Manual for pre-clinical removable prosthodontics

DENTURE PROSTHODONTICS ‘Complete denture prosthodontics’ is defined as that body of knowledge and skills pertaining to the restoration of the edentulous arch with a removable dental prosthesis. While ‘complete denture prosthetics’ is defined as: 1. the replacement of the natural teeth in the arch and their associated parts by artificial substitutes 2. the art and science of the restoration of an edentulous mouth The complete denture treatment is the restoration of a completely edentulous (no teeth) by an artificial substitute called “Complete denture” which is the replacement of the upper (maxillary) and lower (mandibular) lost teeth by an appliance that may replace the lost teeth and their associated adjacent structure. The complete denture treatment is a treatment that deals with a pathological case, of having no teeth that renders the patient lacking the function of cutting the food as well as being psychologically disturbed of having the cosmetic corruption of the appearance of the face by losing the muscular support of the facial expression. The complete denture could be considered unique when compared to other prostheses replacements in the body, since it deals with both function and appearance, or in other words it deals with the physiology and psychology. Replacing missing teeth is a technical as well as a clinical procedure, a denture cannot be thought of like any other part of the body that can be worn or fitted according to size as no denture of one patient can fit another patient’s mouth even if they were twins. 7 The clinical part of the treatment is to obtain the informative anatomical landmarks from the patient oral cavity by the dentist, and transfer it to the laboratory where the technical part is taken over by the technician. The clinical and the technical aspects of the complete denture fabrication have got an ample intermingling relation that makes the dentist as well as the technician, scientifically and technically attentive of the work of the other. The complete procedure of making a denture should be made clear to the dental student prior to the clinic attendance, thus preparing the student to be fully aware of both the technical (preclinical) as well as the clinical aspects of the treatment and by mastering both it will be possible to understand the sequential steps and their consequences

Reshaping Antibody Diversity

SummarySome species mount a robust antibody response despite having limited genome-encoded combinatorial diversity potential. Cows are unusual in having exceptionally long CDR H3 loops and few V regions, but the mechanism for creating diversity is not understood. Deep sequencing reveals that ultralong CDR H3s contain a remarkable complexity of cysteines, suggesting that disulfide-bonded minidomains may arise during repertoire development. Indeed, crystal structures of two cow antibodies reveal that these CDR H3s form a very unusual architecture composed of a β strand “stalk” that supports a structurally diverse, disulfide-bonded “knob” domain. Diversity arises from somatic hypermutation of an ultralong DH with a severe codon bias toward mutation to cysteine. These unusual antibodies can be elicited to recognize defined antigens through the knob domain. Thus, the bovine immune system produces an antibody repertoire composed of ultralong CDR H3s that fold into a diversity of minidomains generated through combinations of somatically generated disulfides

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

Functional analysis of the ubiquitin ligase Hrd1p with the ubiquitin-conjugating enzyme Ubc7p

Ubiquitin is a covalent protein tag that alters the stability or behavior of a growing list of proteins. Covalent attachment of ubiquitin to target proteins occurs through a cascade of enzymes: Ubiquitin is charged by a ubiquitin-activating enzyme (E1), and transferred to a ubiquitin-conjugating enzyme (E2). Then, transfer of ubiquitin from E2 to a target protein is brokered by a ubiquitin ligase (E3). A critical aspect of E3 function is the selection of a particular E2 to accomplish ubiquitination of a substrate. We examined the requirements for correct E2-E3 specificity in the RING-H2 ubiquitin ligase Hrd1p, an ER-localized protein known to use primarily Ubc7p for its function. Versions of Hrd1p containing the RING motif from homologous E3s were unable to carry out Hrd1p function, revealing a requirement for the specific Hrd1p RING motif in vivo. An in vitro assay revealed that these RING motifs were sufficient to function as ubiquitin ligases, but that they did not display the E2 specificity predicted from in vivo results. We further refined the in vitro assay of Hrd1p function by demanding not only ubiquitin ligase activity, but also specific activity that recapitulated both the E2 specificity and RING selectivity observed in vivo. Doing so revealed that correct E2 engagement by Hrd1p required the presence of portions of the Hrd1p soluble cytoplasmic domain outside the RING motif, the placement of the Hrd1p ubiquitin ligase in the ER membrane, and presentation of Ubc7p in the cytosolic context. We confirmed that these conditions supported the ubiquitination of Hrd1p itself, and the transfer of ubiquitin to the prototype substrate Hmg2p-GFP, validating Hrd1p self-ubiquitination as a viable assay of ligase function. During these studies we observed enhanced Ubc7p-dependent ubiquitination in the presence of soluble Cue1p, which interacts with Ubc7p in vivo. Soluble Cue1p promoted the transfer of ubiquitin from Ubc7p to other ubiquitin molecules in solution. We also observed that this stimulation of Ubc7p by Cue1p and the anchoring of Ubc7p to the ER membrane by Cue1p were both necessary for Ubc7p function in vivo. Ubc7p activation by Cue1p was observed at the ER and with Ubc7p relocated to a cytosolic E3. In total, these studies have substantially improved and expanded our understanding of how Hrd1p functions to degrade proteins in the E

Functional analysis of the ubiquitin ligase Hrd1p with the ubiquitin-conjugating enzyme Ubc7p

Ubiquitin is a covalent protein tag that alters the stability or behavior of a growing list of proteins. Covalent attachment of ubiquitin to target proteins occurs through a cascade of enzymes: Ubiquitin is charged by a ubiquitin-activating enzyme (E1), and transferred to a ubiquitin-conjugating enzyme (E2). Then, transfer of ubiquitin from E2 to a target protein is brokered by a ubiquitin ligase (E3). A critical aspect of E3 function is the selection of a particular E2 to accomplish ubiquitination of a substrate. We examined the requirements for correct E2-E3 specificity in the RING-H2 ubiquitin ligase Hrd1p, an ER-localized protein known to use primarily Ubc7p for its function. Versions of Hrd1p containing the RING motif from homologous E3s were unable to carry out Hrd1p function, revealing a requirement for the specific Hrd1p RING motif in vivo. An in vitro assay revealed that these RING motifs were sufficient to function as ubiquitin ligases, but that they did not display the E2 specificity predicted from in vivo results. We further refined the in vitro assay of Hrd1p function by demanding not only ubiquitin ligase activity, but also specific activity that recapitulated both the E2 specificity and RING selectivity observed in vivo. Doing so revealed that correct E2 engagement by Hrd1p required the presence of portions of the Hrd1p soluble cytoplasmic domain outside the RING motif, the placement of the Hrd1p ubiquitin ligase in the ER membrane, and presentation of Ubc7p in the cytosolic context. We confirmed that these conditions supported the ubiquitination of Hrd1p itself, and the transfer of ubiquitin to the prototype substrate Hmg2p-GFP, validating Hrd1p self-ubiquitination as a viable assay of ligase function. During these studies we observed enhanced Ubc7p-dependent ubiquitination in the presence of soluble Cue1p, which interacts with Ubc7p in vivo. Soluble Cue1p promoted the transfer of ubiquitin from Ubc7p to other ubiquitin molecules in solution. We also observed that this stimulation of Ubc7p by Cue1p and the anchoring of Ubc7p to the ER membrane by Cue1p were both necessary for Ubc7p function in vivo. Ubc7p activation by Cue1p was observed at the ER and with Ubc7p relocated to a cytosolic E3. In total, these studies have substantially improved and expanded our understanding of how Hrd1p functions to degrade proteins in the E

Medical miracle in the Quran

Quran, to the Muslim, is the irrefutable, inimitable Word of Allah(Subhanaho Wa Talah). It was revealed by Allah Almighty, through the instrument of Prophet Muhammad(peace be Upon Him). The Prophet (peace be Upon Him) himself had no role in authoring the Quran, he was merely a human secretary, repeating the dictates of the Divine Creator. The Holy Qur'an is the Holy Book of ISLAM. The verses of the Holy Qur'an were revealed to Prophet Muhammad (peace be Upon Him)by the Angel Jebreel over the period of twenty three years. One or more verses were revealed at a time. The Holy Qur'an is a complete constitution that Allah (SWT) Bestowed on mankind. Its verses give ALLAH's rules and laws for all aspects of life. As well as Quran tells a wide range of scientific phenomena. Concentrating on the medical ones including the human developmental stages, the physiology of the human body, the effect of practicing worships on improving the health, the nutrition aspect as well as controlling diseases, these fact in addition to many others were brought to Prophet Muhammad (peace be Upon Him) since more than 1400 years. The modern science only within the last century proved the reality of these fact to be considered as scientific miracles, from ALLAH

The clinical effect of different self-performed plaque control modalities on the gingival inflammation among a sample of Malaysian adults

Objectives: the aim of this study was to investigate the efficacy of different approach of self-performed plaque removal (mechanical Vs chemical) on the periodontal health status among a sample of Malaysian adults. Methods: thirty seven systemically healthy patients, 20-30 years old and with gingivitis, were recruited for the study. They were randomized into three different groups according to the self-performed plaque control practice (group 1, group 2, and group 3). All subjects received supra and subgingival scaling, and detailed oral self-care demonstration according to mode of oral self-care for each group. The periodontal parameters gingival index GI, plaque index PI, and bleeding on propping BOP were evaluated at baseline and after two months. Results: The results showed improvements for all periodontal clinical parameters for subjects in group 2 and 3, and significant reduction of BOP levels for subjects in group 3 with chemical and mechanical plaque control compared to group 1 with manual tooth brushing only. Conclusion: Dental health professionals should emphasize on the improvement of quality of self-performed mechanical plaque removal and use of adjunct chemical plaque control mouthwashes

Assays for protein retrotranslocation in ERAD.

Elimination of misfolded proteins by endoplasmic reticulum (ER)-associated protein degradation (ERAD) ensures that proteins proceeding through the secretory pathway are correctly folded and processed, which is critical to minimize ER stress. All ERAD pathways include a protein translocation process termed retrotranslocation, in which ubiquitinated misfolded substrates are extracted from the ER and degraded by the cytosolic 26S proteasome. Despite being integral to ERAD, the retrotranslocation process has been largely obscure. Recently, an explosion of discoveries has provided key mechanistic insights into this novel route of protein transport. These advances were facilitated by the development of in vitro and in vivo assays that utilize components from the yeast Saccharomyces cerevisiae. The assays permit detailed study of the distinct steps in ERAD-linked retrotranslocation, including ubiquitination of selected ERAD substrates, substrate removal from the ER, maintenance of cytosolic substrate solubility in the cytosol, and substrate degradation. Here we provide detailed protocols for these assays that pertain to work on retrotranslocation of integral membrane proteins (ERAD-M substrates), with the expectation that these approaches can be adapted for many related biochemical processes