Biography:

Xiongwu Wu has his expertise in molecular simulation and method development. He developed Self-Guided Molecular/Langevin Dynamics simulation (SGMD/SGLD) methods that enable molecular simulation to access long-time scale events. He has developed core-weighted grid-threading method for rigid fitting of proteins into low resolution cryo-EM maps and Map-restrained SGLD (MapSGLD) method to flexible fit protein structures into cryo-EM maps. He is also the developer for both molecular simulation and modeling packages AMBER and CHARMM

Abstract:

Kinesins are motor proteins that move unidirectionally along microtubules as they hydrolyze ATP. Although the general features of the kinesin walking mechanism are becoming increasingly clear, some key questions remain unanswered, such as how they convert the chemical energy of ATP into mechanical energy and walk processively. In this study, through molecular simulations and free energy calculations, we found that in aqueous solution, kinesin favors an extended form with its microtubule-binding interface (MTBI) motif unfolded, as seen in a recent X-ray structure of kinesin-8. Through the flexible fitting of two newly released cryo-electron microscopy (cryo-EM) maps, we derived atomic structures of the kinesin dimer-microtubule complexes in both two-head-bound and one-head bound states. Free energy calculations showed that kinesin bound to microtubules has a lower free energy than the extended form and that the free energy difference is in the range of the free energy released by ATP hydrolysis. The transition between the extended and compact forms, the structural differences of the leading and trailing heads and atomic force simulations lead us to a completely new mechanism by which kinesin dimers walk on microtubules.

Biography:

Wolfgang Fischer is a Professor at the Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taiwan. He has obtained his PhD in Chemistry at Heidelberg University, Germany, working in the field of vibrational spectroscopy in 1991. He has worked for years in USA like in Boston University as Postdoctoral Fellow working on bacteriorhodopsin using vibrational spectroscopy; Germany in Analytical Chemistry, working on ion channels as potential biosensors; Oxford University as EU Marie Curie Research Fellow and later as Lecturer, working on viral ion channels using bilayer recordings and molecular dynamics simulations and later moved to Taiwan. His field of research is on biophysical aspects describing dynamics and energetic of protein-protein interactions (PPIs) of membrane proteins. The focus is on the development of computational platform technologies to support structural modeling for drug discovery and design as well as for materials sciences.

Abstract:

Computational methods comprise a valuable tool to close the sequence-structure gap, especially for membrane proteins. At this stage, secondary structure prediction programs are available to identify putative stretches of helical transmembrane domains (TMDs) while few programs are developed to predict a beta sheet fold as the membrane spanning motif. With the knowledge about the putative TMDs, here adopting a helical motif, at hand these TMDs can be assembled into a tertiary structure and finally into putative quaternary structures using docking approaches. As a test case, viral channel forming proteins (VCPs), sometimes also called viroporins, are used to develop strategies to generate plausible structures. VCPs are about five time smaller than human ion channels and therefore used as a miniaturized system to investigate how ion channels are formed. Using E5 protein of human papilloma virus type 16 (HPV-16), the assembly of a polytopic membrane protein with three TMDs is presented in its hexameric form. Using a docking approach, the monomeric form is generated first before assembling into the hexamer. The quality of the model is assessed using potential of mean force calculations (PMF) identifying weak ion selectivity. Principle component analysis (PCA) of the data from a classical molecular dynamics simulation reveal asymmetric dynamics of the monomers. These dynamics are compared with those derived for other VCPs such as polytopic p7 of hepatitis C virus (HCV) with two TMDs and bitopic M2 of influenza A. Finally, coarse grained simulations are applied to probe the formation of the quaternary structure of e.g., Vpu of HIV-1.

Biography:

Anil Batta is presently an Associate Professor and Senior Consultant in Govt. Medical College, Amritsar, Punjab, India. He has received his MBBS and MD in Medical Biochemistry from Govt. Medical College, Patiala in 1984 and 1991, respectively. His research interest is mainly in clinical application especially cancer and drug de-addiction. He has supervised more than 15 MD, MSc and Doctorate researches and published more than 30 international research papers. He is the Chief-Editor of America’s Journal of Biochemistry. He is also working as an Advisor to the Editorial Board of International Journal of Biological and Medical Research. He is also a Deputed Advisor to Pakistan Medical Journal of Biochemistry. He has been attached as Technical Advisor to various national and international conferences in Biochemistry, also with hi-tech endocrinal, genetics and automated labs of GGS Medical College, Faridkot.

Abstract:

Aim: It is known that in patients with Diabetic Foot Syndrome severe forms of mental disadaptation are observed. They are manifested psycho-emotional disorders and poor treatment compliance. The aim of this work was to study the forms of mental disadaptation in patients with Diabetic Foot Syndrome and the role of psychological and somatic factors in their development.

Method: The following parameters: Levels of anxiety and depression, alexithymia, irrational cognitive principles, personality profile, severity of somatic disorders and treatment compliance were studied in 120 Diabetic Foot Syndrome patients.

Result: The study revealed two main groups of patients with various forms of mental disadaptation and some relationship of psycho-emotional and somatic disorders. In the first patient’s group with severe form mental disadaptation, there were observed high level of alexithymia, depression, the prevalence of psychopathic personality types, combined with deep encephalopathy, cognitive disorders and long duration of disease. A poor compliance of treatment, the progressive deterioration of the disease, large number of lower limb amputations was observed also in this group of patients. In the second patients’ group with less severe form of mental disadaptation, there were observed small level of alexithymia, high anxiety and the prevalence of neurotic personality types and a shorter duration of disease. A good treatment compliance and smaller number of lower limb amputation was also observed in this group of patients.

Biography:

Whitney Yin is an Assistant Professor for University of Texas Medical Branch, USA. She has received Doctoral degree (PhD) in Department of Pharmacology and Toxicology. She is the Editorial Board Member of many peer reviewed journals and has many publications in national and international journals to her credit. She is committed to highest standards of excellence and it proves through her authorship of many books.

Abstract:

Like all high-fidelity DNA polymerases, human mitochondrial DNA polymerase, Pol-g contains polymerization (pol) activity for DNA synthesis and proofreading exonuclease (exo) activity for error correction. Pol-g is a holoenzyme consists of a catalytic subunit Pol-gA and accessory subunit Pol-gB. Pol-gA contains all enzymatic activity including pol, exo and deoxyribose phosphate (dRP) lyase, Pol-gB contains no enzymatic activity of its own but regulates all Pol-gA activates, consequently, the holoenzyme has higher processive and elevated dRP lyase activity. We determined crystal structures of Pol-g ternary complex with primer/template DNA and an incoming nucleotide to understand how the two active sites communicate with each other. The ternary complex reveals a b-hairpin situated between the two active sites in Pol-gA could transfer the information of nucleotide misincorporation in the pol site to the exo site 40Å away for excision. Our enzymatic studies indicate that Pol-g variants in the b-hairpin completely abolish pol activity while retains full exo activity. Additionally, we performed molecular simulation and found the hairpin region are energetically destabilized with perturbation of Pol-g variants in either pol or exo active sites, revealing for the first time that the two active sites are energetically coupled and DNA strand shuttling is accompanied by destabilization of the path connecting the pol and exo sites.

Biography:

Joel I Osorio is the CEO and Founder of Biotechnology and Regenerative Medicine at RegenerAge International™. He is the Vice President of International Clinical Development for Bioquark, Inc. and Chief Clinical Officer at ReAnima™ Advanced Biosciences. He is an Advance Fellow by the American Board of Anti-Aging and Regenerative Medicine (A4M), Visiting Scholar at University of North Carolina at Chapel Hill (Dermatology) and Fellow in Stem Cell Medicine by the American Academy of Anti-Aging Medicine and University of South Florida.

Abstract:

As it has been previously demonstrated that coelectroporation of Xenopus laevis frog oocytes with normal cells and cancerous cell lines induces the expression of pluripotency markers and in experimental murine model studies, mRNA extract (Bioquantine®) purified from intra and extra-oocyte liquid phases of electroporated oocytes showed potential as a treatment for a wide range of conditions, including Spinal Cord Injury (SCI) among others. The current study observed beneficial changes with Bioquantine® administration in a patient with a severe SCI. Pluripotent stem cells have therapeutic and regenerative potential in clinical situations CNS disorders even cancer. One method of reprogramming somatic cells into pluripotent stem cells is to expose them to extracts prepared from Xenopus laevis oocytes. The positive human findings for spinal cord injury with the results from previous animal studies with experimental models of traumatic brain injury and SCI respectively as our evidence and due to ethical reasons, legal restrictions and a limited number of patients, we were able to treat only a very small number of patients, deciding to include in our protocol the RestoreSensor SureScan to complete it. Based on the electrical stimulation for rehabilitation and regeneration after spinal cord injury published by Hamid and MacEwan, we designed an improved delivery method for the in situ application of MSCs and Bioquantine® in combination with the RestoreSensor® SureScan®. To the present day the patient who suffered a complete section of spinal cord at T12-L1 shows an improvement in sensitivity, strength in striated muscle and smooth muscle connection, 13 months after the first treatment and 6 months after the placement of RestoreSensor® at the level of the lesion, showing an evident improvement on his therapy of physical rehabilitation (legs movement) on crawling forward and backwards and standing on his feet for the first time and showing a progressively important functionality on both limbs.

Biography:

Lisa M Domke is currently a PhD student in the Helmholtz Group for Cell Biology of Professor Werner W Franke at German Cancer Research Center, Germany. She has prepared her Master’s thesis with one of the pioneers in cancer research, Professor Dr. Robert A Weinberg at the Massachusetts Institute of Technology (MIT) in Cambridge, USA. The nature of her degree in Biotechnology has allowed her to learn various analytical as well as light and electron microscopical techniques and to work in different fields of life sciences.

Abstract:

Mature seminiferous tubules (STs) of mammalian testes comprise the Sertoli cells and germ cells and are tightly surrounded by a special peritubular cell wall. Using biochemical, immunocytochemical and electron microscopical methods, we have determined that STs differ from all other epithelia by the absence of cytokeratin intermediate filaments (IFs) but are rich in vimentin IFs, do not contain major epithelial marker structures and molecules such as desmosomes or E-cadherin-based adherens junctions (AJs) but contain exclusively N-cadherin-based AJs. In Sertoli cells, we have found two new junction structures: (1) N-cadherin-based areae adhaerentes which often represent even very large areas connecting Sertoli cells with each other or with germ cells. (2) Special AJs arranged in closely and regularly spaced rows of tight junction-like structures and associated with 5-8 nm wide cytoplasm-to-cytoplasm channels (cribelliform junctions). The seminiferous tubule cells are attached to the peritubular wall by a well-developed basal lamina but lack hemidesmosomes and hemidesmosomal marker molecules. The peritubular wall is a stack system of layers of extracellular matrix (ECM) structures alternating with monolayers of very flat lamellar smooth muscle cells (LSMCs). These LSMCs represent differentiated smooth muscle cells (SMCs; positive for smooth muscle α-actin, the corresponding myosin light and heavy chains, α-actinin, tropomyosin, smoothelin, desmin, vimentin, filamin, talin, dystrophin, caldesmon, calponin and protein SM22α). The cells are laterally connected often in overlapping protrusions by AJs containing cadherin-11 as the predominant cadherin, and also P-cadherin and rarely N-cadherin, anchored in cytoplasmic plaques containing β-catenin, proteins p120 and p0071, plakoglobin and protein myozap. LSMCs also contain typical SMC structures such as dense bodies, plasma membrane-associated focal adhesions and caveolae. Thus, we conclude that these LSMCs represent a specific SMC type and not just myoid cells or myofibroblasts as stated in the literature.

Biography:

Jacob Anderson C Sanchez is a Faculty/Researcher of the Pampanga State Agricultural University. His main objective is to conduct researches related to the development of Aglibut sweet tamarind using molecular biology techniques. He is passionate in conducting researches that are essential in ensuring the profit of the marginalized sector. He has also presented his various researches in international conferences at Singapore, Japan, and France.

Abstract:

Aglibut sweet tamarind is a priority commodity of the Pampanga State Agricultural University (PSAU). However, this variety looks like sour tamarind especially when they are still seedlings. This may result in potential economic loss for farmers or business capitalists who would venture in this lucrative business. Therefore, this study aimed to obtain their molecular identification using cpDNA (rbcL, matK) and nrDNA (ITS) markers; to determine the relationships of the samples using Maximum Likelihood and Maximum Parsimony Cladograms and to evaluate the universality of ITS, rbcL and matK in tamarind. BLAST results showed that majority of the samples belong to Tamarindus indica with 99-100% homology. Maximum Parsimony (MP) and Maximum Likelihood (ML) for matK showed that Aglibut sweet tamarind formed a monophyletic group with PSAU’s sour tamarind and paraphyletic to wild-type sour tamarind obtained from Lubao, Pampanga. On the other hand, MP and ML for ITS did not show a fully resolved tree. For the universality, results showed that matK had 100% PCR and sequencing success rates. Meanwhile, ITS showed 100% PCR success rate and 83% sequencing success, whereas rbcL did not work well for the samples. Hence, we conclude that DNA barcodes matK and ITS are the genetic markers that can be used for molecular identification of Aglibut and sour tamarind samples. More importantly, we report that Aglibut sweet tamarind has closer genetic relationship with the PSAU sour tamarind than other varieties

Biography:

Chantal Prévost is a Researcher at the Theoretical Biochemistry Laboratory (LBT) of the French National Research Center (CNRS), in Paris. She has developed a strong expertise in studying complex biological processes in silico via the integrative exploration of unstable macromolecular self-assembly substates. She has elaborated new algorithms for flexible macromolecular docking and protein fiber modeling. She presently applies this expertise to tackling the mechanism of homologous recombination as well as exploring the architecture of oligomeric assemblies, in collaboration with the Prentiss team in Harvard University, USA

Abstract:

Homologous recombination (HR) is an essential biological process common to all living cells that maintains the genome integrity by faithfully repairing double-strand breaks (DSBs). The HR process searches the genome for a region that is homologous to the broken DNA and uses this region as a template to restore the DNA integrity, via the capture of the complementary strand that gets paired with the damaged DNA. Nucleofilaments resulting from the polymerization of a recombinase (RecA in prokaryotes) on each damaged DNA strand recruit the genomic DNA, test it for homology and promote strand exchange. The coordination of dynamic stages with different time and length scales enables the process to be simultaneously fast and stringent. By combining docking explorations and molecular dynamics simulations at the atomic level, we have integrated the results from 30 years studies into new structural insights on the HR process. We propose a mechanism for the initial recognition/strand exchange phase, where more than 80% of non-homologous sequences are eliminated, that uses mechanical tension in the DNA to locally destabilize the base pairing interactions in the searched DNA and perform swift homology tests via pairing exchange. We also investigated the role of ATP hydrolysis in the slower phases of HR using molecular dynamics simulations. These simulations, based on the hypothesis that the filament can change the internal arrangement of its monomers upon ATP hydrolysis, revealed how hydrolysis may promote reverse strand exchange in the filament. This provides a structural interpretation to the observed destabilization of the strand exchange product within filaments where ATP is hydrolyzed.