Measuring Relative Wind Speeds in Stratospheric Balloons with Cup Anemometers: The TASEC-Lab Mission.

This paper shows wind speed measurements from the TASEC-Lab experiment in a stratospheric balloon mission. The mission was launched in July 2021 from León (Spain) aerodrome. Measurements of horizontal wind speed in relation to the balloon gondola were successfully carried out with a cup anemometer. According to the available literature, this is the first time a cup anemometer has been used in a stratospheric balloon mission. The results indicate the need to consider the horizontal wind speed from the balloon ascent phase for thermal calculations of the mission.

Early Detection of Vascular Obstruction in Microvascular Flaps Using a Thermographic Camera.

BACKGROUND: In microsurgical reconstruction, vascular obstruction occurs in approximately 20% of patients. Close monitoring is central to their care. Clinical/Doppler detection of vascular obstruction could be enhanced by thermography. METHODS: A diagnostic test design included consecutive cases of hospitalized patients, ≥18 years old, who underwent surgery with free flaps. Two researchers separately evaluated patients with clinical/Doppler methods and thermographic camera hourly for 24 hours, every 2 hours for the next 24 hours, and then every 3 hours until discharge. The gold standard was visualization of thrombus or vascular obstruction during surgical reintervention. Sensitivity, specificity, positive/negative predictive value (PPV/NPV), and a delta temperature receiver operating characteristic (ROC) curve were calculated. RESULTS: A total of 2,364 tests were performed with a thermographic camera in 40 patients (31 females, 9 males) aged 50.12 ± 9.7 years. There were 28 deep inferior epigastric perforator, 5 anterolateral thigh, 3 radial, 2 scapular, 1 fibular, and 1 anteromedial thigh flaps included. Six (15%) had postoperative vascular obstruction (5 venous and 1 arterial). One flap developed partial necrosis and one total necrosis (overall survival 97.5%). ROC curve (area 0.97) showed the best results at ≥ 1.8°C of difference to the surrounding skin. Considering two consecutive positive evaluations, the sensitivity was 93%, specificity 96%, PPV 57%, and NPV 99%. The thermal imaging camera allows to identify the obstruction between 2 and 12 hours before the clinical method. CONCLUSION: Utilizing a thermographic camera can reduce detection time of vascular obstruction by several hours in microvascular free flaps that include the cutaneous island. This method proves useful for early diagnosis of postoperative vascular obstruction.

Genetic variation among African swine fever genotype II viruses, eastern and central Europe.

African swine fever virus (ASFV) was first reported in eastern Europe/Eurasia in 2007. Continued spread of ASFV has placed central European countries at risk, and in 2014, ASFV was detected in Lithuania and Poland. Sequencing showed the isolates are identical to a 2013 ASFV from Belarus but differ from ASFV isolated in Georgia in 2007.

Characterization of the Protective Cellular Immune Response in Pigs Immunized Intradermally with the Live Attenuated African Swine Fever Virus (ASFV) Lv17/WB/Rie1.

Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, especially in sensitive host species and focused on unravelling protective mechanisms, will contribute to the development of safer and more effective vaccines. The present study provides a detailed analysis of phenotypic and functional data on cellular responses induced by intradermal immunization and subsequent boosting of domestic pigs with the naturally attenuated field strain Lv17/WB/Rie1, as well as the mechanisms underlying protection against intramuscular challenge with the virulent genotype II Armenia/07 strain. The transient increase in IL-8 and IL-10 in serum observed after immunization might be correlated with survival. Protection was also associated with a robust ASFV-specific polyfunctional memory T-cell response, where CD4CD8 and CD8 T cells were identified as the main cellular sources of virus-specific IFNγ and TNFα. In parallel with the cytokine response, these T-cell subsets also showed specific cytotoxic activity as evidenced by the increased expression of the CD107a degranulation marker. Along with virus-specific multifunctional CD4CD8 and CD8 T-cell responses, the increased levels of antigen experienced in cytotoxic CD4 T cells observed after the challenge in immunized pigs might also contribute to controlling virulent infection by killing mechanisms targeting infected antigen-presenting cells. Future studies should elucidate whether the memory T-cell responses evidenced in the present study persist and provide long-term protection against further ASFV infections.

Older Adult Patients in the Emergency Department: Which Patients should be Selected for a Different Approach?

BACKGROUND: While multidimensional and interdisciplinary assessment of older adult patients improves their short-term outcomes after evaluation in the emergency department (ED), this assessment is time-consuming and ill-suited for the busy environment. Thus, identifying patients who will benefit from this strategy is challenging. Therefore, this study aimed to identify older adult patients suitable for a different ED approach as well as independent variables associated with poor short-term clinical outcomes. METHODS: We included all patients ≥65 years attending 52 EDs in Spain over 7 days. Sociodemographic, comorbidity, and baseline functional status data were collected. The outcomes were 30-day mortality, re-presentation, hospital readmission, and the composite of all outcomes. RESULTS: During the study among 96,014 patients evaluated in the ED, we included 23,338 patients ≥65 years-mean age, 78.4±8.1 years; 12,626 (54.1%) women. During follow-up, 5,776 patients (24.75%) had poor outcomes after evaluation in the ED: 1,140 (4.88%) died, 4,640 (20.51) returned to the ED, and 1,739 (7.69%) were readmitted 30 days after discharge following the index visit. A model including male sex, age ≥75 years, arrival by ambulance, Charlson Comorbidity Index ≥3, and functional impairment had a C-index of 0.81 (95% confidence interval, 0.80-0.82) for 30-day mortality. CONCLUSION: Male sex, age ≥75 years, arrival by ambulance, functional impairment, or severe comorbidity are features of patients who could benefit from approaches in the ED different from the common triage to improve the poor short-term outcomes of this population.

A multi gene-approach genotyping method identifies 24 genetic clusters within the genotype II-European African swine fever viruses circulating from 2007 to 2022.

Introduction: African swine fever (ASF) is a contagious viral disease of pigs and wild boar that poses a major threat to the global swine industry. The genotype II African swine fever virus (ASFV) entered the European Union (EU) in 2014 and since then fourteen countries have been affected, Italy and North Macedonia being the last in 2022. While whole genome sequencing remains the gold standard for the identification of new genetic markers, sequencing of multiple loci with significant variations could be used as a rapid and cost-effective alternative to track outbreaks and study disease evolution in endemic areas. Materials and methods: To further our understanding of the epidemiology and spread of ASFV in Europe, 382 isolates collected during 2007 to 2022 were sequenced. The study was initially performed by sequencing the central variable region (CVR), the intergenic region (IGR) between the I73R and I329L genes and the O174L and K145R genes. For further discrimination, two new PCRs were designed to amplify the IGR between the 9R and 10R genes of the multigene family 505 (MGF505) and the IGR between the I329L and I215L genes. The sequences obtained were compared with genotype II isolates from Europe and Asia. Results: The combination of the results obtained by sequencing these variable regions allowed to differentiate the European II-ASFV genotypes into 24 different groups. In addition, the SNP identified in the IGR I329L-I215L region, not previously described, grouped the viruses from North Macedonia that caused the 2022 outbreaks with viruses from Romania, Bulgaria, Serbia and Greece, differentiating from other genotype II isolates present in Europe and Asia. Furthermore, tandem repeat sequence (TRS) within the 9R-10R genes of the multigene family 505 (MGF505) revealed eight different variants circulating. Discussion: These findings describe a new multi-gene approach sequencing method that can be used in routine genotyping to determine the origin of new introductions in ASF-free areas and track infection dynamics in endemic areas.

[Impacto de la dependencia funcional de los pacientes mayores atendidos en los servicios de Urgencias españoles durante la primera ola pandémica de la COVID-19 sobre la mortalidad a 30, 180 y 365 días en función del diagnóstico (COVID versus no COVID).] / Impact of functional dependency of elderly patients seen in Spanish emergency departments during the first wave of the COVID-19 pandemic on mortality at 30, 180 and 365 days depending on the diagnosis (COVID versus non-COVID).

OBJECTIVE: Functional assessment is part of geriatric assessment. How it is performed in hospital Emergency Departments (ED) is poorly understood, let alone its prognostic value. The aim of this paper was to investigate whether baseline disability to perform basic activities of daily living (BADL) was an independent prognostic factor for death after the index visit to the ED during the first wave of the COVID-19 pandemic and whether it had a different impact on patients with and without diagnosis of COVID-19. METHODS: A retrospective observational study of the EDEN-Covid (Emergency Department and Elder Needs during COVID) cohort was carried out, consisting of all patients aged ≥65 years seen in 52 Spanish EDs selected by chance during 7 consecutive days (30/3/2020 to 5/4/2020). Demographic, clinical, functional, mental and social variables were analyzed. Dependence was categorized with the Barthel index (BI) as independent (BI=100), mild-moderate dependence (100>BI>60) and severe-total dependence (BI<60), and their crude and adjusted association was evaluated with mortality at 30, 180 and 365 days using COX proportional hazards models. RESULTS: Of 9,770 enrolled patients with a mean age of 79 years, 51% were men, 6,305 (64.53%) were independent, 2,340 (24%) had mild-moderate dependence, and 1,125 (11.5%) severe-total dependence. The number of deaths at 30 days in these three groups was 500 (7.9%), 521 (22.3%) and 378 (33.6%), respectively; at 180 days it was 757 (12%), 725 (30.9%) and 526 (46.8%); and at 365 days 954 (15.1%), 891 (38.1%) and 611 (54.3%). In relation to independent patients, the adjusted risks (hazard ratio) of dying within 30 days associated with mild-moderate and severe-total dependency were 1.91 (95% CI: 1.66-2.19) and 2.51. (2.11-2.98); at 180 days they were 1.88 (1.68-2.11) and 2.64 (2.28-3.05); and at 365 days they were 1.82 (1.64-2.02) and 2.47 (2.17-2.82). This negative impact of dependency on mortality was greater in patients diagnosed with COVID-19 than in non-COVID-19 (p interaction at 30, 180 and 365 days of 0.36, 0.05 and 0.04). CONCLUSIONS: The functional dependence of older patients who attend Spanish EDs during the first wave of the pandemic is associated with mortality at 30, 180 and 365 days, and this risk is significantly higher in patients treated for COVID-19.

OBJETIVO: La valoración funcional forma parte de la valoración geriátrica. No se conoce bien cómo se realiza en los servicios de Urgencias hospitalarios (SUH) y menos aún su valor pronóstico. El objetivo de este trabajo fue investigar si la dependencia funcional basal para realizar las actividades básicas de la vida diaria (ABVD) era un factor pronóstico independiente de muerte tras la visita índice al SUH durante la primera ola pandémica de la COVID-19 y si tuvo un impacto diferente en pacientes con y sin diagnóstico de COVID-19. METODOS: Se realizó un estudio observacional retrospectivo de la cohorte EDEN-Covid (Emergency Department and Elder Needs during COVID) formada por todos los pacientes de edad mayor o igual a 65 años atendidos en 52 SUH españoles, seleccionados por oportunidad durante siete días consecutivos (del 30 de marzo al 5 de abril de 2020). Se analizaron variables demográficas, clínicas, funcionales, mentales y sociales. La dependencia se categorizó con el índice de Barthel (IB) en independiente (IB=100), dependencia leve-moderada (100>IB>60) y dependencia grave-total (IB<60), y se evaluó su asociación cruda y ajustada con la mortalidad a 30, 180 y 365 días mediante modelos de riesgos proporcionales de COX. RESULTADOS: De 9.770 pacientes incluidos con una media de edad de 79 años, un 51% eran hombres, 6.305 (64,53%) eran independientes, 2.340 (24%) tenían dependencia leve-moderada y 1.125 (11,5%) dependencia grave-total. El número de fallecidos a 30 días en estos tres grupos fue 500 (7,9%), 521 (22,3%) y 378 (33,6%), respectivamente; a 180 días fue 757 (12%), 725 (30,9%) y 526 (46,8%); y a 365 días 954 (15,1%), 891 (38,1%) y 611 (54,3%). En relación a los pacientes independientes, los riesgos (hazard ratio) ajustados de fallecer a 30 días, asociados a dependencia leve-moderada y grave-total, fueron 1,91 (IC 95%: 1,66-2,19) y 2,51 (2,11-2,98); a 180 días fueron de 1,88 (1,68-2,11) y 2,64 (2,28-3,05); y a 365 días fueron 1,82 (1,64-2,02) y 2,47 (2,17-2,82). Este impacto negativo de la dependencia sobre la mortalidad fue mayor en pacientes diagnosticados de COVID-19 que en los no COVID-19 (p interacción a 30, 180 y 365 días de 0,36, 0,05 y 0,04). CONCLUSIONES: La dependencia funcional de los pacientes mayores que acuden a SUH españoles durante la primera ola pandémica se asocia a mortalidad a 30, 180 y 365 días, y este riesgo es significativamente mayor en los pacientes atendidos por COVID-19.

Bin1 attenuation suppresses experimental colitis by enforcing intestinal barrier function.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with defects in intestinal barriers that rely upon cellular tight junctions. Thus, identifying genes that could be targeted to enforce tight junctions and improve barrier function may lead to new treatment strategies for IBD. AIMS: This preclinical study aimed to evaluate an hypothesized role for the tumor suppressor gene Bin1 as a modifier of the severity of experimental colitis. METHODS: We ablated the Bin1 gene in a mosaic mouse model to evaluate its effects on experimental colitis and intestinal barrier function. Gross pathology, histology and inflammatory cytokine expression patterns were characterized and ex vivo physiology determinations were conducted to evaluate barrier function in intact colon tissue. RESULTS: Bin1 attenuation limited experimental colitis in a sexually dimorphic manner with stronger protection in female subjects. Colitis suppression was associated with an increase in basal transepithelial electrical resistance (TER) and a decrease in paracellular transepithelial flux, compared to control wild-type animals. In contrast, Bin1 attenuation did not affect short circuit current, nor did it alter the epithelial barrier response to non-inflammatory permeability enhancers in the absence of inflammatory stimuli. CONCLUSIONS: Bin1 is a genetic modifier of experimental colitis that controls the paracellular pathway of transcellular ion transport regulated by cellular tight junctions. Our findings offer a preclinical validation of Bin1 as a novel therapeutic target for IBD treatment.

African swine fever virus p72 genotype IX in domestic pigs, Congo, 2009.

African swine fever virus p72 genotype IX, associated with outbreaks in eastern Africa, is cocirculating in the Republic of the Congo with West African genotype I. Data suggest that viruses from eastern Africa are moving into western Africa, increasing the threat of outbreaks caused by novel viruses in this region.

African swine fever viruses with two different genotypes, both of which occur in domestic pigs, are associated with ticks and adult warthogs, respectively, at a single geographical site.

The role of the ancestral sylvatic cycle of the African swine fever virus (ASFV) is not well understood in the endemic areas of eastern Africa. We therefore analysed the ASF infection status on samples collected from 51 free-ranging warthogs (Phacocherus africanus) and 1576 Ornithodorus porcinus ticks from 26 independent warthog burrows at a single ranch in Kenya. Abattoir samples from 83 domestic pigs without clinical symptoms, originating from specific locations with no recent reported ASF outbreaks were included in this study. All samples were derived from areas of central Kenya, where ASF outbreaks have been reported in the past. Infection with ASFV was confirmed in 22 % of O. porcinus pools, 3.22 % of adult warthog serum samples and 49 % of domestic pig serum samples by using p72-based PCR. All of the warthog sera were positive for anti-ASFV antibodies, investigated by using ELISA, but none of the domestic pig sera were positive. Twenty O. porcinus-, 12 domestic pig- and three warthog-derived viruses were genotyped at four polymorphic loci. The ASFV isolates from ticks and domestic pigs clustered within p72 genotype X. By contrast, ASF viruses genotyped directly from warthog sera, at same locality as the tick isolates, were within p72 genotype IX and genetically similar to viruses causing recent ASF outbreaks in Kenya and Uganda. This represents the first report of the co-existence of different ASFV genotypes in warthog burrow-associated ticks and adult wild warthogs. The data from this and earlier studies suggest transfer of viruses of at least two different p72 genotypes, from wild to domestic pigs in East Africa.

Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase.

Topical application of phorbol myristate acetate (PMA) elicits intense local inflammation that facilitates outgrowth of premalignant lesions in skin after carcinogen exposure. The inflammatory response to PMA treatment activates immune stimulatory mechanisms. However, we show here that PMA exposure also induces plasmacytoid dendritic cells (pDCs) in local draining lymph nodes (dLNs) to express indoleamine 2,3 dioxygenase (IDO), which confers T cell suppressor activity on pDCs. The induced IDO-mediated inhibitory activity in this subset of pDCs was potent, dominantly suppressing the T cell stimulatory activity of other DCs that comprise the major fraction of dLN DCs. IDO induction in pDCs depended on inflammatory signaling by means of IFN type I and II receptors, the TLR/IL-1 signaling adaptor MyD88, and on cellular stress responses to amino acid withdrawal by means of the integrated stress response kinase GCN2. Consistent with the hypothesis that T cell suppressive, IDO(+) pDCs elicited by PMA exposure create local immune privilege that favors tumor development, IDO-deficient mice exhibited a robust tumor-resistant phenotype in the standard DMBA/PMA 2-stage carcinogenesis model of skin papilloma formation. Thus, IDO is a key immunosuppressive factor that facilitates tumor progression in this setting of chronic inflammation driven by repeated topical PMA exposure.

Kaposi sarcoma presenting as yellow-green penile plaques in a black man with HIV.

Kaposi sarcoma characteristically presents with violaceous papules, plaques, or nodules due to the vascular nature of the lesions. We present the case of a human immunodeficiency virus (HIV)-positive black man with yellow-green penile plaques. Biopsy results revealed leukoedema and slitlike vascular spaces. Immunohistochemistry was positive for CD31 and CD34. He was treated with highly active antiretroviral therapy (HAART) and the penile plaques improved. Localized yellow-green penile plaques are an uncommon presentation of the well-known clinical entity, Kaposi sarcoma. This case underscores the varied clinical presentations that can occur in skin of color and the importance of histopathology in the assessment of uncharacteristic clinical presentations, especially in immunosuppressed patients.

Dynamics of African swine fever virus (ASFV) infection in domestic pigs infected with virulent, moderate virulent and attenuated genotype II ASFV European isolates.

This study aimed to compare the infection dynamics of three genotype II African swine fever viruses (ASFV) circulating in Europe. Eighteen domestic pigs divided into three groups were infected intramuscularly or by direct contact with two haemadsorbent ASFVs (HAD) from Poland (Pol16/DP/ OUT21) and Estonia (Est16/WB/Viru8), and with the Latvian non-HAD ASFV (Lv17/WB/Rie1). Parameters, such as symptoms, pathogenicity, and distribution of the virus in tissues, humoral immune response, and dissemination of the virus by blood, oropharyngeal and rectal routes, were investigated. The Polish ASFV caused a case of rapidly developing fatal acute disease, while the Estonian ASFV caused acute to sub-acute infections and two animals survived. In contrast, animals infected with the ASFV from Latvia developed a more subtle, mild, or even subclinical disease. Oral excretion was sporadic or even absent in the attenuated group, whereas in animals that developed an acute or sub-acute form of ASF, oral excretion began at the same time the ASFV was detected in the blood, or even 3 days earlier, and persisted up to 22 days. Regardless of virulence, blood was the main route of transmission of ASFV and infectious virus was isolated from persistently infected animals for at least 19 days in the attenuated group and up to 44 days in the group of moderate virulence. Rectal excretion was limited to the acute phase of infection. In terms of diagnostics, the ASFV genome was detected in contact pigs from oropharyngeal samples earlier than in blood, independently of virulence. Together with blood, both samples could allow to detect ASFV infection for a longer period. The results presented here provide quantitative data on the spread and excretion of ASFV strains of different virulence among domestic pigs that can help to better focus surveillance activities and, thus, increase the ability to detect ASF introductions earlier.

Dietary methionine restriction improves colon tight junction barrier function and alters claudin expression pattern.

The beneficial effects of caloric restriction in increasing longevity and forestalling age-related diseases are well known. Dietary restriction of methionine also renders similar benefits. We recently showed in a renal epithelial cell culture system that reduction of culture medium methionine by 80% resulted in altered tight junctional (TJ) claudin composition and also improved epithelial barrier function (51). In the current study, we examined the effect of dietary restriction of methionine on TJ barrier function in rat gastrointestinal tissue to see whether this phenomenon also holds true in a tissue model and for a different epithelial cell type. After 28 days on methionine-restricted (MR) diet, rats showed small but significant reductions in the plasma and (intracellular) colonocyte levels of methionine. Colon mucosal sheets from rats on the MR diet showed increased transepithelial electrical resistance with concomitant decrease in paracellular diffusion of (14)C-D-mannitol, suggesting improved barrier function relative to rats on control diet. This improved barrier function could not be explained by changes in colon crypt length or frequency. Neither was the colonocyte mitotic index nor the apoptotic frequency altered significantly. However, TJ composition/structure was being altered by the MR diet. RT-PCR and Western blot analysis showed an increase in the abundance of claudin-3 and an apparent change in the posttranslational modification of occludin, data reinforcing a paracellular barrier alteration. Overall, our data suggest that reduction in dietary intake of methionine results in improved epithelial barrier function by inducing altered TJ protein composition.

Non-hematopoietic expression of IDO is integrally required for inflammatory tumor promotion.

Indoleamine 2,3-dioxygenase (IDO) is generally considered to be immunosuppressive but recent findings suggest this characterization oversimplifies its role in disease pathogenesis. Recently, we showed that IDO is essential for tumor outgrowth in the classical two-stage model of inflammatory skin carcinogenesis. Here, we report that IDO loss did not exacerbate classical inflammatory responses. Rather, IDO induction could be elicited by environmental signals and tumor promoters as an integral component of the inflammatory tissue microenvironment even in the absence of cancer. IDO loss had limited impact on tumor outgrowth in carcinogenesis models that lacked an explicit inflammatory tumor promoter. In the context of inflammatory carcinogenesis where IDO was critical to tumor development, the most important source of IDO was radiation-resistant non-hematopoietic cells, consistent with evidence that loss of the IDO regulatory tumor suppressor gene Bin1 in transformed skin cells facilitates IDO-mediated immune escape by a cell autonomous mechanism. Taken together, our results identify IDO as an integral component of 'cancer-associated' inflammation that tilts the immune system toward tumor support. More generally, they promote the concept that mediators of immune escape and cancer-associated inflammation may be genetically synonymous.

Arginase I induction by modified lipoproteins in macrophages: a peroxisome proliferator-activated receptor-gamma/delta-mediated effect that links lipid metabolism and immunity.

Macrophages are phagocytic cells that play essential roles in innate immunity and lipid homeostasis. The uptake of modified lipoproteins is an important early event in the development of atherosclerosis. We analyzed the ability of modified low-density lipoprotein (LDL) (oxidized and acetylated) to alter the expression and activity of arginases (ArgI and ArgII) in macrophages. We show that ArgI expression is potently induced by both oxidized and acetylated LDL in macrophages. We further show that this effect is mediated by peroxisome proliferator-activated receptors (PPAR). ArgI expression is highly responsive to agonists for PPARgamma and PPARdelta but not PPARalpha. Moreover, the induction of ArgI by both PPAR agonists and IL-4 is blocked in macrophages from PPARgamma- and PPARdelta-deficient mice. Functionally, PPAR activity induces macrophage activation toward a more Th2 immune phenotype in a model of Leishmania major infection. We show that PPARgamma and -delta ligands promote intracellular amastigote growth in infected macrophages, and this effect is dependent on both PPAR expression and Arg activity. Collectively, our results strongly suggest that ArgI is a key marker of the alternative program triggered by PPAR in macrophages.

Bin1 ablation in mammary gland delays tissue remodeling and drives cancer progression.

Genes that modify oncogenesis may influence dormancy versus progression in cancer, thereby affecting clinical outcomes. The Bin1 gene encodes a nucleocytosolic adapter protein that interacts with and suppresses the cell transforming activity of Myc. Bin1 is often attenuated in breast cancer but its ability to negatively modify oncogenesis or progression in this context has not been gauged directly. In this study, we investigated the effects of mammary gland-specific deletion of Bin1 on initiation and progression of breast cancer in mice. Bin1 loss delayed the outgrowth and involution of the glandular ductal network during pregnancy but had no effect on tumor susceptibility. In contrast, in mice where tumors were initiated by the ras-activating carcinogen 7,12-dimethylbenz(a)anthracene, Bin1 loss strongly accentuated the formation of poorly differentiated tumors characterized by increased proliferation, survival, and motility. This effect was specific as Bin1 loss did not accentuate progression of tumors initiated by an overexpressed mouse mammary tumor virus-c-myc transgene, which on its own produced poorly differentiated and aggressive tumors. These findings suggest that Bin1 loss cooperates with ras activation to drive progression, establishing a role for Bin1 as a negative modifier of oncogenicity and progression in breast cancer.

Bin1 ablation increases susceptibility to cancer during aging, particularly lung cancer.

Age is the major risk factor for cancer, but few genetic pathways that modify cancer incidence during aging have been described. Bin1 is a prototypic member of the BAR adapter gene family that functions in vesicle dynamics and nuclear processes. Bin1 limits oncogenesis and is often attenuated in human cancers, but its role in cancer suppression has yet to be evaluated fully in vivo. In the mouse, homozygous deletion of Bin1 causes developmental lethality, so to assess this role, we examined cancer incidence in mosaic null mice generated by a modified Cre-lox technology. During study of these animals, one notable phenotype was an extended period of female fecundity during aging, with mosaic null animals retaining reproductive capability until the age of 17.3 +/- 1.1 months. Through 1 year of age, cancer incidence was unaffected by Bin1 ablation; however, by 18 to 20 months of age, approximately 50% of mosaic mice presented with lung adenocarcinoma and approximately 10% with hepatocarcinoma. Aging mosaic mice also displayed a higher incidence of inflammation and/or premalignant lesions, especially in the heart and prostate. In mice where colon tumors were initiated by a ras-activating carcinogen, Bin1 ablation facilitated progression to more aggressive invasive status. In cases of human lung and colon cancers, immunohistochemical analyses evidenced frequent attenuation of Bin1 expression, paralleling observations in other solid tumors. Taken together, our findings highlight an important role for Bin1 as a negative modifier of inflammation and cancer susceptibility during aging.

Attenuated and non-haemadsorbing (non-HAD) genotype II African swine fever virus (ASFV) isolated in Europe, Latvia 2017.

A non-haemadsorbing (non-HAD) ASF virus (ASFV) genotype II, namely Lv17/WB/Rie1, was isolated from a hunted wild boar in Latvia in 2017. Domestic pigs experimentally infected with the non-HAD ASFV developed a nonspecific or subclinical form of the disease. Two months later, these animals were fully protected when exposed to other domestic pigs infected with a related virulent HAD genotype II ASFV.

Effect of boar semen supplementation with recombinant heat shock proteins during summer.

Artificial insemination (AI) in pigs is mainly performed with refrigerated boar semen. There is a marked negative seasonal effect on the quality of boar sperm, mainly due to relatively greater ambient temperatures; to counteract this thermal stress, sperm cells possess natural defensive mechanisms such as Heat Shock Proteins (HSPs) that prevent protein denaturation. Thus, the objective of this research was to improve the quality of commercial boar semen collected during the summer when ambient temperatures are greater using recombinant HSPs. For this purpose, different concentrations (0.1, 0.5 and 1 µg/ml) of recombinant heat shock proteins (HSPD1, HSPA8 or HSP86) were added to commercial boar semen and there was cooling for 48 h at 17 °C. After this storage period, sperm quality was assessed by analyzing sperm viability, mitochondrial membrane potential and plasma membrane lipid organization using flow cytometry; additionally, sperm motility was examined using a CASA system. Also, in vitro fertilization (IVF) using HSP-supplemented boar semen was performed and the quality of the embryos produced was evaluated using quantitative real-time polymerase chain reaction (qPCR) analyzing the relative abundance of mRNA transcripts for genes encoding for embryo quality-related proteins (BAX, TFAM, POLG and POG2). Sperm quality variables, blastocyst rates and the abundance of mRNA transcripts for the selected genes were not affected by the presence of recombinant HSPs at any concentration. These results indicate that the supplementation of commercial seminal doses with recombinant HSPs does not improve boar sperm quality or fertility during the summer months when ambient temperatures are greater.