Plant protection products containing nanomaterials that alter the functionality or risk profile of active ingredients (nano-enabled pesticides) promise many benefits over conventional pesticide products. These benefits may include improved formulation characteristics, easier application, better targeting of pest species, increased efficacy, lower application rates, and enhanced environmental safety. After many years of research and development, nano-enabled pesticides are starting to make their way into the market. The introduction of this technology raises a number of issues for regulators, including how does the ecological risk assessment of nano-enabled pesticide products differ from that of conventional plant protection products? In this paper, a group drawn from regulatory agencies, academia, research, and the agrochemicals industry offers a perspective on relevant considerations pertaining to the problem formulation phase of the ecological risk assessment of nano-enabled pesticides.
The negative effects of incarceration on child well-being are often linked to the economic insecurity of formerly incarcerated parents. Researchers caution, however, that the effects of parental incarceration may be small in the presence of multiple-partner fertility and other family complexity. Despite these claims, few studies have directly observed either economic insecurity or the full extent of family complexity. We study parent-child relationships with a unique data set that includes detailed information about economic insecurity and family complexity among parents just released from prison. We find that stable private housing, more than income, is associated with close and regular contact between parents and children. Formerly incarcerated parents see their children less regularly in contexts of multiple-partner fertility and in the absence of supportive family relationships. Significant housing and family effects are estimated even after we control for drug use and crime, which are themselves negatively related to parental contact. The findings point to the constraints of material insecurity and the complexity of family relationships on the contact between formerly incarcerated parents and their children.
Intracellular delivery of M6P/IGFII receptor inhibitors exhibits better efficacy than extracellular inhibitors to regulate TGFβ1 mediated upregulation of profibrotic marker, collagen I.
Research on incarceration has focused on prisons, but jail detention is far more common than imprisonment. Jails are local institutions that detain people before trial or incarcerate them for short sentences for low-level offenses. Research from the 1970s and 1980s viewed jails as “managing the rabble,” a small and deeply disadvantaged segment of urban populations that struggled with problems of addiction, mental illness, and homelessness. The 1990s and 2000s marked a period of mass criminalization in which new styles of policing and court processing produced large numbers of criminal cases for minor crimes, concentrated in low-income communities of color. In a period of widespread criminal justice contact for minor offenses, how common is jail incarceration for minority men, particularly in poor neighborhoods? We estimate cumulative risks of jail incarceration with an administrative data file that records all jail admissions and discharges in New York City from 2008 to 2017. Although New York has a low jail incarceration rate, we find that 26.8% of Black men and 16.2% of Latino men, in contrast to only 3% of White men, in New York have been jailed by age 38 y. We also find evidence of high rates of repeated incarceration among Black men and high incarceration risks in high-poverty neighborhoods. Despite the jail’s great reach in New York, we also find that the incarcerated population declined in the study period, producing a large reduction in the prevalence of jail incarceration for Black and Latino men.
It has been hypothesized that the bifunctional enzyme DmpFG channels its intermediate, acetaldehyde, from one active site to the next using a buried intermolecular channel identified in the crystal structure. This channel appears to switch between an open and a closed conformation depending on whether the coenzyme NAD(+) is present or absent. Here, we applied molecular dynamics and metadynamics to investigate channeling within DmpFG in both the presence and absence of NAD(+). We found that substrate channeling within this enzyme is energetically feasible in the presence of NAD(+) but was less likely in its absence. Tyr-291, a proposed control point at the channel's entry, does not appear to function as a molecular gate. Instead, it is thought to orientate the substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at the channel's exit appear to have an important role in controlling the entry of acetaldehyde into the DmpF active site.
Previous researchers examining romantic couples' dynamics have highlighted important behaviors, such as sacrifice motives, that can enhance or detract from relationship quality. It is equally as important to understand what individual characteristics contribute to these relationship behaviors. We examined how daily sacrifice motives (i.e., approach and avoidance) and attachment insecurity (i.e., anxiety and avoidance) interact to predict relationship quality in a sample of 81 same-sex couples (58 ϭ female, 23 ϭ male couples). Using 14-day daily diary data, we hypothesized that daily approach motives would be positively associated with relationship quality, whereas daily avoidance motives would be negatively associated with relationship quality. As expected, results showed a positive association between daily approach motives, and a negative association between avoidance motives, and relationship quality; however, these associations were moderated by attachment insecurity and gender. Specifically, we found that approach motives were associated with greater relationship quality, and avoidance motives with lower relationship quality, for women low in attachment insecurity and men high in attachment insecurity. Results highlight the importance of understanding the nuances in the associations among sacrifice motives, attachment, and relationship quality, for men and women in same-sex relationships.
Voltage gated sodium channels are the target of a range of local anesthetic, anti-epileptic and anti-arrhythmic compounds. But, gaining a molecular level understanding of their mode of action is difficult as we only have atomic resolution structures of bacterial sodium channels not their eukaryotic counterparts. In this study we used molecular dynamics simulations to demonstrate that the binding sites of both the local anesthetic benzocaine and the anti-epileptic phenytoin to the bacterial sodium channel NavAb can be altered significantly by the introduction of point mutations. Free energy techniques were applied to show that increased aromaticity in the pore of the channel, used to emulate the aromatic residues observed in eukaryotic Nav1.2, led to changes in the location of binding and dissociation constants of each drug relative to wild type NavAb. Further, binding locations and dissociation constants obtained for both benzocaine (660 μM) and phenytoin (1 μM) in the mutant channels were within the range expected from experimental values obtained from drug binding to eukaryotic sodium channels, indicating that these mutant NavAb may be a better model for drug binding to eukaryotic channels than the wild type.
Background: Airway hyper-responsiveness (AHR) is a key feature of asthma and a causal relationship between airway inflammation and AHR has been identified. The aim of the current study was to clarify the effect of proinflammatory cytokines and asthma medication on primary human airway smooth muscle (ASM) inositol phosphate (IPx) signalling and define the regulatory loci involved.
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