Host seeking parasitic nematodes use specific odors to assess host resources.

Entomopathogenic nematodes (EPNs) are insect parasites used as biological control agents. Free-living infective juveniles (IJs) of EPNs employ host-seeking behaviors to locate suitable hosts for infection. We found that EPNs can differentiate between naïve and infected hosts, and that host attractiveness changes over time in a species-specific manner. We used solid-phase microextraction and gas chromatography/mass spectrometry to identify volatile chemical cues that may relay information about a potential host's infection status and resource availability. Among the chemicals identified from the headspace of infected hosts, 3-Methyl-2-buten-1-ol (prenol) and 3-Hydroxy-2-butanone (AMC) were selected for further behavioral assays due to their temporal correlation with the behavioral changes of IJs towards the infected hosts. Both compounds were repulsive to IJs of Steinernema glaseri and S. riobrave in a dose-dependent manner when applied on an agar substrate. Furthermore, the repulsive effects of prenol were maintained when co-presented with the uninfected host odors, overriding attraction to uninfected hosts. Prenol was attractive to dauers of some free-living nematodes and insect larvae. These data suggest that host-associated chemical cues may have several implications in EPN biology, not only as signals for avoidance and dispersal of conspecifics, but also as attractants for new potential hosts

Association of Long-Term Trajectories of Neighborhood Socioeconomic Status With Weight Change in Older adults

IMPORTANCE: Studying long-term changes in neighborhood socioeconomic status (SES) may help to better understand the associations between neighborhood exposure and weight outcomes and provide evidence supporting neighborhood interventions. Little previous research has been done to examine associations between neighborhood SES and weight loss, a risk factor associated with poor health outcomes in the older population. OBJECTIVE: to determine whether improvements in neighborhood SES are associated with reduced likelihoods of excessive weight gain and excessive weight loss and whether declines are associated with increased likelihoods of these weight outcomes. DESIGN, STUDY, AND PARTICIPANTS: This cohort study was conducted using data from the National Institutes of Health-AARP (formerly known as the American Association of Retired Persons) Diet and Health study (1995-2006). The analysis included a cohort of 126 179 adults (aged 50-71 years) whose neighborhoods at baseline (1995-1996) were the same as at follow-up (2004-2006). All analyses were performed from December 2018 through December 2020. EXPOSURES: Living in a neighborhood that experienced 1 of 8 neighborhood SES trajectories defined based on a national neighborhood SES index created using data from the US Census and American Community Survey. The 8 trajectory groups, in which high, or H, indicated rankings at or above the sample median of a specific year and low, or L, indicated rankings below the median, were HHH (ie, high in 1990 to high in 2000 to high in 2010), or stable high; HLL, or early decline; HHL, or late decline; HLH, or transient decline; LLL, or stable low; LHH, or early improvement; LLH, or late improvement; and LHL, or transient improvement. MAIN OUTCOMES AND MEASURES: Excessive weight gain and loss were defined as gaining or losing 10% or more of baseline weight. RESULTS: Among 126 179 adults, 76 225 (60.4%) were men and the mean (SD) age was 62.1 (5.3) years. Improvements in neighborhood SES were associated with lower likelihoods of excessive weight gain and weight loss over follow-up, while declines in neighborhood SES were associated with higher likelihoods of excessive weight gain and weight loss. Compared with the stable low group, the risk was significantly reduced for excessive weight gain in the early improvement group (odds ratio [OR], 0.87; 95% CI, 0.79-0.95) and for excessive weight loss in the late improvement group (OR, 0.89; 95% CI, 0.80-1.00). Compared with the stable high group, the risk of excessive weight gain was significantly increased for the early decline group (OR, 1.19; 95% CI, 1.08-1.31) and late decline group (OR, 1.13; 95% CI, 1.04-1.24) and for excessive weight loss in the early decline group (OR, 1.15; 95% CI, 1.02-1.28). The increases in likelihood were greater when the improvement or decline in neighborhood SES occurred early in the study period (ie, 1990-2000) and was substantiated throughout the follow-up (ie, the early decline and early improvement groups). Overall, we found a linear association between changes in neighborhood SES and weight outcomes, in which every 5 percentile decline in neighborhood SES was associated with a 1.2% to 2.4% increase in the risk of excessive weight gain or loss (excessive weight gain: OR, 1.01; 95% CI, 1.00-1.02 for women; OR, 1.02; 95% CI, 1.01-1.03 for men; excessive weight loss: OR, 1.02; 95% CI, 1.01-1.03 for women; OR, 1.02; 95% CI, 1.01-1.03 for men; P for- trend \u3c .0001). CONCLUSIONS AND RELEVANCE: These findings suggest that changing neighborhood environment was associated with changes in weight status in older adults

MicroRNAs Located in the Hox Gene Clusters Are Implicated in Huntington's Disease Pathogenesis

Transcriptional dysregulation has long been recognized as central to the pathogenesis of Huntington's disease (HD). MicroRNAs (miRNAs) represent a major system of post-transcriptional regulation, by either preventing translational initiation or by targeting transcripts for storage or for degradation. Using next-generation miRNA sequencing in prefrontal cortex (Brodmann Area 9) of twelve HD and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-615-3p and miR-1247-5p) up-regulated in HD at genome-wide significance (FDR q-value<0.05). Three of these, miR-196a-5p, miR-196b-5p and miR-615-3p, were expressed at near zero levels in control brains. Expression was verified for all five miRNAs using reverse transcription quantitative PCR and all but miR-1247-5p were replicated in an independent sample (8HD/8C). Ectopic miR-10b-5p expression in PC12 HTT-Q73 cells increased survival by MTT assay and cell viability staining suggesting increased expression may be a protective response. All of the miRNAs but miR-1247-5p are located in intergenic regions of Hox clusters. Total mRNA sequencing in the same samples identified fifteen of 55 genes within the Hox cluster gene regions as differentially expressed in HD, and the Hox genes immediately adjacent to the four Hox cluster miRNAs as up-regulated. Pathway analysis of mRNA targets of these miRNAs implicated functions for neuronal differentiation, neurite outgrowth, cell death and survival. In regression models among the HD brains, huntingtin CAG repeat size, onset age and age at death were independently found to be inversely related to miR-10b-5p levels. CAG repeat size and onset age were independently inversely related to miR-196a-5p, onset age was inversely related to miR-196b-5p and age at death was inversely related to miR-615-3p expression. These results suggest these Hox-related miRNAs may be involved in neuroprotective response in HD. Recently, miRNAs have shown promise as biomarkers for human diseases and given their relationship to disease expression, these miRNAs are biomarker candidates in HD

MicroRNAs located in the Hox gene clusters are implicated in huntington\u27s disease pathogenesis

Transcriptional dysregulation has long been recognized as central to the pathogenesis of Huntington\u27s disease (HD). MicroRNAs (miRNAs) represent a major system of post-transcriptional regulation, by either preventing translational initiation or by targeting transcripts for storage or for degradation. Using next-generation miRNA sequencing in prefrontal cortex (Brodmann Area 9) of twelve HD and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-615-3p and miR-1247-5p) up-regulated in HD at genome-wide significance (FDR q-value \u3c 0.05). Three of these, miR-196a-5p, miR-196b-5p and miR-615-3p, were expressed at near zero levels in control brains. Expression was verified for all five miRNAs using reverse transcription quantitative PCR and all but miR-1247-5p were replicated in an independent sample (8HD/8C). Ectopic miR-10b-5p expression in PC12 HTT-Q73 cells increased survival by MTT assay and cell viability staining suggesting increased expression may be a protective response. All of the miRNAs but miR-1247-5p are located in intergenic regions of Hox clusters. Total mRNA sequencing in the same samples identified fifteen of 55 genes within the Hox cluster gene regions as differentially expressed in HD, and the Hox genes immediately adjacent to the four Hox cluster miRNAs as up-regulated. Pathway analysis of mRNA targets of these miRNAs implicated functions for neuronal differentiation, neurite outgrowth, cell death and survival. In regression models among the HD brains, huntingtin CAG repeat size, onset age and age at death were independently found to be inversely related to miR-10b-5p levels. CAG repeat size and onset age were independently inversely related to miR-196a-5p, onset age was inversely related to miR-196b-5p and age at death was inversely related to miR-615-3p expression. These results suggest these Hox-related miRNAs may be involved in neuroprotective response in HD. Recently, miRNAs have shown promise as biomarkers for human diseases and given their relationship to disease expression, these miRNAs are biomarker candidates in HD

A JWST NIRSpec Phase Curve for WASP-121b: Dayside Emission Strongest Eastward of the Substellar Point and Nightside Conditions Conducive to Cloud Formation

We present the first exoplanet phase curve measurement made with the JWST NIRSpec instrument, highlighting the exceptional stability of this newly-commissioned observatory for exoplanet climate studies. The target, WASP-121b, is an ultrahot Jupiter with an orbital period of 30.6 hr. We analyze two broadband light curves generated for the NRS1 and NRS2 detectors, covering wavelength ranges of 2.70-3.72 micron and 3.82-5.15 micron, respectively. Both light curves exhibit minimal systematics, with approximately linear drifts in the baseline flux level of 30 ppm/hr (NRS1) and 10 ppm/hr (NRS2). Assuming a simple brightness map for the planet described by a low-order spherical harmonic dipole, our light curve fits suggest that the phase curve peaks coincide with orbital phases $3.36 \pm 0.11$ deg (NRS1) and $2.66 \pm 0.12$ deg (NRS2) prior to mid-eclipse. This is consistent with the strongest dayside emission emanating from eastward of the substellar point. We measure planet-to-star emission ratios of $3,924 \pm 7$ ppm (NRS1) and $4,924 \pm 9$ ppm (NRS2) for the dayside hemisphere, and $136 \pm 8$ ppm (NRS1) and $630 \pm 10$ ppm (NRS2) for the nightside hemisphere. The latter nightside emission ratios translate to planetary brightness temperatures of $926 \pm 12$ K (NRS1) and $1,122 \pm 10$ K (NRS2), which are low enough for a wide range of refractory condensates to form, including enstatite and forsterite. A nightside cloud deck may be blocking emission from deeper, hotter layers of the atmosphere, potentially helping to explain why cloud-free 3D general circulation model simulations systematically over-predict the nightside emission for WASP-121b.Comment: Accepted for publication in Astrophysical Journal Letters on December 29, 202

A JWST NIRSpec Phase Curve for WASP-121b: Dayside Emission Strongest Eastward of the Substellar Point and Nightside Conditions Conducive to Cloud Formation

We present the first exoplanet phase-curve measurement made with the JWST NIRSpec instrument, highlighting the exceptional stability of this newly commissioned observatory for exoplanet climate studies. The target, WASP-121b, is an ultrahot Jupiter with an orbital period of 30.6 hr. We analyze two broadband light curves generated for the NRS1 and NRS2 detectors, covering wavelength ranges of 2.70–3.72 μm and 3.82–5.15 μm, respectively. Both light curves exhibit minimal systematics, with approximately linear drifts in the baseline flux level of 30 ppm hr−1 (NRS1) and 10 ppm hr−1 (NRS2). Assuming a simple brightness map for the planet described by a low-order spherical harmonic dipole, our light-curve light curve fits suggest that the phase curve peaks coincide with orbital phases 3.°36 ± 0.°11 (NRS1) and 2.°66 ± 0.°12 (NRS2) prior to mideclipse. This is consistent with the strongest dayside emission emanating from eastward of the substellar point. We measure planet-to-star emission ratios of 3924 ± 7 ppm (NRS1) and 4924 ± 9 ppm (NRS2) for the dayside hemisphere and 136 ± 8 ppm (NRS1) and 630 ± 10 ppm (NRS2) for the nightside hemisphere. The latter nightside emission ratios translate to planetary brightness temperatures of 926 ± 12 K (NRS1) and 1122 ± 10 K (NRS2), which are low enough for a wide range of refractory condensates to form, including enstatite and forsterite. A nightside cloud deck may be blocking emission from deeper, hotter layers of the atmosphere, potentially helping to explain why cloud-free 3D general circulation model simulations systematically overpredict the nightside emission for WASP-121b

COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

<p>Abstract</p> <p>Background</p> <p>Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation.</p> <p>Methods</p> <p>Tumor COX-2, HER2 and estrogen receptor α (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival.</p> <p>Results</p> <p>COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196.</p> <p>Conclusions</p> <p>Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.</p

MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer

We previously reported that miR-1 is among the most consistently down-regulated miRs in primary human prostate tumors. In this follow-up study, we further corroborated this finding in an independent data set and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a candidate predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer. Overexpression of miR-1 in these cells led to growth inhibition and down-regulation of genes in pathways regulating cell cycle progression, mitosis, DNA replication/repair and actin dynamics. This observation was further corroborated with protein expression analysis and 3′-UTR-based reporter assays, indicating that genes in these pathways are either direct or indirect targets of miR-1. A gene set enrichment analysis revealed that the miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters the cellular organization of F-actin and inhibits tumor cell invasion and filipodia formation. In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility