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Objectives: The purpose of this study was twofold: (a) to profile body composition and physical fitness characteristics of collegiate American football starters and (b) to examine differences in key performance indicators across position groups. These indicators included select measures of body composition, joint kinematics, as well as muscular strength and power., Methods: Sixteen National Collegiate Athletic Association (NCAA) Division-II American football athletes (age: 22.25 ± 1.1 years; height: 183.75 ± 7.8 cm; and body mass: 97.22 ± 20.39 kg) volunteered to participate in this study. A Kruskal-Wallis one-way analysis of variance by ranks test with Dunn test post-hoc adjustments was used to examine position differences between Line ( n = 3), Big Skill ( n = 6), and Skill ( n = 7) position groups with α priori set at p < 0.05., Results: The findings of this study suggest that significant differences in body composition ( p = 0.004), muscular strength ( p = 0.01), and muscular power ( p = 0.03) exist between position groups. However, no significant differences were observed in joint kinematics as assessed by the bilateral squat test ( p > 0.05)., Conclusions: Therefore, key findings from this study suggest that although significant differences in body composition, muscular strength, and muscular power exist, an emphasis should be placed on the regular assessment, development, and maintenance of optimal joint kinematics within collegiate American football populations as this appears to be a shared key performance indicator among starters.

This study aimed to investigate the acute effects of lower limb wearable resistance on maximal horizontal deceleration biomechanics, across two different assessments. Twenty recreationally trained team sport athletes performed acceleration to deceleration assessments (ADA), and 5-0-5 change of direction (COD) tests across three load conditions (unloaded, 2% of BW, 4% of body weight (BW)), with load attached to the anterior and posterior thighs and shanks. Linear mixed effect models with participant ID as the random effect, and load condition as the fixed effect were used to study load-specific biomechanical differences in deceleration mechanics across both tests. Primary study findings indicate that for the ADA, in the 4% BW condition, participants exhibited significantly greater degrees of Avg Approach Momentum, as well as significant reductions in deceleration phase center of mass (COM) drop, and Avg Brake Step ground contact deceleration (GCD) in both the 2% BW, and 4% BW condition, compared to the unloaded condition. In the 5-0-5 tests, participants experienced significant reductions in Avg Approach Velocity, Avg deceleration (DEC), and Stopping Time in the 4% BW condition compared to the unloaded condition. Similar to the ADA test, participants also experienced significant reductions in Avg Brake Step GCD in both the 2% BW and 4% BW conditions, and significant increases in Avg Approach Momentum in the 4% BW condition, compared to the unloaded condition. Therefore, findings suggest that based on the test, and metric of interest, the addition of lower limb wearable resistance led to acute differences in maximal horizontal deceleration biomechanics. However, future investigations are warranted to further explore if the use of lower limb wearable resistance could present as an effective training tool in enhancing athlete's horizontal deceleration and change of direction performance., Competing Interests: There are no conflicts of interest to report for any of the authors., (Copyright: © 2024 Philipp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: Cabarkapa, D, Johnson, QR, Cabarkapa, DV, Philipp, NM, Eserhaut, DA, and Fry, AC. Changes in countermovement vertical jump force-time metrics during a game in professional male basketball players. J Strength Cond Res 38(7): 1326-1329, 2024-As technology within elite basketball advances and is more available to sporting organizations, novel approaches for assessing and addressing athletic performance during practice or competition are being continuously explored. The aim of this investigation was to examine changes in neuromuscular performance during live basketball play. Eight professional male basketball players volunteered to participate in this study. The testing procedures were conducted during a pre-tournament camp over a span of 2 days. During the first day, the athletes were familiarized with the testing procedures, and baseline measurements were obtained. Using a uni-axial force plate system sampling at 1,000 Hz, each athlete performed 3 countermovement vertical jumps (CVJ) without an arm swing before proceeding with their regular training activities. During the second day of the pre-tournament camp, the athletes repeated identical CVJ testing procedures before the start of the first quarter and post-first, second, third, and fourth quarter of a simulated 5-on-5 basketball game. Repeated-measures testing design was used to examine statistically significant differences in various force-time metrics of interest in comparison to the baseline levels (p < 0.05). Besides a trivial decrease in eccentric mean force, the findings of this study revealed no statistically significant changes in any force-time metrics of interest within both eccentric and concentric phases of the CVJ (i.e., mean and peak force and power, jump height, impulse, velocity, and contraction time). Thus, we can conclude that these variables were not sensitive to acute fatigue, suggesting that the neuromuscular performances of professional male basketball players tend to remain unchanged throughout a 5-on-5 simulated game., (Copyright © 2024 National Strength and Conditioning Association.)

Given its fast-growing popularity and unique on-court competitive demands, 3 × 3 basketball has captured a considerable amount of attention over recent years. However, unlike research focused on studying 5 × 5 basketball players, there is a lack of scientific literature focused on examining countermovement vertical jump (CMJ) and sprint performance characteristics of 3 × 3 athletes. Thus, the purpose of the present study was to compare force-time metrics during both eccentric and concentric phases of the CMJ and acceleration and deceleration capabilities between 3 × 3 and 5 × 5 top-tier professional male basketball athletes. Ten 3 × 3 and eleven 5 × 5 professional basketball players volunteered to participate in the present study. Upon completion of a standardized warm-up, each athlete performed three maximum-effort CMJs, followed by two 10 m sprints. A uni-axial force plate system sampling at 1,000 Hz was used to analyze CMJ force-time metrics and a radar gun sampling at 47 Hz was used to derive sprint acceleration-deceleration measures. Independent t-tests and Hedge's g were used to examine between-group statistically significant differences ( p  < 0.05) and effect size magnitudes. The findings of the present study reveal that 3 × 3 and 5 × 5 professional male basketball players tend to display similar neuromuscular performance characteristics as no significant differences were observed in any force-time metric during both eccentric and concentric phases of the CMJ ( g  = 0.061-0.468). Yet, prominent differences were found in multiple measures of sprint performance, with large effect size magnitudes ( g  = 1.221-1.881). Specifically, 5 × 5 basketball players displayed greater average and maximal deceleration and faster time-to-stop than their 3 × 3 counterparts. Overall, these findings provide reference values that sports practitioners can use when assessing athletes' CMJ and sprint performance capabilities as well as when developing sport-specific training regimens to mimic on-court competitive demands., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cabarkapa, Johnson, Aleksic, Cabarkapa, Philipp, Sekulic, Krsman, Trunic and Fry.)

Abstract: Thompson, MB, Johnson, QR, Lindsay, KG, and Dawes, JJ. Development of an abbreviated model for predicting functional movement screen score within tactical populations. J Strength Cond Res 38(3): 607-611, 2024-The Functional Movement Screen (FMS) is a tool commonly used to identify compensations when performing 7 specific movement patterns. Timely administration of the full FMS is largely dependent on the practitioner's familiarity and experience with the screening battery. When working in populations that are time-poor (i.e., tactical professionals), administration of the full movement pattern battery is not always feasible. The purpose of this study was to determine which, if any, combination of movement patterns that comprise the FMS could be used to predict total score on this screen among first responders. Functional Movement Screen scores for 99 male subjects (mean ± SD; age: 37.55 ± 9.83 years; height: 180.38 ± 6.59 cm; and body mass: 97.87 ± 15.32 kg) and 9 female subjects (age: 33.22 ± 3.99 years; height: 172.11 ± 8.19 cm; and body mass: 83.99 ± 14.09 kg) from a single law enforcement and fire agency were used for this analysis. Subjects performed the full FMS, which consisted of the following movement patterns: deep squat (DS), hurdle step (HS), in-line lunge (ILL), shoulder mobility (SM), active straight leg raise (ASLR), trunk stability push-up (PU), and rotary stability (RS). A stepwise regression was used to determine the best predictors of the FMS 7-pattern model based on the model's R2. Cronbach's alpha and Guttman's lambda-2 were used to determine the reliability of the proposed models. The regression indicated that a 4-pattern model consisting of DS, ILL, SM, and PU was sufficient to predict approximately 84% of the full model (adjusted R2 = 0.84, p ≤ 0.001). This 4-pattern model was shown to be reliable with the 7-pattern model (α = 0.93, λ = 0.93). Using this modified version of the FMS may allow practitioners working in tactical populations a time-efficient method of identifying dysfunctional movement and determine whether the full 7-pattern model of the FMS should be considered., (Copyright © 2024 National Strength and Conditioning Association.)

With force plates being widely implemented for neuromuscular performance assessment in sport-specific settings and various force-time metrics being able to differentiate athletes based on their performance capabilities, the purpose of the present study was to examine the differences in countermovement vertical jump (CVJ) characteristics between starting and non-starting professional male basketball players (e.g., ABA League). Twenty-three athletes (height = 199.2 ± 7.7 kg, body mass = 94.2 ± 8.2 kg, age = 23.8 ± 4.9 years) volunteered to participate in the present investigation. Upon completion of a standardized warm-up protocol, each athlete performed three maximal-effort CVJs without an arm swing while standing on a uni-axial force plate system sampling at 1,000 Hz. Independent t -tests were used to examine statistically significant differences ( p  < 0.05) in each force-time metric between starters ( n  = 10) and non-starters ( n  = 13). No significant differences in any of the CVJ force-time metrics of interest were observed between the two groups, during both the eccentric and concentric phases of the movement (i.e., impulse, duration, peak velocity, and mean and peak force and power). Moreover, starters and non-starters demonstrated similar performance on CVJ outcome (e.g., jump height) and strategy metrics (e.g., countermovement depth). Overall, these findings suggest that at the professional level of play, the ability to secure a spot in the starting lineup is not primarily determined by the players' CVJ performance characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Cabarkapa, Cabarkapa, Aleksic, Philipp, Scott, Johnson and Fry.)

Over time, the interest in developing stable photosensitizers (PS) which both absorb and emit light in the red region (650 and 950 nm) has gained noticeable interest. Recently, carbon dots (CDs) have become the material of focus to act as a PS due to their high extinction coefficient, low cytotoxicity, and both high photo and thermal stability. In this work, a Federal and Drug Association (FDA) approved Near Infra-Red (NIR) organic fluorophore used for photo-imaging, indocyanine green (ICG), has been explored as a precursor to develop water-soluble red emissive CDs which possess red emission at 697 nm. Furthermore, our material was found to yield favorable red-imaging capabilities of glioblastoma stem-like cells (GSCs) meanwhile boasting low toxicity. Additionally with post modifications, our CDs have been found to have selectivity towards tumors over healthy tissue as well as crossing the blood-brain barrier (BBB) in zebrafish models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cystic fibrosis (CF) is a recessive genetic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The recent development of a class of drugs called "correctors", which repair the structure and function of mutant CFTR, has greatly enhanced the life expectancy of CF patients. These correctors target the most common disease causing CFTR mutant F508del and are exemplified by the FDA-approved VX-809. While one binding site of VX-809 to CFTR was recently elucidated by cryo-electron microscopy, four additional binding sites have been proposed in the literature and it has been theorized that VX-809 and structurally similar correctors may engage multiple CFTR binding sites. To explore these five binding sites, ensemble docking was performed on wild-type CFTR and the F508del mutant using a large library of structurally similar corrector drugs, including VX-809 (lumacaftor), VX-661 (tezacaftor), ABBV-2222 (galicaftor), and a host of other structurally related molecules. For wild-type CFTR, we find that only one site, located in membrane spanning domain 1 (MSD1), binds favorably to our ligand library. While this MSD1 site also binds our ligand library for F508del-CFTR, the F508del mutation also opens a binding site in nucleotide binding domain 1 (NBD1), which enables strong binding of our ligand library to this site. This NBD1 site in F508del-CFTR exhibits the strongest overall binding affinity for our library of corrector drugs. This data may serve to better understand the structural changes induced by mutation of CFTR and how correctors bind to the protein. Additionally, it may aid in the design of new, more effective CFTR corrector drugs.

Introduction: The primary aim of Reserve Officers' Training Corps (ROTC) programs is to prepare cadets for future military service. To successfully complete one of these programs and perform active duty responsibilities, cadets must be able to complete a variety of physical tasks. Therefore, performing movement screening may be useful for identifying potential movement disparities that could lead to injury. The purpose of this investigation was to determine whether sex-related differences in movement patterns exist on the Functional Movement Screen (FMS). The FMS is a tool that uses seven functional movements to assess movement pattern deficits and asymmetries; deep squat, hurdle step, inline lunge (ILL), shoulder mobility, active straight-leg raise (ASLR), trunk stability pushup (TSPU), and rotary stability., Materials and Methods: Archived data for 93 (male, n = 69; female n = 24) ROTC cadets were provided to the primary investigators for analysis. Independent t-tests (P < .05) were conducted to analyze differences in assessments between sexes., Results: Significant differences between sexes were observed on the ILL (P = .014), ASLR (P < .001), and TSPU (P < .001). Females scored higher on both the ILL (2.13 ± 0.54) and ASLR (2.04 ± 0.69) compared with males (1.81 ± 0.52 and 1.48 ± 0.58). Males scored significantly higher (P ≤ .001) on the TSPU (2.57 ± .581) compared with females (2.00 ± .417). No significant differences were observed in the deep squat (P = .865), hurdle step (P = .829), shoulder mobility (P = .342), and rotary stability (P = .230) assessments., Conclusions: Sex differences in the ILL, ASLR, and TSPU may be because of greater mobility in the ankle and hamstrings and reduced upper-body muscle mass for females compared with males. Males performed better than females on the TSPU test. In conclusion, sex-related differences in FMS performance do exist within the ROTC population. Additionally, these differences should be taken into consideration when designing specific exercise programs for ROTC cadets., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this study was to determine if significant relationships exist between absolute and relative lower-body power and selected measures of speed among male and female collegiate basketball players. Archived performance testing data from 29 (male = 14; female = 15) NCAA division II collegiate basketball players were used for this analysis. These measures included lane agility, 10-yard sprint, and shuttle run time (sec). A Pearson's correlation coefficient was used to determine if significant relationships existed between measures of lower-body power and linear sprint time, change of direction speed (CODS), and shuttle performance. Statistical significance was set a priori at p ≤ 0.05. A significant large correlation was found between absolute power and lane agility ( r = 0.54, p = 0.05) among male players. No significant correlations were found between absolute or relative power for 10-yard sprint times, lane agility, or shuttle run performance ( p > 0.05). Females showed no significant correlations between relative power and lane agility ( r = -0.25, p = 0.37) or 10-yard sprint ( r = -0.47, p = 0.08), but did show a significant large correlation ( r = -0.64, p = 0.01) between relative power and shuttle run performance. Generating high amounts of relative power is vital in intermittent team sports such as basketball. In particular, this study provided evidence that relative power in female collegiate basketball players is significantly related to shuttle run ability.

Firefighters are required to perform a wide array of physically demanding job tasks, such as forcible entry, charged hose advances and victim extractions. An adequate level of muscular strength and power are required to successfully perform these tasks. The purpose of this study is to investigate the differences in stronger and weaker firefighters in measures of power. Archived data for twenty-seven (age = 34.3 ± 7.9 yr, body height = 176.3 ± 7.2 cm, body mass = 89.4 ± 15.7 kg) full-time firefighters were analyzed. Participants were placed into one of two groups [i.e., stronger (HIGH) ( n = 13) and weaker (LOW) ( n = 14)], based on their relative isometric mid-thigh pull (IMTPr) performance. Power measures included counter-movement jump (CMJ) height, and peak anaerobic power in watts (PAPW). Significant mean score differences were not discovered between HIGH and LOW IMTPr groups on any measures of lower-body power. Moderate positive correlations were observed between IMTP and CMJ (r = .519; p = .01). This study identified significant differences in absolute and relative strength between firefighters who were able to lift at least 2.0× their bodyweight versus those who were not. Additionally, absolute strength (as assessed by the IMTP) was significantly and positively correlated to CMJ height when compared to their weaker counterparts. These findings may provide insight into approaches for improving occupational performance and durability through the physical development of firefighters via strength and conditioning programs which focus on developing absolute strength, relative strength, and power.

There is evidence to suggest that aquatic plyometric training (APT) may be an effective and safer alternative to traditional land-based plyometric training (LPT) when training to increase jump performance. The aim of this review was to critically examine the current literature regarding the effects of APT vs. LPT on jump performance in athletic populations. Key terms were employed in five separate databases to complete the current review. Available articles were screened for inclusion and exclusion criteria to determine which studies were deemed eligible for review. Outcome measure in these studies included those assessing lower extremity power and jump performance (i.e., drop jumps, broad jumps, sergeant jumps, repeated countermovement jumps, and vertical jumps). All but one of the studies included in this critical review showed significant improvements in jump performance after LPT and APT interventions. Both LPT and APT groups experienced similar increases in jump performance and lower-body power, pre- to post-test, in the majority of the studies examined in this review. LPT and APT have the ability to improve lower extremity explosive strength and jump performance within athletic populations. Improvements in lower body power may improve overall athletic performance. Observations from this review may be used by sport coaches, strength coaches, and athletes alike to weigh the pros and cons of both forms of plyometric training. Observations from this review may also be used to weigh the pros and cons of APT over LPT in terms of reducing risk of injury.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States. Pancreatic tumors are minimally infiltrated by T cells and are largely refractory to immunotherapy. Accordingly, the role of T-cell immunity in pancreatic cancer has been somewhat overlooked. Here, we hypothesized that immune resistance in pancreatic cancer was induced in response to antitumor T-cell immune responses and that understanding how pancreatic tumors respond to immune attack may facilitate the development of more effective therapeutic strategies. We now provide evidence that T-cell-dependent host immune responses induce a PDAC-derived myeloid mimicry phenomenon and stimulate immune resistance. Three KPC mouse models of pancreatic cancer were used: the mT3-2D (Kras +/LSL-G12D ; Trp53 +/LSL-R172H ; Pdx1-Cre) subcutaneous and orthotopic models, as well as the KP1 (p48- CRE / LSL - Kras /Trp53 flox/flox ) subcutaneous model. KPC cancer cells were grown in immunocompetent and immunodeficient C57BL/6 mice and analyzed to determine the impact of adaptive immunity on malignant epithelial cells, as well as on whole tumors. We found that induced T-cell antitumor immunity, via signal transducer and activator of transcription 1 (STAT1), stimulated malignant epithelial pancreatic cells to induce the expression of genes typically expressed by myeloid cells and altered intratumoral immunosuppressive myeloid cell profiles. Targeting the Janus Kinase (JAK)/STAT signaling pathway using the FDA-approved drug ruxolitinib overcame these tumor-protective responses and improved anti-PD-1 therapeutic efficacy. These findings provide future directions for treatments that specifically disable this mechanism of resistance in PDAC., (©2021 American Association for Cancer Research.)

This study sought to determine if significant relationships exist between lower-body power measures to sprint and change of direction speed (CODS) in Division II collegiate women's lacrosse athletes. Archived data for 17 NCAA Division II female lacrosse athletes was provided to the investigators for analysis. Jumping performance was assessed using a countermovement jump (CMJ), squat jump (SJ), and standing broad jump (SBJ). Sprint speed was measured at 10m and 30m, of a 30m sprint. CODS was evaluated using a T-Test (TT), a modified T-Test (MTT), and the 5-0-5 Agility Test (5-0-5). No significant relationships were found between absolute power measures and any sprint or CODS tests. However, relative power (relative CMJ and SJ) had significant relationships with all CODS and sprints speeds above 10m. Only the CMJ and relative CMJ were related to 10m sprint speed. SBJ distance had significant relationships with all CODS tests and 30m speed, while relative SBJ distance significantly correlated with 5-0-5 speed. Relative lower-body power was significantly related to speed and CODS in Division II female lacrosse athletes. Strength and conditioning professionals should focus on lower-body power development as a key component in preparing female lacrosse athletes for their sport.

Carotenoids are pigment molecules that protect biomembranes against degradation and may be involved in the formation of functional bacterial membrane microdomains. Little is known on whether different types of carotenoids have different effects on the membrane or if there is any concentration dependence of these effects. In this work, we present results from molecular dynamics simulations of phospholipid bilayers containing different amounts of either β-carotene or zeaxanthin. Both β-carotene and zeaxanthin show the ability to laterally condense the membrane lipids and reduce their inter-leaflet interactions. With increasing concentrations, both carotenoids increase the bilayer thickness and rigidity. The results reveal that carotenoids have similar effects to cholesterol on regulating the behavior of fluid-phase membranes, suggesting that they could function as sterol substitutes and confirming their potential role in the formation of functional membrane domains.

Simulated fire ground scenarios (SFGS) provide firefighters with an opportunity to maintain skills, receive feedback, and optimize performance. Although there is extensive research on heart rate (HR) changes in the firefighter population, few examine the differences between positions. Firefighters are primarily responsible for fire suppression and control (23), officers for emergency operations and organizational management, paramedics for providing on-scene emergency medical care, and drivers are responsible for driving the fire apparatus. Utilizing HR analysis to quantify the physical demands of SFGS among firefighting crews by position. Sixty-seven male (age: 38.97 ± 9.17; ht: 177.99 ± 6.45 cm. wt: 88.83 ± 13.55 kg) firefighters (FF) participated in this investigation. FF crews performed two SFGS involving the suppression and control of a structural fire. Participants were outfitted with heart rate (HR) monitors and average heart rate (HRavg) and maximum heart rate (HRmax) data were collected for each of the two SFGS. Significant differences were observed for Age (P = 0.01), APMHR (P = 0.01), HRmax 1 (P = 0.04), and HRmax 2 (P = 0.04) in which firefighters had higher values for Age-predicted maximal heart rate (APMHR), HRmax 1 , HRmax 2 compared to the officers. SFGS can be very physically demanding events that may elicit maximal or near maximal HR responses regardless of position. Based on the metabolic demands of these events and the individual firefighter's capabilities, this information can be used to develop resistance training and conditioning programs that optimize performance at maximal or near maximal heart rates.

INTRODUCTION: Body composition (BC) measurements are used to determine qualification for enlistment and to ensure active members are meeting standards. Although there is extensive research on BC in active-duty military, very few have examined ROTC cadets. The purpose of this study was to identify and quantify differences in BC between freshman/sophomore [underclass (UND)] and junior/senior [upperclass (UPP)] ROTC cadets by using bioelectrical impedance spectroscopy (BIS). METHODS: UND ( N = 21) and UPP ( N = 15) Air Force ROTC cadets volunteered for this study. BIS was used to measure fat mass percentage (FM%), fat free mass percentage (FFM%), total body water percentage (TBW%), extracellular fluid percentage (ECF%), and intracellular fluid percentage (ICF%). Separate one-way ANOVAs were run between UND and UPP for all dependent variables with a Bonferroni correction factor. Additionally, a Pearson correlation between abdominal circumference (AC) and FM% was conducted. RESULTS: No significant differences were observed between the UND and UPP groups' BMI. However, significant differences were observed for ECF%, ICF%, TBW%, FFM%, and FM% in which the UPP had a higher TBW%, ICF%, FFM%, and a lower ECF% and FM% compared to the UND. CONCLUSIONS: This study observed significant differences in BC across class ranks in ROTC cadets. Findings from this study suggest that due to an increased exposure to ROTC training, UPP cadets have a more ideal body composition (FFM% and FM%) when compared to UND cadets. Johnson QR, Mackey CS, Muddle TD, Smith DB, DeFreitas JM. Body composition comparison of upper- and underclass Reserve Officers Training Corps cadets . Aerosp Med Hum Perform. 2019; 90(9):813-818.

Amino-bridged gel polymer P1 was discovered to catalyze alkyne halo-functionalization in excellent yields, regioselectivity, functional group compatibility, and recyclability. We have observed that both aromatic and aliphatic alkynes can be converted to α,α-dihalogenated ketones in the presence of polymer P1 under metal-free conditions at room temperature within a short reaction time.

Carotenoids have been found to be important in improving the integrity of biomembranes in eukaryotes. However, the molecular details of how carotenoids modulate the physical properties of biomembranes are unknown. To this end, we have conducted a series of molecular dynamics simulations of different biologically-relevant membranes in the presence of carotenoids. The carotenoid effect on the membrane was found to be specific to the identity of the carotenoid and the composition of the membrane itself. Therefore, different classes of carotenoids produce a different effect on the membrane, and different membrane phases are affected differently by carotenoids. It is apparent from our data that carotenoids do trigger the bilayer to become thinner. The mechanism by which this occurs depends on two competing factors, the ability of the lipid tails of opposing monolayers to either (1) compress or (2) interdigitate as the bilayer condenses. Indeed, carotenoids directly influence the physical properties via these two mechanisms, thus compacting the bilayer. However, the degree to which these competing mechanisms are utilized depends on the bilayer phase and the carotenoid identity.

We have developed a method to capture the essential conformational dynamics of folded biopolymers using statistical analysis of coarse-grained segment-segment contacts. Previously, the residue-residue contact analysis of simulation trajectories was successfully applied to the detection of conformational switching motions in biomolecular complexes. However, the application to large protein systems (larger than 1000 amino acid residues) is challenging using the description of residue contacts. Also, the residue-based method cannot be used to compare proteins with different sequences. To expand the scope of the method, we have tested several coarse-graining schemes that group a collection of consecutive residues into a segment. The definition of these segments may be derived from structural and sequence information, while the interaction strength of the coarse-grained segment-segment contacts is a function of the residue-residue contacts. We then perform covariance calculations on these coarse-grained contact matrices. We monitored how well the principal components of the contact matrices is preserved using various rendering functions. The new method was demonstrated to assist the reduction of the degrees of freedom for describing the conformation space, and it potentially allows for the analysis of a system that is approximately tenfold larger compared with the corresponding residue contact-based method. This method can also render a family of similar proteins into the same conformational space, and thus can be used to compare the structures of proteins with different sequences.

Interfacial proteins function in unique heterogeneous solvent environments, such as water-oil interfaces. One important example is microbial lipase, which is activated in an oil-water emulsion phase and has many important enzymatic functions. A unique aprotic dipolar organic solvent, dimethyl sulfoxide (DMSO), has been shown to increase the activity of lipases, but the mechanism behind this enhancement is still unknown. Here, all-atom molecular dynamics simulations of lipase in a binary solution were performed to examine the effects of DMSO on the dynamics of the gating mechanism. The amphiphilic α5 region of the lipase was a focal point for the analysis, since the structural ordering of α5 has been shown to be important for gating under other perturbations. Compared to the closed-gorge ensemble in an aqueous environment, the conformational ensemble shifts towards open-gorge structures in the presence of DMSO solvents. Increased width of the access channel is particularly prevalent in 45% and 60% DMSO concentrations (w/w). As the amount of DMSO increases, the α5 region of the lipase becomes more α-helical, as we previously observed in studies that address water-oil interfacial and high pressure activation. We believe that the structural ordering of α5 plays an essential role on gating and lipase activity., (© 2016 Wiley Periodicals, Inc.)

The promiscuous protein retinoid X receptor (RXR) displays essential allosteric regulation of several members in the nuclear hormone receptor superfamily via heterodimerization and (anti)cooperative binding of cognate ligands. Here, the structural basis of the positive allostery of RXR and constitutive androstane receptor (CAR) is revealed. In contrast, a similar computational approach had previously revealed the mechanism for negative allostery in the complex of RXR and thyroid receptor (TR). By comparing the positive and negative allostery of RXR complexed with CAR and TR respectively, we reported the promiscuous allosteric control involving RXR. We characterize the allosteric mechanism by expressing the correlated dynamics of selected residue-residue contacts which was extracted from atomistic molecular dynamics simulation and statistical analysis. While the same set of residues in the binding pocket of RXR may initiate the residue-residue interaction network, RXR uses largely different sets of contacts (only about one-third identical) and allosteric modes to regulate TR and CAR. The promiscuity of RXR control may originate from multiple factors, including (1) the frustrated fit of cognate ligand 9c to the RXR binding pocket and (2) the different ligand-binding features of TR (loose) versus CAR (tight) to their corresponding cognate ligands.

A special class of proteins adopts an inactive conformation in aqueous solution and activates at an interface (such as the surface of lipid droplet) by switching their conformations. Lipase, an essential enzyme for breaking down lipids, serves as a model system for studying such interfacial proteins. The underlying conformational switch of lipase induced by solvent condition is achieved through changing the status of the gated substrate-access channel. Interestingly, a lipase was also reported to exhibit pressure activation, which indicates it is drastically active at high hydrostatic pressure. To unravel the molecular mechanism of this unusual phenomenon, we examined the structural changes induced by high hydrostatic pressures (up to 1500 MPa) using molecular dynamics simulations. By monitoring the width of the access channel, we found that the protein undergoes a conformational transition and opens the access channel at high pressures (>100 MPa). Particularly, a disordered amphiphilic α5 region of the protein becomes ordered at high pressure. This positive correlation between the channel opening and α5 ordering is consistent with the early findings of the gating motion in the presence of a water-oil interface. Statistical analysis of the ensemble of conformations also reveals the essential collective motions of the protein and how these motions contribute to gating. Arguments are presented as to why heightened sensitivity to high-pressure perturbation can be a general feature of switchable interfacial proteins. Further mutations are also suggested to validate our observations. Proteins 2016; 84:820-827. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

In this work, a facile one-pot reaction for the formation of metal nanoparticles in a water solution through the use of n-(2-aminoethyl)-3-aminosilanetriol is presented. This compound can be used to effectively reduce and complex metal salts into metal core nanoparticles coated with the compound. By controlling the concentrations of salt and silane one is able to control reaction rates, particle size, and nanoparticle coating. The effects of these changes were characterized through transmission electron microscopy (TEM), UV-Vis spectrometry (UV-Vis), Nuclear Magnetic Resonance spectroscopy (NMR) and Fourier Transform Infrared spectroscopy (FTIR). A unique aspect to this reaction is that usually silanes hydrolyze and cross-link in water; however, in this system the silane is water-soluble and stable. It is known that silicon and amino moieties can form complexes with metal salts. The silicon is known to extend its coordination sphere to form penta- or hexa-coordinated species. Furthermore, the silanol group can undergo hydrolysis to form a Si-O-Si silica network, thereby transforming the metal nanoparticles into a functionalized nanocomposites.

Carbohydrate recognition by proteins, such as lectins and other (bio)molecules, can be essential for many biological functions. Recently, interest has arisen due to potential protein and drug design and future bioengineering applications. A quantitative measurement of carbohydrate-protein interaction is thus important for the full characterization of sugar recognition. We focus on the aspect of utilizing computer simulations and biophysical models to evaluate the strength and specificity of carbohydrate recognition in this review. With increasing computational resources, better algorithms and refined modeling parameters, using state-of-the-art supercomputers to calculate the strength of the interaction between molecules has become increasingly mainstream. We review the current state of this technique and its successful applications for studying protein-sugar interactions in recent years.

Understanding allosteric mechanisms is essential for the physical control of molecular switches and downstream cellular responses. However, it is difficult to decode essential allosteric motions in a high-throughput scheme. A general two-pronged approach to performing automatic data reduction of simulation trajectories is presented here. The first step involves coarse-graining and identifying the most dynamic residue-residue contacts. The second step is performing principal component analysis of these contacts and extracting the large-scale collective motions expressed via these residue-residue contacts. We demonstrated the method using a protein complex of nuclear receptors. Using atomistic modeling and simulation, we examined the protein complex and a set of 18 glycine point mutations of residues that constitute the binding pocket of the ligand effector. The important motions that are responsible for the allostery are reported. In contrast to conventional induced-fit and lock-and-key binding mechanisms, a novel "frustrated-fit" binding mechanism of RXR for allosteric control was revealed., Competing Interests: Notes The authors declare no competing financial interest.

Glycosylation is an essential modification of proteins and lipids by the addition of carbohydrate residues. These attached carbohydrates range from single monomers to elaborate branched glycans. Here, we examine how the level of glycosylation affects the conformation of a semiflexible peptide linker using the example of the hinge peptide from immunoglobulin A. Three sets of atomistic models of this hinge peptide with varying degrees of glycosylation are constructed to probe how glycosylation affects the physical properties of the linker. We found that glycosylation greatly altered the predominant conformations of the peptide, causing it to become elongated in reference to the unglycosylated form. Furthermore, glycosylation restricts the conformational exploration of the peptide. At the residue level, glycans are found to introduce a bias for the formation of more extended secondary structural elements for glycosylated serines. Additionally, the flexibility of this semiflexible proline-rich peptide is significantly reduced by glycosylation.

The amphiphilic peptide of the triacylglycerol lipase derived from Pseudomonas aeruginosa plays a critical role in guarding the gate for ligand access. Conformations of this peptide at several water-oil interfaces and in protein environments were compared using atomistic simulations with explicit solvents. In oil-containing solvents, this peptide is able to retain a folded structure. Interestingly, when the peptide is immersed in a low-polarity solvent environment, it exhibits a "coalesced" helix structure, which has both α- and 3(10)-helix components. The observation that the 3(10)-helical conformation is populated in a highly nonpolar environment is consistent with a previous report on polymethylalanine. Frequent interconversions of the secondary structure (between α-helix and 3(10)-helix) of the peptide are also observed. We further studied how this solvent-induced structural transition may be connected to the trigger mechanism of lipase gating and how the lipase senses the hydrophobic-hydrophilic interface.

Understanding how organic solvent-stable proteins can function in anhydrous and often complex solutions is essential for the study of the interaction of protein and molecular immiscible interfaces and the design of efficient industrial enzymes in nonaqueous solvents. Using an extremophilic lipase from Pseudomonas aeruginosa as an example, we investigated the conformational dynamics of an organic solvent-tolerant enzyme in complex solvent milieux. Four 100-ns molecular dynamics simulations of the lipase were performed in solvent systems: water, hexane, and two mixtures of hexane and water, 5% and 95% (w/w) hexane. Our results show a solvent-dependent structural change of the protein, especially in the region that regulates the admission of the substrate. We observed that the lipase is much less flexible in hexane than in aqueous solution or at the immiscible interface. Quantified by the size of the accessible channel, the lipase in water has a closed-gate conformation and no access to the active site, while in the hexane-containing systems, the lipase is at various degrees of open-gate state, with the immiscible interface setup being in the widely open conformation ensembles. The composition of explicit solvents in the access channel showed a significant influence on the conformational dynamics of the protein. Interestingly, the slowest step (bottleneck) of the hexane-induced conformational switch seems to be correlated with the slow dehydration dynamics of the channel.