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Le diagnostic et le traitement du cancer laissent rarement les survivants et leurs proches physiquement et psychologiquement indemnes. Les services dont ils ont besoin dépassent le seul traitement médical, c’est-à-dire qu’il leur faut une variété de soins de soutien répondant à leurs besoins physiques, sociaux, informationnels et émotionnels. La présente étude a pour objectif de répertorier les services de soutien destinés aux survivants du cancer, aux membres de leur famille et à leurs proches aidants qui sont disponibles dans la province du Nouveau-Brunswick, au Canada. Pour ce faire, nous avons procédé à une analyse de l’environnement, ce qui nous a permis de constater que les services disponibles dans la province ne sont pas facilement repérables ou accessibles. On a observé tout particulièrement des lacunes dans les services aux survivants, à leur famille et à leurs proches, en phase post-traitement.

Cancer diagnosis and treatment often have significant physical and psychological implications for both the survivor and their family/caregivers. Necessary services extend beyond medical treatment and include a variety of supportive care services (SCS) that address individuals’ physical, social, educational, and emotional needs. This study seeks to map the SCS available in the province of New Brunswick (NB), Canada, for cancer survivors, their families, and their caregivers. An environmental scan was conducted to assess current SCS available in NB. While some SCS exist in NB, they are not always easily accessible or identifiable, and gaps in services were prevalent. In particular, a gap in services was found for individuals who are no longer actively receiving cancer treatment, as well as for family members and caregivers.

The Mycobacterium tuberculosis ATP-binding cassette transporter Rv1747 is a putative exporter of cell wall biosynthesis intermediates. Rv1747 has a cytoplasmic regulatory module consisting of two pThr-interacting Forkhead-associated (FHA) domains connected by a conformationally disordered linker with two phospho-acceptor threonines (pThr). The structures of FHA-1 and FHA-2 were determined by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, respectively. Relative to the canonical 11-strand β-sandwich FHA domain fold of FHA-1, FHA-2 is circularly permuted and lacking one β-strand. Nevertheless, the two share a conserved pThr-binding cleft. FHA-2 is less stable and more dynamic than FHA-1, yet binds model pThr peptides with moderately higher affinity (∼50 μM versus 500 μM equilibrium dissociation constants). Based on NMR relaxation and chemical shift perturbation measurements, when joined within a polypeptide chain, either FHA domain can bind either linker pThr to form intra- and intermolecular complexes. We hypothesize that this enables tunable phosphorylation-dependent multimerization to regulate Rv1747 transporter activity.

The characterization of active and non-active histidines demonstrates its role in probing the electrostatic interactions along the reaction pathway of a glycoside hydrolase. The results show that histidine play very significant structural and functional roles in the hydrolase because of its diverse ionization behaviors.

A key part in the cytokinetic mechanism of Schizosaccharomyces pombe is the contractile ring myosin, which consists of two heavy chains (Myo2p), two essential light chains (Cdc4p) and two regulatory light chains. NMR spectroscopy is used to compare the structure, stability, and dynamics of the isolated N- and C-terminal domains with one another and with native Cdc4p.

Research has been conducted on endo-beta-1,4-xylanase 10A from Streptomyces lividans xylanase which includes a 130-residue C-terminal family 13 carbohydrate-binding module. The effect of this mulivalency on carbohydrate binding has been investigated via the use of NMR spectroscopy and the results are reported.

Research has been conducted on the endo-beta-(1,4)-xylanase from Bacillus circulans (BCX). Some BCX variants containing active site residue substitutions have been analyzed via NMR spectroscopy and X-ray crystallography and the results are described.

Research has been conducted on the Cellulomonas fimi 1,4-beta-glucanase CenC cellulose-binding domains. The tertiary structure of these domains has been investigated via heteronuclear magnetic resonance spectroscopy.

The resolution structure of the glycosyl-enzyme intermediate is formed on the retaining beta-1,4-xylanase from Bacillus circulans. An analysis of the 1.8 Angstroms resolution structure of the intermediate shows that atoms C5, O5, C1 and C2 of the sugar attains coplanarity as required at the oxocarbenium ion-like transition phases of the double-displacement catalytic mechanism. Several differences beyond the distortion of the sugar moiety are observed following X-ray crystallographic analysis.

A study was conducted to examine the interactions of the N-terminal cellulose-binding domain from Cellulomonas fimi beta-1,4-glucanase CenC with calcium by calorimetry and nuclear magnetic resonance (NMR) spectroscopy. A 50 mM sodium chloride was utilized as a buffer for the NMR studies while a line shape analysis was carried out to determine calcium kinetics. Results indicated that metal ion binding was thermodynamically correlated with native-state stability.

A study was conducted to analyze the thermal stability and oligosaccharide-binding thermodynamics of the N-terminal cellulose-binding domain of the Cellulomonas fimi endoglucanase cenC. Differential scanning calorimetry was utilized to measure stability and oligosaccharide-binding thermodynamics. Results revealed that the intramolecular link in the Cellulose fimi gene contributed to the stability of the endoglucanase cenC and a global two-dimensional minimization routine was utilized to regress the unfolding thermodynamics for the endoglucanase cenC-cellopentaose system.

A research was conducted to study the dynamic behavior of His149 in Bacillus circulans xylanase (BCX) and its relationship with a bound water molecule. Nuclear magnetic resonance spectroscopy was utilized to determine the structure and dynamic environment of the histidine residue. Hydrogen exchange measurements were carried out on unlabeled BCX under varying conditions. Results showed that His149 plays a major role in BCX because of its evolutionary conservation.

The implications for phosphorylation and molecular recognition of Bacillus subtilis response regulator (Spo0F) was investigated by employing high-resolution magnetic resonance structure. Results revealed the presence of relative charge distribution residues located at the site of phosphorylation. This is essential in providing specificity for protein-protein interactions and determining lifetimes of the phosphorylated state.

The structure of the N-terminal cellulose-binding domain from Cellulomonas fimi 1,4-beta-glucanase CenC was determined by multidimensional heteronuclear nuclear magnetic resonance spectroscopy. The results revealed 10 beta-strands which were folded into two antiparallel beta-sheets, forming a jelly-roll beta-sandwich. The strands of the protein surface were shorter than those found in the opposite side of the protein, resulting in a five-stranded binding cleft containing hydrophobic residues at the center and flanked by polar hydrogen-bonding groups.

The N-terminal cellulose-binding domain (CBDN1) from Cellulomonas fimi beta-1,4-glucanase CenC binds amorphous but not crystalline cellulose. The structural and thermodynamic bases of cellulose binding were studied through NMR and difference ultraviolet absorbance spectroscopy in conjunction with calorimetry. The CBDN1 cellulose-binding site spans about five glucosyl units. The cellooligosaccharides bind along a five-stranded beta-sheet that forms a concave face of the jelly-roll beta-sandwich structure of CBDN1.

Selective isotopic labelling and 13C-NMR studies on the pK(sub a) values of the catalytic glutamic acid residues in wild type/mutant Bacillus circulans (BCX) and subtilis xylanases reveal a two-step hydrolysis mechanism involving a covalent glycosyl-enzyme intermediate. The double-displacement reaction of BCX may be broken into glycosylation and deglycosylation steps. The glycosylation step produces the glycosyl-enzyme intermediate and deglycosylation regenerates the native enzyme. These protonation and deprotonation steps are governed by glutamic ionization states.

Conformational changes, including local protein folding, play important roles in protein-DNA interactions. Here, studies of the transcription factor Ets-1 provided evidence that local protein unfolding also can accompany DNA binding. Circular dichroism and partial proteolysis showed that the secondary structure of the Ets-1 Dna-binding domain is unchanged in the presence of DNA. In contrast, DNA allosterically induced the unfolding of an α helix that lies within a flanking region involved in the negative regulation of DNA binding. These findings suggest a structural basis for the intramolecular inhibition of DNA binding and a mechanism for the cooperative partnerships that are common features of many eukaryotic transcription factors., Sequence-specific recognition of DNA by transcription factors is mediated by independent protein modules. The autonomy of Dna-binding domains has recently been challenged by the finding that inhibitory regions, which lie [...]