In vitro evolution predicts emerging SARS-CoV-2 mutations with high affinity for ACE2 and cross-species binding.

Emerging SARS-CoV-2 variants are creating major challenges in the ongoing COVID-19 pandemic. Being able to predict mutations that could arise in SARS-CoV-2 leading to increased transmissibility or immune evasion would be extremely valuable in development of broad-acting therapeutics and vaccines, and prioritising viral monitoring and containment. Here we use in vitro evolution to seek mutations in SARS-CoV-2 receptor binding domain (RBD) that would substantially increase binding to ACE2. We find a double mutation, S477N and Q498H, that increases affinity of RBD for ACE2 by 6.5-fold. This affinity gain is largely driven by the Q498H mutation. We determine the structure of the mutant-RBD:ACE2 complex by cryo-electron microscopy to reveal the mechanism for increased affinity. Addition of Q498H to SARS-CoV-2 RBD variants is found to boost binding affinity of the variants for human ACE2 and confer a new ability to bind rat ACE2 with high affinity. Surprisingly however, in the presence of the common N501Y mutation, Q498H inhibits binding, due to a clash between H498 and Y501 side chains. To achieve an intermolecular bonding network, affinity gain and cross-species binding similar to Q498H alone, RBD variants with the N501Y mutation must acquire instead the related Q498R mutation. Thus, SARS-CoV-2 RBD can access large affinity gains and cross-species binding via two alternative mutational routes involving Q498, with route selection determined by whether a variant already has the N501Y mutation. These mutations are now appearing in emerging SARS-CoV-2 variants where they have the potential to influence human-to-human and cross-species transmission.

A call-to-action to assist in efforts to protect owl monkeys (Aotus spp.).

The majority of the 11 species of owl monkeys (Aotus spp.) have declining populations or are listed as data deficient. Deforestation due to agriculture, development, or logging poses threats to owl monkeys throughout their range. In some areas, Aotus are hunted for bushmeat or trapped for the wildlife trade. In Colombia, the country with the greatest number of Aotus species, owl monkeys are also threatened by civil unrest. To help combat these challenges, nonprofit organizations and field researchers in habitat countries have successfully implemented a variety of conservation projects such as censusing and monitoring owl monkey populations, establishing protected areas, reforesting degraded areas, filing lawsuits to protect wild populations, helping law enforcement with environmental regulation, and promoting environmental education. We highlight some of the conservation successes and suggest actions people around the world can take to contribute to these important efforts.

Learning from public health practice: the development of a library of community-centered practice examples.

BACKGROUND: Valuable learning derived from public health practice can be captured through practice-based case studies, also known as practice examples. Practice examples of participatory interventions supplement the evidence base by providing information on the complexities of implementation in communities. This paper reports on a Public Health England project to build a bank of community-centered practice examples based on robust processes of collection and curation. METHODS: The multidisciplinary project had three phases: (i) development and piloting a process to collect practice examples, (ii) refining review processes and gathering further examples via national and regional teams (iii) maintenance of an accessible collection on the library platform. RESULTS: The project resulted in a searchable collection of 55 practice examples illustrating participatory approaches in public health practice. The collection shows diversity in terms of settings, population, focus and type of approach used to work with communities. A secondary outcome was the development of generic guidance and templates for further collections on public health topics. CONCLUSIONS: This project illustrates how information on the implementation of community-centered approaches in real-life contexts can be gathered and disseminated through a transferable process. Having collections of practice examples supports knowledge exchange in public health as learning is shared.

GSK137, a potent small-molecule BCL6 inhibitor with in vivo activity, suppresses antibody responses in mice.

B-cell lymphoma 6 (BCL6) is a zinc finger transcriptional repressor possessing a BTB-POZ (BR-C, ttk, and bab for BTB; pox virus and zinc finger for POZ) domain, which is required for homodimerization and association with corepressors. BCL6 has multiple roles in normal immunity, autoimmunity, and some types of lymphoma. Mice bearing disrupted BCL6 loci demonstrate suppressed high-affinity antibody responses to T-dependent antigens. The corepressor binding groove in the BTB-POZ domain is a potential target for small compound-mediated therapy. Several inhibitors targeting this binding groove have been described, but these compounds have limited or absent in vivo activity. Biophysical studies of a novel compound, GSK137, showed an in vitro pIC50 of 8 and a cellular pIC50 of 7.3 for blocking binding of a peptide derived from the corepressor silencing mediator for retinoid or thyroid hormone receptors to the BCL6 BTB-POZ domain. The compound has good solubility (128 µg/ml) and permeability (86 nM/s). GSK137 caused little change in cell viability or proliferation in four BCL6-expressing B-cell lymphoma lines, although there was modest dose-dependent accumulation of G1 phase cells. Pharmacokinetic studies in mice showed a profile compatible with achieving good levels of target engagement. GSK137, administered orally, suppressed immunoglobulin G responses and reduced numbers of germinal centers and germinal center B cells following immunization of mice with the hapten trinitrophenol. Overall, we report a novel small-molecule BCL6 inhibitor with in vivo activity that inhibits the T-dependent antigen immune response.

Ethnography of a parasite: A quantitative ethnographic observation of forest malaria in the Amazon basin.

Aims: Malaria in the Amazon basin is persistently more prevalent among low density populations (1-4 people/km2). Describing malaria transmission in small populations, such as ethnic minorities in the Amazon basin, living in reserves in groups that amount to 110-450 individuals, is fundamental for the implementation of adequate interventions. Here, we examine malaria transmission in a context of high prevalence in a small population of Nükak ethnicity (ethnic group n=400-650 individuals, study group, n=108 individuals) living in the peri-urban area of a city with 35,000 inhabitants in the Amazon basin. Methods: Using methods from behavioral ecology, we conducted a quantitative ethnography and collected data to inform of individual behavioral profiles. Individual malarial infection reports were available from the local public health offices, so each behavioral profile was associated with an epidemic profile for the past 5 years. Results: Our research shows that, in-line with current opinion, malaria among the Nükak is not associated with an occupational hazard risk and follows a holoendemic pattern, where children are most susceptible to the parasite. Parasite loads of malarial infection among the Nükak persist at much higher rates than in any other neighboring ethnicity, which indicates an association between high incidence rates and endemicity. Conclusions: We hypothesize that malarial infection in the forest follows a pattern where the parasite persists in pockets of holoendemicity, and occupational hazard risk for individuals outside those pockets is associated with behaviors that take place in the proximity of the pockets of endemicity.

Synthetic Lethal Screen Demonstrates That a JAK2 Inhibitor Suppresses a BCL6-dependent IL10RA/JAK2/STAT3 Pathway in High Grade B-cell Lymphoma.

We demonstrate the usefulness of synthetic lethal screening of a conditionally BCL6-deficient Burkitt lymphoma cell line, DG75-AB7, with a library of small molecules to determine survival pathways suppressed by BCL6 and suggest mechanism-based treatments for lymphoma. Lestaurtinib, a JAK2 inhibitor and one of the hits from the screen, repressed survival of BCL6-deficient cells in vitro and reduced growth and proliferation of xenografts in vivo BCL6 deficiency in DG75-AB7 induced JAK2 mRNA and protein expression and STAT3 phosphorylation. Surface IL10RA was elevated by BCL6 deficiency, and blockade of IL10RA repressed STAT3 phosphorylation. Therefore, we define an IL10RA/JAK2/STAT3 pathway each component of which is repressed by BCL6. We also show for the first time that JAK2 is a direct BCL6 target gene; BCL6 bound to the JAK2 promoter in vitro and was enriched by ChIP-seq. The place of JAK2 inhibitors in the treatment of diffuse large B-cell lymphoma has not been defined; we suggest that JAK2 inhibitors might be most effective in poor prognosis ABC-DLBCL, which shows higher levels of IL10RA, JAK2, and STAT3 but lower levels of BCL6 than GC-DLBCL and might be usefully combined with novel approaches such as inhibition of IL10RA.

Relative tooth size at birth in primates: Life history correlates.

OBJECTIVES: Dental eruption schedules have been closely linked to life history variables. Here we examine a sample of 50 perinatal primates (28 species) to determine whether life history traits correlate with relative tooth size at birth. MATERIALS AND METHODS: Newborn primates were studied using serial histological sectioning. Volumes of deciduous premolars (dp2 -dp4 ), replacement teeth (if any), and permanent molars (M1-2/3 ) of the upper jaw were measured and residuals from cranial length were calculated with least squares regressions to obtain relative dental volumes (RDVs). RESULTS: Relative dental volumes of deciduous or permanent teeth have an unclear relationship with relative neonatal mass in all primates. Relative palatal length (RPL), used as a proxy for midfacial size, is significantly, positively correlated with larger deciduous and permanent postcanine teeth. However, when strepsirrhines alone are examined, larger RPL is correlated with smaller RDV of permanent teeth. In the full sample, RDVs of deciduous premolars are significantly negatively correlated with relative gestation length (RGL), but have no clear relationship with relative weaning age. RDVs of molars lack a clear relationship with RGL; later weaning is associated with larger molar RDV, although correlations are not significant. When strepsirrhines alone are analyzed, clearer trends are present: longer gestations or later weaning are associated with smaller deciduous and larger permanent postcanine teeth (only gestational length correlations are significant). DISCUSSION: Our results indicate a broad trend that primates with the shortest RGLs precociously develop deciduous teeth; in strepsirrhines, the opposite trend is seen for permanent molars. Anthropoids delay growth of permanent teeth, while strepsirrhines with short RGLs are growing replacement teeth concurrently. A comparison of neonatal volumes with existing information on extent of cusp mineralization indicates that growth of tooth germs and cusp mineralization may be selected for independently.

Allogrooming in Male-Female Pairs of Captive Owl Monkeys (Aotus nancymaae).

Owl monkeys (Aotus spp.) are socially monogamous, yet allogrooming is reported to be rare. Because Aotus are nocturnal and arboreal, allogrooming is difficult to observe in natural settings. We observed 21 male-female pairs of captive Aotus nancymaae during 2 nonconsecutive study periods in order to describe the details of allogrooming between mates (partner grooming). We found that grooming bouts are brief and consist of tugging the hair or skin with flexed fingers and/or the mouth. Males groomed females most often, and their rates of partner grooming were negatively related to age. Partner grooming occurred regardless of mating behavior. Camera trap data revealed that the rate of partner grooming (1.50 bouts/h) is greater than that recorded from our direct observations in the early evenings (0.51 bouts/h, in 2013; 0.37 bouts/h in 2003) given that most bouts occurred later in the night. A positive relationship between the rates of the parents' partner grooming and those of their offspring later in life suggests intergenerational transmission. This relationship is influenced by the fathers' rates of partner grooming. We conclude that allogrooming in Aotus is a normal part of their behavioral repertoire that likely serves social functions similar to those in other pair-bonded primates.

Owl monkeys (Aotus spp.) perform self- and social anointing in captivity.

Several species of primates, including owl monkeys (Aotus spp.), anoint by rubbing their fur with odiferous substances. Previous research has shown that capuchin monkeys (Cebus and Sapajus) anoint socially by rubbing their bodies together in groups of two or more while anointing. Owl monkeys housed at the DuMond Conservancy have been observed to anoint over the last 10 years, and we report detailed new information on the anointing behavior of this population, including descriptions of social anointing which occurs frequently. We first investigated the occurrence of self-anointing in 35 Aotus spp. presented with millipedes. Detailed descriptions regarding body regions anointed were obtained for all anointers (n = 28). The median duration for a self-anointing bout was 3.6 min (range from approx. 2 s to 14.15 min). While the latency and length of anointing bouts showed considerable interindividual differences, no statistically significant differences were found between sexes, wild- or captive-born owl monkeys or across age groups. However, we found the lower back and tail were anointed at a rate significantly greater than other body parts, but there were no differences in these patterns across sex or wild- or captive-born owl monkeys. More recently, social anointing was investigated in 26 Aotus spp. presented with millipedes, of which half were observed to anoint socially. The average duration for all social anointing bouts was 72.88 s, with a median duration of 30 s (range 5-322 s). A detailed ethogram was also generated that included behaviors that were performed while anointing, including facial expressions and vocalizations. The intraindividual variability for 8 monkeys used in both investigations is discussed. These findings extend our knowledge of anointing and confirm the existence of social anointing in another genus with a unique biology (nocturnal and socially monogamous) distinct from capuchins.

Growth and microanatomy of the paranasal sinuses in two species of New World monkeys.

Paranasal sinuses of living apes and humans grow with positive allometry, suggesting a novel mechanism for bone enlargement. Here, we examine the paranasal sinuses of the owl monkey (Aotus spp.) and a tamarin (Saguinus midas) across postnatal development. The prediction that paranasal sinuses grow disproportionately faster than the main nasal chamber is tested. We used diffusible iodine-based contrast-enhanced computed tomography and histology to study sinuses in eight Aotus and three tamarins ranging from newborn to adult ages. Sinuses were segmented at the mucosa-air cavity interface and measured in volume. All sinuses were lined by a ciliated respiratory epithelium, except for the ethmoid air cells in Aotus, which are lined in part by olfactory epithelium. An age comparison indicates that only the maxillary sinus and ethmoid air cells are present in newborns, and two additional sinuses (invading the orbitosphenoid and the frontal bone), do not appear until late infancy or later. Comparing newborns and adults, the main nasal airway is 10 times larger in the adult Aotus and ~ 6.5 times larger in adult Saguinus. In contrast, the maxillary sinus far exceeds this magnitude of difference: 24 times larger in the adult Aotus and 46 times larger in adult Saguinus. The frontal sinuses add significantly to total paranasal space volume in both species, but this growth is likely delayed until juvenile age. Results suggest ethmoid air cells expand the least. These results support our prediction that most paranasal sinuses have a distinctly higher growth rate compared to the main nasal chamber.

The effect of bariatric surgery in the difficult asthma-obesity phenotype: a case report.

INTRODUCTION: Obesity and asthma have become increasingly prevalent conditions in recent years; they often coexist and place a significant burden on the National Health Service. Asthma in the obese is more difficult to treat than in those with a normal body mass index (BMI) and is associated with resistance to traditional asthma therapies and increased use of healthcare resources. Weight loss can improve asthma control in such patients. The degree of weight loss achieved through dietary strategies, however, is often only modestly successful in this group. Bariatric surgery is increasingly used to achieve sustained significant weight loss in morbid obesity. It may offer under-recognized benefit in the difficult asthma-obesity phenotype. CASE STUDY: We describe the case of a 32-year-old female with difficult asthma who had a BMI of 45 kg/m(2) at the time of referral to our clinic. Her asthma was uncontrolled despite maximal inhaled therapy, oral therapy with Zafirlukast, and daily high-dose (25 mg) oral prednisolone. Additional therapies (subcutaneous Terbutaline and the steroid-sparing agent Methotrexate) had little impact on asthma control and she remained morbidly obese. She underwent gastric bypass surgery and, over the following 18 months, her BMI dropped to 27.7 kg/m(2), her corticosteroid dose was reduced to 7.5 mg (adrenal insufficiency proven), and maintenance inhaled therapy and oral medications were stopped as she maintained good asthma control. CONCLUSION: This case demonstrates the dramatic improvement that bariatric surgery can have on asthma symptoms and medication use in morbidly obese patients with very difficult to control asthma.

A Scoping Review of Approaches to Improving Quality of Data Relating to Health Inequalities.

Identifying and monitoring of health inequalities requires good-quality data. The aim of this work is to systematically review the evidence base on approaches taken within the healthcare context to improve the quality of data for the identification and monitoring of health inequalities and describe the evidence base on the effectiveness of such approaches or recommendations. Peer-reviewed scientific journal publications, as well as grey literature, were included in this review if they described approaches and/or made recommendations to improve data quality relating to the identification and monitoring of health inequalities. A thematic analysis was undertaken of included papers to identify themes, and a narrative synthesis approach was used to summarise findings. Fifty-seven papers were included describing a variety of approaches. These approaches were grouped under four themes: policy and legislation, wider actions that enable implementation of policies, data collection instruments and systems, and methodological approaches. Our findings indicate that a variety of mechanisms can be used to improve the quality of data on health inequalities at different stages (prior to, during, and after data collection). These findings can inform us of actions that can be taken by those working in local health and care services on approaches to improving the quality of data on health inequalities.

Effect of digital psychoeducation and peer support on the mental health of family carers supporting individuals with psychosis in England (COPe-support): a randomised clinical trial.

BACKGROUND: Psychoeducation delivered face-to-face is effective in alleviating mental health morbidities in family carers of individuals with psychosis. However, research in such interventions delivered online is scarce. We evaluated the effectiveness of a digital multicomponent intervention-COPe-support-in improving carers' mental wellbeing and caregiving-related outcomes. METHODS: In this two-arm, individually randomised, superiority trial, people aged 18 years or older who provided at least weekly support in any format for a relative or close friend affected by psychosis across England were randomly assigned (1:1) to either COPe-support or a passive online information resource using an independent online system. Participants were recruited through 30 mental health UK National Health Service trusts. The study team were masked to allocation and assessment of outcomes as all data collection took place online. Participants had access to either condition for 40 weeks and were advised to spend at least half an hour per week over the initial 20 weeks to go through materials at their own pace and to allow time to integrate knowledge and skills learned into practice. It was not feasible to mask participants or the online facilitator to intervention allocation. COPe-support provided psychoeducation on psychosis-related caregiving strategies and forums with professionals and other carers, and the control intervention comprised a passive online information resource. The primary outcome at 20 weeks was mental wellbeing measured by the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS; minimally clinically important difference [MCID] 3). This trial is registered with ISRCTN, 89563420. FINDINGS: Between March 1, 2018, and Feb 14, 2020, 407 participants were randomly assigned, with 204 allocated to COPe-support and 203 allocated to control. The participants (mean age 53·1 years, SD 13·2) were mostly female (330 [81%] of 407 participants) and White (359 [88%] of 407 participants). 346 (85%) of 407 participants provided primary endpoint data, 174 (85%) of 204 participants in the COPe-support group and 172 (85%) of 203 participants in the control group. The mean WEMWBS score at 20 weeks was 44·5 (SD 8·31) for the COPe-support group and 43·3 (9·19) for the control group. We found no evidence of a difference in wellbeing between the two groups (adjusted mean difference 0·37, 95% CI -1·14 to 1·88; p=0·63). In the COPe-support group, 106 (52%) of 204 participants met the complier definition of a minimum of two logins in separate weeks. The complier average causal effect analysis increased the difference in WEMWBS scores (adjusted difference 0·83, 95% CI -1·45 to 3·11; p=0·47), but this was lower than the MCID. There were no adverse events. INTERPRETATION: Our findings did not support the use of COPe-support over a passive online information resource. However, further research to optimise digital interventions adjunctive to face-to-face support for carers remains important. FUNDING: National Institute for Health Research.

mtDNA diversity in Azara's owl monkeys (Aotus azarai azarai) of the Argentinean Chaco.

Owl monkeys (Aotus spp.) inhabit much of South America yet represent an enigmatic evolutionary branch among primates. While morphological, cytogenetic, and immunological evidence suggest that owl monkey populations have undergone isolation and diversification since their emergence in the New World, problems with adjacent species ranges, and sample provenance have complicated efforts to characterize genetic variation within the genus. As a result, the phylogeographic history of owl monkey species and subspecies remains unclear, and the extent of genetic diversity at the population level is unknown. To explore these issues, we analyzed mitochondrial DNA (mt DNA) variation in a population of wild Azara's owl monkeys (Aotus azarai azarai) living in the Gran Chaco region of Argentina. We sequenced the complete mitochondrial genome from one individual (16,585 base pairs (bp)) and analyzed 1,099 bp of the hypervariable control region (CR) and 696 bp of the cytochrome oxidase II (COII) gene in 117 others. In addition, we sequenced the mitochondrial genome (16,472 bp) of one Nancy Ma's owl monkey (A. nancymaae). Based on the whole mtDNA and COII data, we observed an ancient phylogeographic discontinuity among Aotus species living north, south, and west of the Amazon River that began more than eight million years ago. Our population analyses identified three major CR lineages and detected a high level of haplotypic diversity within A. a. azarai. These data point to a recent expansion of Azara's owl monkeys into the Argentinean Chaco. Overall, we provide a detailed view of owl monkey mtDNA variation at genus, species, and population levels.

Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against Pseudomonas aeruginosa.

This study describes a novel series of UDP-N-acetylglucosamine acyltransferase (LpxA) inhibitors that was identified through affinity-mediated selection from a DNA-encoded compound library. The original hit was a selective inhibitor of Pseudomonas aeruginosa LpxA with no activity against Escherichia coli LpxA. The biochemical potency of the series was optimized through an X-ray crystallography-supported medicinal chemistry program, resulting in compounds with nanomolar activity against P. aeruginosa LpxA (best half-maximal inhibitory concentration (IC50) <5 nM) and cellular activity against P. aeruginosa (best minimal inhibitory concentration (MIC) of 4 µg/mL). Lack of activity against E. coli was maintained (IC50 > 20 µM and MIC > 128 µg/mL). The mode of action of analogues was confirmed through genetic analyses. As expected, compounds were active against multidrug-resistant isolates. Further optimization of pharmacokinetics is needed before efficacy studies in mouse infection models can be attempted. To our knowledge, this is the first reported LpxA inhibitor series with selective activity against P. aeruginosa.

Mated pairs of owl monkeys (Aotus nancymaae) exhibit sex differences in response to unfamiliar male and female conspecifics.

In socially monogamous species, mate-guarding could be a reproductive strategy that benefits both males and females, especially when males contribute to parental care. By actively guarding mates, males may reduce their chances of being cuckolded, whereas females that mate-guard may reduce the likelihood that their mates will desert them or acquire additional mates, and hence limit or reduce paternal care of offspring. Owl monkeys (Aotus spp.) are socially monogamous with biparental care of young and, hence, potential beneficiaries of mate-guarding. We presented mated pairs of captive owl monkeys (A. nancymaae) with unfamiliar male and female conspecifics, to determine if either member of the pair exhibits intraspecific aggression toward an intruder or stays close to its mate, behaviors indicative of mate-guarding. Male mates were more responsible for the maintenance of close proximity between mates than females. Male mates also exhibited elevated levels of behavior that signify arousal when presented with a male conspecific. These responses by mated male owl monkeys are consistent with patterns that may help prevent cuckoldry.

Insect-foraging in captive owl monkeys (Aotus nancymaae).

Whereas the diets of diurnal primate species vary greatly, almost all nocturnal primate species consume insects. Insect-foraging has been described in nocturnal prosimians but has not been investigated in owl monkeys (Aotus spp.). We studied 35 captive owl monkeys (Aotus nancymaae) in order to describe their foraging behavior and to determine if there were any age or sex differences in their ability to capture insect prey. Because owl monkeys cooperate in parental care and in food-sharing, we expected social interactions involving insect prey. We found that owl monkeys most often snatched flying insects from the air and immobilized crawling insects against a substrate using their hands. Immatures and adult female owl monkeys attempted to capture prey significantly more often than did adult males; however, there was no difference in the proportion of attempts that resulted in capture. Social interactions involving prey appeared similar to those with provisioned food, but possessors of prey resisted begging attempts more so than did possessors of other food. Owl monkeys attempted to capture prey often (mean = 9.5 +/- 5.8 attempts/h), and we speculate that the protein and lipid content of captured prey is important for meeting the metabolic demands for growth and reproduction.

Time taken from primary care referral to a specialist centre diagnosis of idiopathic pulmonary fibrosis: an opportunity to improve patient outcomes?

For patients with IPF, length of time in healthcare systems prior to review in an ILD clinic reflects disease severity and may impact upon patient outcome https://bit.ly/2TkO26r.

Comparative dental anatomy in newborn primates: Cusp mineralization.

Previous descriptive work on deciduous dentition of primates has focused disproportionately on great apes and humans. To address this bias in the literature, we studied 131 subadult nonhominoid specimens (including 110 newborns) describing deciduous tooth morphology and assessing maximum hydroxyapatite density (MHD). All specimens were CT scanned at 70 kVp and reconstructed at 20.5-39 µm voxels. Grayscale intensity from scans was converted to hydroxyapatite (HA) density (mg HA/cm3 ) using a linear conversion of grayscale values to calibration standards of known HA density (R2 = .99). Using Amira software, mineralized dental tissues were captured by segmenting the tooth cusps first and then capturing the remainder of the teeth at descending thresholds of gray levels. We assessed the relationship of MHD of selected teeth to cranial length using Pearson correlation coefficients. In monkeys, anterior teeth are more mineralized than postcanine teeth. In tarsiers and most lemurs and lorises, postcanine teeth are the most highly mineralized. This suggests that monkeys have a more prolonged process of dental mineralization that begins with incisors and canines, while mineralization of postcanine teeth is delayed. This may in part be a result of relatively late weaning in most anthropoid primates. Results also reveal that in lemurs and lorises, MHD of the mandibular first permanent molar (M1 ) negatively correlates with cranial length. In contrast, the MHD of M1 positively correlates with cranial length in monkeys. This supports the hypothesis that natural selection acts independently on dental growth as opposed to mineralization and indicates clear phylogenetic differences among primates.