This document discusses how bacteria sense and respond to surfaces. It describes different types of surface signals bacteria can detect, including osmolarity, chemicals, and mechanical signals. It also explains how bacteria use various structures and pathways to transduce these surface signals, such as extracellular appendages like flagella, transporters, sensor kinases, response regulators, and two-component signaling systems. While research has provided insights into these surface sensing mechanisms, key questions remain about how bacteria precisely detect mechanical forces and how signaling pathways interact and integrate multiple surface signals.
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Access to large-scale omics datasets i.e. genomics, transcriptomics, proteomics, metabolomics, phenomics, etc. has revolutionized biology and led to the emergence of systems approaches to advance our understanding of biological processes. With decreasing time and cost to generate these datasets, omics data integration has created both exciting opportunities and immense challenges for biologists, computational biologists, biostatisticians and biomathematicians. Genomics, transcriptomics, proteomics, and metabolomics together they help to bring out the best of characters in plants.
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Regulation of gene expression in prokaryotes and viruses includes gene expression mechanism of prokaryotes such as lac operon ,trp operon, feedback inhibition, types of temporal response, positive and negative gene regulation. It also includes mechanisms such as reverse transcriptase in viruses.
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Regulation of gene expression in prokaryotes and virusesNOOR ARSHIA
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Se deja accesible la presentación de la tesis “Objetos de Aprendizaje con eXeLearning y GeoGebra para la definición y representación geométrica de operaciones con vectores y sus aplicaciones”, defendida el 18 de enero de 2017 en el Programa de Doctorado en Formación en la Sociedad del Conocimiento de la Universidad de Salamanca, concretamente dentro de las líneas de investigación del GRupo de investigación en InterAcción y eLearning (GRIAL), que es Unidad de Investigación Consolidad (UIC081) de la Junta de Castilla y León (García-Peñalvo, 2016; García-Peñalvo et al., 2012).
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Microorganisms cause virtually all pathoses of the pulp and periapical tissues.
Once bacterial invasion of pulp tissues has taken place, both non-specific inflammation and specific immunologic response of the host have a profound effect on the progress of the disease.
Endodontic infection develops in root canals devoid of host defenses,
pulp necrosis (as a sequel to caries, trauma, periodontal disease,or iatrogenic operative procedures)
or pulp removal for treatment.
Biofilm-induced oral diseases.
ROUTES OF ROOT CANAL INFECTION
Caries
• Trauma-induced fractures
• Cracks
• Restorative procedures
• Scaling and root planing
• Attrition
• Abrasion
• Gaps in the cementoenamel junction
at the cervical root surface
• Dentinal tubules
• Direct pulp exposure
• Periodontal disease
• Anachoresis
Mechanisms of Microbial Pathogenicity and Virulence Factors
Pathogenicity : The ability of a microorganism to cause disease.
Virulence: Degree of pathogenicity of a microorganism.
Some microorganisms routinely cause disease in a given host and are called primary pathogens.
Other microorganisms cause disease only when host defenses are impaired and are called opportunistic pathogens by changing the balance of the host–bacteria relationship.
Bacterial strategies that contribute to pathogenicity include the ability to coaggregate and form biofilms.
In the pathogenesis of primary apical periodontitis
Bacteria in caries lesions form authentic biofilms adhered to dentin.
Diffusion of bacterial products through dentinal tubules induces pulpal inflammation
After pulp exposure, the exposed pulp tissue is in direct contact with bacteria and their products
and responds with severe inflammation. Some tissue invasion by bacteria may also occur.
Bacteria in the battlefront have to survive the attack from the host defenses and at the same time acquire nutrients to keep themselves alive.
In this bacteria–pulp clash, the latter invariably is “defeated” and becomes necrotic, so bacteria move forward and “occupy the territory”—that is, they colonize the necrotic tissue.
These events advance through tissue compartments, coalesce, and move toward the apical part of the canal until virtually the entire root canal is necrotic and infected.
At this stage, involved bacteria can be regarded as the early root canal colonizers or pioneer species (play an important role in the initiation of the apical periodontitis disease process, modify the environment, making it conducive to the establishment of other bacterial groups)
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Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
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Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Manipulating bacterial cell fate via signal transduction
1.
2. 1. Introduction
2. Surface sensing
3. Different types of signals
4. Sensors
5. Enveloped sensors
6. Signal transduction
7. Conclusion:
3. Unicellularity
of bacteria
• Multicellular communities in the presence of biotic
or abiotic surfaces
• Biofilms
• Swarming motility
• Both biofilm and swarming e.g E- coli, P. aeruginosa
Resistance to
adverse
conditions
• Resistance to antibiotics and metal
treatments
• High cell density protects Salmonella,
Bacillus, Serratia [Butler, 2010] and E. coli
[Perrin, unpublished data] against biocides
• Result is increased virulence [ James 2008 ]
Bioremedia-
tion
• Knowledge of the molecular basis of the behavior of
switch
• identification of the switch signals
4. Biofilm formation:
Free-floating bacterium collides with a surface
Biofilm development is the anchorage of the cell to a support (cellular or
abiotic)
Cascade of
physiological
reactions
Different species
and different
experimental
conditions
repression of motility
functions, production of
more adherence factors,
and production of
exopolysaccharides
[Beloin 2008 ]
Numerous highly
diverse
stimuli affect biofilm
formation
contact-dependent
signalling [Belango 2009]
5. Osmolarity
• differences in water
activity = allowing
bacteria to recognize a
solid-liquid interface
• sessile
bacteria=higher
concentration of
intracellular
potassium, compared
to the free-floating
cells.
• ion-sensitive field
effect transistor
(ISFET) [Possonet
2008 ]
• Curli-proficient
[Leugene 2003]
Chemicals
• metabolites (glucose,
indole, polyamines
etc)
• inorganic molecules
(iron, phosphate),
• quorum signals
• antimicrobials (host-
derived molecules
such as bile salt,
epinephrin and
norepinephrin,
antibiotics, metals,
detergents, H2O2
etc)[Karatan 2009]
Mechanical signals
respond to surface
contact
surface stiffness=
genetic
program=specific
pattern of adhesion and
cytoskeletal
Organization [Discher
2005]
Increase in substrate
stiffness=
Staph.epidermis and E-
coli [ Litcher 2008]
6. Signals Contd……
P. aeruginosa responds to increasing surface stiffness (produced by raising the
concentrations of agar in solid media) by an increase in the production of type IV
pili.
Surface attachment appears, then, to regulate not only the production but
also the polar localization of the pilus component. [Cowles 2010]
Urinary tract-associated E. coli often produce adhesive type 1 pili exhibiting
the adhesin FimH at the tip.
FimH binds to glycoproteins carrying high-mannose-type oligosaccharide
chains and, more generally, to mannose.
A histidine tagged version of FimH has been created to enable transgenic E.
coli to attach to immobilized nickel.
The transcriptional response to attachment was then compared in modified E.
coli cells (beads coated with nickel) and in parental cells (agarose beads coated
with mannose) suggesting that a mechanical signal is transmitted from the
outside to the intracellular structures, following fimbrial adhesion [Bhomkar
2010]
7. Extracellular appendages:
Flagella = role in adherence to host cells, clumping, and biofilm formation
in many ways [Anderson 2010]
act as adhesins
cessation of flagellar motility and repression of flagellar gene transcription.
a molecular clutch [Blair 2008]
mutations in the flagellar motor : bacteria is immobilized on a surface =flagellar
motor stops, the ion flow through the motor ceases and the membrane
potential is transiently increased= signal for biofilm formation
Bacterial Flagellum
Basal body Hook Filament
8. Swarming: coordinated translocation of a cell population across a solid or
semi-solid surface driven by type IV pili or flagella Proteus mirabilis and in
Vibrio parahemolyticus[Jarell 2008]
No data available on the use of the flagellum as a mechanosensor and one
pending question is how widespread this role might be?????
Sensing mechanism allowing the cell to distinguish a
“semi-solid surface” (swarming) from a solid surface (biofilm) is still obscure
[Wang 2012]
9. Transporters:
efficient co-sensors e.g Fumarate sensing: signalling pathway involving
DcuS/DcuR, controlling the response to extracellular fumarate. [Kleefeld
2009]
Outer membrane protein OmpA in E. coli, and its ortholog OprF in P.
aeruginosa, are both involved in biofilm formation, as well as having a variety
of other functions
OmpA induces envelope stress Cpx signalling pathway [Ma Q 2009]
NlpE/Cpx pathway.
Via Cpx, Bae, Rcs, Psp and σE pathways
Chemical
stresses
Physico-
chemical
stresses
mechanical
stresses
response to various stresses applied the envelope
either by use protein phosphorylation in response to environmental
stimuli or sigma E regulated release or binding of a transcriptional
factor.
10. Scr pathway. In V. parahaemolyticus, the scrABC operon controls the switch between
swarming and biofilm formation via the inverse regulation of lateral flagella genes (laf) and
capsular polysaccharide genes (cps)
Focal adhesion. A focal adhesion is an anchoring junction of the cell to a substrate. In
eukaryotic cells, it links the internal actin-myosin network to the extracellular matrix
through transmembrane linkers, such as integrins.[Maureillo 2010]
Cytoplasmic sensors
H-NS. H-NS is a nucleoid-associated protein acting as a global regulator of gene expression,
and it is essential for bacterial virulence and environmental adaptation [Higgins 1988]
Frz pathway. The soil bacteria M. xanthus uses [Bao 2009]
Conclusion
• sensing obviously occurs at multiple levels, extracellular appendages, the envelope, and/or
cytoplasmic sensors
• surface-sensors are all proteins but the mechanisms of mechanical force sensing via
proteins are still obscure.
• molecular basis by which the flagellum communicates with the transcriptional machinery
is still poorly understood
• physical (temperature) or chemical (pH) parameters, protein deformation probably plays a
major role in response to mechanical forces.
11. Modularization of signalling pathways:
On the basis of genome analysis, one-component systems appear to be more widely
distributed, and more abundant, in bacteria.
experiments investigating E. coli biofilm formation identified the transfer of phosphate
groups by two-component signal transduction systems as the main mechanism employed
to process environmental information [Nifa 2007]
13. Response Regulator:
Two domains constitute the RR, a highly conserved receiver domain (REC) and a
variable output or effector domain.
Phosphorylation mediates dimerization of the receiver domains and activates
transcriptional function, or enzymatic activity in the case of diguanylate cyclase
catalytic domains [Gao 2010]
Auxiliary-regulators:
Recently concept of co-sensors or auxiliary regulators modulating phosphotransfer
along the basic two-component signalling pathway has emerged.
Auxiliary regulators are widespread, both in Gram-positive and Gram-negative
bacteria, and can be found either in the cytoplasm (for example E. coli PII protein as
the modulator of the NtrBC pathway in the nitrogen response) or in the inner
membrane (for example IgaA and MzrA) [Gerken 2010]
14. Numerous regulatory devices ensuring signal transduction in
response to surface-sensing have been identified in bacteria but the
nature of the signal detected is still difficult to approach
experimentally.
The role of extracellular appendages, such as flagella, in
surfacesensing and, more generally, mechanisms of
mechanotransduction need to be investigated.
An exciting hypothesis is that large proteic assemblies, able to both
sense and regulate the response to a surface, may exist in bacteria.
Moreover, although huge progress has been made in the
characterization of individual regulatory pathways, we are just
beginning to address the complexity of the interactions between
the different elements.
Evaluating the in vivo extent of the numerous possibilities of
crosstalk is a major challenge.