Global economic slowdown forced a rethink and relook at these agents like old wine in a new bottle. Several studies, especially those using ‘T2T’ have shown that the most important trick PLX4032 research buy to achieve remission or low disease activity in RA is early aggressive approach rather than the choice of the medications. Modern management

of RA should, therefore, be directed by this approach. Early and continued suppression of rogue autoimmune cells and their products to delay or abort their attempt to gain autonomy seems to be the key to successful treatment in RA. A number of studies in the recent past have reaffirmed the faith in the conventional DMARDs with favourable efficacy profile such as hydroxychloroquine, sulphasalazine, methotrexate (MTX) and leflunomide, especially when used in a combination regimen. One such combination popularly called ‘triple therapy’ (hydroxychloroquine + sulphasalazine + methotrexate) with or without very low dose steroid has passed the test of time. Much to the disappointment of proponents of biologics as the first line therapy, new studies have found combination of synthetic DMARDs non-inferior to the coveted biologics alongwith

greatest economic advantage to their credit, provided the treatment is started early and intensity of dosage is guided and adjusted by T2T approach. Addition of other inexpensive agents like vitamin D and fish oil can add even further benefit and have been variably reported. However, the strongest point NVP-BEZ235 datasheet that remains in favour of the biologics is the rapid onset of action and radiological healing; these advantages, unfortunately, are enjoyed only by privileged few with funding support from state, insurance or self. Whether to use biologics in early disease or in patients who have persistently active disease despite conventional DMARDs, therefore, is more of a sociopolitical issue than a scientific one. In the following paras, DCLK1 we will dissect out these issues with facts.

All biological agents including tumour necrosis factor (TNF) inhibitors namely Infliximab, Etanercept, Adalimumab, Golimumab and Certolizumab, interleukin-6 antagonist Tocilizumab, T cell costimulatory antagonist Abatacept, B cell depleting agent Rituximab and the upcoming JAK signaling inhibitor Tofacitinib have proven their efficacy in active RA patients who failed MTX in clinical trials. In addition to the treatment goal of achieving symptomatic relief, these biologic agents in combination with MTX as an anchor drug have also shown superiority over MTX monotherapy in clinical outcomes including induction of remission, retardation of structural deformity and preservation of physical function in established RA as well as in early RA, with the exception of Tocilizumab which has been shown to be superior to MTX even as monotherapy by itself alone.

Global economic slowdown forced a rethink and relook at these agents like old wine in a new bottle. Several studies, especially those using ‘T2T’ have shown that the most important trick Sirolimus chemical structure to achieve remission or low disease activity in RA is early aggressive approach rather than the choice of the medications. Modern management

of RA should, therefore, be directed by this approach. Early and continued suppression of rogue autoimmune cells and their products to delay or abort their attempt to gain autonomy seems to be the key to successful treatment in RA. A number of studies in the recent past have reaffirmed the faith in the conventional DMARDs with favourable efficacy profile such as hydroxychloroquine, sulphasalazine, methotrexate (MTX) and leflunomide, especially when used in a combination regimen. One such combination popularly called ‘triple therapy’ (hydroxychloroquine + sulphasalazine + methotrexate) with or without very low dose steroid has passed the test of time. Much to the disappointment of proponents of biologics as the first line therapy, new studies have found combination of synthetic DMARDs non-inferior to the coveted biologics alongwith

greatest economic advantage to their credit, provided the treatment is started early and intensity of dosage is guided and adjusted by T2T approach. Addition of other inexpensive agents like vitamin D and fish oil can add even further benefit and have been variably reported. However, the strongest point Olaparib mw that remains in favour of the biologics is the rapid onset of action and radiological healing; these advantages, unfortunately, are enjoyed only by privileged few with funding support from state, insurance or self. Whether to use biologics in early disease or in patients who have persistently active disease despite conventional DMARDs, therefore, is more of a sociopolitical issue than a scientific one. In the following paras, IKBKE we will dissect out these issues with facts.

All biological agents including tumour necrosis factor (TNF) inhibitors namely Infliximab, Etanercept, Adalimumab, Golimumab and Certolizumab, interleukin-6 antagonist Tocilizumab, T cell costimulatory antagonist Abatacept, B cell depleting agent Rituximab and the upcoming JAK signaling inhibitor Tofacitinib have proven their efficacy in active RA patients who failed MTX in clinical trials. In addition to the treatment goal of achieving symptomatic relief, these biologic agents in combination with MTX as an anchor drug have also shown superiority over MTX monotherapy in clinical outcomes including induction of remission, retardation of structural deformity and preservation of physical function in established RA as well as in early RA, with the exception of Tocilizumab which has been shown to be superior to MTX even as monotherapy by itself alone.

Some regenerative ability, however, is found also in reptiles and birds, and even in mammals. The recognition that neurogenesis indeed occurs in the CNS

of all adult vertebrates challenges the view that there is a simple relationship between maintenance of neurogenic regions in the adult CNS and regenerative capability. The aim of this review is to revisit this relationship in the light of recent literature focusing on selected examples of neurogenesis and regeneration, and discuss possible frameworks that may help to elucidate the relationship SCH772984 between adult neurogenesis and regeneration. This could provide useful paradigms for harnessing regeneration in the human CNS. “
“Neuron firing patterns underpin the detection and processing of stimuli, DNA Synthesis inhibitor influence synaptic interactions, and contribute

to the function of networks. To understand how intrinsic membrane properties determine firing patterns, we investigated the biophysical basis of single and repetitive firing in spinal neurons of hatchling Xenopus laevis tadpoles, a well-understood vertebrate model; experiments were conducted in situ. Primary sensory Rohon–Beard (RB) neurons fire singly in response to depolarising current, and dorsolateral (DL) interneurons fire repetitively. RB neurons exhibited a large tetrodotoxin-sensitive sodium current; in DL neurons, the sodium current density was significantly lower. High-voltage-activated calcium currents were similar in both neuron Methocarbamol types. There was no evidence of persistent sodium currents, low-voltage-activated calcium currents, or hyperpolarisation-activated currents. In RB neurons, the potassium current was dominated by a tetraethylammonium-sensitive slow component (IKs); a fast component (IKf), sensitive to 4-aminopyridine, predominated

in DL neurons. Sequential current-clamp and voltage-clamp recordings in individual neurons suggest that high densities of IKs prevent repetitive firing; where IKs is small, IKf density determines the frequency of repetitive firing. Intermediate densities of IKs and IKf allow neurons to fire a few additional spikes on strong depolarisation; this property typifies a novel subset of RB neurons, and may activate escape responses. We discuss how this ensemble of currents and firing patterns underpins the operation of the Xenopus locomotor network, and suggest how simple mechanisms might underlie the similar firing patterns seen in the neurons of diverse species. “
“A burst of action potentials in hippocampal neurons is followed by a slow afterhyperpolarization (sAHP) that serves to limit subsequent firing. A reduction in the sAHP accompanies acquisition of several types of learning, whereas increases in the sAHP are correlated with cognitive impairment. The present study demonstrates in vitro that activity-dependent bidirectional plasticity of the sAHP does not require synaptic activation, and depends on the pattern of action potential firing.

Three 1-L beakers were filled with 200 mL of theront solution each at a concentration of 6800 theronts mL−1. Edwardsiella ictaluri was added to each beaker as follows:

(1) 0 CFU mL−1; (2) 4 × 105 CFU mL−1; and (3) 4 × 107 CFU mL−1. After exposure to E. ictaluri for 1 h, theronts were harvested by centrifugation in 50-mL tubes at 240 g BMS-354825 for 3 min and the supernatant discarded. Theronts were then washed (three times) with fresh tank water and centrifuged, and the supernatant was discarded to remove nonadherent bacteria. After washing, theronts were suspended in 100 mL tank water and enumerated with a Sedgwick-Rafter cell (Xu et al., 2000). Six 2-L beakers were used with 1 L water and 30 channel catfish fingerlings distributed in each container. The fish (3.3 ± 0.5 cm in length and 0.3 ± 0.1 g in weight) were acclimated to laboratory conditions 3 days prior to the trial. Water in each beaker was reduced to 0.5 L. The theronts exposed to various concentrations of E. ictaluri were added to each beaker at 1000 theronts fish−1 (two beakers for each treatment). Five fish were sampled from each beaker at 4 h, 1 day, and 2 days post-theront exposure. The remaining 15 fish in each beaker were monitored for mortality. Each sampled fish was put in a 1.5-mL microcentrifuge tube, labeled, and washed with sterile water three times. Each fish was homogenized after adding 0.5 mL sterile water to a clean microcentrifuge

tube using a 1.5-mL pellet pestle. Half of the fish tissue from each sample was transferred to a 15-mL tube with 5 mL brain heart infusion click here (BHI) broth containing 100 μg mL−1 ampicillin and incubated at 28 °C for 24 h with shaking. The pZsGreen-transformed stiripentol E. ictaluri was able to grow in BHI with ampicillin, but other autochthonous bacteria were inhibited. The presence of E. ictaluri was examined by florescence microscopy at 24 h postculture. The remaining fish tissue was frozen at −20 °C for DNA extraction and used for qPCR. The tissues preserved at −20 °C were used to extract DNA and quantitate E. ictaluri with qPCR. Total genomic DNA of E. ictaluri

in fish tissues was extracted by the DNeasy Tissue kit and eluted into 200 μL water according to the manufacturer’s instructions. DNA yield and purity were determined using a Nanodrop ND-1000. The gDNA was stored at −20 °C until use. One-step qPCR was performed as described by Bilodeau et al. (2003) using E. ictaluri-specific primers (forward 5′-ACTTATCGCCCTCGCAACTC-3′ and reverse 5′-CCTCTGATAAGTGGTTCTCG-3′) and a dual-labeled probe (5′-CCTCACATATTGCTTCAGCGTCGAC-3′). Reactions were completed using an Applied Biosystems 7500 with the following conditions: 50 °C for 2 min, 95 °C for 2 min followed by 40 cycles of 95 °C for 15 s and 60 °C for 1 min. Extracted DNA from fish tissue (1 μL) was used as template in qPCR, and the DNA concentration in fish tissue was determined via the standard curve [threshold cycle (Ct) values vs. DNA concentration of E. ictaluri].

We also found that the relative frequency of trauma and injuries in travelers increased with advancing age, which may result from age-related decreased sensory, motor, and perceptual skills. Deaths were four times more frequent in the older group compared

to the younger one and mainly caused by infectious diseases which reflects the predominance of specialized infectious diseases clinics in GeoSentinel network, when deaths in travelers are usually caused by trauma and non-communicable diseases.11 The major strength of our analysis is its multicenter nature, which provided a large number of participants from many countries and captured all traveler types, and its focus on proportionate morbidity. The limitations of this method of analysis have been recently discussed.32 In particular, because the denominator data (number of travelers) cannot be ascertained, it is not possible to calculate incidence rates Depsipeptide nmr or absolute risk. Also, this data might not be representative of the overall population of travelers, and the results do not represent the broad spectrum of illnesses typically seen at non-specialized

primary care practices where mild or self-limited conditions present with higher frequency. Due to the nature of GeoSentinel clinics, illnesses acquired after travel to non-tropical destinations or non-infectious PD0332991 price travel-related illnesses may be underrepresented. Underlying chronic diseases are not documented by GeoSentinel which does not allow evaluation of their influence on travel-associated morbidity. However,

the GeoSentinel database (and associated analyses) has nevertheless been identified as a valuable source of data on the epidemiology GBA3 of travel-related illnesses.13,32,33 In conclusion, older travelers represent a minority of patients in travel clinics but they are usually sicker with a higher relative proportion of life-threatening diseases (LRTI, HAPE, severe P falciparum malaria, cardiovascular disease, and pulmonary embolism),34 as well as a higher proportion of death, compared to younger patients. Older travelers should be specifically targeted for the prevention of such diseases and advised to obtain travel insurance that covers chronic stable medical conditions, acute illnesses, accidents, evacuation, and death. GeoSentinel is supported by a cooperative agreement (5U50CI000359) from the Centers for Disease Control and Prevention and by an initial pilot grant from the International Society of Travel Medicine. The authors state they have no conflicts of interest to declare. In addition to the authors, members of the GeoSentinel Surveillance Network who contributed data (in descending order) are as follows: Prativa Pandey, CIWEC Clinic Travel Medicine Center, Kathmandu, Nepal; Kevin C. Kain, University of Toronto, Toronto, Canada; Gerd-Dieter Burchard, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany; Michael D. Libman, Brian Ward, and J.

, 2011). The isobaric tag for relative and absolute quantitation (iTRAQ) Compound Library concentration and liquid chromatography tandem mass spectrometry (LC-MS/MS) assays were performed by Beijing Protein Innovation (BPI) using previously described methods (Chao et al., 2010). Differentially expressed genes were identified based on at least a twofold expression change and a P-value < 0.05 relative to the WT control. The identified proteins were assigned the appropriate gene numbers by reference to the S. suis strain 05ZYH33 genome (Chen et al., 2007). Where appropriate, the data were analysed using Student's t-test, and a value of P < 0.05 was considered significant. Via genome analysis

of S. suis 05ZYH33, we found that peptides encoded by 05SSU2148 and 05SSU2149 ERK inhibitors exhibit 25% and 30% amino acid sequence identity with the VirR and VirS proteins of C. perfringens strain 13 (Shimizu et al., 2002), respectively, forming a TCS belonging to the widespread LytR/AlgR family. 05SSU2148 and 05SSU2149

were accordingly renamed virR and virS. Sequence analysis of the virRS locus suggested that these overlapping genes are co-transcribed. Like most bacterial response regulators, VirR (237 aa) has a C-terminal helix-turn-helix DNA-binding domain for promoter recognition and transcriptional control of target genes. In its N-terminal region, VirR contains a typical receiver domain that receives the signal from its sensor partner. virS encodes a 435-aa protein with seven N-terminal transmembrane domains (predicted by tmhmm server v. 2.0 software) and a C-terminal Inositol oxygenase transmitter domain that includes a classical histidine kinase and an ATPase motif. A survey of the publicly available complete genome sequences of S. suis revealed the presence of a VirR/VirS homologue in other S. suis isolates, including

the European strain P1/7, the Vietnamese strain BM407 and 7 Chinese strains (98HAH12, SC84, GZ1, A7, ST1, JS14 and SS12). This suggests a wide distribution of the VirR/VirS system among S. suis isolates. Despite the well-characterized function of the VirR/VirS system in C. perfringens infection, the role of this TCS in S. suis remained unclear. To address this issue, an isogenic virRS knockout mutant (ΔvirRS) was constructed in strain 05ZYH33 by allelic replacement with a constitutive spc cassette (Supporting information, Fig. S1). The growth curves of WT and ΔvirRS cultured in THY medium at 37 °C were compared, and no significant difference was observed (Fig. 1). When streaked on THY plates supplemented with 5% sheep blood, ΔvirRS and WT colonies displayed a similar haemolytic phenotype. However, observation with a light microscope revealed that the mean chain length of the ΔvirRS mutant was much shorter than that of WT under the same growth conditions (Fig. 2a).

Although injecting drug users showed a less marked improvement in CD4 cell count over time than other risk groups, they showed a similar improvement in detectable viral load. In the decade (1998–2008) since the introduction of combination antiretroviral therapy (cART), the rates of AIDS-related deaths and pathological events have dramatically decreased in Western Europe [1]. The declining trends over time in the prevalence of immunosuppression and Y-27632 in vivo detectable viraemia [2,3] reflect the impact of the

successful use of cART, together with increases in drug uptake [4]. The best predictor of disease progression is the current absolute CD4 cell count, but the patient’s age, current HIV RNA viral load (VL) and pre-ART AIDS diagnoses have also been shown to play a significant role in disease progression [5,6]. Populations of HIV-infected individuals are composed of subgroups with different demographics, and it remains unclear whether virological outcomes vary according to patients’ mode of HIV acquisition,

possibly because of differences in the level of adherence to ART [7]. In addition, different ethnic groups may have different opportunities to access medical care [8]. Other factors, such as hepatitis coinfections and centre of care, may influence patients’ immuno-virological Alpelisib manufacturer outcomes, although previous studies have reported conflicting results, both in the pre-cART and in the cART eras [9–15]. Social and clinical centre-related factors were found to be associated with the level of adherence to cART in previous studies [13–17]. The success of clinical care for HIV-1 infection across demographic groups was analysed in detail in the UK for the period 1999–2004 [13], while the durability and outcome of initial ART were investigated in a Swiss cohort from 2001 to 2005 [18]. Estimates for more recent years, after the introduction of new classes of antiretrovirals, are lacking. Furthermore, because of the well-known

differences in the distribution of mode of transmission and ethnicity between the South and North of Europe [i.e. a higher prevalence of transmission via injecting drug use (IDU) and a lower proportion of transmission via homosexual contact in Italy compared with Northern Europe], it is important to evaluate the impact of ART at ID-8 the population level in different geographical and social settings. The main objective of this work was to evaluate the success rate of ART in Italy in the period 1998–2008. More specifically, we aimed to assess whether the prevalence of patients in Italian clinics with an ‘adverse prognosis’ (defined as a marker visit with CD4 ≤200 cells/μL or VL >50 HIV-1 RNA copies/mL) changed over time and if there were significant differences in the proportion of patients with adverse prognosis according to patient demographics and other characteristics.

The response and adaptation of bacteria to environmental stress are known to be mostly regulated at the level of transcription initiation. This regulation primarily involves alternative sigma factors, which recruit RNA polymerase and facilitate specific promoter recognition and transcription initiation (Paget & Helmann, 2003). Extracytoplasmic function (ECF) sigma factor, the largest group of alternative sigma factors, plays a key role in adaption to environmental conditions (Staron et al., 2009). Furthermore, because bacteria–host RG7204 nmr interaction via surface structures is important in bacterial pathogenesis, ECF sigma factors also regulate

virulence factors (Staron et al., 2009). This is well documented in Mycobacterium tuberculosis (Hahn et al., 2005), Staphylococcus aureus (Shaw et al., 2008), Pseudomonas aeruginosa (Llamas et al., 2009; Wood & Ohman, 2009), and Enterococcus faecalis (Le et al., 2010). Porphyromonas gingivalis, an anaerobic gram-negative bacterium, is an important etiological agent in adult chronic periodontitis. This

organism possesses several cell surface-associated virulence factors (e.g. hydrolytic enzymes, fimbriae, hemagglutinin, capsule, and lipopolysaccharide) that can directly or indirectly affect the periodontium (Yoshimura et al., 2009). In addition, to survive in the microenvironment of an advanced periodontal pocket, it is necessary that the bacteria have the capacity to respond to environmental changes including temperature, pH, the concentration of some nutrients, and oxygen tension. To date, little is known about the relationship between the regulation of adaptive mechanisms, virulence, and sigma factors in P. JAK inhibitor gingivalis. The P. gingivalis W83 genome encodes eight sigma factors, six of which belong to the ECF sigma factor subfamily (PG0162, PG0214,

PG0985, PG1318, PG1660, and PG1827) (Nelson et al., 2003). The PG1318 ECF sigma factor was recently shown to be involved in the regulation of mutation frequency in P. gingivalis (Kikuchi et al., 2009). In this study, we used a PCR-based linear transformation strategy to inactivate the remaining five putative ECF sigma factors, selleck compound and analyzed the virulence-related characteristics of these proteins in P. gingivalis W83. We now report that several of the ECF sigma factors may play a role in virulence regulation and adaptation to oxidative stress. ECF sigma factors encoded by the PG0162 and PG1660 genes are likely involved in the post-transcriptional regulation of the gingipains. The strains and plasmids used in this study are listed in Table 1. Porphyromonas gingivalis strains were grown in a Brain–Heart Infusion (BHI) broth supplemented with 0.5% yeast extract (Difco Laboratories, Detroit, MI), hemin (5 μg mL−1), vitamin K (0.5 μg mL−1), and cysteine (0.1%) (Sigma-Aldrich, St. Louis, MO). Porphyromonas gingivalis strains were maintained in an anaerobic chamber (Coy Manufacturing, Ann Arbor, MI) in 10% H2, 10% CO2, and 80% N2 at 37 °C. The growth rates for P.

Flemming

et al. (2007) proposed seven categories of EPS: structural, sorptive, surface-active, active, informative, redox-active Selleckchem PD 332991 and nutritive EPS. However, only four of these classes occur in molecules identified in B. subtilis: the categories include structural, sorptive, surface-active and active EPS (Table S1). Structural EPS refer to molecules such as neutral polysaccharides, which serve as architectural components in the matrix, facilitating water retention and cell protection. Sorptive EPS are composed of charged polymers, whose function is sorption to other charged molecules involved in cell–surface interactions. Surface-active EPS are molecules with an amphiphilic behavior. These molecules, with different chemical structures and surface properties, are involved in biofilm formation and sometimes possess antibacterial or antifungal activities. The active EPS group is the most diverse group and includes all extracellular proteins produced by B. subtilis. Only those enzymes required for biofilm formation and architecture are discussed. Structural EPS are mainly composed of neutral polysaccharides that lend structure to the exopolymeric matrix.

These exopolysaccharides are formed in the biofilm matrix Trametinib in vivo of many bacterial species for example Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae and Enterobacter aerogenes (Morikawa et al., 2006; Ryder et al., 2007). However, only a few studies report the

isolation and identification of exopolysaccharides Verteporfin purchase from B. subtilis. The best-studied exopolysaccharide produced by B. subtilis is levan type I and II. Levan type I consists of β-2,6-linked d-fructose units, whereas type II is a fructose polymer with a glucose residue linked to the terminal fructose by α-glycoside bond. Levan can be synthesized outside the cell following the extrusion of the extracellular enzyme levansucrase (Abdel-Fattah et al., 2005; El-Refai et al., 2009). Further details on levansucrase extrusion and induction are included in the section describing active EPS. Levan is widely distributed and produced by various plants and microorganisms including B. subtilis strains 327UH, ISS3119, QB112 and Pseudomonas sp. (Yamamoto et al., 1985; Pereira et al., 2001; Shida et al., 2002). In Pseudomonas, it has been suggested that levan forms a capsule protecting against the attack of bacteriophages and also helps prevent cell desiccation (Paton, 1960). Capsule formation draws nutrients by attracting solutes and creating an osmotic gradient until equilibrium is reached (Paton, 1960). Another ecological role of levan has been described for Paenibacillus (formerly Bacillus) polymyxa CF43, where this polysaccharide facilitates the aggregation of root-adhering soil on wheat plants (Bezzate et al., 2001).

, 1957; Girodeau et al., 1986; Lloyd et al., 2004). Attempts to express the Mt-dapF (Rv 2726c) in E. coli failed, in spite of the highly efficient T7 promoter in the pET28 vector. It was reasoned out that the lack of dapF expression was related to poor translation (Usha et al., 2006). Mt-dapF was subsequently cloned and over-expressed using a novel codon

alteration strategy and the purified recombinant enzyme functionally characterized (Usha et al., 2006). The Km for meso-DAP was determined to be 1217 μM. Mt-DapF exists as a monomer. Dithiothreitol is required for Mt-DapF activity, consistent with its requirement for two reduced active site thiols (Usha et al., 2006). Mt-DapF activity is inactivated in the presence of nanomolar click here concentrations of the three different thiol-specific alkylating agents (Usha et al., 2008). Site-directed mutagenesis confirmed that the two conserved Cys87 and Cys226 residues were involved in catalysis (Usha et al., 2008). The crystal structure of

the unliganded form of Mt-DapF has been refined to 2.6 Ǻ resolution. Mt-DapF is made up of two pseudosymmetrical α/β domains (Usha et al., 2009). The active site is located in the cleft between domains I and II. The ribbon model of Mt-DapF selleck chemical is shown in Fig. 2. Tyr76 is unique to suborder Corynebacterineae DapF, suggesting a route to the design of a species-specific inhibitor (Usha et al., 2009). In mycobacteria, and most Gram-negative bacteria, the third residue in the peptidoglycan (PG) pentapeptide is d,l (meso)-diaminopimelic acid (Schleifer

& Kandler, 1972). During exponential phase, mycobacteria cross-link the third (meso-DAP) residue and the fourth (d-Ala) residue of adjacent stem peptides (Schleifer & Kandler, 1972; Wietzerbin et al., 1974). On entering stationary phase, mycobacteria incorporate increasing amounts of meso-DAPmeso-DAP linkages, which results in an unusually high DAP content (Wietzerbin et al., 1974; Cirillo et al., 1994a). meso-DAP Glutathione peroxidase is essential for both types of mycobacterial PG cross-linking. The percentage of cross-linking is very high (70–80%) in Mycobacterium species compared to E. coli (20–30%) (Cirillo et al., 1994b; Matsuhashi, 1994). meso-DAP is introduced into the PG network as part of the cross-linking moiety between the polysaccharide fibres (Ghuysen, 1980) (Fig. 3). In addition, the synthesis of meso-DAP is required for protein synthesis, because after decarboxylation, it yields l-lysine. Orthologues in M. tuberculosis of most of the DAP biosynthesis enzymes have been stably expressed in soluble form and functionally characterized. The crystal structures of most of the DAP biosynthesis enzymes have been solved and the chemical mechanisms studied.