Raman pH profiles for nucleic acid constituents I. Cytidine and uridine ribonucleosides.

Raman spectra of aqueous solutions of uridine and cytidine have been recorded as a function of pH with the band intensities and vibrational frequencies monitored to determine bands which may be considered as diagnostic of the concentration of the various species. Quantitative band intensity measurements indicate that not all pH-sensitive bands can be considered as diagnostic of the pK value for the acid form of the nucleoside, and for the percent species in solution. Although the accuracy of the Raman band intensity method is inherently less than that of the titrimetric or visible-ultraviolet spectrophotometric methods, the pK values and percent species agree well with those obtained from these methods. The utility of the results obtained from the pH profiles for cytidine is discussed in terms of the effect of acidification on the structural and conformational characteristics of polycytidylic acid in solution.     

Male‐specific alterations in structure of isolation call sequences of mouse pups with 16p11.2 deletion

16p11.2 deletion is one of the most common gene copy variations that increases the susceptibility to autism and other neurodevelopmental disorders. This syndrome leads to developmental delays, including speech impairment and delays in expressive language and communication skills. To study developmental impairment of vocal communication associated with 16p11.2 deletion syndrome, we used the 16p11.2del mouse model and performed an analysis of pup isolation calls (PICs). The earliest PICs at postnatal day 5 from 16p11.2del pups were found altered in a male‐specific fashion relative to wild‐type (WT) pups. Analysis of sequences of ultrasonic vocalizations (USVs) emitted by pups using mutual information between syllables at different positions in the USV spectrograms showed that dependencies exist between syllables in WT mice of both sexes. The order of syllables was not random; syllables were emitted in an ordered fashion. The structure observed in the WT pups was identified and the pattern of syllable sequences was considered typical for the mouse line. However, typical patterns were totally absent in the 16p11.2del male pups, showing on average random syllable sequences, while the 16p11.2del female pups had dependencies similar to the WT pups. Thus, we found that PICs were reduced in number in male 16p11.2 pups and their vocalizations lack the syllable sequence order emitted by WT males and females and 16p11.2 females. Therefore, our study is the first to reveal sex‐specific perinatal communication impairment in a mouse model of 16p11.2 deletion and applies a novel, more granular method of analysing the structure of USVs.     

Dormancy and germination: making every seed count in restoration

From 50 to 90% of wild plant species worldwide produce seeds that are dormant upon maturity, with specific dormancy traits driven by species' occurrence geography, growth form, and genetic factors. While dormancy is a beneficial adaptation for intact natural systems, it can limit plant recruitment in restoration scenarios because seeds may take several seasons to lose dormancy and consequently show low or erratic germination. During this time, seed predation, weed competition, soil erosion, and seed viability loss can lead to plant re‐establishment failure. Understanding and considering seed dormancy and germination traits in restoration planning are thus critical to ensuring effective seed management and seed use efficiency. There are five known dormancy classes (physiological, physical, combinational, morphological, and morphophysiological), each requiring specific cues to alleviate dormancy and enable germination. The dormancy status of a seed can be determined through a series of simple steps that account for initial seed quality and assess germination across a range of environmental conditions. In this article, we outline the steps of the dormancy classification process and the various corresponding methodologies for ex situ dormancy alleviation. We also highlight the importance of record‐keeping and reporting of seed accession information (e.g. geographic coordinates of the seed collection location, cleaning and quality information, storage conditions, and dormancy testing data) to ensure that these factors are adequately considered in restoration planning.     

Evaluation of Effects of Harvest on Alligator Populations in Louisiana

Biologists with the Louisiana Department of Wildlife and Fisheries, Louisiana, USA, have managed statewide annual harvest of alligators (Alligator mississippiensis) for 35 years (1981–present). We collected and analyzed harvest data for Louisiana alligators to determine the effects of harvest on the population structure, focusing on the larger size classes (≥274 cm) of this slow-growing species. Linear regression analyses revealed that body size-class structure, based on overall average size and the percentage of animals harvested in the larger size classes was relatively stable. Annual aerial alligator nest counts indicated a continual growth of the population, and over time harvested alligators maintained a constant average size. Analyses of population size (based on number of nests and population modeling) indicated that the current annual harvest represents approximately 3% of the population. Linear regression analysis showed that annual hunter success declined only slightly during the study period, and the scheduling of the hunt season after the hatch period and recommended hunting in areas not frequented by breeding females provides economic opportunities for hunters to participate in a sustainable harvest that preserves the larger size classes of alligators in the population. Strict enforcement of existing laws was a key factor responsible for the success of this harvest program. Comparison of alligator population size and number of harvest-related citations indicated that illegal harvest did not have a negative effect on population size, and linear regression analyses revealed that the rate of increase in citations was lower than the increase in populations over the study period. The results of this harvest program indicated that alligators can be hunted in a sustainable manner if hunting is conducted after the hatch period and occurs in areas that primarily exclude the harvest of adult females, and strict law enforcement curbs illegal activities that negatively affect populations. © 2021 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society.     

Protective impacts of household-based tuberculosis contact tracing are robust across endemic incidence levels and community contact patterns

There is an emerging consensus that achieving global tuberculosis control targets will require more proactive case finding approaches than are currently used in high-incidence settings. Household contact tracing (HHCT), for which households of newly diagnosed cases are actively screened for additional infected individuals is a potentially efficient approach to finding new cases of tuberculosis, however randomized trials assessing the population-level effects of such interventions in settings with sustained community transmission have shown mixed results. One potential explanation for this is that household transmission is responsible for a variable proportion of population-level tuberculosis burden between settings. For example, transmission is more likely to occur in households in settings with a lower tuberculosis burden and where individuals mix preferentially in local areas, compared with settings with higher disease burden and more dispersed mixing. To better understand the relationship between endemic incidence levels, social mixing, and the impact of HHCT, we developed a spatially explicit model of coupled household and community transmission. We found that the impact of HHCT was robust across settings of varied incidence and community contact patterns. In contrast, we found that the effects of community contact tracing interventions were sensitive to community contact patterns. Our results suggest that the protective benefits of HHCT are robust and the benefits of this intervention are likely to be maintained across epidemiological settings.     

Aging in Mice Reduces the Ability to Sustain Sleep/Wake States

One of the most significant problems facing older individuals is difficulty staying asleep at night and awake during the day. Understanding the mechanisms by which the regulation of sleep/wake goes awry with age is a critical step in identifying novel therapeutic strategies to improve quality of life for the elderly. We measured wake, non-rapid eye movement (NREM) and rapid-eye movement (REM) sleep in young (2–4 months-old) and aged (22–24 months-old) C57BL6/NIA mice. We used both conventional measures (i.e., bout number and bout duration) and an innovative spike-and-slab statistical approach to characterize age-related fragmentation of sleep/wake. The short (spike) and long (slab) components of the spike-and-slab mixture model capture the distribution of bouts for each behavioral state in mice. Using this novel analytical approach, we found that aged animals are less able to sustain long episodes of wakefulness or NREM sleep. Additionally, spectral analysis of EEG recordings revealed that aging slows theta peak frequency, a correlate of arousal. These combined analyses provide a window into the mechanisms underlying the destabilization of long periods of sleep and wake and reduced vigilance that develop with aging.     

Cabozantinib Inhibits Growth of Androgen-Sensitive and Castration-Resistant Prostate Cancer and Affects Bone Remodeling

Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.