Using Participatory Risk Mapping (PRM) to Identify and Understand People's Perceptions of Crop Loss to Animals in Uganda

Considering how people perceive risks to their livelihoods from local wildlife is central to (i) understanding the impact of crop damage by animals on local people and (ii) recognising how this influences their interactions with, and attitudes towards, wildlife. Participatory risk mapping (PRM) is a simple, analytical tool that can be used to identify and classify risk within communities. Here we use it to explore local people''s perceptions of crop damage by wildlife and the animal species involved. Interviews (n = 93, n = 76) and seven focus groups were conducted in four villages around Budongo Forest Reserve, Uganda during 2004 and 2005. Farms (N = 129) were simultaneously monitored for crop loss. Farmers identified damage by wildlife as the most significant risk to their crops; risk maps highlighted its anomalous status compared to other anticipated challenges to agricultural production. PRM was further used to explore farmers'' perceptions of animal species causing crop damage and the results of this analysis compared with measured crop losses. Baboons (Papio anubis) were considered the most problematic species locally but measurements of loss indicate this perceived severity was disproportionately high. In contrast goats (Capra hircus) were considered only a moderate risk, yet risk of damage by this species was significant. Surprisingly, for wild pigs (Potamochoerus sp), perceptions of severity were not as high as damage incurred might have predicted, although perceived incidence was greater than recorded frequency of damage events. PRM can assist researchers and practitioners to identify and explore perceptions of the risk of crop damage by wildlife. As this study highlights, simply quantifying crop loss does not determine issues that are important to local people nor the complex relationships between perceived risk factors. Furthermore, as PRM is easily transferable it may contribute to the identification and development of standardised approaches of mitigation across sites of negative human-wildlife interaction.     

ESTROGEN METABOLISM IN MEN

In studies of men''s capacity for estrogen inactivation in health and disease, it was observed that patients with prostatic cancer had enhanced ability to inactivate estrogenic hormones. This ability might well lead to excessive androgen stimulation, thereby providing favorable hormonal environment for the development of prostatic cancer. Extension or regression of the malignant process did not affect this peculiar pattern of estrogen metabolism. It is possible, therefore, that the pattern may not be related to the cancer process itself but to some inherent tendency in the individual. Upon speculation as to whether or not this tendency is found in the liver, which is known to be the principal site of estrogen inactivation, studies of patients with liver damage were carried out and the results indicated that the liver possesses a tremendous reserve for inactivation of the estrogens in men.Studies on estrogen concentration in the bile indicated that estrogens are not eliminated rapidly from the human body through the biliary tract. However, this does not hold true for experimental animals.Observations on endogenous estrogen excretion in men did not support the concept that benign prostatic hypertrophy is due to an elevated estrogen-androgen ratio.     

无居民海岛开发生态损害评估——以象山县大羊屿岛为例

无居民海岛独特的生态系统和地理位置决定了受损后的修复成本极高、开发难度极大,其保护与开发已经成为国内外学界关注的重点。基于海岛生态系统服务价值理论构建了无居民海岛开发的生态损害评估模型,以我国首个公开拍卖使用权的大羊屿岛为例验证模型的科学性和可行性,并与2018年调整后的无居民海岛使用金征收标准中生态损害成本额度进行对比分析。研究结果表明：（1）大羊屿岛开发的生态损害补偿金为1644.82万元。其中,陆域开发行为所需的生态损害补偿金为890.19万元,高于海洋开发行为所造成的生态损害补偿金;（2）通过本文计算的海岛陆域生态损害补偿金高出现行海岛使用金标准中的生态损害成本371.90万元,2018年旅游用岛使用金征收标准仍有上调空间。对无居民海岛开发的生态损害评估可以增强政府和企业对于海岛资源的保护意识,重新权衡无居民海岛开发的利弊,避免对海岛资源过度和盲目的开发。     

Improving care: a study of orthopaedic outpatient referrals.

OBJECTIVE--To identify aspects of outpatient referral in which general practitioners'', consultants'', and patients'' satisfaction could be improved. DESIGN--Questionnaire survey of general practitioners, consultant orthopaedic surgeons, and patients referred to an orthopaedic clinic. SETTING--Orthopaedic clinic, Doncaster Royal Infirmary. SUBJECTS--628 consecutive patients booked into the orthopaedic clinic. MAIN OUTCOME MEASURES--Views of the general practitioners as recorded both when the referral letter was received and again after the patient had been seen, views of the consultants as recorded at the time of the clinic attendance, and views of the patients as recorded immediately after the clinic visit and some time later. RESULTS--Consultants rated 213 of 449 referrals (42.7%) as possibly or definitely inappropriate, though 373 of 451 patients (82.7%) reported that they were helped by seeing the consultant. Targets for possible improvement included information to general practitioners about available services, communication between general practitioners and consultants, and administrative arrangements in clinics. Long waiting times were a problem, and it seemed that these might be reduced if general practitioners could provide more advice on non-surgical management. Some general practitioners stated that they would value easier telephone access to consultants for management advice. It was considered that an alternative source of management advice on musculoskeletal problems might enable more effective use to be made of specialist orthopaedic resources. Conclusion--A survey of patients'' and doctors'' views of referrals may be used to identify aspects in which the delivery of care could be made more efficient. Developing agreed referral guidelines might help general practitioners to make more effective use of hospital services.     

Oxidative Damage and Motor Neurone Disease Difficulties in the Measurement of Protein Carbonyls in Human Brain Tissue

It has been suggested in the literature that elevated oxidative protein damage, measured as protein carbonyls, is present in the nervous system of patients with sporadic motor neurone disease (MND). However, the actual reported levels of brain protein carbonyls vary over a wide range. We show here that this is probably due to the use of different protocols for the carbonyl assay; results differ depending on when the dinitrophenylhydrazine reagent is added and at what stage in the procedure protein is assayed for the calculation of carbonyls on a unit protein basis. Using a range of different procedures, we were unable to confirm reports of elevated protein carbonyls in motor cortex from brains of patients with MND. We also measured thiobarbituric acid-reactive material in the brain samples using an HPLC-based TBA test in the presence of butylated hydroxytoluene. In general, there was no significant elevation of TBARS in MND motor cortex. However, four patients showed values higher than any of the control patients (both 'normal' control and 'disease control'). There was no correlation of TBARS with protein carbonyl values. We suggest that oxidative damage in motor cortex in sporadic MND, if it occurs, may be confined to a small group of patients and may affect different molecular targets in each patient.     

oxLDL-Induced Lipid Accumulation in Glomerular Podocytes: Role of IFN-γ, CXCL16, and ADAM10

Previous studies have shown that lipid accumulation plays an important role in the pathogenesis and development of glomerular sclerosis. oxLDL caused damage in renal mesangial cells, endothelial cells, and podocytes, and podocytes might be the major victim of oxLDL insult. However, the regulatory mechanism of how oxLDL induces the damage of podocytes remains to be elucidated. In this study, oil red staining was used to investigate the lipid accumulation in podocytes. Moreover, the effects of CXCL16 antibody, IFN-γ, and ADAM10 inhibitor on oxLDL intake and CXCL16 expression were also explored to elucidate the regulatory factors of lipid accumulation in podocytes.     

Hepatic cell division and tissue repair: a key to survival after liver injury

The survival of patients suffering from severe liver damage depends heavily on the ability of the remaining hepatocytes to regenerate and replace the dead or dying cells; death usually occurs when the regenerating ability of the liver is compromised owing to heavy damage to the liver. The current approach to therapy aims only to block additional liver injury from hepatotoxicants or hepatic disease. It hepatocellular regeneration and tissue repair could be stimulated after hepatic damage by a therapeutically compatible mechanism, then it might be possible to prevent death arising from serious liver injury.     

SUMO Modification Regulates BLM and RAD51 Interaction at Damaged Replication Forks

The gene mutated in Bloom''s syndrome, BLM, is important in the repair of damaged replication forks, and it has both pro- and anti-recombinogenic roles in homologous recombination (HR). At damaged forks, BLM interacts with RAD51 recombinase, the essential enzyme in HR that catalyzes homology-dependent strand invasion. We have previously shown that defects in BLM modification by the small ubiquitin-related modifier (SUMO) cause increased γ-H2AX foci. Because the increased γ-H2AX could result from defective repair of spontaneous DNA damage, we hypothesized that SUMO modification regulates BLM''s function in HR repair at damaged forks. To test this hypothesis, we treated cells that stably expressed a normal BLM (BLM+) or a SUMO-mutant BLM (SM-BLM) with hydroxyurea (HU) and examined the effects of stalled replication forks on RAD51 and its DNA repair functions. HU treatment generated excess γ-H2AX in SM-BLM compared to BLM+ cells, consistent with a defect in replication-fork repair. SM-BLM cells accumulated increased numbers of DNA breaks and were hypersensitive to DNA damage. Importantly, HU treatment failed to induce sister-chromatid exchanges in SM-BLM cells compared to BLM+ cells, indicating a specific defect in HR repair and suggesting that RAD51 function could be compromised. Consistent with this hypothesis, RAD51 localization to HU-induced repair foci was impaired in SM-BLM cells. These data suggested that RAD51 might interact noncovalently with SUMO. We found that in vitro RAD51 interacts noncovalently with SUMO and that it interacts more efficiently with SUMO-modified BLM compared to unmodified BLM. These data suggest that SUMOylation controls the switch between BLM''s pro- and anti-recombinogenic roles in HR. In the absence of BLM SUMOylation, BLM perturbs RAD51 localization at damaged replication forks and inhibits fork repair by HR. Conversely, BLM SUMOylation relieves its inhibitory effects on HR, and it promotes RAD51 function.     

Analysis of DNA damage and repair accompanying differentiation in the intestinal crypt.

The ability to process damaged DNA may vary between cells depending on their differentiated status. However, there is little in vivo data available and it is not intuitively obvious how the activity of specific repair pathways may vary between different subpopulations (e.g. stem cells and proliferative, committed and differentiated cells) of a particular tissue. To obtain such information for the intestinal epithelium, we have developed an assay that detects differences in the way different regions of the crypt (stem, proliferative and maturation zones) respond to DNA damage. The assay is a variant of the ''comet'' assay, which detects DNA strand breaks by measuring the proportion of DNA migrating from individual cells, or in this case intact isolated crypts, in an electrophoretic field. The method is quantitative, with the amount of migrating DNA being proportional to the number of strand breaks. Isolated crypts are repair competent and spatial differences are apparent with some agents. The assay has the potential to characterize the repair properties of cells at different stages of differentiation within the crypt, determine the characteristics that might predispose them to damage and may help in understanding the route of stem cell mutation.     

GDNF对神经干细胞增殖、分化的影响

神经干细胞(neural stem cells,NSCs)具有如下特点:(1)可以向神经组织分化或源自神经系统的一部分。(2)具备维持和更新的自主能力。(3)可通过细胞分裂增殖。以上特点决定了它的应用价值,被公认为治疗阿尔茨海默氏病,帕金森氏症,脊髓损伤,中风等神经退行性疾病的最佳方案。用干细胞治疗癌症,免疫相关性疾病,和其他疾病被认为是很有创新的新疗法,可能有一天会扩展到修复和补充大脑损伤。胶质细胞源性神经营养因子(glial Cell line一derived neurotrophic factor,GDNF)为TGF一β超家族的一员,具有很强神经保护作用,大量实验研究证实GDNF可促进帕金森病大鼠模型的中脑神经干细胞定向分化为多巴胺能神经元,同时大量实验发现其可促进神经干细胞增殖及分化,为神经干细胞的应用奠定了基础。     

Measuring Rao's Q diversity index from remote sensing: An open source solution

Measuring biodiversity is a key issue in ecology to guarantee effective indicators of ecosystem health at different spatial and time scales. However, estimating biodiversity from field observations might present difficulties related to costs and time needed. Moreover, a continuous data update for biodiversity monitoring purposes might be prohibitive. From this point of view, remote sensing represents a powerful tool since it allows to cover wide areas in a relatively low amount of time. One of the most common indicators of biodiversity is Shannon's entropy H′, which is strictly related to environmental heterogeneity, and thus to species diversity. However, Shannon's entropy might show drawbacks once applied to remote sensing data, since it considers relative abundances but it does not explicitly account for distances among pixels’ numerical values. In this paper we propose the use of Rao's Q applied to remotely sensed data, providing a straightforward R-package function to calculate it in 2D systems. We will introduce the theoretical rationale behind Rao's index and then provide applied examples based on the proposed R function.     

Redox control of iron regulatory proteins

Abstract

Increasing evidence suggests an important role of oxidant-induced damage in the progress of senescent changes, providing support for the free radical theory of aging proposed by Harman in 1956. However, considering that biological organisms continuously renew their structures, it is not clear why oxidative damage should accumulate with age. No strong evidence has been provided in favor of the concept of aging as an accumulation of synthetic errors (e.g. Orgels `error-catastrophe' theory and the somatic mutation theory). Rather, we believe that the process of aging may derive from imperfect clearance of oxidatively damaged, relatively indigestible material, the accumulation of which further hinders cellular catabolic and anabolic functions. From this perspective, it might be predicted that: (i) suppression of oxidative damage would enhance longevity; (ii) accumulation of incompletely digested material (e.g. lipofuscin pigment) would interfere with cellular functions and increase probability of death; (iii) rejuvenation during reproduction is mainly provided by dilution of undigested material associated with intensive growth of the developing organism; and (iv) age-related damage starts to accumulate substantially when development is complete, and mainly affects postmitotic cells and extracellular matrix, not proliferating cells. There is abundant support for all these predictions.     

Possible mechanisms of anosognosia: a defect in self-awareness.

Anosognosia of hemiplegia is of interest for both pragmatic and theoretical reasons. We discuss several neuropsychological theories that have been proposed to explain this deficit. Although for psychological reasons people might deny deficits, the denial hypothesis cannot account for the hemispheric asymmetries associated with this disorder and cannot explain why some patients might deny one deficit and recognize another equally disabling deficit. There is some evidence that faulty feedback from sensory deficits, spatial neglect and asomatognosia might be responsible for anosognosia in some patients. However, these feedback hypotheses cannot account for anosognosia in all patients. Although the hemispheric disconnection hypothesis is appealing, disconnection is probably only a rare cause of this disorder. The feedforward intentional theory of anosognosia suggests that the discovery of weakness is dependent on attempted action and some patients might have anosognosia because they do not attempt to move. We present evidence that supports this theory. The presence of one mechanism of anosognosia, however, does not preclude the possibility that other mechanisms might also be working to produce this disorder. Although a large population study needs to be performed, we suspect that anosognosia might be caused by several of the mechanisms that we have discussed. On the basis of the studies of impaired corporeal self-awareness that we have reviewed, we can infer that normal self-awareness is dependent on several parallel processes. One must have sensory feedback and the ability to attend to both one''s body and the space where parts of the body may be positioned or acting. One must develop a representation of the body, and this representation must be continuously modified by expectations (feedforward) and knowledge of results (feedback).     

Effect of an oral serotonin antagonist,ketanserin, on plasma ACTH concentrations in Nelson's syndrome.

A study was performed to see whether ketanserin, a serotonin antagonist, would reduce the raised concentrations of adrenocorticotrophic hormone (ACTH) in patients with Nelson''s syndrome. Six patients who had undergone bilateral adrenalectomy for Cushing''s disease and who had Nelson''s syndrome were given ketanserin 40 mg twice daily and placebo, for at least two months each, in a double blind crossover study. Ketanserin had no effect on ACTH concentrations. In healthy people serotonin seems to have a stimulatory role in the regulation of ACTH secretion, and the effect of ketanserin in reducing the ACTH response to hypoglycaemia suggested that it might prove useful in Nelson''s syndrome. These results show that it is not indicated in these patients.     

Early detection of high disease activity in juvenile idiopathic arthritis by sequential monitoring of patients' health-related quality of life scores

Juvenile idiopathic arthritis (JIA) is a chronic disease. During its “high disease activity (HDA)” stage, JIA can cause severe pain, and thus could seriously affect patients' physical and psychological health. Early detection of the HDA stage of JIA can reduce the damage of the disease by treating it at an early stage and alleviating the painful experience of the patients. So far, no effective cure of JIA has been found, and one major goal of disease management is to improve patients' quality of life. To this end, patients' health-related quality of life (HRQOL) scores are routinely collected over time from JIA patients. In this paper, we demonstrate that a new statistical methodology called dynamic screening system (DySS) is effective for early detection of the HDA stage of JIA. By this approach, a patient's HRQOL scores are monitored sequentially, and a signal is given by DySS once the longitudinal pattern of the scores is found to be significantly different from the pattern of patients with low disease activity. Dimension reduction of the observed HRQOL scores and the corresponding impact on the performance of DySS are also discussed.     

HCMV-Infected Cells Maintain Efficient Nucleotide Excision Repair of the Viral Genome while Abrogating Repair of the Host Genome

Many viruses subvert the host cell''s ability to mount and complete various DNA damage responses (DDRs) after infection. HCMV infection of permissive fibroblasts activates host DDRs at the time of viral deposition and during replication, but the DDRs remain uncompleted without arrest or apoptosis. We believe this was in part due to partitioning of the damage response and double strand break repair components. After extraction of soluble proteins, the localization of these components fell into three groups: specifically associated with the viral replication centers (RCs), diffused throughout the nucleoplasm and excluded from the RCs. Others have shown that cells are incapable of processing exogenously introduced damage after infection. We hypothesized that the inability of the cells to process damage might be due to the differential association of repair components within the RCs and, in turn, potentially preferential repair of the viral genome and compromised repair of the host genome. To test this hypothesis we used multiple strategies to examine repair of UV-induced DNA damage in mock and virus-infected fibroblasts. Comet assays indicated that repair was initiated, but was not completed in infected cells. Quantitative analysis of immunofluorescent localization of cyclobutane pyrimidine dimers (CPDs) revealed that after 24 h of repair, CPDs were significantly reduced in viral DNA, but not significantly changed in the infected host DNA. To further quantitate CPD repair, we developed a novel dual-color Southern protocol allowing visualization of host and viral DNA simultaneously. Combining this Southern methodology with a CPD-specific T4 endonuclease V alkaline agarose assay to quantitate repair of adducts, we found efficient repair of CPDs from the viral DNA but not host cellular DNA. Our data confirm that NER functions in HCMV-infected cells and almost exclusively repairs the viral genome to the detriment of the host''s genome.     

Patient and general practitioner delays in acute myocardial infarction

The longest component of the total delay in coming under coronary care is patient delay, and it has been suggested that public education might be used to make it shorter. The patterns of patient delay were studied in 450 patients with acute myocardial infarction uncomplicated by cardiac arrest out of hospital, of whom 243 had a previous history of ischaemic heart disease. Patient delays had a skewed distribution with a modal delay of up to one hour, a median delay of two hours, and a mean delay of 10 hours. Two thirds of patients had sought help from their general practitioners within four hours of the onset of symptoms. During the first four hours the longer that patients delayed the lower was the subsequent mortality (27%, 18%, and 9% for delays of one hour or less, up to two hours, and up to four hours, respectively), but patients who delayed four to eight hours had the highest mortality of all (38%). Neither the median value nor the pattern of patient delays was altered by a previous history of ischaemic heart disease.There were pronounced differences in doctor delays, depending on the patient''s age, delay time, and ultimate place of treatment, showing that the doctors'' behaviour was influenced before they had seen their patients. Nevertheless, the median total delay for patients aged up to 70 was one hour 35 minutes, and a higher proportion of patients were seen early after infarction than in recent hospital trials of thrombolytic treatment.These findings suggest that the patients'' call for help and the doctors'' response may be at an instinctive level according to the patients'' distress; these patterns of behaviour may be difficult to modify by public education.     

COVID-19 disease and malignant cancers: The impact for the furin gene expression in susceptibility to SARS-CoV-2

Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients'' susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin''s expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues using online databases, and our IHC. As a result, furin presented with biased expression profiles in normal tissues, showing 12.25-fold higher than ACE2 in the lungs. The furin expression in tumors were significantly increased in ESCA and TGCT, and decreased in DLBC and THYM, indicating furin may play critical mechanistic functions in COVID-19 viral entry into cells in these cancer patients. Line with furin over/downexpression, furin promoter hypo-/hyper-methylation may be the regulatory cause of disease and lead to pathogenesis of ESCA and THYM. Furthermore, presence of FURIN-201 isoform with functional domains (P_proprotein, Peptidase_S8 and S8_pro-domain) is highest in all cancer types in comparison to other isoforms, demonstrating its use in tumorigenesis and SARS-Cov-2 entry into tumor tissues. Furin mutation frequency was highest in UCES, and its mutation might elevate ACE2 expression in LUAD and UCEC, reduce ACE2 expression in COAD, elevate HSPA5 expression in PAAD, and elevate TMPRSS2 expression in BRCA. These results showed that furin mutations mostly increased expression of ACE2, HSPA5, and TMPRSS2 in certain cancers, indicating furin mutations might facilitate COVID-19 cell entry in cancer patients. In addition, high expression of furin was significantly inversely correlated with long overall survival (OS) in LGG and correlated with long OS in COAD and KIRC, indicating that it could be used as a favorable prognostic marker for cancer patients'' survival. GO and KEGG demonstrated that furin was mostly enriched in genes for metabolic and biosynthetic processes, retinal dehydrogenase activity, tRNA methyltransferase activity, and genes involving COVID-19, further supporting its role in COVID-19 and cancer metabolism. Moreover, Cordycepin (CD) inhibited furin expression in a dosage dependent manner. Altogether, furin''s high expression might not only implies increased susceptibility to SARS-CoV-2 and higher severity of COVID-19 symptoms in cancer patients, but also it highlights the need for cancer treatment and therapy during the COVID-19 pandemic. CD might have a potential to develop an anti-SARS-CoV-2 drug through inhibiting furin expression.     

Nerve growth factor serum level is reduced in patients with sensorineural hearing impairment: possible clinical implications

Nerve growth factor (NGF) is the first and best characterised member of a family of neurotrophic factor. NGF is produced by numerous cells and it is present in physiologically relevant amounts in the bloodstream. It is known to promote the survival of peripheral sensory neurons and can be potentially useful as a therapeutic agent in neuronal system. On the both these observations we based our hypothesis that low circulating NGF might lead to sensorineural hearing loss (SNHL). To address this question we measured the levels of NGF in the bloodstream of patients affected by SNHL. The results showed that the amount of circulating NGF in these patients is significantly lower compared to levels found in patients not affected by this deficit. The results of the present study demonstrated that NGF might be a useful candidate for preventing the damage and promoting recovery or degeneration of the auditory pathways in humans.     

Porcine Lactic Dehydrogenase in the Serum of Patients Treated by Extracorporeal Porcine Liver Perfusion

Porcine lactic dehydrogenase (L.D.H.) has been found in the serum of four patients in hepatic coma treated by extracorporeal porcine liver perfusion. A comparison between the porcine L.D.H. isoenzyme pattern in the patients'' serum and that in porcine serum and liver extract indicates that the porcine L.D.H. is derived from the pig liver. This finding reflects damage to the pig liver cells sustained during porcine hepatectomy and subsequent perfusion. Possibly patients might develop immune reactions against porcine substances when these entered the circulation, especially if perfusion was repeated after an interval of some time.