The late Ordovician Soom Shale Lagerstȁtte: an extraordinary post-glacial fossil and sedimentary record

Fossils of the Late Ordovician Soom Shale Lagerstätte are characterized by exceptional preservation of their soft tissues in clay minerals. The low-diversity community lived in an unusual cold-water setting, dominated by anoxic bottom waters, in the immediate aftermath of the Hirnantian glaciation. Giant conodonts represented by complete tooth sets, and one with trunk musculature and liver preserved, unarmoured jawless fish, lobopods and enigmatic taxa are some of the more important fossils. Furthermore, this Lagerstätte also preserves biomineralized Ordovician taxa such as brachiopods, orthoconic nautiloids and trilobites. It is important in capturing the only known examples of many taxa, extending temporal ranges of others and providing a unique glimpse of a post-glacial refugium, at a time when other Lagerstätten are unknown

Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B.

BackgroundUBE4B is an E3/E4 ubiquitin ligase whose gene is located in chromosome 1p36.22. We analyzed the associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and with tumor prognostic features and histology.MethodsWe evaluated the association of UBE4B gene expression with neuroblastoma patient outcomes using the R2 Platform. We screened neuroblastoma tumor samples for UBE4B protein expression using immunohistochemistry. FISH for UBE4B and 1p36 deletion was performed on tumor samples. We then evaluated UBE4B expression for associations with prognostic factors and with levels of phosphorylated ERK in neuroblastoma tumors and cell lines.ResultsLow UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression was associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels were associated with high-risk features. UBE4B protein levels were also associated with levels of phosphorylated ERK.ConclusionsWe have demonstrated associations between UBE4B gene expression and neuroblastoma patient outcomes and prognostic features. Reduced UBE4B protein expression in neuroblastoma tumors was associated with high-risk features, a lack of differentiation, and with ERK activation. These results suggest UBE4B may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions and that UBE4B expression may mediate neuroblastoma differentiation

Single nucleotide variants (SNVs) define senescence-accelerated SAMP8 mice, a model of a geriatric condition

One of the major challenges in neurodegenerative research is modeling systemic aging. Here, senescence-accelerated mice such as the multigenic SAMP8 (senescence accelerated prone 8) mice are useful as they are characterized by an early manifestation of s

Functional brain imaging studies of youth depression: A systematic review

AbstractBackgroundThere is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD.MethodsA literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13–18 and 19–25years of age, respectively.ResultsTwenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in “extended medial network” regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition.ConclusionsYouth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression

Immune Reconstitution Inflammatory Syndrome and the Influence of T Regulatory Cells: A Cohort Study in the Gambia

The factors associated with the development of immune reconstitution inflammatory syndrome in HIV patients commencing antiretroviral therapy have not been fully elucidated. Using a longitudinal study design, this study addressed whether alteration in the levels of T regulatory cells contributed to the development of IRIS in a West African cohort of HIV-1 and HIV-2 patients. Seventy-one HIV infected patients were prospectively recruited to the study and followed up for six months. The patients were categorized as IRIS or non-IRIS cases following published clinical guidelines. The levels of T regulatory cells were measured using flow cytometry at baseline and all follow-up visits. Baseline cytokine levels of IL-2, IL-6, IFN-(Gamma), TNF-(Alpha), MIP-1(Beta), IL-1, IL-12, IL-13, and IL-10 were measured in all patients

Olfactory sulcus morphology in patients with current and past major depression

Olfactory deficits have been reported in major depressive disorder (MDD). However, it remains largely unknown whether MDD is associated with abnormalities in olfactory sulcus morphology, a potential marker of olfactory system development. This magnetic resonance imaging study investigated the length and depth of the olfactory sulcus in 29 currently depressed patients, 27 remitted depressed patients, and 33 age- and gender-matched healthy control subjects. Both current and remitted MDD patients had significantly shallower olfactory sulci bilaterally as compared with controls. Only for male subjects, the right olfactory sulcus was significantly shorter in remitted MDD patients than in controls. The right sulcus depth was negatively correlated with number of depressive episodes in the entire MDD group and with residual depressive symptoms in the remitted MDD group. Medication status, presence of melancholia, and comorbidity with anxiety disorders did not affect the sulcus morphology. These findings suggest that abnormality of the olfactory sulcus morphology, especially its depth, may be a trait-related marker of vulnerability to major depression

KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians.

BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation. HBV is highly prevalent in The Gambia and the commonest cause of liver disease. The Gambia Liver Cancer Study was a matched case-control study conducted between September 1997 and January 2001 where cases with liver disease were identified in three tertiary referral hospitals and matched with out-patient controls with no clinical evidence of liver disease. METHODS: We typed 15 KIR genes using the polymerase chain reaction with sequence specific primers (PCR-SSP) in 279 adult Gambians, 136 with liver disease (HCC or Cirrhosis) and 143 matched controls. We investigated effects of KIR genotypes and haplotypes on HBV infection and associations with cirrhosis and HCC. RESULTS: Homozygosity for KIR group A gene-content haplotype was associated with HBsAg carriage (OR 3.7, 95% CI 1.4-10.0) whilst telomeric A genotype (t-AA) was associated with reduced risk of e antigenaemia (OR 0.2, 95% CI 0.0-0.6) and lower viral loads (mean log viral load 5.2 vs. 6.9, pc = 0.022). One novel telomeric B genotype (t-ABx2) containing KIR3DS1 (which is rare in West Africa) was also linked to e antigenaemia (OR 8.8, 95% CI 1.3-60.5). There were no associations with cirrhosis or HCC. CONCLUSION: Certain KIR profiles may promote clearance of hepatitis B surface antigen whilst others predispose to e antigen carriage and high viral load. Larger studies are necessary to quantify the effects of individual KIR genes, haplotypes and KIR/HLA combinations on long-term viral carriage and risk of liver cancer. KIR status could potentially inform antiviral therapy and identify those at increased risk of complications for enhanced surveillance

Sex differences in the neural correlates of emotion: evidence from neuroimaging.

a b s t r a c t Sex differences in emotional processes represent some of the most robust sex stereotypes worldwide. However, empirical support for these stereotypes is lacking, especially from research utilizing objective measures, such as neuroimaging methodologies. We conducted a selective review of functional neuroimaging studies that have empirically tested for sex differences in the association between brain function and emotional processes (including perception, reactivity, regulation and experience). Evidence was found for marked sex differences in the neural mechanisms underlying emotional processes, and in most cases suggested that males and females use different strategies during emotional processing, which may lead to sex differences in the observed (or subjectively reported) emotional process. We discuss how these findings may offer insight into the mechanisms underlying sex differences in emotional behaviors, and outline a number of methodological considerations for future research. Importantly, results suggest that sex differences should not be ignored in research investigating the neurobiology of emotion