Reticulons bind sphingolipids to activate the endoplasmic reticulum cell cycle checkpoint, the ER surveillance pathway.

The inheritance of a functional endoplasmic reticulum (ER) is ensured by the ER stress surveillance (ERSU) pathway. Here, we made the unexpected discovery that reticulon 1 (Rtn1) and Yop1, well-known ER-curvature-generating proteins, each possess two sphingolipid-binding motifs within their transmembrane domains and that these motifs recognize the ER-stress-induced sphingolipid phytosphingosine (PHS), resulting in an ER inheritance block. Upon binding PHS, Rtn1/Yop1 accumulate on the ER tubule, poised to enter the emerging daughter cell, and cause its misdirection to the bud scars (i.e., previous cell division sites). Amino acid changes in the conserved PHS-binding motifs preclude Rtn1 or Yop1 from binding PHS and diminish their enrichment on the tubular ER, ultimately preventing the ER-stress-induced inheritance block. Conservation of these sphingolipid-binding motifs in human reticulons suggests that sphingolipid binding to Rtn1 and Yop1 represents an evolutionarily conserved mechanism that enables cells to respond to ER stress.

Prostate cancer treatment in Portugal: a nationwide analysis.

Different treatment options exist for localized prostate cancer. Treatments performed in high-volume hospitals are associated with better results. Our objective was to describe time trends in prostate cancer treatments in Portugal and case volume per hospital. We used the national database of diagnosis-related group of the Portuguese Central Administration of the Health System to describe the number of radical prostatectomy (RP), brachytherapy (BT) and external radiotherapy (eRT) treatments performed in all National Health System hospitals. There was a rapid increase in the annual number of RP until 2006 and then a deceleration; BT treatments augmented significantly until 2011. The utilization of eRT also increased, surpassing RP after 2010. From the 46 hospitals performing RP, only eight had a case-volume > 50 treatments/year, and from the nine hospitals performing BT, only four accomplished > 15 treatments/year. In the 11 hospitals with eRT, nine performed > 50/year. Regarding RP, there was negative correlation between the hospital volume and length of stay (r = - 0.303; p = 0.041). In the Portuguese National Health Service there was a steep increase in the number of prostate cancer treatments, and there is an ample margin for concentration of RP and BT treatments, for improvement of the hospitals case volume.

Synergy between highly dispersed Ni nanocrystals and graphitized carbon derived from a single source as a strategy for high performance Lithium-Sulfur batteries.

Due to their higher energy density, lower prices, and more environmentally friendly active components, Li-S batteries will soon compete with the current Li-ion batteries. However, issues persist that hinder this implementation, such as the poor conductivity of S and sluggish kinetics due to the polysulfide shuttle, among others. Herein, Ni nanocrystals encapsulated in a C matrix are obtained by a novel strategy based on the thermal decomposition of a Ni oleate-oleic acid complex at low-to-moderate temperatures: 500 and 700 °C. The two C/Ni composites were employed as hosts in Li-S batteries. Although the C matrix is amorphous at 500 °C, it is highly graphitized at 700 °C. At this moderate temperature, the simultaneous generation of Ni nanocrystals and the carbon matrix enhances the catalytic activity of Ni toward the graphitization process, which is negligible if starting from a mixture of a Ni salt and carbon source, even when calcined at temperatures as high as 1000 °C. The electrode made from the C/Ni composite obtained at 700 °C exhibits a high reversible capacity and an enhanced rate capability, much better not only than the C/Ni composite obtained at 500 °C but than others based on amorphous C calcined at very high temperatures, around 1000 °C. These properties are attributed to an increase in the electrical conductivity parallel to the ordering of the layers. We believe this work provides a new strategy to design C-based composites capable of combining the formation of nanocrystalline phases and the control of the C structure with superior electrochemical properties for Li-S batteries.

Effect of the percentage of Bos taurus inheritance on the fertility of Holstein×Zebu and Brown Swiss×Zebu cows in the Mexican tropics

Background: No dairy breed or crossbreed has superior overall performance in all environments; therefore, it is necessary to determine which crossbreed is the most suitable for the Mexican tropic and what proportion of European breed is optimum for reproduction. Objective: To assess the effect of the proportion of Bos taurus (Bt) genes on reproductive performance of Holstein×Zebu (HZ) and Brown Swiss×Zebu (BZ) cows, and compare reproductive performance of these genotypes in a dual- purpose production system. Methods: Cows were maintained in a rotational grazing system on African star grass (Cynodon plectostachyus) in Veracruz, Mexico. Cows were milked twice daily. Calves were kept tied to the side of their dams while the cows were milked. Results: The percentage of Bt genes did not affect (p>0.05) fertility traits (age at first calving, days to first service after calving, services per conception, conception rate at first service, days open until conception, gestation length, and calving interval) of BZ cows. In contrast, HZ cows with less than 75% Holstein (H) genes were 0.3 years younger (p<0.05) at first calving and had 39.8 fewer days open (p<0.05) than HZ cows with 75% H genes or more. In addition, the calving interval of HZ cows with less than 75% H genes was 44.8 days shorter (p<0.05) than that of HZ cows with 75% H genes or more. The HZ cows had five fewer days pregnant and were 22.8 kg heavier at calving (p<0.05) than BZ cows. Conclusions: The effect of the percentage of Bt genes on cow fertility depends on the dairy breed used. In general, BZ and HZ cows present similar reproductive performance.

Antecedentes: Ninguna raza lechera o cruce tiene un desempeño general superior en todos los ambientes; por lo tanto, es necesario determinar cuál cruce lechero es más apropiado en el trópico mexicano y qué proporción de raza europea es óptima para la reproducción. Objetivo: Evaluar el efecto de la proporción de genes Bos taurus (Bt) en el desempeño reproductivo de vacas cruzadas Holstein×Cebú (HC) y Pardo Suizo×Cebú (PC), y comparar el desempeño reproductivo de estos dos genotipos en un sistema de producción doble propósito. Métodos: Las vacas se mantuvieron en un sistema de pastoreo rotacional en zacate Estrella de África (Cynodon plectostachyus) en Veracruz, México. Las vacas se ordeñaron dos veces al día. Los becerros se mantuvieron atados, a un costado de sus madres mientras éstas se ordeñaron. Resultados: El porcentaje de genes Bt no afectó (p>0,05) ninguna característica de fertilidad (edad a primer parto, días a primer servicio después del parto, servicios por concepción, tasa de preñez a primer servicio, días abiertos a la concepción, duración de la gestación, e intervalo entre partos) de las vacas PC. En contraste, las vacas HC con menos de 75% de genes Holstein (H) fueron 0,3 años más jóvenes (p<0,05) al primer parto y tuvieron 39,8 días abiertos menos (p<0,05) que las vacas HC con 75% de genes H o más. Además, el intervalo entre partos de las vacas HC con menos de 75% de genes H fue 44,8 días más corto (p<0,05) que el de las vacas HC con 75% de genes H o más. Las vacas HC tuvieron cinco días de gestación menos y fueron 22,8 kg más pesadas al parto (p<0,05) que las PC. Conclusiones: El efecto del porcentaje de genes Bt sobre la fertilidad de la vaca depende de la raza lechera usada. En general, las vacas PC y HC tienen similar desempeño reproductivo.

Antecedentes: Nenhuma raça ou cruza leiteira tem desempenho geral superior em todos os ambientes; portanto, é necessário determinar qual cruza leiteira é mais apropriada no trópico mexicano e qual proporção da raça europeia é ideal para a reprodução das vacas. Objetivo: Avaliar o efeito da proporção de genes Bos taurus (Bt) no desempenho reprodutivo de vacas Holandês×Zebu (HZ) e Pardo Suíço×Zebu (PZ), e comparar o desempenho reprodutivo desses dois genótipos em sistema de produção de dupla aptidão. Métodos: As vacas foram mantidas em sistema de pastoreio rotacional em capim Estrela de África (Cynodon plectostachyus) em Veracruz, México. As vacas foram ordenhadas duas vezes por dia. Os bezerros foram mantidos ao lado de suas mães enquanto eram ordenhadas. Resultados: A porcentagem dos genes Bt não afetou (p>0,05) nenhuma característica de fertilidade (idade ao primeiro parto, número de dias para o primeiro serviço pós-parto, serviços por concepção, taxa de prenhes no primeiro serviço, dias abertos, período de gestação e intervalo entre partos) das vacas PZ. Em contraste, vacas HC com menos de 75% dos genes Holandês (H) eram 0,3 anos mais jovens (p<0,05) no primeiro parto e tiveram 39,8 dias abertos a menos (p<0,05) do que as vacas HZ com 75% ou mais dos genes H. Além disso, o intervalo de parto das vacas HZ com menos de 75% dos genes H foram 44,8 dias mais curtos (p<0,05) do que as vacas HZ com 75% ou mais de genes H. As vacas HZ tiveram cinco dias de gestação a menos e foram 22,8 kg mais pesadas no parto (p<0,05) do que as PZ. Conclusões: O efeito da porcentagem de genes Bt na fertilidade da vaca dependeu da raça leiteira utilizada. Em geral, as vacas PZ e HZ tiveram desempenho reprodutivo semelhante.

Tick fauna in non-anthropogenic areas in Mato Grosso do Sul, Brazil, with the presence of the Rickettsia parkeri strain Atlantic rainforest in Amblyomma ovale.

The aim of this study was to evaluate tick fauna and identify the possible presence of Rickettsia spp. in ticks of the genus Amblyomma from two environmental preservation areas in different regions of Mato Grosso do Sul state, Brazil. CO2 traps, visual observation and cloth dragging were used to capture ticks. Three hundred ticks were submitted to the hemolymph test, and samples that showed organisms morphologically compatible with Rickettsia were used for rickettsial DNA detection by PCR. DNA was extracted using guanidine-phenol isothiocyanate, and the primers CS78 and CS323 were used for PCR, which amplified a 401-base pair fragment of the citrate synthase (gltA) gene. If positive, the DNA sample was tested by primers Rr190.70p and Rr190.602n that produce a 530 bp amplicon of the ompA gene that is present only in rickettsiae of the spotted fever group. A total of 1,745 adult ticks were collected, including 1,673 specimens of Amblyomma sculptum, 63 of Amblyomma coelebs, five of Amblyomma naponense and four of Amblyomma ovale. Thirteen ticks of the species A. ovale, A. coelebs and A. sculptum showed structures compatible with Rickettsia inside the hemocytes; after DNA extraction, the presence of Rickettsia spp. in a sample of A. ovale was confirmed by PCR in both analyzed fragments. In the sequencing analysis, 100% identity for the Rickettsia parkeri strain Atlantic rainforest was obtained according to GenBank. The two environmental preservation areas showed A. sculptum as the predominant species, as well as the presence of marked seasonality for this species. This paper is the first report of the R. parkeri strain Atlantic rainforest in A. ovale ticks in the state of Mato Grosso do Sul, Brazil.

Can serum endoglin be used to improve the diagnostic performance in prostate cancer?

PURPOSE: New biomarkers may contribute to avoid unnecessary biopsies resulting from the suboptimal performance of prostate-specific antigen (PSA) testing. This study aimed to assess serum endoglin as a prostate cancer (PCa) diagnostic tool among biopsy candidates. METHODS: A total of 262 consecutive patients referred for prostate biopsy based on abnormal digital rectal examination and/or elevated total PSA (tPSA) who had serum endoglin assessed by solid-phase enzyme-linked immunosorbent assay were selected. Receiver operating characteristic curves were used to compare the predictive accuracy of different combinations of biomarkers to distinguish between PCa and benign prostatic conditions, and to identify cut-offs that maximize the ability of endoglin to rule out patients for biopsy (highest sensitivities). RESULTS: Serum endoglin levels were higher in patients with PCa (median: 7.86 vs. 5.88 pg/mL, P < 0.001). Among patients with baseline tPSA ≤ 10 ng/mL the area under the curve was 0.69 for endoglin. Approximately one-quarter of the patients had serum endoglin < 4.92 ng/mL (sensitivity: 90.3%; specificity: 32.8%), and the probability of PCa varied from 37.7% before testing to 15.2% among those with low endoglin levels [negative predictive value (NPV) = 84.8%]. When restricting the analyses to patients with free/total PSA ratio > 0.25, the probability of cancer was less than 5% among those with serum endoglin < 6.04 ng/mL (sensitivity: 93.8%; specificity: 56.1%), corresponding to a NPV of 95.8%; this could allow sparing approximately 40% of patients from biopsy. CONCLUSIONS: Serum endoglin may be useful in clinical practice to distinguish between PCa and non-cancer patients among prostatic biopsy candidates.

Regulation of the early stages of endoplasmic reticulum inheritance during ER stress.

The endoplasmic reticulum (ER) is one of the largest cytoplasmic organelles in eukaryotic cells and plays a role in many cellular processes, such as the production and quality control of secretory protein, lipid synthesis, and calcium homeostasis. The ER cannot be generated de novo, and thus its proper inheritance during cell division is paramount to the health and survival of the daughter cells. Although previous work has uncovered the cytoskeletal components involved, we still lack a comprehensive understanding of the intricate steps of and the cytoplasmic and membrane-bound components involved in ER inheritance. To directly address these issues, we utilized microfluidics and genetic analyses to show that before nuclear migration, early ER inheritance can be further divided into three distinctive steps. Moreover, we demonstrated that perturbing each of these steps affects the cell's ability to mitigate ER stress. Thus, proper ER inheritance is essential to ensuring a healthy, functional cell.

Horse welfare at slaughter: A novel approach to analyse bruised carcasses based on severity, damage patterns and their association with pre-slaughter risk factors.

The study presents a novel veterinary forensic approach to analyse the bruising of horse carcasses, based on the nature of the bruises and how they are grouped in certain anatomical areas. Data on pre-slaughter logistics was obtained for 113 journeys with horses that travelled from Mexico and the USA to a Mexican abattoir. We found that carcass bruising was a highly prevalent problem (79% of carcasses had bruising) and was especially problematic in journeys lasting longer than 12 h, independently of the animal's country of origin, sex, age, lairage time or vehicle type. Multivariable logistic regression showed that the most severe bruises were not dispersed randomly on the carcass and that their distribution was associated with the presence of medium-sized bruises on the abdominal wall, front and rear limb. Cluster analysis suggested four damage patterns based on bruise location: severe and concentrated bruising, as well as non-severe bruises on the rear limb, thoracic-wall or more dispersed throughout the carcass.

Welfare of horses from Mexico and the United States of America transported for slaughter in Mexico: Fitness profiles for transport and pre-slaughter logistics.

Every year thousands of horses from Mexico and the United States of America (USA) are transported to slaughter in Mexico, but little is known about their welfare or pre-slaughter logistics. In this study, we recorded the origin, sex, age and condition of horses (121 journeys, 2648 animals) upon arrival to an abattoir in northern Mexico, including transport details. Horse welfare was measured indirectly via individual scores for body condition, coat quality, lameness, ocular and nasal discharge, as well as reactivity to a chute restraint test, all performed shortly after unloading. The average journey duration was 9.69 (±7.6) hours for horses from Mexico and 16.77 (±4.51) hours for horses from the USA (77 % of all journeys). The prevalence of ocular discharge, nasal discharge, skin wounds, lameness and diarrhoea, were 23 %, 12 %, 11 %, 9 %, 1 % (respectively) of all the horses observed, with no significant differences between Mexican and American horses (P ≥ 0.05). During the chute test the American horses were calmer than the Mexican ones (P < 0.001), who were more restless and aggressive (P = 0.001). Likewise, vocalizations in their three variants during the restraint, neigh/whinny (P = 0.018), nicker (P < 0.001), and snort (P = 0.018), were more common in horses from Mexico. In order to help characterize fitness for transport, a two-step cluster analysis was applied using the welfare indicators, suggesting the existence of four clusters (C) evaluated on arrival at the abattoir (from good to very poor fitness): good (profile C4, n = 769, 29.1 %), average (profile C1, n = 799 horses, 30.2 %), poor (profile C3, n = 586, 22.1 %) and very poor (profile C2, n = 494, 18.6 %). In fact, the C4 best welfare group had 0% lame, 0% nasal discharge, 16.4 % ocular discharge, 7.9 % skin wounds. Instead, the C2 poorest welfare group had 45.8 % lame, 61.1 % nasal discharge, 42.8 % ocular discharge, and 19.9 % skin wounds. Results show potential for using nasal discharge, lameness and ocular discharge as key indicators of horse fitness and welfare on abattoir. The study provides detailed scientific data to help establish strategies regarding optimal days of recovery post-transport and fattening for homogenization of weights between animals of different origins, logistic planning, and optimization of logistic resources to minimize the biological cost of long-distance transport.

Prostate cancer screening in Portugal: prevalence and perception of potential benefits and adverse effects.

INTRODUCTION: Opportunistic screening for prostate cancer has been widely used, though organized programs are not recommended. We aimed to estimate the prevalence of prostate cancer screening and the perception of potential benefits and harms of screening, among the Portuguese general population. METHODS: A representative sample of Portuguese-speaking inhabitants in mainland Portugal was selected, using a stratified probabilistic sampling procedure; men above 40 were considered for analysis (n = 414). Data on sociodemographic characteristics, lifetime use and usual frequency of prostate cancer screening (prostate-specific antigen test or digital rectal examination) and perception of potential benefits and adverse effects of cancer screening were assessed using face-to-face interviews, by structured questionnaire. RESULTS: The proportion of participants who reported having been submitted to prostate cancer screening at least once in their lifetime was 44.2% (95% confidence interval: 37.5-51.0; 13.8% only digital rectal examination, 12.2% only prostate-specific antigen test, and 18.2% digital rectal examination and prostate-specific antigen test). As potential benefits of cancer screening, the options "knowledge of not having the disease", "earlier detection" and "more effective treatment" were selected by 55.8%, 12.9% and 31.3% of the participants, respectively. Regarding potential adverse effects, the most and least frequently identified were 'anxiety while waiting for the results' (55.1%) and 'false negatives' (38.0%), respectively. CONCLUSIONS: Almost half of the men between 40 and 79 years old declared that they have been screened for prostate cancer. Nearly one-third of the participants considered that reassurance of a negative result was the main potential benefit of screening, whereas most failed to identify the most frequent adverse effects.

Evidence of acaricide resistance in different life stages of Amblyomma mixtum and Rhipicephalus microplus (Acari: Ixodidae) collected from the same farm in the state of Veracruz, Mexico.

The objectives of this study were to evaluate the resistance of Amblyomma mixtum and Rhipicephalus microplus ticks from co-infested bovines from the Veracruz region in Mexico to different acaricide families and to demonstrate the viability of the packet test on different A. mixtum instars. The following acaricide families were used: a combination (cypermethrin 15 g + chlorpyrifos 25 g + citronella 1 g + butoxide piperonyl 15 g), amidine (formamidine 12.5 g), pyrethroid (cypermethrin 15 g), and organophosphate (dichlorvos 60 g + chlorpyrifos 20 g). Regarding the packet test in both species, resistance was found for the pyrethroid and amidine families in A. mixtum and R. microplus, as efficacy did not surpass 40 %, including in immature instars; regarding the adult immersion test in R. microplus, the efficacy was 93.3 % for the amidine family and 26.2 % for the pyrethroid family. The proposed methodology is an alternative technique to optimize resistance detection in immature ticks with a heteroxenous life cycle.

Transfer of the Septin Ring to Cytokinetic Remnants in ER Stress Directs Age-Sensitive Cell-Cycle Re-entry.

During cell division, the inheritance of a functional endoplasmic reticulum (ER) is ensured by the endoplasmic reticulum stress surveillance (ERSU) pathway. Activation of ERSU causes the septin ring to mislocalize, which blocks ER inheritance and cytokinesis. Here, we uncover that the septin ring in fact translocates to previously utilized cell division sites called cytokinetic remnants (CRMs). This unconventional translocation requires Nba1, a negative polarity regulator that normally prevents repolarization and re-budding at CRMs. Furthermore, septin ring translocation relies on the recruitment and activation of a key ERSU component Slt2 by Bem1, without activating Cdc42. Failure to transfer all septin subunits to CRMs delays the cell's ability to re-enter the cell cycle when ER homeostasis is restored and hinders cell growth after ER stress recovery. Thus, these deliberate but unprecedented rearrangements of cell polarity factors during ER stress safeguard cell survival and the timely cell-cycle re-entry upon ER stress recovery.

Occurrence of Amblyomma mixtum on the water buffalo (Bubalus bubalis) in Mexico.

The water buffalo (Bubalus bubalis) is an Asian species of bovine that was introduced in Mexico in 1992 as an alternative for milk and meat production. To date, no surveys have been conducted to identify ticks acquired by water buffaloes since their arrival in the country. Here we report, for the first time, the presence of Amblyomma mixtum, a neotropical tick in the Amblyomma cajennense complex, found on water buffaloes from Mexico and discuss its possible implications in veterinary public health for the region.

Primary mesenchymal chondrosarcoma of the kidney: A case report and review of literature.

Primary mesenchymal chondrosarcoma of the kidney is extremely rare, with only nine cases reported in the English literature. We report a new case of this disease. A 35-year-old man, presented with flank pain, episodic gross hematuria and a painless palpable mass in left abdominal quadrant. Computed tomography scan identified a left renal tumor with 20 cm, with no evidence of regional or metastatic spread disease. The patient underwent radical nephrectomy. The immunohistopathological diagnosis was mesenchymal chondrosarcoma of the kidney. At 18 months of follow-up, there was no evidence of recurrence or distant metastasis. Primary renal chondrosarcoma is so rare that its prognosis is unknown. Disease recurrence is unpredictable and when it is detected, the prognosis is poor. The radical nephrectomy with complete resection of the tumor with wide resection free margins is recommended, and the patients need long-term and close surveillance, with particular attention to local recurrence and uncommon sites of metastization.

Sphingolipids activate the endoplasmic reticulum stress surveillance pathway.

Proper inheritance of functional organelles is vital to cell survival. In the budding yeast, Saccharomyces cerevisiae, the endoplasmic reticulum (ER) stress surveillance (ERSU) pathway ensures that daughter cells inherit a functional ER. Here, we show that the ERSU pathway is activated by phytosphingosine (PHS), an early biosynthetic sphingolipid. Multiple lines of evidence support this: (1) Reducing PHS levels with myriocin diminishes the ability of cells to induce ERSU phenotypes. (2) Aureobasidin A treatment, which blocks conversion of early intermediates to downstream complex sphingolipids, induces ERSU. (3) orm1Δorm2Δ cells, which up-regulate PHS, show an ERSU response even in the absence of ER stress. (4) Lipid analyses confirm that PHS levels are indeed elevated in ER-stressed cells. (5) Lastly, the addition of exogenous PHS is sufficient to induce all ERSU phenotypes. We propose that ER stress elevates PHS, which in turn activates the ERSU pathway to ensure future daughter-cell viability.

Efficacy profile of Cypermethrin and Chlorpyrifos based acaricides on Rhipicephalus microplus control on cattle in the rearing phase, naturally infested and exposed to tick fever agents in central Brazil.

The objective of this work was to evaluate the efficacy of two cypermethrin- and chlorpyrifos-based acaricides in controlling Rhipicephalus microplus in a naturally infested bovine herd and in in vitro tests, as well as to monitor the animals for tick fever. Male bovines in the rearing phase were used, with 30 Brangus and 30 Nellore animals naturally infested. The groups were composed as follows: 15 Nellore treated, 15 Nellore control, 15 Brangus treated and 15 Brangus control. Every 18 days, the animals were monitored for tick count, acaricide treatment, weight, blood pack cell volume, and clinical signs. For in vitro tests, the larval packet test, adult immersion test and DNA amplification for tick fever diagnosis were performed. In the first animal treatment period, product 1 (cypermethrin, 15 g + chlorpyrifos, 25 g + citronellal, 1 g) was used; in the second period, product 2 (cypermethrin, 15 g + chlorpyrifos, 30 g + fenthion, 15 g) was used. In Brangus animals, the mean efficacy was 35.1% and 95.8% in the first and second periods, respectively, for the same animals. For Nellore animals, the efficacy in periods one and two was 51% and 97.1%, respectively. The in vitro results showed efficacy above 95% for the two challenged acaricides. The Brangus animals showed a high production of ticks associated with the presence of tick fever agents, which could generate risks for the disease's enzootic stability.

Life cycle of Amblyomma mixtum (Acari: Ixodidae) parasitizing different hosts under laboratory conditions.

Amblyomma mixtum is a tick species in the Amblyomma cajennense complex. The known geographic range of A. mixtum extends from Texas in the USA to western Ecuador and some islands in the Caribbean. Amblyomma mixtum is a vector of disease agents of veterinary and public health importance. The objective of this study was to describe the life cycle of A. mixtum under laboratory conditions. Bovines, rabbits and sheep were infested with larvae, nymphs, and adult ticks under controlled conditions to assess several biological parameters. Eggs, larvae, nymphs and adults were kept in an incubator (27 °C temperature and 80% relative humidity) when they were off the host. The average life cycle of A. mixtum was 88 and 79 days when fed on rabbits and cattle, respectively. Sheep were found to be unsuitable because no ticks attached. The rabbit is a more practical host to maintain a colony of A. mixtum under laboratory conditions. The data from this study can be considered as an example for the life cycle of A. mixtum. However, caution must be exercised when making comparisons to the biology of A. mixtum in its natural habitat.

Prostate cancer incidence and mortality in Portugal: trends, projections and regional differences.

There is a large geographical variability in prostate cancer incidence and mortality trends, mostly because of heterogeneity in control efforts across regions. We aimed to describe the time trends in prostate cancer incidence and mortality in Portugal, overall and by region, and to estimate the number of incident cases and deaths in 2020. The number of cases and incidence rates in 1998-2009 were collected from the Regional Cancer Registries. The number of deaths and mortality rates were obtained from the WHO mortality database (1988-2003 and 2007-2013) and Statistics Portugal (2004-2006; 1991-2013 by region). JoinPoint analyses were used to identify significant changes in trends in age-standardized incidence and mortality rates. Incidence and mortality predictions for 2020 were performed using Poisson regression models and population projections provided by Statistics Portugal. In Portugal, prostate cancer incidence has been increasing since 1998 (1.8%/year), with the exception of the North Region, with a decrease since 2006 (-3.2%/year). An overall mortality decline has been observed since 1997 (-2.2%/year), although there were two patterns of mortality variation at the regional level: one with an inflection point or significant variation in the rates and the other without significant variation. If these trends are maintained, ∼8600 incident cases and 1700 deaths may be expected to occur in Portugal in 2020. Despite the overall increasing incidence and decreasing mortality, there is a large heterogeneity across regions. Future studies should address regional differences in the trends of prostate specific antigen screening and in the effective management of prostate cancer.

Reticulons Regulate the ER Inheritance Block during ER Stress.

Segregation of functional organelles during the cell cycle is crucial to generate healthy daughter cells. In Saccharomyces cerevisiae, ER stress causes an ER inheritance block to ensure cells inherit a functional ER. Here, we report that formation of tubular ER in the mother cell, the first step in ER inheritance, depends on functional symmetry between the cortical ER (cER) and perinuclear ER (pnER). ER stress induces functional asymmetry, blocking tubular ER formation and ER inheritance. Using fluorescence recovery after photobleaching, we show that the ER chaperone Kar2/BiP fused to GFP and an ER membrane reporter, Hmg1-GFP, behave differently in the cER and pnER. The functional asymmetry and tubular ER formation depend on Reticulons/Yop1, which maintain ER structure. LUNAPARK1 deletion in rtn1Δrtn2Δyop1Δ cells restores the pnER/cER functional asymmetry, tubular ER generation, and ER inheritance blocks. Thus, Reticulon/Yop1-dependent changes in ER structure are linked to ER inheritance during the yeast cell cycle.

The ER Stress Surveillance (ERSU) pathway regulates daughter cell ER protein aggregate inheritance.

Stress induced by cytoplasmic protein aggregates can have deleterious consequences for the cell, contributing to neurodegeneration and other diseases. Protein aggregates are also formed within the endoplasmic reticulum (ER), although the fate of ER protein aggregates, specifically during cell division, is not well understood. By simultaneous visualization of both the ER itself and ER protein aggregates, we found that ER protein aggregates that induce ER stress are retained in the mother cell by activation of the ER Stress Surveillance (ERSU) pathway, which prevents inheritance of stressed ER. In contrast, under conditions of normal ER inheritance, ER protein aggregates can enter the daughter cell. Thus, whereas cytoplasmic protein aggregates are retained in the mother cell to protect the functional capacity of daughter cells, the fate of ER protein aggregates is determined by whether or not they activate the ERSU pathway to impede transmission of the cortical ER during the cell cycle.