The genome sequence of the Gold Triangle, Hypsopygia costalis (Fabricius, 1775).

We present a genome assembly from an individual male Hypsopygia costalis (the Gold Triangle; Arthropoda; Insecta; Lepidoptera; Pyralidae). The genome sequence is 818 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules with the Z sex chromosome assembled. The mitochondrial genome has also been assembled and is 15.3 kilobases in length. Gene annotation of this assembly on Ensembl identified 19,248 protein coding genes.

The Concise Guide to PHARMACOLOGY 2023/24: Transporters.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16182. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

A SACS deletion variant in Great Pyrenees dogs causes autosomal recessive neuronal degeneration.

ARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is a human neurological disorder characterized by progressive cerebellar ataxia and peripheral neuropathy. A recently recognized disorder in Great Pyrenees dogs is similarly characterized by widespread central nervous system degeneration leading to progressive cerebellar ataxia and spasticity, combined with peripheral neuropathy. Onset of clinical signs occurred in puppies as young as 4 months of age, with slow progression over several years. A multi-generation pedigree suggested an autosomal recessive mode of inheritance. Histopathology revealed consistent cerebellar Purkinje cell degeneration, neuronal degeneration in brainstem nuclei, widespread spinal cord white matter degeneration, ganglion cell degeneration, inappropriately thin myelin sheaths or fully demyelinated peripheral nerve fibers, and normal or only mild patterns of denervation atrophy in skeletal muscles. Genome-wide single nucleotide polymorphism (SNP) genotype data was collected from 6 cases and 26 controls, where homozygosity mapping identified a 3.3 Mb region on CFA25 in which all cases were homozygous and all controls were either heterozygous or homozygous for alternate haplotypes. This region tagged the SACS gene where variants are known to cause ARSACS. Sanger sequencing of SACS in affected dogs identified a 4 bp deletion that causes a frame shift and truncates 343 amino acids from the C terminus of the encoded sacsin protein (p.Val4244AlafsTer32). Our clinical and histopathological descriptions of this canine disorder contribute to the description of human ARSACS and represents the first naturally occurring large animal model of this disorder.

The genome sequence of the White-shouldered Marble, Apotomis turbidana (Hübner, 1825).

We present a genome assembly from an individual male Apotomis turbidana (the White-shouldered Marble; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 720.5 megabases in span. Most of the assembly is scaffolded into 28 chromosomal pseudomolecules, including the assembled Z sex chromosome. The mitochondrial genome has also been assembled and is 16.8 kilobases in length. Gene annotation of this assembly on Ensembl identified 22,646 protein coding genes.

The genome sequence of the Elbow-stripe Grass-veneer, Agriphila geniculea (Haworth, 1811).

We present a genome assembly from an individual female Agriphila geniculea (the Elbow-stripe Grass-veneer; Arthropoda; Insecta; Lepidoptera; Crambidae). The genome sequence is 781.6 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 15.4 kilobases in length. Gene annotation of this assembly on Ensembl identified 22,132 protein coding genes.

The genome sequence of the White-barred Gold, Micropterix aruncella (Scopoli, 1763).

We present a genome assembly from an individual female Micropterix aruncella (the White-barred Gold; Arthropoda, Insecta, Lepidoptera; Micropterigidae). The genome sequence is 1,079 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the assembled Z sex chromosome. The mitochondrial genome has also been assembled and is 15.0 kilobases in length.

Poverty dynamics and the determining factors among East African smallholder farmers.

CONTEXT: Rapid economic development in East Africa is matched by extremely dynamic smallholder livelihoods. Objective: To quantify the changes in poverty of smallholder farmers, to evaluate the potential of farm and off-farm activities to alleviate poverty, and to evaluate the potential barriers to poverty alleviation. METHODS: The analyses were based on a panel survey of 600 households undertaken in 2012 and re-visited approximately four years later in four sites in East Africa. The sites represented contrasting smallholder farming systems, linked to urban centres undergoing rapid economic and social change (Nairobi, Kampala, Kisumu, and Dar-es-Salaam). The surveys assessed farm management, farm productivity, livelihoods, and various measures of household welfare. RESULTS AND CONCLUSIONS: Almost two thirds of households rose above or fell below meaningful poverty thresholds - more than previously measured in this context - but overall poverty rates remained constant. Enhanced farm value production and off-farm income proved to be important mechanisms to rise out of poverty for households that were already resource-endowed. However, households in the poorest stratum in both panels appeared to be stuck in a poverty trap. They owned significantly fewer productive assets in the first panel compared to other groups (land and livestock), and these baseline assets were found to be positively correlated with farm income in the second panel survey. Equally these households were also found to be among the least educated, while education was found to be an important enabling factor for the generation of high value off-farm income. SIGNIFICANCE: Rural development that aims to stimulate increases in farm produce value as a means to alleviate poverty are only viable for already resource-endowed households, as they have the capacity to enhance farm value production. Conversely, the alleviation of extreme poverty should focus on different means, perhaps cash transfers, or the development of more sophisticated social safety nets. Furthermore, while off-farm income presents another important mechanism for poverty alleviation in rural areas, these opportunities are restricted to those households that have had access to education. As more households turn to off-farm activities to supplement or replace their livelihoods, farming approaches will also change affecting the management of natural resources. These dynamics ought to be better understood to better manage land-use transitions.

A history of shoulder instability is more common in young patients undergoing total shoulder arthroplasty.

BACKGROUND: Previous studies have shown an association between shoulder instability and the development of glenohumeral arthritis leading to total shoulder arthroplasty (TSA). The primary goal of this study was to evaluate if a history of shoulder instability was more common in patients aged <50 years undergoing TSA. The secondary objective was to determine if a history of prior surgical stabilization is more common in patients aged <50 years undergoing TSA. METHODS: Using the military health system data repository (MDR) and the Military Analysis and Reporting Tool (M2), we identified 489 patients undergoing primary TSA from October 1, 2013, to May 1, 2020, within the Military Health System (MHS). Patients aged <50 years were matched 1:2 with patients aged ≥50 years based on sex, race, and military status, with the final study population comprising 240 patients who underwent primary TSA during the study period. Electronic medical records were examined, and factors showing univariate association (P < .2) were included in a binary logistic regression analysis to determine associations between demographic or clinical factors and TSA prior to age 50 years. RESULTS: The groups differed significantly in shoulder arthritis subtype, with the older group having significantly more primary osteoarthritis (78% vs. 51%, P < .001). The younger group had significantly more patients with a history of shoulder instability (48% vs. 12%, P < .001), prior ipsilateral shoulder surgery of any type (74% vs. 34%, P < .001), and prior ipsilateral shoulder stabilization surgery (31% vs. 5%, P < .001). In the resultant logistic regression model, a history of shoulder instability (OR 5.0, P < .001) and a history of any prior ipsilateral shoulder surgery (OR 3.5, P < .001) were associated with TSA prior to the age of 50 years. CONCLUSIONS: Shoulder instability is a risk factor for TSA before age 50 years. It is unclear how surgical stabilization influences the development of secondary glenohumeral arthritis in shoulder instability. Patients should be counseled that recurrent instability could lead to earlier TSA, regardless of whether surgical stabilization is performed.

The genome sequence of the Crescent Bell, Epinotia bilunana (Haworth, 1811).

We present a genome assembly from an individual male Epinotia bilunana (the Crescent Bell; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 659.0 megabases in span. Most of the assembly is scaffolded into 28 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.4 kilobases in length.

The genome sequence of the Heath Knot-horn, Apomyelois bistriatella (Hulst, 1887).

We present a genome assembly from an individual female Apomyelois bistriatella (the Heath Knot-horn; Arthropoda; Insecta; Lepidoptera; Pyralidae). The genome sequence is 389.6 megabases in span. Most of the assembly is scaffolded into 32 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 15.2 kilobases in length.

The genome sequence of the Diamond-back Marble, Eudemis profundana (Denis & Schiffermüller, 1775).

We present a genome assembly from an individual male Eudemis profundana (the Diamond-back Marble; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 691.3 megabases in span. Most of the assembly is scaffolded into 28 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.5 kilobases in length.

The genome sequence of the Ashy Button, Acleris sparsana (Denis & Schiffermüller, 1775).

We present a genome assembly from an individual male Acleris sparsana (the Ashy Button; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 589.5 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.4 kilobases in length. Gene annotation of this assembly on Ensembl identified 22,123 protein coding genes.

The genome sequence of the Ruddy Flat-body, Agonopterix subpropinquella (Stainton, 1849).

We present a genome assembly from an individual male Agonopterix subpropinquella (the Ruddy Flat-body; Arthropoda; Insecta; Lepidoptera; Depressariidae). The genome sequence is 667.9 megabases in span. Most of the assembly is scaffolded into 28 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.5 kilobases in length. Gene annotation of this assembly on Ensembl identified 18,796 protein coding genes.

The genome sequence of the Lichen Button, Acleris literana (Linnaeus, 1758).

We present a genome assembly from an individual male Acleris literana (the Lichen Button; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 674.9 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.4 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,577 protein coding genes.

MRI of a middle ear cholesteatoma in a cat.

A 9-year-old Maine coon cat presented with right-sided Horner and facial nerve paralysis. Magnetic resonance imaging (MRI) showed a heterogeneously contrast-enhancing mass occupying the right dorsolateral compartment of the tympanic cavity and extending into the ventromedial compartment, which was expanded and fluid filled. A ventral bulla osteotomy was performed to debulk the soft tissue mass. Histopathology revealed a cholesteatoma. The cat showed slow improvement of clinical signs and was euthanized eleven months postoperatively for unrelated causes. The MRI characteristics of middle ear cholesteatoma in the present case varied from those described in humans and dogs.

Impact of SLC43A3/ENBT1 Expression and Function on 6-Mercaptopurine Transport and Cytotoxicity in Human Acute Lymphoblastic Leukemia Cells.

6-Mercaptopurine (6-MP) is used extensively in the treatment of acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases. Our laboratory determined previously, using a recombinant HEK293 cell model, that the SLC43A3-encoded equilibrative nucleobase transporter 1 (ENBT1) transports 6-MP into cells and significantly impacts the cytotoxicity of 6-MP in that model. To further investigate the clinical relevance of this finding, we now extend this work to an analysis of the impact of SLC43A3/ENBT1 expression and function on 6-MP uptake and cytotoxicity in leukemic lymphoblasts, the therapeutic target of 6-MP in ALL. A panel of ALL cell lines was assessed for SLC43A3/ENBT1 expression, ENBT1 function, and sensitivity to 6-MP. There was a significant difference in SLC43A3 expression among the cell lines that positively correlated with the rate of ENBT1-mediated 6-MP uptake. Cells with the lowest expression of SLC43A3 (SUP-B15: Vmax = 22± 5 pmol/µl per second) were also significantly less sensitive to 6-MP-induced cytotoxicity than were the highest expressing cells (ALL-1: Vmax = 69 ± 10 pmol/µl per second). Furthermore, knockdown of ENBT1 using short hairpin RNA interference (shRNAi) in RS4;11 cells caused a significant decrease in ENBT1-mediated 6-MP uptake (Vmax: RS4;11 = 40 ± 4 pmol/µl per second; RS4;11 shRNAi = 26 ± 3 pmol/µl per Second) and 6-MP cytotoxicity (EC50: RS4;11 = 0.58 ± 0.05 µM; RS4;11 shRNAi =1.44 ± 0.59 µM). This study showed that ENBT1 is a major contributor to 6-MP uptake in leukemia cell lines and may prove to be a biomarker for the therapeutic efficacy of 6-MP in patients with ALL. SIGNIFICANCE STATEMENT: This study shows that SLC43A3-encoded equilibrative nucleobase transporter 1 is responsible for the transport of 6-mercaptopurine (6-MP) into leukemia cells and that its level of expression can impact the cytotoxicity of 6-MP. Further studies are warranted to investigate the therapeutic implications in patient populations.

Perceived effects of COVID-19 restrictions on smallholder farmers: Evidence from seven lower- and middle-income countries.

CONTEXT: The COVID-19 pandemic caused unprecedented global disruption and continues to wreak havoc. Dire predictions were made about the risks to smallholder farmers in lower- and middle- income, but hard data have been lacking. We present the results from 9201 interviews with smallholder farmers from seven countries. OBJECTIVE: The objectives are to describe: i) how farmers perceive the key effects of the COVID-19 pandemic and containment measures on livelihoods and food security; ii) the effects on agricultural activities; iii) the coping strategies households deployed. METHODS: Household surveys were conducted as part of ongoing monitoring programs during the latter half of 2020. Sites in seven countries were covered: Burundi; Kenya; Rwanda; Tanzania; Uganda; Zambia; and Vietnam. Findings are representative of smallholder farmers across multiple districts per country. RESULTS AND CONCLUSIONS: The effects of the COVID-19 containment measures were widespread and often perceived to be severe. Food purchase, off-farm income, sale of farm produce, and access to crop inputs were all affected. In locations under more stringent restrictions during the time of the survey, up to 80% of households had to reduce food consumption and/or variety. Almost all households with off-farm incomes reported reductions, by half on average. A half to three-quarters of households (depending on the location) with income from farm sales reported losses compared to the pre-pandemic situation. In locations with more relaxed containment measures in place during the time of the survey, less frequent and less severe economic and food security outcomes were perceived by the respondent, with around 20% of households reporting negative outcomes. Mobility restrictions, reduced market access, crashes in sale price for agricultural goods, and soaring prices for food purchase were key factors. Sale prices generally dropped for all agricultural products in any given location, and affected not only high-value perishable products, but also staple crops such as maize and cassava. Depending on the location, between 30% and 90% of the households applied coping strategies in response to the pandemic during 2020. There was an almost complete absence of official aid amongst households interviewed. SIGNIFICANCE: Our results raise the thorny issue of how best to balance containment of disease against the wellbeing of the vulnerable rural population in lower- and middle-income countries. There is a risk that the buffering capacity of rural people will become exhausted. Possible policy measures to limit negative outcomes include i) tiered mobility restrictions with travel allowed for economic reasons; ii) short-term price guarantee schemes to stabilise the food system; iii) direct aid; iv) the timely re-installation of distribution channels for agricultural inputs.

Farm and Livelihood Characteristics After ITM Vaccination Against East Coast Fever in Tanzania.

East Coast Fever is a critical cattle disease in East and Southern Africa which is currently mainly controlled through frequent chemical removal of ticks, the disease vector. However, a vaccine conveying life-long immunity has existed for some time, known as the infection and treatment method (ITM), although it has so far not been widely adopted because of its cost, demanding distribution system and regulatory reservations. Also, despite having proved effective on the animal level, the promoters of the vaccine have not been able to show much evidence of its benefits on the herd, farm and household levels. This study, based on a cross-sectional survey of 994 cattle keepers throughout Tanzania, aims to provide such evidence by comparing indicators of herd productivity, of farm management and success as well as of household livelihoods between households that have adopted the ITM vaccine for some years with those that have only recently adopted it. Econometric models identify the contribution of ITM adoption to indicator values together with various other determining factors amongst 277 long-term adopters of ITM and the control group of 118 recent adopters as well as 118 matched farmers without access to ITM. The results confirm that ITM adoption is positively associated with all three indicators of herd-productivity considered in this study. However, it does not support any of the three indicators of farm management and only one out of four indicators representing farm success. Nevertheless, the adoption of ITM shows a positive association with all four indicators of household livelihood. Investigating the chain of intermediate outcomes, indicators of herd productivity, such as milk yield, are significantly linked to higher feed expenses, contributing to increased livestock productivity and ultimately income and food availability. Overall, these results therefore support the promotion of ITM as a beneficial technology for the sustainable development of rural livestock keepers.

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Transporters.

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15543. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Clinical features and outcome of acquired myasthenia gravis in 94 dogs.

BACKGROUND: Factors known to be associated with outcome of acquired myasthenia gravis (MG) in dogs are limited. HYPOTHESIS/OBJECTIVES: Of dogs with MG, advancing age and comorbid neoplasia are associated with poor long-term prognosis and low rates of remission. ANIMALS: Ninety-four client-owned dogs with MG diagnosed by acetylcholine receptor antibody (AChR Ab) assay between 2001 and 2019 from a university clinic and 3 private clinics in the United States. METHODS: Cases were retrospectively evaluated and data were collected to determine clinical signs, treatment, and response to therapy defined by means of a clinical scoring rubric. Immunological remission was defined as a return of the AChR Ab concentration to <0.6 nmol/L. Multivariable binary logistic regression analysis was used to identify clinical criteria predicting remission. RESULTS: An anticholinesterase drug was used to treat 90/94 (96%) dogs, which in 63/94 (67%) was the sole treatment; other drugs included immune modulators. Clinical remission (lack of clinical signs ≥4 weeks after treatment cessation) was observed in 29 (31% [95% confidence interval (CI): 22.4-40.8%]) dogs, clinical response (lack of clinical signs on treatment) in 14 (15% [95% CI: 9.0-23.6%]) dogs, clinical improvement (on treatment) in 24 (26% [95% CI: 17.8-35.2%]) dogs, and no clinical improvement in 27 (29% [95% CI: 20.5-38.6%]) dogs. Immunological remission was observed in 27/46 (59%) dogs, with clinical remission in all 27. Younger age (P = .04) and comorbid endocrine disease (P = .04) were associated with clinical remission. Initial AChR Ab concentration (P = .02) and regurgitation (P = .04) were negatively associated with clinical remission. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical remission in MG is less likely in older dogs and dogs presenting with regurgitation or high initial AChR Ab concentration, but more likely in younger dogs and dogs with comorbid endocrine disease.