Conclusions: The draft genome sequence of

S.similar to coelicoflavus ZG0656 revealed the putative biosynthetic gene cluster of acarviostatins and a putative pathway of acarviostatin production. Significance and Impact of the Study: To our knowledge, S.similar to coelicoflavus ZG0656 is the first strain in this species for which a genome sequence has been reported. The analysis of sct-cluster provided selleck inhibitor important insights into the biosynthesis of acarviostatins. This work will be a platform for producing novel variants and yield improvement.”
“Neuroinflammation has been implicated in the pathology of neurodegenerative processes such as Parkinson’s disease (PD). Using the golden hamster (GH) 6-hydroxydopamine (6-OHDA) model, we investigated whether the attenuation

of neuroinflammation influences the onset and progression of dopamine cell degeneration. 6-OHDA-injected GH received a treatment of minocycline (MINO), prednisolone (Pred) or a combination of minocycline and prednisolone (MINO + Pred). Immunohistochemistry for tyrosine hydroxylase (TH), Iba-1 and glial fibrillary acidic protein (GFAP) was used to evaluate lesions in the nigrostriatal axis and the amount of activated microglia and astroglia, respectively. RT-PCR was used to measure mRNA levels of cytokines and trophic neuroprotective factors. The three anti-inflammatory treatments Selleck Bromosporine dramatically reduced activated microglia in the nigrostriatal axis. In addition, TH-immunostaining showed that the positive areas in the ipsilateral striatum of either MINO or Pred groups were higher than that of control. However, only in Pred group this recovery was significant. mRNA measurements demonstrated lower levels

of TNF-alpha, iNOS, BDNF and GDNF in Pred group when compared with controls. The results suggest that TH-immunopositive fibers have the ability to recover after 6-OHDA-induced toxicity of dopaminergic neurons, and this recovery may be due to a decrease in the microglial production of TNF-alpha and iNOS. (c) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Kappa agonists can attenuate reinstatement of cocaine-seeking behavior RepSox nmr induced by cocaine priming. The mechanisms underlying this effect have not been characterized fully but may have a serotonergic component as kappa agonists also increase the release of serotonin (5-hydroxytryptamine, 5-HT).

This study investigated the role of kappa opioid receptor and 5-HT mechanisms in kappa agonist-induced attenuation of cocaine priming in monkeys.

Squirrel monkeys were trained to self-administer cocaine (0.18-0.3 mg/kg/injection) under a second-order schedule in which drug seeking was maintained jointly by cocaine injections and a cocaine-paired visual stimulus. In extinction sessions, saline was substituted for cocaine, and the cocaine-paired stimulus was omitted.

For the chemical phase it is shown that the cross-bridge model of Hai and Murphy [1988. Am. J. Physiol. Cell Physiol. 254, C99-C106] is included in the developed evolution law as a special case. In order to show the specific features and the potential of the proposed continuum model a uniaxial extension test of a tissue strip is analysed in detail and the related kinematics Blasticidin S and stress-stretch relations are derived. Parameter studies point to coupling phenomena; in particular the tissue response is analysed

in terms of the calcium ion level. The model for smooth muscle contraction may significantly contribute to current modelling efforts of smooth muscle tissue responses. (C) 2010 Elsevier Ltd. All rights reserved.”
“3,4-Methylenedioxymethamphetamine (MDMA)

or ‘ecstasy’ has been associated with memory deficits during abstinence and intoxication. The human neuropharmacology of MDMA-induced memory impairment is unknown. This find more study investigated the role of 5-HT2A and 5-HT1A receptors in MDMA-induced memory impairment. Ketanserin is a 5-HT2A receptor blocker and pindolol a 5-HT1A receptor blocker. It was hypothesized that pretreatment with ketanserin and pindolol would protect against MDMA-induced memory impairment. Subjects (N = 17) participated in a double-blind, placebo-controlled, within-subject design involving six experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 min. T1-T2 combinations were: placebo-placebo, pindolol 20 mg-placebo, ketanserin 50 mg-placebo, placebo-MDMA 75 mg, pindolol 20 mg-MDMA 75 mg, and ketanserin 50 mg-MDMA 75 mg. Memory function was assessed at Tmax of MDMA by means of a word-learning task (WLT), a spatial memory task and a prospective memory task. MDMA significantly impaired performance in all memory tasks. Pretreatment with a 5-HT2A receptor blocker selectively interacted with subsequent MDMA treatment and prevented MDMA-induced impairment Farnesyltransferase in the WLT, but not in the spatial and

prospective memory task. Pretreatment with a 5-HT1A blocker did not affect MDMA-induced memory impairment in any of the tasks. Together, the results demonstrate that MDMA-induced impairment of verbal memory as measured in the WLT is mediated by 5-HT2A receptor stimulation. Neuropsychopharmacology (2011) 36, 1932-1939; doi:10.1038/npp.2011.80; published online 11 May 2011″
“In animal development, the growth of a tissue or organ is timely arrested when it reaches the stereotyped correct size. How this is robustly controlled remains poorly understood. The prevalent viewpoint, which is that morphogen gradients, due to their organizing roles in development, are directly responsible for growth arrest, cannot explain a number of observations. Recent findings from studies of the Drosophila wing have revealed that the interpretation of the Wingless gradient requires signaling-induced self-inhibition and that cell proliferation is controlled by graded vestigial expression.

Salmonella prevalence decreased (P = 0.0001) on day-5 and when examined across days in cows exposed to sprinklers prior to milking. Antimicrobial susceptibility screening found very few isolates that were multi-drug resistant. All selleck chemicals Enterococcus isolates were susceptible to vancomycin.

This study demonstrated a significant decrease in faecal prevalence of Salmonella in lactating cattle following exposure to sprinklers administered prior to milking.

Identification of current dairy management techniques that are also effective in reducing on-farm prevalence of pathogenic bacteria

could have significant food safety and environmental implications.”
“Evidence from mammalian studies suggests that brain derived neurotrophic factor (BDNF) and its receptor, trk B, are upregulated in neuronal cell bodies after injury. Although fish possess neurotrophins and display rapid functional and morphological recovery after central nervous system (CNS) injury, to date few studies have examined neurotrophin expression during CNS regeneration. In this study, RT-PCR was used to investigate the effect of complete spinal cord transection on the mRNA expression of BDNF and its receptor, trk B, in the eel brain at a range of timepoints after injury. The spatial expression pattern of BDNF mRNA in the brain was also assessed before

and after injury using in situ hybridization. Marked changes Selleck CP673451 in BDNF and trk B mRNA levels in the eel brain were not detected during the recovery period after cord transection. In addition, the spatial expression pattern of BDNF mRNA in the eel brain appeared unchanged after injury. Our results are in contrast with the increase reported in mammals

but are in CB-839 chemical structure line with studies examining neurotrophin expression during CNS regeneration in other anamniotic vertebrates. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“To use experimental design techniques and a multiple logistic regression model to optimize a microbiological inhibition test with dichotomous response for the detection of Penicillin G in milk.

A 2(3) x 2(2) robust experimental design with two replications was used. The effects of three control factors (V: culture medium volume, S: spore concentration of Geobacillus stearothermophilus, I: indicator concentration), two noise factors (Dt: diffusion time, Ip: incubation period) and their interactions were studied. The V, S, Dt, Ip factors and V x S, V x Ip, S x Ip interactions showed significant effects.

The use of 100 mu l culture medium volume, 2 x 10(5) spores ml(-1), 60 min diffusion time and 3 h incubation period is recommended. In these elaboration conditions, the penicillin detection limit was of 3.9 mu g l(-1), similar to the maximum residue limit (MRL). Of the two noise factors studied, the incubation period can be controlled by means of the culture medium volume and spore concentration.

The unchanged expression of Na(v)1.6 contrasts to our previous finding that showed an increased expression of Na(v)1.7 at both typical and atypical nodal sites within painful samples. Together, these findings suggest there is not a simple replacement of one isoform with another, but rather an increased co-expression of multiple isoforms at both intact and remodeling/demyelinating (atypical) nodal sites within the painful dental pulp. The resultant heterogeneous population of isoforms may produce unique axonal excitability properties that could contribute

to spontaneous pain sensations that are common in toothache. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Objective: The matrix metalloproteinases (MMPs) have been implicated in the aggressive course of non-small cell lung cancer (NSCLC). However, there are a large number of MMP subtypes PDK inhibitor with diverse

proteolytic substrates and different induction pathways. This study tested the hypothesis that a differential MMP profile would exist between NSCLC and normal lung and that MMP patterns AZD5363 solubility dmso would differ between NSCLC histologic types.

Methods: NSCLC samples and remote normal samples were obtained from patients with stage I or II NSCLC with either squamous cell (n = 22) or adenocarcinoma (n = 19) histologic characteristics. Absolute concentrations for each of the MMP subclasses were determined by a calibrated and validated multiplex suspension array: collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), lysins (MMP-2 and -7), and elastase (MMP-12).

Results: Overall, MMP levels were significantly increased in NSCLC compared with normal. For example, MMP-1 and PD173074 in vivo MMP-7 increased by approximately 10-fold in NSCLC (P < .05). Moreover, a different MMP portfolio was observed between NSCLC histologic types. For example MMP-1, -8, -9, and -12 increased by more than 4-fold in squamous cell versus adenocarcinoma

(P < .05). In those patients who had recurrence within 3 years of resection, 3-fold higher levels of MMP-8 and -9 were observed (P < .05).

Conclusion: Increased levels of a number of MMP types occur with NSCLC, but the MMP profile was distinctly different between histologic types and in those patients with recurrence. These different MMP profiles may be important in the mechanistic basis for the natural history of different NSCLC types, as well as identifying potential prognostic and therapeutic targets. (J Thorac Cardiovasc Surg 2010; 139: 984-90)”
“Glutamate neurotransmission is highly regulated, largely by glutamate transporters. In the spinal cord, the glutamate transporter GLT-1 is primarily responsible for glutamate clearance. Downregulation of GLT-1 can occur in activated astrocytes, and is associated with increased extracellular glutamate and neuroexcitation. Among other conditions, astrocyte activation occurs following repeated opioids and in models of chronic pain.

(C)

2010 Elsevier Ltd. All rights reserved.”
“The neural substrates of auditory motion processing are, at present, still a matter of debate. It has been hypothesized that motion information is, as in the visual system, processed separately from other aspects of auditory information, such as stationary location. Here we aimed to differentiate the location of auditory motion processing in human cortex using low-frequency repetitive transcranial magnetic stimulation (rTMS) in combination with a psychophysical task of motion discrimination. rTMS was applied offline to right posterior superior temporal gyrus, right inferior parietal lobule, right dorsal premotor cortex, or right primary Buparlisib ic50 somatosensory cortex (as reference site). A significant decrease in performance was obtained exclusively for sounds presented in left hemispace after rTMS over the right inferior parietal lobule (BA 40). This finding indicates that the inferior parietal lobule plays a crucial role in the analysis of moving sound, with an apparent contralaterality of cortical processing. Combined with previous studies which have demonstrated effects of rTMS on static sound localization for both inferior parietal and posterior temporal cortices, the results suggest a hierarchical Proteases inhibitor processing of auditory

spatial information, with higher-order functions

of motion analysis, such as discrimination of motion direction, mainly taking place beyond the temporal lobe. (C) 2010 Elsevier Ltd. All rights reserved.”
“The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. One way to investigate the cognitive and neural underpinnings of speech perception is by investigating patients with speech perception deficits but with preserved ability in other domains of language. One such case CB-839 is reported here: patient NL shows highly impaired speech perception despite normal hearing ability and preserved semantic knowledge, speaking, and reading ability, and is thus classified as a case of pure word deafness (PWD). NL has a left temporoparietal lesion without right hemisphere damage and DTI imaging suggests that he has preserved cross-hemispheric connectivity, arguing against an account of PWD as a disconnection of left lateralized language areas from auditory input. Two experiments investigated whether NL’s speech perception deficit could instead result from an underlying problem with rapid temporal processing. Experiment 1 showed that NL has particular difficulty discriminating sounds that differ in terms of rapid temporal changes, be they speech or non-speech sounds.

These findings have implications for the development of novel immunotherapeutic approaches to

this common viral infection.”
“Objective: Many studies have examined the effects of cerebrovascular changes on check details treatment response in geriatric depression. However, few such studies have examined the relationship between cerebrovascular changes and long-term prognosis. We examined the effects of cerebrovascular changes on the course of geriatric depressive symptoms, dementia rates, and mortality over a follow-up period of approximately 10 years. Method: Participants were 84 patients with major depression (age of onset over 50 years); patients suffering from strokes, neurological disorders, and other psychiatric disorders Belnacasan mouse were excluded. Magnetic resonance imaging findings were used

to classify all patients into silent cerebral infarction (SCI)-positive (n = 37) or SCI-negative groups (n = 47). Prognoses were ascertained using a review of clinical charts and mailed questionnaires. Results: Only 5% of patients with SCI were able to maintain remission whereas 36% of patients without SCI were able to do so. Total duration of depressive episodes was significantly longer in the SCI-positive group than in the SCI-negative group. SCI was also associated with a higher risk of dementia. Conclusion: The results of this long-term follow-up study demonstrate that the presence of SCI is associated with a relatively poor prognosis in geriatric depression. Copyright (C) 2010 S. Karger AG, Basel”
“The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected trigeminal ganglionic sensory neurons. Expression of the first 1.5 kb of LAT coding sequences MTMR9 is sufficient for the wild-type reactivation phenotype in small animal models of infection. The ability of the first 1.5 kb of LAT coding sequences to inhibit apoptosis is important for the latency-reactivation

cycle. Several studies have also concluded that LAT inhibits productive infection. To date, a functional LAT protein has not been identified, suggesting that LAT is a regulatory RNA. Two small RNAs (sRNAs) were previously identified within the first 1.5 kb of LAT coding sequences. In this study, we demonstrated that both LAT sRNAs were expressed in the trigeminal ganglia of mice latently infected with an HSV-1 strain that expresses LAT but not when mice were infected with a LAT null mutant. LAT sRNA1 and sRNA2 cooperated to inhibit cold shock-induced apoptosis in mouse neuroblastoma cells. LAT sRNA1, but not LAT sRNA2, inhibited apoptosis less efficiently than both sRNAs. When rabbit skin cells were cotransfected with plasmids that express LAT sRNA1 and HSV-1 genomic DNA, the amount of infectious virus released was reduced approximately 3 logs.

To further explore the mechanisms of FB1 neurotoxicity, we here investigated the effects of acute FB1 co-exposure with glutamate and in the low magnesium model of epilepsy on neuronal calcium

level, mitochondrial membrane potential, and cell death in glio-neuronal cultures. FB1 increased the glutamate-induced calcium signal in neurons and changed neuronal calcium signals to more sustained intracellular calcium rises in the low magnesium model of epilepsy click here that coincided with mitochondrial membrane potential depolarization. FB1 co-exposure increased the percentage of dead neurons in low magnesium conditions dose dependently when compared with low magnesium exposure only, whereas in FB1 and glutamate co-exposure neuronal death remained unchanged when compared with glutamate treatment only. Our results show that FB1 makes neurons more vulnerable to glutamate-induced toxicity and epileptiform conditions, indicating that FB1 can enhance the detrimental effect of these conditions on neurons. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Rationale Cocaine strengthens behaviors associated with its administration. The stress response by individuals that are defeated in a brief aggressive confrontation can also promote enduring behavioral consequences similar to those of stimulants.

Objectives The study intends

to find whether intermittent episodes of defeat promote cocaine’s reinforcing effects by triggering selleck chemical N-methyl-D-aspartic acid (NMDA)-receptor-mediated plasticity in the ventral tegmental area (VTA).

Materials and methods Long-Evans rats were investigated after four social defeats in three experiments. Two experiments examined systemic or intra-VTA antagonism of NMDA receptors during stress on the later expression of behavioral sensitization and cocaine self-administration during fixed E7080 and progressive ratio (PR) schedules of reinforcement (0.3 mg/kg/infusion), including a novel 24-h variable-dose continuous access binge (0.2, 0.4, and 0.8 mg/kg/infusion,

delivered in an irregular sequence). Third, the expression of receptor proteins NR1 (NMDA) and GluR1 [alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)] were examined in VTA and nucleus accumbens.

Results Intermittent defeats augment locomotor responses to cocaine and increase cocaine taking. Rates of responding during binges are increased after defeat stress. These effects are prevented when NMDA or AMPA receptor antagonists are administered before defeats. VTA infusions of the NMDA antagonist AP-5 (5 nmol/side) before stress prevents locomotor sensitization to cocaine and intensified responding for cocaine during a PR schedule or binge. Episodic defeats increase GluR1 AMPA subunit protein expression in the VTA.

The Wnt3a-treated smooth muscle cells displayed increased extracellular matrix synthesis, as measured by collagen I and III mRNA expression, along with increased expression of MMP2 and MMP9, but decreased TIMP2 levels. The Wnt3a-induced change in cell phenotype was associated with increased expression of the gap junction protein connexin 43. Consistent with this, Wnt3a-treated smooth muscle cells displayed enhanced intercellular communication, as measured by the scrape-loading dye transfer technique. The canonical Wnt antagonist, dickkopf-related protein 1, completely reversed the contractile protein and connexin 43 expression

seen in the Wnt3a-treated cells, suggesting these changes were dependent on canonical Wnt signaling. Collectively, this data suggest Wnt3a promotes a contractile and secretory phenotype in vascular smooth muscle GW4869 manufacturer cells that is associated with increased gap junction communication. Laboratory Investigation (2012) 92, 246-255; doi:10.1038/labinvest.2011.164; published online 21 November 2011″
“Introduction: TNFR2-Fc and IL-1ra-Fc are recombinant cytokine ligands that target TNF and IL-1. TNFR2-Fc-IL-1ra, a dual-domain agent that incorporates both ligands, allows bifunctional binding of

IL-1 receptors and TNF. This study was designed to characterize Tc-99m-labeled selleck compound forms of these ligands, Tc-99m-IL-1ra-Fc (IF), Tc-99m-TNFR2-Fc (TF), and Tc-99m-TNFR2-Fc-IL-1ra (TFI), for inflammation imaging.

Methods: The cytokine ligands were labeled with Tc-99m by a direct approach via 2-iminothiolane (2-IT) reduction at various 2-IT/protein molar ratios. In vivo inflammation targeting studies were carried out in a mouse ear edema model created by topical application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the right ear of ICR mice.

Results: Radiolabeling yields increased

with increasing amounts of 2-IT. When the 2-IT/protein ratio reached 1000, the radiolabeling yield was greater than 90% without significant colloid production. TPA-treated ears showed high radioligand uptake, which was clearly detected by SPECT and autoradiographic imaging. The activities (%ID/g) in the inflamed and control ears at 3 h after injection were 2.76 +/- 0.20 vs. 0.69 +/- 0.12 for IF, 5.86 +/- 0.40 vs. 2.86 +/- 0.61 for TF, and 7.61 +/- 0.86 vs. 1.99 +/- 0.31 for TFI (P<0.05 vs. controls). TFI showed significantly higher uptake others in the inflamed ears compared to TF and IF (P<0.05). Blocking study results indicated specificity of radioligand binding with decreased radioactive uptake in the inflamed ears. Western blotting and ELISA analysis further confirmed a high expression of IL-1 beta and TNF-alpha in the inflamed ears.

Conclusions: Tc-99m-labeled cytokine ligands are a promising approach for detecting and understanding the inflammatory process. TFI may be more useful than the single-domain ligands for noninvasive detection of inflammatory sites. (c) 2012 Elsevier Inc. All rights reserved.

Early interventions can improve the life chances of young children living in deprived areas.”
“The introduction of two concepts, “”local module”" and “”receptor heteromer”", facilitates the understanding of the role of interactions between different neurotransmitters in the brain. In artificial cell systems, cannabinoid CB, receptors form receptor heteromers

with dopamine D(2), adenosine A(2A) and mu opioid receptors. There is indirect but compelling evidence for the existence of the same selleck chemicals CB, receptor heteromers in striatal local modules centered in the dendritic spines of striatal GABAergic efferent neurons, particularly at a postsynaptic location. Their analysis provides new clues for the role of endocannabinoids in striatal function, which cannot only be considered as retrograde signals that inhibit neurotransmitter release. Recent studies using a new method to detect heteromerization SHP099 of more than two proteins, which consists of sequential

BRET-FRET (SRET) analysis, has demonstrated that CB(1), D(2) and A(2A) receptors can form heterotrimers in transfected cells. It is likely that functional CB(1)-A(2A)-D(2) receptor heteromers can be found where they are highly co-expressed, in the dendritic spines of GABAergic enkephalinergic neurons. The functional properties of these multiple receptor heteromers and their role in striatal function need to be determined. Published by Elsevier Ltd.”
“Background How much the successful implementation of the most effective (ie, best-practice) interventions could reduce socioeconomic inequalities of coronary heart disease mortality is not known. We assessed this issue in an occupational cohort study comparing low

with high socioeconomic groups.

Methods We undertook a prospective cohort study on 17 186 male civil servants aged 40-69 years between 1967 and 1970 in the UK (the Whitehall study). Socioeconomic position was based on employment grade. We compared the potential reduction in excess coronary heart disease mortality in men of low with those of high socioeconomic position with either best-practice interventions (reduction of systolic blood pressure by 10 mm Hg, of total cholesterol by 2 mmol/L, and of blood glucose by Selleck THZ1 1 mmol/L in pre-diabetic people; halving the prevalence of non-insulin-dependent diabetes; and complete cessation of cigarette smoking) or primordial prevention.

Findings 15-year absolute risk of death due to coronary heart disease per 100 men, standardised to age 55 years, was 11.0 for men in the low employment grade group and 7.5 for those in the high grade group. Population-wide best-practice interventions would reduce coronary heart disease mortality by 57%, and the difference in mortality between socioeconomic groups by 69%. For primordial prevention, the corresponding reductions would be 73% and 86%, respectively.

The acquisition of new RdRps may lead to a faster mutation rate and increased genetic diversity, improving overall GII. 3 fitness.”
“DC-SIGN (dendritic cell-specific ICAM-3 grabbing non-integrin) and Langerin are homologous C-type lectins

expressed as cell-surface receptors on different populations of dendritic cells (DCs). DC-SIGN interacts with glycan structures on HIV-1, facilitating virus survival, Flavopiridol transmission and infection, whereas Langerin, which is characteristic of Langerhans cells (LCs), promotes HIV-1 uptake and degradation. Here we describe a comprehensive comparison of the glycan specificities of both proteins by probing a synthetic carbohydrate microarray comprising 275 sugar compounds using the bacterially produced and fluorescence-labeled, monomeric carbohydrate-recognition domains (CRDs) of DC-SIGN and Langerin. In this side-by-side study DC-SIGN was found to preferentially bind internal mannose residues of high-mannose-type saccharides and the fucose-containing blood-type antigens H, A, B, Le(a), Le(b) Le(x), Le(y), sialyl-Le(a) as well as sulfatated derivatives of Le(a) and Le(x). In contrast, Langerin appeared to recognize a different spectrum of compounds, especially those containing terminal mannose, terminal N-acetylglucosamine and 6-sulfogalactose residues, but also the blood-type antigens H, A and B. Of the Lewis antigens,

only Le(b), Le(y), sialyl-Le(a) and the sialyl-Le(x) derivative with 6-sulfatation at https://www.selleckchem.com/products/sch-900776.html the galactose (sialyl-6SGal Le(x)) were weakly bound by Langerin. Notably, Ca(2)-independent glycan-binding activity of Langerin could not be detected either by probing the glycan array or by isothermal titration calorimetry of the CRD with mannose and mannobiose. The precise knowledge of carbohydrate specificity of DC-SIGN and Langerin receptors resulting

from our study may aid the future design of microbicides that specifically affect the DC-SIGN/HIV-1 interaction while not compromising the protective function of Langerin.”
“Kaposi’s Sarcoma-associated herpesvirus click here (KSHV) is maintained as a stable episome in latently infected pleural effusion lymphoma (PEL) cells. Episome maintenance is conferred by the binding of the KSHV-encoded LANA protein to the viral terminal repeats (TR). Here, we show that DNA replication in the KSHV TR is coupled with DNA recombination and mediated in part through the cellular replication fork protection factors Timeless (Tim) and Tipin. We show by two-dimensional (2D) agarose gel electrophoresis that replication forks naturally stall and form recombination-like structures at the TR during an unperturbed cell cycle. Chromatin immunoprecipitation (ChIP) assays revealed that Tim and Tipin are selectively enriched at the KSHV TR during S phase and in a LANA-dependent manner. Tim depletion inhibited LANA-dependent TR DNA replication and caused the loss of KSHV episomes from latently infected PEL cells.