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Hancock AM,Frostig RD
Testing the effects of sensory stimulation as a collateral-based therapeutic for ischemic stroke in C57BL/6J and CD1 mouse strains.
PLoS One. 2017;12(9):e0183909
Utilizing a rat model of ischemic stroke, we have previously shown that sensory stimulation can completely protect rats from impending ischemic damage of cortex if this treatment is delivered within the first two hours post-permanent middle cerebral artery occlusion (pMCAo). The current study sought to extend our findings in rats to mice, which would allow new avenues of research not available in rats. Thus, young adult C57BL/6J and CD1 mice were tested for protection from ischemic stroke with the same protective sensory stimulation-based treatment. Cortical activity and blood flow were assessed with intrinsic signal optical imaging (ISOI) and laser speckle imaging (LSI), respectively, and histological analysis (TTC) was performed at the completion of the experiments. Standing in stark contrast to the positive results observed in rats, in both strains we found that there were no differences between treated and untreated mice at 24 hours post-pMCAo in terms of infarct volume, negative functional imaging results, and major reduction in retrograde collateral blood flow as compared to pre-pMCAo baseline and surgical controls. Also, no differences were found between the strains in terms of theses variables. Potential reasons for the differences between rats and mice are discussed.
PMID: 28902897

Cooke DL,McCoy DB,Halbach VV,Hetts SW,Amans MR,Dowd CF,Higashida RT,Lawson D,Nelson J,Wang CY,Kim H,Werb Z,McCulloch C,Hashimoto T,Su H,Sun Z
Endovascular Biopsy: In Vivo Cerebral Aneurysm Endothelial Cell Sampling and Gene Expression Analysis.
Transl Stroke Res. 2017 Sep 13;
There is limited data describing endothelial cell (EC) gene expression between aneurysms and arteries partly because of risks associated with surgical tissue collection. Endovascular biopsy (EB) is a lower risk alternative to conventional surgical methods, though no such efforts have been attempted for aneurysms. We sought (1) to establish the feasibility of EB to isolate viable ECs by fluorescence-activated cell sorting (FACS), (2) to characterize the differences in gene expression by anatomic location and rupture status using single-cell qPCR, and (3) to demonstrate the utility of unsupervised clustering algorithms to identify cell subpopulations. EB was performed in 10 patients (5 ruptured, 5 non-ruptured). FACS was used to isolate the ECs and single-cell qPCR was used to quantify the expression of 48 genes. Linear mixed models and exploratory multilevel component analysis (MCA) and self-organizing maps (SOMs) were performed to identify possible subpopulations of cells. ECs were collected from all aneurysms and there were no adverse events. A total of 437 ECs was collected, 94 (22%) of which were aneurysmal cells and 319 (73%) demonstrated EC-specific gene expression. Ruptured aneurysm cells, relative controls, yielded a median p value of 0.40 with five genes (10%) with p values
PMID: 28900857

Albitar M,Ma W,Lund L,Shahbaba B,Uchio E,Feddersen S,Moylan D,Wojno K,Shore N
A Multi-Center Prospective Study to Validate an Algorithm Using Urine and Plasma Biomarkers for Predicting Gleason ≥3+4 Prostate Cancer on Biopsy.
J Cancer. 2017;8(13):2554-2560
Background: Unnecessary biopsies and overdiagnosis of prostate cancer (PCa) remain a serious healthcare problem. We have previously shown that urine- and plasma-based prostate-specific biomarkers when combined can predict high grade prostate cancer (PCa). To further validate this test, we performed a prospective multicenter study recruiting patients from community-based practices. Patients and Methods: Urine and plasma samples from 2528 men were tested prospectively. Results were correlated with biopsy findings, if a biopsy was performed as deemed necessary by the practicing urologist. Of the 2528 patients, biopsy was performed on only 524 (21%) patients. Results: Of the 524 patients, Gleason≥3+4 PCa was found in 161 (31%) and Gleason ≥4+3 was found in 62 (12%) of the patients. The urine/plasma biomarkers algorithm showed sensitivity and specificity of 75% and 69% for predicting Gleason ≥3+4. However, upon incorporating prostate size and prior history of biopsy in the algorithm, we achieved a sensitivity between 97% and 86% and a specificity between 36% and 57%, dependent on the used cut-off point. Sensitivity for predicting PCa Gleason ≥4+3 was between 96% and 99% and specificity between 59% and 37%, dependent on the cut-off point. Diagnosis of Gleason ≥3+4 was missed in 1% to 3% of tested patients and of Gleason ≥4+3 in 0.2% to 1%. Conclusion: This test when integrated with prostate volume and the prior prostate biopsy enhance the sensitivity and specificity for predicting the presence of high grade prostate cancer with negative predictive value (NPV) of 90% to 97% for Gleason ≥3+4 and between 98% to 99% for Gleason ≥4+3.
PMID: 28900493

Butler BJ,Loftus EF
Discrepancy detection in the retrieval-enhanced suggestibility paradigm.
Memory. 2017 Sep 12;:1-10
Retrieval-enhanced suggestibility (RES) refers to the finding that immediately recalling the details of a witnessed event can increase susceptibility to later misinformation. In three experiments, we sought to gain a deeper understanding of the role that retrieval plays in the RES paradigm. Consistent with past research, initial testing did increase susceptibility to misinformation - but only for those who failed to detect discrepancies between the original event and the post-event misinformation. In all three experiments, subjects who retrospectively detected discrepancies in the post-event narratives were more resistant to misinformation than those who did not. In Experiments 2 and 3, having subjects concurrently assess the consistency of the misinformation narratives negated the RES effect. Interestingly, in Experiments 2 and 3, subjects who had retrieval practice and detected discrepancies were more likely to endorse misinformation than control subjects who detected discrepancies. These results call attention to limiting conditions of the RES effect and highlight the complex relationship between retrieval practice, discrepancy detection, and misinformation endorsement.
PMID: 28899262

Chou B,Mirau P,Jiang T,Wang SW,Shea KJ
Tuning Hydrophobicity in Abiotic Affinity Reagents: Polymer Hydrogel Affinity Reagents for Molecules with Lipid-like Domains.
Biomacromolecules. 2016 May 09;17(5):1860-8
Hydrophobic interactions often dominate the associative forces between biomacromolecules. A synthetic affinity reagent must be able to exploit and optimize these interactions. We describe synthesis of abiotic affinity reagents that sequester biomacromolecules with lipid-like domains. NIPAm-based copolymer nanoparticles (NPs) containing C4-C8 hydrophobic groups were evaluated for their affinity for lipopolysaccharides (LPS), the lipophilic component of the outer membrane of Gram-negative bacteria. Optimal affinity was found for NPs incorporating a linear C4 hydrocarbon group. 1D and 2D (1)H NMR studies revealed that in water, the longer chain (C6 and C8) alkyl groups in the hydrogel NPs were engaged in intrachain association, rendering them less available to interact with LPS. Optimal LPS-NP interaction requires maximizing hydrophobicity, while avoiding side chain aggregation. Polymer compositions with high LPS binding were grafted onto agarose beads and evaluated for LPS clearance from solution; samples containing linear C4 groups also showed the highest LPS clearance capacity.
PMID: 27064286

Jia J,Li C,Luo S,Liu-Smith F,Yang J,Wang X,Wang N,Lai B,Lei T,Wang Q,Xiao S,Shao Y,Zheng Y
Yes-Associated Protein Contributes to theDevelopment of Human Cutaneous Squamous Cell Carcinoma via ActivationofRAS.
J Invest Dermatol. 2016 Jun;136(6):1267-77
Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignant tumors with an increasing incidence. Studies have shown that Yes-associated protein (YAP) participates in the development of a variety of tumors as an oncogene, but to our knowledge its role in cSCC has not been reported. In this study, we used immunohistochemistry to show that YAP expression was elevated in cSCC samples of different stages versus in normal skin and that it was well correlated with the progression of the disease. Down-regulation of YAP in cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing growth arrest during the G1/S phase transition, promoted apoptosis, and reduced invasion and migration abilities invitro. Conversely, overexpression of YAP promoted cell proliferation and protected cells against basal and chemotherapy-induced apoptosis. These oncogenic effects of YAP were associated with activation of the RAS protein and its downstream AKT and ERK. Using a mouse xenograft model, we further showed that YAP depletion inhibited cSCC tumor growth invivo. Our results suggested that YAP is involved in the carcinogenesis and development of cSCC and that it may serve as a biomarker or therapeutic target of this disease.
PMID: 26902922

Lorden AL,Jiang L,Radcliff TA,Kelly KA,Ohsfeldt RL
Potentially Preventable Hospitalizations and the Burden of Healthcare-Associated Infections.
Health Serv Res Manag Epidemiol. 4:2333392817721109
An estimated 4% of hospital admissions acquired healthcare-associated infections (HAIs) and accounted for $9.8 (USD) billion in direct cost during 2011. In 2010, nearly 140 000 of the 3.5 million potentially preventable hospitalizations (PPHs) may have acquired an HAI. There is a knowledge gap regarding the co-occurrence of these events.
PMID: 28894766

Okita K,Morales AM,Dean AC,Johnson MC,Lu V,Farahi J,Mandelkern MA,London ED
Striatal dopamine D1-type receptor availability: no difference from control but association with cortical thickness in methamphetamine users.
Mol Psychiatry. 2017 Sep 12;
Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity. Thus, both receptor subtypes may contribute to methamphetamine-induced alterations in cortical morphology and behavior. In this study, 21 methamphetamine-dependent subjects and 23 healthy controls participated in positron emission tomography and structural magnetic resonance imaging for assessment of striatal D1- and D2-type receptor availability and cortical gray-matter thickness, respectively. Although D2-type receptor availability (BPnd) was lower in the methamphetamine group, as shown previously, the groups did not differ in D1-type BPnd. In the methamphetamine group, mean cortical gray-matter thickness was negatively associated with cumulative methamphetamine use and craving for the drug. Striatal D1-type but not D2-type BPnd was negatively associated with global mean cortical gray-matter thickness in the methamphetamine group, but no association was found between gray-matter thickness and BPnd for either dopamine receptor subtype in the control group. These results suggest a role of striatal D1-type receptors in cortical adaptation to chronic methamphetamine use.Molecular Psychiatry advance online publication, 12 September 2017; doi:10.1038/mp.2017.172.
PMID: 28894300

Chung AS,Miller SM,Sun Y,Xu X,Zweifel LS
Sexual congruency in the connectome and translatome of VTA dopamine neurons.
Sci Rep. 2017 Sep 11;7(1):11120
The ventral tegmental area (VTA) dopamine system is important for reward, motivation, emotion, learning, and memory. Dysfunctions in the dopamine system are linked to multiple neurological and neuropsychiatric disorders, many of which present with sex differences. Little is known about the extent of heterogeneity in the basic organization of VTA dopamine neurons with regard to sex. Here, we characterized the cell-specific connectivity of VTA dopamine neurons, their mRNA translational profile, and basic electrophysiological characteristics in a common strain of mice. We found no major differences in these metrics, except for differential expression of a Y-chromosome associated mRNA transcript, Eif2s3y, and the X-linked, X-inactivation transcript Xist. Of note, Xist transcript was significantly enriched in dopamine neurons, suggesting tight regulation of X-linked gene expression to ensure sexual congruency. These data indicate that the features that make dopamine neurons unique are highly concordant and not a principal source of sexual dimorphism.
PMID: 28894175

Davis EP,Stout SA,Molet J,Vegetabile B,Glynn LM,Sandman CA,Heins K,Stern H,Baram TZ
Exposure to unpredictable maternal sensory signals influences cognitive development across species.
Proc Natl Acad Sci U S A. 2017 Sep 11;
Maternal care is a critical determinant of child development. However, our understanding of processes and mechanisms by which maternal behavior influences the developing human brain remains limited. Animal research has illustrated that patterns of sensory information is important in shaping neural circuits during development. Here we examined the relation between degree of predictability of maternal sensory signals early in life and subsequent cognitive function in both humans (n = 128 mother/infant dyads) and rats (n = 12 dams; 28 adolescents). Behaviors of mothers interacting with their offspring were observed in both species, and an entropy rate was calculated as a quantitative measure of degree of predictability of transitions among maternal sensory signals (visual, auditory, and tactile). Human cognitive function was assessed at age 2 y with the Bayley Scales of Infant Development and at age 6.5 y with a hippocampus-dependent delayed-recall task. Rat hippocampus-dependent spatial memory was evaluated on postnatal days 49-60. Early life exposure to unpredictable sensory signals portended poor cognitive performance in both species. The present study provides evidence that predictability of maternal sensory signals early in life impacts cognitive function in both rats and humans. The parallel between experimental animal and observational human data lends support to the argument that predictability of maternal sensory signals causally influences cognitive development.
PMID: 28893979

Sumida K,Molnar MZ,Potukuchi PK,George K,Thomas F,Lu JL,Yamagata K,Kalantar-Zadeh K,Kovesdy CP
Changes in Albuminuria and Subsequent Risk of Incident Kidney Disease.
Clin J Am Soc Nephrol. 2017 Sep 11;
Albuminuria is a robust predictor of CKD progression. However, little is known about the associations of changes in albuminuria with the risk of kidney events outside the settings of clinical trials.
PMID: 28893924

Guo Y,Rousseau J,Hsu AS,Kehoe P,Daviss M,Flores S,Renno P,Saunders K,Phillips S,Evangelista LS
Emotional and Behavioral Health Needs in Elementary School Students in an Underserved Hispanic Community.
J Sch Nurs. 2017 Jan 01;:1059840517726857
High rates of mental health problems in adolescents have been well documented; less is known about elementary school children in disadvantaged communities. We examined emotional and behavioral health needs in 202 third and fourth graders enrolled in a charter school in a largely Hispanic community. The child-reported Revised Child Anxiety and Depression Scale-25 and Teacher's Report Form were used to evaluate mental health needs as perceived by these children and their teachers. The prevalence of teacher-reported depression and child self-reported anxiety was 7.0% and 6.67%, respectively. Living in a single parent household was found to be a specific risk factor in that those children had higher rates of emotional and behavioral problems than children living with both parents. Evidence of higher depression and anxiety identified in this sample compared to national representative data suggests the need for development of culturally sensitive early prevention and intervention in this underserved community.
PMID: 28893118

Crespo A,Rodriguez-Granillo A,Lim VT
Quantum-Mechanics Methodologies in Drug Discovery: Applications of Docking and Scoring in Lead Optimization.
Curr Top Med Chem. 2017;17(23):2663-2680
The development and application of quantum mechanics (QM) methodologies in computer- aided drug design have flourished in the last 10 years. Despite the natural advantage of QM methods to predict binding affinities with a higher level of theory than those methods based on molecular mechanics (MM), there are only a few examples where diverse sets of protein-ligand targets have been evaluated simultaneously. In this work, we review recent advances in QM docking and scoring for those cases in which a systematic analysis has been performed. In addition, we introduce and validate a simplified QM/MM expression to compute protein-ligand binding energies. Overall, QMbased scoring functions are generally better to predict ligand affinities than those based on classical mechanics. However, the agreement between experimental activities and calculated binding energies is highly dependent on the specific chemical series considered. The advantage of more accurate QM methods is evident in cases where charge transfer and polarization effects are important, for example when metals are involved in the binding process or when dispersion forces play a significant role as in the case of hydrophobic or stacking interactions.
PMID: 28685695

Blum SA,Easter QT
Single Turnover at Molecular Polymerization Catalysts Reveals Spatiotemporally Resolved Reactions.
Angew Chem Int Ed Engl. 2017 Sep 11;
Multiple active individual molecular ruthenium catalysts were pinpointed within growing polynorbornene, revealing reaction dynamics and location information that is unavailable through traditional ensemble experiments. These experiments are the first single-turnover fluorescence microscopy imaging at any molecular catalyst and achieve the detection of individual monomer reactions at an industrially important molecular ruthenium ring-opening metathesis polymerization (ROMP) catalyst under synthetically relevant catalytic conditions (e.g., unmodified industrial catalyst, ambient pressure, condensed phase, ~0.03 M monomer). These results further establish the key fundamentals of this imaging technique for characterizing the reactivity and location of molecular catalysts even when they are the minor components.
PMID: 28892589

Sahyouni R,Moshtaghi O,Haidar YM,Mahboubi H,Moshtaghi A,Lin HW,Djalilian HR
Vertigo in Vestibular Schwannoma Patients Due to Other Pathologies.
Otol Neurotol. 2017 Sep 07;
To report findings from a cohort of vestibular schwannoma (VS) patients presenting with vertigo from a secondary comorbid vestibular disorder; and to discuss management strategies for this subset of patients presenting with both episodic vertigo and VS.
PMID: 28891872

Hlr G,Heckhausen J,Hoppmann CA,Infurna FJ,Wagner GG,Ram N,Gerstorf D
Levels of and changes in life satisfaction predict mortality hazards: Disentangling the role of physical health, perceived control, and social orientation.
Psychol Aging. 2017 Sep;32(6):507-520
It is well documented that well-being typically evinces precipitous decrements at the end of life. However, research has primarily taken a postdictive approach by knowing the outcome (date of death) and aligning, in retrospect, how well-being has changed for people with documented death events. In the present study, we made use of a predictive approach by examining whether and how levels of and changes in life satisfaction prospectively predict mortality hazards and delineate the role of contributing factors, including health, perceived control, and social orientation. To do so, we applied shared parameter growth-survival models to 20-year longitudinal data from 10,597 participants (n = 1,560 [15%] deceased; age at baseline: M = 44 years, SD = 17, range = 18-98 years) from the national German Socio-Economic Panel Study. Our findings showed that lower levels and steeper declines of life satisfaction each uniquely predicted higher mortality risks. Results also revealed moderating effects of age and perceived control: Life satisfaction levels and changes had stronger predictive effects for mortality hazards among older adults. Perceived control was associated with lower mortality hazards; however, this effect was diminished for those who experienced accelerated life satisfaction decline. Variance decomposition suggests that predictive effects of life satisfaction trajectories were partially unique (3%-6%) and partially shared with physical health, perceived control, and social orientation (17%-19%). Our discussion focuses on the strengths and challenges of a predictive approach to link developmental changes (in life satisfaction) to mortality hazards, and considers implications of our findings for healthy aging. (PsycINFO Database Record
PMID: 28891665

Balakirev ES,Saveliev PA,Ayala FJ
Complete Mitochondrial Genomes of the Cherskii's Sculpin Cottus czerskii and Siberian Taimen Hucho taimen Reveal GenBank Entry Errors: Incorrect Species Identification and Recombinant Mitochondrial Genome.
Evol Bioinform Online. 2017;13:1176934317726783
The complete mitochondrial (mt) genome is sequenced in 2 individuals of the Cherskii's sculpin Cottus czerskii. A surprisingly high level of sequence divergence (10.3%) has been detected between the 2 genomes of C czerskii studied here and the GenBank mt genome of C czerskii (KJ956027). At the same time, a surprisingly low level of divergence (1.4%) has been detected between the GenBank C czerskii (KJ956027) and the Amur sculpin Cottus szanaga (KX762049, KX762050). We argue that the observed discrepancies are due to incorrect taxonomic identification so that the GenBank accession number KJ956027 represents actually the mt genome of C szanaga erroneously identified as C czerskii. Our results are of consequence concerning the GenBank database quality, highlighting the potential negative consequences of entry errors, which once they are introduced tend to be propagated among databases and subsequent publications. We illustrate the premise with the data on recombinant mt genome of the Siberian taimen Hucho taimen (NCBI Reference Sequence Database NC_016426.1; GenBank accession number HQ897271.1), bearing 2 introgressed fragments (0.9?kb [kilobase]) from 2 lenok subspecies, Brachymystax lenok and Brachymystax lenok tsinlingensis, submitted to GenBank on June 12, 2011. Since the time of submission, the H taimen recombinant mt genome leading to incorrect phylogenetic inferences was propagated in multiple subsequent publications despite the fact that nonrecombinant H taimen genomes were also available (submitted to GenBank on August 2, 2014; KJ711549, KJ711550). Other examples of recombinant sequences persisting in GenBank are also considered. A GenBank Entry Error Depositary is urgently needed to monitor and avoid a progressive accumulation of wrong biological information.
PMID: 28890653

Hellman F,Hoffmann A,Tserkovnyak Y,Beach GSD,Fullerton EE,Leighton C,MacDonald AH,Ralph DC,Arena DA,Drr HA,Fischer P,Grollier J,Heremans JP,Jungwirth T,Kimel AV,Koopmans B,Krivorotov IN,May SJ,Petford-Long AK,Rondinelli JM,Samarth N,Schuller IK,Slavin AN,Stiles MD,Tchernyshyov O,Thiaville A,Zink BL
Interface-Induced Phenomena in Magnetism.
Rev Mod Phys. 89(2)
This article reviews static and dynamic interfacial effects in magnetism, focusing on interfacially-driven magnetic effects and phenomena associated with spin-orbit coupling and intrinsic symmetry breaking at interfaces. It provides a historical background and literature survey, but focuses on recent progress, identifying the most exciting new scientific results and pointing to promising future research directions. It starts with an introduction and overview of how basic magnetic properties are affected by interfaces, then turns to a discussion of charge and spin transport through and near interfaces and how these can be used to control the properties of the magnetic layer. Important concepts include spin accumulation, spin currents, spin transfer torque, and spin pumping. An overview is provided to the current state of knowledge and existing review literature on interfacial effects such as exchange bias, exchange spring magnets, spin Hall effect, oxide heterostructures, and topological insulators. The article highlights recent discoveries of interface-induced magnetism and non-collinear spin textures, non-linear dynamics including spin torque transfer and magnetization reversal induced by interfaces, and interfacial effects in ultrafast magnetization processes.
PMID: 28890576

Alaghband Y,Kwapis JL,Lpez AJ,White AO,Aimiuwu OV,Al-Kachak A,Bodinayake KK,Oparaugo NC,Dang R,Astarabadi M,Matheos DP,Wood MA
Distinct roles for the deacetylase domain of HDAC3 in the hippocampus and medial prefrontal cortex in the formation and extinction of memory.
Neurobiol Learn Mem. 2017 Sep 07;
Histone deacetylases (HDACs) are chromatin modifying enzymes that have been implicated as powerful negative regulators of memory processes. HDAC3 has been shown to play a pivotal role in long-term memory for object location as well as the extinction of cocaine-associated memory, but it is unclear whether this function depends on the deacetylase domain of HDAC3. Here, we tested whether the deacetylase domain of HDAC3 has a role in object location memory formation as well as the formation and extinction of cocaine-associated memories. Using a deacetylase-dead point mutant of HDAC3, we found that selectively blocking HDAC3 deacetylase activity in the dorsal hippocampus enhanced long-term memory for object location, but had no effect on the formation of cocaine-associated memory. When this same point mutant virus of HDAC3 was infused into the prelimbic cortex, it failed to affect cocaine-associated memory formation. With regards to extinction, impairing the HDAC3 deacetylase domain in the infralimbic cortex had no effect on extinction, but a facilitated extinction effect was observed when the point mutant virus was delivered to the dorsal hippocampus. These results suggest that the deacetylase domain of HDAC3 plays a selective role in specific brain regions underlying long-term memory formation of object location as well as cocaine-associated memory formation and extinction.
PMID: 28890149

Sanathara NM,Garau C,Alachkar A,Wang L,Wang Z,Nishimori K,Xu X,Civelli O
Melanin concentrating hormone modulates oxytocin-mediated marble burying.
Neuropharmacology. 2017 Sep 06;
Repetitive and perseverative behaviors are common features of a number of neuropsychiatric diseases such as Angelman's syndrome, Tourette's syndrome, obsessive-compulsive disorder, and autism spectrum disorders. The oxytocin system has been linked to the regulation of repetitive behavior in both animal models and humans, but many of its downstream targets have still to be found. We report that the melanin-concentrating hormone (MCH) system is a target of the oxytocin system in regulating one repetitive behavior, marble burying. First we report that nearly 60% of MCH neurons express oxytocin receptors, and demonstrate using rabies mediated tract tracing that MCH neurons receive direct presynaptic input from oxytocin neurons. Then we show that MCH receptor knockout (MCHR1KO) mice and MCH ablated animals display increased marble burying response while central MCH infusion decreases it. Finally, we demonstrate the downstream role of the MCH system on oxytocin mediated marble burying by showing that central infusions of MCH and oxytocin alone or together reduce it while antagonizing the MCH system blocks oxytocin-mediated reduction of this behavior. Our findings reveal a novel role for the MCH system as a mediator of the role of oxytocin in regulating marble-burying behavior in mice.
PMID: 28888943

Kuhlman KR,Boyle CC,Irwin MR,Ganz PA,Crespi CM,Asher A,Petersen L,Bower JE
Childhood maltreatment, psychological resources, and depressive symptoms in women with breast cancer.
Child Abuse Negl. 2017 Sep 07;72:360-369
Childhood maltreatment is associated with elevated risk for depression across the human lifespan. Identifying the pathways through which childhood maltreatment relates to depressive symptoms may elucidate intervention targets that have the potential to reduce the lifelong negative health sequelae of maltreatment exposure. In this cross-sectional study, 271 women with early-stage breast cancer were assessed after their diagnosis but before the start of adjuvant treatment (chemotherapy, radiation, endocrine therapy). Participants completed measures of childhood maltreatment exposure, psychological resources (optimism, mastery, self-esteem, mindfulness), and depressive symptoms. Using multiple mediation analyses, we examined which psychological resources uniquely mediated the relationship between childhood maltreatment and depressive symptoms. Exposure to maltreatment during childhood was robustly associated with lower psychological resources and elevated depressive symptoms. Further, lower optimism and mindfulness mediated the association between childhood maltreatment and elevated depressive symptoms. These results support existing theory that childhood maltreatment is associated with lower psychological resources, which partially explains elevated depressive symptoms in a sample of women facing breast cancer diagnosis and treatment. These findings warrant replication in populations facing other major life events and highlight the need for additional studies examining childhood maltreatment as a moderator of treatment outcomes.
PMID: 28888809

King J,Penner AM,Bandelj N,Kanjuo-Mrcela A
Market transformation and the opportunity structure for gender inequality: A cohort analysis using linked employer-employee data from Slovenia.
Soc Sci Res. 2017 Sep;67:14-33
PMID: 28888282

Geng G,Myers RJ,Qomi MJA,Monteiro PJM
Densification of the interlayer spacing governs the nanomechanical properties of calcium-silicate-hydrate.
Sci Rep. 2017 Sep 08;7(1):10986
Calciuam-silicate-hydrate (C-S-H) is the principal binding phase in modern concrete. Molecular simulations imply that its nanoscale stiffness is 'defect-driven', i.e., dominated by crystallographic defects such as bridging site vacancies in its silicate chains. However, experimental validation of this result is difficult due to the hierarchically porous nature of C-S-H down to nanometers. Here, we integrate high pressure X-ray diffraction and atomistic simulations to correlate the anisotropic deformation of nanocrystalline C-S-H to its atomic-scale structure, which is changed by varying the Ca-to-Si molar ratio. Contrary to the 'defect-driven' hypothesis, we clearly observe stiffening of C-S-H with increasing Ca/Si in the range 0.8?≤?Ca/Si?≤?1.3, despite increasing numbers of vacancies in its silicate chains. The deformation of these chains along the b-axis occurs mainly through tilting of the Si-O-Si dihedral angle rather than shortening of the Si-O bond, and consequently there is no correlation between the incompressibilities of the a- and b-axes and the Ca/Si. On the contrary, the intrinsic stiffness of C-S-H solid is inversely correlated with the thickness of its interlayer space. This work provides direct experimental evidence to conduct more realistic modelling of C-S-H-based cementitious material.
PMID: 28887517

Parker I,Evans KT,Ellefsen K,Lawson DA,Smith IF
Lattice light sheet imaging of membrane nanotubes between human breast cancer cells in culture and in brain metastases.
Sci Rep. 2017 Sep 08;7(1):11029
Membrane nanotubes are cytosolic protrusions with diameters
PMID: 28887508

Sureshchandra S,Wilson RM,Rais M,Marshall NE,Purnell JQ,Thornburg KL,Messaoudi I
Maternal Pregravid Obesity Remodels the DNA Methylation Landscape of Cord Blood Monocytes Disrupting Their Inflammatory Program.
J Immunol. 2017 Sep 08;
Prepregnancy maternal obesity is associated with adverse outcomes for the offspring, including increased incidence of neonatal bacterial sepsis and necrotizing enterocolitis. We recently reported that umbilical cord blood (UCB) monocytes from babies born to obese mothers generate a reduced IL-6/TNF-a response to TLR 1/2 and 4 ligands compared to those collected from lean mothers. These observations suggest altered development of the offspring's immune system, which in turn results in dysregulated function. We therefore investigated transcriptional and epigenetic differences within UCB monocytes stratified by prepregnancy maternal body mass index. We show that UCB monocytes from babies born to obese mothers generate a dampened response to LPS stimulation compared with those born to lean mothers, at the level of secreted immune mediators and transcription. Because gene expression profiles of resting UCB monocytes from both groups were comparable, we next investigated the role of epigenetic differences. Indeed, we detected stark differences in methylation levels within promoters and regulatory regions of genes involved in TLR signaling in resting UCB monocytes. Interestingly, the DNA methylation status of resting cells was highly predictive of transcriptional changes post-LPS stimulation, suggesting that cytosine methylation is one of the dominant mechanisms driving functional inadequacy in UCB monocytes obtained from babies born to obese mothers. These data highlight a potentially critical role of maternal pregravid obesity-associated epigenetic changes in influencing the function of an offspring's monocytes at birth. These findings further our understanding of mechanisms that explain the increased risk of infection in neonates born to mothers with high prepregnancy body mass index.
PMID: 28887432

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