The role of frontal cortical-basal ganglia circuits in simple and sequential visuomotor learning

Imaging, recording and lesioning studies implicate the basal ganglia and anatomically related regions of frontal cortex in visuomotor learning. Two experiments were conducted to elucidate the role of frontal cortex and striatum in visuomotor learning. Several tasks were used to characterize motor function including: a visuomotor reaction time (VSRT) task, measuring response speed and accuracy to luminance cues; simple stimulus-response (S-R) learning, measuring VSRT improvements when cues occurred in consistent locations over several trials; and a serial reaction time (SRT) task measuring motor sequence learning. SRT learning was characterized by incremental changes in reaction time (RT) when trained with the same sequence across daily sessions and by abrupt RT changes when switched to random sequence sessions. In experiment 1, rats with excitotoxic lesions in primary (M1) or secondary (M2) motor cortex, primary and secondary (M1M2) motor cortices, medial prefrontal cortex (mPF) or sham surgery were tested on these tasks. Cortical lesions slowed RT in the VSRT task but did not impair short- or long-term simple S-R learning. Cortical lesions increased RTs for the initial response of a 5-response sequence in the SRT task that was exacerbated when performing repeated (learned) sequences. All groups demonstrated visuomotor sequence learning including incremental changes in RTs for later responses in learned sequences that reversed abruptly when switched to random sequences. Rats in experiment 2 were given lesions in dorsolateral striatum, dorsomedial striatum, complete dorsal striatum, ventral striatum and sham surgery. Rats with ventral striatal lesions were unimpaired on any visuomotor task demonstrating shorter RTs than controls on most measures. Dorsomedial striatal lesions significantly impaired all VSRT performance measures. Striatal lesions had no effect on short or long-term simple S-R learning. Lesions involving dorsomedial striatum disrupted initiation of motor sequences in the SRT task. This impairment was exaggerated when performing well-learned sequences. Striatal lesions did not disrupt the incremental RT changes of later responses in the sequence indicative of motor learning. Results suggest that cortico-striatal circuits are involved in initiating learned motor sequences consistent with a role in motor planning. These circuits do not appear essential for acquisition or execution of learned visuomotor sequences

Religious Coping and Spiritual Struggle Among Emergency Room Patients With Suicidal Intent

Previous literature has shown religion and spirituality to be protective factors for depressive symptoms and suicidal ideation, and that spiritual struggle is associated with increases in suicidal ideation. However, in some cases, positive religious coping may also be associated with risk factors for suicidality. The present study explored aspects of spiritual struggle or religious coping that were spontaneously offered and noted in a medical record during a standard emergency room risk assessment involving the Collaborative Assessment and Management of Suicidality (CAMS). Among 839 archival records from emergency department settings in Yamhill County, Oregon, in 2015 and 2016, only 36 interviews met criteria. It was hypothesized that those with expressed spiritual or religious struggle would indicate a higher risk for suicide through self-report compared with those who express positive religious coping. The current study found no association between self-report of suicidal intent severity and style of spiritual or religious coping, perhaps in part because the number of interviews that met criteria were far fewer than expected. Several possible explanations are considered

Sibling Mother-Infant Attachment: Different Patterns of Interaction Lead to Similar Relationships

PURPOSE: To investigate the role of maternal sensitivity and interactive behavior in sibling attachment non-/concordance. RESULTS:1) Global measures of sensitivity suggest that mothers of concordant-secure and non-concordant infants demonstrate a similar degree of sensitivity towards each child. 2) Mothers with non-concordant infants interact more similarly with each child on domains of maternal sensitivity, compared to mothers whose infants are concordant. CONCLUSION: The quality of the attachment relationship in families with non-concordant mother-infant relationships –in contrast to families with concordant dyads –does not appear to be systematically affected by maternal sensitivity as typically assessed. More detailed assessment of the interactions suggest that mothers with non-concordant relationships with their infants may be unable to adapt their behaviour to suit the unique needs of each child

The Puzzle of Sibling Attachment Non-Concordance: Implications of Categorical versus Continuous Approaches to Attachment

PURPOSE OF THE CURRENT STUDY: To determine whether characterizing the quality of attachment as a continuous measure impacts the extent to which siblings’ attachment relationships are judged concordant. To investigate whether continuous measures of attachment provide additional information regarding the similarity of more specific aspects of siblings attachment relationships

Allelic Variation in \u3cem\u3eCXCL16\u3c/em\u3e Determines CD3\u3csup\u3e+\u3c/sup\u3e T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P \u3c 0.000001) and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and EqCXCL16Sb exert a dominant mode of inheritance. Most importantly, the protein isoform EqCXCL16S but not EqCXCL16R can function as an EAV cellular receptor. Although both molecules have equal chemoattractant potential, EqCXCL16S has significantly higher scavenger receptor and adhesion properties compared to EqCXCL16R

Carbon, Metals, and Grain Size Correlate with Bacterial Community Structure in Sediments of a High Arsenic Aquifer

Bacterial communities can exert significant influence on the biogeochemical cycling of arsenic (As). This has globally important implications since As in drinking water affects the health of over 100 million people worldwide, including in the Ganges–Brahmaputra Delta region of Bangladesh where geogenic arsenic in groundwater can reach concentrations of more than 10 times the World Health Organization’s limit. Thus, the goal of this research was to investigate patterns in bacterial community composition across gradients in sediment texture and chemistry in an aquifer with elevated groundwater As concentrations in Araihazar, Bangladesh. We characterized the bacterial community by pyrosequencing 16S rRNA genes from aquifer sediment samples collected at three locations along a groundwater flow path at a range of depths between 1.5 and 15 m. We identified significant differences in bacterial community composition between locations in the aquifer. In addition, we found that bacterial community structure was significantly related to sediment grain size, and sediment carbon (C), manganese (Mn), and iron (Fe) concentrations. Deltaproteobacteria and Chloroflexi were found in higher proportions in silty sediments with higher concentrations of C, Fe, and Mn. By contrast, Alphaproteobacteria and Betaproteobacteria were in higher proportions in sandy sediments with lower concentrations of C and metals. Based on the phylogenetic affiliations of these taxa, these results may indicate a shift to more Fe-, Mn-, and humic substance-reducers in the high C and metal sediments. It is well-documented that C, Mn, and Fe may influence the mobility of groundwater arsenic, and it is intriguing that these constituents may also structure the bacterial community

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body. Gpr182 knockdown had no effect on homeostatic intestinal proliferation in vivo, but led to marked increases in proliferation during intestinal regeneration following irradiation-induced injury. In the ApcMin mouse model, which forms spontaneous intestinal adenomas, reductions in Gpr182 led to more adenomas and decreased survival. Loss of Gpr182 enhanced organoid growth efficiency ex vivo in an EGF-dependent manner. Gpr182 reduction led to increased activation of ERK1/2 in basal and challenge models, demonstrating a potential role for this orphan GPCR in regulating the proliferative capacity of the intestine. Importantly, GPR182 expression was profoundly reduced in numerous human carcinomas, including colon adenocarcinoma. Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling–induced proliferation, particularly during regeneration and adenoma formation

The Otterbein Miscellany - June 1974

https://digitalcommons.otterbein.edu/miscellany/1002/thumbnail.jp

Wealth Building in Rural America: Programs, Policies, Research

Wealth Building in Rural America: Programs, Policies, Researc

Response to gefitinib and erlotinib in Non-small cell lung cancer: a retrospective study

<p>Abstract</p> <p>Background</p> <p>In Non-small cell lung cancer (NSCLC), an overactive epidermal growth factor receptor (EGFR) pathway is a component of the malignant phenotype. Two tyrosine kinase inhibitors (TKIs) of EGFR, gefinitib and erlotinib, have been used with variable benefit.</p> <p>Methods</p> <p>We have analyzed outcome data of a population of NSCLC patients that received these TKIs to determine the benefit derived and to define the clinical and molecular parameters that correlate with response. Tumor tissue from a subgroup of these patients was analyzed by immunohistochemistry to measure the expression level of EGFR and four activated (phosphorylated) members of the pathway, pEGFR, pERK, pAKT, and pSTAT3.</p> <p>Results</p> <p>Erlotinib was slightly superior to gefitinib in all measures of response, although the differences were not statistically significant. The most robust clinical predictors of time to progression (TTP) were best response and rash (p < 0.0001). A higher level of pEGFR was associated with longer TTP, while the total EGFR level was not associated with response. Higher levels of pAKT and pSTAT3 were also associated with longer TTP. In contrast, a higher level of pERK1/2 was associated with shorter TTP.</p> <p>Conclusion</p> <p>These observations suggest the hypothesis that tumor cells that have activated EGFR pathways, presumably being utilized for survival, are clinically relevant targets for pathway inhibition. An accurate molecular predictive model of TKI response should include activated members of the EGFR pathway. TKIs may be best reserved for tumors expressing pEGFR and pAKT or pSTAT, and little pERK. In the absence of molecular predictors of response, the appearance of a rash and a positive first scan are good clinical indicators of response.</p