Evaluation of the Effect of Occlusal Calibration in Periodontitis Patients with Occlusal Trauma Using T-Scan.

BACKGROUND: High occlusal forces in patients with untreated periodontitis may reflect occlusal trauma-associated periodontal conditions. Occlusal analysis using T-scan might provide the distribution of occlusal loading forces in periodontitis patients. The study aimed to evaluate the effect of occlusal trauma in periodontitis patients and occlusal calibration using a T-scan. MATERIALS AND METHODS: A total of 30 periodontitis patients were recruited for the study. Patients were categorized into two groups: Group I: scaling and root planing followed by T-scan recording and no occlusal calibration; Group II: scaling and root planing followed by occlusal calibration using T-scan. Clinical parameters, orthopantomogram (OPG) and T-scan evaluation were evaluated at baseline, 3-month and 6-month intervals. RESULTS: Significant improvements in clinical parameters were noted at different time intervals after occlusal calibration using T-scan. At 3-month intervals, mean pocket depth showed statistically significant difference among the test group in the right (upper and lower) and left lower quadrant at P = 0.01, 0.002 and 0.005, respectively. Mean clinical attachment level (CAL) showed statistically significant difference among the test group in the right upper, right lower and left lower quadrants at P = 0.02, 0.001 and 0.009, respectively, at 3 months. The comparison of the mean gingival index (GI) at 6 months showed statistically significant difference among test and control groups at 6 months in different study quadrants (P = 1 in right upper, 0.009 in right lower, <0.001 in left upper and <0.001 in left lower). Mean pocket depth at the 6-month follow-up showed statistically significant difference among the test group in all the study quadrants (P = <0.001 in right upper, <0.001 in right lower, 0.003 in left upper and 0.005 in left lower). Mean CAL showed statistically significant difference among the test group in all the study quadrants at 6-month intervals (P = 0.02 in right upper, <0.001 in right lower, 0.01 in left upper and 0.04 in left lower). The bone defect height showed a statistically significant difference only in the right upper quadrant among both the test groups at the 6-month follow-up (P = 0.02). Comparing the mean percentage of force on both sides of the jaw showed a statistically significant difference among the test group at 6 months (P = 0.001 on the left side and 0.001 on the right side). CONCLUSION: The occlusal correction using T-scan showed a positive association between probing pocket depth (PPD) and CAL at different time intervals from baseline to 6 months when these parameters were compared after occlusal adjustments.

A Comprehensive Analysis of Y-Chromosome Microdeletions and Their Relationship to Male Infertility and Lifestyle Variables.

BACKGROUND: Male infertility is the inability of a male to conceive a fertile female during at least a year of unprotected sexual activity. A variety of medical conditions and treatments cause male infertility. Y chromosome microdeletion is an important cause of infertility among males. Various epidemiological factors also play a role in the occurrence of infertility. Our study aims to determine the association between Y-chromosome microdeletion and age, sperm count, body mass index (BMI), alcohol, and tobacco consumption. METHODS: This study was conducted in 70 male infertility cases. Data was collected from 2018 to 2023 at the Genetic Lab, Department of Anatomy, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India. Demographic profiles, including age, sperm count, weight and height, and history of smoking and drinking, were collected from individuals. BMI was calculated, and chromosome analysis was done for Y chromosome microdeletion. Both multiplex and singleplex methods were used to determine the microdeletion using a thermocycler (Applied Biosystems, VeritiTM 96-well Fast Thermal Cycler, 0.2 ml USA) in AZF, and the association between age, sperm count, BMI, alcohol, and tobacco was determined. RESULTS: The number of regions deleted among individuals varies from one to seven. Regions Sy746, Sy143, and Sy145 were found to be commonly deleted. We found a positive, but not statistically significant, correlation between age and microdeletion (point biserial correlation coefficient (r) = 0.2, p-value = 0.097). When comparing age with sperm count, the results showed a negative correlation, highlighting the influence of age on sperm count (r (68) = 0.284, p = 0.017). In comparing BMI and microdeletion, no significant relationship (χ² = 3.7, p = 0.296) indicated independence between them. According to our observations, microdeletion affects all smokers and 45% of non-smokers. We found a significant association between smoking and microdeletion (χ2 = 4.49, P = 0.034). There was no statistically significant relationship between microdeletion and drinking (χ²(3) = 5.65, p = 0.13). CONCLUSION: We discovered a significant positive association between smoking and a positive, but not statistically significant, correlation between age, BMI, and drinking, as well as a microdeletion. There are probably a lot of unidentified variables that affect successful fertilization and implantation. These could include variables that affect fertility and the success of reproduction on an environmental, genetic, and epigenetic level. The study reveals that Y chromosome microdeletion and other epidemiological factors coexist concurrently in cases of infertility. Assessing these variables is crucial for infertile patients. A community-based, comprehensive survey is required to assess the overall consequences of various epidemiological factors on infertility.

BAR domain is essential for early endosomal trafficking and dynamics in Ascochyta rabiei.

Ascochyta blight disease is a devastating disease caused by the fungal pathogen Ascochyta rabiei that threatens chickpea production around the globe. Endocytic mechanism has a significant role in fungal growth and virulence. The underlying biology of biogenesis of central component of endocytosis viz Rab5 vesicles, is not completely understood. The involvement of F-BAR domain containing protein (ArF-BAR) in various cellular processes that collectively make ArF-BAR as an important virulence determinant. Here, we report that ArF-BAR is involved in biogenesis and motility of early endosome. In the absence of ArF-BAR gene (Δarf-bar), fungal mutants exhibited reduced number of EGFP coated ArRab5 vesicles, along with the considerable reduction in their dynamics. Here, we show that ArF-BAR interacts with clathrin light chain (ArCLC), specifically with its F-BAR domain. These findings suggests the novel role of ArF-BAR in biogenesis and dynamics of early endosome. Additionally, ArF-BAR is involved in clathrin-mediated mechanism of endocytosis which is required for host infection and disease development. Identification of this pathway offers new impending targets for disease intervention in plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03451-5.

Silencing KCC2 in mouse dorsal hippocampus compromises spatial and contextual memory.

Delayed upregulation of the neuronal chloride extruder KCC2 underlies the progressive shift in GABA signaling polarity during development. Conversely, KCC2 downregulation is observed in a variety of neurological and psychiatric disorders often associated with cognitive impairment. Reduced KCC2 expression and function in mature networks may disrupt GABA signaling and promote anomalous network activities underlying these disorders. However, the causal link between KCC2 downregulation, altered brain rhythmogenesis, and cognitive function remains elusive. Here, by combining behavioral exploration with in vivo electrophysiology we assessed the impact of chronic KCC2 downregulation in mouse dorsal hippocampus and showed it compromises both spatial and contextual memory. This was associated with altered hippocampal rhythmogenesis and neuronal hyperexcitability, with increased burst firing in CA1 neurons during non-REM sleep. Reducing neuronal excitability with terbinafine, a specific Task-3 leak potassium channel opener, occluded the impairment of contextual memory upon KCC2 knockdown. Our results establish a causal relationship between KCC2 expression and cognitive performance and suggest that non-epileptiform rhythmopathies and neuronal hyperexcitability are central to the deficits caused by KCC2 downregulation in the adult mouse brain.

A streamable large-scale clinical EEG dataset for Deep Learning.

Deep Learning has revolutionized various fields, including Computer Vision, Natural Language Processing, as well as Biomedical research. Within the field of neuroscience, specifically in electrophysiological neuroimaging, researchers are starting to explore leveraging deep learning to make predictions on their data without extensive feature engineering. The availability of large-scale datasets is a crucial aspect of allowing the experimentation of Deep Learning models. We are publishing the first large-scale clinical EEG dataset that simplifies data access and management for Deep Learning. This dataset contains eyes-closed EEG data prepared from a collection of 1,574 juvenile participants from the Healthy Brain Network. We demonstrate a use case integrating this framework, and discuss why providing such neuroinformatics infrastructure to the community is critical for future scientific discoveries.

Active Dendrites and Local Field Potentials: Biophysical Mechanisms and Computational Explorations.

Neurons and glial cells are endowed with membranes that express a rich repertoire of ion channels, transporters, and receptors. The constant flux of ions across the neuronal and glial membranes results in voltage fluctuations that can be recorded from the extracellular matrix. The high frequency components of this voltage signal contain information about the spiking activity, reflecting the output from the neurons surrounding the recording location. The low frequency components of the signal, referred to as the local field potential (LFP), have been traditionally thought to provide information about the synaptic inputs that impinge on the large dendritic trees of various neurons. In this review, we discuss recent computational and experimental studies pointing to a critical role of several active dendritic mechanisms that can influence the genesis and the location-dependent spectro-temporal dynamics of LFPs, spanning different brain regions. We strongly emphasize the need to account for the several fast and slow dendritic events and associated active mechanisms - including gradients in their expression profiles, inter- and intra-cellular spatio-temporal interactions spanning neurons and glia, heterogeneities and degeneracy across scales, neuromodulatory influences, and activitydependent plasticity - towards gaining important insights about the origins of LFP under different behavioral states in health and disease. We provide simple but essential guidelines on how to model LFPs taking into account these dendritic mechanisms, with detailed methodology on how to account for various heterogeneities and electrophysiological properties of neurons and synapses while studying LFPs.

Modulation of fungal virulence through CRZ1 regulated F-BAR-dependent actin remodeling and endocytosis in chickpea infecting phytopathogen Ascochyta rabiei.

Polarized hyphal growth of filamentous pathogenic fungi is an essential event for host penetration and colonization. The long-range early endosomal trafficking during hyphal growth is crucial for nutrient uptake, sensing of host-specific cues, and regulation of effector production. Bin1/Amphiphysin/Rvs167 (BAR) domain-containing proteins mediate fundamental cellular processes, including membrane remodeling and endocytosis. Here, we identified a F-BAR domain protein (ArF-BAR) in the necrotrophic fungus Ascochyta rabiei and demonstrate its involvement in endosome-dependent fungal virulence on the host plant Cicer arietinum. We show that ArF-BAR regulates endocytosis at the hyphal tip, localizes to the early endosomes, and is involved in actin dynamics. Functional studies involving gene knockout and complementation experiments reveal that ArF-BAR is necessary for virulence. The loss-of-function of ArF-BAR gene results in delayed formation of apical septum in fungal cells near growing hyphal tip that is crucial for host penetration, and impaired secretion of a candidate effector having secretory signal peptide for translocation across the endoplasmic reticulum membrane. The mRNA transcripts of ArF-BAR were induced in response to oxidative stress and infection. We also show that ArF-BAR is able to tubulate synthetic liposomes, suggesting the functional role of F-BAR domain in membrane tubule formation in vivo. Further, our studies identified a stress-induced transcription factor, ArCRZ1 (Calcineurin-responsive zinc finger 1), as key transcriptional regulator of ArF-BAR expression. We propose a model in which ArCRZ1 functions upstream of ArF-BAR to regulate A. rabiei virulence through a mechanism that involves endocytosis, effector secretion, and actin cytoskeleton regulation.

FOS licenses early events in stem cell activation driving skeletal muscle regeneration.

Muscle satellite cells (SCs) are a quiescent (non-proliferative) stem cell population in uninjured skeletal muscle. Although SCs have been investigated for nearly 60 years, the molecular drivers that transform quiescent SCs into the rapidly dividing (activated) stem/progenitor cells that mediate muscle repair after injury remain largely unknown. Here we identify a prominent FBJ osteosarcoma oncogene (Fos) mRNA and protein signature in recently activated SCs that is rapidly, heterogeneously, and transiently induced by muscle damage. We further reveal a requirement for FOS to efficiently initiate key stem cell functions, including cell cycle entry, proliferative expansion, and muscle regeneration, via induction of "pro-regenerative" target genes that stimulate cell migration, division, and differentiation. Disruption of one of these Fos/AP-1 targets, NAD(+)-consuming mono-ADP-ribosyl-transferase 1 (Art1), in SCs delays cell cycle entry and impedes progenitor cell expansion and muscle regeneration. This work uncovers an early-activated FOS/ART1/mono-ADP-ribosylation (MARylation) pathway that is essential for stem cell-regenerative responses.

Transcript profiling reveals potential regulators for oxidative stress response of a necrotrophic chickpea pathogen Ascochyta rabiei.

Necrotrophic pathogens experience host-generated oxidative stress during pathogenesis. They overcome such hostile environment by intricate mechanisms which are largely understudied. In this article, reference-based transcriptome analysis of a devastating Ascochyta Blight (AB) disease causing chickpea pathogen Ascochyta rabiei was explored to get insights into survival mechanisms under oxidative stress. Here, expression profiling of mock-treated and menadione-treated fungus was carried out by RNA-Seq approach. A significant number of genes in response to oxidative stress were overrepresented, suggestive of a robust and coordinated defense system of A. rabiei. A total 73 differentially expressed genes were filtered out from both the transcriptomes, among them 64 were up-regulated and 9 were found down-regulated. The gene ontology and KEGG mapping were conducted to comprehend the possible regulatory roles of differentially expressed genes in metabolic networks and biosynthetic pathways. Transcript profiling, KEGG pathway and gene ontology-based enrichment analysis revealed 12 (16.43%) stress responsive factors, 25 (34.24%) virulence associated genes, 10 (13.69%) putative effectors and 28 (38.35%) important interacting proteins associated with various metabolic pathways. In addition, genes with differential expression were further explored for underlying putative pathogenicity factors. We identified five genes ST47_g10291, ST47_g9396, ST47_g10294, ST47_g4395, and ST47_g7191 that were common to stress and fungal pathogenicity. The factors recognized in this work can be used to establish molecular tools to explain the regulatory gene networks engaged in stress response of fungal pathogens and disease management.

Anatomical Correlation of Core Muscle Activation in Different Yogic Postures.

Faulty postures due to sedentary lifestyle cause weakening of core muscles which contributes to increased incidence of musculoskeletal disorders (MSDs). Although a few research studies have quantified the core muscle activity in various yogic exercises used in rehabilitation programs, evidence correlating it to functional anatomy is scarce. Such information is important for exercise prescription when formulating treatment plans for MSDs. Therefore, the objective of this review article is to examine the literature and analyze the muscle activity produced across various yoga postures to determine which type of yoga posture elicits the highest activation for the core muscle in individuals. Literature search was performed using the following electronic databases: Cochrane Library, NCBI, PubMed, Google Scholar, EMBASE, and web of science. The search terms contained: Core muscle activation and yogic posture OR yoga and rehabilitation OR intervention AND Electromyography. Activation of specific core muscle involved asanas which depended on trunk and pelvic movements. Description of specific yogic exercise as they relate to core muscles activation is described. This information should help in planning yogic exercises that challenge the muscle groups without causing loads that may be detrimental to recovery and pain-free movement. Knowledge of activation of muscles in various yogic postures can assist health-care practitioners to make appropriate decisions for the designing of safe and effective evidence-based yoga intervention for MSDs.

The Ossified Bifid Superior Transverse Scapular Ligament Causing a Double Suprascapular Foramen: A Case Report.

Ossified bifid superior transverse scapular ligament causing a double suprascapular foramen is a very rare finding. This ossified ligament reduces the suprascapular space by half of its original size. It is one of the precipitating factors of suprascapular nerve entrapment. Here we describe a double suprascapular foramen in a dry left scapula of Indian origin. There were two bony bars bridging the suprascapular notch thereby making two foramina. The bony bars were 'V' shaped with its apex attached to the lateral side of the suprascapular notch. The upper foramen was large and triangular whereas the lower foramen was small and oval. Considering the shape of the foramen and the 'V' shaped attachment of the bony bars, we conclude it to be due to the ossification of bifid superior transverse scapular ligament. A double suprascapular foramen should always be kept in mind while diagnosing and treating suprascapular nerve entrapment. Knowledge about the double suprascapular foramen would be useful to orthopaedic surgeons who perform decompression for suprascapular nerve entrapment through arthroscopy and open procedures.

HCN channels enhance spike phase coherence and regulate the phase of spikes and LFPs in the theta-frequency range.

What are the implications for the existence of subthreshold ion channels, their localization profiles, and plasticity on local field potentials (LFPs)? Here, we assessed the role of hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in altering hippocampal theta-frequency LFPs and the associated spike phase. We presented spatiotemporally randomized, balanced theta-modulated excitatory and inhibitory inputs to somatically aligned, morphologically realistic pyramidal neuron models spread across a cylindrical neuropil. We computed LFPs from seven electrode sites and found that the insertion of an experimentally constrained HCN-conductance gradient into these neurons introduced a location-dependent lead in the LFP phase without significantly altering its amplitude. Further, neurons fired action potentials at a specific theta phase of the LFP, and the insertion of HCN channels introduced large lags in this spike phase and a striking enhancement in neuronal spike-phase coherence. Importantly, graded changes in either HCN conductance or its half-maximal activation voltage resulted in graded changes in LFP and spike phases. Our conclusions on the impact of HCN channels on LFPs and spike phase were invariant to changes in neuropil size, to morphological heterogeneity, to excitatory or inhibitory synaptic scaling, and to shifts in the onset phase of inhibitory inputs. Finally, we selectively abolished the inductive lead in the impedance phase introduced by HCN channels without altering neuronal excitability and found that this inductive phase lead contributed significantly to changes in LFP and spike phase. Our results uncover specific roles for HCN channels and their plasticity in phase-coding schemas and in the formation and dynamic reconfiguration of neuronal cell assemblies.

Morphological variations of sciatic nerve and piriformis muscle in gluteal region during fetal period

Intramuscular drug injection in the gluteal region is often the most frequent cause of sciatic nerve injury in preterm newborns. Local anatomic variation is one of the predisposing causes of iatrogenic sciatic nerve injury. The aim of this morphological study was to assess the relationship of sciatic nerve with the piriformis muscle and to elucidate variations of fusion of piriformis with neighboring muscles in the gluteal region of Indian human preterm fetuses. Four types of relationship of the sciatic nerve with the piriformis muscle were observed in one hundred gluteal regions of fifty spontaneously aborted, formalin-fixed fetuses, aged 20 to 36 week (24 males and 26 females). In 85% of the gluteal regions, the classic pattern was found, in which the two components of the sciatic nerve fuse with each other proximal to the piriformis, and the fused sciatic nerve emerges at the lower border of the piriformis. In the remaining 15% of the gluteal regions, variations in relationship were found. The most common variation, characterized by the passage of the common peroneal component through the piriformis and the emergence of the tibial part at the lower border of the piriformis, was seen in 9% of the gluteal regions. Common peroneal and tibial components passed above and below the muscle respectively in 3%, and the unsplit sciatic nerve passed through the piriformis in 3% of the gluteal regions. Four types of fusion of the piriformis with the neighboring muscles were seen: namely, no fusion; fusion with superior gamellus; fusion with gluteus medius, or fusion with gluteus medius and obturator internus complex in 28%, 43%, 26% and 3% of the gluteal regions respectively. Anatomical variations of the sciatic nerve in relation to the piriformis muscle should be kept in mind while performing medical or surgical interventions in this region

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A 12-year-old African American girl with subacute bilateral ophthalmoplegia.

A twelve-year-old African-American female presented with two week history of progressively worsening headache and fatigue, and vision difficulties for the past week. The physical examination was normal. The neurological evaluation was normal, except for cranial nerves (CN) testing, which showed bilateral restriction of adduction (CN III) and up gaze (CN IV) motions, vertical nystagmus, and left side facial paresis of central origin (CN VII). The bilateral exotropia and ophthalmoplegia are characteristics of WEBINO (Wall-Eyed Bilateral Intranuclear Ophthalmoplegia) syndrome, associated to a brain stem structural lesion. The following causes were evaluated and ruled out: tumor, infection, ischemic stroke, non-infectious inflammation. Pediatric Acquired Demyelinating Syndromes were then considered. Neuromyelitis Optica was ruled out in the absence of neuritis and normal spinal cord MRI. The differential diagnosis between Clinically Isolated Syndrome and Acute Demyelinating Encephalomyelitis, causing an isolated brain stem syndrome, is discussed.

Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle.

Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral "rejuvenating" factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction.

Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy.

The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGF-ß superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging.

Crista terminalis, musculi pectinati, and taenia sagittalis: anatomical observations and applied significance.

Background. The complex architecture of the right atrium, crista terminalis (CT), and the musculi pectinati (MP) poses enormous challenges in electrophysiology and cardiac conduction. Few studies have been undertaken to substantiate the gross features of MP, in relation to the CT, but there is still scarcity of data regarding this. We tried to reinvestigate the gross arrangement of muscle bundles in the right atrium. Methods. Utilizing 151 human hearts and orientation of MP and its variations and relationship to the CT were investigated along with taenia sagittalis (TS). Patterns of MP were grouped in 6 categories and TS under three groups. Result. A plethora of variations were observed. Analysis of all the specimen revealed that 68 samples (45%) were of type 1 category and 27 (18%) fell into type 2 category. Prominent muscular columns were reported in 12 samples (8%). 83 samples (55%) presented with a single trunk of TS. Multiple trunks of TS were reported in 38 samples (25%). Conclusion. Samples with type 6 MP and type B/type C TS, which have a more complex arrangement of fibers, have a tendency to be damaged during cardiac catheterization. Nonetheless, the area as a whole is extremely significant considering the pragmatic application during various cardiac interventions.

Comparative transcriptome analysis of the necrotrophic fungus Ascochyta rabiei during oxidative stress: insight for fungal survival in the host plant.

Localized cell death, known as the hypersensitive response (HR), is an important defense mechanism for neutralizing phytopathogens. The hallmark of the HR is an oxidative burst produced by the host plant. We aimed to identify genes of the necrotrophic chickpea blight fungus Ascochyta rabiei that are involved in counteracting oxidative stress. A subtractive cDNA library was constructed after menadione treatment, which resulted in the isolation of 128 unigenes. A reverse northern blot was used to compare transcript profiles after H(2)O(2), menadione and sodium nitroprusside treatments. A total of 70 unigenes were found to be upregulated by more than two-fold following menadione treatment at different time intervals. A large number of genes not previously associated with oxidative stress were identified, along with many stress-responsive genes. Differential expression patterns of several genes were validated by quantitative real-time PCR (qRT-PCR) and northern blotting. In planta qRT-PCR of several selected genes also showed differential expression patterns during infection and disease progression. These data shed light on the molecular responses of the phytopathogen A. rabiei to overcome oxidative and nitrosative stresses and advance the understanding of necrotrophic fungal pathogen survival mechanisms.

Recombinational repair within heterochromatin requires ATP-dependent chromatin remodeling.

Heterochromatin plays a key role in protection of chromosome integrity by suppressing homologous recombination. In Saccharomyces cerevisiae, Sir2p, Sir3p, and Sir4p are structural components of heterochromatin found at telomeres and the silent mating-type loci. Here we have investigated whether incorporation of Sir proteins into minichromosomes regulates early steps of recombinational repair in vitro. We find that addition of Sir3p to a nucleosomal substrate is sufficient to eliminate yRad51p-catalyzed formation of joints, and that this repression is enhanced by Sir2p/Sir4p. Importantly, Sir-mediated repression requires histone residues that are critical for silencing in vivo. Moreover, we demonstrate that the SWI/SNF chromatin-remodeling enzyme facilitates joint formation by evicting Sir3p, thereby promoting subsequent Rad54p-dependent formation of a strand invasion product. These results suggest that recombinational repair in the context of heterochromatin presents additional constraints that can be overcome by ATP-dependent chromatin-remodeling enzymes.