Design,synthesis and evaluation of 6-(4-((substituted-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)phenanthridine analogues as antimycobacterial agents

Focus in this Letter is made to design and synthesize a series of nineteen new 6-(4-((substituted-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)phenanthridine analogues employing click chemistry and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H₃₇Rv. Among the tested compounds, 7f and 7j exhibited good activity (MIC = 3.125 μg/mL), while 8a displayed excellent activity (MIC = 1.56 μg/mL) against the growth of M. tuberculosis H₃₇Rv. In addition, 7f, 7j and 8a compounds were subjected to cytotoxic studies against mouse macrophage (RAW264.7) cell lines and the selectivity index values are >15 indicating suitability of compounds for further drug development.     

Efficacy of a Y-Design Silastic Elastomer Intrauterine Device as a Horse Contraceptive

To successfully manage population growth rates of free-roaming horses (Equus ferus caballus), an effective, long-acting contraceptive could be beneficial. We evaluated the efficacy and safety of an intrauterine device (IUD) in a breeding trial using seasonal pasture assemblages of 2 males individually pastured in large enclosures (~81 ha) each with 10 females per male. The study took place at a large animal research facility at Oklahoma State University in Stillwater, Oklahoma, USA. Specific objectives of the study were to evaluate the effectiveness of IUDs in preventing pregnancy over 20.5 months with return to fertility assessed over the subsequent 6 months and to evaluate potential effects of this IUD on ovarian function and uterine health (e.g., endometrial inflammation, infection, fibrosis). We developed a Y-design IUD, made of silastic elastomer, and set the desired retention rate at 75%. After procurement of endometrial biopsies, we inserted IUDs into the uteri of 20 females and examined them via transrectal ultrasound every 2 weeks for detection of the device and assessment of uterine health. After 20.5 months we removed the remaining 15 IUDs, obtained a second endometrial biopsy for comparision, and returned the females to their respective males for continued breeding in efforts to assess uterine return to health as indicated by pregnancy rates. The Y-design IUD met the 75% retention rate goal, with 100% contraception in females that retained the device; 12 of 20 treated females became pregnant (i.e. returned to fertility) after removal of the IUD. Based on these results, we conclude that the Y-design IUD is a safe and effective device to control fertility in free-roaming horses. © 2021 The Wildlife Society.     

Erbium(III) ion-doped borate-based glasses for 1.53 μm broad band applications

Novel erbium(III) ion-doped borate-based glasses (Er³⁺:BCNF) by conventional melt-quenching technique were designed and synthesized. The glasses were characterized for their structural, vibrational and spectroscopic properties. The nephelauxetic ratio, bonding parameters, and Judd–Ofelt (JO) intensity parameters (Ω_λ λ = 2, 4 and 6) were determined by using absorption spectrum of 1 mol% Er₂O₃ doped glass. These JO parameters were utilized to derive radiative properties for various excited states of erbium(III) ions. Emission cross-section for ⁴I_13/2 → ⁴I_15/2 transition of erbium(III) ions was computed through McCumber theory. The decay curves for (²H_11/2, ⁴S_3/2) and ⁴I_13/2 levels were recorded and analysed. All the results of Er³⁺:BCNF glasses revealed that the studied glasses are efficient and thermally stable and could be suitable for display devices, optical amplification and green laser applications.     

Genetic evidence of tiger population structure and migration within an isolated and fragmented landscape in Northwest India

Background

Majority of the tiger habitat in Indian subcontinent lies within high human density landscapes and is highly sensitive to surrounding pressures. These forests are unable to sustain healthy tiger populations within a tiger-hostile matrix, despite considerable conservation efforts. Ranthambore Tiger Reserve (RTR) in Northwest India is one such isolated forest which is rapidly losing its links with other tiger territories in the Central Indian landscape. Non-invasive genetic sampling for individual identification is a potent technique to understand the relationships between threatened tiger populations in degraded habitats. This study is an attempt to establish tiger movement across a fragmented landscape between RTR and its neighboring forests, Kuno-Palpur Wildlife Sanctuary (KPWLS) and Madhav National Park (MNP) based on non-invasively obtained genetic data.

Methods

Data from twelve microsatellite loci was used to define population structure and also to identify first generation migrants and admixed individuals in the above forests.

Results

Population structure was consistent with the Central Indian landscape and we could determine significant gene flow between RTR and MNP. We could identify individuals of admixed ancestry in both these forests, as well as first generation migrants from RTR to KPWLS and MNP.

Conclusions

Our results indicate reproductive mixing between animals of RTR and MNP in the recent past and migration of animals even today, despite fragmentation and poaching risk, from RTR towards MNP. Substantial conservation efforts should be made to maintain connectivity between these two subpopulations and also higher protection status should be conferred on Madhav National Park.     

Impact of preexisting adenovirus vector immunity on immunogenicity and protection conferred with an adenovirus-based H5N1 influenza vaccine

The prevalence of preexisting immunity to adenoviruses in the majority of the human population might adversely impact the development of adaptive immune responses against adenovirus vector-based vaccines. To address this issue, we primed BALB/c mice either intranasally (i.n.) or intramuscularly (i.m.) with varying doses of wild type (WT) human adenovirus subtype 5 (HAd5). Following the development of immunity against HAd5, we immunized animals via the i.n. or i.m. route of inoculation with a HAd vector (HAd-HA-NP) expressing the hemagglutinin (HA) and nucleoprotein (NP) of A/Vietnam/1203/04 (H5N1) influenza virus. The immunogenicity and protection results suggest that low levels of vector immunity (<520 virus-neutralization titer) induced by priming mice with up to 10(7) plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virus-neutralization titer) induced by priming mice with 10(8) p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. A further increase in the priming dose to 10(9) p.f.u. allowed only partial protection. These results suggest possible strategies to overcome the variable levels of human immunity against adenoviruses, leading to better utilization of HAd vector-based vaccines.     

Screening for elder mistreatment in dental and medical clinics

doi: 10.1111/j.1741‐2358.2010.00405.x
Screening for elder mistreatment in dental and medical clinics Objective: Elder mistreatment (EM) is a potentially fatal and largely unrecognised problem in the United States. The purpose of this study was to determine the prevalence of EM in busy clinics and specifically, we report on the feasibility of screening for EM as well as the appropriate instrumentation for screening. Background: Prevalence estimates for elder mistreatment vary, but recent data from a national sample of community‐residing adults over 60 years of age indicate that 11.4% of older adults report some form of elder mistreatment. There is a paucity of research related to screening in dental and medical clinics to understand the prevalence in such practice settings. Methods: A cross‐sectional study was conducted from January 2008 to March 2009. We enrolled 241 patients at two clinics: a medical clinic (n = 102) and dental clinics (n = 139). A mini‐mental status exam was conducted with a minimum of 18 or better for inclusion. An elder mistreatment screen was next used [elder assessment instrument (EAI‐R) for medical and Hwalek–Sengstock elder abuse screening test (HS‐EAST) for dental]. Results: For the 241 patients, we were able to compare data from the EAI‐R with the HS‐EAST. This pilot work demonstrates the feasibility of screening for EM in busy clinics since we documented patient enrolment of 20% in the medical clinics and 66% in dental clinics. Patients are willing to answer extremely‐sensitive questions related to elder mistreatment and are also willing to use computer technology for interviewing. Conclusion: Dental and medical clinics are important practice venues to screen for elder mistreatment.     

Synthesis and neurite growth evaluation of new analogues of honokiol, a neolignan with potent neurotrophic activity

A versatile synthetic route is reported towards the preparation of new analogues for potent neurotrophic agent biaryl-type lignan honokiol. A focused 24-membered library of derivatives containing five different groups at 5'-position of honokiol has been prepared in fair to good overall yields. Compared to the natural product, or to analogues with a short alkyl chain in this position, these new derivatives have lost most of the neurotrophic activity.     

Development and validation of candidate gene-specific markers for the major fertility restorer genes, <Emphasis Type="Italic">Rf4</Emphasis> and <Emphasis Type="Italic">Rf3</Emphasis> in rice

Two major nuclear genes, Rf3 and Rf4, are known to be associated with fertility restoration of wild-abortive cytoplasmic male sterility (WA-CMS) in rice. In the present study, through a comparative sequence analysis of the reported putative candidate genes, viz. PPR9-782-(M,I) and PPR762 (for Rf4) and SF21 (for Rf3), among restorer and maintainer lines of rice, we identified significant polymorphism between the two lines and developed a set of PCR-based codominant markers, which could distinguish maintainers from restorers. Among the five markers developed targeting the polymorphisms in PPR9-782-(M,I), the marker RMS-PPR9-1 was observed to show clear polymorphism between the restorer (n = 120) and maintainer lines (n = 44) analyzed. Another codominant marker, named RMS-PPR762 targeting PPR762, displayed a lower efficiency in identification of restorers and maintainers, indicating that PPR9-782-(M,I) is indeed the candidate gene for Rf4. With respect to Rf3, a codominant marker, named RMS-SF21-5 developed targeting SF21, displayed significantly lower efficiency in identification of restorers and non-restorers as compared to the Rf4-specific markers. Validation of these markers in a F₂ mapping population segregating for fertility restoration indicated that Rf4 has a major influence on fertility restoration and Rf3 is a minor gene. Further, the functional marker RMS-PPR9-1 was observed to be very useful in identification of impurities in a seed lot of the popular hybrid, DRRH3. Interestingly, when RMS-PPR9-1 and RMS-SF21-5 were considered in conjunction with analysis, near-complete, marker–trait co-segregation was observed, indicating that deployment of the candidate gene-specific markers both Rf4 and Rf3, together, can be helpful in accurate identification of fertility restorer lines and can facilitate targeted transfer of the two restorer genes into elite varieties through marker-assisted breeding.