Fluvial Depositional Systems of the African Humid Period: An Analog for an Early, Wet Mars in the Eastern Sahara.

A widely hypothesized but complex transition from widespread fluvial activity to predominantly aeolian processes is inferred on Mars based on remote sensing data observations of ancient landforms. However, the lack of analysis of in situ martian fluvial deposits hinders our understanding of the flow regime nature and sustainability of the martian fluvial activity and the hunt for ancient life. Studying analogs from arid zones on Earth is fundamental to quantitatively understanding geomorphic processes and climate drivers that might have dominated during early Mars. Here we investigate the formation and preservation of fluvial depositional systems in the eastern Sahara, where the largest arid region on Earth hosts important repositories of past climatic changes. The fluvial systems are composed of well-preserved single-thread sinuous to branching ridges and fan-shaped deposits interpreted as deltas. The systems' configuration and sedimentary content suggest that ephemeral rivers carved these landforms by sequential intermittent episodes of erosion and deposition active for 10-100s years over ∼10,000 years during the late Quaternary. Subsequently, these landforms were sculpted by a marginal role of rainfall and aeolian processes with minimum erosion rates of 1.1 ± 0.2 mm/yr, supplying ∼96 ± 24 × 1010 m3 of disaggregated sediment to adjacent aeolian dunes. Our results imply that similar martian fluvial systems preserving single-thread, short distance source-to-sink courses may have formed due to transient drainage networks active over short durations. Altogether, this study adds to the growing recognition of the complexity of interpreting climate history from orbital images of landforms.

The birth experience and subsequent maternal caregiving attitudes and behavior: a birth cohort study.

Optimal maternal caregiving is critical for children's healthy development, yet quality of maternal caregiving may be influenced by a negative birth experience. We examined whether the birth experience was associated with maternal caregiving attitudes and behavior throughout the first year. We conducted secondary analysis of the Avon Longitudinal Study of Parents and Children birth cohort on perinatal data. The birth experience was assessed using self-report data on level of support in labor. Maternal caregiving variables were self-report maternal attitudes at one and eight postnatal months, and observed maternal behavior at 12 postnatal months. Data were analyzed using multivariable logistic regression models adjusting for critical covariates at one (N = 4389), eight (N = 4580), and 12 (N = 842) postnatal months. Feeling supported in labor was associated with a report of "immediately falling in love" with one's baby after birth, surveyed at 1 month (adjusted OR 1.41 [95% CI 1.20-1.65]), and with more positive parenting scores at 8 months (adjusted OR 1.56 [95% CI 1.36-1.79]), but not with more positive observed maternal behavior at 12 months. Additional risk factors were identified. Our findings suggest that we may be able to modify the risk of poor postnatal maternal caregiving by supporting women in labor and facilitating a positive birth experience.

Interprofessional education in dental education: An international perspective.

Interprofessional collaborative care (IPC) is defined as working within and across healthcare disciplines and is considered essential to achieve a more inclusive, patient-centred care, provide a means to support patient safety and address global healthcare provider shortages. Interprofessional education (IPE) provides the knowledge and experience students need to achieve these goals. ADEE/ADEA held a joint international meeting 8-9 May 2017, with IPE being one of four topic areas discussed. The highly interactive workshop format, where "everyone was an expert," supported discussion, sharing and creative problem-solving of over seventy-one participants from twenty-nine countries. IPE participants broke out into five groups over a two-day period discussing three main areas: challenges and barriers to implementing IPE within their institution or country; discussion of successful models of introducing and assessing IPE initiatives, and exploring best practices and next steps for implementation for each group member. A mind-mapping model was used to graphically display participants' thoughts and suggestions. Key themes, revealed through the visual mind maps and discussion, included the following: IPE should lead to and enhance patient-centred care; student involvement is key to IPE success; faculty development and incentives can facilitate adoption and implementation of IPE; the role of a "champion" and leadership structure and commitment is important to move IPE forward; and IPE must be tailored to the unique issues found in each country. Overall, there was a high level of interest to continue both collaboration and discussion to learn from others beyond the London meeting.

Metabolomics for informing adverse outcome pathways: Androgen receptor activation and the pharmaceutical spironolactone.

One objective in developing adverse outcome pathways (AOPs) is to connect biological changes that are relevant to risk assessors (i.e., fecundity) to molecular and cellular-level alterations that might be detectable at earlier stages of a chemical exposure. Here, we examined biochemical responses of fathead minnows (Pimephales promelas) to inform an AOP relevant to spironolactone's activation of the androgen receptor, as well as explore other biological impacts possibly unrelated to this receptor. Liquid chromatography with high resolution mass spectrometry (LC-MS) was used to measure changes in endogenous polar metabolites in livers of male and female fish that were exposed to five water concentrations of spironolactone (0, 0.05, 0.5, 5, or 50µgL-1) for 21days. Metabolite profiles were affected at the two highest concentrations (5 and 50µgL-1), but not in the lower-level exposures, which agreed with earlier reported results of reduced female fecundity and plasma vitellogenin (VTG) levels. We then applied partial least squares regression to assess whether metabolite alterations covaried with changes in fecundity, VTG gene expression and protein concentrations, and plasma 17ß-estradiol and testosterone concentrations. Metabolite profiles significantly covaried with all measured endpoints in females, but only with plasma testosterone in males. Fecundity reductions occurred in parallel with changes in metabolites important in osmoregulation (e.g., betaine), membrane transport (e.g., l-carnitine), and biosynthesis of carnitine (e.g., methionine) and VTG (e.g., glutamate). Based on a network analysis program (i.e., mummichog), spironolactone also affected amino acid, tryptophan, and fatty acid metabolism. Thus, by identifying possible key events related to changes in biochemical pathways, this approach built upon an established AOP describing spironolactone's androgenic properties and highlighted broader implications potentially unrelated to androgen receptor activation, which could form a basis for the development of an AOP network.

Dental students' self-perceived communication skills for patient motivation.

AIMS: The aim of this study was to evaluate dental students' self-perceived communication skills for patient motivation over the course of their training. MATERIALS AND METHODS: Pre-clinical and clinical dental students at the University of Bern School of Dental Medicine were surveyed annually from 2008 to 2011 utilising a written questionnaire. Self-reported data were pooled from all classes per time-point in the curriculum. RESULTS: A total of 157 students were surveyed from five classes with an overall response rate of 94.8%. A total of 393 questionnaires were available for analysis. The self-perceived skill-sets for general patient care and patient communication were rated at the end of the first clinical year with mean Visual Analog Scale values of 75.0 ± 1.6 and 75.1 ± 1.5, respectively. During the second clinical year, the self-perceived skills increased in both patient care (82.5 ± 1.2, P = 0.0004) and patient communication (81.4 ± 1.4, P = 0.0034). The students rated their competence higher when providing oral hygiene instructions as opposed to motivating patients to quit tobacco use, modify their diet or employ stress-reduction strategies (P < 0.005). At the end of the pre-clinical year, 74.5% of the students expressed interest in receiving more extensive communication training (P < 0.004). CONCLUSIONS: Though dental students in this study demonstrated a steady increase in their level of comfort motivating patients to utilise oral hygiene instructions, they also expressed the desire for more motivational training early in their curriculum. Therefore, these results may indicate the need to enhance communications training in patient motivation on all behavioural aspects early in the dental curriculum.

Lipids and polyunsaturated fatty acid levels in deliberate self-harm: a 10-year follow-up study.

OBJECTIVES: To evaluate if n-3 polyunsaturated fatty acids (PUFAs) and lipid levels are associated with episodes of self-harm or depression over a 10-year period. METHODS: We included 40 individuals who self-harmed and 40 controls. Episodes of self-harm and depression were ascertained and levels of depression, impulsivity, suicidal ideation and plasma lipid levels measured at baseline and at 10-year follow-up. RESULTS: Further episode(s) of self-harm occurred in 26% of cases. Omega-3 PUFAs or lipids were not predictive of depressive or self-harm episodes. Baseline eicosapentaenoic acid levels were modestly correlated with suicidal ideation at follow-up and dihomo-γ-linolenic acid and arachidonic acid were modestly correlated with motor impulsivity at follow-up in cases. CONCLUSIONS: Despite significant negative correlations at baseline between plasma lipids, n-3 PUFAs and psychopathology, these levels were not predictive of clinical outcome over a 10-year period. Further research however is required due to the relatively low sample size and the risk of selection bias due to loss to follow-up in this study.

Childbirth and symptoms of postpartum depression and anxiety: a prospective birth cohort study.

We investigated associations between aspects of childbirth and elevated postpartum symptoms of depression and anxiety. We employed secondary analysis of perinatal data (N = 4657-4946) from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariable logistic regression models (adjusted for covariates) examined predictors of elevated symptoms of postpartum depression and anxiety. Predictors included the following: type of delivery (normal physiological vs. interventive non-physiological), immediate postpartum complications, and maternal perception of the recent birth experience. The Edinburgh Postnatal Depression Scale assessed elevated symptoms of depression (score ≥ 13), and the Crown-Crisp Experiential Index assessed elevated symptoms of anxiety (score ≥ 9) at 2 and 8 months after delivery. A more negative perception of the recent birth experience was associated with elevated symptoms of anxiety at 2 months [odds ratio (OR) 1.52, 95 % confidence interval (CI) 1.25-1.85] and 8 months (OR 1.30, 95 % CI 1.06-1.60) postpartum but was not associated with elevated symptoms of depression at either time point. Type of delivery (physiological vs. non-physiological) and immediate postpartum complications were not associated with elevated symptoms of depression or anxiety. Our findings suggest that improving women's childbirth experience may decrease the likelihood of postpartum anxiety, but not postpartum depression.

Role of MCP-1 on inflammatory processes and metabolic dysfunction following high-fat feedings in the FVB/N strain.

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) is known to be an important chemokine for macrophage recruitment. Thus, targeting MCP-1 may prevent the perturbations associated with macrophage-induced inflammation in adipose tissue. However, inconsistencies in the available animal literature have questioned the role of this chemokine in this process. The purpose of this study was to examine the role of MCP-1 on obesity-related pathologies. METHODS: Wild-type and MCP-1-deficient mice on an friend virus B NIH (FVB/N) background were assigned to either low-fat diet or high-fat diet (HFD) treatment for a period of 16 weeks. Body weight and body composition were measured weekly and monthly, respectively. Fasting blood glucose and insulin, and glucose tolerance were measured at 16 weeks. Macrophages, T-cell markers, inflammatory mediators and markers of fibrosis were examined in the adipose tissue at the time of killing the mice. RESULTS: As expected, HFD increased adiposity (body weight, fat mass, fat percent and adipocyte size), metabolic dysfunction (impaired glucose metabolism and insulin resistance) macrophage number (CD11b(+)F480(+) cells, and gene expression of EMR1 and CD11c), T-cell markers (gene expression of CD4 and CD8), inflammatory mediators (pNFκB and pJNK, and mRNA expression of MCP-1, CCL5, C-X-C motif chemokine-14, tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) and fibrosis (expression of IL-10, IL-13, TGF-ß and matrix metalloproteinase-2 (MMP2); P<0.05). However, contrary to our hypothesis, MCP-1 deficiency exacerbated many of these responses resulting in a further increase in adiposity (body weight, fat mass, fat percent and adipocyte size), metabolic dysregulation, macrophage markers (EMR1), inflammatory cell infiltration and fibrosis (formation of type I and III collagens, mRNA expression of IL-10 and MMP2; P<0.05). CONCLUSIONS: These data suggest that MCP-1 may be a necessary component of the inflammatory response required for adipose tissue protection, remodeling and healthy expansion in the FVB/N strain in response to HFD feedings.

DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases.

The copy number of DUF1220, a protein domain implicated in human brain evolution, has been linearly associated with autism severity. Given the possibility that autism and schizophrenia are related disorders, the present study examined DUF1220 copy number variation in schizophrenia severity. There are notable similarities between autism symptoms and schizophrenia negative symptoms, and divergence between autism symptoms and schizophrenia positive symptoms. We therefore also examined DUF1220 copy number in schizophrenia subgroups defined by negative and positive symptom features, versus autistic individuals and controls. In the schizophrenic population (N=609), decreased DUF1220 copy number was linearly associated with increasing positive symptom severity (CON1 P=0.013, HLS1 P=0.0227), an association greatest in adult-onset schizophrenia (CON1 P=0.00155, HLS1 P=0.00361). In schizophrenic males, DUF1220 CON1 subtype copy number increase was associated with increased negative symptom severity (P=0.0327), a finding similar to that seen in autistic populations. Subgroup analyses demonstrated that schizophrenic individuals with predominantly positive symptoms exhibited reduced CON1 copy number compared with both controls (P=0.0237) and schizophrenic individuals with predominantly negative symptoms (P=0.0068). These findings support the view that (1) autism and schizophrenia exhibit both opposing and partially overlapping phenotypes and may represent a disease continuum, (2) variation in DUF1220 copy number contributes to schizophrenia disease risk and to the severity of both disorders, and (3) schizophrenia and autism may be, in part, a harmful by-product of the rapid and extreme evolutionary increase in DUF1220 copy number in the human species.

Risk associated with traumatic intracranial bleed and outcome in patients following a fall from a standing position.

BACKGROUND: A fall from a standing position (FFS) is a low impact injury; however, in certain patient populations it can result in serious, complex injuries associated with significant morbidity and mortality. OBJECTIVES: The purpose of the study was to identify the patient population, risk factors and outcomes of intracranial bleed (ICB) after a fall from a standing position. METHODS: Data of all patients from the trauma database at State designated Trauma Center were analyzed who FFS. Patient's demography, clinical information was obtained. An ICB seen on computed tomography (CT) scan was considered positive. RESULTS: From January 2001 through December 2008, 163 patients admitted to the trauma center after FFS. Ninety-one out of 163 patients (56 %) had positive CT scan. There was no significant difference between the groups with a positive or negative CT regarding age (P = 0.07), gender (P = 0.58), race (P = 0.15), Glasgow Coma Scale (P = 0.27), aspirin use (P = 0.06), Plavix (P = 0.92), combination of aspirin and Plavix (P = 0.86) or use of Coumadin (P = 0.82). Patients with ICB had significantly higher injury severity score (ISS) than patients without ICB (P < 0.0001). However, the overall mortality between the groups was not significant (P = 0.66). From a multiple logistic regression model, age ≥70 years was the only predictor for the ICB. CONCLUSION: A high proportion of our patients had positive ICB due to falls from a standing position. No significant differences were seen between the groups in terms of mortality. Age ≥70 years was the only factor for positive ICB. LEVEL OF EVIDENCE: Prognostic study investigating the effect of a patient characteristic on the outcome of the disease, level III.

Replicated linear association between DUF1220 copy number and severity of social impairment in autism.

Sequences encoding DUF1220 protein domains exhibit an exceptional human-specific increase in copy number and have been associated with several phenotypes related to brain size. Autism is a highly heritable and heterogeneous condition characterized behaviorally by social and communicative impairments, and increased repetitive and stereotyped behavior. Given the accelerated brain growth pattern observed in many individuals with autism, and the association between DUF1220 subtype CON1 copy number and brain size, we previously investigated associations between CON1 copy number and autism-related symptoms. We determined that CON1 copy number increase is associated with increasing severity of all three behavioral features of autism. The present study sought to replicate these findings in an independent population (N = 166). Our results demonstrate a replication of the linear relationship between CON1 copy number and the severity of social impairment in individuals with autism as measured by Autism Diagnostic Interview-Revised Social Diagnostic Score, such that with each additional copy of CON1 Social Diagnostic Score increased 0.24 points (SE = 0.11, p = 0.036). We also identified an analogous trend between CON1 copy number and Communicative Diagnostic Score, but did not replicate the relationship between CON1 copy number and Repetitive Behavior Diagnostic Score. Interestingly, these associations appear to be most pronounced in multiplex children. These results, representing the first replication of a gene dosage relationship with the severity of a primary symptom of autism, lend further support to the possibility that the same protein domain family implicated in the evolutionary expansion of the human brain may also be involved in autism severity.

Metabolite profiling of fish skin mucus: a novel approach for minimally-invasive environmental exposure monitoring and surveillance.

The application of 'omics tools to biologically based monitoring and surveillance of aquatic environments shows considerable promise for complementing chemical monitoring in ecological risk assessments. However, few of the current approaches offer the ability to sample ecologically relevant species (e.g., fish) in a way that produces minimal impact on the health of the organism(s) under study. In the current study we employ liquid chromatography tandem mass spectrometry (LC-MS/MS) to assess the potential for skin mucus-based metabolomics for minimally invasive sampling of the fathead minnow (FHM; Pimephales promelas). Using this approach we were able to detect 204 distinct metabolites in the FHM skin mucus metabolome representing a large number of metabolite classes. An analysis of the sex specificity of the skin mucus metabolome showed it to be highly sexually dimorphic with 72 of the detected metabolites showing a statistically significant bias with regard to sex. Finally, in a proof-of-concept fashion we report on the use of skin mucus-based metabolomics to assess exposures in male and female fathead minnows to an environmentally relevant concentration of bisphenol A, a nearly ubiquitous environmental contaminant and an established endocrine active chemical.

Effects of adding supplemental tallow to diets containing distillers dried grains with solubles on fatty acid digestibility in growing pigs.

An experiment was conducted to measure the apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of fatty acids in diets containing 0 or 30% corn distillers dried grains with solubles (DDGS) and 0, 5, or 10% tallow. Barrows (n = 24; initial BW = 25 kg) were surgically fitted with a T-cannula at the distal ileum. Pigs (n = 4/diet) were randomly assigned to diets: corn-soybean meal control (CON), CON plus 5% tallow (5T0D), CON plus 10% tallow (10T0D), CON plus 30% DDGS (0T30D), CON plus 5% tallow and 30% DDGS (5T30D), and CON plus 10% tallow and 30% DDGS (10T30D). Eight replicates per treatment were achieved by randomizing diets among pigs for a second collection period. Each pig was fed their respective diet for a 5-d adaptation period followed by 3-d fecal collection and 2-d ileal digesta collection periods. The AID and ATTD of fatty acids was calculated using the index method and acid-insoluble ash as an indigestible marker. When tallow was added to diets with 0% DDGS, there was no effect on AID of palmitic acid (C16:0) or SFA, while AID of stearic acid (C18:0) was increased (66.87% for CON, 72.06% for 5T0D, and 76.81% for 10T0D; P < 0.01). However, when diets contained 30% DDGS, the AID of all SFA was reduced as levels of tallow increased C16:0 (77.62% for 0T30D, 69.66% for 5T30D, and 68.43% for 10T30D), C18:0 (85.87% for 0T30D, 64.08% for 5T30D, and 61.25% for 10T30D), and SFA (79.88% for 0T30D, 68.23% for 5T30D, and 66.29% for 10T30D). The AID of MUFA was not affected when tallow was added to diets with 30% DDGS but actually increased in 5T0D and 10T0D. The amount of apparent ileal digested fatty acids increased with the addition of DDGS and tallow regardless of their digestibility. Amounts of ileal digested MUFA and PUFA increased when both DDGS (P < 0.01) and tallow (P < 0.01) were included in the diet compared to when either ingredient was excluded. For ileal digestible SFA, an interaction (P < 0.01) between DDGS and tallow was observed. Interactions between DDGS and tallow were observed for ATTD of all fatty acids (P < 0.01), except for linoleic acid and PUFA, which were not affected by dietary treatment. The amount of ileal digestible PUFA increased with tallow addition independent from the inclusion level of DDGS and it was a function the dietary concentration of the fatty acid. Adding tallow to corn-soybean based diets increased the amount of digested SFA, but in diets with DDGS, the increment in amount of ileal digestible SFA was less prominent due to lesser digestibility of SFA.

Effects of adding supplemental tallow to diets containing 30% distillers dried grains with solubles on growth performance, carcass characteristics, and pork fat quality in growing-finishing pigs.

Crossbred pigs (n = 315) were blocked by initial BW (6.8 ± 1.1 kg) and randomly assigned to 1 of 4 dietary treatments to evaluate the effects of dietary inclusion of tallow and corn distillers dried grains with solubles (DDGS) on pig growth, carcass traits, and pork fat quality. Diets consisted of a corn-soybean meal control diet (CON) and another 3 corn-soybean meal diets containing 5% tallow (T), 30% DDGS (D), or 5% tallow plus 30% DDGS (TD) in a 2 × 2 factorial arrangement of treatments. Diets were formulated to contain similar levels of available P and standardized ileal digestible Lys:ME among treatments. Pigs were housed in 40 pens, with 7 to 8 pigs per pen, to provide 10 replicates per treatment. Overall ADG did not differ among treatments. Compared with CON (2.76 kg/d) and T (2.59 kg/d), feeding 30% DDGS reduced the ADFI (interaction, P > 0.05) of pigs when fed with 5% tallow (2.45 kg/d for TD) but not when fed alone (2.76 kg/d for D). There was no effect of DDGS on overall G:F, but pigs fed diets with tallow had greater (P < 0.01) G:F (0.4) than pigs fed no tallow (0.37). Feeding tallow increased (P < 0.01) HCW, carcass yield, and backfat depth of pigs independent of DDGS. Feeding DDGS reduced (P < 0.01) belly firmness, as measured by belly flop angle, independent of tallow (D = 71.8° and TD = 57.7° vs. CON = 134.0° and T = 113.4°) and tallow also tended to reduce belly firmness (P < 0.10). Feeding DDGS and tallow reduced the concentration of SFA in belly fat, while the concentration of MUFA were increased (P < 0.01) by feeding tallow but not DDGS. Conversely, feeding DDGS increased (P < 0.01) the concentration of PUFA in belly fat but there was no effect of tallow. An interaction (P = 0.03) between DDGS and tallow for iodine value (IV) of belly fat was observed, in which addition of tallow or DDGS increased the IV of belly fat (64.22 for T and 71.22 for D vs. 59.01 for CON) but addition of both reduced IV (67.88 for TD). The IV of belly fat and backfat were correlated (P < 0.01) with the IV product of the diet fed in phase 3 (r = 0.49 and r = 0.81, respectively). In conclusion, adding 5% tallow to 30% DDGS diets improved G:F and carcass yield while reducing the IV of belly fat. However, pork fat firmness as measured by belly flop angle was not improved.

Generation of mice lacking DUF1220 protein domains: effects on fecundity and hyperactivity.

Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question, we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. In a hypothesis generating exercise, these mice were evaluated by 197 different phenotype measurements. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ(2) = 19.1, df = 2, p = 7.0 × 10(-5)). Further extensive phenotypic analyses suggest hyperactivity (p < 0.05) of DUF1220 mice and changes in gene expression levels of brain associated with distinct neurological functions and disease. Other changes that met statistical significance include an increase in plasma glucose concentration (as measured by area under the curve, AUC 0-30 and AUC 30-120) in male mutants, fasting glucose levels, reduce sodium levels in male mutants, increased levels of the liver functional indicator ALAT/GPT in males, levels of alkaline phosphatase (also an indicator of liver function), mean R and SR amplitude by electrocardiography, elevated IgG3 levels, a reduced ratio of CD4:CD8 cells, and a reduced frequency of T cells; though it should be noted that many of these differences are quite small and require further examination. The linking of DUF1220 loss to a hyperactive phenotype is consistent with separate findings in which DUF1220 over expression results in a down-regulation of mitochondrial function, and potentially suggests a role in developmental metabolism. Finally, the substantially reduced fecundity we observe associated with KO mice argues that the ancestral DUF1220 domain provides an important biological functionthat is critical to survivability and reproductive success.

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates.

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Self-sustained oscillations in blood flow through a honeycomb capillary network.

Numerical simulations of unsteady blood flow through a honeycomb network originating at multiple inlets and terminating at multiple outlets are presented and discussed under the assumption that blood behaves as a continuum with variable constitution. Unlike a tree network, the honeycomb network exhibits both diverging and converging bifurcations between branching capillary segments. Numerical results based on a finite difference method demonstrate that as in the case of tree networks considered in previous studies, the cell partitioning law at diverging bifurcations is an important parameter in both steady and unsteady flow. Specifically, a steady flow may spontaneously develop self-sustained oscillations at critical conditions by way of a Hopf bifurcation. Contrary to tree-like networks comprised entirely of diverging bifurcations, the critical parameters for instability in honeycomb networks depend weakly on the system size. The blockage of one or more network segments due to the presence of large cells or the occurrence of capillary constriction may cause flow reversal or trigger a transition to unsteady flow.

Guidelines for the use of cell lines in biomedical research.

Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise.