The secret life of chromatin tethers

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The secret life of chromatin tethers

Interactions between heterochromatin and the nuclear lamina are mediated by structural proteins that function to tether heterochromatin to the nuclear periphery. Here, we present an overview of the PRR14 chromatin tether, focusing on PRR14 protein structure and the mechanisms underlying PRR14 interactions with heterochromatin and the nuclear lamina in interphase and mitosis.


The nuclear envelope plays an essential role in organizing the genome inside of the nucleus. The inner nuclear membrane is coated with a meshwork of filamentous lamin proteins that provide a surface to organize a variety of cellular processes. A subset of nuclear lamina- and membrane-associated proteins functions as anchors to hold transcriptionally silent heterochromatin at the nuclear periphery. While most chromatin tethers are integral membrane proteins, a limited number are lamina-bound. One example is the mammalian proline-rich 14 (PRR14) protein. PRR14 is a recently characterized protein with unique function that is different from other known chromatin tethers. Here, we review our current understanding of PRR14 structure and function in organizing heterochromatin at the nuclear periphery.

A highly sensitive PCR method for A1 allele detection in A2 milk samples without DNA isolation

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Abstract

We previously developed a genotyping method to detect the A1 and A2 alleles of the bovine β-casein gene. This method required DNA extraction from hair samples. Recently, demand for A2 milk (milk from cows homozygous for the A2 allele) has increased, and dairy farms are required to have certification to produce A2 milk. Here, we describe the development of a new, simple, and sensitive genotyping method for the β-casein gene that does not require DNA extraction. This method uses the CycleavePCR technique and can amplify the β-casein gene directly from raw milk samples. Genotypes obtained from the milk samples (n = 27) were completely coincident with those obtained from genomic DNA. In addition, this method could quantify the A1 allele in the milk samples. The limit of detection for the A1 allele in A2 milk was 2%. The copy numbers of the A1 allele corresponding to the 2% detection limit were estimated to be 30.5 ± 24.3 molecules/μL. These findings indicate that this new genotyping method is simple and fast for detecting the A1 allele in milk samples and can therefore be potentially used to certify A2 milk.

The opposite effect of tapinarof between IMQ and IL‐23 induced psoriasis mouse models

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Abstract

Tapinarof is an aryl hydrocarbon receptor (AHR) ligand which is used to treat plaque psoriasis in adults. However, the underlying mechanism is not yet fully understood. In this study, we applied two of the most studied psoriasis mouse models: topical application of imiquimod (IMQ) and subcutaneous injection of IL-23. Although both models successfully induced psoriasis-like lesions in mice, tapinarof had a completely opposite effect on the two models. Tapinarof decreased the expression of multiple essential cytokines involved in the pathological IL-23/IL-17/IL-22 axis and ameliorated IMQ-induced psoriatic dermatitis, inhibiting keratinocyte proliferation and abnormal differentiation. However, in the IL-23-injection-model, tapinarof instead aggravated the disease. Here, tapinarof increased epidermal thickness and differentiated epidermal dysplasia in mice. Our data suggest that tapinarof may have different effects on varied types of psoriasis.

Artificial intelligence (BirdNET) supplements manual methods to maximize bird species richness from acoustic data sets generated from regional monitoring

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Canadian Journal of Zoology, Ahead of Print.
Processing methods that maximize species richness from acoustic recordings obtained from regional monitoring programs can increase detections of uncommon, rare, and cryptic species and provide key information on species status and distribution. Using data from regional bird monitoring in Yukon, Canada, we (1) compared the number of bird species detected (species richness) and the cost associated with four acoustic processing methods (Listening, Visual Scanning, Recognizer, and Recognizer with Validation) and (2) combined Listening and Recognizer with Validation information to increase detections of all bird species at the ecoregion scale. We used comprehensive Visual Scanning to detect all bird species on the recordings. We processed ∼1% of the recordings using Listening and detected 56% of the bird community with 71.5 h of human effort. We used Recognizer (multispecies recognizer BirdNET) with Validation and detected 89% of the bird community with ∼22% of the effort required for Visual Scanning (56 and 257 h, respectively). As an application of our approach, we combined Listening and Recognizer with Validation to process recordings from five northern ecoregions and found a 23%–63% increase in the number of bird species detected with little additional effort. Combining Listening and Recognizer with Validation can maximize species detections from large passive acoustic monitoring data sets.

MULT: A new BMI reference to assess nutritional status of multi‐ethnic children and adolescents

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Abstract

Objectives

To develop a new Body Mass Index (BMI) reference (MULT) based on longitudinal data of multi-ethnic populations and to compare it to international BMI references.

Methods

The MULT BMI reference was constructed through the LMS method and the Generalized Additive Models for Location Scale and Shape (GAMLSS), with 81 310 observations of 17 505 subjects aged 0–22 years old, from the United Kingdom, Ethiopia, Peru, India, Vietnam, Brazil, and Portugal. Outlier values were removed based on weight z-scores (population level) and based on BMI z-scores using the linear mixed effects model (individual level). The MULT M, S and L curves were compared to the ones of the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), International Obesity Task Force (IOTF), and Dutch Growth Study (DUTCH). The MULT BMI percentile cutoffs for overweight and obesity were calculated using the adult BMI values of 25 and 30 kg/m2 at 17, 18, 19, and 20 years old.

Results

MULT presented the lowest mean BMI values for the ages 102–240 months for boys and 114–220 months for girls. MULT S values were similar to the WHO and IOTF for children under 60 months of age and the highest during puberty, while the L curve showed to be more symmetric than the other BMI references.

Conclusion

The MULT BMI reference was constructed based on recent data of populations from 10 countries, being a good option to assess the nutritional status of multi-ethnic populations.

Rigosertib is more potent than wortmannin and rapamycin against adult T‐cell leukemia‐lymphoma

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Rigosertib is more potent than wortmannin and rapamycin against adult T-cell leukemia-lymphoma

HTLV-1 downregulation of the mRNA level may occur as a negative feedback response to increased PI3K-Akt-mTOR phosphorylation by HTLV-1. Rigosertib was more effective than wortmannin and rapamycin in inducing cell cycle arrest, as well as a significant late apoptosis in the Inf-3T3 and MT-2 cells.


Abstract

Human T lymphotropic virus type 1 (HTLV-1) infection can cause adult T-cell lymphoblastic leukemia (ATLL), an incurable, chemotherapy-resistant malignancy. In a quest for new therapeutic targets, our study sought to determine the levels of AKT, mTOR, and PI3K in ATLL MT-2 cells, HTLV-1 infected NIH/3T3 cells (Inf-3T3), and HTLV-1 infected patients (Carrier, HAM/TSP, and ATLL). Furthermore, the effects of rigosertib, wortmannin, and rapamycin on the PI3K/Akt/mTOR pathway to inhibit the proliferation of ATLL cells were examined. The results showed that mRNA expression of Akt/PI3K/mTOR was down-regulated in carrier, HAM/TSP, and ATLL patients, as well as MT-2, and Inf-3T3 cells, compared to the healthy individuals and untreated MT-2 and Inf-3T3 as controls. However, western blotting revealed an increase in the phosphorylated and activated forms of AKT and mTOR. Treating the cells with rapamycin, wortmannin, and rigosertib decreased the phosphorylated forms of Akt and mTOR and restored their mRNA expression levels. Using these inhibitors also significantly boosted the expression of the pro-apoptotic genes, Bax/Bcl-2 ratio as well as the expression of the tumor suppressor gene p53 in the MT-2 and Inf-3T3cells. Rigosertib was more potent than wortmannin and rapamycin in inducing sub-G1 and G2-M cell cycle arrest, as well as late apoptosis in the Inf-3T3 and MT-2 cells. It also synergized the cytotoxic effects of vincristine. These findings demonstrate that HTLV-1 downregulation of the mRNA level may occur as a negative feedback response to increased PI3K-Akt-mTOR phosphorylation by HTLV-1. Therefore, using rigosertib alone or in combination with common chemotherapy drugs may be beneficial in ATLL patients.

Incidence and genetic diversity of raspberry bushy dwarf virus (RBDV) in Rubus spp. in Turkey

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Incidence and genetic diversity of raspberry bushy dwarf virus (RBDV) in Rubus spp. in Turkey

Raspberry bushy dwarf virus (RBDV), recently renamed to Idaeovirus rubi, is one of the most common viruses infecting Rubus species worldwide but there is still a limited number of genome sequences available in the GenBank database and the majority of the sequences include partial sequences of RNA-1 and RNA-2. The distribution and incidence of RBDV in main raspberry and blackberry growing provinces in Turkey were monitored during 2015–2019 and 537 Rubus spp. samples were tested by both DAS-ELISA and RT-PCR. Among the tested samples, 36 samples tested positive for RBDV by DAS-ELISA and 67 samples by RT-PCR. There was relatively low nucleotide diversity among the Turkish isolates. Turkish isolates shared 93%–97.7%, 84.3%–98.9%, and 85%–99.2% nucleotide sequence identities with available sequences in the GenBank, in partial RNA-1, movement protein (MP) and coat protein (CP) genes, respectively. In the phylogenetic tree constructed for RNA-1, MP, and CP sequences, all Turkish raspberry isolates were clustered in a distinct clade. However, the blackberry isolates showed considerable variation in nucleotide sequences and were placed in three distinct groups. The divergent blackberry isolates showed high variability in MP (84.5%–89.3%) and CP (85.5%–89.7%) regions and were placed in a distinct group. The rest of the blackberry isolates clustered together with sweet cherry RBDV isolates adjacent to the grapevine clade or together with raspberry isolates. The comparative analysis conducted on three RNA segments of RBDV highlighted the high sequence diversity of Turkish RBDV isolates.


Abstract

Raspberry bushy dwarf virus (RBDV), recently renamed to Idaeovirus rubi, is one of the most common viruses infecting Rubus species worldwide but there is still a limited number of genome sequences available in the GenBank database and the majority of the sequences include partial sequences of RNA-1 and RNA-2. The distribution and incidence of RBDV in main raspberry and blackberry growing provinces in Turkey were monitored during 2015–2019 and 537 Rubus spp. samples were tested by both DAS-ELISA and RT-PCR. Among the tested samples, 36 samples tested positive for RBDV by DAS-ELISA and 67 samples by RT-PCR. There was relatively low nucleotide diversity among the Turkish isolates. Turkish isolates shared 93%–97.7%, 84.3%–98.9%, and 85%–99.2% nucleotide sequence identities with available sequences in the GenBank, in partial RNA-1, movement protein (MP) and coat protein (CP) genes, respectively. In the phylogenetic tree constructed for RNA-1, MP, and CP sequences, all Turkish raspberry isolates were clustered in a distinct clade. However, the blackberry isolates showed considerable variation in nucleotide sequences and were placed in three distinct groups. The divergent blackberry isolates showed high variability in MP (84.5%–89.3%) and CP (85.5%–89.7%) regions and were placed in a distinct group. The rest of blackberry isolates clustered together with sweet cherry RBDV isolates adjacent to the grapevine clade or together with raspberry isolates. The comparative analysis conducted on three RNA segments of RBDV highlighted the high sequence diversity of Turkish RBDV isolates. This study also emphasizes the importance of regular monitoring of RBDV infections in Turkey, with special regard to those Rubus spp. and grapevine accessions employed in conservation and selection programmes. In particular, the presence of new RBDV genetic variants and infection of Rubus species must be taken into account to choose a correct detection protocol and management strategy.

Human cold adaptation: An unfinished agenda v2.0

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Abstract

Background

Research on human extreme cold climate adaptations has benefitted from a recent resurgence since Ted Steegmann laid out his Human Cold Adaptation Agenda in 2007. Human biologists have drastically expanded our knowledge in this area during the last 15 years, but we still have a great deal more work to do to fulfill the cold climate adaptation agenda.

Methods

Here, I follow Steegmann's example by providing a review of cold climate adaptations and setting forth a new, expanded agenda.

Results

I review the foundational work on cold climate adaptations including classic Bergmann, Allen, and Thomson rules as well as early work assessing metabolic differences among Indigenous cold climate populations. From there, I discuss some of the groundbreaking work currently taking place on cold climate adaptations such as brown adipose tissue (a heat generating organ), physical activity levels, metabolic rates, and behavioral/cultural mechanisms. Finally, I present a path forward for future research with a focus on some of the basic extreme cold adaptations as well as how human biologists should approach the effects of climate change on human health and well-being, particularly within a cold climate context.

Conclusion

The Arctic has felt the dramatic effects of climate change sooner and more acutely than other parts of the world, making it an ideal location for studying both cold climate adaptations and climate change resilience. Human biologists have a great deal to contribute to the conversation on not only adaptations to extreme cold, but also the ways in which climate change is being embodied by cold climate populations.

Begomovirus diversity in tomato crops in Costa Rica

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Begomovirus diversity in tomato crops in Costa Rica

Begomoviruses, including PepGMV, ToYMoV, ToLCSiV and TYLCV, were detected in Costa Rica, presenting challenges due to their recombination and wide host range. However, understanding of TYLCV's spread and the distribution of other bipartite begomoviruses in the country remains limited. In a study analyzing 429 georeferenced tomato samples, TYLCV was found in all six provinces, with varying prevalence. Alajuela, Cartago, and Heredia were the most affected regions. The presence of TYLCV correlated with the presence of the B. tabaci MED whitefly, offering valuable insights for disease management and crop enhancement strategies.


Abstract

Begomoviruses (Geminiviridae family) are characterized by their high recombination rate and a wide range of hosts, making their control difficult. In Costa Rica, various species of bipartite begomoviruses have been reported, which are Pepper golden mosaic virus (PepGMV), Tomato yellow mottle virus (ToYMoV), Tomato leaf curl Sinaloa virus (ToLCSiV) and the monopartite begomovirus Tomato yellow leaf curl virus (TYLCV). Since the TYLCV first report in Costa Rica, neither additional knowledge has been produced on how this begomovirus has spread in the country's territory nor on the distribution of the other bipartite species. A total of 429 tomato samples collected during the years 2015–2016 were used to study these aspects. Each sample was georeferenced and analysed with various techniques such as nucleic acid hybridization, polymerase chain reaction (PCR) and sequencing for the begomoviruses previously reported in Costa Rica. It was found that the presence/absence of the different species can vary, depending on the province. TYLCV is present in the six provinces analysed in this work, with a proportion from 3.7 to 86.6 per cent. Alajuela, Cartago, and Heredia are the provinces most affected by tomato-infecting begomoviruses. Fourteen different haplotypes of TYLCV were detected, but all were identified as TYLCV-IL. The distribution of TYLCV was related to the presence of the whitefly Bemisia tabaci MED, especially in the country's main tomato production areas. This information allows the phytosanitary surveillance services to develop strategies for the integrated management of the disease and to contribute data to the genetic improvement programmes of the crop.

Examining the associations between testosterone and biomarkers as men age

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Abstract

Objectives

Testosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone-binding globulin (SHBG), using a large nationally-representative data set (National Health and Nutrition Examination Survey; NHANES).

Methods

NHANES is a cross-sectional survey, physical examination, and laboratory evaluation of a nationally-representative sample of a non-institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013–2014 and NHANES 2015–2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), insulin, glucose, and age.

Results

An overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA-IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA-IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre-diabetic HOMA-IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables.

Conclusion

The results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.