Eastern Ghats tragedy: If the mines don’t get them… the dams will

“We hunt the leopard. I can show you how we track them too,” said the Konda Reddi tribal villager. We were at Villarthi village, in a remote forested stretch between the towns of Upper Sileru and Donkarayi in the northern Eastern Ghats of Andhra Pradesh’s Visakhapatnam district. Across the border lay Odisha. Historically this region supported a rich floral diversity, but in recent decades the Eastern Ghats have largely been ignored in favour of other hill regions across India. The rediscovery of the Indian golden gecko Calodactylodes aureus and the Jeypore ground gecko Geckoella jeyporensis, earlier presumed locally extinct has caused some resurgence of public interest, but not enough to make a significant difference. Several researchers have begun to study the faunal diversity of this incredible region, but the hazards confronting this landscape seem almost insurmountable

Obesity and Factors that Contribute to Obesity among Pre- Adolescents Attending Day Private Primary Schools in Nairobi, Kenya

Obesity is a diet-related condition and it refers to an abnormally high proportion of body fat. Various studies carried out in the United States reveal that obesity stems right from childhood. Childhood obesity is the most prevalent and common nutritional condition among the urban population and it is becoming an area of public concern. Cited literature suggests that feeding habits, especially during infancy and childhood predisposes the child to obesity in adulthood.  This was a descriptive study aimed at investigating obesity and factors that contribute to obesity among Pre-adolescents. The respondents were randomly selected from two day private primary schools in Nairobi. Systematic random sampling was used to select pupils from each school making a sample of 120 pupils. School head-teachers were also included in the sample. Data were collected by use of questionnaires, an interview schedule and an observation checklist. Both qualitative and quantitative data were collected. Qualitative data were analyzed by coding raw data into common themes to form patterns.  Quantitative data were analyzed by computer through the use of Statistical Package for Social Sciences (SPSS). Linear regression analysis was used to test the hypothesis.  Results were reported using frequencies and percentages. The study showed that there was a significant relationship between eating habits of the pre-adolescents and obesity. Eating food three times a day and eating any time were positively correlated with obesity. In the schools studied, 40% of the respondents ate food three times in a day while (50%) consumed food at any time of the day.  The reasons given for these trends of food consumption were: availability of money, peer pressure, boredom and influence by media.  Skipping meals had a very significant relationship with obesity.  The t-statistic of –2.88 was significant at 5% significant level.  This implied that an obese person could reduce their BMI by 2.0 points by skipping meals.  On the other hand, eating between meals was positively correlated with obesity and the result was significant at 10% significant level.  Data collected indicated that 55.8% of the respondents ate between meals. A third of the respondents were found to have a BMI of over 26, which indicates evidence of overweight. Keywords: Obesity, Eating habits, Overweight, Body Mass Index (BMI), Activity Pattern

Structural basis for bending of organic crystals

Bending is observed in organic crystals when the packing is anisotropic in such a way that strong and weak interaction patterns occur in nearly perpendicular directions

The Epidemiology of Hypoxemic Pneumonia among Young Infants in Malawi

We describe hypoxemic pneumonia prevalence in outpatient and inpatient settings, in-hospital mortality, and clinical guideline performance for identifying hypoxemia in young infants in Malawi. In this retrospective analysis of a prospective cohort study, we investigate infants younger than 2 months participating in pneumonia surveillance at seven hospitals and 18 outpatient health centers in Malawi between 2011 and 2014. Logistic regression, multiple imputations with chained equations, and pattern mixture modeling were used to determine the association between peripheral oxyhemoglobin saturation (SpO2) levels and hospital mortality. We describe referral recommendations based on clinical characteristics and SpO2 distributions. Among 1,879 analyzed cases, SpO2 < 90% was more prevalent among outpatient health center cases than that among hospitalized cases (22.6% versus 13.5%, 95% CI: 17.6–28.4% and 12.0–15.3%, respectively). A larger proportion of hospitalized infants had signs of respiratory distress than infants at health centers (67.7% versus 56.6%, P < 0.001) and the signs were higher in male versus female infants (56.7% versus 40.6%, P < 0.001). An SpO2 of 90–92% and < 90% was associated with similarly increased odds of in-hospital mortality (adjusted odds ratio [aOR]: 4.3 and 4.4, 95% CI: 1.7–11.1 and 1.8–10.5, respectively). Unrecorded, or unobtainable, SpO2 was highly associated with mortality (n = 127, aOR: 18.1; 95% CI: 7.6–42.8). Four of 22 (18%) infants at health centers who did not meet clinical referral criteria had an SpO2 ≤ 92%. Clinicians should consider hospital referral in young infants with SpO2 ≤ 92%. Infants with unobtainable SpO2 readings should be considered a high-risk group, and hospital referral of these cases may be appropriate

Cyclic β^2,3-amino acids improve the serum stability of macrocyclic peptide inhibitors targeting the SARS-CoV-2 main protease

Due to their constrained conformations, cyclic β2,3-amino acids (cβAA) are key building blocks that can fold peptides into compact and rigid structures, improving peptidase resistance and binding affinity to target proteins, due to their constrained conformations. Although the translation efficiency of cβAAs is generally low, our engineered tRNA, referred to as tRNAPro1E2, enabled efficient incorporation of cβAAs into peptide libraries using the flexible in vitro translation (FIT) system. Here we report on the design and application of a macrocyclic peptide library incorporating three kinds of cβAAs: (1R,2S)-2-aminocyclopentane carboxylic acid (β1), (1S,2S)-2-aminocyclohexane carboxylic acid (β2), and (1R,2R)-2-aminocyclopentane carboxylic acid. This library was applied to an in vitro selection against the SARS-CoV-2 main protease (Mpro). The resultant peptides, BM3 and BM7, bearing one β2 and two β1, exhibited potent inhibitory activities with IC50 values of 40 nM and 20 nM, respectively. BM3 and BM7 also showed remarkable serum stability with half-lives of 48 h and &gt;168 h, respectively. Notably, BM3A and BM7A, wherein the cβAAs were substituted with alanine, lost their inhibitory activities against Mpro and displayed substantially shorter serum half-lives. This observation underscores the significant contribution of cβAA to the activity and stability of peptides. Overall, our results highlight the potential of cβAA in generating potent and highly stable macrocyclic peptides with drug-like properties

Polyfluoroalkyl Compounds in Texas Children from Birth through 12 Years of Age

Background: For > 50 years, polyfluoroalkyl compounds (PFCs) have been used worldwide, mainly as surfactants and emulsifiers, and human exposure to some PFCs is widespread

Modifying the m6A brain methylome by ALKBH5-mediated demethylation: a new contender for synaptic tagging

Synaptic plasticity processes, which underlie learning and memory formation, require RNA to be translated local to synapses. The synaptic tagging hypothesis has previously been proposed to explain how mRNAs are available at specific activated synapses. However how RNA is regulated, and which transcripts are silenced or processed as part of the tagging process is still unknown. Modification of RNA by N6-methyladenosine (m6A/m) influences the cellular fate of mRNA. Here, by advanced microscopy, we showed that m6A demethylation by the eraser protein ALKBH5 occurs at active synaptic ribosomes and at synapses during short term plasticity. We demonstrated that at activated glutamatergic post-synaptic sites, both the YTHDF1 and YTHDF3 reader and the ALKBH5 eraser proteins increase in co-localisation to m6A-modified RNAs; but only the readers showed high co-localisation to modified RNAs during late-stage plasticity. The YTHDF1 and YTHFDF3 readers also exhibited differential roles during synaptic maturation suggesting that temporal and subcellular abundance may determine specific function. m6A-sequencing of human parahippocampus brain tissue revealed distinct white and grey matter m6A methylome profiles indicating that cellular context is a fundamental factor dictating regulated pathways. However, in both neuronal and glial cell-rich tissue, m6A effector proteins are themselves modified and m6A epitranscriptional and posttranslational modification processes coregulate protein cascades. We hypothesise that the availability m6A effector protein machinery in conjunction with RNA modification, may be important in the formation of condensed synaptic nanodomain assemblies through liquid-liquid phase separation. Our findings support that m6A demethylation by ALKBH5 is an intrinsic component of the synaptic tagging hypothesis and a molecular switch which leads to alterations in the RNA methylome, synaptic dysfunction and potentially reversible disease states

First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg