High temporal resolution RNA-seq time course data reveals widespread synchronous activation between mammalian lncRNAs and neighboring protein-coding genes.

The advent of massively parallel sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long noncoding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Expression of lncRNAs is strongly linked with adjacent protein-coding gene expression, suggesting potential cis-regulatory functions. A more detailed understanding of these regulatory roles may be obtained through careful examination of the precise timing of lncRNA expression relative to adjacent protein-coding genes. Despite the diversity of reported lncRNA regulatory mechanisms, where causal cis-regulatory relationships exist, lncRNA transcription is expected to precede changes in target gene expression. Using a high temporal resolution RNA-seq time course, we profiled the expression dynamics of several thousand lncRNAs and protein-coding genes in synchronized, transitioning human cells. Our findings reveal that lncRNAs are expressed synchronously with adjacent protein-coding genes. Analysis of lipopolysaccharide-activated mouse dendritic cells revealed the same temporal relationship observed in transitioning human cells. Our findings suggest broad-scale cis-regulatory roles for lncRNAs are not common. The strong association between lncRNAs and adjacent genes may instead indicate an origin as transcriptional by-products from active protein-coding gene promoters and enhancers.

Inequities in PrEP use according to Medicare status in a publicly funded sexual health clinic; a retrospective analysis.

New HIV diagnoses continue to disproportionately affect overseas-born men who have sex with men (MSM). A retrospective study of all pre-exposure prophylaxis (PrEP)-eligible MSM attending Sydney Sexual Health Centre for the first time in 2021 analysed self-reported PrEP-use, PrEP prescribed at the initial consult, and PrEP taken during 2021 using binomial logistic regression models. A total of 1367 clients were included in the analysis, 716 (52.4%) were born overseas and 414 (57.8%) were Medicare-ineligible. Medicare-ineligible clients were less likely to be on PrEP at initial visit (OR 0.45, 95% CI 0.26-0.77). This study suggests inequities in PrEP access and/or awareness in Medicare-ineligible MSM in Australia.

Evaluation of published population pharmacokinetic models to inform tacrolimus dosing in adult heart transplant recipients.

BACKGROUND AND AIM: Identification of the most appropriate population pharmacokinetic model-based Bayesian estimation is required prior to its implementation in routine clinical practice to inform tacrolimus dosing decisions. This study aimed to determine the predictive performances of relevant population pharmacokinetic models of tacrolimus developed from various solid organ transplant recipient populations in adult heart transplant recipients, stratified based on concomitant azole antifungal use. Concomitant azole antifungal therapy alters tacrolimus pharmacokinetics substantially, necessitating dose adjustments. METHODS: Population pharmacokinetic models of tacrolimus were selected (n = 17) for evaluation from a recent systematic review. The models were transcribed and implemented in NONMEM version 7.4.3. Data from 85 heart transplant recipients (2387 tacrolimus concentrations) administered the oral immediate-release formulation of tacrolimus (Prograf) were obtained up to 391 days post-transplant. The performance of each model was evaluated using: (i) prediction-based assessment (bias and imprecision) of the individual predicted tacrolimus concentration of the fourth dosing occasion (MAXEVAL = 0, FOCE-I) from 1-3 prior dosing occasions; and (ii) simulation-based assessment (prediction-corrected visual predictive check). Both assessments were stratified based on concomitant azole antifungal use. RESULTS: Regardless of the number of prior dosing occasions (1-3) and concomitant azole antifungal use, all models demonstrated unacceptable individual predicted tacrolimus concentration of the fourth dosing occasion (n = 152). The prediction-corrected visual predictive check graphics indicated that these models inadequately predicted observed tacrolimus concentrations. CONCLUSION: All models evaluated were unable to adequately describe tacrolimus pharmacokinetics in adult heart transplant recipients included in this study. Further work is required to describe tacrolimus pharmacokinetics for our heart transplant recipient cohort.

Weedy and seedy: the rapid evolution of life-history characteristics in an introduced daisy.

Despite the importance of life-history characteristics in determining a species' success, we still lack basic information about some fundamental life-history elements found across the life cycle of introduced plants. Our study assesses rapid evolutionary divergence in life-history characteristics of the beach daisy Arctotheca populifolia by comparing introduced Australian and source South African plants and measuring eight key variables including seed mass, germination, reproductive output and survival. This is the first study that compares the life history of an introduced plant species with its single original source population, providing a precise and powerful method for detecting evolutionary divergence. We found that introduced A. populifolia has evolved a suite of weedy life-history characteristics in less than 90 years: the introduced plants use a live-fast die-young strategy of germination and survival and produce significantly more inflorescences and more seeds that germinate faster. This knowledge adds to the remarkable data that we already have on the rapid evolutionary divergence occurring in the morphology, physiology and defence of this introduced plant and highlights the speed and scope of evolutionary divergence possible in plants. To fully understand and manage the future of our plant species, we must consider their potential for ongoing change in key aspects of life history.

Stock delineation of striped snakehead, Channa striata using multivariate generalised linear models with otolith shape and chemistry data.

Otoliths are commonly used to discriminate between fish stocks, through both elemental composition and otolith shape. Typical studies also have a large number of elemental compositions and shape measures relative to the number of otolith samples, with these measures exhibiting strong mean-variance relationships. These properties make otolith composition and shape data highly suitable for use within a multivariate generalised linear model (MGLM) framework, yet MGLMs have never been applied to otolith data. Here we apply both a traditional distance based permutational multivariate analysis of variance (PERMANOVA) and MGLMs to a case study of striped snakehead (Channa striata) in India. We also introduce the Tweedie and gamma distributions as suitable error structures for the MGLMs, drawing similarities to the properties of Biomass data. We demonstrate that otolith elemental data and combined otolith elemental and shape data violate the assumption of homogeneity of variance of PERMANOVA and may give misleading results, while the assumptions of the MGLM with Tweedie and gamma distributions are shown to be satisfied and are appropriate for both otolith shape and elemental composition data. Consistent differences between three groups of C. striata were identified using otolith shape, otolith chemistry and a combined otolith shape and chemistry dataset. This suggests that future research should be conducted into whether there are demographic differences between these groups which may influence management considerations. The MGLM method is widely applicable and could be applied to any multivariate otolith shape or elemental composition dataset.

Multiple pygmy blue whale acoustic populations in the Indian Ocean: whale song identifies a possible new population.

Blue whales were brought to the edge of extinction by commercial whaling in the twentieth century and their recovery rate in the Southern Hemisphere has been slow; they remain endangered. Blue whales, although the largest animals on Earth, are difficult to study in the Southern Hemisphere, thus their population structure, distribution and migration remain poorly known. Fortunately, blue whales produce powerful and stereotyped songs, which prove an effective clue for monitoring their different 'acoustic populations.' The DGD-Chagos song has been previously reported in the central Indian Ocean. A comparison of this song with the pygmy blue and Omura's whale songs shows that the Chagos song are likely produced by a distinct previously unknown pygmy blue whale population. These songs are a large part of the underwater soundscape in the tropical Indian Ocean and have been so for nearly two decades. Seasonal differences in song detections among our six recording sites suggest that the Chagos whales migrate from the eastern to western central Indian Ocean, around the Chagos Archipelago, then further east, up to the north of Western Australia, and possibly further north, as far as Sri Lanka. The Indian Ocean holds a greater diversity of blue whale populations than thought previously.

Artificial eyespots on cattle reduce predation by large carnivores.

Eyespots evolved independently in many taxa as anti-predator signals. There remains debate regarding whether eyespots function as diversion targets, predator mimics, conspicuous startling signals, deceptive detection, or a combination. Although eye patterns and gaze modify human behaviour, anti-predator eyespots do not occur naturally in contemporary mammals. Here we show that eyespots painted on cattle rumps were associated with reduced attacks by ambush carnivores (lions and leopards). Cattle painted with eyespots were significantly more likely to survive than were cross-marked and unmarked cattle, despite all treatment groups being similarly exposed to predation risk. While higher survival of eyespot-painted cattle supports the detection hypothesis, increased survival of cross-marked cattle suggests an effect of novel and conspicuous marks more generally. To our knowledge, this is the first time eyespots have been shown to deter large mammalian predators. Applying artificial marks to high-value livestock may therefore represent a cost-effective tool to reduce livestock predation.

Retrospective analysis of a Bi-National Colorectal Cancer Audit to characterize stage II colon cancer patients who were offered adjuvant chemotherapy.

BACKGROUND: Adjuvant chemotherapy for stage II colon cancer is a controversial area with treatment often reserved for patients with high-risk clinicopathological features. The aim of this study was to characterize which patients with stage II disease were offered adjuvant chemotherapy in an Australian and New Zealand setting. METHODS: Data was retrospectively collected from the prospectively maintained Bi-National Colorectal Cancer Audit. Data from all patients with their first episode of stage II colon cancer from January 2007 to January 2019 were included. RESULTS: A total of 3763 patients were identified in the Bi-National Colorectal Cancer Audit database with stage II colon cancer, of which 715 were offered chemotherapy (19%). Patients were at significant greater odds of being offered chemotherapy for stage II disease if they were <55 years old, from an urban area, discussed in a multidisciplinary team (MDT) meeting, had a greater operative urgency, a lower American Society of Anesthesiologists score, had a T4 tumour or had less than 12 lymph nodes harvested. CONCLUSION: In Australia and New Zealand the appropriate patients with high-risk features are more likely to be offered chemotherapy in line with current guideline recommendations; however, this may not be the case for regional patients. A large proportion of patients were not discussed at MDT meeting- given the decision to provide adjuvant chemotherapy for stage II disease remains a controversial area, and the likely small survival benefit offered by adjuvant chemotherapy, appropriate patient selection is critical and best discussed in an MDT setting.