The highly improved genome of Ixodes scapularis with X and Y pseudochromosomes.

Ixodes scapularis, the black-legged tick, is the principal vector of the Lyme disease spirochete, Borrelia burgdorferi, and is responsible for most of the ∼470,000 estimated Lyme disease cases annually in the USA. Ixodes scapularis can transmit six additional pathogens of human health significance. Because of its medical importance, I. scapularis was the first tick genome to be sequenced and annotated. However, the first assembly, I. scapularis Wikel (IscaW), was highly fragmented because of the technical challenges posed by the long, repetitive genome sequences characteristic of arthropod genomes and the lack of long-read sequencing techniques. Although I. scapularis has emerged as a model for tick research because of the availability of new tools such as embryo injection and CRISPR-Cas9-mediated gene editing yet the lack of chromosome-scale scaffolds has slowed progress in tick biology and the development of tools for their control. Here we combine diverse technologies to produce the I. scapularis Gulia-Nuss (IscGN) genome assembly and gene set. We used DNA from eggs and male and female adult ticks and took advantage of Hi-C, PacBio HiFi sequencing, and Illumina short-read sequencing technologies to produce a chromosome-level assembly. In this work, we present the predicted pseudochromosomes consisting of 13 autosomes and the sex pseudochromosomes: X and Y, and a markedly improved genome annotation compared with the existing assemblies and annotations.

Cas9-mediated gene editing in the black-legged tick, Ixodes scapularis, by embryo injection and ReMOT Control.

Despite their capacity to acquire and pass on an array of debilitating pathogens, research on ticks has lagged behind other arthropod vectors, such as mosquitoes, largely because of challenges in applying available genetic and molecular tools. CRISPR-Cas9 is transforming non-model organism research; however, successful gene editing has not yet been reported in ticks. Technical challenges for injecting tick embryos to attempt gene editing have further slowed research progress. Currently, no embryo injection protocol exists for any chelicerate species, including ticks. Herein, we report a successful embryo injection protocol for the black-legged tick, Ixodes scapularis, and the use of this protocol for genome editing with CRISPR-Cas9. We also demonstrate that the ReMOT Control technique could be successfully used to generate genome mutations outside Insecta. Our results provide innovative tools to the tick research community that are essential for advancing our understanding of the molecular mechanisms governing pathogen transmission by tick vectors and the underlying biology of host-vector-pathogen interactions.

Men's Interest in Allying with a Previous Combatant for Future Group Combat.

Intra- and intergroup conflict are likely to have been recurrent features of human evolutionary history; however, little research has investigated the factors that affect men's combat alliance decisions. The current study investigated whether features of previous one-on-one combat with an opponent affect men's interest in allying with that opponent for future group combat. Fifty-eight undergraduate men recruited from a psychology department subject pool participated in a one-on-one laboratory fight simulation. We manipulated fight outcome (between-subjects), perceived fighter health asymmetry (within-subjects), and the presence of a witness (within-subjects) over six sets of five rounds of fighting. Following each set, we asked men how interested they would be in allying with their opponent for future group combat. We found that men were more interested in allying with their opponent for future group combat if their opponent won the fight or if a witness was present, but perceived fighter-health asymmetry did not affect men's decision to ally with their opponent. Exploratory analyses revealed a two-way interaction between fight outcome and the presence of a witness, such that winners without a witness present expressed less interest in allying with their opponent for future group combat. Our findings suggest that men attend to the benefits of allying with a man who has demonstrated relatively superior fighting ability. Alliance with a previous opponent for group combat may vary with the relationship value of the opponent and the utility of demonstrating cooperativeness to third-party observers. These findings inform our understanding of coalition formation.

Do Men Produce Higher Quality Ejaculates When Primed With Thoughts of Partner Infidelity?

Sperm competition theory can be used to generate the hypothesis that men alter the quality of their ejaculates as a function of sperm competition risk. Using a repeated measures experimental design, we investigated whether men produce a higher quality ejaculate when primed with cues to sperm competition (i.e., imagined partner infidelity) relative to a control prime. Men ( n = 45) submitted two masturbatory ejaculates-one ejaculate sample for each condition (i.e., sperm competition and control conditions). Ejaculates were assessed on 17 clinical parameters. The results did not support the hypothesis: Men did not produce higher quality ejaculates in the sperm competition condition relative to the control condition. Despite the null results of the current research, there is evidence for psychological and physiological adaptations to sperm competition in humans. We discuss methodological limitations that may have produced the null results and present methodological suggestions for research on human sperm competition.

Endorsement of Social and Personal Values Predicts the Desirability of Men and Women as Long-Term Partners.

A prospective romantic partner's desirability as a long-term partner may be affected by the values that he or she endorses. However, few studies have examined the effects of "values" on a person's desirability as a long-term partner. We hypothesized that individuals who endorse social values (vs. personal values) will be perceived as more desirable long-term partners (Hypothesis 1) and that the endorsement of social values will be especially desirable in a male (vs. female) long-term partner (Hypothesis 2). The current study employed a 2 (sex of prospective partner: male vs. female) × 2 (values of prospective partner: personal vs. social) × 2 (physical attractiveness of prospective partner: unattractive vs. highly attractive) mixed-model design. Participants were 339 undergraduates (174 men, 165 women), with ages varying between 18 and 33 years ( M = 19.9, SD = 3.6), and mostly in a romantic relationship (53.7%). Participants reported interest in a long-term relationship with prospective partners depicted in four scenarios (within subjects), each varying along the dimensions of values (personal vs. social) and physical attractiveness (unattractive vs. highly attractive). Individuals endorsing personal values (vs. social values) and men (vs. women) endorsing personal values were rated as less desirable as long-term partners. The current research adds to the partner preferences literature by demonstrating that an individual's ascribed values influence others' perceptions of desirability as a long-term partner and that these effects are consistently sex differentiated, as predicted by an evolutionary perspective on romantic partner preferences.

Post-Fight Respect Signals Valuations of Opponent's Fighting Performance.

The current research explores whether humans process inputs about combat (e.g., assessments of formidability) that produce outputs of post-fight respect (e.g., shaking an opponent's hand when the fight ends). Using an online questionnaire (Study 1, n = 132), an in-person questionnaire (Study 2, n = 131), and an in-lab fight simulation (Study 3, n = 58), we investigated whether participants were more likely to receive (Studies 1 and 3) and display (Studies 2 and 3) post-fight respect as a function of the fight outcome (Hypothesis 1), use of fight tactics (Hypothesis 2), fighter asymmetries (Hypothesis 3), fighter ranking (Hypothesis 4), and the presence of witnesses (Hypothesis 5). The results support Hypotheses 1 to 4 concerning expectations of receiving post-fight respect, and support only Hypotheses 2 and 3 concerning displays of post-fight respect. We suggest that post-fight respect signals positive valuations of fighting performance that may function to maintain valuable relationships within the social group.

Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication.

HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection.

Does human ejaculate quality relate to phenotypic traits?

A given man's phenotype embodies cues of his ancestral ability to effectively defend himself and his kin from harm, to survive adverse conditions, and to acquire status and mating opportunities. In this review, we explore the hypothesis that a man's phenotype also embodies cues to fertility or the probability that an ejaculate will fertilize ova. Female mate choice depends on the ability to discern the quality of a male reproductive partner through his phenotype, and male fertility may be among the traits that females have evolved to detect. A female who selects as mates males that deliver higher quality ejaculates will, on average, be more fecund than her competitors. Data on several non-human species demonstrate correlations between ejaculate quality and secondary sexual characteristics that inform female mate choice, suggesting that females may select mates in part on the basis of fertility. While the non-human literature on this topic has advanced, the human literature remains limited in scope and there is no clear consensus on appropriate methodologies or theoretical positions. We provide a comprehensive review and meta-analysis of this literature, and conclude by proposing solutions to the many issues that impede progress in the field. In the process, we hope to encourage interest and insight from investigators in other areas of human mating and reproductive biology. Am. J. Hum. Biol. 28:318-329, 2016. © 2015 Wiley Periodicals, Inc.

How Sexually Dimorphic Are Human Mate Preferences?

Previous studies on sex-differentiated mate preferences have focused on univariate analyses. However, because mate selection is inherently multidimensional, a multivariate analysis more appropriately measures sex differences in mate preferences. We used the Mahalanobis distance (D) and logistic regression to investigate sex differences in mate preferences with data secured from participants residing in 37 cultures (n = 10,153). Sex differences are large in multivariate terms, yielding an overall D = 2.41, corresponding to overlap between the sexes of just 22.8%. Moreover, knowledge of mate preferences alone affords correct classification of sex with 92.2% accuracy. Finally, pattern-wise sex differences are negatively correlated with gender equality across cultures but are nonetheless cross-culturally robust. Discussion focuses on implications in evaluating the importance and magnitude of sex differences in mate preferences.

Physical strength and dance attractiveness: Further evidence for an association in men, but not in women.

OBJECTIVES: Physical strength provides information about male quality and can be assessed from facial and body morphology. Research on perception of dance movements indicates that body movement also provides information about male physical strength. These relationships have not been investigated for women. METHODS: We investigated relationships of handgrip strength (HGS) and dance attractiveness perception in 75 men and 84 women. RESULTS: We identified positive relationships between HGS and opposite-sex assessments of dance attractiveness for men but not women. CONCLUSIONS: The replication of previous research investigating relationships between dance attractiveness and physical strength in men corroborates the hypothesis that dance movements provide information about male quality. We argue that these relationships are interpretable in contexts of inter- and intra-sexual selection.

Integrating body movement into attractiveness research.

People judge attractiveness and make trait inferences from the physical appearance of others, and research reveals high agreement among observers making such judgments. Evolutionary psychologists have argued that interest in physical appearance and beauty reflects adaptations that motivate the search for desirable qualities in a potential partner. Although men more than women value the physical appearance of a partner, appearance universally affects social perception in both sexes. Most studies of attractiveness perceptions have focused on third party assessments of static representations of the face and body. Corroborating evidence suggests that body movement, such as dance, also conveys information about mate quality. Here we review evidence that dynamic cues (e.g., gait, dance) also influence perceptions of mate quality, including personality traits, strength, and overall attractiveness. We recommend that attractiveness research considers the informational value of body movement in addition to static cues, to present an integrated perspective on human social perception.

Sperm Competition Risk and Sexual Coercion Predict Copulatory Duration in Humans.

A man whose romantic partner is sexually unfaithful is at risk of sperm competition and cuckoldry-unwitting investment in offspring to whom he is genetically unrelated. Men, therefore, may have evolved mechanisms to solve the adaptive problems of sperm competition and cuckoldry. The current research investigates another potential anti-cuckoldry tactic: reducing in-pair copulation (IPC) duration, thereby more quickly placing his sperm into competition. We hypothesize that IPC duration will be negatively correlated with female infidelity (Hypothesis 1). We further hypothesize that IPC duration will be negatively correlated with sexual coercion (Hypothesis 2). Results of Study 1 (men's reports, n = 410) indicate that both men's perceptions of female infidelity and men's sexual coercion predict shorter IPC duration. Results of Study 2 (women's reports, n = 455) did not provide statistical support for the study hypotheses. The current research provides an initial investigation of men's adjustment of copulatory duration and suggests that men reduce IPC duration and ejaculate more quickly at the couple's most recent copulation, in response to greater risk of sperm competition and in the context of sexual coercion.

Men's Benefit-Provisioning Mate Retention Behavior Mediates the Relationship Between Their Agreeableness and Their Oral Sex Behaviors.

Men perform oral sex on their romantic partner as part of a broader benefit-provisioning mate retention strategy and men higher in Agreeableness are especially likely to provision their partner with benefits. The current research explored whether men's benefit-provisioning mate retention behavior mediated the relationship between their Agreeableness and their oral sex behaviors in their long-term romantic relationship. Men (n = 346) in a committed, sexual, heterosexual relationship completed the Mate Retention Inventory-a 104-item instrument that assesses the frequency with which they performed various mate retention behaviors during the past month, a 40-item personality inventory, and reported on a questionnaire their interest in and the time they spent performing oral sex on their romantic partner during their most recent sexual encounter with her. The results indicated that men higher in Agreeableness reported greater interest in and spent more time performing oral sex on their partner, and that their benefit-provisioning mate retention behaviors partially mediated these relationships. The current research is the first to investigate the relationship between personality dimensions and oral sex behaviors and adds to a growing body of research documenting that mate retention strategies influence sexual behavior.

The implicit rules of combat.

Conspecific violence has been pervasive throughout evolutionary history. The current research tested the hypotheses that individuals implicitly categorize combative contexts (i.e., play fighting, status contests, warfare, and anti-exploitative violence) and use the associated contextual information to guide expectations of combative tactics. Using U.S. and non-U.S. samples, Study 1 demonstrated consistent classification of combative contexts from scenarios for which little information was given and predictable shifts in the acceptability of combative tactics across contexts. Whereas severe tactics (e.g., eye-gouging) were acceptable in warfare and anti-exploitative violence, they were unacceptable in status contests and play fights. These results suggest the existence of implicit rules governing the contexts of combat. In Study 2, we explored the reputational consequences of violating these implicit rules. Results suggest that rule violators (e.g., those who use severe tactics in a status contest) are given less respect. These are the first studies to implicate specialized mechanisms for aggression that use contextual cues of violence to guide expectations and behavior.

Partner attractiveness moderates the relationship between number of sexual rivals and in-pair copulation frequency in humans (Homo sapiens).

Nonhuman males attend to the number of potential sexual rivals in the local environment to assess sperm competition risk. Males of these species sometimes perform more frequent in-pair copulations to increase the likelihood of success in sperm competition. Here, we extend this research to humans, Homo sapiens. We secured self-report data from 393 men in a committed, sexual, heterosexual relationship. The results indicate that men whose in-pair partner has more male coworkers and friends (i.e., potential sexual rivals) also perform more frequent in-pair copulations, but only among men who perceive their partner to be particularly attractive relative to assessments of partners by other men in the sample. This research is the first to empirically investigate the number of potential male rivals in the local environment as a cue to sperm competition risk in humans. Discussion addresses limitations of the current research and highlights directions for future research.

Oral sex, semen displacement, and sexual arousal: testing the ejaculate adjustment hypothesis.

Male Indian Flying Foxes (Pteropus giganteus) that spend more time performing oral sex on a female also spend more time copulating with her. In humans, men who spend more time copulating with their regular partner also perform more "semen-displacing" copulatory behaviors (e.g., deeper, more vigorous penile thrusting). We investigated whether men who spend more time performing oral sex on their regular partner also spend more time copulating with her and perform more semen-displacing copulatory behaviors. We proposed and tested the ejaculate adjustment hypothesis for men's copulatory behaviors: Men adjust their copulatory behaviors to increase their sexual arousal and consequent ejaculate quality, thereby increasing their chances of success in sperm competition. Two hundred and thirty-three men in a committed, heterosexual relationship responded to questions about their copulatory behavior and sexual arousal during their most recent sexual encounter with their long-term partner. The results indicated that men who spend more time performing oral sex on their partner also spend more time copulating with her, perform more semen-displacing copulatory behaviors, and report greater sexual arousal. We discuss limitations to the current research and highlight the heuristic value of sperm competition theory for understanding human sexual behaviors.

The relationship between objective sperm competition risk and men's copulatory interest is moderated by partner's time spent with other men.

Men who spend a greater proportion of time apart from their female partner since the couple's last copulation are at greater "objective" sperm competition risk. We propose a novel cue to sperm competition risk: the time she spends with her male friends. Four hundred and twenty men in a committed, heterosexual, sexual relationship completed a questionnaire. The results indicate that men at greater objective sperm competition risk report less time desired until the couple's next copulation, greater interest in copulating with their partner, and greater anger, frustration, and upset in response to their partner's sexual rejection, but only among men whose partner spends more time with her male friends. These results remain after controlling statistically for the participant's age and their partner's age. We discuss limitations of the current research, and discuss how research in human sperm competition can inform social issues, including men's partner-directed sexual coercion.

Is cunnilingus-assisted orgasm a male sperm-retention strategy?

We secured data from 243 men in committed, sexual, heterosexual relationships to test the sperm retention hypothesis of oral sex. We predicted that, among men who perform cunnilingus on their partner, those at greater risk of sperm competition are more likely to perform cunnilingus until their partner achieves orgasm (Prediction 1), and that, among men who ejaculate during penile-vaginal intercourse and whose partner experiences a cunnilingus-assisted orgasm, ejaculation will occur during the brief period in which female orgasm might function to retain sperm (Prediction 2). The results support Prediction 1 but not Prediction 2. We discuss limitations of the current research and discuss how these results may be more consistent with alternative hypotheses regarding female orgasm and oral sex.

Rifampin inhibits Toll-like receptor 4 signaling by targeting myeloid differentiation protein 2 and attenuates neuropathic pain.

Rifampin has been used for the treatment of bacterial infections for many years. Clinically, rifampin has been found to possess immunomodulatory effects. However, the molecular target responsible for the immunosuppressive effects of rifampin is not known. Herein, we show that rifampin binds to myeloid differentiation protein 2 (MD-2), the key coreceptor for innate immune TLR4. Rifampin blocked TLR4 signaling induced by LPS, including NF-κB activation and the overproduction of proinflammatory mediators nitric oxide, interleukin 1ß, and tumor necrosis factor α in mouse microglia BV-2 cells and macrophage RAW 264.7 cells. Rifampin's inhibition of TLR4 signaling was also observed in immunocompetent rat primary macrophage, microglia, and astrocytes. Further, we show that rifampin (75 or 100 mg/kg b.i.d. for 3 d, intraperitoneal) suppressed allodynia induced by chronic constriction injury of the sciatic nerve and suppressed nerve injury-induced activation of microglia. Our findings indicate that MD-2 is a important target of rifampin in its inhibition of innate immune function and contributes to its clinically observed immune-suppressive effect. The results also suggest that rifampin may be repositioned as an agent for the treatment of neuropathic pain.

Development of ß-amino alcohol derivatives that inhibit Toll-like receptor 4 mediated inflammatory response as potential antiseptics.

Toll-like receptor 4 (TLR4) induced proinflammatory signaling has been directly implicated in severe sepsis and represents an attractive therapeutic target. Herein, we report our investigations into the structure-activity relationship and preliminary drug metabolism/pharmacokinetics study of ß-amino alcohol derivatives that inhibit the TLR4 signaling pathway. Lead compounds were identified from in vitro cellular examination with micromolar potency for their inhibitory effects on TLR4 signaling and subsequently assessed for their ability to suppress the TLR4-induced inflammatory response in an ex vivo whole blood model. In addition, the toxicology, specificity, solubility, brain-blood barrier permeability, and drug metabolism of several compounds were evaluated. Although further optimizations are needed, our findings lay the groundwork for the future drug development of this class of small molecule agents for the treatment of severe sepsis.