These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific

recognition of the nucleobase opposite the AP site by the Watson-Crick Selleck BKM120 base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3′-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending selleck chemicals on the complementary combination with the nucleobase opposite the AP site; that

is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the learn more AP site. (C) 2012 Elsevier Ltd. All rights reserved.”
“GATA-1 controls hematopoietic development by activating and repressing gene transcription, yet the in vivo mechanisms that specify these opposite activities are unknown. By examining the composition

of GATA-1-associated 123 protein complexes in a conditional erythroid rescue system as well as through the use of tiling arrays we detected the SCL/TAL1, LMO2, Ldb1, E2A complex at all positively acting GATA-1-bound elements examined. Similarly, the SCL complex is present at all activating GATA elements in megakaryocytes and mast cells. In striking contrast, at sites where GATA-1 functions as a repressor, the SCL complex is depleted. A DNA-binding defective form of SCL maintains association with a subset of active GATA elements indicating that GATA-1 is a key determinant for SCL recruitment. Knockdown of LMO2 selectively impairs activation but not repression by GATA-1. ETO-2, an SCL-associated protein with the potential for transcription repression, is also absent from GATA-1-repressed genes but, unlike SCL, fails to accumulate at GATA-1 activated genes. Together, these studies identify the SCL complex as a critical and consistent determinant of positive GATA-1 activity in multiple GATA-1-regulated hematopoietic cell lineages. (Blood.

The choice of tracheostomy or cricothyrotomy to establish an airway depends on the patients’ clinical condition, for instance; cricothyrotomy should be preferred in patients with cervicothoracal injury or

dislocation who suffer from respiratory dysfunction. Furthermore; if a patient is under risk of hypoxia or anoxia due to a difficult airway, cricothyrotomy should be preferred rather than tracheostomy.”
“The study describes the effects of growth light conditions on growth and morphology of stokplants and LBH589 solubility dmso rooting ability of cuttings for mass clonal propagation of jackfruit (Artocarpus heterophyllus Lam.) without application of rooting hormone. Forty five days-old containerized stockplants were placed under three different levels of light: full

sun (Red to far red ratio 1.25), partial shade (R: FR 1; 60% of full sun) and deep shade (R: FR 0.4; 3% of full sun) for 45 days. Half of the stockplants growing in partial shade or deep shade were transferred to full sun for another 15 days and growth and morphology of shoots and rooting ability of cuttings were investigated. Growth and morphology of shoots and rooting ability of cuttings was significantly affected by the growth light conditions of stockplants. Internode number was significantly fewer, but internode length, leaf area and specific leaf area was higher in deep shade and deep shade to full sun regime. Leaf weight per unit area was decreased gradually, when sun-grown stockplants were transferred selleck to deep shade or partial shade and regained on returning them from the shade to full sun. The highest rooting percentage (100%), maximum number of root (6.3) and root dry selleck chemical weight (62 mg) per cutting was obtained from the cuttings of deep shade to full sun regime followed by deep shade and the lowest was in full sun regime without application of any rooting hormone. (C) 2011 Friends Science Publishers”
“Systems externally reinforced by 123 bonded fibre reinforced polymers (FRP) are widely used in the retrofitting and strengthening of reinforced concrete (RC) structures. A drawback of the usage of this technique

lies on the uncertainty of the long term behaviour of those reinforcements. Researchers have paid heed to this aspect and a number of tests and alternative techniques have recently been described. An experimental programme developed to supplement work of the authors recently published and which focused on specimens not submitted to aggressive environments is described. The specimens used have the same geometry as in the previous paper, but they were exposed to salt fog cycles and dry/wet cycles with salt water for periods of 3000 h, 5000 h and 10,000 h. The interface of the glass fiber polymeric composite (GFRP)-to-concrete was characterized after the systems underwent such aggressive conditions. The GFRP wrap comprised of two layers and wet lay-up technique was used on its preparation and application.

Overexpression of Best-3 significantly attenuated Panobinostat ic50 TNF alpha-induced expression of adhesion molecules and chemokines, and subsequently inhibited the adhesion of monocytes to human umbilical vein endothelial cells (HUVECs). Conversely, knockdown of Best-3 with siRNA resulted

in an enhancement on TNF alpha-induced expression of adhesion molecules and chemokines and adhesion of monocytes to HUVECs. Furthermore, overexpression of Best-3 with adenovirus dramatically ameliorated inflammatory response in TNF alpha-injected mice. Mechanistically, we found up-regulation of Best-3 inhibited TNF alpha-induced IKK beta and I kappa B alpha phosphorylation, I kappa B alpha degradation and NF-kappa B translocation. Our results demonstrated that Best-3 is an endogenous inhibitor of NF-kappa B signaling pathway in endothelial cells, suggesting that forced Best-3 expression may be a novel approach for the treatment of vascular inflammatory diseases.”
“Faced with the concern that an increasing number of airway management devices were being introduced into clinical selleck chemical practice with little or no prior evidence of their clinical efficacy or safety, the Difficult Airway Society formed a working party (Airway Device

123 evaluation Project Team) to establish a process by which the airway management community within the profession could itself lead a process of formal device/equipment evaluation. Although there are several national and international regulations governing which products can come on to the market and be legitimately sold, there has hitherto been no formal professional guidance relating to how products should

be selected (i.e. purchased). The Airway Device Evaluation Project Team’s first PD-1/PD-L1 inhibitor review task was to formulate such advice, emphasising evidence-based principles. Team discussions led to a definition of the minimum level of evidence needed to make a pragmatic decision about the purchase or selection of an airway device. The Team concluded that this definition should form the basis of a professional standard, guiding those with responsibility for selecting airway devices. We describe how widespread adoption of this professional standard can act as a driver to create an infrastructure in which the required evidence can be obtained. Essential elements are that: (i) the Difficult Airway Society facilitates a coherent national network of research-active units; and (ii) individual anaesthetists in hospital trusts play a more active role in local purchasing decisions, applying the relevant evidence and communicating their purchasing decisions to the Difficult Airway Society.”
“The objective of this study was to examine the differences in oscillatory brain dynamics in Alzheimer’s disease (AD) according to age at onset using quantitative electroencephalography (EEG).

In vitro silencing of COUP-TFII reduces the cell growth and invasiveness

and it strongly inhibits angiogenesis, an effect mediated by the regulation of VEGF-C. In nude mice, COUP-TFII silencing reduces tumor growth by 40%. Our results suggest that COUP-TFII might be an important regulator of the behavior of pancreatic adenocarcinoma, thus representing a possible new target for pancreatic cancer therapy. What’s new? The orphan nuclear receptor COUP-TFII influences many biological BYL719 chemical structure processes, and may play a role in pancreatic cancer. In this study, the authors discovered that COUP-TFII expression predicts poor outcome in pancreatic cancer. By silencing COUP-TFII in tumor cells, they were able to slow tumor growth and inhibit angiogenesis. The receptor may be an attractive target for therapy, they speculate, if a ligand can be identified that modulates its activity.”
“Background and purpose Endosaccular coil embolization and parent artery occlusion (PAO) are established endovascular techniques for treatment of cavernous carotid aneurysms. We performed a systematic review of published series Crenolanib price on endovascular treatment of cavernous carotid aneurysms to determine outcomes and complications associated with endovascular coiling and PAO of cavernous carotid

artery aneurysms. Methods In September 2013, we conducted a computerized search of MEDLINE and EMBASE for reports on endovascular treatment of intracranial cavernous carotid aneurysms from January 1990 to August 2013. Comparisons were made in periprocedural complications and outcomes MI-503 cost between coiling and PAO patients who did not receive bypass. Event rates were pooled across studies using random effects metaanalysis. Results 20 studies with 509 patients and 515 aneurysms were included in this systematic review. Aneurysm occlusion rates at bigger than 3 months after operation were significantly higher in the PAO without bypass group (93.0%, 95% CI 86.0 to 97.0) compared with the coiling

group (67.0%, 95% CI 55.0 to 77.0) (p smaller than 0.01). Retreatment rates were significantly lower in the PAO without bypass group (6.0%, 95% CI 2.0 to 12.0) compared with the coiling group (18.0%, 95% CI 12.0 to 26.0) (p=0.01). Coiling patients had a similar morbidity rate (3.0%, 95% CI 2.0 to 6.0) compared with PAO without bypass patients (7.0%, 95% CI 3.0 to 12.0) (p=0.13). Coiling patients had a similar mortality rate (0.0%, 95% CI 0.0 to 6.0) compared with PAO without bypass patients (4.0%, 95% CI 1.0 to 9.0) (p=0.68). Conclusions Evidence from non-comparative studies suggests that traditional endovascular options are highly effective in treating cavernous sinus aneurysms. PAO is associated with a higher rate of complete occlusion. Periprocedural morbidity and mortality rates are not negligible, especially in patients receiving PAO.

Conclusions: This study shows that the SN abnormality observed by TCS

is a specific feature, which can be helpful in the process of PD diagnosing.”
“The activation-induced cytidine deaminase (AID; also known as AICDA) enzyme is required for somatic hypermutation and class switch recombination at the immunoglobulin locus(1). In germinal-centre B cells, AID is 123 highly expressed, and has an inherent mutator activity that helps generate antibody diversity(2). However, AID may also regulate gene expression epigenetically by directly deaminating 5-methylcytosine in concert with base-excision repair to exchange cytosine(3). This pathway promotes gene demethylation, thereby removing epigenetic memory. For example, AID promotes active demethylation of the genome in primordial germ cells(4). SNX-5422 datasheet However, different studies have suggested either a requirement(5)

or a lack of function(6) for AID in promoting pluripotency in somatic nuclei after fusion with embryonic stem cells. Here we tested directly whether AID regulates epigenetic memory by comparing the relative ability of cells lacking AID to reprogram from a differentiated murine cell type to an induced pluripotent stem cell. We show that Aid-null cells are transiently hyper-responsive to the reprogramming process. Although they initiate expression of pluripotency genes, they fail to stabilize in the pluripotent state. The genome of Aid-null cells remains hypermethylated in reprogramming cells, and hypermethylated genes associated with pluripotency fail to be stably upregulated, including many MYC target LY3039478 mouse genes. Recent studies identified a late step of reprogramming associated with methylation status(7), and implicated a secondary

set of pluripotency network components(8). AID regulates this late step, removing epigenetic memory to stabilize the pluripotent state.”
“Here, 4EGI-1 we present LNCipedia (http://www.lncipedia.org), a novel database for human long non-coding RNA (lncRNA) transcripts and genes. LncRNAs constitute a large and diverse class of non-coding RNA genes. Although several lncRNAs have been functionally annotated, the majority remains to be characterized. Different high-throughput methods to identify new lncRNAs (including RNA sequencing and annotation of chromatin-state maps) have been applied in various studies resulting in multiple unrelated lncRNA data sets. LNCipedia offers 21 488 annotated human lncRNA transcripts obtained from different sources. In addition to basic transcript information and gene structure, several statistics are determined for each entry in the database, such as secondary structure information, protein coding potential and microRNA binding sites. Our analyses suggest that, much like microRNAs, many lncRNAs have a significant secondary structure, in-line with their presumed association with proteins or protein complexes.

We report a patient with bilateral superior altitudinal hemianopia.\n\nCase Report: A 40-year-old man developed bilateral superior altitudinal hemianopia secondary to bilateral parahippocampal and fusiform gyrus lesions. Vision loss was acute, and onset bilateral and simultaneous. Complete neuro-ophthalmologic examinations were performed. His best corrected visual acuity was 20/20 in each eye. Macula and compound inhibitor retina examinations were normal. Visual fields were characterized by bilateral upper hemianopia. Cerebral magnetic resonance imaging (MRI) confirmed the presence of symmetrical lesions confined within both bilateral parahippocampal and fusiform gyri. Blood tests, transesophageal echocardiographic examination,

and Doppler ultrasonography of the vertebrobasilar arterial system and carotids were normal.\n\nConclusion: We conclude that embolic events may induce a bilateral superior altitudinal hemianopia.”
“Background: Major surgery and severe trauma typically lead to massive blood loss requiring rapid transfusion of large amounts of blood products. It has been suggested that fresh, unrefrigerated whole blood provides a haemostatic advantage in this setting. The aim of the current study PLX3397 cell line was to compare the clot formation parameters of fresh, unrefrigerated whole blood and whole blood reconstituted from components stored for varying

periods of time, using rotational thromboelastography (ROTEM (R)). Methods: Fresh whole blood and reconstituted whole blood using combinations of CAL-101 chemical structure non-leucoreduced red cell units (stored for 7, 14, 21, 28, or 35 days), platelet concentrates (stored for 1, 3 or 5 days), and fresh frozen plasma (stored for 6 months) were analysed using ROTEM. Measurements of the clotting time (CT), clot formation time (CFT), and maximal clot firmness (MCF) were compared between units of fresh whole blood and reconstituted whole blood samples. Results: There was no difference in the haemostatic parameters measured of fresh whole blood

and reconstituted whole blood using red cell units stored for less than 21 days. ROTEM demonstrated that the CT and CFT were significantly shorter for reconstituted whole blood samples using red cells stored for longer than 21 days when compared to fresh whole blood and to reconstituted whole blood samples using red cell units stored for less than 21 days. The CT was inversely correlated to the duration of platelet storage. The MCF was unchanged regardless of duration of blood product storage. Conclusion: Fresh unrefrigerated whole blood and blood products stored for short duration (less than 21 days) were not superior to those stored for longer durations.”
“Immune responses and DNA damage repair are two fundamental processes that have been characterized extensively, but the links between them remain largely unknown. We report that multiple bacterial, fungal and oomycete plant pathogen species induce double-strand breaks (DSBs) in host plant DNA.

When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented selleck screening library endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus 3 implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophlls in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage. (Am J Pathol 2011, 179:199-210; DOI: 10.1016/j.ajpath.2011.03.013)”
“Induction

of inducible nitric oxide synthase (iNOS) may be involved in carcinogenesis of the stomach, because nitric oxide (NO) derived from iNOS can exert DNA damage CUDC-907 molecular weight and post-transcriptional modification of target proteins. In the present study, we investigated the correlation between endoscopic findings and iNOS mRNA expression/NO-modified proteins in the gastric

mucosa.\n\nFifty patients were prospectively selected from subjects who underwent upper gastrointestinal chromoendoscopy screening for abdominal complaints. The Helicobacter pylori (H. pylori) status of patients was determined by anti-H. pylori IgG antibody levels. We classified the mucosal area of the fundus as F0, fine small granules; F1, edematous large granules without a sulcus between granules; F2, reduced-size granules with a sulcus between granules; and F3, irregular-sized granules with extended sulcus between granules. Gastritis was graded using the visual analog scale of the Updated Sydney System. The expression of interleukin (IL)-8 and iNOS mRNA was assayed in gastric biopsy specimens by reverse transcription-polymerase chain reaction. NO-modified proteins were analyzed by Western blotting using novel monoclonal antibodies against nitrotyrosine.\n\nA total of 91.7% (11/12) of the F0 group was H. pylori-negative, whereas 94.7% (36/38) of the F1-3 groups was H. pylori-positive. Spearman’s analysis showed good correlation between the endoscopic grading and the score of chronic inflammation (r = 0.764) and glandular atrophy (r = 0.751). The

expression of IL-8 mRNA was significantly increased in F1, F2, and F3 cases compared with the F0 group, with no significant differences among them. iNOS mRNA was significantly increased in the F3 group compared with the other find more groups, with increased nitration of tyrosine residues of proteins.\n\nThe proposed classification by chromoendoscopy is useful for screening patients for atrophic and iNOS-expressing gastric mucosa with NO-modified proteins in H. pylori-associated atrophic gastric mucosa.”
“In the present study, the role of kainate (KA) receptors in hypnosis and analgesia induced by emulsified inhalation anesthetics was investigated. A mouse model of hypnosis and analgesia was established by an intraperitoneal injection of emulsified enflurane, isoflurane or sevoflurane.

The activation of the JAK-1/STAT-1 signaling pathway and the expessions of TNF-alpha, IL-1 beta and IL-6 proteins were investigated in AR42J cells induced with cerulein and treated with either PBS, RPM, or AG490. One group of cells was left untreated as a control group. Subsequently the activity of NF-kappa B was evaluated. Rats were given RPM or AG490

just before the induction of SAP, the severity of which was assessed at 24 h. The findings revealed that the up-regulated expressions of JAK-1/STAT-1, STAT-3 protein Fer-1 supplier were closely correlated with the transcription of TNF-alpha, IL-1 beta, and IL-6 in cerulein-stimulated cells. Administration of RPM or AG490 decreased the activity of NF-kappa B and inhibited the release of TNF-alpha, IL-1 beta, and IL-6. The reflective markers of severity of SAP were also decreased by RPM or AG490 treatment compared to SAP rats. This study indicates that the JAK-1/STAT-1

signaling pathway activity is an early event in pancreatic inflammatory injury. Therefore, early NSC23766 datasheet treatment with its inhibitors might be beneficial for attenuation of pancreatic injury in SAP.”
“Genetic transformation of the Indian medicinal plant, Bacopa monnieri, using a gene encoding cryptogein, a proteinaceous elicitor, via Ri and Ti plasmids, were established and induced bioproduction of bacopa saponins in crypt-transgenic plants were obtained. Transformed roots obtained with A. rhizogenes strain LBA 9402 crypt on selection medium containing kanamycin (100 mg l(-1)) dedifferentiated 432 forming callus and redifferentiated to roots which, spontaneously showed shoot bud induction. Ri crypt-transformed plants thus obtained showed integration and expression of rol genes as well as crypt

gene. Ti crypt-transformed B. monnieri plants were established following transformation with disarmed A. tumefaciens strain harboring crypt. Transgenic plants showed significant enhancement in growth and bacopa saponin content. Bacopasaponin D (1.4-1.69 %) was maximally enhanced in transgenic plants containing crypt. In comparison to Ri-transformed plants, Ri crypt-transformed plants showed significantly (p a parts per thousand currency sign 0.05) enhanced accumulation of bacoside A(3), bacopasaponin Momelotinib D, bacopaside II, bacopaside III and bacopaside V. Produced transgenic lines can be used for further research on elicitation in crypt-transgenic plants as well as for large scale production of saponins.\n\nKey message The cryptogein gene, which encodes a proteinaceous elicitor is associated with increase in secondary metabolite accumulation-either alone or in addition to the increases associated with transformation by A. rhizogenes.”
“Bartonella spp. infection has been reported in association with an expanding spectrum of symptoms and lesions.

It is assumed that the same model is applicable both in vivo and in vitro. Materials and methods: In the present study, we compared proliferating marrow cells freshly isolated from healthy individuals with proliferating

lymphocytes in cultures. Results: We demonstrate that during progression of freshly collected human bone marrow cells through G(1), S and G(2)/M, only Cdk1 combined with cyclins A and B(1) was distinctly present and active, and its activity gradually increased. In contrast, in vitro growing mitogen-stimulated lymphocytes had perfectly scheduled sequential expression of all four cyclins and Cdk1 and Cdk2 activities. Conclusion: Our findings demonstrate that the pattern of cyclin expression

and Cdk activity in bone marrow in vivo is distinctly different from the one observed for normal cells in vitro. Because proliferating bone marrow cells ATM Kinase Inhibitor are predominantly expanding populations of committed progenitors, it is likely that during the expansion phase their cell-cycle progression is pre-programmed, being driven solely by Cdk1 combined either with cyclin A or with cyclin B(1). Expansion of progenitor cells thus may not require buy CBL0137 the early steps of cell-cycle regulation, associated with triggering progression by availability of growth factors and mitogens.”
“Development of technology to deliver foreign gene(s) to a specific organ/tissue is one of the major challenges in gene therapy. Here, we show liver- and lobe-specific gene transfer following the continuous microinstillation of plasmid DNA (pDNA)

onto the liver surface in mice. Naked pDNA was continuously instilled onto the right medial liver lobe using syringe pump in male ddY mice. Our previous studies showed liver- EX 527 inhibitor and lobe-selective gene expression after instillation of 30 mu l of pDNA solution onto the liver surface, but gene expression was also found in the other liver lobe, kidney and spleen. To improve target site selectivity of gene expression, the instillation volume was decreased; however, non-specific gene expression in the other liver lobe and diaphragm was still detected. To prevent immediate diffusion of the pDNA solution, we performed continuous microinstillation of pDNA using a syringe pump; as a result, target site selectivity was greatly improved. As for instillation speed, 5 min infusion was enough to prevent diffusion of pDNA solution. 123 Furthermore, transfection efficiency in the target site was maintained when instillation speed was slowed. Wiping off residual pDNA solution from the applied liver lobe resulted in a further improvement in selectivity, suggesting not only immediate diffusion, but also gradual diffusion, are important factors for successful target site-specific gene transfer.

A higher throughput of the pool test protocol on cobas s 201 became apparent when the daily workload was more than 400 donations.\n\nTigris ID-NAT format was significantly more sensitive than cobas s 201 MP-NAT in detecting HCV RNA and HIV RNA dilution panels, but despite the 1:6 dilution factor in s 201 the difference in sensitivity was not significant for some of the HBV genotype panels. Both NAT systems demonstrated

acceptable operational performance, but for routine use further improvement in system reliability is desirable.”
“Both the 5-HT2A selleck chemical receptor (R) antagonist M100907 and the 5-HT2CR agonist MK212 attenuate cocaine-induced dopamine release and hyperlocomotion. This study examined whether these drugs interact to reduce cocaine hyperlocomotion and Fos expression in the striatum and prefrontal cortex. We first determined from dose-effect functions a low dose of both M100907 and MK212 that failed to alter cocaine (15 mg/kg, i.p.) hyperlocomotion. Subsequently, we examined whether these subthreshold doses given together would attenuate cocaine hyperlocomotion, consistent with a 5-HT2A/5-HT2CR interaction. Separate groups of rats received two sequential drug injections 5 min apart immediately before a 1-h locomotion test as 123 follows: (1) saline + saline, (2) saline + cocaine,

(3) 0.025 mg/kg M100907 + cocaine, (4) 0.125 mg/kg MK212 + cocaine, or (5) cocktail combination of 0.025 mg/kg M100907 and 0.125 mg/kg MK212 + cocaine. Brains were extracted for Fos immunohistochemistry 90 min after the second injection. We next examined the effects of 0.025 mg/kg M100907 and buy Quizartinib 0.125 mg/kg MK212, alone and in combination, on spontaneous locomotor activity. While neither drug given alone produced any effects, the M100907/MK212 cocktail attenuated cocaine hyperlocomotion as well as cocaine-induced Fos expression in the dorsolateral caudate-putamen (CPu), but had no effect on spontaneous locomotion. The

findings suggest that 5-HT2ARs and 5-HT2CRs interact to attenuate cocaine hyperlocomotion and Fos expression in the CPu, and that the CPu is a potential locus of the interactive effects between these 5-HT2R subtypes on behavior. Further research investigating combined 5-HT2AR antagonism and 5-HT2CR agonism as a treatment for cocaine dependence is warranted. Cell Cycle inhibitor Synapse, 2012. (c) 2012 Wiley Periodicals, Inc.”
“Lignocellulosic biomass, the most abundant polymer on Earth, is typically composed of three major constituents: cellulose, hemicellulose, and lignin. The crystallinity of cellulose, hydrophobicity of lignin, and encapsulation of cellulose by the lignin-hemicellulose matrix are three major factors that contribute to the observed recalcitrance of lignocellulose. By means of designer cellulosome technology, we can overcome the recalcitrant properties of lignocellulosic substrates and thus increase the level of native enzymatic degradation.