Role of PFKFB3-driven glycolysis in vessel sprouting.

Vessel sprouting by migrating tip and proliferating stalk endothelial cells (ECs) is controlled by genetic signals (such as Notch), but it is unknown whether metabolism also regulates this process. Here, we show that ECs relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation. Mechanistically, PFKFB3 not only regulated EC proliferation but also controlled the formation of filopodia/lamellipodia and directional migration, in part by compartmentalizing with F-actin in motile protrusions. Mosaic in vitro and in vivo sprouting assays further revealed that PFKFB3 overexpression overruled the pro-stalk activity of Notch, whereas PFKFB3 deficiency impaired tip cell formation upon Notch blockade, implying that glycolysis regulates vessel branching.

The ER Stress Sensor PERK Coordinates ER-Plasma Membrane Contact Site Formation through Interaction with Filamin-A and F-Actin Remodeling.

Loss of ER Ca2+ homeostasis triggers endoplasmic reticulum (ER) stress and drives ER-PM contact sites formation in order to refill ER-luminal Ca2+. Recent studies suggest that the ER stress sensor and mediator of the unfolded protein response (UPR) PERK regulates intracellular Ca2+ fluxes, but the mechanisms remain elusive. Here, using proximity-dependent biotin identification (BioID), we identified the actin-binding protein Filamin A (FLNA) as a key PERK interactor. Cells lacking PERK accumulate F-actin at the cell edges and display reduced ER-PM contacts. Following ER-Ca2+ store depletion, the PERK-FLNA interaction drives the expansion of ER-PM juxtapositions by regulating F-actin-assisted relocation of the ER-associated tethering proteins Stromal Interaction Molecule 1 (STIM1) and Extended Synaptotagmin-1 (E-Syt1) to the PM. Cytosolic Ca2+ elevation elicits rapid and UPR-independent PERK dimerization, which enforces PERK-FLNA-mediated ER-PM juxtapositions. Collectively, our data unravel an unprecedented role of PERK in the regulation of ER-PM appositions through the modulation of the actin cytoskeleton.

Not all poor are equal: the perpetuation of poverty through blaming those who have been poor all their lives.

The economic crisis of 2008 severely affected the welfare states. As the economic situation of a country worsens, the resources that the public administration can devote to improve the situation of the people also decrease, endangering the advancement of those in a disadvantaged situation. People who have always lived in poverty, besides having their opportunities reduced, also face negative public views that affect the perceived legitimacy of such public aid, which can in turn be a mechanism for perpetuating their situation. Two studies (N = 252 and N = 266) analyse how a person in persistent poverty is perceived compared to a person in poverty due to the crisis-a circumstantial poverty. We also study some feasible mechanisms underlying this different perception, as well as their effects on attitudes toward social protection policies. In Study 1, results indicated that people showed more favourable attitudes toward social protection policies when they perceived someone in poverty due to the crisis, compared to the target who had been in poverty all his/her life. Individualistic attributions for poverty mediated this effect: when people think of someone in persistent poverty, they make more individualistic attributions concerning their situation, which leads to worse attitudes toward social protection policies. Identification with the group moderates this relation. Furthermore, Study 2 showed that participants perceive people who are in poverty because of economic crisis as more deserving of help than people who have always been poor. Some theoretical and practical implications for intergroup relations and public policy are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03804-6.

Assessment of the effects of health and financial threat on prosocial and antisocial responses during the COVID-19 pandemic: The mediating role of empathic concern.

This research aims to elucidate the connection of perceived health and financial threat linked to the COVID-19 pandemic with the willingness to engage in prosocial and antisocial behaviors, while also testing the potential mediating role of empathic concern. During the lockdown period, a sample of Spanish community members (N = 702) filled in a multi-measure online survey. Our results revealed that (a) COVID-19 health (but not financial) threat predicted a greater tendency to express prosocial actions, (b) none of these forms of COVID-19 threat predicted antisocial inclinations, and (c) empathic concern mediated the effects of COVID-19 health threat on both prosocial and antisocial tendencies. Findings speak to the ongoing debate about whether individuals most psychologically impacted by the pandemic would tend to respond in a more prosocial or antisocial manner.

Visualizing RNA granule transport and translation in living neurons.

In polarized cells, such as neurons, the synthesis of an mRNA does not ensure its proper cellular expression. Most mature transcripts require the association with RNA-binding proteins, resulting in the formation of RNA granules, which are then transported within the cytoplasm along the cytoskeleton and delivered to their proper subcellular locations, where they can be locally translated. Here we review current microscopy methods that have been developed to visualize RNA granule formation, transport and translation at the single cell level with a special emphasis on the MS2 and SunTag systems. They include the labeling of mRNAs and RNA-binding proteins in living cells or even the detection of newly synthesized proteins in situ.

Preventing parastomal hernias with systematic intraperitoneal specifically designed mesh.

BACKGROUND: Parastomal hernia is a very common complication after stoma formation. Current surgical techniques for repairing parastomal hernia have unsatisfactory results. We aim to assess our preliminary experience with prophylactic mesh placement at the time of stoma formation. METHODS: Data were prospectively recorded. A specifically designed mesh made of polyvinyl fluoride with central conduit (Dynamesh IPST®) was fixed using an intra-peritoneal onlay technique. Safety was evaluated by means of surgical data and frequency of mesh-related complications, efficacy by the rate of parastomal hernias. RESULTS: Thirty-four patients were included in the study. Three of them died before a year of follow up (not related to the stoma), so they were excluded. The other 31 patients (11 women and 20 men) were prospectively followed up after different pathologies resulting in a permanent colostomy. Twelve months after surgery CT-Scan imaging revealed two (6.4%) parastomal hernias, one of them already clinically suspected. During the follow up, 29% of the patients (n = 9) developed another type of hernia (incisional, inguinal or both). In five patients (16.1%) a light stomal retraction of the otherwise slightly prominent ostomy was observed. Median clinical follow-up was 17.5 months (range 12-34). CONCLUSION: Prophylactic parastomal mesh placement might be a safe and effective procedure with a potential to reduce the risk of parastomal hernia. Routine use of this technique should be further analysed.

VEGF modulates NMDA receptors activity in cerebellar granule cells through Src-family kinases before synapse formation.

NMDA type glutamate receptors (NMDARs) are best known for their role in synaptogenesis and synaptic plasticity. Much less is known about their developmental role before neurons form synapses. We report here that VEGF, which promotes migration of granule cells (GCs) during postnatal cerebellar development, enhances NMDAR-mediated currents and Ca(2+) influx in immature GCs before synapse formation. The VEGF receptor Flk1 forms a complex with the NMDAR subunits NR1 and NR2B. In response to VEGF, the number of Flk1/NR2B coclusters on the cell surface increases. Stimulation of Flk1 by VEGF activates Src-family kinases, which increases tyrosine phosphorylation of NR2B. Inhibition of Src-family kinases abolishes the VEGF-dependent NR2B phosphorylation and amplification of NMDAR-mediated currents and Ca(2+) influx in GCs. These findings identify VEGF as a modulator of NMDARs before synapse formation and highlight a link between an activity-independent neurovascular guidance cue (VEGF) and an activity-regulated neurotransmitter receptor (NMDAR).

Unforgiveness in the Light of Sexual Infidelity: Anxious Attachment to the Partner and Personal Distress as Correlates.

It has been widely documented that infidelity is established as one of the main causes of relationship breakdowns. Likewise, the empirical literature has also revealed the association between anxious attachment and personal distress with unforgiveness motivations. However, there is no known research that has examined the role of anxious attachment to the partner, personal distress, and unforgiveness motivations in infidelity and even less, taking into account the perspective of the offended person. Through a correlational study (N = 304 Spanish participants from the general population [M = 26.25, SD = 9.62]), we examined the relationship between unforgiveness motivations (revenge and avoidance motivations for unforgiveness), anxious attachment to the partner, and personal distress experienced after a hypothetical sexual infidelity from the perspective of the offended person. The results showed that anxious attachment was positively associated with revenge motivation for unforgiveness and personal distress. Moreover, high levels of anxious attachment to the partner were only associated with higher avoidance motivation for unforgiveness through increased levels of personal distress. Last but not least, we discuss these findings and their possible repercussions for intimate relationships.

Gendered Social Perceptions of "The Poor": Differences in Individualistic Attributions, Stereotypes, and Attitudes Toward Social Protection Policies.

Poverty is a phenomenon that affects men and women differently. In the current research, we examined social perceptions of poor men and women across three experiments focusing on attributions for poverty, classist attitudes, and stereotypes about poor people. In Study 1, participants from the general population (N = 484) made more individualistic (dispositional) attributions for men's poverty compared to women's poverty, blaming men more for their poverty. Participants also believed that men would manage the assistance they received from the state more poorly than women. These patterns were observed across all three studies. In Study 2 (N = 256), we also found that more individualistic attributions for why men were in poverty predicted more negative attitudes toward social protection policies concerning men. In Study 3 (N = 358), we replicated the results observed in Study 2, and found that women in poverty were described as mor communal and competent than men in poverty. We interpret these results considering the operation of traditional gender roles as well as the parallelism between stereotypes of women and poor people. Our results are relevant to the framing of the proposals by social organizations, political parties, and emancipation movements that advocate for policies and programs to address poverty. Supplementary Information: The online version contains supplementary material available at 10.1007/s11199-023-01375-9.

Understanding the Components and Determinants of Police Attitudes Toward Intervention in Intimate Partner Violence Against Women: A Systematic Review.

Police officers are society's first interveners in intimate partner violence against women (IPVAW) and are essential for victim safety. Despite IPVAW laws, police attitudes influence their real actions during IPVAW intervention. However, the fuzzy conceptualization of the construct deters the pursuit of conclusive evidence. This systematic review sought to identify the components of police attitudes toward intervention in IPVAW and their determinants. A search was conducted through several databases (e.g., Web of Science). Papers were included if they (a) provided original empirical findings or were review studies, (b) were published between 1990 and 2019, (c) were written in Spanish or English, (d) alluded to police officers, and (e) focused on police attitudes toward intervention in IPVAW or their determinants. Fifty-seven papers were included. The studied components of police attitudes toward intervention in IPVAW extracted from the literature were tolerance of IPVAW, minimal police involvement, unsupportive and supportive attitudes toward the legal system and legislation against IPVAW, understanding of the complex nature of abuse, and IPVAW intervention as an important police task. Moreover, the central role of individual and situational determinants in police attitudes toward intervention in IPVAW was confirmed, whereas organizational and societal determinants were studied scarcely. This review proposes a framework upon which to build operational definition of police attitudes toward intervention in IPVAW and includes remarks on police backgrounds and the situational characteristics of IPVAW events that are essential in shaping police procedures for managing them. Empirical evidence should be transferred to police training and standard operating procedures.

RNA supply drives physiological granule assembly in neurons.

Membraneless cytoplasmic condensates of mRNAs and proteins, known as RNA granules, play pivotal roles in the regulation of mRNA fate. Their maintenance fine-tunes time and location of protein expression, affecting many cellular processes, which require complex protein distribution. Here, we report that RNA granules-monitored by DEAD-Box helicase 6 (DDX6)-disassemble during neuronal maturation both in cell culture and in vivo. This process requires neuronal function, as synaptic inhibition results in reversible granule assembly. Importantly, granule assembly is dependent on the RNA-binding protein Staufen2, known for its role in RNA localization. Altering the levels of free cytoplasmic mRNA reveals that RNA availability facilitates DDX6 granule formation. Specifically depleting RNA from DDX6 granules confirms RNA as an important driver of granule formation. Moreover, RNA is required for DDX6 granule assembly upon synaptic inhibition. Together, this data demonstrates how RNA supply favors RNA granule assembly, which not only impacts subcellular RNA localization but also translation-dependent synaptic plasticity, learning, and memory.

Women's Risk Perception and Responses to Intimate Partner Sexual Coercion: The Role of Type of Tactic, Previous Experience, and Myths Acceptance.

Sexual coercion is among the subtlest forms of sexual violence in an intimate relationship and sometimes goes unnoticed by victims. The present study analyzed factors that potentially mitigate women's negative perceptions of intimate partner sexual coercion (IPSC). A total of 427 women completed an online survey, in which they were shown vignettes illustrating a growing risk of sexual coercion according to the perpetrators' use of different coercive tactics. Participants replied to questions that reflected their risk perception, their perceptions of perpetrator behavior, and the probability of their leaving the relationship. The survey also queried their previous IPSC experience, and their degree of acceptance of sexual aggression myths. According to the results, women exposed to positive (vs. negative) verbal sexual coercion (VSC) condition decided to leave the abusive situation later (risk response), presented a longer time lag between the moment they recognized the risk and the moment they responded to it, perceived the perpetrator's behavior as more acceptable and excusable, and were less likely to leave the relationship. Finally, greater myth acceptance and previous IPSC experience predicted a lower probability of leaving the relationship, due to delayed risk responses and to perceiving the perpetrator's behavior as more acceptable and excusable. This was true regardless of the type of coercive tactic used by the perpetrator. The results highlight the need to consider the type of coercive tactic, previous experience, and myths acceptance as risk factors that may impede a woman to adequately perceive and respond to an intimate partner's sexual violence.

Women's Experience of Sexual Coercion and Reactions to Intimate Partner Sexual Violence.

Sexual coercion is one of the most subtle manifestations of gender-based violence and may profoundly affect victims' sexuality. This research analyzed the association of previous experiences of sexual coercion by an intimate partner (intimate partner sexual coercion [IPSC]) with women's reactions and responses to a scenario of sexual violence. Female college undergraduates (N = 207) completed a computer task in which they watched a video about a couple that ended in a woman having unwanted sex with her male partner. Participants answered several questions about tolerance (risk recognition, risk response, delays in behavioral response, and probability of leaving the relationship). They also responded about their level of commitment to their current partner, as well as their previous experience of sexual coercion. Results showed no differences between victims and nonvictims on the time they took to perceive the situation of sexual violence as threatening (risk recognition). However, victims of current sexual coercion took more time deciding to leave the abusive situation of the video (risk response), required a greater time lag between risk recognition and risk response, and they would be less likely to leave the relationship than victims of past sexual coercion and nonvictims. Finally, commitment predicted later risk recognition and risk response only for victims of past sexual coercion. Overall, the results suggested that previous sexual coercion by an intimate partner and being committed to the relationship may be risk factors associated with the increase of women's tolerance toward situations involving the risk of sexual victimization.

Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy.

PTEN-induced kinase 1 (PINK1) is a short-lived protein required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane proteins synaptojanin 2 binding protein (SYNJ2BP) and synaptojanin 2 (SYNJ2) are required for tethering Pink1 mRNA to mitochondria via an RNA-binding domain in SYNJ2. This neuron-specific adaptation for the local translation of PINK1 provides distal mitochondria with a continuous supply of PINK1 for the activation of mitophagy.

Enhancement of endogenous neurogenesis in ephrin-B3 deficient mice after transient focal cerebral ischemia.

Cerebral ischemia stimulates endogenous neurogenesis. However, the functional relevance of this phenomenon remains unclear because of poor survival and low neuronal differentiation rates of newborn cells. Therefore, further studies on mechanisms regulating neurogenesis under ischemic conditions are required, among which ephrin-ligands and ephrin-receptors (Eph) are an interesting target. Although Eph/ephrin proteins like ephrin-B3 are known to negatively regulate neurogenesis under physiological conditions, their role in cerebral ischemia is largely unknown. We therefore studied neurogenesis, brain injury and functional outcome in ephrin-B3(-/-) (knockout) and ephrin-B3(+/+) (wild-type) mice submitted to cerebral ischemia. Induction of stroke resulted in enhanced cell proliferation and neuronal differentiation around the lesion site of ephrin-B3(-/-) compared to ephrin-B3(+/+) mice. However, prominent post-ischemic neurogenesis in ephrin-B3(-/-) mice was accompanied by significantly increased ischemic injury and motor coordination deficits that persisted up to 4 weeks. Ischemic injury in ephrin-B3(-/-) mice was associated with a caspase-3-dependent activation of the signal transducer and activator of transcription 1 (STAT1). Whereas inhibition of caspase-3 had no effect on brain injury in ephrin-B3(+/+) animals, infarct size in ephrin-B3(-/-) mice was strongly reduced, suggesting that aggravated brain injury in these animals might involve a caspase-3-dependent activation of STAT1. In conclusion, post-ischemic neurogenesis in ephrin-B3(-/-) mice is strongly enhanced, but fails to contribute to functional recovery because of caspase-3-mediated aggravation of ischemic injury in these animals. Our results suggest that ephrin-B3 might be an interesting target for overcoming some of the limitations of further cell-based therapies in stroke.

Role of delta-like-4/Notch in the formation and wiring of the lymphatic network in zebrafish.

OBJECTIVE: To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development. METHODS AND RESULTS: In zebrafish embryos, sprouts from the axial vein have lymphangiogenic potential because they give rise to the first lymphatics. Knockdown of delta-like-4 (Dll4) or its receptors Notch-1b or Notch-6 in zebrafish impaired lymphangiogenesis. Dll4/Notch silencing reduced the number of sprouts producing the string of parchordal lymphangioblasts; instead, sprouts connecting to the intersomitic vessels were formed. At a later phase, Notch silencing impaired navigation of lymphatic intersomitic vessels along their arterial templates. CONCLUSIONS: These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network.

Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation.

Dendritic spines are small protrusions emerging from dendrites that receive excitatory input. The process of spine morphogenesis occurs both in the developing brain and during synaptic plasticity. Molecules regulating the cytoskeleton are involved in spine formation and maintenance. Here we show that reverse signaling by the transmembrane ligands for Eph receptors, ephrinBs, is required for correct spine morphogenesis. The molecular mechanism underlying this function of ephrinBs involves the SH2 and SH3 domain-containing adaptor protein Grb4 and the G protein-coupled receptor kinase-interacting protein (GIT) 1. Grb4 binds by its SH2 domain to Tyr392 in the synaptic localization domain of GIT1. Phosphorylation of Tyr392 and the recruitment of GIT1 to synapses are regulated by ephrinB activation. Disruption of this pathway in cultured rat hippocampal neurons impairs spine morphogenesis and synapse formation. We thus show an important role for ephrinB reverse signaling in spine formation and have mapped the downstream pathway involved in this process.

Victim blaming and exoneration of the perpetrator in domestic violence: the role of beliefs in a just world and ambivalent sexism.

The existence of domestic violence is closely linked to several ideological factors that include sexism and other beliefs about society in general, namely the belief in a just world. In this study, which involved 485 people of both sexes aged between 18 and 70 years, we analyzed the influence of these ideological variables of the perceivers and characteristics of the situation on judgments of a gender aggression--blaming the victim and exonerating the perpetrator. Results showed differences in the reactions of observers depending on the cause that triggered the aggression. Participants blamed the victim and exonerated the aggressor more when no cause of the aggression was mentioned than when a cause was mentioned (the woman wanted to separate, to see an old male friend, or simply to take a trip with her female friends). We also found clear effects of hostile sexism and just world beliefs on the dependent variables. Results showed that the influence of just world beliefs depended on the fact of mention or not a cause for the aggression.

Elucidating the Effect of Perceived Power on Destructive Responses during Romantic Conflicts.

Prior research has indicated that the people one loves the most, such as their romantic partners, ironically, are also the people toward whom they often direct destructive behaviors in times of conflict, and such destructive responses become one of the most challenging relationship problems. Identifying the conditions that promote destructive (vs. constructive) conflict-resolution strategies is a crucial gap requiring study to help individuals build healthier and happier relationships. Across three studies (total N = 728), we examined whether (a) power is related to direct destructive (vs. constructive) responses during romantic conflicts; (b) this effect was moderated by the seriousness of the conflict and the relationship's inclusiveness. In Study 1, participants involved in romantic relationships completed scales assessing interpersonal power, the conflict's seriousness, their relationship's inclusiveness, and conflict-resolution responses. In Studies 2-3, the participants were randomly assigned to complete an essay in which the conflict's seriousness and power were experimentally manipulated. Findings from hierarchical regression analyses consistently showed that power led to destructive (and lower constructive) responses. However, this only occurred when the participants faced severe conflicts and their partner was not central to their self-concept. An internal meta-analysis of the studies confirmed the reliability and significance of these relationships; |r's| =.13-37. Together, these results support the proposition that power asymmetries can threaten relationships by driving destructive responses during romantic conflicts, and untangle the conditions under which this happens. The conflict's seriousness and the inclusiveness of the relationship may be considered to provide skills that help individuals navigate their relationships' life challenges.

Large-Scale Monitoring of Resistance to Coumaphos, Amitraz, and Pyrethroids in Varroa destructor.

Varroa destructor is an ectoparasitic mite causing devastating damages to honey bee colonies around the world. Its impact is considered a major factor contributing to the significant seasonal losses of colonies recorded every year. Beekeepers usually rely on a reduced set of acaricides to manage the parasite, usually the pyrethroids tau-fluvalinate or flumethrin, the organophosphate coumaphos, and the formamidine amitraz. However, the evolution of resistance in the mite populations is leading to an unsustainable scenario with almost no alternatives to reach an adequate control of the mite. Here, we present the results from the first large-scale and extensive monitoring of the susceptibility to acaricides in the Comunitat Valenciana, one of the most prominent apicultural regions in Spain. Our ultimate goal is to provide beekeepers with timely information to help them decide what would be the best alternative for a long-term control of the mites in their apiaries. Our data show that there is a significant variation in the expected efficacy of coumaphos and pyrethroids across the region, indicating the presence of a different ratio of resistant individuals to these acaricides in each population. On the other hand, the expected efficacy of amitraz was more consistent, though slightly below the expected efficacy according to the label.