Nocturnal cooling of urban areas governs the evolution of thermal state and many thermal-driven environmental issues in cities, especially those suffer strong urban heat island (UHI) effect. Advances in the fundamental understanding of the underlying physics of nighttime UHI involve disentangling complex contributing effects and remains an open challenge. In this study, we develop new numerical algorithms to characterize the thermodynamics of urban nocturnal cooling based on solving the energy balance equations for both the landscape surface and the overlying atmosphere. Further, a scaling law is proposed to relate the UHI intensity to a range of governing mechanisms, including the vertical and horizontal transport of heat in the surface layer, the urban-rural breeze, and the possible urban expansion. The accuracy of proposed methods is evaluated against in-situ urban measurements collected in cities with different geographic and climatic conditions. It is found that the vertical and horizontal contributors modulate the nocturnal UHI at distinct elevation in the atmospheric boundary layer.
Most molecular fingerprinting techniques, including denaturing gradient gel electrophoresis (DGGE) [1], comparative genomic hybridization (CGH) [2], real-time polymerase chain reaction (RT-PCR) [3], destroy community structure and/or cellular integrity, therefore lost the info. of the spatial locus and the in situ genomic copy number of the cells. An alternative technique, fluorescence in situ hybridization (FISH) doesn't require sample disintegration but needs to develop specific markers and doesn't provide info. related to genomic copy number.
Here, a microbial analysis tool, Spatial Analytical Microbial Imaging (SAMI), is described. An application was performed with a mixture of Synechocystis sp. PCC 6803 and E. coli K-12 MG1655. The intrinsic property of their genome, reflected by the average fluorescence intensity (AFI), distinguished them in 3D. And their growth rates were inferred by comparing the total genomic fluorescence binding area (GFA) with that of the pure culture standards. A 93% of accuracy in differentiating the species was achieved.
• SAMI does not require sample disintegration and preserves the community spatial structure.
• It measures the 3D locus of cells within the mixture and may differentiate them according to the property of their genome.
• It allows assessment of the growth rate of the cells within the mixture by comparing their genomic copy number with that of the pure culture standards.
Atypical brainstem modulation of pain might contribute to changes in sensory processing typical of migraine. The study objective was to investigate whether migraine is associated with brainstem structural alterations that correlate with this altered pain processing. MRI T1-weighted images of 55 migraine patients and 58 healthy controls were used to: (1) create deformable mesh models of the brainstem that allow for shape analyses; (2) calculate volumes of the midbrain, pons, medulla and the superior cerebellar peduncles; (3) interrogate correlations between regional brainstem volumes, cutaneous heat pain thresholds, and allodynia symptoms. Migraineurs had smaller midbrain volumes (healthy controls = 61.28 mm3, SD = 5.89; migraineurs = 58.80 mm3, SD = 6.64; p = 0.038), and significant (p < 0.05) inward deformations in the ventral midbrain and pons, and outward deformations in the lateral medulla and dorsolateral pons relative to healthy controls. Migraineurs had a negative correlation between ASC-12 allodynia symptom severity with midbrain volume (r = − 0.32; p = 0.019) and a positive correlation between cutaneous heat pain thresholds with medulla (r = 0.337; p = 0.012) and cerebellar peduncle volumes (r = 0.435; p = 0.001). Migraineurs with greater symptoms of allodynia have smaller midbrain volumes and migraineurs with lower heat pain thresholds have smaller medulla and cerebellar peduncles. The brainstem likely plays a role in altered sensory processing in migraine and brainstem structure might reflect severity of allodynia and hypersensitivity to pain in migraine.
Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.
We used the Affymetrix® Genome-Wide Human SNP Array 6.0 to identify heterospecific markers and compare copy number and structural genomic variation between humans and rhesus macaques. Over 200,000 human copy number variation (CNV) probes were mapped to a Chinese and an Indian rhesus macaque sample. Observed genomic rearrangements and synteny were in agreement with the results of a previously published genomic comparison between humans and rhesus macaques. Comparisons between each of the two rhesus macaques and humans yielded 206 regions with copy numbers that differed by at least two fold in the Indian rhesus macaque and human, 32 in the Chinese rhesus macaque and human, and 147 in both rhesus macaques. The detailed genomic map and preliminary CNV data are useful for better understanding genetic variation in rhesus macaques, identifying derived changes in human CNVs that may have evolved by selection, and determining the suitability of rhesus macaques as human models for particular biomedical studies.
Background: Peru is characterized by high cervical cancer incidence and mortality rates. The country also experiences significant gaps in quality cervical cancer screening coverage for the population.
Objective: This descriptive mixed methods study conducted in Cusco, Peru, aimed to assess the attitudes and perceptions of medical staff, health care workers, and patients toward a cervical cancer screening program that included both clinic-based and community outreach services conducted by a nongovernmental organization clinic (CerviCusco). The study also explored patient knowledge and attitudes around cervical cancer and about the human papillomavirus (HPV) to inform patient education efforts.
Methods: The study employed structured interviews with key informants (n=16) primarily from CerviCusco, which provides cervical cancer prevention, screening, diagnosis and treatment services, and surveys with a sample of patients (n=30) receiving services at the clinic and at screening campaigns.
Results: The majority of key informant medical staff participants felt that the general public had a very negative view of government health services. One theme running throughout the interviews was the perception that the general population lacked a culture of preventive health care and would wait until symptoms were severe before seeking treatment. Regarding services that were received by patients at CerviCusco, the participants responded that the prices were reasonable and more affordable than some private clinics. Patients attending the rural health campaigns liked that the services were free and of good quality.
Conclusion: CerviCusco has demonstrated its capacity to provide screening outreach campaigns to populations who had not previously had access to liquid-based cytology services. The finding that patients had generally low levels of knowledge about cervical cancer and the HPV vaccine prompted the development of culturally and linguistically appropriate educational and promotional materials to improve the educational component of the periodic campaigns conducted primarily in rural areas of Andean Peru.
Telomerase is a ribonucleoprotein (RNP) enzyme that requires an integral telomerase RNA (TR) subunit, in addition to the catalytic telomerase reverse transcriptase (TERT), for enzymatic function. The secondary structures of TRs from the three major groups of species, ciliates, fungi, and vertebrates, have been studied extensively and demonstrate dramatic diversity. Herein, we report the first comprehensive secondary structure of TR from echinoderms—marine invertebrates closely related to vertebrates—determined by phylogenetic comparative analysis of 16 TR sequences from three separate echinoderm classes. Similar to vertebrate TR, echinoderm TR contains the highly conserved template/pseudoknot and H/ACA domains. However, echinoderm TR lacks the ancestral CR4/5 structural domain found throughout vertebrate and fungal TRs. Instead, echinoderm TR contains a distinct simple helical region, termed eCR4/5, that is functionally equivalent to the CR4/5 domain. The urchin and brittle star eCR4/5 domains bind specifically to their respective TERT proteins and stimulate telomerase activity. Distinct from vertebrate telomerase, the echinoderm TR template/pseudoknot domain with the TERT protein is sufficient to reconstitute significant telomerase activity. This gain-of-function of the echinoderm template/pseudoknot domain for conferring telomerase activity presumably facilitated the rapid structural evolution of the eCR4/5 domain throughout the echinoderm lineage. Additionally, echinoderm TR utilizes the template-adjacent P1.1 helix as a physical template boundary element to prevent nontelomeric DNA synthesis, a mechanism used by ciliate and fungal TRs. Thus, the chimeric and eccentric structural features of echinoderm TR provide unparalleled insights into the rapid evolution of telomerase RNP structure and function.
Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole genome sequencing analysis of 133 rhesus macaques revealed >43.7 million single nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and non-coding variation, and its cellular consequences. Despite modestly higher levels of non-synonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of non-synonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease.
Mutations in ribosomal RNA (rRNA) have traditionally been detected by the primer extension assay, which is a tedious and multistage procedure. Here, we describe a simple and straightforward fluorescence assay based on binary deoxyribozyme (BiDz) sensors. The assay uses two short DNA oligonucleotides that hybridize specifically to adjacent fragments of rRNA, one of which contains a mutation site. This hybridization results in the formation of a deoxyribozyme catalytic core that produces the fluorescent signal and amplifies it due to multiple rounds of catalytic action. This assay enables us to expedite semi- quantification of mutant rRNA content in cell cultures starting from whole cells, which provides information useful for optimization of culture preparation prior to ribosome isolation. The method requires less than a microliter of a standard Escherichia coli cell culture and decreases analysis time from several days (for primer extension assay) to 1.5 h with hands-on time of ∼10 min. It is sensitive to single-nucleotide mutations. The new assay simplifies the preliminary analysis of RNA samples and cells in molecular biology and cloning experiments and is promising in other applications where fast detection/ quantification of specific RNA is required.
MicroRNAs (miRNAs) regulate gene output by targeting degenerate elements in mRNAs and have undergone drastic expansions in higher metazoan genomes. The evolutionary advantage of maintaining copies of highly similar miRNAs is not well understood, nor is it clear what unique functions, if any, miRNA family members possess. Here, we study evolutionary patterns of metazoan miRNAs, focusing on the targeting preferences of the let-7 and miR-10 families. These studies reveal hotspots for sequence evolution with implications for targeting and secondary structure. High-throughput screening for functional targets reveals that each miRNA represses sites with distinct features and regulates a large number of genes with cooperative function in regulatory networks. Unexpectedly, given the high degree of similarity, single-nucleotide changes grant miRNA family members with distinct targeting preferences. Together, our data suggest complex functional relationships among miRNA duplications, novel expression patterns, sequence change, and the acquisition of new targets.