Publications

Take a deeper look into all the publications produced by researchers at The Dartmouth Institute.

Brand J, Masterson TD, Emond JA, Lansigan R, Gilbert-Diamond D

2020 Jan 17;:104610doi: 10.1016/j.appet.2020.104610

Attentional bias to food cues may be a risk factor for childhood obesity, yet there are few paradigms to measure such biases in young children. Therefore, the present work introduces an eye-tracking visual search task to measure attentional bias in young children.

Appetite|2020 Jan 17

Shaker M, Chalil JM, Tran O, Vlahiotis A, Shah H, King T, Green TD, Greenhawt M

2020 Jan 16;pii: S1081-1206(20)30009-0. doi: 10.1016/j.anai.2020.01.004

Peanut allergy (PA) affects ∼1.6 million US children. The current standard of care is strict avoidance and prompt reaction treatment. PA healthcare costs and healthcare resource utilization (HCRU) are poorly understood.

Ann Allergy Asthma Immunol|2020 Jan 16

Yang W, Trahan GD, Howell ED, Speck NA, Jones KL, Gillen AE, Riemondy K, Hesselberth J, Bryder D, Ernst P

2020 Jan 16;pii: S2213-6711(19)30448-5. doi: 10.1016/j.stemcr.2019.12.009

The Mixed Lineage Leukemia (MLL1, KMT2A) gene is critical for development and maintenance of hematopoietic stem cells (HSCs), however, whether this protein is limiting for HSC development is unknown due to lack of physiologic model systems. Here, we develop an MLL1-inducible embryonic stem cell (ESC) system and show that induction of wild-type MLL1 during ESC differentiation selectively increases hematopoietic potential from a transitional c-Kit/Cd41 population in the embryoid body and also at sites of hematopoiesis in embryos. Single-cell sequencing analysis illustrates inherent heterogeneity of the c-Kit/Cd41 population and demonstrates that MLL1 induction shifts its composition toward multilineage hematopoietic identities. Surprisingly, this does not occur through increasing Hox or other canonical MLL1 targets but through an enhanced Rac/Rho/integrin signaling state, which increases responsiveness to Vla4 ligands and enhances hematopoietic commitment. Together, our data implicate a Rac/Rho/integrin signaling axis in the endothelial to hematopoietic transition and demonstrate that MLL1 actives this axis.

Stem Cell Reports|2020 Jan 16

Smith NB, Sippel LM, Rozek DC, Spangler PT, Traber D, Straud CL, Hoff R, Harpaz-Rotem I

2020 Jan 17;doi: 10.1002/da.22993

Suicidal thoughts are common among veterans with posttraumatic stress disorder (PTSD). The aim of this study was to examine the prevalence and correlates of four courses of suicidal (SI) among veterans receiving residential PTSD treatment.

Depress Anxiety|2020 Jan 17

ElTanbouly MA, Zhao Y, Nowak E, Li J, Schaafsma E, Le Mercier I, Ceeraz S, Lines JL, Peng C, Carriere C, Huang X, Day M, Koehn B, Lee SW, Silva Morales M, Hogquist KA, Jameson SC, Mueller D, Rothstein J, Blazar BR, Cheng C, Noelle RJ

2020 Jan 17;367(6475)pii: eaay0524. doi: 10.1126/science.aay0524

Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit the development of autoimmunity. Unlike all other NCRs that are expressed on activated T lymphocytes, V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is expressed on naïve T cells. We report an unexpected heterogeneity within the naïve T cell compartment in mice, where loss of VISTA disrupted the major quiescent naïve T cell subset and enhanced self-reactivity. Agonistic VISTA engagement increased T cell tolerance by promoting antigen-induced peripheral T cell deletion. Although a critical player in naïve T cell homeostasis, the ability of VISTA to restrain naïve T cell responses was lost under inflammatory conditions. VISTA is therefore a distinctive NCR of naïve T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance.

Science|2020 Jan 17

Gabrielli J, Tanski SE

2020 Jan 16;:9922819901008doi: 10.1177/0009922819901008

Clin Pediatr (Phila)|2020 Jan 16

Jacobs BL, Yabes JG, Lopa SH, Heron DE, Chang CH, Bekelman JE, Nelson JB, Bynum JPW, Barnato AE, Kahn JM

2020 Jan 13;pii: S0090-4295(20)30012-1. doi: 10.1016/j.urology.2019.11.049

To develop prostate cancer-specific physician-hospital networks to define hospital-based units that more accurately group hospitals, providers, and the patients they serve.

Urology|2020 Jan 13

Lefferts JA, Loehrer AP, Yan S, Green DC, Deharvengt SJ, LeBlanc RE

2020 Jan 14;doi: 10.1111/cup.13646

Undifferentiated melanoma should be considered in the differential diagnosis of sarcomatoid cutaneous malignancies to ensure that patients receive the correct treatment. Dermatopathologists should recognize the pitfalls of relying too heavily on immunohistochemistry to establish this diagnosis and consider ancillary tests, including single nucleotide polymorphism (SNP) copy number arrays and targeted next generation sequencing (NGS), when a definitive diagnosis cannot be rendered on a primary or metastatic tumor. This technology can also help to exclude a collision of melanoma and sarcoma when both differentiated and undifferentiated components are juxtaposed. We describe an exceedingly rare, illustrative example of undifferentiated sarcomatoid melanoma presenting as a pedunculated nodule. The clinical context and presence of a small differentiated component helped to establish the diagnosis; however, the transition from differentiated to undifferentiated melanoma was accompanied by an abrupt loss of S100, Sox10, MITF, MelanA and HMB45 with gain of CD10 and p63 staining. SNP copy number array and NGS revealed shared chromosomal copy number changes and overlapping mutations with additional aberrances detected exclusively in the sarcomatoid component; thus, excluding a collision tumor and confirming our putative impression of melanoma with progression to an undifferentiated sarcomatoid phenotype. This article is protected by copyright. All rights reserved.

J Cutan Pathol|2020 Jan 14

Salas LA, Lundgren SN, Browne EP, Punska EC, Anderton DL, Karagas MR, Arcaro KF, Christensen BC

2020 Jan 16;pii: ddz301. doi: 10.1093/hmg/ddz301

Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. DNA methylation was assessed using Illumina HumanMethylation450k in 87 breast milk samples. Through an Epigenome Wide Association Study we explored CpG sites associated with a breast cancer diagnosis in the prospectively collected milk samples from the breast that would develop cancer compared with women without a diagnosis of breast cancer using linear mixed effects models adjusted for history of breast biopsy, age, RefFreeCellMix cell estimates, time of delivery, array chip, and subject as random effect. We identified 58 differentially methylated CpG sites associated with a subsequent breast cancer diagnosis (q-value < 0.05). Nearly all CpG sites associated with a breast cancer diagnosis were hypomethylated in cases compared with controls and were enriched for CpG islands. In addition, inferred repeat element methylation was lower in breast milk DNA from cases compared to controls, and cases exhibited increased estimated epigenetic mitotic tick rate as well as DNA methylation age compared with controls. Breast milk has utility as a biospecimen for prospective assessment of disease risk, for understanding the underlying molecular basis of breast cancer risk factors and improving primary and secondary prevention of breast cancer.

Hum Mol Genet|2020 Jan 16

Guevara RB, Fox BA, Bzik DJ

2020 Jan 15;5(1)pii: e00851-19. doi: 10.1128/mSphere.00851-19

After differentiation is triggered, the tachyzoite-stage parasitophorous vacuole membrane (PVM) has been hypothesized to transition into the cyst membrane that surrounds the cyst wall and encloses bradyzoites. Here, we tracked the localization of two PVM dense granule (GRA) proteins (GRA5 and GRA7) after differentiation of the tachyzoite stage parasitophorous vacuole into the mature cyst. GRA5 and GRA7 were visible at the cyst periphery at 6 h and at all later times after differentiation, suggesting that the PVM remained intact as it transitioned into the cyst membrane. By day 3 postdifferentiation, GRA5 and GRA7 were visible in a continuous pattern at the cyst periphery. In mature 7- and 10-day-old cysts permeabilized with a saponin pulse, GRA5 and GRA7 were localized to the cyst membrane and the cyst wall regions. Cysts at different stages of cyst development exhibited differential susceptibility to saponin permeabilization, and, correspondingly, saponin selectively removed GRA5 from the cyst membrane and cyst wall region in 10-day-old cysts. GRA5 and GRA7 were localized at the cyst membrane and cyst wall region at all times after differentiation of the parasitophorous vacuole, which supports a previous model proposing that the PVM develops into the cyst membrane. In addition, evaluation of Δ, Δ, Δ, Δ, and Δ mutants revealed that PVM-localized GRAs were crucial to support the normal rate of accumulation of cyst wall proteins at the cyst periphery. establishes chronic infection in humans by forming thick-walled cysts that persist in the brain. Once host immunity wanes, cysts reactivate to cause severe, and often lethal, toxoplasmic encephalitis. There is no available therapy to eliminate cysts or to prevent their reactivation. Furthermore, how the cyst membrane and cyst wall structures develop is poorly understood. Here, we visualized and tracked the localization of parasitophorous vacuole membrane (PVM) dense granules (GRA) proteins during cyst development PVM-localized GRA5 and GRA7 were found at the cyst membrane and cyst wall region throughout cyst development, suggesting that the PVM remains intact and develops into the cyst membrane. In addition, our results show that genetic deletion of PVM GRAs reduced the rate of accumulation of cyst wall cargo at the cyst periphery and suggest that PVM-localized GRAs mediate the development and maturation of the cyst wall and cyst membrane.

mSphere|2020 Jan 15

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