Dynamics of Hot QCD Matter -- Current Status and Developments

The discovery and characterization of hot and dense QCD matter, known as Quark Gluon Plasma (QGP), remains the most international collaborative effort and synergy between theorists and experimentalists in modern nuclear physics to date. The experimentalists around the world not only collect an unprecedented amount of data in heavy-ion collisions, at Relativistic Heavy Ion Collider (RHIC), at Brookhaven National Laboratory (BNL) in New York, USA, and the Large Hadron Collider (LHC), at CERN in Geneva, Switzerland but also analyze these data to unravel the mystery of this new phase of matter that filled a few microseconds old universe, just after the Big Bang. In the meantime, advancements in theoretical works and computing capability extend our wisdom about the hot-dense QCD matter and its dynamics through mathematical equations. The exchange of ideas between experimentalists and theoreticians is crucial for the progress of our knowledge. The motivation of this first conference named "HOT QCD Matter 2022" is to bring the community together to have a discourse on this topic. In this article, there are 36 sections discussing various topics in the field of relativistic heavy-ion collisions and related phenomena that cover a snapshot of the current experimental observations and theoretical progress. This article begins with the theoretical overview of relativistic spin-hydrodynamics in the presence of the external magnetic field, followed by the Lattice QCD results on heavy quarks in QGP, and finally, it ends with an overview of experiment results.Comment: Compilation of the contributions (148 pages) as presented in the `Hot QCD Matter 2022 conference', held from May 12 to 14, 2022, jointly organized by IIT Goa & Goa University, Goa, Indi

Designed Metalloproteins: From Structurally Characterized Scaffolds to Helical Bundles.

Fundamental studies using two classes of de novo designed alpha-helical scaffolds (three-stranded coiled coils or a single chain three-helix bundle), spectroscopy, and X-ray crystallography are exploited to enhance our understanding of the biochemistry of heavy metals Cd(II), Hg(II), and Pb(II) in thiol-rich de novo designed peptides. The X-ray structure of a parallel three-stranded coiled coil (CoilSer L9C) is determined to 1.36 Å resolution in its non-metallated form (Rw= 18.2%; Rf= 21.5%). Cys side chains show alternate conformations and are partially (15%) preorganized for metal binding at the polypeptide interior. How the physical properties of two Cd(II) ions bound in “identical” first coordination spheres at different topological positions within the same three-stranded coiled coil peptide vary has been investigated. GrandL16PenL19IL23PenL26I sequesters two Cd(II) ions in trigonal planar CdS3 geometries with similar physical properties; however, these two sites are not independent from each other. Metallation state (apo or [Cd(pep)(Hpep)2]+ or [Cd(pep)3]-) of one site perturbs the physical properties of the second site. GrandL12AL16CL26AL30C binds two Cd(II) ions as 4-coordinate CdS3O (O = water molecule) at both the binding sites, but with dramatically different properties. The 4-coordinate sites display differences in thermodynamic (pKa2 for Cd(II) binding ranging from 9.9 to 13.9) and kinetic (L26AL30C is more dynamic than L12AL16C site) properties depending on their location. Exchange studies have been performed to understand the mechanism of insertion of Cd(II) into and out of helical scaffolds. A multi-site exchange scheme is invoked. Free Cd(II) is believed to interact with surface Glutamates before being bound within the peptide interior. The process occurs on the slow exchange regime with rates ranging from 5.8 to 10.9 ms. CdS3 sites do not exchange on the NMR time scale. A tris(cysteine) metal binding site was engineered at the C-terminal end of an existing de novo designed three-helix bundle yielding alpha3DIV, a well folded and stable protein capable of binding heavy metals with high affinity (>10^7 M-1). Hg(II) is complexed as a linear HgS2 (low pH) / trigonal planar HgS3 complex (high pH), Cd(II) as four coordinate CdS3O/CdS3N (N = His72), and Pb(II) as trigonal pyramidal PbS3 species.Ph.D.ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/84478/1/saumen_1.pd

A De Novo Designed Trimeric Metalloprotein as a Ni_p Model of the Acetyl-CoA Synthase

We present a Nip site model of acetyl coenzyme-A synthase (ACS) within a de novo-designed trimer peptide that self-assembles to produce a homoleptic Ni(Cys)3 binding motif. Spectroscopic and kinetic studies of ligand binding demonstrate that Ni binding stabilizes the peptide assembly and produces a terminal NiI-CO complex. When the CO-bound state is reacted with a methyl donor, a new species is quickly produced with new spectral features. While the metal-bound CO is albeit unactivated, the presence of the methyl donor produces an activated metal-CO complex. Selective outer sphere steric modifications demonstrate that the physical properties of the ligand-bound states are altered differently depending on the location of the steric modification above or below the Ni site

High Reactivation of BK Virus Variants in Asian Indians with Renal Disorders and During Pregnancy

There is resurgence of interest in the study of occurrence, genotype and pathogenic associations of human Polyomavirus BK and JC in recent years. In the present study, we have ascertained the presence of BK virus shed in the urine samples of pregnant women and immunocompromised patients, for the first time in Asian Indian population, and have also characterised the prevalent genotypes of the non-coding control regions (NCCRs) of these natural isolates. The results strongly suggest a very high incidence, as well as degree, of BK virus reactivation in this population groups assayed. Approximately 65% of the patients and pregnant women together, tested positive based on polymerase chain reaction (PCR) analysis, and these results were further confirmed by Southern hybridisation and dot blot against BKV specific probes. The NCCRs of the several Indian endemic strains were analysed by sequencing PCR products, amplified directly from urine samples, with oligonucleotide primers designed from the constant region of T-Antigen and VP2 coding sequences. The typical features of the NCCRs of these Indian strains appeared to be comparable and related to the archetypal strain BKV (WW) with some alterations in few key positions. Apart from these subtle alterations, neither any major DNA rearrangement within the NCCR region nor any drastic modification marked BKV strains found in nephropathy and in the healthy subjects (pregnancy). However, in some of the immunocompromised patients studied, the degree of reactivations re- flected by viruria, appeared to be much higher compared to other reports

Abiotic Reactivity of De Novo Designed Artificial Copper Peptides (ArCuPs): The Case of C-H Activation

We report a series of de novo designed Artificial Cu Peptides (ArCuPs) that oxidize and peroxygenate C-H bonds of model abiotic substrates via electrochemically generated Cu-oxygen species using H2O2 as the terminal oxidant, akin to native Cu enzymes. Detailed assessment of kinetic parameters established the catalytic nature of the ArCuPs. Selective alteration of outer sphere steric at the d layers above and below the Cu site allows facilitated access of substrates, where a more pronounced effect on catalysis is observed when space is created at the d layer below the Cu site via Ile to Ala mutation producing a kcat of 6.2 s-1, TONmax of 14800 and catalytic proficiency (kcat/KM/kuncat) of 340 M-1 for the oxidation of benzyl alcohol. Independent spectroscopic studied revealed that the rate of formation of the Cu-oxygen species and the spectroscopic feature of the most active variant is distinct compared to the other ArCuPs. Systematic alteration of outer sphere hydrophobicity led to a correlated tuning of the T2 Cu site redox potentials by ~80 mV. The enhanced activity of the ArCuP variant is attributed to a combination of steric effect that allows easy access of substrates, the nature of Cu-oxygen species, and stability of this construct compared to others, where Ile to Ala mutation unexpectedly leads to a higher thermostability which is further augmented by Cu binding

Superior Vena Cava Syndrome due to Thrombosis: A Rare Paraneoplastic Presentation of Bronchogenic Carcinoma

Superior vena cava (SVC) syndrome is not an uncommon occurrence in patients with malignancy and it is often described as a medical emergency. In majority of the cases, SVC syndrome occurs due to mechanical obstruction of the SVC by extraluminal compression with primary intrathoracic malignancies. However, intraluminal obstruction due to thrombosis can also produce symptoms and signs of SVC syndrome. Clot-related SVC obstruction is mostly associated with indwelling central venous catheter and pacemaker leads, although such thrombosis can occur spontaneously in a background of a hypercoagulable state, e.g., malignancy. Here, an unusual case of sudden onset SVC syndrome has been reported, which on initial radiologic evaluation was found to have a lung nodule without any significant mediastinal mass or adenopathy compressing SVC. Subsequent investigation with Doppler ultrasonography of the neck showed thrombosis in the right internal jugular, right subclavian and right brachiocephalic vein, which was responsible for SVC syndrome. Histopathological evaluation of lung nodule confirmed presence of an adenocarcinoma. Therefore, venous thromboembolism as a paraneoplastic syndrome should be kept in mind while evaluating a case of SVC obstruction in a cancer patient. Management of the underlying disease is of prime importance in such cases and anticoagulation is the mainstay of therapy. Ability to identify paraneoplastic syndrome may have a significant effect on clinical outcome, ranging from early diagnosis to improved quality of life of the patient

Controlling and fine tuning the physical properties of two identical metal coordination sites in de novo designed three stranded coiled coil peptides

Herein we report how de novo designed peptides can be used to investigate whether the position of a metal site along a linear sequence that folds into a three stranded α-helical coiled coil defines the physical properties of Cd(II) ions in either CdS(3) or CdS(3)O (O-being an exogenous water molecule) coordination environments. Peptides are presented that bind Cd(II) into two identical coordination sites that are located at different topological positions at the interior of these constructs. The peptide grandL16PenL19IL23PenL26I binds two Cd(II) as trigonal planar 3-coordinate CdS(3) structures whereas grandL12AL16CL26AL30C sequesters two Cd(II) as pseudotetrahedral 4-coordinate CdS(3)O structures. We demonstrate how for the first peptide, having a more rigid structure, the location of the identical binding sites along the linear sequence does not affect the physical properties of the two bound Cd(II). However, because these are rigid aggregates, the sites are not completely independent as Cd(II) bound to one of the sites ((113)Cd NMR chemical shift of 681 ppm) is perturbed by the metallation state (apo or [Cd(pep)(Hpep)(2)](+) or [Cd(pep)(3)](−)) of the second center ((113)Cd NMR chemical shift of 686 ppm). grandL12AL16CL26AL30C shows a completely different behavior. The physical properties of the two bound Cd(II) ions indeed depend on the position of the metal center, having pK(a2) values for the equilibrium [Cd(pep)(Hpep)(2)](+) → [Cd(pep)(3)](−) + 2H(+) (corresponding to deprotonation and coordination of cysteine thiols) that range from 9.9 to 13.9. In addition, the L26AL30C site shows dynamic behavior, which is not observed for the L12AL16C site. These results indicate that for these systems one cannot simply assign a “4-coordinate structure” and assume certain physical properties for that site since important factors such as packing of the adjacent Leu, size of the intended cavity (endo vs exo) and location of the metal site play crucial roles in determining the final properties of the bound Cd(II)

Nanosecond Dynamics at Protein Metal Sites: An Application of Perturbed Angular Correlation (PAC) of γ\gamma-Rays Spectroscopy

Metalloproteins are essential to numerous reactions in nature, and constitute approximately one-third of all known proteins. Molecular dynamics of proteins has been elucidated with great success both by experimental and theoretical methods, revealing atomic level details of function involving the organic constituents on a broad spectrum of time scales. However, the characterization of dynamics at biomolecular metal sites on nanosecond time scales is scarce in the literature. The aqua ions of many biologically relevant metal ions exhibit exchange of water molecules on the nanosecond time scale or faster, often defining their reactivity in aqueous solution, and this is presumably also a relevant time scale for the making and breaking of coordination bonds between metal ions and ligands at protein metal sites. Ligand exchange dynamics is critical for a variety of elementary steps of reactions in metallobiochemistry, for example, association and dissociation of metal bound water, association of substrate and dissociation of product in the catalytic cycle of metalloenzymes, at regulatory metal sites which require binding and dissociation of metal ions, as well as in the transport of metal ions across cell membranes or between proteins involved in metal ion homeostasis. In Perturbed Angular Correlation of γ-rays (PAC) spectroscopy, the correlation in time and space of two γ-rays emitted successively in a nuclear decay is recorded, reflecting the hyperfine interactions of the PAC probe nucleus with the surroundings. This allows for characterization of molecular and electronic structure as well as nanosecond dynamics at the PAC probe binding site. Herein, selected examples describing the application of PAC spectroscopy in probing the dynamics at protein metal sites are presented, including (1) exchange of Cd2+ bound water in de novo designed synthetic proteins, and the effect of remote mutations on metal site dynamics; (2) dynamics at the β-lactamase active site, where the metal ion appears to jump between the two adjacent sites; (3) structural relaxation in small blue copper proteins upon 111Ag+ to 111Cd2+ transformation in radioactive nuclear decay; (4) metal ion transfer between two HAH1 proteins with change in coordination number; and (5) metal ion sensor proteins with two coexisting metal site structures. With this Account, we hope to make our modest contribution to the field and perhaps spur additional interest in dynamics at protein metal sites, which we consider to be severely underexplored. Relatively little is known about detailed atomic motions at metal sites, for example, how ligand exchange processes affect protein function, and how the amino acid composition of the protein may control this facet of metal site characteristics. We also aim to provide the reader with a qualitative impression of the possibilities offered by PAC spectroscopy in bioinorganic chemistry, especially when elucidating dynamics at protein metal sites, and finally present data that may serve as benchmarks on a relevant time scale for development and tests of theoretical molecular dynamics methods applied to biomolecular metal sites