrophage phagocytosis and NK cell cytotoxicity in the healthy host and suppress systemic inflammation in the host with inflammation by the modulation of gut microbiota and IL-10 to TNF-α expression ratio in immune cells.

Calcifying characteristics of peripheral vascular smooth muscle cells of chronic kidney disease patients with critical limb ischemia.

The role of vascular smooth muscle cells (VSMCs) in vascular calcification, which is related to chronic kidney disease (CKD), has been studied in greater detail in the major arteries relative to the peripheral arteries. We compared the calcifying characteristics of peripheral VSMCs relative to non-pathologic major VSMCs in patients with severe peripheral artery disease (PAD). We isolated peripheral VSMCs from the posterior tibial artery of 10 patients with CKD who underwent below-knee amputation for critical limb ischemia (CLI). Using normal human aortic VSMCs as a control group, we cultured the cells in normal and high phosphate media for 10 days, and subsequently tested by immunofluorescence staining. We compared the calcification levels between the two groups using various assays, tests for cell viability, and scanning electron microscopy. As a result, calcification of pathologic peripheral VSMCs increased significantly with time (p = 0.028) and was significantly higher than that in human aortic VSMCs in calcium assays (p = 0.043). Dead cells in the pathologic VSMC group were more distinct in high phosphate media than in human aortic VSMCs. In conclusion, VSMCs from the peripheral artery of patients with severe CKD and CLI who underwent amputation surgery showed marked calcifying characteristics compared to normal human aortic VSMCs.

Metabolic co-dependence gives rise to collective oscillations within biofilms.

Cells that reside within a community can cooperate and also compete with each other for resources. It remains unclear how these opposing interactions are resolved at the population level. Here we investigate such an internal conflict within a microbial (Bacillus subtilis) biofilm community: cells in the biofilm periphery not only protect interior cells from external attack but also starve them through nutrient consumption. We discover that this conflict between protection and starvation is resolved through emergence of long-range metabolic co-dependence between peripheral and interior cells. As a result, biofilm growth halts periodically, increasing nutrient availability for the sheltered interior cells. We show that this collective oscillation in biofilm growth benefits the community in the event of a chemical attack. These findings indicate that oscillations support population-level conflict resolution by coordinating competing metabolic demands in space and time, suggesting new strategies to control biofilm growth.

Development of breast phantoms using a 3D printer and glandular dose evaluation.

In this study, breast phantoms were fabricated by emulating glandular and adipose tissues separately using a three-dimensional (3D) printer. In addition, direct and quantitative glandular dose evaluations were performed. A quantitative method was developed to evaluate the glandular and adipose tissues separately when performing glandular dose evaluations. The variables used for glandular dose evaluation were breast thickness, glandular tissue ratio, and additional filter materials. The values obtained using a Monte Carlo simulation and those measured using a glass dosimeter were compared and analyzed. The analysis showed that as the glandular tissue ratio increased, the dose decreased by approximately 10%, which is not a significant variation. The comparison revealed that the simulated values of the glandular dose were approximately 15% higher than the measured values. The use of silver and rhodium filters resulted in a mean simulated dose of 1.00 mGy and 0.72 mGy, respectively, while the corresponding mean measured values were 0.89 mGy ± 0.03 mGy and 0.62 mGy ± 0.02 mGy. The mean glandular dose can be reliably evaluated by comparing the simulated and measured values.

Caffeic Acid Phenethyl Ester-Incorporated Radio-Sensitive Nanoparticles of Phenylboronic Acid Pinacol Ester-Conjugated Hyaluronic Acid for Application in Radioprotection.

We synthesized phenylboronic acid pinacol ester (PBPE)-conjugated hyaluronic acid (HA) via thiobis(ethylamine) (TbEA) linkage (abbreviated as HAsPBPE conjugates) to fabricate the radiosensitive delivery of caffeic acid phenetyl ester (CAPE) and for application in radioprotection. PBPE was primarily conjugated with TbEA and then PBPE-TbEA conjugates were conjugated again with hyaluronic acid using carbodiimide chemistry. CAPE-incorporated nanoparticles of HAsPBPE were fabricated by the nanoprecipitation method and then the organic solvent was removed by dialysis. CAPE-incorporated HAsPBPE nanoparticles have a small particle size of about 80 or 100 nm and they have a spherical shape. When CAPE-incorporated HAsPBPE nanoparticles were irradiated, nanoparticles became swelled or disintegrated and their morphologies were changed. Furthermore, the CAPE release rate from HAsPBPE nanoparticles were increased according to the radiation dose, indicating that CAPE-incorporated HAsPBPE nanoparticles have radio-sensitivity. CAPE and CAPE-incorporated HAsPBPE nanoparticles appropriately prevented radiation-induced cell death and suppressed intracellular accumulation of reactive oxygen species (ROS). CAPE and CAPE-incorporated HAsPBPE nanoparticles efficiently improved survivability of mice from radiation-induced death and reduced apoptotic cell death. We suggest that HAsPBPE nanoparticles are promising candidates for the radio-sensitive delivery of CAPE.

Relationship between calf muscle cross-sectional area and ankle fracture.

BACKGROUND: Whether calf muscles and peroneal muscles have a role in the occurrence of an ankle fractures remains unclear. This study aimed to quantify the calf muscle mass and peroneal muscle mass in patients with an ankle fracture and in controls, then to analyze them together with demographic factors to identify the effects of the regional muscles on the risk of developing ankle fracture. METHODS: A total of 101 ankles with computed tomography (CT) images were retrospectively reviewed. Of them, 51 ankles showed fractures (all unilateral) and 50 ankles, in controls who underwent CT for screening the other diseases, were clinically diagnosed with simple contusion. The cross-sectional areas (CSA) of the calf muscles and the peroneal muscles were measured at approximately 6 cm above the Achilles myotendinous junction in the axial plane of ankle CT. These parameters were compared between the two groups and analyzed with respect to age, sex, body mass index (BMI), laterality, and bone attenuations of the ankle. RESULTS: The demographic factors, including bone attenuation of the ankle showed no significant association with ankle fracture. The ratio of the CSA of the peroneal muscle group to the CSA of the entire calf muscle group was smaller in patients with an fracture (0.12 ± 0.03) than in controls (0.14 ± 0.02) (p = 0.027). The odds ratio for the effect of the calf muscle CSA on the risk of developing ankle fractures was 1.38 (95% confidence interval 1.12-1.69, p = 0.003), whereas that for the effect of peroneal muscle CSA on the risk of developing ankle fractures was 0.18 (95% confidence interval 0.05 to 0.66, p = 0.010). CONCLUSION: The ratio of the peroneal muscle CSA to the entire calf muscle CSA was negatively related to the occurrence of ankle fractures in this study. Further prospective studies on whether peroneal muscle-strengthening exercise are effective in preventing ankle fractures may be needed. LEVEL OF EVIDENCE: III, case-control study.

Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function.

Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures.