The risk analysis index demonstrates exceptional discrimination in predicting frailty's impact on neurosurgical length of stay quality metrics.

BACKGROUND: Quality measures determine reimbursement rates and penalties in value-based payment models. Frailty impacts these quality metrics across surgical specialties. We compared the discriminatory thresholds for the risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for the outcomes of extended length of stay (LOS [eLOS]), prolonged LOS within 30 days (pLOS), and protracted LOS (LOS > 30). METHODS: Patients ≥18 years old who underwent neurosurgical procedures between 2012 and 2020 were queried from the ACS-NSQIP. We performed receiver operating characteristic analysis, and multivariable analyses to examine discriminatory thresholds and identify independent associations. RESULTS: There were 411,605 patients included, with a median age of 59 years (IQR, 48-69), 52.2% male patients, and a white majority 75.2%. For eLOS: RAI C-statistic 0.653 (95% CI: 0.652-0.655), versus mFI-5 C-statistic 0.552 (95% CI: 0.550-0.554) and increasing patient age C-statistic 0.573 (95% CI: 0.571-0.575). Similar trends were observed for pLOS- RAI: 0.718, mFI-5: 0.568, increasing patient age: 0.559, and for LOS>30- RAI: 0.714, mFI-5: 0.548, and increasing patient age: 0.506. Patients with major complications had eLOS 10.1%, pLOS 26.5%, and LOS >30 45.5%. RAI showed a larger effect for all three outcomes, and major complications in multivariable analyses. CONCLUSION: Increasing frailty was associated with three key quality metrics that is, eLOS, pLOS, LOS > 30 after neurosurgical procedures. The RAI demonstrated a higher discriminating threshold compared to both mFI-5 and increasing patient age. Preoperative frailty screening may improve quality metrics through risk mitigation strategies and better preoperative communication with patients and their families.

Pet collars containing tetrachlorvinphos (TCVP): evaluation of the results of torsion and on-animal release studies and implications for post-application consumer exposure and risk analysis.

Tetrachlorvinphos (TCVP) is the pesticidal active ingredient found in some flea and tick collars for dogs and cats. Recent studies sponsored by The Hartz Mountain Corporation, confirm the safety of TCVP as an active ingredient in pet collars. Based upon data from these new studies and results previously relied upon by the U.S. Environmental Protection Agency, the following conclusions have been made: Torsion study data clearly indicate that approximately 93% of released formulation from TCVP containing pet collars is in a liquid phase immediately following activation.Further, even more relevant to human health risk analysis associated with post-application exposures, in vivo data from dogs wearing TCVP pet collars definitively document that TCVP dust released from the collar is rapidly absorbed into the sebum. The maximum ratio of dust to liquid was 0.023% dust to 99.977% liquid.In vivo fur data provide scientific evidence confirming that the mechanism of dissemination of TCVP from pet collars is as a liquid suspended or dissolved in the animal's sebum, even though it may be released from the collar as a solid. Thus, potential post-application exposure to TCVP, including immediately following collar placement, is almost entirely to a liquid phase.Based upon EPA's refined and conservative "untrimmed" collar risk assessment, post-application incidental oral hand-to-mouth activity by children aged 1 to <2 years of age results in margins of exposure significantly greater than the level of concern of 1000, and therefore do not present unreasonable health risk.

Leg Press and Chest Press Power Normative Values by Half Decade in Older Women.

ABSTRACT: Parrino, RL, Martinez, KJ, Konlian, JA, Conti, JM, and Signorile, JF. Leg press and chest press power normative values by half decade in older women. J Strength Cond Res 38(5): 991-998, 2024-Neuromuscular power is essential for the performance of most activities of daily living and the maintenance of functional independence throughout the aging process. Power declines rapidly in later life; however, this decline may be reduced or delayed with early detection and intervention. Therefore, this study provides leg press and chest press power normative values for older women. Women's power data for this analysis included 229 participants, 60-90 years of age. Power testing was conducted on Keiser A420 pneumatic leg press and chest press machines following a standardized protocol. Data were stratified into half-decade age groups and analyzed using a 1-way ANOVA. Descriptive statistics and quartile rankings are reported, and significant differences between age groups are outlined. There were significant differences in absolute and relative leg press peak power between the age groups ( p < 0.05). However, there were no significant differences in absolute or relative chest press peak power between the age groups. This research established normative values and quartile rankings for leg press and chest press power in older women 60-90 years of age, allowing comparative evaluations with patients and subjects by clinicians and researchers, respectively. These values should improve exercise interventions designed to improve power production by providing assessments of subjects' current status and allowing comprehensive monitoring of progress.

Assembly and architecture of Escherichia coli divisome proteins FtsA and FtsZ.

During Escherichia coli cell division, an intracellular complex of cell division proteins known as the Z-ring assembles at midcell during early division and serves as the site of constriction. While the predominant protein in the Z-ring is the widely conserved tubulin homolog FtsZ, the actin homolog FtsA tethers the Z-ring scaffold to the cytoplasmic membrane by binding to FtsZ. While FtsZ is known to function as a dynamic, polymerized GTPase, the assembly state of its partner, FtsA, and the role of ATP are still unclear. We report that a substitution mutation in the FtsA ATP-binding site impairs ATP hydrolysis, phospholipid vesicle remodeling in vitro, and Z-ring assembly in vivo. We demonstrate by transmission electron microscopy and Förster Resonance Energy Transfer that a truncated FtsA variant, FtsA(ΔMTS) lacking a C-terminal membrane targeting sequence, self assembles into ATP-dependent filaments. These filaments coassemble with FtsZ polymers but are destabilized by unassembled FtsZ. These findings suggest a model wherein ATP binding drives FtsA polymerization and membrane remodeling at the lipid surface, and FtsA polymerization is coregulated with FtsZ polymerization. We conclude that the coordinated assembly of FtsZ and FtsA polymers may serve as a key checkpoint in division that triggers cell wall synthesis and division progression.

Estimated Dermal Penetration of Tetrachlorvinphos (TCVP) in Humans Based on In Silico Modeling and In Vitro and In Vivo Data.

Tetrachlorvinphos (TCVP) is the pesticidal active ingredient in some collars for dogs and cats. The objective of this study was to provide a refined estimate of dermal penetration of TCVP in humans using in silico predictions as well as in vitro and in vivo data. The in vivo dermal absorption of TCVP was previously studied in the rat and shown to be saturable, ranging from 21.7% (10 µg/cm2) down to 3% (1000 µg/cm2) Subsequent in silico predictions were conducted for rats and humans to provide initial evaluations of species and dose-dependent differences in dermal absorption. A definitive comparison of TCVP systemic exposure in rat and human following dermal application was then conducted via a standard in vitro assay. TCVP dose levels of 10, 100, or 1000 µg/cm2 were applied to excised rat and human skin mounted in flow-through diffusion cells. The vehicle was 1% hydroxypropylmethylcellulose (HPMC) in water. An additional 5 µg/cm2 dose was applied to excised human skin only. The in vitro dermal absorption of TCVP was also assessed from artificial sebum at dose levels of 5, 10, or 100 µg/cm2 applied to human skin only. Utilizing the so-called triple pack approach with in vitro and in vivo rat data and in vitro human data, dermal absorption for TCVP was calculated for humans. In silico modeling indicated absorption of TCVP through human skin might be 3- to 4- fold lower than rat skin at all application levels, with a maximum dermal absorption of 9.6% at the lowest exposure of 10 µg/cm2, down to 0.1% at 1000 µg/cm2. Similar species differences were also found in the definitive in vitro absorption assays. Modeling overestimated TCVP human dermal absorption (9.6%) as compared to excised human skin results (1.7%) for the HPMC vehicle at the lowest exposure (10 µg/cm2), with better agreement at the higher exposures. Conversely, modeling accurately predicted rat dermal absorption (27.9%) as compared to in vivo rat results (21.7%) at the lowest exposure in HPMC, with diminished agreement at the higher exposures. As a first approximation, in silico estimates of dermal absorption are useful; however, these tend to be more variable than in vitro or in vivo measurements. TCVP dermal penetration measured in vitro was lower in 1% HPMC vehicle as compared to artificial sebum. For the 1% HPMC vehicle, in vitro rat dermal absorption was similar to data obtained for in vivo rats, giving confidence in the triple pack approach. In consideration of the triple pack approach, estimated human dermal absorption from 1% HPMC was ≤2%. Based upon excised human skin determinations directly, estimated human dermal absorption of TCVP from artificial sebum was ≤7%.

Degradation of MinD oscillator complexes by Escherichia coli ClpXP.

MinD is a cell division ATPase in Escherichia coli that oscillates from pole to pole and regulates the spatial position of the cell division machinery. Together with MinC and MinE, the Min system restricts assembly of the FtsZ-ring to midcell, oscillating between the opposite ends of the cell and preventing FtsZ-ring misassembly at the poles. Here, we show that the ATP-dependent bacterial proteasome complex ClpXP degrades MinD in reconstituted degradation reactions in vitro and in vivo through direct recognition of the MinD N-terminal region. MinD degradation is enhanced during stationary phase, suggesting that ClpXP regulates levels of MinD in cells that are not actively dividing. ClpXP is a major regulator of growth phase-dependent proteins, and these results suggest that MinD levels are also controlled during stationary phase. In vitro, MinC and MinD are known to coassemble into linear polymers; therefore, we monitored copolymers assembled in vitro after incubation with ClpXP and observed that ClpXP promotes rapid MinCD copolymer destabilization and direct MinD degradation by ClpXP. The N terminus of MinD, including residue Arg 3, which is near the ATP-binding site in sequence, is critical for degradation by ClpXP. Together, these results demonstrate that ClpXP degradation modifies conformational assemblies of MinD in vitro and depresses Min function in vivo during periods of reduced proliferation.

The differential actions of clozapine and other antipsychotic drugs on the translocation of dopamine D2 receptors to the cell surface.

Most clinically available antipsychotic drugs (APDs) bind dopamine D2 receptors (D2R) at therapeutic concentrations, and it is thought that they suppress psychotic symptoms by serving as competitive antagonists of dopamine at D2R. Here, we present data that demonstrate that APDs act independently of dopamine at an intracellular pool of D2R to enhance transport of D2R to the cell surface and suggest that APDs can act as pharmacological chaperones at D2R. Among the first- and second-generation APDs that we tested, clozapine exhibited the lowest efficacy for translocating D2R to the cell surface. Thus, our observations could provide a cellular explanation for some of the distinct therapeutic characteristics of clozapine in schizophrenia. They also suggest that differential intracellular actions of APDs at their common G protein-coupled receptor (GPCR) target, D2R, could contribute to differences in their clinical profiles.

MinC N- and C-Domain Interactions Modulate FtsZ Assembly, Division Site Selection, and MinD-Dependent Oscillation in Escherichia coli.

The Min system in Escherichia coli, consisting of MinC, MinD, and MinE proteins, regulates division site selection by preventing assembly of the FtsZ-ring (Z-ring) and exhibits polar oscillation in vivo MinC antagonizes FtsZ polymerization, and in vivo, the cellular location of MinC is controlled by a direct association with MinD at the membrane. To further understand the interactions of MinC with FtsZ and MinD, we performed a mutagenesis screen to identify substitutions in minC that are associated with defects in cell division. We identified amino acids in both the N- and C-domains of MinC that are important for direct interactions with FtsZ and MinD in vitro, as well as mutations that modify the observed in vivo oscillation of green fluorescent protein (GFP)-MinC. Our results indicate that there are two distinct surface-exposed sites on MinC that are important for direct interactions with FtsZ, one at a cleft on the surface of the N-domain and a second on the C-domain that is adjacent to the MinD interaction site. Mutation of either of these sites leads to slower oscillation of GFP-MinC in vivo, although the MinC mutant proteins are still capable of a direct interaction with MinD in phospholipid recruitment assays. Furthermore, we demonstrate that interactions between FtsZ and both sites of MinC identified here are important for assembly of FtsZ-MinC-MinD complexes and that the conserved C-terminal end of FtsZ is not required for MinC-MinD complex formation with GTP-dependent FtsZ polymers.IMPORTANCE Bacterial cell division proceeds through the coordinated assembly of the FtsZ-ring, or Z-ring, at the site of division. Assembly of the Z-ring requires polymerization of FtsZ, which is regulated by several proteins in the cell. In Escherichia coli, the Min system, which contains MinC, MinD, and MinE proteins, exhibits polar oscillation and inhibits the assembly of FtsZ at nonseptal locations. Here, we identify regions on the surface of MinC that are important for contacting FtsZ and destabilizing FtsZ polymers.

FtsA reshapes membrane architecture and remodels the Z-ring in Escherichia coli.

Cell division in prokaryotes initiates with assembly of the Z-ring at midcell, which, in Escherichia coli, is tethered to the inner leaflet of the cytoplasmic membrane through a direct interaction with FtsA, a widely conserved actin homolog. The Z-ring is comprised of polymers of tubulin-like FtsZ and has been suggested to provide the force for constriction. Here, we demonstrate that FtsA exerts force on membranes causing redistribution of membrane architecture, robustly hydrolyzes ATP and directly engages FtsZ polymers in a reconstituted system. Phospholipid reorganization by FtsA occurs rapidly and is mediated by insertion of a C-terminal membrane targeting sequence (MTS) into the bilayer and further promoted by a nucleotide-dependent conformational change relayed to the MTS. FtsA also recruits FtsZ to phospholipid vesicles via a direct interaction with the FtsZ C-terminus and regulates FtsZ assembly kinetics. These results implicate the actin homolog FtsA in establishment of a Z-ring scaffold, while directly remodeling the membrane and provide mechanistic insight into localized cell wall remodeling, invagination and constriction at the onset of division.

Immune Mediators Important for a Protective Secondary Response to Babesia microti.

Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk factors for severe disease include general immune suppression, advanced age (>50) and lack of a spleen. However, severe disease can occur in the absence of any known risk factors. The degree to which tick-transmitted B. microti infection confers protection from subsequent exposure is largely unexplored. This is an important question as both the prevalence and geographic range of tick-transmitted B. microti infection continues to increase and individuals in endemic regions may have multiple exposures over their lifetime. In the current study we used a mouse model to evaluate the degree to which primary infection with B. microti protected against secondary challenge with the same parasite strain. We show that CD4 T cells, and to a lesser extent B cells, contribute to protection. However, mice exhibited significant protection from secondary parasite challenge even in the absence of either CD4 T cells or B cells. The protection mediated by CD4 T cells did not depend on their production of IFN-γ as mice with a targeted gene deletion for the IFN-γ receptor remained fully protected against secondary challenge. Other factors including inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88, important for toll-like receptors, IL-18 and IL-1 signaling, were not important for protection against primary or secondary challenge with B. microti. Thus, our study shows that resolution of primary infection with B. microti results in robust protection against secondary challenge with parasites, at least in the short term. Further studies are needed to evaluate the length of protection and the degree to which protection is impacted by parasite heterogeneity. Although we show an important role for CD4 T cells in protection against secondary challenge, our results suggest that no single aspect of the immune system is solely responsible for adequate protection against secondary challenge with B. microti.

The Weight of Frailty in Neurosurgery Patients: Analyzing the Combined Effect of Frailty and Body Mass Index on 30-Day Postoperative Mortality.

OBJECTIVE: There is a rising prevalence of overweight and obese persons in the US, and there is a paucity of information about the relationship between frailty and body mass index. Therefore, we examined discrimination thresholds and independent relationships of the risk analysis index (RAI), modified frailty index-5 (mFI-5), and increasing patient age in predicting 30-day postoperative mortality. METHODS: This retrospective American College of Surgeons National Surgical Quality Improvement Program analysis compared all overweight or obese adult patients who underwent neurosurgery procedures between 2012 and 2020. We compared discrimination using receiver operating characteristic curve analysis for RAI, mFI-5, and increasing patient age. Furthermore, multivariable analyses, as well as subgroup analyses by procedure type i.e., spine, skull base, and other (vascular and functional) were performed, and reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 315,725/412,909 (76.5%) neurosurgery patients, with a median age of 59 years (interquartile range: 48-68), predominately White 76.7% and male 54.3%. Receiver operating characteristic analysis for 30-day postoperative mortality demonstrated a higher discriminatory threshold for RAI (C-statistic: 0.790, 95%CI: 0.782-0.800) compared to mFI-5 (C-statistic: 0.692, 95%CI: 0.620-0.638) and increasing patient age (C-statistic: 0.659, 95%CI: 0.650-0.668). Multivariable analyses showed a dose-dependent association and a larger magnitude of effect by RAI: frail patients OR: 11.82 (95%CI: 10.57-13.24), and very frail patients OR: 31.19 (95%CI: 24.87-39.12). A similar trend was observed in all subgroup analyses i.e., spine, skull base, and other (vascular and functional) procedures (P ≤ 0.001). CONCLUSIONS: Increasing frailty was associated with a higher rate of 30-day postoperative mortality, with a dose-dependent effect. Furthermore, the RAI had a higher threshold for discrimination and larger effect sizes than mFI-5 and increasing patient age. These findings support RAI's use in preoperative assessments, as it has the potential to improve postoperative outcomes through targeted interventions.

The Associations Between Quadriceps Tendon Graft Thickness and Isokinetic Performance.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) using the quadriceps tendon is an increasingly popular technique. Both partial-thickness quadriceps tendon (PT-Q) and full-thickness quadriceps tendon (FT-Q) graft depths are employed. HYPOTHESIS/PURPOSE: This study was designed to assess isokinetic peak torque, average power, and total work during knee extension in patients with FT-Q or PT-Q grafts for ACLR. We hypothesized that both groups would show lower isokinetic values for the operated side, with greater deficits in the FT-Q group than in the PT-Q group. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 26 patients who underwent ACLR with either an FT-Q or PT-Q graft were recruited between June 2021 and November 2021. Patients underwent isokinetic knee extension testing at > 1 year after surgery. Mixed repeated-measures analysis of covariance with least square difference post hoc testing was used to determine significant differences or interactions for all variables. RESULTS: Peak torque was significantly lower for the operated limb than the nonoperated limb in the FT-Q group (mean difference [MD] ± standard error [SE], -38.6 ± 8.3 Ncm [95% CI, -55.7 to -21.5 Ncm]; P < .001; d = 0.90) but not in the PT-Q group (MD ± SE, -7.3 ± 7.7 Ncm [95% CI, -23.2 to 8.5 Ncm]; P = .348; d = 0.20). Similarly, average power for the operated limb was lower than that for the nonoperated limb in the FT-Q group (MD ± SE, -53.6 ± 13.4 W [95% CI, -81.3 to -26.9 W]; P < .001; d = 0.88) but not in the PT-Q group (MD ± SE, -4.1 ± 12.4 W [95% CI, -29.8 to 21.5 W]; P = .742; d = 0.07), and total work was lower for the operated limb compared with the nonoperated limb in the FT-Q group (MD ± SE, -118.2 ± 27.1 J [95% CI, -174.3 to -62.2 J]; P < .001; d = 0.96) but not in the PT-Q group (MD ± SE, -18.3 ± 25.1 J [95% CI, -70.2 to 33.6 J]; P = .472; d = 0.15). CONCLUSION: The FT-Q group showed significant deficits in the operated limb compared with the nonoperated limb for all isokinetic variables. In contrast, no significant differences were found between the nonoperated and operated limbs for the PT-Q group.

Impact of Quadriceps Tendon Graft Thickness on Electromechanical Delay and Neuromuscular Performance After ACL Reconstruction.

Background: Both partial- and full-thickness quadriceps tendon (QT) graft harvests are used for anterior cruciate ligament reconstruction (ACLR). Purpose: To evaluate the impact of QT graft harvest depth (full or partial thickness) on electromechanical delay (EMD), peak torque (PT), and rate of torque development (RTD) after ACLR. Study Design: Controlled laboratory study. Methods: A total of 26 patients who underwent either partial-thickness (n = 14) or full-thickness (n = 12) autograft QT ACLR were recruited between June and November 2021 (>1 year before participation). Patients performed isokinetic knee extension testing with surface electromyography of the quadriceps muscles. Mixed repeated-measures analysis of variance with least significant difference post hoc testing was used to determine significant differences (mean difference [MD] ± SE) or interactions for all variables. Results: A significant speed×depth interaction was seen for the vastus medialis (P = .005). Pairwise analyses showed significantly longer EMD for the partial-thickness graft than the full-thickness graft (MD ± SE, 19.92 ± 6.33 ms; P = .006). In the partial-thickness graft, the EMD was significantly longer at 90 deg/s versus 180 deg/s (MD ± SE, 19.11 ± 3.95 ms; P < .001) and 300 deg/s (MD ± SE, 16.43 ± 5.30 ms; P = .006). For PT, the full-thickness graft had a significantly lower PT on the operated versus nonoperated side at all speeds (MD ± SE: 90 deg/s, -57.0 ± 10.5 N·m, P < .001; 180 deg/s, -26.0 ± 10.2 N·m, P = .020; 300 deg/s, -20.3 ± 8.9 N·m, P = .034). For RTD, the full-thickness graft showed significantly Slower RTD for the operated versus nonoperated side at all time points (MD ± SD: RTD0-25 (0-25% of the range of motion), -131.3 ± 50.9 N·m/s, P = .018; RTD25-50, -197.0 ± 72.5 N·m/s, P = .014; RTD50-75, -113.3 ± 39.8 N·m/s, P = .013; RTD75-100, -149.4 ± 35.9 N·m/s, P < .001). Conclusion: Compared with partial-thickness QT, full-thickness QT showed a shorter vastus medialis EMD at higher loading, and therefore greater stiffness, as well as slower RTD and lower PT across all testing speeds. Clinical Relevance: The impact of full-thickness QT autograft on EMD and neuromuscular performance should be considered for ACLR.

Vulnerability and social justice as factors in emergent U.S. nanotechnology risk perceptions.

As an emerging domain of risk research, nanotechnologies engender novel research questions, including how new technologies are encountered given different framing and contextual detail. Using data from a recent U.S. national survey of perceived risks (N= 1,100), risk versus benefit framings and the specific social positions from which people encounter or perceive new technologies are explored. Results indicate that vulnerability and attitudes toward environmental justice significantly influenced risk perceptions of nanotechnology as a broad class, while controlling for demographic and affective factors. Comparative analyses of different examples of nanotechnology applications demonstrated heightened ambivalence across acceptability when risk versus benefit information was provided with application descriptions (described in short vignettes as compared to the general category "nanotechnology," absent of risk or benefit information). The acceptability of these nano-specific vignettes varied significantly in only some cases given indexes of vulnerability and attitudes toward environmental justice. However, experimental narrative analyses, using longer, more comprehensive descriptive passages, show how assessments of risks and benefits are tied to the systematically manipulated psychometric qualities of the application (its invasiveness and controllability), risk messaging from scientists, and the social implications of the technology with regard to justice. The article concludes with discussion of these findings for risk perception research and public policy related to nanotechnology and possibly other emerging technologies.

Proteolysis-Dependent Remodeling of the Tubulin Homolog FtsZ at the Division Septum in Escherichia coli.

During bacterial cell division a dynamic protein structure called the Z-ring assembles at the septum. The major protein in the Z-ring in Escherichia coli is FtsZ, a tubulin homolog that polymerizes with GTP. FtsZ is degraded by the two-component ATP-dependent protease ClpXP. Two regions of FtsZ, located outside of the polymerization domain in the unstructured linker and at the C-terminus, are important for specific recognition and degradation by ClpXP. We engineered a synthetic substrate containing green fluorescent protein (Gfp) fused to an extended FtsZ C-terminal tail (residues 317-383), including the unstructured linker and the C-terminal conserved region, but not the polymerization domain, and showed that it is sufficient to target a non-native substrate for degradation in vitro. To determine if FtsZ degradation regulates Z-ring assembly during division, we expressed a full length Gfp-FtsZ fusion protein in wild type and clp deficient strains and monitored fluorescent Z-rings. In cells deleted for clpX or clpP, or cells expressing protease-defective mutant protein ClpP(S97A), Z-rings appear normal; however, after photobleaching a region of the Z-ring, fluorescence recovers ~70% more slowly in cells without functional ClpXP than in wild type cells. Gfp-FtsZ(R379E), which is defective for degradation by ClpXP, also assembles into Z-rings that recover fluorescence ~2-fold more slowly than Z-rings containing Gfp-FtsZ. In vitro, ClpXP cooperatively degrades and disassembles FtsZ polymers. These results demonstrate that ClpXP is a regulator of Z-ring dynamics and that the regulation is proteolysis-dependent. Our results further show that FtsZ-interacting proteins in E. coli fine-tune Z-ring dynamics.

The Protein Chaperone ClpX Targets Native and Non-native Aggregated Substrates for Remodeling, Disassembly, and Degradation with ClpP.

ClpX is a member of the Clp/Hsp100 family of ATP-dependent chaperones and partners with ClpP, a compartmentalized protease, to degrade protein substrates bearing specific recognition signals. ClpX targets specific proteins for degradation directly or with substrate-specific adaptor proteins. Native substrates of ClpXP include proteins that form large oligomeric assemblies, such as MuA, FtsZ, and Dps in Escherichia coli. To remodel large oligomeric substrates, ClpX utilizes multivalent targeting strategies and discriminates between assembled and unassembled substrate conformations. Although ClpX and ClpP are known to associate with protein aggregates in E. coli, a potential role for ClpXP in disaggregation remains poorly characterized. Here, we discuss strategies utilized by ClpX to recognize native and non-native protein aggregates and the mechanisms by which ClpX alone, and with ClpP, remodels the conformations of various aggregates. We show that ClpX promotes the disassembly and reactivation of aggregated Gfp-ssrA through specific substrate remodeling. In the presence of ClpP, ClpX promotes disassembly and degradation of aggregated substrates bearing specific ClpX recognition signals, including heat-aggregated Gfp-ssrA, as well as polymeric and heat-aggregated FtsZ, which is a native ClpXP substrate in E. coli. Finally, we show that ClpX is present in insoluble aggregates and prevents the accumulation of thermal FtsZ aggregates in vivo, suggesting that ClpXP participates in the management of aggregates bearing ClpX recognition signals.

The bacterial cell division regulators MinD and MinC form polymers in the presence of nucleotide.

The Min system of proteins, consisting of MinC, MinD and MinE, is essential for normal cell division in Escherichia coli. MinC forms a polar gradient to restrict placement of the division septum to midcell. MinC localization occurs through a direct interaction with MinD, a membrane-associating Par-like ATPase. MinE stimulates ATP hydrolysis by MinD, thereby releasing MinD from the membrane. Here, we show that MinD forms polymers with MinC and ATP without the addition of phospholipids. The topological regulator MinE induces disassembly of MinCD polymers. Two MinD mutant proteins, MinD(K11A) and MinD(ΔMTS15), are unable to form polymers with MinC.

Nanotoxicology: characterizing the scientific literature, 2000-2007.

Understanding the toxicity of nanomaterials and nano-enabled products is important for human and environmental health and safety as well as public acceptance. Assessing the state of knowledge about nanotoxicology is an important step in promoting comprehensive understanding of the health and environmental implications of these new materials. To this end, we employed bibliometric techniques to characterize the prevalence and distribution of the current scientific literature. We found that the nano-toxicological literature is dispersed across a range of disciplines and sub-fields; focused on in vitro testing; often does not specify an exposure pathway; and tends to emphasize acute toxicity and mortality rather than chronic exposure and morbidity. Finally, there is very little research on consumer products, particularly on their environmental fate, and most research is on the toxicity of basic nanomaterials. The implications for toxicologists, regulators and social scientists studying nanotechnology and society are discussed.

Anticipating the perceived risk of nanotechnologies.

Understanding emerging trends in public perceptions of nanomaterials is critically important for those who regulate risks. A number of surveys have explored public perceptions of their risks and benefits. In this paper we meta-analyse these surveys to assess the extent to which the following four hypotheses derived from previous studies of new technologies might be said to be valid for nanotechnologies: risk aversion will prevail over benefit appreciation; an increase in knowledge will not result in reduced aversion to risks; judgements will be malleable and subject to persuasion given risk-centric information; and contextual, psychometric and attitudinal predictors of perceived risk from prior studies can help anticipate future perceptions of nanotechnologies. We find that half the public has at least some familiarity with nanotechnology, and those who perceive greater benefits outnumber those who perceive greater risks by 3 to 1. However, a large minority of those surveyed (44%) is unsure, suggesting that risk judgements are highly malleable. Nanotechnology risk perceptions also appear to contradict some long-standing findings. In particular, unfamiliarity with nanotechnology is, contrary to expectations, not strongly associated with risk aversion and reduced 'knowledge deficits' are correlated with positive perceptions in this early and controversy-free period. Psychometric variables, trust and affect continue to drive risk perceptions in this new context, although the influence of both trust and affect is mediated, even reversed, by demographic and cultural variables. Given the potential malleability of perceptions, novel methods for understanding future public responses to nanotechnologies will need to be developed.

Health and safety practices in the nanomaterials workplace: results from an international survey.

This article reports the findings of an international survey of nanomaterials firms and laboratories regarding their environmental health and safety (EHS) programs, engineering controls, personal protective equipment (PPE), exposure monitoring, waste disposal, product stewardship, and risk beliefs. While many participants reported not believing that nanomaterials pose special risks, nanospecific EHS programs were still widely reported. Most nanospecific EHS programs appeared to build from general EHS programs but included nanospecific workplace engineering controls and recommendations for clothing, gloves, eye protection, and respirators. Organizations with nanospecific EHS programs also reported providing product (safe use) guidance to consumers. However, workplace monitoring and nanospecific waste disposal were uneven and were only associated with the subset of organizations believing in special risks. A majority of organizations expressed a need for more toxicological information and EHS guidance. Overall, this study suggests that nanomaterials firms and laboratories are already attentive to nanospecific EHS and product stewardship issues. However, improved risk communication is needed to further the implementation of related programs. Organizations that are wholly inattentive to EHS would likely engage in nanospecific EHS upon implementing a staffed, general EHS program.