What Women Want? The State of the Art regarding the Treatment of Young Women with Hypoactive Sexual Desire Disorder.

BACKGROUND: Hypoactive sexual desire disorder (HSDD) in premenopausal women involves biological, psychological, and social aspects. In the European Society for Sexual Medicine meeting in Rotterdam in February 2023, several leading experts in the field discussed the multifaceted nature of this disorder and the state of the art regarding treatment at a round table. This review reflects the information discussed at this event and further discusses current controversies. SUMMARY: HSDD is the most prevalent female-estimated sexual disorder reported by 28% of the 40% premenopausal women with sexual dysfunction. Flibanserin and bremelanotide are the only approved medications to treat HSDD in the USA, and none are approved in Europe. Lybrido, Lybridos, and Lorexys are under development. There are several psychological factors with impact in sexual desire, including depression and sexual abuse. Feminine sexual scripts, the pleasure gap, and structural inequalities also affect sexual desire. Evidence strongly supports the value of combining medical and psychological approaches in the treatment of HSDD, but there is ongoing controversy regarding the pharmacological treatment of young women with HSDD. However, some women seem open and would like to have access to drug treatment. KEY MESSAGES: The treatment of HSDD in young women requires a mixed treatment approach that addresses the disorder's complexity. Despite clinicians seeming to be divided between using pharmacological and/or psychosocial approaches, some women might respond better to one type of intervention over the others. This calls for the development of tools that assess the best approach for each person, including their will and informed choice.

Sexual boredom and sexual desire in long-term relationships: a latent profile analysis.

BACKGROUND: Research suggests a general link between sexual boredom and sexual desire, but its understanding is currently very limited. AIM: To identify distinct (latent) groups of women and men in long-term relationships based on their reported levels of sexual boredom and sexual desire. METHODS: Latent profile analysis (LPA) was conducted in an online sample of 1223 Portuguese participants aged 18 and 66 years (mean ± SD, 32.75 ± 6.11), using indicators of sexual boredom and partner-related, attractive other-related, and solitary sexual desire to categorize participants. Multinomial logistic regression analysis was carried out to explore predictors and correlates of the latent profiles. OUTCOMES: Sexual boredom was assessed by the Sexual Boredom Scale, while sexual desire was measured with the Sexual Desire Inventory. RESULTS: As compared with women, men reported higher levels of sexual boredom and sexual desire. LPA indicated 3 profiles in women and 2 profiles in men. Among women, P1 was characterized by above-average sexual boredom, below-average partner- and attractive other-related sexual desire, and very low solitary sexual desire; P2 by below-average sexual boredom, attractive other-related sexual desire, and solitary sexual desire and above-average partner-related sexual desire; and P3 by above-average sexual boredom, attractive other-related sexual desire, and solitary sexual desire and below-average partner-related sexual desire. In men, P1 was characterized by high sexual boredom, above-average partner-related sexual desire, and high attractive other-related and solitary sexual desire and P2 by below-average sexual boredom and above-average partner-related, attractive other-related, and solitary sexual desire. The latent profiles did not differ according to relationship duration. Overall, the sole consistent correlate of the latent categorization was sexual satisfaction. CLINICAL IMPLICATIONS: In women, above-average levels of sexual boredom were linked to below-average levels of partner-related desire, which suggests likely benefits of helping the couple to minimize or cope better with their sexual routines. In men, participants in the 2 profiles did not differ in partner-related sexual desire, suggesting that clinical interventions dealing with male sexual boredom should investigate factors beyond the current relationship. STRENGTHS AND LIMITATIONS: This study explored different facets of sexual desire and used LPA, rendering advantages over previous research. The male sample has lower statistical power than the female sample. CONCLUSION: Patterns of sexual boredom and sexual desire among individuals in long-term monogamous relationships are distinct and consistently related to sexual satisfaction in women and men and to relationship satisfaction among only women, which have important clinical ramifications.

CusProSe: a customizable protein annotation software with an application to the prediction of fungal secondary metabolism genes.

We report here a new application, CustomProteinSearch (CusProSe), whose purpose is to help users to search for proteins of interest based on their domain composition. The application is customizable. It consists of two independent tools, IterHMMBuild and ProSeCDA. IterHMMBuild allows the iterative construction of Hidden Markov Model (HMM) profiles for conserved domains of selected protein sequences, while ProSeCDA scans a proteome of interest against an HMM profile database, and annotates identified proteins using user-defined rules. CusProSe was successfully used to identify, in fungal genomes, genes encoding key enzyme families involved in secondary metabolism, such as polyketide synthases (PKS), non-ribosomal peptide synthetases (NRPS), hybrid PKS-NRPS and dimethylallyl tryptophan synthases (DMATS), as well as to characterize distinct terpene synthases (TS) sub-families. The highly configurable characteristics of this application makes it a generic tool, which allows the user to refine the function of predicted proteins, to extend detection to new enzymes families, and may also be applied to biological systems other than fungi and to other proteins than those involved in secondary metabolism.

Clinical Considerations of Ehlers-Danlos Syndrome for Implant Dentistry: Two Case Reports.

Ehlers-Danlos Syndrome (EDS) is a group of congenital connective tissue disorders that commonly affect joints, muscles, soft tissue, and blood circulation in the affected population. Many oral manifestations are displayed in EDS patients that can include gingival recession, lack of attached gingiva, early severe periodontal disease, and dental caries. However, the literature is limited and oftentimes contradictory regarding dental implants in EDS patients. The aim of this study is to report two successful cases of implants placed in EDS patients, one treated with bone augmentation and both restored with prosthetic implant rehabilitations. Int J Periodontics Restorative Dent 2023;43:e81-e87. doi: 10.11607/prd.5842.

Ehlers-Danlos Syndrome in Prosthodontics, Periodontology, and Implant Dentistry: A Systematic Review of the Literature

Ehlers-Danlos Syndrome (EDS) is one of the most common congenital connective tissue disorders, affecting the synthesis and production of collagen cells. The medical implications for joints, muscles, soft tissue, and blood circulation have been documented in the literature. Many oral manifestations are displayed in EDS patients, including gingival recession, lack of attached gingiva, early severe periodontitis, and dental anomalies and dental caries. However, the literature is limited and oftentimes contradictory, and therefore provides no consensus for guidelines regarding prosthodontic, periodontal, and implant treatment of patients with EDS. Therefore, the aim of this systematic review was to analyze the pertinent literature regarding prosthodontics, periodontology, and implant dentistry in EDS patients.

Repair of a Non-Retentive Crown Over a Press-Fit Implant Placed 30 Years Prior: A Case Report.

Dental implant treatment has been proven to be a successful therapy to rehabilitate single, partial, and fully edentulous sites. Evidence shows that the use of implant-supported restorations is predictable and can deliver long-term success. However, discontinuation of implant systems can be challenging for prosthesis maintenance. In this case report, a 70-year-old female patient presented to the implant department at New York University College of Dentistry with a press-fit implant with a one-piece cementable abutment that was placed more than 30 years prior. The patient's chief complaint was that the crown kept falling off. Upon evaluation, it was found that the implant was well-integrated in bone with no signs of infection. Explantation and replacement of the well-integrated implant was not considered the best option. An alternative approach was to address the retention of the abutment. The purpose of this case report is to demonstrate an intraoral technique for fabricating a custom cement-retained crown over a non-retentive one-piece press-fit implant.

A Cluster Analysis on Sexual Boredom Profiles in A Community Sample of Men and Women.

Research evidence of the attributes of sexual boredom is extremely limited. Understanding variability in the experience of sexual boredom may offer relevant insights for the field of human sexuality. This study aimed to explore the co-occurrence of sexual boredom and other sexuality-related dimensions. The sample consisted of 1021 participants aged between 18 and 75 years old (M = 32.68, SD = 8.79). A gender-stratified cluster analysis was performed to classify individuals regarding their scores on sexual boredom, general boredom, sexual sensation seeking, sexual desire, sexual excitation, sexual pleasure, and sexual satisfaction. A three-cluster solution was revealed for both men and women. Based on our findings, we put forward a profile for the sexually bored individual, who is more likely to be married or cohabiting with a partner, to have a boredom prone personality, to lack sexual sensation seeking, experience low sexual pleasure and satisfaction, and to present with sexual arousal and/or desire problems. Women dealing with sexual boredom might present low sexual desire for their partner but experience high sex desire for attractive others. Results are critically discussed and implications for sexual therapy explored.

Women's Sexual Health During the Pandemic of COVID-19: Declines in Sexual Function and Sexual Pleasure.

PURPOSE OF THE REVIEW: The World Health Association declared COVID-19 a pandemic more than 1 year ago. We conducted a systematic review of the literature on the topic of women's sexual health during the pandemic, with a focus on sexual function and sexual pleasure. Our aim is to describe current findings and to discuss implications for women's sexual health during this period. RECENT FINDINGS: Thirty-four articles, from 18 countries, were identified. These studies addressed topics ranging from individual aspects, such as cognitive, emotional, and personality factors affecting sexuality during the pandemic, to contextual factors, including relationship, childrearing, and employment status in this period. SUMMARY: Research identified a deterioration of women's sexual function across countries, with an emphasis on sexual desire. Most studies found decreases in the frequency of sexual intercourse during the pandemic and increases in solitary sexual behavior. Many women also experienced declines in sexual satisfaction and relationship satisfaction. Findings suggested that gender inequalities contributed to lower indices of sexual function and satisfaction, and might have exacerbated the pleasure gap between men and women.

A Systematic Review on Sexual Boredom.

BACKGROUND: Empirical data on sexual boredom are scarce and unsystematized, contrasting with the literature on general boredom. AIM: The aim of this review of literature is to verify how sexual boredom is defined in previous research and which relationships were found with sexual functioning, relationship dynamics, or gender. METHODS: A systematic search was conducted in EBSCO, Scopus, Web of Science, and PubMed databases for papers published until August 2020. Search terms used were "sexual boredom" or "sexual tedium" or "sexual indifference" or "sexual monotony" or a combination of "boredom" and "sexual activity" or "intercourse". This systematic review followed PRISMA guidelines. OUTCOMES: Articles were grouped in general boredom and sexuality research and in sexual boredom research. RESULTS: This review consists of 43 articles, of which 31 are quantitative studies, 8 are qualitative studies, and 4 are mixed-method studies. Studies concerning general boredom and sexuality include research on diverse aspects of sexual behavior, namely solitary sexual behavior, extra-dyadic sex, compulsive sexual behavior, and risky sexual behavior. Sexual boredom research included papers regarding personality, sexual response, and varied aspects of sexual behavior. CLINICAL IMPLICATIONS: Findings suggest sexual boredom is related with sexual response, sexual satisfaction, and hypersexuality, which renders clinical relevance. Sexual boredom impacts well-being, and further research should focus on exploring potential mechanisms underpinning this sexual problem. STRENGTHS AND LIMITATIONS: To the authors' knowledge, this is the only existing systematic review of sexual boredom and allowed identifying key features of sexual boredom and related aspects. However, because most studies are correlational, and several do not use comprehensive measures of sexual boredom, no causal relationships were identified. CONCLUSION: This review indicates the construct of sexual boredom includes individual, relationship, and societal aspects. However, no definition of sexual boredom includes these, and current knowledge does not allow formulating a model or a theory of sexual boredom. de Oliveira L, Carvalho J, Nobre P. A Systematic Review on Sexual Boredom. J Sex Med 2021;18:565-581.

Patterns of sexual behavior and psychological processes in asexual persons: a systematic review.

Asexuality is commonly regarded as lack of sexual attraction. Research in asexuality grew progressively in the past two decades. However, asexuals' patterns of sexual behavior and psychological processes were not yet systematized. This review searched for articles that could potentially help establishing these patterns. Articles published in English until December 31st 2019 were retrieved from Medline, Embase, Cochrane, EBSCO, PubMed, Scopus, and PsycARTICLES. A systematic search was conducted using an exhaustive list of key terms regarding asexuality and sexual behavior following PRISMA guidelines. Of the 195 initially retrieved, only 23 were considered for this review. Of the 23 articles, 16 were quantitative studies, 5 were qualitative studies, and 2 comprised quantitative and qualitative studies. Overall, current findings suggest that asexuals present great heterogeneity of sexual behaviors and psychological processes regarding sexuality, including different aspects and types of interpersonal and romantic relationships, sexual attitudes or fantasies. Conversely, data did not find support for the claim that asexuals present impaired sexual functioning. The little geographic and cultural diversity of the samples is a major limitation in these studies, preventing the properly representation of asexuals. Furthermore, asexuals may benefit from evidence on the biopsychosocial factors shaping sexual, emotional, and relationship well-being, as far as such evidence is built upon asexuals' lenses, rather than on heteronormativity criteria.

Perceptions of sexual boredom in a community sample.

This study explored the definitions of sexual boredom in a large community sample of Portuguese individuals. A thematic analysis of written responses to the question "What is sexual boredom for you?" was conducted with 653 participants aged 18 to 75 (M = 33.14; SD = 9.01) of multiple genders, sexual orientations, and relationship types. Three main themes were identified: definitions of sexual boredom, predisposing and maintenance factors of sexual boredom, and managing of sexual boredom. Sexual monotony, sexual desire, and hedonic value stand out as defining features of sexual boredom. Findings suggest the need of a multidimensional measure of sexual boredom.

Psychosocial and Behavioral Aspects of Women's Sexual Pleasure: A Scoping Review.

Objectives: To clarify the psychosocial and behavioral factors related to women's sexual pleasure. Methods: A search was conducted on EBSCO and Web of Science databases using the key terms "female sexual pleasure" and "women sexual pleasure" and following PRISMA guidelines. Results: 76 articles were identified, referring to sexual practices, individual factors, interpersonal factors, societal factors, and ways of enhancing sexual pleasure. Conclusions: Age, sexual experience, arousability, body-esteem, sexual autonomy, and sexual assertiveness seem to benefit women's sexual pleasure, while sexual compliance and a gender power imbalance seem to compromise it. Additional research regarding non-western and non-heterosexual women is still required.

Misdosing of Non-Vitamin K Antagonist Oral Anticoagulants in Primary Care.

PURPOSE: Prescription patterns of non-vitamin K antagonist oral anticoagulants (NOACs) are unknown among primary care physicians, where most patients with nonvalvular atrial fibrillation (NVAF) are diagnosed and followed up. The goal of this study was to evaluate overdosing and underdosing of NOACs in patients with NVAF followed up in primary care and determine their clinical predictors. METHODS: This multicenter cross-sectional study included all patients with NVAF followed up in 13 primary care units in the center region of Portugal. Patients receiving antithrombotic regimens other than NOACs and patients with missing data were excluded. FINDINGS: The study included 858 patients with NVAF on an NOAC regimen. Overall, 30.3% were prescribed an off-label dosage (25.4% with infratherapeutic dosing [ITD] and 4.9% with supratherapeutic dosing). Chronic kidney disease (odds ratio, 14.0; 95% CI, 5.4-36.5; P < 0.001) and female sex (odds ratio, 2.6; 95% CI, 1.2-5.7; P < 0.001) were independent predictors of supratherapeutic dosing. We also found a significant effect of chronic kidney disease on ITD (odds ratio, 0.22; 95% CI, 0.258-0.678; P < 0.001). IMPLICATIONS: In primary care, NOACs are frequently prescribed with unadjusted dosages, generally infratherapeutic. Attention should be paid to women and patients with chronic kidney disease.

The Link Between Boredom and Hypersexuality: A Systematic Review.

BACKGROUND: Some conceptualizations of hypersexuality posit boredom as a possible trigger of hypersexual behavior. AIM: This work aims to review published articles addressing the link between boredom and hypersexuality to investigate if this relationship can yet be established based on current empirical data. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies, published until September 2019, were retrieved from EBSCO, Scopus, Web of Science, and PubMed. A systematic search was conducted using an exhaustive list of key terms combining "boredom" with "hypersexuality," "sexual impulsivity," "sexual compulsivity," and "sexual addiction." Only articles presenting empirical results concerning the relationship between boredom and hypersexuality were considered. RESULTS: From the initial poll of 76 articles, only 19 articles were included in our final selection. Of the total studies, 16 were quantitative studies and 3 were qualitative studies. 4 studies were validation studies of hypersexuality-related measures, 11 studies concerned online sexual activity, and 3 reported sexual boredom. 7 studies with men used non-heterosexual samples. 5 studies used samples with both women and men, and 1 study used a sample of women only. Most studies indicate a positive association between boredom and hypersexuality, although 4 did not. IMPLICATIONS: Further studies with diversified samples are still indispensable, as female samples are not portrayed and research is much focused on online sexual activity. Future research should explore the relationship between boredom and hypersexuality within specific behavioral specifiers including masturbation, pornography use, sexual behavior with consenting adults, cybersex, telephone sex, and strip clubs. STRENGTHS AND LIMITATIONS: To the authors' knowledge, this is the first review looking at the possible link between boredom and hypersexuality. Investigation on the topic is scarce, and several of the studies included in this review correspond to anecdotal evidences of the phenomenon, as only few studies used appropriate measures of boredom. CONCLUSION: Although current literature identifies a link between boredom and hypersexuality, further substantive research is still much needed to clarify the associations between the 2 constructs. de Oliveira L, Carvalho J. The Link Between Boredom and Hypersexuality: A Systematic Review. J Sex Med 2020;17:994-1004.

The Revisited Genome of Bacillus subtilis Bacteriophage SPP1.

Bacillus subtilis bacteriophage SPP1 is a lytic siphovirus first described 50 years ago [1]. Its complete DNA sequence was reported in 1997 [2]. Here we present an updated annotation of the 44,016 bp SPP1 genome and its correlation to different steps of the viral multiplication process. Five early polycistronic transcriptional units encode phage DNA replication proteins and lysis functions together with less characterized, mostly non-essential, functions. Late transcription drives synthesis of proteins necessary for SPP1 viral particles assembly and for cell lysis, together with a short set of proteins of unknown function. The extensive genetic, biochemical and structural biology studies on the molecular mechanisms of SPP1 DNA replication and phage particle assembly rendered it a model system for tailed phages research. We propose SPP1 as the reference species for a new SPP1-like viruses genus of the Siphoviridae family.

Bacteriophage SPP1 pac Cleavage: A Precise Cut without Sequence Specificity Requirement.

In many tailed bacteriophages, DNA packaging is initiated by recognition and cleavage of a specific sequence pac by the small (TerS) and large (TerL) terminase subunits. It was previously shown that the SPP1 pac region has two sequences where TerS binds (pacR and pacL), flanking the segment where TerL cleaves the SPP1 DNA (pacC). However, the pac-specific sequences required to achieve this endonucleolytic cut were not established. Their characterization is essential to understand the underlying mechanism. We show that the pacR sequence localized within 35bp downstream of the pac cut can be extensively degenerated, including its c1 and c2 repeats, and that only a disruption of a 5-bp polyadenine tract impairs the pac cleavage. This result together with deletion analysis of pacL shows that the specific DNA sequences required for targeting the terminase for pac cleavage are considerably shorter than the large region bound by TerS. Furthermore, extensive degeneration of the 6-bp target sequence within pacC where pac cleavage occurs reveals that TerL maintains, remarkably, its precise position of cleavage. Studies with SPP1-related phages show the conservation of the cut position, irrespective of the sequence variation in pacC and in pacR or the changes in pacL-pacC distance. Mechanistically, our data are compatible with a model in which TerS interactions with part of the pacL sequence and a poly-A tract in pacR are sufficient to orient very accurately the TerL nuclease to a defined pacC position. They also demonstrate that the resulting precise cut at pacC is independent of the targeted DNA sequence.

Evidências de validade da Global Measure of Relationship Satisfaction (GMREL) em três amostras da população portuguesa / Evidence for the validity of the Global Measure of Relationship Satisfaction (GMREL) in three Portuguese samples

A satisfação relacional representa um construto de pertinência reconhecida para a avaliação rela-cional e em estreita conexão com diversas valências da saúde. A Global Measure of Relationship Satisfaction (GMREL) é formada por cinco itens e pretende avaliar a satisfação global com o companheiro/a no contexto de uma relação íntima. Foram estudadas as evidências de validade de construto e precisão dos escores desta escala em três amostras da população portuguesa, nomeadamente uma amostra clínica de pessoas com problemas relacionais (N = 56), uma amostra comunitária de pessoas sem estes problemas (N = 95) e uma amostra da comunidade de ambos os géneros (N= 669). A Escala de Avaliação da Satisfação em Áreas da Vida Conjugal foi empregue para investigar a validade convergente do instrumento, a Body Appearance Cognitive Distraction Scale para a validade divergente e, por fim, o estudo da Roc Curve com a amostra clínica e da comunidade para a validade discriminante. Os resultados indicam que a escala apresenta boas qualidades psicométricas para utilização em contexto clínico e de investigação.(AU)

Relationship satisfaction represents a well-known, pertinent construct for relationship assessment with strong connection to several health ranges. The Global Measure of Relationship Satisfaction (GMREL) is composed of five items and aims to evaluate the global satisfaction with the partner in an intimate relationship context. The purpose of this study was to observe the psychometric qualities of this scale in three Portuguese samples, namely a clinical sample of individuals with marital problems (N = 56), a normative sample of individuals without these problems (N = 95) and a community sample of both genders (N = 669). The Marital Life Areas Satisfaction Evaluation Scale was used to investigate the instrument's convergent validity; the Body Appearance Cognitive Distraction Scale for the divergent validity, and the Roc Curve study of clinical and community samples was used to assess the discriminant validity. The results show that the instrument presents good psychometric qualities for clinical and investigation purposes.(AU)

Evidências de validade da Global Measure of Relationship Satisfaction (GMREL) em três amostras da população portuguesa / Evidence for the validity of the Global Measure of Relationship Satisfaction (GMREL) in three Portuguese samples

A satisfação relacional representa um construto de pertinência reconhecida para a avaliação rela-cional e em estreita conexão com diversas valências da saúde. A Global Measure of Relationship Satisfaction (GMREL) é formada por cinco itens e pretende avaliar a satisfação global com o companheiro/a no contexto de uma relação íntima. Foram estudadas as evidências de validade de construto e precisão dos escores desta escala em três amostras da população portuguesa, nomeadamente uma amostra clínica de pessoas com problemas relacionais (N = 56), uma amostra comunitária de pessoas sem estes problemas (N = 95) e uma amostra da comunidade de ambos os géneros (N= 669). A Escala de Avaliação da Satisfação em Áreas da Vida Conjugal foi empregue para investigar a validade convergente do instrumento, a Body Appearance Cognitive Distraction Scale para a validade divergente e, por fim, o estudo da Roc Curve com a amostra clínica e da comunidade para a validade discriminante. Os resultados indicam que a escala apresenta boas qualidades psicométricas para utilização em contexto clínico e de investigação.

Relationship satisfaction represents a well-known, pertinent construct for relationship assessment with strong connection to several health ranges. The Global Measure of Relationship Satisfaction (GMREL) is composed of five items and aims to evaluate the global satisfaction with the partner in an intimate relationship context. The purpose of this study was to observe the psychometric qualities of this scale in three Portuguese samples, namely a clinical sample of individuals with marital problems (N = 56), a normative sample of individuals without these problems (N = 95) and a community sample of both genders (N = 669). The Marital Life Areas Satisfaction Evaluation Scale was used to investigate the instrument's convergent validity; the Body Appearance Cognitive Distraction Scale for the divergent validity, and the Roc Curve study of clinical and community samples was used to assess the discriminant validity. The results show that the instrument presents good psychometric qualities for clinical and investigation purposes.

Headful DNA packaging: bacteriophage SPP1 as a model system.

Tailed bacteriophages and herpesviruses package DNA inside the viral capsid by a powerful molecular motor. This packaging machine is composed of the portal protein, which provides a gate for DNA entry, the large terminase subunit whose ATPase activity fuels DNA translocation, and most frequently, a small terminase subunit that recognizes the viral packaging site. Here we review the mechanisms how the virulent Bacillus subtilis phage SPP1 packages DNA into a preformed procapsid. Encapsidation of the SPP1 DNA follows a processive unidirectional headful mechanism that starts with the recognition and cleavage of a unique genomic sequence (pac) by the viral terminase. The viral genome is then translocated through the central channel of the portal protein found at a single vertex of the procapsid. Packaging is terminated by an endonucleolytic cleavage of the concatemeric DNA substrate, following by disassembly of the packaging motor and closure of the portal system by the gatekeepers preventing leakage of the viral genome. Recent advances are providing new molecular insights on the mechanisms that ensure precise coordination of these critical steps required to accomplish the packaging encapsidation cycle.

The nuclease domain of the SPP1 packaging motor coordinates DNA cleavage and encapsidation.

The large terminase subunit is a central component of the genome packaging motor from tailed bacteriophages and herpes viruses. This two-domain enzyme has an N-terminal ATPase activity that fuels DNA translocation during packaging and a C-terminal nuclease activity required for initiation and termination of the packaging cycle. Here, we report that bacteriophage SPP1 large terminase (gp2) is a metal-dependent nuclease whose stability and activity are strongly and preferentially enhanced by Mn(2+) ions. Mutation of conserved residues that coordinate Mn(2+) ions in the nuclease catalytic site affect the metal-induced gp2 stabilization and impair both gp2-specific cleavage at the packaging initiation site pac and unspecific nuclease activity. Several of these mutations block also DNA encapsidation without affecting ATP hydrolysis or gp2 C-terminus binding to the procapsid portal vertex. The data are consistent with a mechanism in which the nuclease domain bound to the portal switches between nuclease activity and a coordinated action with the ATPase domain for DNA translocation. This switch of activities of the nuclease domain is critical to achieve the viral chromosome packaging cycle.