Intrinsically disordered proteins in a physics-based world

Intrinsically disordered proteins (IDPs) are a newly recognized class of functional proteins that rely on a lack of stable structure for function. They are highly prevalent in biology, play fundamental roles, and are extensively involved in human diseases. For signaling and regulation, IDPs often fold into stable structures upon binding to specific targets. The mechanisms of these coupled binding and folding processes are of significant importance because they underlie the organization of regulatory networks that dictate various aspects of cellular decision-making. This review first discusses the challenge in detailed experimental characterization of these heterogeneous and dynamics proteins and the unique and exciting opportunity for physics-based modeling to make crucial contributions, and then summarizes key lessons from recent de novo simulations of the structure and interactions of several regulatory IDPs.     

XAFS Investigation of Platinum Impurities in Phosphate Glasses

The coordination environments of Pt impurities in a ternary K-aluminophosphate (KAP) glass and commercial K,Mg-aluminophosphate (KMAP) laser glasses have been investigated by Pt L _III-edge X-ray absorption fine structure (XAFS) spectroscopy. Pt valence in the KAP glass depends on the melt preparation atmosphere. Pt⁴⁺ ions form in melts that are bubbled with oxygen, whereas metallic Pt particles form when these same samples are remelted in air. Residual chlorine in KMAP glasses has an effect on Pt bonding. In chlorine-free samples, Pt⁴⁺ ions are coordinated with ∼5.4 (8) oxygen atoms with an average distance of 2.02 (1) Å. For glasses with low chlorine contents (<200 ppm Cl), the Pt⁴⁺ ions have both O and Cl atoms in the first coordination shell. As the Cl concentration increases, the number of O nearest neighbors decreases and for Cl:Pt > 5, only Cl nearest neighbors are observed. Pt⁴⁺ ions in these latter glasses are coordinated by ∼5.5 (8) Cl atoms at an average distance of 2.27 (2) Å.     

School closures reduced social mixing of children during COVID-19 with implications for transmission risk and school reopening policies

School closures may reduce the size of social networks among children, potentially limiting infectious disease transmission. To estimate the impact of K–12 closures and reopening policies on children''s social interactions and COVID-19 incidence in California''s Bay Area, we collected data on children''s social contacts and assessed implications for transmission using an individual-based model. Elementary and Hispanic children had more contacts during closures than high school and non-Hispanic children, respectively. We estimated that spring 2020 closures of elementary schools averted 2167 cases in the Bay Area (95% CI: −985, 5572), fewer than middle (5884; 95% CI: 1478, 11.550), high school (8650; 95% CI: 3054, 15 940) and workplace (15 813; 95% CI: 9963, 22 617) closures. Under assumptions of moderate community transmission, we estimated that reopening for a four-month semester without any precautions will increase symptomatic illness among high school teachers (an additional 40.7% expected to experience symptomatic infection, 95% CI: 1.9, 61.1), middle school teachers (37.2%, 95% CI: 4.6, 58.1) and elementary school teachers (4.1%, 95% CI: −1.7, 12.0). However, we found that reopening policies for elementary schools that combine universal masking with classroom cohorts could result in few within-school transmissions, while high schools may require masking plus a staggered hybrid schedule. Stronger community interventions (e.g. remote work, social distancing) decreased the risk of within-school transmission across all measures studied, with the influence of community transmission minimized as the effectiveness of the within-school measures increased.     

Arthroscopic or open Bankart procedures: what are the costs?

The cost implications and resource utilization of arthroscopic and open Bankart procedures were evaluated to determine if differences exist between these procedures when performed in a community setting. Billing and hospital records of consecutive patients who underwent either open or arthroscopic Bankart procedures at the three facilities in our city during an 18-month period were analyzed. Procedure type (open or arthroscopic), location (hospital or surgicenter), operation time, operating room time, postanesthesia care unit time, step-down area time, charges for each of these, and anesthesiologist charges were analyzed for 11 open and 13 arthroscopic Bankart procedures. Open procedures took longer and required more operating room time than arthroscopic procedures regardless of location (P < .01). Open procedures required longer postanesthesia care unit time than arthroscopic procedures (P < .01). Facility made no difference. Anesthesia fees were less for arthroscopic ($882) than open Bankarts ($1,075) (P = .002). Total facility and anesthesia fees were less for arthroscopic ($4,747) than for open Bankarts ($6,062) (P = .05). The arthroscopic Bankart repair was performed more quickly than the open Bankart procedure, regardless of facility choice, and resulted in lower total charges. A surgicenter is less expensive whether these procedures are performed arthroscopically or open.     

Short communication: Progression of Johne's disease curtailed by a probiotic

The naturally occurring inflammatory bowel disease Johne's, caused by Mycobacterium avium ssp. paratuberculosis (MAP), has many clinical manifestations in common with the human inflammatory bowel disease Crohn's disease. In addition, both lack preventive and curative therapies. Because a high percentage of Crohn's patients harbor MAP, it is not surprising that MAP is at the center of controversy as to its contribution. Special concern is being raised as to what role, if any, food animals play in transmission of MAP to humans. Because management practices, presently considered the best way to control the spread of MAP, have not and most likely will not eliminate MAP from food animals, other preventive or curative measures are needed. The results presented herein show that a unique bacterium, Dietzia ssp. C79793-74, used as a probiotic, was therapeutic for adult paratuberculosis animals, and resulted in a cure rate of 37.5%.