TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes.

The endothelium is a major target of the proinflammatory cytokine, tumor necrosis factor alpha (TNFα). Exposure of endothelial cells (EC) to proinflammatory stimuli leads to an increase in mitochondrial metabolism; however, the function and regulation of elevated mitochondrial metabolism in EC in response to proinflammatory cytokines remain unclear. Studies using high-resolution metabolomics and 13C-glucose and 13C-glutamine labeling flux techniques showed that pyruvate dehydrogenase activity (PDH) and oxidative tricarboxylic acid cycle (TCA) flux are elevated in human umbilical vein ECs in response to overnight (16 h) treatment with TNFα (10 ng/mL). Mechanistic studies indicated that TNFα mediated these metabolic changes via mitochondrial-specific protein degradation of pyruvate dehydrogenase kinase 4 (PDK4, inhibitor of PDH) by the Lon protease via an NF-κB-dependent mechanism. Using RNA sequencing following siRNA-mediated knockdown of the catalytically active subunit of PDH, PDHE1α (PDHA1 gene), we show that PDH flux controls the transcription of approximately one-third of the genes that are up-regulated by TNFα stimulation. Notably, TNFα-induced PDH flux regulates a unique signature of proinflammatory mediators (cytokines and chemokines) but not inducible adhesion molecules. Metabolomics and ChIP sequencing for acetylated modification on lysine 27 of histone 3 (H3K27ac) showed that TNFα-induced PDH flux promotes histone acetylation of specific gene loci via citrate accumulation and ATP-citrate lyase-mediated generation of acetyl CoA. Together, these results uncover a mechanism by which TNFα signaling increases oxidative TCA flux of glucose to support TNFα-induced gene transcription through extramitochondrial acetyl CoA generation and histone acetylation.

Loss of TGFß-Mediated Repression of Angiopoietin-2 in Pericytes Underlies Germinal Matrix Hemorrhage Pathogenesis.

BACKGROUND: TGF (transforming growth factor)-ß pathway is central to blood-brain barrier development as it regulates cross talk between pericytes and endothelial cells. Murine embryos lacking TGFß receptor Alk5 (activin receptor-like kinase 5) in brain pericytes (mutants) display endothelial cell hyperproliferation, abnormal vessel morphology, and gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH), leading to perinatal lethality. Mechanisms underlying how ALK5 signaling in pericytes noncell autonomously regulates endothelial cell behavior remain elusive. METHODS: Transcriptomic analysis of human brain pericytes with ALK5 silencing identified differential gene expression. Brain vascular cells isolated from mutant embryonic mice with GMH-IVH and preterm human IVH brain samples were utilized for target validation. Finally, pharmacological and genetic inhibition was used to study the therapeutic effects on GMH-IVH pathology. RESULTS: Herein, we establish that the TGFß/ALK5 pathway robustly represses ANGPT2 (angiopoietin-2) in pericytes via epigenetic remodeling. TGFß-driven SMAD (suppressor of mothers against decapentaplegic) 3/4 associates with TGIF1 (TGFß-induced factor homeobox 1) and HDAC (histone deacetylase) 5 to form a corepressor complex at the Angpt2 promoter, resulting in promoter deacetylation and gene repression. Moreover, murine and human germinal matrix vessels display increased ANGPT2 expression during GMH-IVH. Isolation of vascular cells from murine germinal matrix identifies pericytes as a cellular source of excessive ANGPT2. In addition, mutant endothelial cells exhibit higher phosphorylated TIE2 (tyrosine protein kinase receptor). Pharmacological or genetic inhibition of ANGPT2 in mutants improves germinal matrix vessel morphology and attenuates GMH pathogenesis. Importantly, genetic ablation of Angpt2 in mutant pericytes prevents perinatal lethality, prolonging survival. CONCLUSIONS: This study demonstrates that TGFß-mediated ANGPT2 repression in pericytes is critical for maintaining blood-brain barrier integrity and identifies pericyte-derived ANGPT2 as an important pathological target for GMH-IVH.

Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability.

The role of serum response factor (Srf), a central mediator of actin dynamics and mechanical signaling, in cell identity regulation is debated to be either a stabilizer or a destabilizer. We investigated the role of Srf in cell fate stability using mouse pluripotent stem cells. Despite the fact that serum-containing cultures yield heterogeneous gene expression, deletion of Srf in mouse pluripotent stem cells leads to further exacerbated cell state heterogeneity. The exaggerated heterogeneity is detectible not only as increased lineage priming but also as the developmentally earlier 2C-like cell state. Thus, pluripotent cells explore more variety of cellular states in both directions of development surrounding naïve pluripotency, a behavior that is constrained by Srf. These results support that Srf functions as a cell state stabilizer, providing rationale for its functional modulation in cell fate intervention and engineering.

The change in handgrip strength, after physical exercise, is moderated by digit ratio (2D:4D): A study among the young adults in Poland.

BACKGROUND: The digit ratio (2D:4D), the ratio of the lengths of second (2D) to the fourth (4D) fingers, is a proxy indicator of prenatal androgen exposure. On average, males display lower 2D:4D than females. Previous studies have shown that lower 2D:4D ratios were associated with better sports and physical abilities. AIM: To assess whether a challenge condition, imposed by intense exercise, could increase handgrip strength (HGS) associated with 2D:4D. METHODS: This cross-sectional experimental study included 90 healthy young Polish adults (40 males, 50 females). They underwent intense physical exercise, before (7 days) and after which they were measured for HGS and 2D:4D. Height and weight were also measured. Analyses of Covariance were employed to delineate associations. RESULTS: 2D:4D had significant predictive effects on the differences in HGS (DHGS) measured in two occasions, without and after, physical exercises. The lower was the 2D:4D, the higher the DHGS, particularly, for the left hand. CONCLUSION: The results reconfirmed that the link between prenatal testosterone exposure (indicated by 2D:4D) and physical strength depends on the context, such as a challenged condition.

Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity.

BACKGROUND: Vascular smooth muscle cell (VSMC) phenotypic switching contributes to cardiovascular diseases. Epigenetic regulation is emerging as a key regulatory mechanism, with the methylcytosine dioxygenase TET2 acting as a master regulator of smooth muscle cell phenotype. The histone acetyl-transferases p300 and CREB-binding protein (CBP) are highly homologous and often considered to be interchangeable, and their roles in smooth muscle cell phenotypic regulation are not known. METHODS: We assessed the roles of p300 and CBP in human VSMC with knockdown, in inducible smooth muscle-specific knockout mice (inducible knockout [iKO]; p300iKO or CBPiKO), and in samples of human intimal hyperplasia. RESULTS: P300, CBP, and histone acetylation were differently regulated in VSMCs undergoing phenotypic switching and in vessel remodeling after vascular injury. Medial p300 expression and activity were repressed by injury, but CBP and histone acetylation were induced in neointima. Knockdown experiments revealed opposing effects of p300 and CBP in the VSMC phenotype: p300 promoted contractile protein expression and inhibited migration, but CBP inhibited contractile genes and enhanced migration. p300iKO mice exhibited severe intimal hyperplasia after arterial injury compared with controls, whereas CBPiKO mice were entirely protected. In normal aorta, p300iKO reduced, but CBPiKO enhanced, contractile protein expression and contractility compared with controls. Mechanistically, we found that these histone acetyl-transferases oppositely regulate histone acetylation, DNA hydroxymethylation, and PolII (RNA polymerase II) binding to promoters of differentiation-specific contractile genes. Our data indicate that p300 and TET2 function together, because p300 was required for TET2-dependent hydroxymethylation of contractile promoters, and TET2 was required for p300-dependent acetylation of these loci. TET2 coimmunoprecipitated with p300, and this interaction was enhanced by rapamycin but repressed by platelet-derived growth factor (PDGF) treatment, with p300 promoting TET2 protein stability. CBP did not associate with TET2, but instead facilitated recruitment of histone deacetylases (HDAC2, HDAC5) to contractile protein promoters. Furthermore, CBP inhibited TET2 mRNA levels. Immunostaining of cardiac allograft vasculopathy samples revealed that p300 expression is repressed but CBP is induced in human intimal hyperplasia. CONCLUSIONS: This work reveals that p300 and CBP serve nonredundant and opposing functions in VSMC phenotypic switching and coordinately regulate chromatin modifications through distinct functional interactions with TET2 or HDACs. Targeting specific histone acetyl-transferases may hold therapeutic promise for cardiovascular diseases.

Is 2D:4D digit ratio related to avowed religion? A study among Mongolian young males from Ulaanbaatar.

BACKGROUND: The ratio of the second- (2D) to fourth (4D) digit lengths of hand (2D:4D) is a proxy marker of the relative testosterone and estrogen concentration during a relatively narrow period of fetal development that might affect behavioral and personality characteristics. AIM: To estimate the differences in 2D:4D between different religious groups among a sample of young adult males in Mongolia. METHODS: Two hundred and sixty-five Mongolian male students with mean age of 20.5 (SD = 1.7) years from different universities in Ulan Bator, were included in the study. Information on age, religious affiliation, marital status and parental education were obtained directly from each study participant. Digit lengths were measured from scanned images by using the ImageJ software 1.53 K. One-way analysis of variance was employed to evaluate whether they were significant differences in 2D:4D ratio between groups, along with Scheffe's post hoc comparison. RESULTS: Study participants significantly differed in 2D:4D across religion. Left 2D:4D, but not the right, showed a significant difference between religions, with Muslims exhibiting the highest 2D:4D mean and the lowest DR-L . CONCLUSION: Our study suggests that the 2D:4D ratio is related to the participants' religion. However, the distinctiveness of the Muslim students from study participants belonging to other religious groups in this study could also be related to ethnic differences, given that the students were Kazakhs. This is, to our knowledge, the only study looking at the relationship between the 2D:4D ratio and religious affiliation and, thus, further research is needed to confirm its results.

Fine and gross motor skills in 7-10 years old Indian children exposed to a natural disaster during early development.

Fetal life and infancy are extremely sensitive to adverse environmental conditions. This study aimed to assess the effect of exposure to a natural disaster (cyclone Aila) in utero or during infancy on fine and gross motor functions in preadolescent Indian children. The study was conducted in West Bengal, India, and included approximately 700 children (7-10 years old) who were prenatally or postnatally exposed to cyclone Aila and a nonaffected group. Anthropometric measures included height, weight, and birthweight. Socioeconomic status was based on parental education, family size, and income. Motor functions were assessed using the short form of Bruininks-Oseretsky Test of Motor Proficiency (BOT-2). Statistical analyses included, for example, generalized linear models. There were no differences in motor functions relative to the timing of the exposure (trimester) during pregnancy. Compared to the controls, prenatal Aila exposure resulted in poorer performance in all BOT-2 subtests, except for fine motor precision, strength, and balance (the last in boys), while postnatal Aila exposure, compared to the controls, resulted in poorer performance in manual dexterity, bilateral coordination, balance (girls only), and speed and agility. Early life exposure to a natural disaster has long-term adverse effect on motor proficiency in children. By inference, the welfare of pregnant women and infants should be of particular concern for emergency and health services during an environmental cataclysm.

TET2 Protects Against Vascular Smooth Muscle Cell Apoptosis and Intimal Thickening in Transplant Vasculopathy.

BACKGROUND: Coronary allograft vasculopathy (CAV) is a devastating sequela of heart transplant in which arterial intimal thickening limits coronary blood flow. There are currently no targeted therapies to prevent or reduce this pathology that leads to transplant failure. Vascular smooth muscle cell (VSMC) phenotypic plasticity is critical in CAV neointima formation. TET2 (TET methylcytosine dioxygenase 2) is an important epigenetic regulator of VSMC phenotype, but the role of TET2 in the progression of CAV is unknown. METHODS: We assessed TET2 expression and activity in human CAV and renal transplant samples. We also used the sex-mismatched murine aortic graft model of graft arteriopathy (GA) in wild-type and inducible smooth muscle-specific Tet2 knockout mice; and in vitro studies in murine and human VSMCs using knockdown, overexpression, and transcriptomic approaches to assess the role of TET2 in VSMC responses to IFNγ (interferon γ), a cytokine elaborated by T cells that drives CAV progression. RESULTS: In the present study, we found that TET2 expression and activity are negatively regulated in human CAV and renal transplant samples and in the murine aortic graft model of GA. IFNγ was sufficient to repress TET2 and induce an activated VSMC phenotype in vitro. TET2 depletion mimicked the effects of IFNγ, and TET2 overexpression rescued IFNγ-induced dedifferentiation. VSMC-specific TET2 depletion in aortic grafts, and in the femoral wire restenosis model, resulted in increased VSMC apoptosis and medial thinning. In GA, this apoptosis was tightly correlated with proliferation. In vitro, TET2-deficient VSMCs undergo apoptosis more readily in response to IFNγ and expressed a signature of increased susceptibility to extrinsic apoptotic signaling. Enhancing TET2 enzymatic activity with high-dose ascorbic acid rescued the effect of GA-induced VSMC apoptosis and intimal thickening in a TET2-dependent manner. CONCLUSIONS: TET2 is repressed in CAV and GA, likely mediated by IFNγ. TET2 serves to protect VSMCs from apoptosis in the context of transplant vasculopathy or IFNγ stimulation. Promoting TET2 activity in vivo with systemic ascorbic acid reduces VSMC apoptosis and intimal thickening. These data suggest that promoting TET2 activity in CAV may be an effective strategy for limiting CAV progression.

Low-dose Aspirin prevents hypertension and cardiac fibrosis when thromboxane A2 is unrestrained.

Enhanced platelet activation has been reported in patients with essential hypertension and heart failure. The possible contribution of platelet-derived thromboxane (TX)A2 in their pathophysiology remains unclear. We investigated the systemic TXA2 biosynthesis in vivo and gene expression of its receptor TP in 22 essential hypertension patients and a mouse model of salt-sensitive hypertension. The contribution of platelet TXA2 biosynthesis on enhanced blood pressure (BP) and overload-induced cardiac fibrosis was explored in mice by treating with low-dose Aspirin, resulting in selective inhibition of platelet cyclooxygenase (COX)-1-dependent TXA2 generation. In essential hypertensive patients, systemic biosynthesis of TXA2 [assessed by measuring its urinary metabolites (TXM) reflecting predominant platelet source] was enhanced together with higher gene expression of circulating leukocyte TP and TGF-ß, vs. normotensive controls. Similarly, in hypertensive mice with prostacyclin (PGI2) receptor (IP) deletion (IPKO) fed with a high-salt diet, enhanced urinary TXM, and left ventricular TP overexpression were detected vs. normotensive wildtype (WT) mice. Increased cardiac collagen deposition and profibrotic gene expression (including TGF-ß) was found. Low-dose Aspirin administration caused a selective inhibition of platelet TXA2 biosynthesis and mitigated enhanced blood pressure, cardiac fibrosis, and left ventricular profibrotic gene expression in IPKO but not WT mice. Moreover, the number of myofibroblasts and extravasated platelets in the heart was reduced. In cocultures of human platelets and myofibroblasts, platelet TXA2 induced profibrotic gene expression, including TGF-ß1. In conclusion, our results support tailoring low-dose Aspirin treatment in hypertensive patients with unconstrained TXA2/TP pathway to reduce blood pressure and prevent early cardiac fibrosis.

Mother's education level is associated with anthropometric failure among 3- to 12-year-old rural children in Purba Medinipur, West Bengal, India.

Maternal education plays a central role in children's health and nutrition. Living conditions and socioeconomic status are linked with mother's education, which in turn determines the health and development of a child. The Composite Index of Anthropometric Failure (CIAF) is a single indicator that reflects overall rate of three conventional indices of undernutrition: underweight, stunting and wasting. The study was undertaken among 621 rural Bengalee children (308 boys and 313 girls) aged 3-12 years from the Purba Medinipur district of West Bengal, India. Height (cm) and weight (kg) were recorded and NCHS standard values used to calculate z-scores (<-2SD). The same data were used to calculate CIAF as an indicator of 'anthropometric failure' (AF) or undernutrition. The prevalence of AF among the children was 59.40%. Chi-squared analysis was employed to evaluate the significance of differences in the prevalence of CIAF between the sexes and the association between nutritional indicators and socioeconomic parameters in the two sexes. Multiple binary logistic regression (MBLR) analyses (including the forward stepwise method) were also performed. Odds ratios with 95% confidence intervals were used to assess the risk of having AF. Results showed that mother's education was significantly associated with undernutrition (AF) controlling for the other factors considered. A very high prevalence of undernutrition is persisting in this region of India despite national nutritional supplementation programmes being operational. More attention to the improvement of living conditions and hygiene, and more particularly the education of women, in this population might be effective in attaining improved child growth and health.

Nutritional and weight status of Indian mother-child dyads experienced by a natural disaster.

Natural disasters have detrimental effects not only on local infrastructure in an affected population but may also have an impact on the human biological condition, particularly during critical periods of life. This study aimed to assess the nutritional and weight status of women and their children who had experienced cyclone Aila prenatally and postnatally in comparison with a non-affected neighbouring group. The study sample involved N = 597 dyads consisting of mothers and their prepubertal children prenatally or postnatally (during infancy) exposed to a natural disaster and a control group from a neighbouring region (West Bengal, India). The analysed anthropometric indices involved body mass index (BMI) and mid-upper arm circumference (MUAC). Moreover, several socioeconomic characteristics were collected (mother's and father's education, family size and family income). Analyses revealed that the group factor (Aila-exposed or non-exposed groups) had the highest impact on both children's and their mothers' BMI and MUAC (p < 0.001) in comparison with socioeconomic variables. Surprisingly, both mothers and their children revealed deteriorated nutritional and relative weight status several years after the occurrence of cyclone Aila, which is in opposition to the results obtained in developed countries, where prenatal maternal stress caused by the natural disaster led to the subsequent higher risk of excessive weight in affected children.

Promoters to Study Vascular Smooth Muscle.

Smooth muscle cells (SMCs) are a critical component of blood vessel walls that provide structural support, regulate vascular tone, and allow for vascular remodeling. These cells also exhibit a remarkable plasticity that contributes to vascular growth and repair but also to cardiovascular pathologies, including atherosclerosis, intimal hyperplasia and restenosis, aneurysm, and transplant vasculopathy. Mouse models have been an important tool for the study of SMC functions. The development of smooth muscle-expressing Cre-driver lines has allowed for exciting discoveries, including recent advances revealing the diversity of phenotypes derived from mature SMC transdifferentiation in vivo using inducible CreER T2 lines. We review SMC-targeting Cre lines driven by the Myh11, Tagln, and Acta2 promoters, including important technical considerations associated with these models. Limitations that can complicate study of the vasculature include expression in visceral SMCs leading to confounding phenotypes, and expression in multiple nonsmooth muscle cell types, such as Acta2-Cre expression in myofibroblasts. Notably, the frequently employed Tagln/ SM22α- Cre driver expresses in the embryonic heart but can also confer expression in nonmuscular cells including perivascular adipocytes and their precursors, myeloid cells, and platelets, with important implications for interpretation of cardiovascular phenotypes. With new Cre-driver lines under development and the increasing use of fate mapping methods, we are entering an exciting new era in SMC research.

Determining a global mid-upper arm circumference cut-off to assess underweight in adults (men and non-pregnant women).

OBJECTIVE: To determine if a global mid-upper arm circumference (MUAC) cut-off can be established to classify underweight in adults (men and non-pregnant women). DESIGN: We conducted an individual participant data meta-analysis (IPDMA) to explore the sensitivity (SENS) and specificity (SPEC) of various MUAC cut-offs for identifying underweight among adults (defined as BMI < 18·5 kg/m2). Measures of diagnostic accuracy were determined every 0·5 cm across MUAC values from 19·0 to 26·5 cm. A bivariate random effects model was used to jointly estimate SENS and SPEC while accounting for heterogeneity between studies. Various subgroup analyses were performed. SETTING: Twenty datasets from Africa, South Asia, Southeast Asia, North America and South America were included. PARTICIPANTS: All eligible participants from the original datasets were included. RESULTS: The total sample size was 13 835. Mean age was 32·6 years and 65 % of participants were female. Mean MUAC was 25·7 cm, and 28 % of all participants had low BMI (<18·5 kg/m2). The area under the receiver operating characteristic curve for the pooled dataset was 0·91 (range across studies 0·61-0·98). Results showed that MUAC cut-offs in the range of ≤23·5 to ≤25·0 cm could serve as an appropriate screening indicator for underweight. CONCLUSIONS: MUAC is highly discriminatory in its ability to distinguish adults with BMI above and below 18·5 kg/m2. This IPDMA is the first step towards determining a global MUAC cut-off for adults. Validation studies are needed to determine whether the proposed MUAC cut-off of 24 cm is associated with poor functional outcomes.

SMAD4 Prevents Flow Induced Arteriovenous Malformations by Inhibiting Casein Kinase 2.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder that causes arteriovenous malformations (AVMs). Mutations in the genes encoding Endoglin ( ENG) and activin-receptor-like kinase 1 ( AVCRL1 encoding ALK1) cause HHT type 1 and 2, respectively. Mutations in the SMAD4 gene are present in families with juvenile polyposis-HHT syndrome that involves AVMs. SMAD4 is a downstream effector of transforming growth factor-ß (TGFß)/bone morphogenetic protein (BMP) family ligands that signal via activin-like kinase receptors (ALKs). Ligand-neutralizing antibodies or inducible, endothelial-specific Alk1 deletion induce AVMs in mouse models as a result of increased PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) signaling. Here we addressed if SMAD4 was required for BMP9-ALK1 effects on PI3K/AKT pathway activation. METHODS: The authors generated tamoxifen-inducible, postnatal, endothelial-specific Smad4 mutant mice ( Smad4iΔEC). RESULTS: We found that loss of endothelial Smad4 resulted in AVM formation and lethality. AVMs formed in regions with high blood flow in developing retinas and other tissues. Mechanistically, BMP9 signaling antagonized flow-induced AKT activation in an ALK1- and SMAD4-dependent manner. Smad4iΔEC endothelial cells in AVMs displayed increased PI3K/AKT signaling, and pharmacological PI3K inhibitors or endothelial Akt1 deletion both rescued AVM formation in Smad4iΔEC mice. BMP9-induced SMAD4 inhibited casein kinase 2 ( CK2) transcription, in turn limiting PTEN phosphorylation and AKT activation. Consequently, CK2 inhibition prevented AVM formation in Smad4iΔEC mice. CONCLUSIONS: Our study reveals SMAD4 as an essential effector of BMP9-10/ALK1 signaling that affects AVM pathogenesis via regulation of CK2 expression and PI3K/AKT1 activation.

The validity of mid-upper arm circumference as an indicator of low BMI in population screening for undernutrition: a study among adult slum dwellers in eastern India.

OBJECTIVE: To explore the possibility for a statistically appropriate value of mid-upper arm circumference (MUAC) to identify the state of severe undernutrition, based on very low BMI, among adult Indian slum dwellers. DESIGN: Cross-sectional study on adults. Height and MUAC were recorded and BMI was computed. Chronic energy deficiency (CED) was determined using the WHO international guidelines as BMI<18·5 kg/m2 and normal as BMI≥18·5 kg/m2. Besides calculating mean, sd and 25th, 50th and 75th percentile values, multiple linear regression analysis was undertaken to assess the associations between age, MUAC and BMI. Receiver-operating characteristic curve analysis was performed to determine the best MUAC cut-off to identify CED status. The χ 2 test was used to assess significance of the difference in CED prevalence across MUAC categories. SETTING: An urban slum in Midnapore town, West Bengal State, India. SUBJECTS: Male (n 467) and female (n 488) Indian slum dwellers. RESULTS: MUAC of 22·7 and 21·9 cm, respectively, in males and females were the best cut-off points to differentiate CED from non-CED. CONCLUSIONS: Results supported the validity of the WHO-recommended MUAC cut-offs for adults. There is still a need to establish statistically appropriate MUAC cut-offs to predict undernutrition and morbidity.

FURTHER EVIDENCE OF AN ASSOCIATION BETWEEN LOW SECOND-TO-FOURTH DIGIT RATIO (2D:4D) AND SELECTION FOR THE UNIFORMED SERVICES: A STUDY AMONG POLICE PERSONNEL IN WROCLAW, POLAND.

Males and females differ in their preference for occupations and sporting activities, and differ also in risk-taking attitudes. In addition to other explanations, prenatal hormone exposure has been implicated in these gender-associated differences. The ratio of the relative lengths of the second-to-fourth digits (2D:4D) is a proxy indicator of prenatal exposure to testosterone relative to oestrogen. The 2D:4D ratio has been found to be associated with choice of occupation, particularly among females. This study investigated whether 2D:4D differed between police officers and a control group of civilians in Wroclaw, Poland. Participants were 147 male and 55 female police officers and 91 male and 75 female civilian controls. The police officers had to undergo rigorous physical ability tests during recruitment and their job bore relatively higher risk, whereas the controls had a normal civilian lifestyle. Height, weight, hand grip strength and lengths of the second and fourth digits were measured. Analyses of variance and covariance were employed to assess the significance of difference in digit ratio between groups (police officers and civilians) allowing for interaction with sex. The policewomen, compared with the female controls, were taller and had stronger hand grip strength, but had lower 2D:4D in the right hand and average 2D:4D of both hands. However, male and female police officers slightly differed only in the right hand digit ratio but not in the left hand ratio or the average for the two hands. However, the control group showed significant sex differences in all digit ratios with higher (feminine) mean values in females. The study provides further evidence that prenatal testosterone exposure, as reflected in the 2D:4D ratio, might have an association with choice of occupation, particularly among females.

SPORTS PREFERENCE AND DIGIT RATIO (2D:4D) AMONG FEMALE STUDENTS IN WROCLAW, POLAND.

Humans exhibit sex differences in competitiveness, sensation seeking and risk-taking attitude, which are required in sports. These attributes are often linked to prenatal testosterone (PT) exposure. The second-to-fourth digit length ratio (2D:4D) is an indicator of PT exposure. A lower 2D:4D indicates higher PT exposure and vice versa. Males generally have a lower 2D:4D than females. Sensation- and/or thrill-seeking behaviours have also been found to be negatively associated with 2D:4D. Boxing and judo are considered to be high-risk sports. Voluntary participation in judo/boxing in contrast to aerobics can be guided by such behaviours and thus have an association with lower 2D:4D. This cross-sectional study included 167 female students from a military academy in Wroclaw, Poland. Of them, 119 had voluntarily chosen aerobic exercise, and 48 opted for judo/boxing. Height, weight and second and fourth digit lengths were measured. Physical fitness was assessed using Eurofit tests. The two groups showed similar physical fitness and body size. However, the judo/boxing group had significantly lower mean 2D:4D values than the aerobics group. It is proposed that voluntary choice of participation in a sport discipline by women could be linked to the 'organizational' effect of intrauterine testosterone exposure during prenatal growth.

Is Increased Facial Asymmetry Associated With The Use Of Hormonal Contraceptive Among Polish Young Women In Wroclaw?

Fluctuating asymmetry (FA) is the small random deviations from a perfect bilateral symmetry in a morphological trait. It is considered as an indicator of biological quality and developmental stability of individual. Adverse environmental conditions and high levels of sex steroids may increase FA. Symmetry in women was found to be related with phases of the menstrual cycles (MC). This cross sectional study aimed to compare facial symmetry between women using and not using hormonal contraceptives with reference to the phases of their fertile and non-fertile phases of MC. Participants were 150 young adult Polish female students in Wroclaw, Poland. Facial photograph of each woman was taken and information on the use of hormonal contraception, date of menarche, number of days past since the last menstruation (beginning of bleeding) were collected. Measurements of facial asymmetry were taken digitally in pixels on facial photographs by using ImageJ software. The results revealed that the women who used HC had a significantly higher total and central facial FA than those who did not use HC. However, the women in relatively non fertile phase did not demonstrate a difference in FA among the non-users of HC.

Physical Fitness And Digit Ratio (2D:4D) In Male Students From Wroclaw, Poland.

There is sex-difference in humans as regards aerobic efficiency, physical strength and endurance and the sex difference is greatly dependent upon differential concentration of testosterone during different phases of growth and development including the intrauterine phase or prenatal growth. Second-to-fourth digit lengths ratio (2D:4D) is an putative indicator of prenatal testosterone exposure. Lower 2D:4D indicates higher prenatal testosterone exposure and vice versa. Males generally have lower 2D:4D than females. This cross-sectional study investigated the relationship between the fitness measures and 2D:4D in young adult Polish males. The study included 118 Polish male students first course in General Kosciuszko Military Academy of Land Forces in Wroclaw. Their mean (+SD) age was 20.4 (+1.60) years. Eurofit test set was employed to assess physical fitness. Apart from height, weight, second and fourth digit lengths, hand grip strength was also measured by a standard isometric dynamometer. The study showed a weak relationship between 2D:4D of right hand and results of physical fitness tests. The smaller was the 2D:4D, the better was the result of endurance and strength tests. This finding was in accord with reports by other studies, indicating that individuals with smaller 2D:4D tend to perform better in these aspects of physical ability. However, we also found an opposite relationship with the results to agility tests. Male students with higher 2D:4D scored better in 5x10 meters shuttle run. This finding did not match with results reported by other studies. This study indicated towards possibility that an association between low 2D:4D and sport and athletic achievement and also physical performances were due to, at least in part, the action of prenatal testosterone. Further studies are required to investigate the relationship of fitness parameters with digit ratio and ultimately with prenatal testosterone exposure.