Application of a distinctly bent, trinuclear, end-to-end azide bridged, mixed valence cobalt(iii/ii/iii) complex in the fabrication of photosensitive Schottky barrier diodes.

A mixed-valence trinuclear cobalt(iii)-cobalt(ii)-cobalt(iii) complex, [(µ-1,3-N3)Co3L(N3)3]·MeOH has been synthesized using a tetradentate N2O2 donor 'reduced Schiff base' ligand, H2L {1,3-bis(2-hydroxybenzylamino)2,2-dimethylpropane} and azide as anionic co-ligand. The complex has been characterised by elemental analysis, IR, UV-vis spectroscopy and single-crystal X-ray diffraction studies etc. The cobalt(iii)-cobalt(ii)-cobalt(iii) skeleton in the complex is non-linear and non-centrosymmetric. The redox behavior of the complex was studied by using Cyclic Voltammetry (CV). The complex is found to be a semiconductor material as confirmed by determining the band gap of this complex by experimental as well as theoretical studies. The band gap in the solid state has been determined experimentally. The conductivity of the synthesized complex based device improves considerably in illumination conditions from the non-illuminated conditions. The complex has also been used to fabricate Schottky barrier diodes.

Formation of H-bonding networks in the solid state structure of a trinuclear cobalt(iii/ii/iii) complex with N2O2 donor Schiff base ligand and glutaric acid as bridging co-ligand: synthesis, structure and DFT study.

A trinuclear linear mixed-valence centrosymmetric cobalt(iii)-cobalt(ii)-cobalt(iii) complex, [CoII{(µ-L)(µ-Hglu)CoIII(OH2)}2](ClO4)2·6H2O has been synthesized during tetradentate N2O2 donor 'Schiff base' ligand, H2L {N,N'-bis(salicylidene)-1,3-diaminopropane} and glutaric acid (H2glu) as anionic co-ligand. The complex has been characterized by spectroscopic measurements and its solid state structure has been determined by single crystal X-ray diffraction analysis. The supra-molecular assembly formed by the hydrogen bonding interactions in the solid state of the complex has been analysed using DFT calculations.

Clinical evaluation of a low-coverage whole-genome test for detecting homologous recombination deficiency in ovarian cancer.

BACKGROUND: The PAOLA-1/ENGOT-ov25 trial showed that maintenance olaparib plus bevacizumab increases survival of advanced ovarian cancer patients with homologous recombination deficiency (HRD). However, decentralized solutions to test for HRD in clinical routine are scarce. The goal of this study was to retrospectively validate on tumor samples from the PAOLA-1 trial, the decentralized SeqOne assay, which relies on shallow Whole Genome Sequencing (sWGS) to capture genomic instability and targeted sequencing to determine BRCA status. METHODS: The study comprised 368 patients from the PAOLA-1 trial. The SeqOne assay was compared to the Myriad MyChoice HRD test (Myriad Genetics), and results were analyzed with respect to Progression-Free Survival (PFS). RESULTS: We found a 95% concordance between the HRD status of the two tests (95% Confidence Interval (CI); 92%-97%). The Positive Percentage Agreement (PPA) of the sWGS test was 95% (95% CI; 91%-97%) like its Negative Percentage Agreement (NPA) (95% CI; 89%-98%). In patients with HRD-positive tumors treated with olaparib plus bevacizumab, the PFS Hazard Ratio (HR) was 0.38 (95% CI; 0.26-0.54) with SeqOne assay and 0.32 (95% CI; 0.22-0.45) with the Myriad assay. In patients with HRD-negative tumors, HR was 0.99 (95% CI; 0.68-1.42) and 1.05 (95% CI; 0.70-1.57) with SeqOne and Myriad assays. Among patients with BRCA-wildtype tumors, those with HRD-positive tumors, benefited from olaparib plus bevacizumab maintenance, with HR of 0.48 (95% CI: 0.29-0.79) and of 0.38 (95% CI: 0.23 to 0.63) with the SeqOne and Myriad assay. CONCLUSION: The SeqOne assay offers a clinically validated approach to detect HRD.

Structure-directing role of CH⋯X (X = C, N, S, Cl) interactions in three ionic cobalt complexes: X-ray investigation and DFT study using QTAIM Vr predictor to eliminate the effect of pure Coulombic forces.

Three cobalt complexes, namely [CoIII(HL1)2(N3)2]ClO4 (1), [CoIII(L2)(HL2)(N3)]ClO4·1.5H2O (2), and [CoIII(L3)(HL3)(NCS)]2 [CoIICl2(NCS)2] (3), where HL1 = 2-(3-(dimethylamino)propyliminomethyl)-6-methoxyphenol, HL2 = 2-(2-(dimethylamino)ethyliminomethyl)-4,6-dichlorophenol, and HL3 = 2-(2-(dimethylamino)ethyliminomethyl)-6-methoxyphenol, as potential tridentate N2O-donor Schiff base ligands, were synthesized and characterized using elemental analysis, IR and UV-vis spectroscopy, and single-crystal X-ray diffraction studies. All three were found to be monomeric ionic complexes. Complex 1 crystallizes in the orthorhombic space group Pbcn, whereas both complexes 2 and 3 crystallize in triclinic space groups, P1̄. Further, 1 and 2 are cationic complexes of octahedral cobalt(iii) with perchlorate anions, whereas complex 3 contains a cationic part of octahedral cobalt(iii) and an anionic part of tetrahedral cobalt(ii). Hydrogen-bonding interactions involving aromatic and aliphatic CH bonds as H-bond donors and the pseudo-halide co-ligands as H-bond acceptors were established, which are important aspects governing the X-ray packing. These interactions were analyzed theoretically using the quantum theory of atoms in molecules (QTAIM) and non-covalent interaction plot (NCI plot) analyses. Moreover, energy decomposition analysis (EDA) was performed to analyze the stabilization of the complexes in terms of the electrostatic, dispersion, and correlation forces.

Short tandem repeats bind transcription factors to tune eukaryotic gene expression.

Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)-DNA affinities and apparent on-rates by about 70-fold by directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. STRs maximize the number of weakly preferred microstates near target sites, thereby increasing TF density, with impacts well predicted by statistical mechanics. Confirming that STRs also affect TF binding in cells, neural networks trained only on in vivo occupancies predicted effects identical to those observed in vitro. Approximately 90% of TFs preferentially bound STRs that need not resemble known motifs, providing a cis-regulatory mechanism to target TFs to genomic sites.

An insight into the hydrogen bonding, halogen bonding and chalcogen bonding interactions in manganese(iii) complexes with N2O2donor salicylidine Schiff base ligands.

Four manganese(iii) complexes, [MnL1(H2O)2]ClO4·H2O (1), [MnL2(H2O)2]ClO4 (2), [MnL3(DMSO)(H2O)]ClO4 (3) and [MnL4(DMSO)(H2O)]ClO4 (4), where H2L1 = N,N'-bis(5-bromosalicylidene)-1,3-diaminopropane, H2L2 = 2,2-dimethyl-N,N-bis(3-methyloxysalicylidene)-1,3-diaminopropane, H2L3 = N,N'-bis(5-chlorosalicylidene)-2,2-dimethyl-1,3-diaminopropane and H2L4 = 2-hydroxy-N,N'-bis(3-ethyloxysalicylidene)-1,3-diaminopropane are tetradentate N2O2-donor ligands and DMSO = dimethyl sulfoxide, have been synthesized and characterised by elemental analysis, IR and UV-vis spectroscopy and single-crystal X-ray diffraction studies. All are monomeric complexes. Complex 1 crystallises in orthorhombic space group P212121, complex 3 crystallises in triclinic space group P-1, whereas complexes 2 and 4 crystallize in monoclinic space groups, C2/c and C2/m respectively. In all the complexes, manganese(iii) has a six-coordinated pseudo-octahedral geometry in which imine nitrogen atoms and phenolate oxygen atoms of the deprotonated di-Schiff base constitute the equatorial plane. In complexes 1 and 2, water molecules are present in the fifth and sixth coordination sites in the axial positions while in complexes 3 and 4 they are occupied by one water and one DMSO. The coordinated water molecules initiate hydrogen-bonded networks in all complexes. DFT calculations have been carried out to analyze two aspects of these complexes viz. the formation of halogen (HaB) and chalcogen bonding (ChB) interactions in complexes 1 and 3 where the electron donor is the perchlorate anion and the acceptor either bromine or chlorine atoms for the HaBs and the sulfur atom of the coordinated DMSO for the ChB. In addition, other intermolecular effects are discussed in the solid state for complexes 1, 2 and 4, where the hydrogen atoms of the coordinated water molecules interact with the electron rich cavities formed by the phenolate and alkyloxy oxygen atoms of the Schiff-base ligand.

More efficient and inclusive time-to-event trials with covariate adjustment: a simulation study.

Adjustment for prognostic covariates increases the statistical power of randomized trials. The factors influencing the increase of power are well-known for trials with continuous outcomes. Here, we study which factors influence power and sample size requirements in time-to-event trials. We consider both parametric simulations and simulations derived from the Cancer Genome Atlas (TCGA) cohort of hepatocellular carcinoma (HCC) patients to assess how sample size requirements are reduced with covariate adjustment. Simulations demonstrate that the benefit of covariate adjustment increases with the prognostic performance of the adjustment covariate (C-index) and with the cumulative incidence of the event in the trial. For a covariate that has an intermediate prognostic performance (C-index=0.65), the reduction of sample size varies from 3.1% when cumulative incidence is of 10% to 29.1% when the cumulative incidence is of 90%. Broadening eligibility criteria usually reduces statistical power while our simulations show that it can be maintained with adequate covariate adjustment. In a simulation of adjuvant trials in HCC, we find that the number of patients screened for eligibility can be divided by 2.4 when broadening eligibility criteria. Last, we find that the Cox-Snell [Formula: see text] is a conservative estimation of the reduction in sample size requirements provided by covariate adjustment. Overall, more systematic adjustment for prognostic covariates leads to more efficient and inclusive clinical trials especially when cumulative incidence is large as in metastatic and advanced cancers. Code and results are available at https://github.com/owkin/CovadjustSim .

DOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal.

Mechanisms by which specific histone modifications regulate distinct gene networks remain little understood. We investigated how H3K79me2, a modification catalyzed by DOT1L and previously considered a general transcriptional activation mark, regulates gene expression during cardiogenesis. Embryonic cardiomyocyte ablation of Dot1l revealed that H3K79me2 does not act as a general transcriptional activator, but rather regulates highly specific transcriptional networks at two critical cardiogenic junctures: embryonic cardiogenesis, where it was particularly important for left ventricle-specific genes, and postnatal cardiomyocyte cell cycle withdrawal, with Dot1L mutants having more mononuclear cardiomyocytes and prolonged cardiomyocyte cell cycle activity. Mechanistic analyses revealed that H3K79me2 in two distinct domains, gene bodies and regulatory elements, synergized to promote expression of genes activated by DOT1L. Surprisingly, H3K79me2 in specific regulatory elements also contributed to silencing genes usually not expressed in cardiomyocytes. These results reveal mechanisms by which DOT1L successively regulates left ventricle specification and cardiomyocyte cell cycle withdrawal.

External control arm analysis: an evaluation of propensity score approaches, G-computation, and doubly debiased machine learning.

BACKGROUND: An external control arm is a cohort of control patients that are collected from data external to a single-arm trial. To provide an unbiased estimation of efficacy, the clinical profiles of patients from single and external arms should be aligned, typically using propensity score approaches. There are alternative approaches to infer efficacy based on comparisons between outcomes of single-arm patients and machine-learning predictions of control patient outcomes. These methods include G-computation and Doubly Debiased Machine Learning (DDML) and their evaluation for External Control Arms (ECA) analysis is insufficient. METHODS: We consider both numerical simulations and a trial replication procedure to evaluate the different statistical approaches: propensity score matching, Inverse Probability of Treatment Weighting (IPTW), G-computation, and DDML. The replication study relies on five type 2 diabetes randomized clinical trials granted by the Yale University Open Data Access (YODA) project. From the pool of five trials, observational experiments are artificially built by replacing a control arm from one trial by an arm originating from another trial and containing similarly-treated patients. RESULTS: Among the different statistical approaches, numerical simulations show that DDML has the smallest bias followed by G-computation. In terms of mean squared error, G-computation usually minimizes mean squared error. Compared to other methods, DDML has varying Mean Squared Error performances that improves with increasing sample sizes. For hypothesis testing, all methods control type I error and DDML is the most conservative. G-computation is the best method in terms of statistical power, and DDML has comparable power at [Formula: see text] but inferior ones for smaller sample sizes. The replication procedure also indicates that G-computation minimizes mean squared error whereas DDML has intermediate performances in between G-computation and propensity score approaches. The confidence intervals of G-computation are the narrowest whereas confidence intervals obtained with DDML are the widest for small sample sizes, which confirms its conservative nature. CONCLUSIONS: For external control arm analyses, methods based on outcome prediction models can reduce estimation error and increase statistical power compared to propensity score approaches.

Homoleptic Ni(II) dithiocarbamate complexes as pre-catalysts for the electrocatalytic oxygen evolution reaction.

Four new functionalized Ni(II) dithiocarbamate complexes of the formula [Ni(Lx)2] (1-4) (L1 = N-methylthiophene-N-3-pyridylmethyl dithiocarbamate, L2 = N-methylthiophene-N-4-pyridylmethyl dithiocarbamate, L3 = N-benzyl-N-3-pyridylmethyl dithiocarbamate, and L4 = N-benzyl-N-4-pyridylmethyl dithiocarbamate) have been synthesized and characterized by IR, UV-vis, and 1H and 13C{1H} NMR spectroscopic techniques. The solid-state structure of complex 1 has also been determined by single crystal X-ray crystallography. Single crystal X-ray analysis revealed a monomeric centrosymmetric structure for complex 1 in which two dithiocarbamate ligands are bonded to the Ni(II) metal ion in a S^S chelating mode resulting in a square planar geometry around the nickel center. These complexes are immobilized on activated carbon cloth (CC) and their electrocatalytic performances for the oxygen evolution reaction (OER) have been investigated in aqueous alkaline solution. All the complexes act as pre-catalysts for the OER and undergo electrochemical anodic activation to form Ni(O)OH active catalysts. Spectroscopic and electrochemical characterization revealed the existence of the interface of molecular complex/Ni(O)OH, which acts as the real catalyst for the OER. The active catalyst obtained from complex 2 showed the best OER activity achieving 10 mA cm-2 current density at an overpotential of 330 mV in 1.0 M aqueous KOH solution.

Insights into the transformation of VO2+ motif to VO3+, V2O34+ and VO2+ motifs and their interconversion along with a detailed mechanistic study of their anti-cancer activity in SiHa cervical cancer cells.

The basic criteria for the formation of complexes with VO3+, V2O34+ and VO2+ motifs from the VO2+ motif and their interconversion were explored utilizing two multidentate O,N-donor hydrazone ligands namely, E-2-Hydroxy-N'-(4-oxopentan-2-ylidine)benzohydrazide (H3L1) and E-2-Hydroxy-N'-(4-oxo-4-phenylbutan-2-ylidine)benzohydrazide (H3L2), derived from the condensation of 2-hydroxybenzoylhydrazide with acetylacetone and benzoylacetone respectively. Under aerobic condition, the possibility of forming complexes with different motifs in different solvents with varying pH was examined theoretically by computational methods with results that were verified experimentally. This study reveals that under aerobic condition, complexes with VO3+ (1,2) and V2O34+ (3, 4) motifs were formed in protic CH3OH and neutral CHCl3 solvent respectively while the formation of complexes (5-14) with VO2+ motif required protic CH3OH solvent and higher pH (≥ 7). Interconversion of VO3+, V2O34+ and VO2+ motifs are associated with specific acid-base equilibria, substantiated by 51V NMR titrations. Complexes containing these three motifs exhibited promising in vitro anticancer activity in SiHa cervical cancer cells without affecting healthy cells; among them complexes (5-14) with VO2+ motif are more potent. A detailed systematic mechanistic study was carried out, utilizing the two most potent complexes 5 and 6 (IC50 = 13, 6 µM respectively), which indicates that cytotoxicity and anti-proliferative activity of these complexes are manifested through oxidative stress induced apoptotic pathways (caspase mediated).

A Quinoxaline-Naphthaldehyde Conjugate for Colorimetric Determination of Copper Ion.

This work facilitates detection of bivalent copper ion by a simple Schiff base probe QNH based on a quinoxaline-naphthaldehyde framework. The detailed study in absorption spectroscopy and theoretical aspects and crystal study of the probe and probe-copper complex has been discussed. The detection limit of the probe in the presence of Cu2+ is 0.45 µM in HEPES-buffer/acetonitrile (3/7, v/v) medium for absorption study. The reversibility of the probe-copper complex has been investigated by EDTA. The selective visual detection of copper has been established also in gel form.

A family of amphiphilic dioxidovanadium(V) hydrazone complexes as potent carbonic anhydrase inhibitors along with anti-diabetic and cytotoxic activities.

A family of dioxidovanadium(V) complexes (1-4) of the type [Na(H2O)x]+[VVO2(HL1-4)]- (x = 4, 4.5 and 7) where HL2- represents the dianionic form of 2-hydroxybenzoylhydrazone of 2-hydroxyacetophenone (H2L1, complex 1), 2-hydroxy-5-methylacetophenone (H2L2, complex 2), 2-hydroxy-5-methoxyacetophenone (H2L3, complex 3) and 2-hydroxy-5-chloroacetophenone (H2L4, complex 4), have been synthesized and characterized by analytical and spectral methods. These complexes exhibited the potential abilities to suppress the erythrocytes carbonic anhydrase enzymatic activity in type 1 and type 2 diabetic patients (in vitro), promising antidiabetic activity against T2 diabetic mice (in vivo). They also exhibited significant cytotoxic activity against cervical cancer (SiHa) cells (in vitro) as the IC50 value of complexes 1, 2 and 4 is substantially lower than the value found for cisplatin while that of 3 is comparable and follow the order: 4 < 1 < 2 < 3 and can kill the cells by apoptosis via the generation of reactive oxygen species (ROS). The complexes are soluble both in water and octanol media and also non-toxic at working concentrations. The antidiabetic activity of these four complexes follows the order: 4 > 2 > 1 > 3 while both the carbonic anhydrase and cytotoxic activity follow the order: 4 > 1 > 2 > 3 suggesting that complex 4, containing electron withdrawing Cl atom is the most reactive while 3 with electron donating OCH3 group is the least reactive species. The molecular docking study on hCA-I and hCA-II demonstrates that complexes interact via hydrogen bonding as well as different types of π-stacking.

Strategic Substitution of -OH/-NR2 (R=Et, Me) Imparts Colorimetric Switching between F- and Hg2+ by Salicyaldehyde/Benzaldehyde-Quinoxaline Conjugates.

We herein report two salicyaldehyde-quinoxaline (HQS and HQSN) conjugates and a benzaldehyde-quinoxaline (QBN) conjugate to fabricate selective chemosensors for F- and Hg2+ in the micromolar range. This work demonstrates how sensing outcomes are affected by modulating proton acidity by introducing an electron donating group, -NEt2 , in the probe backbone. Interestingly, the un-substituted probe HQS can selectively detect F- , whereas HQSN and QBN are selective for Hg2+ . In order to gain insights into the mechanism of sensing, geometry optimizations have been carried out on QS(-1) , QS(-1) ⋅⋅⋅HF, QSN(-1) and QSN(-1) ⋅⋅⋅HF and the experimental data are validated in terms of free energy and pKa values. Detailed DFT and TD-DFT analyses provide ample support towards the mechanism of sensing of the analytes.

Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium.

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151-171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389-407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227-3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE-Bruch's membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE-BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD.

Ferrocene-Functionalized Dithiocarbamate Zinc(II) Complexes as Efficient Bifunctional Catalysts for the One-Pot Synthesis of Chromene and Imidazopyrimidine Derivatives via Knoevenagel Condensation Reaction.

Four new mononuclear/coordination polymeric (CP) zinc(II) complexes (1-4) of ferrocenyl/pyridyl-functionalized dithiocarbamate ligands, N-ferrocenylmethyl-N-butyl dithiocarbamate (L1), N-ferrocenylmethyl-N-ethylmorpholine dithiocarbamate (L2), N-ferrocenylmethyl-N-2-(diethylamino)ethylamine dithiocarbamate (L3), and N-4-methoxybenzyl-N-3-methylpyridyl dithiocarbamate (L4), have been synthesized and characterized by elemental analyses, IR, UV-vis, and 1H and 13C{1H} NMR spectroscopic techniques. The solid-state structures of complexes 1, 3, and 4 have been determined by single-crystal X-ray crystallography as well as powder X-ray diffraction. Single-crystal X-ray crystallography revealed a monomeric structure for complex 1 but 1D polymeric structures for complexes 3 and 4. In all complexes, dithiocarbamate ligands are bonded to the Zn(II) metal ion in a S^S chelating mode, and in the CPs, N atoms on the 2-(diethylamino)ethylamine and 3-pyridyl functionalities in the ligands on the neighboring molecules are also bonded to metal centers, leading to the formation of either a discrete tetrahedral molecule in 1 or 1D CP structures in 3 and 4. The Zn(II) metal centers in the polymeric structures exhibited either square-pyramidal or octahedral geometries. The supramolecular structures in these complexes are sustained via C-H···π (ZnCS2, chelate; 3 and 4), C-H···π, and H···H interactions. The catalytic performances of complexes have also been assessed in the Knoevenagel condensation and one-pot multicomponent reactions. Catalysis results showed that the CP 3 acts as a heterogeneous bifunctional catalyst with excellent transformation efficiency at low catalyst loading.

Integrating deep learning CT-scan model, biological and clinical variables to predict severity of COVID-19 patients.

The SARS-COV-2 pandemic has put pressure on intensive care units, so that identifying predictors of disease severity is a priority. We collect 58 clinical and biological variables, and chest CT scan data, from 1003 coronavirus-infected patients from two French hospitals. We train a deep learning model based on CT scans to predict severity. We then construct the multimodal AI-severity score that includes 5 clinical and biological variables (age, sex, oxygenation, urea, platelet) in addition to the deep learning model. We show that neural network analysis of CT-scans brings unique prognosis information, although it is correlated with other markers of severity (oxygenation, LDH, and CRP) explaining the measurable but limited 0.03 increase of AUC obtained when adding CT-scan information to clinical variables. Here, we show that when comparing AI-severity with 11 existing severity scores, we find significantly improved prognosis performance; AI-severity can therefore rapidly become a reference scoring approach.

Taste perception and lifestyle: insights from phenotype and genome data among Africans and Asians.

Taste is essential for the interaction of animals with their food and has co-evolved with diet. Humans have peopled a large range of environments and present a wide range of diets, but little is known about the diversity and evolution of human taste perception. We measured taste recognition thresholds across populations differing in lifestyles (hunter gatherers and farmers from Central Africa, nomad herders, and farmers from Central Asia). We also generated genome-wide genotype data and performed association studies and selection scans in order to link the phenotypic variation in taste sensitivity with genetic variation. We found that hunter gatherers have lower overall sensitivity as well as lower sensitivity to quinine and fructose than their farming neighbors. In parallel, there is strong population divergence in genes associated with tongue morphogenesis and genes involved in the transduction pathway of taste signals in the African populations. We find signals of recent selection in bitter taste-receptor genes for all four populations. Enrichment analysis on association scans for the various tastes confirmed already documented associations and revealed novel GO terms that are good candidates for being involved in taste perception. Our framework permitted us to gain insight into the genetic basis of taste sensitivity variation across populations and lifestyles.