Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge.

Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether such activities are sufficient for protection is unclear. We previously identified an antibody to the variable 2 (V2) apex of the HIV-1 Env trimer (PGT145) that potently directs the lysis of SIV-infected cells by NK cells but poorly neutralizes SIV infectivity. To determine if ADCC is sufficient for protection, separate groups of six rhesus macaques were treated with PGT145 or a control antibody (DEN3) by intravenous infusion followed five days later by intrarectal challenge with SIVmac239. Despite high concentrations of PGT145 and potent ADCC activity in plasma on the day of challenge, all animals became infected and viral loads did not differ between the PGT145- and DEN3-treated animals. To determine if PGT145 can protect against a neutralization-sensitive virus, two additional groups of six macaques were treated with PGT145 and DEN3 and challenged with an SIVmac239 variant with a single amino acid change in Env (K180S) that increases PGT145 binding and renders the virus susceptible to neutralization by this antibody. Although there was no difference in virus acquisition, peak and chronic phase viral loads were significantly lower and time to peak viremia was significantly delayed in the PGT145-treated animals compared to the DEN3-treated control animals. Env changes were also selected in the PGT145-treated animals that confer resistance to both neutralization and ADCC. These results show that ADCC is not sufficient for protection by this V2-specific antibody. However, protection may be achieved by increasing the affinity of antibody binding to Env above the threshold required for neutralization.

RegulonDB v12.0: a comprehensive resource of transcriptional regulation in E. coli K-12.

RegulonDB is a database that contains the most comprehensive corpus of knowledge of the regulation of transcription initiation of Escherichia coli K-12, including data from both classical molecular biology and high-throughput methodologies. Here, we describe biological advances since our last NAR paper of 2019. We explain the changes to satisfy FAIR requirements. We also present a full reconstruction of the RegulonDB computational infrastructure, which has significantly improved data storage, retrieval and accessibility and thus supports a more intuitive and user-friendly experience. The integration of graphical tools provides clear visual representations of genetic regulation data, facilitating data interpretation and knowledge integration. RegulonDB version 12.0 can be accessed at https://regulondb.ccg.unam.mx.

Cost-effectiveness of COVID rapid diagnostic tests for patients with severe/critical illness in low- and middle-income countries: A modeling study.

BACKGROUND: Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice. METHODS AND FINDINGS: We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza. CONCLUSIONS: COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs.

Unravelling heterogeneous malaria transmission dynamics in the Peruvian Amazon: insights from a cross-sectional survey.

BACKGROUND: Malaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health's "Zero Malaria Plan" targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative. METHODS: A cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors. RESULTS: The survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species. CONCLUSIONS: The study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon.

Functional characterization of biodegradable films obtained from whole Paecilomyces variotii biomass.

The indiscriminate use of petroleum-based polymers and plastics for single-use food packaging has led to serious environmental problems due the non-biodegradable characteristics. Thus, much attention has been focused on the research of new biobased and biodegradable materials. Yeast and fungal biomass are low-cost and abundant sources of biopolymers with highly promising properties for the development of biodegradable materials. This study aimed to select a preparation method to develop new biodegradable films using the whole biomass of Paecilomyces variotii subjected to successive physical treatments including ultrasonic homogenization (US) and heat treatment. Sterilization process had an important impact on the final filmogenic dispersion and mechanical properties of the films. Longer US treatments produced a reduction in the particle size and the application of an intermediate UT treatment contributed favorably to the breaking of agglomerates allowing the second US treatment to be more effective, achieving an ordered network with a more uniform distribution. Samples that were not filtrated after the sterilization process presented mechanical properties similar to plasticized materials. On the other hand, the filtration process after sterilization eliminated soluble and hydratable compounds, which produced a reduction in the hydration of the films.

Spin-Crossing in the (Z)-Selective Alkyne Semihydrogenation Mechanism Catalyzed by Mo3S4 Clusters: A Density Functional Theory Exploration.

Semihydrogenation of internal alkynes catalyzed by the air-stable imidazolyl amino [Mo3S4Cl3(ImNH2)3]+ cluster selectively affords the (Z)-alkene under soft conditions in excellent yields. Experimental results suggest a sulfur-based mechanism with the formation of a dithiolene adduct through interaction of the alkyne with the bridging sulfur atoms. However, computational studies indicate that this mechanism is unable to explain the experimental outcome: mild reaction conditions, excellent selectivity toward the (Z)-isomer, and complete deuteration of the vinylic positions in the presence of CD3OD and CH3OD. An alternative mechanism that explains the experimental results is proposed. The reaction begins with the hydrogenation of two of the Mo3(µ3-S)(µ-S)3 bridging sulfurs to yield a bis(hydrosulfide) intermediate that performs two sequential hydrogen atom transfers (HAT) from the S-H groups to the alkyne. The first HAT occurs with a spin change from singlet to triplet. After the second HAT, the singlet state is recovered. Although the dithiolene adduct is more stable than the hydrosulfide species, the large energy required for the subsequent H2 addition makes the system evolve via the second alternative pathway to selectively render the (Z)-alkene with a lower overall activation barrier.

Evaluating the interactive impact of acculturative stress and anxiety sensitivity on behavioral health outcomes among Latinx during a period of high COVID-19 impact.

As a multi-systemic disease, COVID-19 infection engendered a rise in co-occurring mental and physical health symptoms, particularly affecting the Latinx population. The current work sought to evaluate the main and interactive influence of acculturative stress and anxiety sensitivity in terms of mental and physical health symptoms among 181 Latinx persons (30.4% female, Mage = 34.1 years, SD = 8.20). Data were collected during a period of high COVID-19 impact (2020-2021) and analyses included five separate, two-step hierarchical regressions that were conducted for each of the criterion variables: (1) fear of coronavirus; (2) somatic symptoms; (3) fatigue severity; (4) anxiety symptoms; and (5) depression symptoms. For all analyses, step 1 covariates included years living in the U.S. COVID-19 impact, gender identity, education, and work life distress and home life distress. Results revealed an interactive effect of anxiety sensitivity and acculturative stress on COVID-19 fear, unique main effects for both anxiety sensitivity and acculturative stress on COVID-19 related fear and somatic symptoms, and main effects for anxiety sensitivity alone in relation to fatigue severity, anxiety, and depression. Overall, this study represents an initial investigation of the associations between acculturative stress, anxiety sensitivity, and a range of salient COVID-19 related outcomes among Latinx persons.

Posttraumatic Stress and Alcohol Use Among Hispanic/Latinx University Students: A Moderated Indirect Effect Model of Coping-Related Drinking and Anxiety Sensitivity.

OBJECTIVE: Posttraumatic stress symptoms (PTSS) and anxiety sensitivity (AS) are associated with increased alcohol use and coping-motivated drinking among university students. This study among trauma-exposed Hispanic/Latinx university students sought to examine the indirect effect of PTSS on alcohol use severity through coping-motivated drinking and test the moderating role of AS and AS subfacets. METHODS: University students who identified as Hispanic/Latinx (N = 830) were recruited from a large, urban, southern university and completed online, self-report questionnaires. RESULTS: A significant interactive effect of PTSS and AS on coping-motivated drinking emerged. PTSS exerted a significant indirect effect on alcohol use severity, through coping-motivated drinking. Simple slope analyses revealed that PTSS was associated with coping-motivated drinking across all levels of AS. Post hoc results revealed unique biological sex differences in probable diagnosis odds ratios. CONCLUSIONS: These findings indicate that PTSS and AS are associated with coping-motivated drinking and alcohol use severity in trauma-exposed, Hispanic/Latinx university students.

Pixel-wise rational model for a structured light system.

This Letter presents a novel structured light system model that effectively considers local lens distortion by pixel-wise rational functions. We leverage the stereo method for initial calibration and then estimate the rational model for each pixel. Our proposed model can achieve high measurement accuracy within and outside the calibration volume, demonstrating its robustness and accuracy.

First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.

Zinc-finger nuclease (ZFN)-based in vivo genome editing is a novel treatment that can potentially provide lifelong protein replacement with single intravenous administration. Three first-in-human open-label ascending single-dose phase 1/2 studies were performed in parallel (starting November 2017) primarily to assess safety and tolerability of ZFN in vivo editing therapy in mucopolysaccharidosis I (MPS I) (n = 3), MPS II (n = 9), and hemophilia B (n = 1). Treatment was well tolerated with no serious treatment-related adverse events. At the 1e13 vg/kg dose, evidence of genome editing was detected through albumin-transgene fusion transcripts in liver for MPS II (n = 2) and MPS I (n = 1) subjects. The MPS I subject also had a transient increase in leukocyte iduronidase activity to the lower normal range. At the 5e13 vg/kg dose, one MPS II subject had a transient increase in plasma iduronate-2-sulfatase approaching normal levels and one MPS I subject approached mid-normal levels of leukocyte iduronidase activity with no evidence of genome editing. The hemophilia B subject was not able to decrease use of factor IX concentrate; genome editing could not be assessed. Overall, ZFN in vivo editing therapy had a favorable safety profile with evidence of targeted genome editing in liver, but no long-term enzyme expression in blood.

The Role of Anxiety Sensitivity in the Association Between Childhood Maltreatment and Sleep Disturbance Among Adults in Psychiatric Inpatient Treatment.

ABSTRACT: The present investigation examined associations of childhood maltreatment, anxiety sensitivity (AS), and sleep disturbance among a diverse sample of adults in psychiatric inpatient treatment. We hypothesized that childhood maltreatment would be indirectly associated with greater sleep disturbance through elevated AS. Exploratory analyses examined the indirect effect models with three AS subscales ( i.e. , physical, cognitive, and social concerns) as parallel mediators. A sample of adults in acute-care psychiatric inpatient treatment ( N = 88; 62.5% male; Mage = 33.32 years, SD = 11.07; 45.5% White) completed a series of self-report measures. After accounting for theoretically relevant covariates, childhood maltreatment was indirectly associated with sleep disturbance through AS. Parallel mediation analyses revealed that no individual subscale of AS significantly accounted for this association. These findings suggest that heightened levels of AS may explain the association between childhood maltreatment and sleep disturbance among adults in psychiatric inpatient treatment. Interventions targeting AS can be brief and efficacious and have the potential to improve clinical outcomes among psychiatric populations.

"We usually see a lot of delay in terms of coming for or seeking care": an expert consultation on COVID testing and care pathways in seven low- and middle-income countries.

BACKGROUND: Rapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023. METHODS: We organized a qualitative consultation with ten experts from seven LMICs (India, Indonesia, Malawi, Nigeria, Peru, South Africa, and Zimbabwe) identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses. RESULTS: Participants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis (alongside PCR for Asian/Latin American participants), while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at 'face value' by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab. CONCLUSIONS: Testing does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.

Posttraumatic stress among trauma-exposed Hispanic/Latinx adults: relations to mental health.

Latinx persons are exposed to higher rates of traumatic events and conditional risks for developing posttraumatic stress disorder (PTSD) symptoms and comorbid mental health symptoms compared to other minority groups. The study evaluated PTSD symptom severity for global and specific cluster severity relating to co-occurring anxiety, social anxiety, depression, and suicidal ideation among 326 Latinx adults who endorsed trauma exposure. Results indicated that global PTSD symptom severity was significantly related to greater social anxiety, anxious arousal, depression, and suicidal ideation symptoms. PTSD arousal and reactivity symptom cluster had the strongest relation to anxious arousal, social anxiety, and depression, whereas negative alterations in cognitions and mood symptoms had the strongest association with social anxiety, depression, and suicidal ideation. The findings suggest that global PTSD symptom severity, alongside arousal and reactivity and negative alterations in cognitions and mood, are related to a range of concurrent negative mental health symptoms among trauma exposed Latinx young adults.

Evaluating resilience in terms of COVID-19 related behavioral health among Latinx adults during the coronavirus pandemic.

The mental and behavioral health burden resulting from COVID-19 has disproportionately affected the Latinx population. Yet, no work has investigated the influence of resilience as a protective factor against COVID-19 related consequences. The aim of the current study was to evaluate resilience in relation to COVID-19 related fear, anxiety symptoms, COVID-19 anxiety-related sleep disturbances, and depression among Latinx persons (178 Latinx persons [31.5% female, Mage = 34.1 years, SD = 8.2]). It was hypothesized that greater levels of resilience would be associated with lower levels of all COVID-19 related behavioral health outcomes above and beyond the variance accounted for by years living in the United States (U.S.), degree of COVID-19 exposure, sex, age, education, and COVID-19 related work and financial troubles and home-life distress. Results indicated that greater levels of resilience were associated with lower levels of COVID-19 related fear (ΔR2 = .06, p < .001), anxiety symptoms (ΔR2 = .03, p = .005), COVID-19 anxiety-related sleep disturbances (ΔR2 = .06, p < .001), and depression (ΔR2 = .04, p = .001). Overall, the present study is the first to document the potential importance of resilience in relation to common and clinically significant COVID-19 behavioral health problems among Latinx persons.

Effortful Control Moderates the Relation Between Negative Emotionality and Child Anxiety and Depressive Symptom Severity in Children with Anxiety Disorders.

The present study investigated the interactive effect of reactive (negative emotionality) and regulatory (effortful control) aspects of temperament in the prediction of child anxiety and depressive symptoms. Clinically anxious children and their mothers completed a battery of questionnaires that included self- and mother-ratings of child effortful control, negative emotionality, anxiety, and depressive symptoms. Multiple regression analyses were conducted to examine the moderating effect of effortful control on the relation between negative emotionality and child anxiety and depressive symptom severity. The interaction between negative emotionality and effortful control was statistically significant and simple slopes revealed that as effortful control increased, the relationship between negative emotionality and anxiety and depressive symptoms weakened. Among anxious children high in negative emotionality, greater effortful control was related to less severe anxiety and depressive symptoms. Future work should evaluate whether targeting effortful control leads to reductions in internalizing symptoms among clinically anxious youth.

Childhood exposure to parental threatening behaviors and anxiety in emerging adulthood: Indirect effects of perceived stress.

BACKGROUND: Although childhood exposure to parental threatening behaviors is associated with elevated anxiety in emerging adulthood, the underlying mechanisms remain unexplored. Perceived stress-a subjective experience comprised of feelings of helplessness (being unable to cope or exert control) and poor self-efficacy (confidence in one's ability to manage stressors)-is one candidate mechanism. The present investigation examined the underlying role of perceived stress in the association between childhood exposure to parental threatening behaviors and anxiety symptom severity in a sample of emerging adults. METHODS: Participants (N = 855; Mage = 18.75 years, SD = 1.05, range 18-24; 70.8% female) were recruited from a large state university and administered a battery of self-report questionnaires assessing constructs of interest. RESULTS: Structural equation modeling (SEM) analyses indicated that only greater childhood exposure to maternal threatening behaviors was directly associated with greater feelings of helplessness and lower self-efficacy. Furthermore, only childhood exposure to maternal threatening behaviors was indirectly associated with anxiety severity through greater feelings of helplessness and lower self-efficacy. In contrast, childhood exposure to paternal threatening behaviors was neither directly nor indirectly associated with anxiety severity. LIMITATIONS: Limitations include a cross-sectional design, use of self-report measures, and a nonclinical sample. Replicating these findings in a clinical sample and testing the hypothesized model in a longitudinal design is necessary. CONCLUSIONS: Findings underscore the need for intervention efforts that screen for and target perceived stress in emerging adults exposed to negative maternal parenting behaviors.

Anxiety symptoms and anxiety sensitivity in relation to cigarette dependence, perceived barriers for smoking cessation and quit problems among adult Latinx smokers.

Cigarette smoking is associated with adverse physical and mental health among Latinx adults in the United States. The present investigation sought to explore the main and interactive effects of anxiety symptoms and anxiety sensitivity in relation to cigarette dependence, perceived barriers for smoking cessation, and severity of problems experienced when quitting among adult Latinx smokers. Participants included 338 Latinx adult daily cigarette smokers (Mage = 35.53 years; SD = 8.65; age range 18-61; 37.3% female). Results indicated that anxiety symptoms were associated with greater cigarette dependence, severity of problems when quitting, and perceived barriers for smoking cessation (effect size range: 2%-3% of variance), whereas anxiety sensitivity was related to severity of problems when quitting and perceived barriers for smoking cessation (effect size range: 2%-3% of variance). There was also a statistically significant interaction between anxiety sensitivity and anxiety symptoms for cigarette dependence; anxiety was related to cigarette dependence for Latinx smokers with higher levels of anxiety sensitivity, but not for those with lower levels of anxiety sensitivity. Overall, the present findings indicate that anxiety symptoms and anxiety sensitivity are relevant factors for better understanding cigarette dependence, problems experienced when trying to quit, and perceptions of barriers to quitting among adult Latinx smokers.

The dynamic range of voltage-dependent gap junction signaling is maintained by Ih-induced membrane potential depolarization.

Like their chemical counterparts, electrical synapses show complex dynamics such as rectification and voltage dependence that interact with other electrical processes in neurons. The consequences arising from these interactions for the electrical behavior of the synapse, and the dynamics they create, remain largely unexplored. Using a voltage-dependent electrical synapse between a descending modulatory projection neuron (MCN1) and a motor neuron (LG) in the crustacean stomatogastric ganglion, we find that the influence of the hyperpolarization-activated inward current (Ih) is critical to the function of the electrical synapse. When we blocked Ih with CsCl, the apparent voltage dependence of the electrical synapse shifted by 18.7 mV to more hyperpolarized voltages, placing the dynamic range of the electrical synapse outside of the range of voltages used by the LG motor neuron (-60.2 mV to -44.9 mV). With dual electrode current- and voltage-clamp recordings, we demonstrate that this voltage shift is not due to a change in the properties of the gap junction itself, but is a result of a sustained effect of Ih on the presynaptic MCN1 axon terminal membrane potential. Ih-induced depolarization of the axon terminal membrane potential increased the electrical postsynaptic potentials and currents. With Ih present, the axon terminal resting membrane potential is depolarized, shifting the dynamic range of the electrical synapse toward the functional range of the motor neuron. We thus demonstrate that the function of an electrical synapse is critically influenced by a voltage-dependent ionic current (Ih).NEW & NOTEWORTHY Electrical synapses and voltage-gated ionic currents are often studied independently from one another, despite mounting evidence that their interactions can alter synaptic behavior. We show that the hyperpolarization-activated inward ionic current shifts the voltage dependence of electrical synaptic transmission through its depolarizing effect on the membrane potential, enabling it to lie within the functional membrane potential range of a motor neuron. Thus, the electrical synapse's function critically depends on the voltage-gated ionic current.

Neuronal membrane glycoprotein (nmgp-1) gene deficiency affects chemosensation-related behaviors, dauer exit and egg-laying in Caenorhabditis elegans.

The nervous system monitors the environment to maintain homeostasis, which can be affected by stressful conditions. Using mammalian models of chronic stress, we previously observed altered brain levels of GPM6A, a protein involved in neuronal morphology. However, GPM6A's role in systemic stress responses remains unresolved. The nematode Caenorhabditis elegans expresses a GPM6A ortholog, the neuronal membrane glycoprotein 1 (NMGP-1). Because of the shared features between nematode and mammalian nervous systems and the vast genetic tools available in C. elegans, we used the worm to elucidate the role of GPM6A in the stress response. We first identified nmgp-1 expression in different amphid and phasmid neurons. To understand the nmgp-1 role, we characterized the behavior of nmgp-1(RNAi) animals and two nmgp-1 mutant alleles. Compared to control animals, mutant and RNAi-treated worms exhibited increased recovery time from the stress-resistant dauer stage, altered SDS chemosensation and reduced egg-laying rate resulting in egg retention (bag-of-worms phenotype). Silencing of nmgp-1 expression induced morphological abnormalities in the ASJ sensory neurons, partly responsible for dauer exit. These results indicate that nmgp-1 is required for neuronal morphology and for behaviors associated with chemosensation. Finally, we propose nmgp-1 mutants as a tool to screen drugs for human nervous system pathologies.

Males That Silence Their Father's Genes: Genomic Imprinting of a Complete Haploid Genome.

Genetic conflict is considered a key driver in the evolution of reproductive systems with non-Mendelian inheritance, where parents do not contribute equally to the genetic makeup of their offspring. One of the most extraordinary examples of non-Mendelian inheritance is paternal genome elimination (PGE), a form of haplodiploidy which has evolved repeatedly across arthropods. Under PGE, males are diploid but only transmit maternally inherited chromosomes, while the paternally inherited homologues are excluded from sperm. This asymmetric inheritance is thought to have evolved through an evolutionary arms race between the paternal and maternal genomes over transmission to future generations. In several PGE clades, such as the mealybugs (Hemiptera: Pseudococcidae), paternal chromosomes are not only eliminated from sperm, but also heterochromatinized early in development and thought to remain inactive, which could result from genetic conflict between parental genomes. Here, we present a parent-of-origin allele-specific transcriptome analysis in male mealybugs showing that expression is globally biased toward the maternal genome. However, up to 70% of somatically expressed genes are to some degree paternally expressed, while paternal genome expression is much more restricted in the male reproductive tract, with only 20% of genes showing paternal contribution. We also show that parent-of-origin-specific gene expression patterns are remarkably similar across genotypes, and that genes with completely biparental expression show elevated rates of molecular evolution. Our results provide the clearest example yet of genome-wide genomic imprinting in insects and enhance our understanding of PGE, which will aid future empirical tests of evolutionary theory regarding the origin of this unusual reproductive strategy.