However, tumor progression and eventual invasion of the host is also dependent on the host response in terms of inflammation and antitumor immunity.

This host response provides both a tumor-promoting environment and an immune barrier to tumor progression that the tumor needs to neutralize or overcome in order to progress (reviewed in [80-82]). Indeed for colorectal carcinoma and other types of cancer, the presence of adaptive immune cells within the tumor has been shown to be a better predictor of tumor progression and prognosis than traditional or molecular tumor staging [83]. Tumors have been shown Lapatinib mouse not only to originate in inflamed learn more tissues due to infections, but some human tumors develop in sterile chronic inflammation, due to mechanical, chemical, radiation, or other types of injury, or due to genetic pathology. For example, chronic indwelling of urinary catheters has been shown to be associated with bladder carcinoma [84], chronic exposure to asbestosis is associated with lung cancer and mesothelioma (chemical) [85], and secondary pancreatitis resulting from a mutation in the trypsinogen gene has been associated with pancreatic carcinoma

[86]. Inflammation has been proposed to be involved in the promotion of cancer, in part through the production of reactive oxygen and nitrogen species; both species induce the formation of DNA cross-links, single- or double-strand breaks that can drive genomic instability and mutations within oncogenes and tumor suppressor genes [80, 87-89]. In addition, clear experimental evidence indicates

that inflammation provides a tumor-promoting environment in which stromal cells and infiltrating inflammatory hematopoietic cells, such as macrophages, produce growth and angiogenic factors as well as tissue remodeling enzymes [80, 90-94] (Fig. 1). Activation of certain oncogenes, such as RET, Hras and Kras, has been shown to Urease induce, both in the transformed cells as well as in surrounding tissue, an intrinsic inflammation with a secretory pattern; this pattern is reminiscent of that observed in senescent cells, of inflammatory mediators and chemokines that attract inflammatory hematopoietic cells, thus initiating and amplifying the inflammatory response [95-99]. Inflammation also causes infiltration by bone-marrow-derived tumor-associated macrophages and monocyte-derived myeloid cell subsets [100], which perform a critical protumorigenic function in creating the tumor environment by remodeling healthy tissue to accommodate the expanding tumor, increasing angiogenesis and suppressing antitumor T-cell responses [101, 102].

1) 4, 5. This association and resultant activation of the inflammasome leads to the activation of caspase-1 from its inactive zymogen pro-caspase-1. Active caspase-1 cleaves the pro-forms of the cytokines IL-1β and IL-18 to their active and secreted forms. Caspase-1 may Rucaparib solubility dmso possess additional functions including regulation of glycolysis pathways 6 and unconventional protein secretion 7; however, in vivo studies demonstrating a role for NLRP3 in these processes are lacking to date. In addition to NLRP3, two other NLR family members have been demonstrated to form inflammasomes and activate caspase-1. The NLRP1 inflammasome is a key mediator

of cell death due to anthrax lethal toxin 8 and the NLRC4 inflammasome is activated by numerous Gram-negative bacteria possessing either a type III or type IV secretion system 9–11. NLRC4 may also interact with another cytosolic NLR, Naip5 to activate caspase-1 in response to cytosolic flagellin 12. Recent studies have

also demonstrated that the cytosolic nucleic acid recognition receptors AIM2 and RIG-I can interact with ASC to form caspase-1 activating inflammasomes 13–17. The NLRP3 inflammasome can be activated in response to a wide array of stimuli (Fig. 1). These activators lack structural or functional similarity making it unlikely that their activation is through Talazoparib cost direct interaction with NLRP3. Rather, a common endogenous molecule upon which these pathways converge is likely the actual ligand for NLRP3. Numerous microbes including various bacteria, viruses, fungi and protozoan parasites can activate the NLRP3 inflammasome (reviewed in 18). In addition to microbial activators, endogenous danger signals such as ATP, monosodium urate and amyloid-β have been demonstrated to activate the NLRP3 inflammasome. It is interesting to speculate that NLRP3, or its evolutionary ancestor, originally served a primary role in host

defense against pathogens. But rather than sensing specific conserved PAMP as the TLR do, it is capable of detecting a wide swath of divergent pathogens Etofibrate by detecting one of the major consequences of infection, namely, cellular damage. Sequencing of the sea urchin Strongylocentrotus purpuratus genome revealed 222 TLR and 203 NLR, demonstrating the importance of these innate immune receptors in lower species such as the echinoderms 19. As species evolved and vertebrates developed adaptive immune systems some of these early innate NLR involved in pathogen surveillance have likely been co-opted to serve other functions such as responding to metabolic stress, ischemia and trauma. Recent studies suggest that the NLRP3 inflammasome may play a significant role in metabolic disorders and sterile inflammatory responses including type II diabetes mellitus, gout, Alzheimer’s disease and ischemia 6, 20–23.

4 examined three areas relevant to consideration of the use of antihypertensive therapy that are summarized below: 1. Antihypertensive therapy and development of ESKD

in people with type 2 diabetes and microalbuminuria. Only three RCTs were identified as being of sufficient size and length of follow up namely ABCD, UKPDS and HOPE. Of these ABCD did not include ESKD as an endpoint. In the UKPDS study the prevalence of ESKD was less than 2% with a relative risk for tight control of 0.58 (95% CI: 0.015–2.21) with similar results for death from kidney failure.8 The HOPE Study demonstrated that there was a non-significant relative risk reduction for the requirement for renal dialysis among people treated with ramipril.18 As a consequence of the above two trials, CB-839 cost Newman et al.4 concluded that there was no evidence of a beneficial effect of antihypertensive therapy on the development of ESKD. 2. Antihypertensive therapy and change in GFR in people with type 2 diabetes and microalbuminuria. Three placebo controlled trials in normotensive people were identified.14,25,69 Newman et al.4 considers the data are inconclusive. No appropriate trials comparing different antihypertensive agents and intensive versus moderate BP control were identified. However, later analysis of the ABCD trial70 selleck chemical indicated a significant effect of intensive therapy on the progression

from microalbuminuria to clinical proteinuria, however, there was no change in creatinine clearance and no difference between ACEi

and CCB. Two placebo controlled trials in hypertensive people were identified.71,72 Newman et al.4 concludes that the limited evidence indicates kidney function to remain stable in hypertensive people with type 2 diabetes with microalbuminuria treated with ACEi compared with a decline in the placebo group (36 month follow up). The Parving et al.72 study also indicated a significant reduction in the rate of progression to clinical proteinuria with ARB treatment however, this was not associated with a significant decline in creatinine clearance. Two trials were identified that compared intensive and moderate BP control in hypertensive people with type 2 diabetes with microalbuminuria.8,73 Urocanase However, the UKPDS study was unable to differentiate between normoalbuminuric and microalbuminuric subgroups. In the large ABCD study no significant difference in creatinine clearance was found in either normoalbuminuric or microalbuminuric subgroups. Three appropriate trials were identified comparing different antihypertensive agents in hypertensive people with type 2 diabetes with microalbuminuria.73–75 None of these trials showed significant differences in GFR or creatinine clearance. 3. Antihypertensive therapy and development of clinical proteinuria in people with type 2 diabetes and microalbuminuria. Three randomized placebo-controlled trials in normotensive people with type 2 diabetes with microalbuminuria were identified.

Results. The average length of the “minimal” incisions was 3.9 ± 0.6 cm (range, 3.1–6.1 learn more cm), with an average reduction in length of 51% as compared with the “classical” incisions (range, 30–75%; P < 0.001). There were no perioperative morbidities. Conclusions. Minimally invasive peripheral nerve surgery applied to the above procedures yields successful surgical outcomes while shortening incision lengths and maximizing patient satisfaction without sacrificing patient safety. © 2010 Wiley-Liss, Inc. Microsurgery, 2010. "
“The

gold standard for the treatment of segmental nerve defect is an autogenous nerve graft. However, donor site morbidity is an inevitable complication. We substituted an autogenous

nerve graft with an inside-out vein graft for the treatment of segmental sensory nerve defect and the clinical results were evaluated retrospectively. Eleven patients of sensory nerve defects have undertaken inside-out vein grafts for the recovery of sensation. The involved nerves were digital nerves in three cases, peroneal nerves in two cases, saphenous nerve intwo cases, and superficial radial nerves in four cases. The average length of defects was 2.71 cm (1–6 cm). Donor veins were harvested4 mm longer than nerve defects and everted to promote nerve regeneration. Patients’ objective satisfactions and two-point discriminations were determined, the Semmes-Weinstein monofilament test was performed, and British Medical Council sensory functional scores were evaluated. Selleckchem Wnt inhibitor Sensory functional Erastin clinical trial scores recovered to over S3 in all cases. No donor site morbidity was caused by vein harvesting, and all patients achieved satisfactory results with protective sensation at involved sites. The inside-out vein graft offers a good surgical alternative to an autogenous nerve graft for the reconstruction of sensory nerve defects without donor site morbidity. © 2011 Wiley-Liss, Inc. Microsurgery, 2011. “
“The sensory reconstruction of the lower extremity is one of the main goals in lower extremity

reconstruction. Reconstructive options endowing sensory recovery are limited. The aim of this report is to evaluate the neurotized sural flap in reconstruction of foot and ankle defects. Seven cases that were operated for foot and ankle skin defects with the neurotized sural flap were reported. The largest flap was 10 cm × 14 cm in size. Median age was 38 years. Four defects were on the heel, two were on the ankle, and one was on the dorsum of the foot. The sural nerve was coaptated to a recipient nerve in seven patients. All flaps survived totally. Follow-up time ranged between 9 and 29 months. All cases had hot–cold perception and two-point discrimination at average 14 ± 1.63 mm at 6th month. Sensory conduction test revealed very low action potentials related to stimulation of the flap.

Hamsters that had been treated with anthelmintic 5 weeks after the primary infection (Group 3, primary abbreviated infection), and hence had been without worms for 38 days, by day 73 of the experiment had villi well within the

normal range, and even marginally longer than those of naïve animals (110·9% and 114·6% of control values). The challenge control group (Group 4, given only the second infection) had villi about half the size of those in the naive control group at both time points. Animals that were challenged with A. ceylanicum 4 weeks after removal of their original immunizing infection (Group 5, primary + secondary infections), had villi in the normal range 10 days p.c. (day 73 of the experiment), but this was followed by a progressive downward trend on days 17 and 24 p.c. buy Ribociclib (regression of villus height on days after challenge, confined to Group 5; Rp = 0·94, n = 19, β = −36·2 ± 3·07, t = −11·8, P < 0·001). By day 31 after challenge (day 94 of the experiment), these animals had villi that were almost as short as those in Group 2 (primary continuous infection). Figure 1 also shows the results of measurements of the depths of crypts in the mucosa. In naïve hamsters (Group 1) crypts remained in the middle of the SAHA HDAC purchase normal range (20) across the two time points of the experiment, but increased markedly

in hamsters experiencing the continuous primary infection (Group 2; 307·9% and 316·5%, respectively of control naïve values on days 73 and 94 after infection). Crypt depth returned to the normal range in hamsters after removal of the worms (Group 3, primary abbreviated infection), but was increased in those experiencing an early stage primary infection (Group 4, secondary infection only; 132·87% and 219·2%, respectively of control naïve values on days 10 and 31 p.i.). In hamsters that had experienced the primary

infection, followed by worm clearance and challenge (Group 5), the depth of crypts increased from week to week as the experiment progressed (regression of crypt depth on days after challenge, confined to Group 5; Rp = 0·91, n = 19, β = 23·0 ± 2·56, t = 8·97, P < 0·001). Tacrolimus (FK506) Values for mitotic figures were very similar in naïve control hamsters (Group 1) and hamsters from which worms had been removed on day 35 p.i. (Group 3, primary abbreviated infection), on both days 73 and 94 of the experiment (Figure 2). Hamsters sustaining a chronic uninterrupted primary infection (Group 2, primary continuous infection) had elevated numbers of mitotic figures on both days, whilst those given only the second infection (Group 4) had similar numbers of mitotic figures to naïve animals on day 10 p.i. (day 73 of the experiment), but increased numbers on day 31 p.i.

The dose of intravenous normal saline at 20 mL/kg was selected based on our previous studies and aligned to clinical practice [29, 37]. In addition, all animals were provided with a subcutaneous reservoir of normal saline as a further precaution

against eliciting hydrodynamic differences. That this strategy was reasonably successful was indicated by our finding of a lack of significant difference among all experimental groups in two measures of dehydration: hematocrit and serum lactate. A limitation of our study was that we lacked the equipment to extend this observation to more discriminating measures, such as rodent blood pressure and vascular tone. We first compared the three resuscitation fluids in the simpler model of endotoxemia, using intraperitoneal LPS, a widely employed dose and route of administration https://www.selleckchem.com/products/LDE225(NVP-LDE225).html (e.g., [4, 17]). While no resuscitation fluid significantly influenced LPS-induced leukopenia or the number of adherent leukocytes in the sinusoids, AGP administration, but not that of saline or equimolar albumin in the form of HAS, clearly attenuated both leukocyte adhesion selleck products in the PSV and blockage of sinusoids. AGP-treated mice also exhibited a reduction in average leukocyte adhesion in the sinusoids

that did not reach statistical significance. The incomplete concordance between sinusoidal blockage and sinusoidal leukocyte adherence is not surprising, given that blockage is likely an extreme example of sinusoidal narrowing, and our experimental approach did not permit measurement of overall sinusoidal flow or sinusoidal diameter. Reduced sinusoidal blood flow in sepsis and endotoxemia is derived from both leukocyte-, and platelet-mediated blockage of perfusion in the low shear environment of the sinusoids; perhaps, platelet effects, which we did not measure, predominated in this specific microvascular location. In addition, it is known that different mechanisms contribute to leukocyte adherence in the two hepatic vascular locations [30, 11]. Having demonstrated a superior

protective effect of AGP over HAS and saline in endotoxemia, we turned to click here the more complex but arguably more relevant CLP model, in which we focused on comparing AGP and saline. Administration of endotoxin replicates some of the clinical features of sepsis and septic shock and is consistent with the concept that it is the host response to bacteria, not the bacteria per se, that is most damaging, but only low levels of circulating endotoxin have been reported in clinical studies of septic patients [33]. The surgical CLP model provides a specific abdominal site for infection and exposes mice to a variety of bacterial danger signals [35]. Use of AGP as the resuscitation fluid in CLP demonstrated substantial overlap with the results in the endotoxemia model; its use led to better perfusion of the liver via its sinusoids, and to decreased adhesion to post-sinusoidal vessels.

B7-H3/pMXC and B7-H3/pMXs-neo were used for SCCVII, EL4, E.G7, B16 cells and J558L cells, respectively. Tumour Y-27632 order cells were retrovirally transduced with B7-H3.28 For infecting EL4, SCCVII and B16 cells, pVSV-G was co-transfected

to generate pan-tropic retrovirus. After drug selection, transfectants expressing high levels of B7-H3 were sorted by flow cytometry as described previously.31 The TLT-2 complementary DNA was inserted into pMXs-IG, and control IRES-GFP (pMXs-IG) or TLT-2/pMXs-IG was retrovirally transduced into OT-I CD8+ T cells stimulated with OVA peptide (SIINFEKL).28 GFP+ cells were sorted by flow cytometry and used as mock- or TLT-2-transduced OT-I CD8+ T cells. CD4+ and CD8+ T cells from BALB/c mice were isolated by negative selection, as described previously.28 The purity of the CD4+ and CD8+ T cells was over 95% and 90%, respectively, as confirmed by flow cytometry. For the anti-CD3 mAb-induced co-stimulation assay, isolated T cells (2 × 105/well) were co-cultured with mitomycin C-treated parental P815 or B7-H3-transduced P815 (B7-H3/P815) cells at the indicated responder : stimulator ratios, in the presence of anti-CD3 mAb (145-2C11, 0·2 μg/ml in CD4+ T cells and 1·0 μg/ml in CD8+ T cells). The proliferative responses for the final 18 hr of the 3-day culture and IFN-γ production in the culture

supernatants at 72 hr were then measured.32 Anti-CD3 Antiinfection Compound Library mAb-induced redirected cytotoxicity against P815 and B7-H3/P815 cells was measured by the 6-hr JAM test.33,34 Splenocytes from OT-1 mice were cocultured with mitomycin C-treated E.G7 cells for 3 days for in vitro sensitization.

The cells were harvested, separated into CD8+ T cells, and used as in vitro-sensitized PtdIns(3,4)P2 OT-I CD8+ T cells. Cytotoxicity against E.G7 and B7-H3/E.G7 was measured by a 6-hr JAM test. For the in vivo cytotoxicity assay, E.G7 and B7-H3/E.G7 cells were labelled with CellTracker Orange [5-(and-6)-(((4-chloromethyl)benzoyl)amino)] tetramethylrhodamine (CMTMR; 10 μm, Invitrogen, Carlsbad, CA) and/or carboxyfluorescein diacetate succinimidyl ester (CFSE; 10 μm, Invitrogen). The CMTMR-labelled cells (2 × 106) were mixed with a twofold number of CFSE-labelled parental E.G7 (A-mix) or B7-H3/E.G7 (B-mix) cells (4 × 106) and then the mixed cells were injected intraperitoneally (i.p.) into OT-I mice. Peritoneal exudate cells (PEC) were analysed by flow cytometry after 24 hr. B6 mice were sensitized in vivo by peritoneal injection with DBA/2-originated allogeneic P815 or B7-H3/P815 cells (2 × 107 cells) to evaluate CTL against the alloantigen. After 8 days, PEC were collected and cytotoxicity against P815 and B7-H3/P815 was measured as described above. The OT-I mice received a peritoneal injection of mitomycin C-treated OVA-expressing EL4 (E.G7 or B7-H3/E.G7) cells (2 × 107) to induce OVA-specific CTL. Three days later, PEC were harvested and cytotoxicity against E.G7 and B7-H3/E.G7 was assessed as described above.

Representative images were taken for each condition, using the same exposure time for each filter, to allow comparison of fluorescence intensity between different fields and conditions. Primary cultures of cortical neurons were obtained from C57BL/6 mice, at day 16 of gestation. After dissociation

and centrifugation of the dissected cortices, the tissue was resuspended in Neurobasal medium (Invitrogen, San Diego, CA), supplemented with 2% (v/v) B27 supplement (Invitrogen) and 100 U/ml penicillin/streptomycin (Invitrogen). Cells were plated at a density of 500 000 cells/well in six-well multi-well plates previously coated with poly-l-lysine. Characterization of the embryonic neuronal cultures confirmed the presence of 95% neurons, as determined by GFAP and NeuN-immunostaining. Primary cultures were kept at 37° in a humidified atmosphere Protease Inhibitor Library concentration containing 5% CO2. After 8 days in culture, neurons were incubated for 24 hr with a 1 : 1 mixture of Neurobasal medium (500 μl) and conditioned medium (500 μl). The conditioned medium was obtained from untreated N9 cells, N9 cells exposed to LPS CHIR-99021 supplier (0·1 μg/ml) for 24 hr, and N9 cells transfected with anti-miR-155 or control oligonucleotides 24 hr before exposure to LPS. In parallel experiments neurons were incubated

with LPS (0·1 μg/ml) for 24 hr. Cell viability of primary neuronal cultures was determined by a modified Alamar Blue assay. This assay measures the redox capacity of neurons and allows the determination of cell viability without the detachment

of the cells, so cell integrity is maintained. Briefly, 1 ml Neurobasal medium supplemented with 10% (v/v) of Alamar Blue dye was added to each well following the 24-hr incubation period with conditioned medium or LPS. After 3 hr of incubation at 37°, 150 μl supernatant was collected from each well and transferred to 96-well plates. The optical density of the supernatant was Erlotinib mw measured at 570 and 600 nm in a microplate reader and cell viability was calculated as a percentage of control cells, using the formula: (A570–A600) of treated cells × 100/(A570–A600) of control cells. All data are presented as mean ± standard deviation (SD) and are the result of three independent experiments, each performed at least in triplicate. One-way analysis of variance combined with Tukey post-hoc test was used for multiple comparisons in cell culture experiments. Statistical differences are presented at probability levels of P < 0·05 (*), P < 0·01 (**) and P < 0·001 (***). Calculations were performed with standard statistical software (GraphPad Prism 5, GraphPad Software, La Jolla, USA). Since miR-155 has been described as being up-regulated in various cells of myeloid origin upon their activation and as contributing to the modulation of the immune response mediated by these cells, we first investigated the expression of this miRNA in mouse N9 microglia cells and primary microglia cultures employing qRT-PCR.

Results:  Of 133 927 children, a total of 176 children had NS, which incurred 508 hospital admissions. Nineteen percent of admissions were associated with major infections. Pneumonia was the most common infection (49%), followed by urinary tract infection (UTI), bacteraemia/sepsis, peritonitis and cellulitis. Pneumonia was the most common infection among children age younger than 10 years, whereas UTI was more common among children aged greater than 10 years. NS admission with infections buy Gefitinib had

longer periods of hospital length of stay and higher hospital total costs compared to those without infections. Regression analysis reveals that younger age, regional hospitals, admission hospital located in middle and south areas and admission made see more in spring were associated with increased risk for developing major infections. Conclusions:  While 19% of childhood NS admissions were associated with major infections, young age, admissions made in spring, located in middle and south Taiwan and in regional hospitals were the major associated factors for infection. Age plays an important role in risk and types of infection. “
“Aim:  Cardiovascular disease is the most common cause of death in patients undergoing dialysis. The accuracy of multidetector computed tomography (MDCT) for detecting

coronary disease has not been determined, and little information is available regarding the performance of MDCT in patients undergoing dialysis. Methods:  Twenty-nine patients undergoing dialysis were analyzed and MDCT and coronary angiography (CAng) were performed consecutively. The coronary arteries were divided into four segments for analysis. We compared the significant stenosis lesions (≥50% luminal narrowing) identified by MDCT with those found by CAng. The total coronary artery calcium (CAC) score was determined by summing the individual lesion scores from each of the coronary branches. Results:  One hundred and sixteen

aminophylline coronary artery branches in 29 patients were analyzed. The sensitivity, specificity, and positive and negative predictive values of MDCT for detecting significant coronary artery stenosis (≥50% stenosis) were 68%, 94%, 71% and 93%, respectively. The CAC scores were significantly higher in subjects with coronary artery disease (CAD) (514.0 ± 493.6 vs 254.3 ± 375.3, P = 0.05). The severe CAC score (>500) was related to the presence of significant CAD (P = 0.05) and the sensitivity and specificity for detecting significant CAD were 50% and 80%, respectively. Conclusion:  MDCT is a useful and non-invasive approach for detecting or excluding CAD in patients undergoing dialysis. “
“Aim:  To demonstrate that the evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens (LMLC) is useful to identify patients with a haematuria of glomerular or non-glomerular origin.

Our data are consistent with this hypothesis and we show that these www.selleckchem.com/products/Bortezomib.html types of interchromosomal translocations reflect interchromosomal CSR based on our findings

that AID activity is required. It should be noted, however, that in our VV29 transgenic mice, interchromosomal translocations can occur in vitro, whereas in Δ3′RR transgenic mice interchromosomal translocations can only be detected in vivo. As the VV29 transgene does not contain either the 3′RR or all the Igh locus sequences downstream the Cμ gene, translocation to the endogenous Igh locus is the only CSR mechanism to repair transgene Sμ AID-induced DNA damage. On the other hand, in the Δ3′RR transgene the presence of all of Igh locus S regions together with their surrounding sequences might lead to abortive downstream intrachromosomal CSR processes that compete with the interchromosomal translocation. Based on our findings, together with the previous studies, and the fact that the frequencies of in vitro interchromosomal translocation in the VV29 B cells are orders of

magnitude higher than c-myc/Igh translocation Silmitasertib frequencies 17 yet comparable to the frequencies of interallelic CSR among endogenous Igh loci 2, we conclude that interchromosomal translocations involving the Igh locus occur by an AID-medicated CSR mechanism and occur more often between chromosomes that share Igh-associated regulatory elements. It would be interesting to determine whether the presence of a switch region or Igh enhancer elements near the c-myc gene would

increase the frequency of translocations to the Igh locus. In VV29 B cells that are undergoing CSR, we can find only VV29 VDJ regions expressed with the VV29 transgenic Cμ gene and not the endogenous Cμ gene although we can easily detect the expression of the VV29 region with endogenous Cγ regions. These results indicate that Dolichyl-phosphate-mannose-protein mannosyltransferase VV29 transgene translocations into the Igh locus do not involve trans-switching between the transgene Sμ and the endogenous Sμ regions, implying that Sμ regions may be differentially regulated from downstream S regions, perhaps to give directionality to the CSR machinery. One source of regulation may be chromosomal looping that associates the intronic Eμ enhancer with the downstream 3′RR enhancers during CSR 28. It is possible that DNA looping or protein complexes block Sμ regions from recombining with their chromosomal homologues. On the other hand, the DNA looping structure could leave downstream S regions more exposed to participate in interchromosomal recombination. To our knowledge, this is the first study that has indicated that two homologous Sμ regions do not recombine via trans-switching.