Ape Origins of Human Malaria.

African apes harbor at least twelve Plasmodium species, some of which have been a source of human infection. It is now well established that Plasmodium falciparum emerged following the transmission of a gorilla parasite, perhaps within the last 10,000 years, while Plasmodium vivax emerged earlier from a parasite lineage that infected humans and apes in Africa before the Duffy-negative mutation eliminated the parasite from humans there. Compared to their ape relatives, both human parasites have greatly reduced genetic diversity and an excess of nonsynonymous mutations, consistent with severe genetic bottlenecks followed by rapid population expansion. A putative new Plasmodium species widespread in chimpanzees, gorillas, and bonobos places the origin of Plasmodium malariae in Africa. Here, we review what is known about the origins and evolutionary history of all human-infective Plasmodium species, the time and circumstances of their emergence, and the diversity, host specificity, and zoonotic potential of their ape counterparts.

A two-gene strategy increases iron and zinc concentrations in wheat flour, improving mineral bioaccessibility.

Dietary deficiencies of iron and zinc cause human malnutrition that can be mitigated by biofortified staple crops. Conventional breeding approaches to increase grain mineral concentrations in wheat (Triticum aestivum L.) have had only limited success, and our understanding of the genetic and physiological barriers to altering this trait is incomplete. Here we demonstrate that a transgenic approach combining endosperm-specific expression of the wheat VACUOLAR IRON TRANSPORTER gene TaVIT2-D with constitutive expression of the rice (Oryza sativa) NICOTIANAMINE SYNTHASE gene OsNAS2 significantly increases the total concentration of zinc and relocates iron to white-flour fractions. In two distinct bread wheat cultivars, we show that the so called VIT-NAS construct led to a two-fold increase in zinc in wholemeal flour, to ∼50 µg g-1. Total iron was not significantly increased, but redistribution within the grain resulted in a three-fold increase in iron in highly pure, roller-milled white flour, to ∼25 µg g-1. Interestingly, expression of OsNAS2 partially restored iron translocation to the aleurone, which is iron depleted in grain overexpressing TaVIT2 alone. A greater than three-fold increase in the level of the natural plant metal chelator nicotianamine in the grain of VIT-NAS lines corresponded with improved iron and zinc bioaccessibility in white flour. The growth of VIT-NAS plants in the greenhouse was indistinguishable from untransformed controls. Our results provide insights into mineral translocation and distribution in wheat grain and demonstrate that the individual and combined effects of the two transgenes can enhance the nutritional quality of wheat beyond what is possible by conventional breeding.

CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.

Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. Moreover, seven different guenons (Cercopithecus spp.) shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome.

Sexual minority men's experiences of, and strategies for emotional intimacy in intimate partner relationships.

Emotional intimacy is key to intimate partner relationship quality and satisfaction. For sexual minority men, queer and feminist theorists consistently link emotional intimacy to diverse sexual practices and partnership dynamics formulated within the relationship. This Photovoice study adds to those insights by drawing on individual photovoice interviews with 16 sexual minority men to describe participant's experiences of, and strategies for emotional intimacy in their intimate relationships. Analysis revealed three distinct yet entwined themes: (i) embracing vulnerabilities to drive self-acceptance; (ii) building relationality with partners; and (iii) securing connections with family, friends and community. By embracing vulnerabilities to drive self-acceptance, participants spoke to embodied courage and autonomy as key components for addressing wide-ranging emotional intimacy challenges in their relationships. In theme two, building relationality with partners, participants described how empathy, trust and reciprocity underpinned collaborative work to foster emotional intimacy. Lastly, in securing connections with family, friends and community, acceptance and inclusion were key to participants' sense of belonging and legitimacy which aided their emotional intimacy with partners. The findings provide guidance for tailored programmatic efforts to assist sexual minority men build intimate relationships.

Men's peer support for mental health challenges: future directions for research and practice.

Peer support has a long history of helping people navigate mental health challenges and is increasingly utilized within men's mental health promotion initiatives. Despite considerable research conceptualizing and evaluating peer support in various contexts, little is known about the gendered dimensions of men's peer support and mutual help for mental health. This article provides an empirically informed commentary on men's peer support and informal help-seeking preferences to make recommendations for future directions for research and practice. Research examining men's peer support is emergent and the available evidence suggests that there is potential to conceptually align with many men's values and preferences for mental health help-seeking. Peer support offers a non-clinical, strength-based adjunct to professional support that may aid men in navigating a range of mental health challenges. Consideration must be given to the influence of gender socialization and men's diverse experiences with developing and maintaining peer relationships. It should not be assumed that authentic and supportive relationships will naturally form when men congregate together. As a growing number of interventions and programs emerge targeted at boys and men, there are important opportunities to leverage these health promotion efforts to encourage and coach men to engage in mutual help. Opportunities for research and practice are discussed to better understand and harness the health-promoting potential of peer support for men's mental health.

Hierarchical inference as a source of human biases.

The finding that human decision-making is systematically biased continues to have an immense impact on both research and policymaking. Prevailing views ascribe biases to limited computational resources, which require humans to resort to less costly resource-rational heuristics. Here, we propose that many biases in fact arise due to a computationally costly way of coping with uncertainty-namely, hierarchical inference-which by nature incorporates information that can seem irrelevant. We show how, in uncertain situations, Bayesian inference may avail of the environment's hierarchical structure to reduce uncertainty at the cost of introducing bias. We illustrate how this account can explain a range of familiar biases, focusing in detail on the halo effect and on the neglect of base rates. In each case, we show how a hierarchical-inference account takes the characterization of a bias beyond phenomenological description by revealing the computations and assumptions it might reflect. Furthermore, we highlight new predictions entailed by our account concerning factors that could mitigate or exacerbate bias, some of which have already garnered empirical support. We conclude that a hierarchical inference account may inform scientists and policy makers with a richer understanding of the adaptive and maladaptive aspects of human decision-making.

Disrupted state transition learning as a computational marker of compulsivity.

BACKGROUND: Disorders involving compulsivity, fear, and anxiety are linked to beliefs that the world is less predictable. We lack a mechanistic explanation for how such beliefs arise. Here, we test a hypothesis that in people with compulsivity, fear, and anxiety, learning a probabilistic mapping between actions and environmental states is compromised. METHODS: In Study 1 (n = 174), we designed a novel online task that isolated state transition learning from other facets of learning and planning. To determine whether this impairment is due to learning that is too fast or too slow, we estimated state transition learning rates by fitting computational models to two independent datasets, which tested learning in environments in which state transitions were either stable (Study 2: n = 1413) or changing (Study 3: n = 192). RESULTS: Study 1 established that individuals with higher levels of compulsivity are more likely to demonstrate an impairment in state transition learning. Preliminary evidence here linked this impairment to a common factor comprising compulsivity and fear. Studies 2 and 3 showed that compulsivity is associated with learning that is too fast when it should be slow (i.e. when state transition are stable) and too slow when it should be fast (i.e. when state transitions change). CONCLUSIONS: Together, these findings indicate that compulsivity is associated with a dysregulation of state transition learning, wherein the rate of learning is not well adapted to the task environment. Thus, dysregulated state transition learning might provide a key target for therapeutic intervention in compulsivity.

Training diversity promotes absolute-value-guided choice.

Many decision-making studies have demonstrated that humans learn either expected values or relative preferences among choice options, yet little is known about what environmental conditions promote one strategy over the other. Here, we test the novel hypothesis that humans adapt the degree to which they form absolute values to the diversity of the learning environment. Since absolute values generalize better to new sets of options, we predicted that the more options a person learns about the more likely they would be to form absolute values. To test this, we designed a multi-day learning experiment comprising twenty learning sessions in which subjects chose among pairs of images each associated with a different probability of reward. We assessed the degree to which subjects formed absolute values and relative preferences by asking them to choose between images they learned about in separate sessions. We found that concurrently learning about more images within a session enhanced absolute-value, and suppressed relative-preference, learning. Conversely, cumulatively pitting each image against a larger number of other images across multiple sessions did not impact the form of learning. These results show that the way humans encode preferences is adapted to the diversity of experiences offered by the immediate learning context.

Exploring the practicality and acceptability a brief exercise communication and clinician referral pathway in cancer care: a feasibility study.

BACKGROUND: The majority of cancer patients and cancer care clinicians-CCCs (e.g., oncologists) believe that exercise is an important adjunct therapy that should be embedded in standard practice. Yet, CCCs do not routinely discuss exercise with their patients, nor do they regularly refer them to exercise professionals (e.g., exercise physiologists-EPs). This study evaluated the feasibility and acceptability of an evidence-based approach to improving exercise communication between CCCs and their patients, including an exercise referral pathway. METHODS: Implementation and testing of the Exercise Communication and Referral Pathway (ECRP) occurred in Sydney, Australia. The ECRP included a brief oncology-initiated communication exchange with patients, CCC exercise referral to an EP, followed by EP-initiated telephone consultation with patients concerning tailored exercise advice. Participant perceptions concerning the feasibility and applicability of the ECPR were evaluated. Semi-structured interviews were conducted with CCCs (n = 3), cancer patients (n = 21), and an EP (n = 1). Inductive thematic analysis was undertaken. RESULTS: Analysis generated three themes: (1) Navigating the role of CCCs in the ECRP, suggesting that oncology-initiated communication is a cue to action, however there was a lack of role clarity regarding exercise referral; (2) Implementing Patient-Orientated Care within a Standardised Pathway, highlighting the need for tailored information and advice for patients that reflects individual disease, socio-cultural, and environmental factors, and; (3) Taking Steps Towards Action, revealing the need for structural (e.g., EP initiated contact with patients) and policy changes (i.e., changes to Medicare, direct oncologist referral) to engage patients and better integrate exercise as part of standard care. CONCLUSIONS: Findings provide important insights into improving oncology-patient exercise communication and developing an exercise referral pathway to increase engagement and patient reach. However, individual (e.g., experience, knowledge) and contextual factors (e.g., time, resources) need consideration when implementing an ECRP. TRIAL REGISTRATION: This trial was prospectively registered with the Australian New Zealand Clinical (#ACTRN12620000358943) on March 13, 2020.

"A feeling for run and rhythm": coaches' perspectives of performance, talent, and progression in rowing.

The understanding of rowing performance has been predominantly gained through quantitative sports science-based research. In combination with this objective information, coaches' experiences may provide important contextual information for how this quantitative evidence is implemented into training programmes. The aims of this study were to (1) explore coaches' perspectives of performance indicators for competitive rowing in junior rowers, and (2) identify coaches' recommendations for developing effective technique and movement competency among junior rowers who have the potential to transition to elite competition. Twenty-seven semi-structured interviews were conducted with experienced rowing coaches through purposive sampling of an accredited coaching network. Participants' coaching experience ranged from 5 to 46 (M = 22, SD = 10) years. Data were analysed using thematic analysis. Three overarching themes were identified including, (1) getting the basics right, (2) targeting types of talent, and (3) complexities of performance. Based on these findings, sequence and boat feel, supported through the movement competency provided by hip flexibility and the trunk musculature, were considered critical for executing correct technique. Developing talent and understanding successful performance are both complex concepts when considering the individual athlete. Coaches' perspectives provided insight into key components of performance to enhance our understanding of how to better develop junior rowers.

Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues.

Iron is an essential element involved in a variety of physiological functions. However, excess iron catalyzes the generation of reactive oxygen species (ROS) via the Fenton reaction. Oxidative stress, caused by an increase in intracellular ROS production, can be a contributory factor to metabolic syndromes such as dyslipidemia, hypertension, and type 2 diabetes (T2D). Accordingly, interest has grown recently in the role and use of natural antioxidants to prevent iron-induced oxidative damage. This study investigated the protective effect of the phenolic acids; ferulic acid (FA) and its metabolite ferulic acid 4-O-sulfate disodium salt (FAS) against excess iron-related oxidative stress in murine MIN6 cells and the pancreas of BALB/c mice. Rapid iron overload was induced with 50 µmol/L ferric ammonium citrate (FAC) and 20 µmol/L 8-hydroxyquinoline (8HQ) in MIN6 cells, while iron dextran (ID) was used to facilitate iron overload in mice. Cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, ROS levels were determined by dihydrodichlorofluorescein (H2DCF) cell-permeant probe, iron levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), glutathione, SOD (superoxide dismutase) and lipid peroxidation, and mRNA were assayed with commercially available kits. The phenolic acids enhanced cell viability in iron-overloaded MIN6 cells in a dose-dependent manner. Furthermore, MIN6 cells exposed to iron showed elevated levels of ROS, glutathione (GSH) depletion and lipid peroxidation (p < 0.05) compared to cells that were protected by treatment with FA or FAS. The treatment of BALB/c mice with FA or FAS following exposure to ID increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) gene levels in the pancreas. Consequently, levels of its downstream antioxidant genes, HO-1, NQO1, GCLC and GPX4, increased in the pancreas. In conclusion, this study shows that FA and FAS protect pancreatic cells and liver tissue from iron-induced damage via the Nrf2 antioxidant activation mechanism.

A pragmatic strength and conditioning intervention for firefighters: Feasibility of the Tactical Athlete Resilience Program (TARP).

ISSUE ADDRESSED: Firefighting is physically and mentally taxing and recruits are expected to have optimal health and fitness. However, physical fitness tends to decline following initial training, placing firefighters at an increased risk for stress and injury. Efforts are needed to engage and support firefighters in maintaining adequate health and fitness to withstand the rigorous demands of their occupation. This study examined the feasibility of TARP, a pragmatic strength and conditioning intervention for metropolitan-based firefighters, delivered in collaboration with a professional National Rugby League club. METHODS: A mixed-methods approach was utilised to examine program implementation, recruitment and sample characteristics, intervention satisfaction and acceptability, and participants' response to the intervention. Evaluation measures included field notes taken during steering committee meetings, participant flow data, baseline and follow-up outcome measures, self-report questionnaires, and telephone interviews with a sample of participants. RESULTS: Participants (N = 113) were predominantly men (82%) with a mean age of 43 ± 9.3 years and BMI of 26.6 ± 2.9 kg/m2 . Program satisfaction was high (95% very satisfied or somewhat satisfied) among program completers (42% retention). Key strengths of the program included delivery through the professional sports club, quality of facilities and equipment, and scheduling flexibility. Future programs should consider incorporating education or training to support behaviour change maintenance and strategies to retain participants at follow-up. CONCLUSIONS: Results provide valuable insights into the design and delivery of interventions for firefighters and demonstrate the importance of strong partnerships between community stakeholders.

Zinc induces hephaestin expression via a PI3K-CDX2 dependent mechanism to regulate iron transport in intestinal Caco-2 cells.

Zinc stimulates intestinal iron absorption via induction of divalent metal ion transporter (DMT1) and hephaestin (HEPH). While the increase in DMT1 is mediated via a PI3K/IPR2 axis, the mechanisms of Zn-induced HEPH expression downstream of PI3K remain elusive. In the current study we probed the role of Caudal-related homeobox transcription factor-2 (CDX2) on Zn-induced HEPH expression. Zn treatment of Caco-2 cells increased CDX2 phosphorylation and HEPH protein and mRNA expression. siRNA-silencing of CDX2 inhibited Zn-induced HEPH expression. LY294002, an antagonist of PI3K inhibited Zn-induced phosphorylation of CDX2, and downstream HEPH expression. These results suggest that increased expression of HEPH in intestinal cells following Zn treatment is mediated via a PI3K-CDX2 pathway.

Cognitive control deployment is flexibly modulated by social value in early adolescence.

Recent mechanistic models of cognitive control define the normative level of control deployment as a function of the effort cost of exerting control balanced against the reward that can be attained by exerting control. Despite these models explaining empirical findings in adults, prior literature has suggested that adolescents may not adaptively integrate value into estimates of how much cognitive control they should deploy. Moreover, much work in adolescent neurodevelopment casts social valuation processes as competing with, and in many cases overwhelming, cognitive control in adolescence. Here, we test whether social incentives can adaptively increase cognitive control. Adolescents (Mage  = 14.64, 44 male, N = 87) completed an incentivized cognitive control task in which they could exert cognitive control to receive rewards on behalf of real peers who were rated by all peers in their school grade as being of either high- or low-status. Using Bayesian modeling, we find robust evidence that adolescents exert more cognitive control for high- relative to low-status peers. Moreover, we demonstrate that social incentives, irrespective of their high- or low-status, boost adolescent cognitive control above baseline control where no incentives are offered. Findings support the hypothesis that the cognitive control system in early adolescence is flexibly modulated by social value.

CD4 receptor diversity in chimpanzees protects against SIV infection.

Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells. Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions. Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts. These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes. The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles. In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition. CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan. CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep. One allele was associated with lower SIVcpz prevalence rates in the wild. These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry. Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.

A family-based approach examining perceptions of an Australian TRYathlon series on children's health and development.

Regular physical activity supports children's physical and psychological health and wellbeing, and provides opportunities to build social and emotional skills such as resilience, confidence, and self-efficacy. Research has demonstrated that mass participant sporting events can serve as important social and environmental correlates of physical activity. This study sought to explore parents and children's perceived motivations and perspectives of participation in the Australian Sanitarium Weet-Bix Kids TRYathlon (a non-competitive triathlon series), on children's health and well-being. An exploratory qualitative design utilizing seven focus groups were conducted with 27 family units including 31 parents and 61 children (age 7-15 years old). Data were recorded, professionally transcribed and then analyzed using thematic analysis. Three overarching themes were identified, including (1) motivations for event and physical activity participation, revealing social interaction, peer support and friendly competition as motivators for participation as well as parents' interest in supporting the development of healthy habits; (2) Perceived physical activity, fitness, and developmental benefits, detailing changes to the types of physical activity children performed as well as opportunities for children to develop physical skills and competencies; and (3) Perceived psychosocial benefits of participation, highlighting opportunities for children to develop and demonstrate independence and autonomy through event participation. Notably, parents and children identified benefits beyond immediate participation including increased family engagement and social support. Mass participant events hold the potential to elicit a range of benefits for children and their families; however, further efforts may be needed to engage less active or disengaged families.

The physical and psychological benefits of being physically active during childhood are well established. However, most Australian children do not exercise at sufficient levels to receive the full extent of these health benefits. Research has demonstrated that mass participant sporting events can create supportive environments to engage in physical activity and sport whilst promoting mental, social and emotional well-being, but their impact on youth is unknown. Therefore, this study explored parents and children's perceived motivations and perspectives of participation in a mass participant sporting event, the Australian Sanitarium Weet-Bix Kids TRYathlon, on children's health and well-being. Our research indicated a range of motivators for engaging in the event, including social interaction, peer support, friendly competition and parents' interest in supporting healthy habits. The study also highlighted numerous perceived physical and psychosocial benefits of participation, such as increased physical activity pre and post-event, improved physical competency, enhanced confidence and increased family engagement and social support. Nonetheless, we believe further efforts may be needed to engage less active or disengaged families in the Australian Sanitarium Weet-Bix Kids TRYathlon and promote behaviour change.

Upregulation of Nrf2 Signalling and the Inhibition of Erastin-Induced Ferroptosis by Ferulic Acid in MIN6 Cells.

Ferroptosis is a regulated cell death process characterised by the iron-dependent accumulation of oxidised polyunsaturated fatty acid-containing phospholipids. Its initiation is complicated and involves reactive oxygen species (ROS) and a loss of the activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4). These play critical roles in the development of ferroptotic cell damage by lipid peroxidation. Antioxidant therapy is a promising therapeutic strategy to prevent or even reverse the progression of ferroptosis. This study was designed to demonstrate the protective effect of ferulic acid (FA) against oxidative stress and erastin-mediated ferroptosis in murine MIN6 cells. Cells were treated with FA or its metabolite ferulic acid 4-O-sulfate disodium salt (FAS) and 20 µM of erastin. Cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, iron levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), ROS levels were determined by a dihydrodichlorofluorescein (H2DCF) cell-permeant probe, and glutathione and lipid peroxidation were assayed with commercially available kits. The phenolic acids enhanced cell viability in erastin-treated MIN6 cells in a dose-dependent manner. Furthermore, MIN6 cells exposed to erastin alone showed elevated levels of iron and ROS, glutathione (GSH) depletion, and lipid peroxidation (p < 0.05) compared to cells that were protected by co-treatment with FA or FAS. The treatment of MIN6 cells with FA or FAS following exposure to erastin increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) protein levels. Consequently, levels of its downstream antioxidant proteins, HO-1, NQO1, GCLC, and GPX4, increased. FA and FAS greatly decreased erastin-induced ferroptosis in the presence of the Nrf2 inhibitor, ML385, through the regulation of Nrf2 response genes. In conclusion, these results show that FA and FAS protect MIN6 cells from erastin-induced ferroptosis by the Nrf2 antioxidant protective mechanism.

A double-blind study of empathic support and expectation as mechanisms of symptom change.

Objective: A novel brief intervention was used to investigate how empathic support and expectation can induce changes in mood, anxiety, and perceived stress. Method: Seventy-six undergraduates with high negative affect were assigned to three conditions of a program involving tasks with no known therapeutic benefit. In Group 1: Expectation Only, participants were given a deceptive description of the benefits of the program to quantify the magnitude of symptom change due to expectation alone. In Group 2: Empathic Support + Expectation, participants were also instructed to write about past and current sources of distress and provided with supportive notes each week to quantify the role of empathic support plus expectation. In Group 3: Control, participants were told they were "norming" the instruments. Results: Participants in Groups 1 and 2 demonstrated decreases in depression, anxiety, and rumination, with significant medium effect reductions found in the empathic support plus expectation condition. Conclusions: Evidence suggests that empathic support and expectation cause reduction of symptoms spanning depression and anxiety.

Inhibition of the facilitative sugar transporters (GLUTs) by tea extracts and catechins.

Tea polyphenolics have been suggested to possess blood glucose lowering properties by inhibiting sugar transporters in the small intestine and improving insulin sensitivity. In this report, we studied the effects of teas and tea catechins on the small intestinal sugar transporters, SGLT1 and GLUTs (GLUT1, 2 and 5). Green tea extract (GT), oolong tea extract (OT), and black tea extract (BT) inhibited glucose uptake into the intestinal Caco-2 cells with GT being the most potent inhibitor (IC50 : 0.077 mg/mL), followed by OT (IC50 : 0.136 mg/mL) and BT (IC50 : 0.56 mg/mL). GT and OT inhibition of glucose uptake was partial non-competitive, with an inhibitor constant (Ki ) = 0.0317 and 0.0571 mg/mL, respectively, whereas BT was pure non-competitive, Ki  = 0.36 mg/mL. Oocytes injected to express small intestinal GLUTs were inhibited by teas, but SGLT1 was not. Furthermore, catechins present in teas were the predominant inhibitor of glucose uptake into Caco-2 cells, and gallated catechins the most potent: CG > ECG > EGCG ≥ GCG when compared to the non-gallated catechins (C, EC, GC, and EGC). In Caco-2 cells, individual tea catechins reduced the SGLT1 gene, but not protein expression levels. In contrast, GLUT2 gene and protein expression levels were reduced after 2 hours exposure to catechins but increased after 24 hours. These in vitro studies suggest teas containing catechins may be useful dietary supplements capable of blunting postprandial glycaemia in humans, including those with or at risk to Type 2 diabetes mellitus.

Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites.

Wild-living African apes are endemically infected with parasites that are closely related to human Plasmodium vivax, a leading cause of malaria outside Africa. This finding suggests that the origin of P. vivax was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human P. vivax and its relationship to the ape parasites, we analyzed genome sequence data of P. vivax strains infecting six chimpanzees and one gorilla from Cameroon, Gabon, and Côte d'Ivoire. We found that ape and human parasites share nearly identical core genomes, differing by only 2% of coding sequences. However, compared with the ape parasites, human strains of P. vivax exhibit about 10-fold less diversity and have a relative excess of nonsynonymous nucleotide polymorphisms, with site-frequency spectra suggesting they are subject to greatly relaxed purifying selection. These data suggest that human P. vivax has undergone an extreme bottleneck, followed by rapid population expansion. Investigating potential host-specificity determinants, we found that ape P. vivax parasites encode intact orthologs of three reticulocyte-binding protein genes (rbp2d, rbp2e, and rbp3), which are pseudogenes in all human P. vivax strains. However, binding studies of recombinant RBP2e and RBP3 proteins to human, chimpanzee, and gorilla erythrocytes revealed no evidence of host-specific barriers to red blood cell invasion. These data suggest that, from an ancient stock of P. vivax parasites capable of infecting both humans and apes, a severely bottlenecked lineage emerged out of Africa and underwent rapid population growth as it spread globally.