skip to main content


Search for: All records

Creators/Authors contains: "Bhatt"

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. Free, publicly-accessible full text available January 17, 2026
  2. Abstract

    The type II polyproline helix (PPII) is a fundamental secondary structure of proteins, important in globular proteins, in intrinsically disordered proteins, and at protein‐protein interfaces. PPII is stabilized in part byn→π* interactions between consecutive carbonyls, via electron delocalization between an electron‐donor carbonyl lone pair (n) and an electron‐acceptor carbonyl (π*) on the subsequent residue. We previously demonstrated that changes to the electronic properties of the acyl donor can predictably modulate the strength ofn→π* interactions, with data from model compounds, in solution in chloroform, in the solid state, and computationally. Herein, we examined whether the electronic properties of acyl capping groups could modulate the stability of PPII in peptides in water. InX−PPGY‐NH2peptides (X=10 acyl capping groups), the effect of acyl group identity on PPII was quantified by circular dichroism and NMR spectroscopy. Electron‐rich acyl groups promoted PPII relative to the standard acetyl (Ac−) group, with the pivaloyl andiso‐butyryl groups most significantly increasing PPII. In contrast, acyl derivatives with electron‐withdrawing substituents and the formyl group relatively disfavored PPII. Similar results, though lesser in magnitude, were also observed inX−APPGY‐NH2peptides, indicating that the capping group can impact PPII conformation at both proline and non‐proline residues. The pivaloyl group was particularly favorable in promoting PPII. The effects of acyl capping groups were further analyzed inX–DfpPGY‐NH2andX−ADfpPGY‐NH2peptides, Dfp=4,4‐difluoroproline. Data on these peptides indicated that acyl groups induced order Piv‐ > Ac‐ > For‐. These results suggest that greater consideration should be given to the identity of acyl capping groups in inducing structure in peptides.

     
    more » « less
    Free, publicly-accessible full text available July 19, 2025
  3. We devise an online learning algorithm -- titled Switching via Monotone Adapted Regret Traces (SMART) -- that adapts to the data and achieves regret that is instance optimal, i.e., simultaneously competitive on every input sequence compared to the performance of the follow-the-leader (FTL) policy and the worst case guarantee of any other input policy. We show that the regret of the SMART policy on any input sequence is within a multiplicative factor e/(e−1)≈1.58 of the smaller of: 1) the regret obtained by FTL on the sequence, and 2) the upper bound on regret guaranteed by the given worst-case policy. This implies a strictly stronger guarantee than typical `best-of-both-worlds' bounds as the guarantee holds for every input sequence regardless of how it is generated. SMART is simple to implement as it begins by playing FTL and switches at most once during the time horizon to the worst-case algorithm. Our approach and results follow from an operational reduction of instance optimal online learning to competitive analysis for the ski-rental problem. We complement our competitive ratio upper bounds with a fundamental lower bound showing that over all input sequences, no algorithm can get better than a 1.43-fraction of the minimum regret achieved by FTL and the minimax-optimal policy. We also present a modification of SMART that combines FTL with a ``small-loss" algorithm to achieve instance optimality between the regret of FTL and the small loss regret bound. 
    more » « less
    Free, publicly-accessible full text available July 1, 2025
  4. Free, publicly-accessible full text available July 1, 2025
  5. Abstract

    High‐latitude neutral winds have a number of drivers, both from solar and magnetospheric origins. Because of this, the neutral wind response to changes in ionospheric convection is not well understood. Previous calculations of response times resulted in a wide range of responses, from tens of minutes to hours. We present a new weighted windowed time‐lagged correlation (weighted WTLC) method for calculating the neutral wind response time. This method provides a time evolution of the neutral wind response time and considers the effects of all thermospheric forces, while previous methods were only capable of one or the other. We use data from SDIs, ASIs, and PFISR to calculate the neutral wind response time using this new method in three case studies. The results are visually validated, and the weighted WTLC method was able to correctly calculate the neutral wind response time. The time evolution of the weighted WTLC time is then compared to previous neutral wind response time calculations in order to investigate the role of ion‐drag on neutral winds. For the substorm event on 2013 Feb 28, we see a shorter response time from the weighted WTLC method, ranging from 0 to 15 min, than the e‐folding time, ranging from 30 to 355 min. The relationship between the two calculation methods and their implications about the ion‐drag force is discussed. Using the time‐dependent feature of the weighted WTLC method, we observe the neutral wind response time decrease over the course of a substorm event, indicating ion‐neutral coupling increased as the substorm progressed.

     
    more » « less
    Free, publicly-accessible full text available May 1, 2025
  6. Acyl capping groups stabilize -helices relative to free N-termini by providing one additional C=Oi•••Hi+4–N hydrogen bond. The electronic properties of acyl capping groups might also directly modulate -helix stability: electron-rich N-terminal acyl groups could stabilize the -helix by strengthening both i/i+4 hydrogen bonds and i/i+1 n* interactions. This hypothesis was tested in peptides X–AKAAAKAAAKAAAAKAAGY-NH2, X=different acyl groups. Surprisingly, the most electron-rich acyl groups (pivaloyl, iso-butyryl) strongly destabilized the -helix. Moreover, the formyl group induced nearly identical -helicity as the acetyl group, despite being a weaker electron donor for hydrogen bonds and for n* interactions. Other acyl groups exhibited intermediate -helicity. These results indicate that the electronic properties of the acyl carbonyl do not directly determine -helicity in peptides in water. In order to understand these effects, DFT calculations were conducted on -helical peptides. Using implicit solvation, -helix stability correlated with acyl group electronics, with the pivaloyl group exhibiting closer hydrogen bonds and n* interactions, in contrast to the experimental results. However, DFT and MD calculations with explicit water solvation revealed that hydrogen bonding to water was impacted by the sterics of the acyl capping group. Formyl capping groups exhibited the closest water-amide hydrogen bonds, while pivaloyl groups exhibited the longest. In -helices in the PDB, the highest frequency of close amide-water hydrogen bonds is observed when the N-cap residue is Gly. The combination of experimental and computational results indicates that solvation (hydrogen bonding of water) to the N-terminal amide groups is a central determinant of -helix stability. 
    more » « less
    Free, publicly-accessible full text available May 7, 2025
  7. Free, publicly-accessible full text available July 1, 2025
  8. Convergent evolution is a widespread phenomenon. While there are many examples of convergent evolution at the phenotypic scale, convergence at the molecular level has been more difficult to identify. A classic example of convergent evolution across scales is that of the digestive lysozyme found in ruminants and Colobine monkeys. These herbivorous species rely on foregut fermentation, which has evolved to function more optimally under acidic conditions. Here, we explored if rodents with similar dietary strategies and digestive morphologies have convergently evolved a lysozyme with digestive functions. At the phenotypic level, we find that rodents with bilocular stomach morphologies exhibited a lysozyme that maintained higher relative activities at low pH values, similar to the lysozymes of ruminants and Colobine monkeys. Additionally, the lysozyme of Peromyscus leucopus shared a similar predicted protonation state as that observed in previously identified digestive lysozymes. However, we found limited evidence of positive selection acting on the lysozyme gene in foregut-fermenting species and did not identify patterns of convergent molecular evolution in this gene. This study emphasizes that phenotypic convergence need not be the result of convergent genetic modifications, and we encourage further exploration into the mechanisms regulating convergence across biological scales. 
    more » « less
    Free, publicly-accessible full text available April 1, 2025
  9. Abstract

    Researchers have advocated elevating mouse housing temperatures from the conventional ~22 °C to the mouse thermoneutral point of 30 °C to enhance translational research. However, the impact of environmental temperature on mouse gastrointestinal physiology remains largely unexplored. Here we show that mice raised at 22 °C exhibit whole gut transit speed nearly twice as fast as those raised at 30 °C, primarily driven by a threefold increase in colon transit speed. Furthermore, gut microbiota composition differs between the two temperatures but does not dictate temperature-dependent differences in gut motility. Notably, increased stress signals from the hypothalamic–pituitary–adrenal axis at 22 °C have a pivotal role in mediating temperature-dependent differences in gut motility. Pharmacological and genetic depletion of the stress hormone corticotropin-releasing hormone slows gut motility in stressed 22 °C mice but has no comparable effect in relatively unstressed 30 °C mice. In conclusion, our findings highlight that colder mouse facility temperatures significantly increase gut motility through hormonal stress pathways.

     
    more » « less