By using Red/ET recombineering, the phenalinolactone pathway was reconstituted from two cosmids and heterologously expressed in several Streptomyces strains. The established expression system now provides buy AR-13324 a convenient platform for functional investigations of

the biosynthetic genes and the generation of novel analogues, by genetic engineering of the pathway in Escherichia coli. Deletion of a modifying gene from the expression construct resulted in a novel, unglycosylated phenalinolactone derivative; this demonstrates the promise of this methodology.”
“Cardiovascular diseases are major causes of mortality and disease in the Indian subcontinent, causing more than 25% of deaths. It has been predicted that these diseases will increase rapidly in India and this country will be host to more than half the cases of heart disease in the world within the next 15 years. Coronary heart disease and stroke have increased in both urban and rural areas. Case-control studies indicate that tobacco use, obesity with high waist: hip ratio, high blood pressure, high LDL cholesterol, low HDL cholesterol, abnormal apolipoprotein A-1:B ratio, diabetes, low consumption of fruits and vegetables, sedentary lifestyles and psychosocial https://www.selleckchem.com/products/ganetespib-sta-9090.html stress are important determinants of cardiovascular

diseases in India. These risk factors have increased substantially over the past 50 years and to control further escalation it is important to prevent them. National interventions such as increasing tobacco taxes, labelling unhealthy foods and trans fats, reduction of salt in processed foods and better urban design to promote physical activity may have a wide short-term impact.”
“Many human syndromes

involve a loss of imprinting (LOI) due to a loss (LOM) or a gain of DNA methylation (GOM). Most LOI occur as mosaics and can therefore be difficult to detect with conventional methods. The human imprinted 11p15 region is crucial for the control of fetal growth, and LOI at this locus is associated with two clinical disorders with opposite phenotypes: Beckwith-Wiedemann syndrome (BWS), characterized by fetal overgrowth and a high risk of tumors, and Russell-Silver syndrome (RSS), characterized by intrauterine and postnatal growth restriction. Until recently, we have been using www.selleckchem.com/products/mk-5108-vx-689.html Southern blotting for the diagnosis of RSS and BWS. We describe here a powerful quantitative technique, allele-specific methylated multiplex real-time quantitative PCR (ASMM RTQ-PCR), for the diagnosis of these two complex disorders. We first checked the specificity of the probes and primers used for ASMM RTQ-PCR. We then carried out statistical validation for this method, on both retrospective and prospective populations of patients. This analysis demonstrated that ASMM RTQ-PCR is more sensitive than Southern blotting for detecting low degree of LOI. Moreover, ASMM RTQ-PCR is a very rapid, reliable, simple, safe, and cost effective method. Hum Mutat 32:249-258, 2011. (C) 2011 Wiley-Liss, Inc.

This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (>100 LD50) of Bacillus anthracis (Ames) spores immediately following exposure through 36 h. The primary goal of collecting the data was to support investigators in developing computational models of inhalational anthrax disease. Rabbits were vaccinated prior to exposure with the human vaccine (Anthrax Vaccine Adsorbed, AVA) or were sham-vaccinated, and were then exposed in pairs (one sham and one AVA) so check details disease kinetics could be characterized in equally-dosed

hosts where one group is fully protected and is able to clear the infection (AVA-vaccinated), while the other is susceptible to disease, in which case the bacteria are able to escape containment and replicate learn more uncontrolled (sham-vaccinated rabbits).

Between 4-5% of the presented aerosol dose was retained in the lung of sham- and AVA-vaccinated rabbits as measured by dilution plate analysis of homogenized lung tissue or bronchoalveolar lavage (BAL) fluid. After 6 and 36 h, >80% and >96%, respectively, of the deposited spores were no longer detected in BAL, with no detectable difference between sham- or AVA-vaccinated rabbits. Thereafter, differences between the two groups became find protocol noticeable. In sham-vaccinated rabbits the bacteria were detected in the tracheobronchial lymph nodes (TBLN) 12 h post-exposure and in the circulation at 24 h, a time point which was

also associated with dramatic increases in vegetative CFU in the lung tissue of some animals. In all sham-vaccinated rabbits, bacteria increased in both TBLN and blood through 36 h at which point in time some rabbits succumbed to disease. In contrast, AVA-vaccinated rabbits showed small numbers of CFU in TBLN between 24 and 36 h post-exposure with small numbers of bacteria in the circulation only at 24 h post-exposure. These results characterize and quantify disease progression in naive rabbits following aerosol administration of Ames spores which may be useful in a number of different research applications, including developing quantitative models of infection for use in human inhalational anthrax risk assessment.”
“This paper draws together contributions to a scientific table discussion on obesity at the European Science Open Forum 2008 which took place in Barcelona, Spain. Socioeconomic dimensions of global obesity, including those factors promoting it, those surrounding the social perceptions of obesity and those related to integral public health solutions, are discussed. It argues that although scientific accounts of obesity point to large-scale changes in dietary and physical environments, media representations of obesity, which context public policy, pre-eminently follow individualistic models of explanation.

It might also act as a promising target for both prognostic prediction and therapeutics.”
“The ryanodine receptor (RyR) is a large,

intracellular calcium (Ca2+) channel that is associated with several accessory proteins and is an important component of a cell’s ability to respond to changes in the environment. Three isoforms of the RyR exist and are well documented for skeletal and cardiac muscle and the brain, but the isoforms in non-excitable cells are poorly understood. The aggressiveness of breast cancers in women has been positively correlated with the expression of the RyR in breast tumor tissue, but it is unknown if this is limited to specific isoforms. Identification SHP099 in vivo and characterization of RyRs in cancer models is important in understanding the role of the RyR channel complex in cancer and as a potential therapeutic target. The objective of this report was to identify the RyR isoforms expressed in widely used prostate cancer cell lines, DU-145 and IPI-145 molecular weight LNCaP, and the non-tumorigenic prostate cell line, PWR-1E. Oligonucleotide primers specific for each isoform were used in semi-quantitative and real-time PCR to determine the identification and expression levels of the RyR isoforms. RyR1 was expressed in the highest amount in DU-145 tumor cells, expression was 0.48-fold in the non-tumor

cell line PWR-1E compared to DU-145 cells, and no expression was observed buy GSK1838705A in LNCaP tumor cells. DU-145 cells had the lowest expression of RyR2. The expression was 26- and 15-fold higher in LNCaP and PWR-1E cells, respectively. RyR3 expression was not observed in any of the cell lines. All cell types released Ca2+ in response to caffeine showing they had functional RyRs. Total cellular RyR-associated Ca2+ release is determined by both the number of activated RyRs and its accessory proteins which modulate the receptor. Our results suggest

that the correlation between the expression of the RyR and tumor aggression is not related to specific RyR isoforms, but may be related to the activity and number of receptors. (c) 2012 Elsevier Inc. All rights reserved.”
“Thrombin generates fibrin and activates platelets and endothelium, causing thrombosis and inflammation. Endothelial thrombomodulin (TM) changes thrombin’s substrate specificity toward cleavage of plasma protein C into activated protein C (APC), which opposes its thrombotic and inflammatory activities. Endogenous TM activity is suppressed in pathologic conditions, and antithrombotic interventions involving soluble TM are limited by rapid blood clearance. To overcome this problem, we fused TM with a single chain fragment (scFv) of an antibody targeted to red blood cells.

Patients that demonstrate CI will be randomized to program their rate-adaptive sensors to either MV or XL in a 1:1 ratio. The rate-adaptive sensor will be optimized for each patient using a short walk to determine the appropriate response factor. At a 2-month visit, patients will complete a CPX test with the rate-adaptive sensors in their randomized setting.”
“This article describes the use of Amberlite IRA-910 with different counter ions as excellent polymer-supported reagents in nucleophilic substitution JNJ-26481585 ic50 reactions. The versatility of this protocol allowed the synthesis of a diversified

library of phenacyl derivatives with high yields. The polymeric reagents can be reloaded several times with no loss of their efficiency.”
“The Northwest Atlantic bamboo worm Clymenella torquata, believed to have been imported with commercial oyster culture, was last formally reported from the American Pacific coast

more than 30 years ago from a single location. We report here that it is broadly distributed in British Columbia and is now established in Washington. In Samish Bay, Washington, this tubiculous infaunal worm creates a spongy, porous substrate that has proved detrimental to commercial oyster Selleck SCH727965 farms by causing the oysters to sink into the sediment and suffocate. Little is known about the ecological or economic impacts of this invasion in the Pacific Northwest.”
“Background and objective: Pulmonary embolism (PE) is a common LOXO-101 disease with variable symptoms and high overall mortality. The clinical relevance of the extent of PE is still debatable, and the role of anticoagulation in patients with subsegmental involvement has been contested. Our objective is to describe the clinical details of patients with PE in our hospital and to analyze their prognosis based on the extent of the disease. Materials and methods: Retrospective study of 313 patients diagnosed with PE by chest computed tomography (CT) scan at the Hospital Complex of Pontevedra in Spain

for six years. Predictors of mortality were determined by multivariate analysis. Results: Women accounted for 56% of patients, and patient median age was 70 years (interquartile range 53-78 years). Subsegmental PE accounted for 7% of all cases; these patients were younger and had lower comorbidity; they reported chest pain more often, performed better in blood gas analysis and none of them had proximal deep vein thrombosis (DVT). Patients with subsegmental PE had a higher survival rate. Factors independently associated with mortality were cancer diagnosis and higher comorbidity. Conclusions: Patients with subsegmental PE clinically differ from those with more proximal PE. Underlying diseases have more influence on the prognosis than the extent of the disease. (C) 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved.

campbellii (n = 3), and V

parahaemolyticus selleck compound (n = 1) were capable of growing six successive times in nitrogen-free medium and some of them showed strong nitrogenase activity by means of the acetylene reduction assay (ARA). It was concluded that nitrogen fixation is a common phenotypic trait among Vibrio species of the core group. The fact that different Vibrio species can fix N, might explain why they are so abundant in the mucus of different coral species. (C) 2008 Published by Elsevier GmbH.”
“Asthma is a disease of the airways in which several cytokines such as interleukin (IL)-4, IL-5, IL-13 and tumor necrosis factor-alpha (TNF alpha) play a major role in the development and progression of inflammation, airway hyperresponsiveness, mucus production, and airway remodeling.\n\nThe conventional anti-inflammatory therapies, represented

by inhaled corticosteroids and antileukotrienes, are not always able to provide optimal disease control and it is therefore hoped that cytokine antagonists could achieve this goal in such situations. Anticytokine therapies have been tested in preclinical this website studies and some have entered clinical trials. Anti-IL-4 therapies have been tested in animal models of allergy-related asthma, but because of unclear efficacy their development was discontinued. However, IL-4/IL-13 dual antagonists and IL-13-specific blocking agents are more promising, as they exhibit more sustained anti-inflammatory effects. IL-5 antagonists have been found to be of limited efficacy in clinical studies but might be useful in conditions characterized by severe hypereosinophilia, and in which asthma is one of the disease manifestations. Unlike other chronic inflammatory conditions, such as rheumatoid arthritis, the use of anti-TNF alpha therapies in asthma might be limited by the unfavorable risk/benefit ratio associated with long-term use. The identification PP2 of so-called asthma TNF alpha phenotypes and perhaps the use of a less aggressive treatment regimen might address this important aspect. Other

cytokine antagonists (for example for IL-9 or IL-25) are currently being evaluated in the asthma setting, and could open new therapeutic perspectives based on their efficacy and safety.”
“Background: The doctor’s ability to communicate effectively (with patients, relatives, advocates and healthcare colleagues) relates directly to health outcomes, and so is core to clinical practice. The remediation of medical students’ clinical communication ability is rarely addressed in medical education literature. There is nothing in the current literature reporting a contemporary national picture of how communication difficulties are managed, and the level of consequence (progression implications) for students of performing poorly. This survey aimed to consolidate practices for identifying and processes for managing students who ‘fail’ communication assessments across all UK medical schools.

Both the anthracene and polyamine components of the conjugates play a role in their antiplasmodial effect.”
“We study the effect of limited heat-induced aggregation of BSA on structure development in the water-gelatin-thermally aggregated BSA (BSA(TA)) system. The pH is set at 5.4 and the temperature is higher than the conformation transition temperature of gelatin, but lower than the denaturation temperature of BSA. Dynamic light scattering, check details circular dichroism,

and fluorescence measurements are used to monitor structure changes. Interaction of gelatin with BSA(TA) leads to formation of large complex particles with an average radius similar to 1500 nm. BSA-gelatin complex formation accompanies partial destabilization of the secondary and tertiary structures of BSA and an additional exposure of hydrophobic tryptophan residues on the surface of the globule. It is shown that electrostatic interaction of the oppositely charged groups of BSA(TA) and gelatin is responsible for formation of such complex particles, whereas the secondary forces (hydrophobic interaction and hydrogen bonds) play an important role in stabilization of the complex particles. The zeta potentials of the native and the thermally aggregated BSA

samples were determined, and the solvent quality has been quantified by determining the activity of the protein samples in their saturated solutions. It was shown that steric reasons (large size of the thermally aggregated BSA(TA) particles), and uncomplete charge compensation small molecule library screening of the positively charged gelatin molecules by the negatively charged BSA(TA) particles are the main factors in determining structure formation, while the levels of the activity of the native BSA and BSA(TA) have a smaller effect on the structure of complex. (c) 2012 Elsevier B.V. All CX-6258 cost rights reserved.”
“Objective: Sexual dimorphism in the degree of high blood pressure (BP) has been observed in both animal and human hypertension. However, the mechanisms are still

poorly understood. We tested the hypothesis that long-term loss of sex steroids promotes changes in mesenteric vascular reactivity that impact the maintenance of hypertension in the spontaneously hypertensive rats (SHR).\n\nMethods: Male SHR were sham operated (M-SHAM) or castrated (M-CX), and female SHR were sham-operated (F-SHAM) or ovariectomized (F-OVX) at 3 weeks of age. Seven months later, BP was measured in anesthetized rats, and vascular responsiveness was evaluated in the isolated perfused mesentery.\n\nResults: Mean arterial BP (mm Hg) was significantly greater in M-SHAM (186 +/- 6) compared with F-SHAM (159 +/- 5). Gonadectomy reduced BP in male SHR (M-CX: 160 +/- 4) but had no significant effect in female SHR (F-OVX: 153 +/- 7). Norepinephrine-induced constriction was similar in all groups. Gonadectomy attenuated serotonin-induced vasoconstriction in the mesentery.

(Am J Pathol 2011, 179:211-222; DOI. 10.1016/j.ajpath.2011.03.010)”
“Objectives To determine whether the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction or increased

carotid intima-media thickness (IMT) in a series of Spanish patients with rheumatoid arthritis (RA).\n\nMethods Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital Prexasertib in vivo San Carlos, Madrid, were studied. Patients were genotyped using predesigned TaqMan single nucleotide polymorphism genotyping assays. Moreover, between March and December 2007, a subgroup of unselected RA patients with no history of CV events was studied for the presence of subclinical atherosclerosis by the assessment of the endothelial function (n=126) and the carotid this website artery IMT (n= 110) by ultrasonography studies.\n\nResults No significant differences

in the allele or genotype frequencies for the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms between RA patients with or without CV events were found. It was also the case when we analysed the potential influence of the genotypes in the presence of endothelial dysfunction or increased carotid artery IMT of patients with RA.\n\nConclusion Our results do not show that the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may confer a direct risk of CV disease in patients with RA.”
“This study examined the effects of NH4Cl ingestion on phosphocreatine (PCr) metabolism during 9 min of moderate- (MOD) and heavy- (HVY) intensity constant-load isotonic plantar-flexion exercise. Healthy young adult male subjects (n = 8) completed both a control (CON) and NH4Cl ingestion (ACID) trial. Phosphorus-31 magnetic resonance spectroscopy was used to monitor changes in intracellular pH (pHi), [Pi], [PCr], and [ATP]. During the Middle (3-6 min) see more and Late (6-9 min) stages of HVY, ACID was associated with a higher (P < 0.05) intracellular hydrogen-ion concentration

([H+]i) [Middle: 246 (SD 36) vs. 202 (SD 36) mmol/l]; [Late: 236 (SD 35) vs. 200 (SD 39) mmol/l]. In addition, ACID was associated with a lower (P < 0.05) [PCr] relative to CON during the Early (0-3 min) [18.1 (SD 5.1) vs. 20.4 (SD 5.4) mmol/l] and Middle stages [14.1 (SD 5.4) vs. 16.7 (SD 6.0) mmol/l] of HVY. The amplitude of the primary component of PCr breakdown during the transition to HVY was greater in ACID than CON [14.5 (SD 5.8 vs. 11.3 (SD 4.8) mmol/l], however, the PCr slow component (continued slow decline in [PCr]) showed no difference (P > 0.05). The time constant for PCr breakdown (tau PCr) was greater in HVY than MOD for both conditions [58 (SD 22) vs. 28 (SD 15) s ACID; 51 (SD 20) vs. 29 (SD 14) s CON] (P < 0.05).

Among 1023 buffalo sera tested, 77 (7.5%) had detectable virus neutralising antibodies. The assay had high intra-

and inter-plate repeatability in routine runs. At a cut-off optimised by the TG-ROC at 95% accuracy level, the diagnostic sensitivity of the I-ELISA was 98.7% and diagnostic specificity 99.36% while estimates for the Youden’s index (J) and efficiency (Ef) were 0.98 and 99.31%. When cut-off values determined by traditional statistical approaches Prexasertib order were used, the diagnostic sensitivity was 100% but estimates of J, Ef and other combined measures of diagnostic accuracy were lower compared to those based on cut-off value derived from the TG-ROC. Results of the study indicate that the I-ELISA based on the rNp would be useful for seroepidemiological studies of RVFV infections in African buffalo. (c) 2007 Elsevier B.V. All rights reserved.”
“P>Over one-third of the world population is infected with parasitic helminths, Strongyloides ssp. accounting for approximately 30-100 million infected people. In this study, we employ the experimental system of murine Strongyloides ratti infection to investigate the interaction of this pathogenic nematode with its mammalian host.

We provide a comprehensive kinetic description click here of the immune response to S. ratti infection that was reflected by induction check details of antigen-specific IgM and IgG1, mast cell activation and a Th2-like cytokine response. T cells derived from infected mice displayed an increased IL-3, IL-4, IL-5, IL-13 and IL-10 response to CD3-engagement in comparison with T cells derived from naive mice. The IFN-gamma response to CD3-engagement that was well detectable in T cells derived from naive mice, however, was suppressed in

T cells derived from infected mice. Both, the induction of the S. ratti-specific Th2 response and the suppression of pro-inflammatory cytokines were transient and observed in strict correlation to the course of infection and the number of infective larvae used. Finally, comparing artificial infections induced by subcutaneous injection of larvae to natural infections, we observed similar antigen-specific T cell responses although the natural infection led to a significantly lower worm burden.”
“The site of Hummal is one of several artesian springs in the El Kowm area (Central Syria) that became the focus of archaeological research at the beginning of the 1980s. The archaeological sequence spans the whole Paleolithic period and the spring is therefore a reference site for the Paleolithic in the interior part of the Levant. Archaeological remains are found in a more than 15 m thick succession of deposits that contain Lower, Middle and Upper Paleolithic assemblages.

“
“The aim of our study was to analyze the effects of an antioxidant treatment on markers of oxidative and carbonyl stress in a rat model of obstructive sleep apnea.\n\nWistar rats were randomized into six groups-according to gender and intervention-sham, intermittent hypoxia, and intermittent hypoxia with treatment by vitamins C and E. Rats underwent tracheostomy. The tracheal OICR-9429 cannula was closed for 12 s every minute for 1 h to simulate

obstructive sleep apnea-related intermittent hypoxia. In the treatment group, rats received vitamin C and E 24 h prior to surgery.\n\nThe intervention had a significant effect on advanced oxidation protein products (p = 0.008) and advanced glycation end products-specific fluorescence (p = 0.006) but no effect on malondialdehyde. Oxidation and glycation protein products were higher in intermittent hypoxia groups than in sham and in treated groups.\n\nAntioxidants alleviate oxidative and carbonyl stress in an experimental www.selleckchem.com/products/Cediranib.html model of obstructive sleep apnea. Future studies will show whether such treatment has any clinical value regarding cardiovascular complications of sleep apnea syndrome, preferably in patients with low compliance to continuous positive airway pressure.”
“Resource managers at Fort Benning, Georgia, must maintain environmental conditions necessary for

military training as well as promote longleaf pine (Pinus palustris) habitat. Understory vegetation controls the eventual species composition of these forests but is also sensitive to military activity. Past research from an observational study at this site suggests that impacts from military activity are best indicated by understory plant families and Raunkiaer life forms – specifically an increase in cryptophytes (plants with underground buds) and therophytes (annual plants). Our study GDC-0973 cell line tests that conclusion experimentally using a tracked vehicle

to manipulate an oak-pine forest occurring on an upland-riparian gradient. In May 2003, a D7 bulldozer removed extant vegetation and surface soil organic matter along three treatment transects. Braun-Blanquet vegetation surveys were conducted within plots in mid and late summer during 2003 and 2004. The response of total understory cover, bare ground cover, litter cover, species richness, family richness, Fabaceae cover and life-form cover was analyzed using repeated measures analyses of variance. Total understory cover, bare ground cover, species richness, family richness and cryptophyte cover showed a significant treatment x time interaction reflecting the transient response of these metrics to this isolated disturbance as most metrics returned to control values within two growing seasons. Although therophyte cover did not display significant interactions in this experiment, the increase in cryptophyte cover supports the use of life forms as indicators of mechanized disturbance to understory structure.

In this study, the labelling of a biocytin analogue coupled with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), namely, r-BHD, with gallium-68 (Ga-68) was optimized, and the quality and stability of the preparations were assessed for clinical use.\n\nMaterials and methods Synthesis of Ga-68-r-BHD was carried out by heating a fraction of the Ge-68/Ga-68 eluate in a reactor containing the biocytin analogue with the appropriate buffer. The influence of the

precursor amount (from 2.5 to 140 nmol), the pH of the reaction (from 2 to 5.5) and the buffer species (1.5 mol/l sodium acetate, 1.5 mol/l sodium formate, 4.5 mol/l HEPES) on radiochemical yield and radiochemical purity was assessed. Studies on stability and binding to avidin (Av) were also conducted in different media.\n\nResults click here Under the best labelling condition (56 nmol of precursor, 3.8 pH, sodium formate buffer) synthesis of Ga-68-r-BHD resulted in a yield of 64 +/- 3% (not decay corrected). Radiochemical purity was around 95% because a Ga-68-coordinated sulfoxide form of the ligand was detected as a by-product of the reaction (Ga-68-r-SBHD). The by-product was AZD7762 in vitro identified and characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. At the natural 1:4 Av/Ga-68-r-BHD molar ratio,

affinity results were 62 2 and 80 +/- 2% in saline and human serum, respectively. Stability of Ga-68-r-BHD and of the radiotracer/Av complex remains almost constant over 180 min. Ga-68-r-BHD appears to be a good candidate for clinical applications. Nucl Med Commun 33:1179-1187 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Growth by bone remodeling is one of the key mechanisms responsible for skeletal morphology. This mechanism consists of the coordinated activity of two cellular groups: osteoblasts and osteoclasts, which

are responsible for bone deposition and resorption, respectively. Information obtained from the study of these remodeling Vactosertib cost growth fields allows us to understand how species-specific craniofacial form is achieved. These data can help to explain the facial growth differences among Primates, both extinct and extant. The aim of this study was to obtain the distribution of growth remodeling fields of the Homo heidelbergensis mandible (Atapuerca-SH sample), and to infer the growth processes responsible for its specific morphology. A Reflected Light Microscope (RLM) was used to identify the microfeatures of the bone surface related to bone deposition and resorption. Results show that H. heidelbergensis presents a specific growth field distribution, which differs slightly between immature and adult individuals. Interpretation of these maps indicates that the mandible of H. heidelbergensis presents noteworthy variability in the symphyseal region.