The phylogenetic range of bacterial and viral pathogens of vertebrates

Many major human pathogens are multihost pathogens, able to infect other vertebrate species. Describing the general patterns of host–pathogen associations across pathogen taxa is therefore important to understand risk factors for human disease emergence. However, there is a lack of comprehensive curated databases for this purpose, with most previous efforts focusing on viruses. Here, we report the largest manually compiled host–pathogen association database, covering 2,595 bacteria and viruses infecting 2,656 vertebrate hosts. We also build a tree for host species using nine mitochondrial genes, giving a quantitative measure of the phylogenetic similarity of hosts. We find that the majority of bacteria and viruses are specialists infecting only a single host species, with bacteria having a significantly higher proportion of specialists compared to viruses. Conversely, multihost viruses have a more restricted host range than multihost bacteria. We perform multiple analyses of factors associated with pathogen richness per host species and the pathogen traits associated with greater host range and zoonotic potential. We show that factors previously identified as important for zoonotic potential in viruses—such as phylogenetic range, research effort, and being vector‐borne—are also predictive in bacteria. We find that the fraction of pathogens shared between two hosts decreases with the phylogenetic distance between them. Our results suggest that host phylogenetic similarity is the primary factor for host‐switching in pathogens.     

呼吸道传染病治疗中抗体药物的研发进展

呼吸系统疾病影响着全世界数百万人,主要病变发生在气管、支气管、肺部及胸腔,病变轻者多咳嗽、胸痛,重者呼吸困难、缺氧甚至呼吸衰竭,可造成多种并发症,导致患者严重残疾甚至死亡。治疗性抗体的临床使用为肺癌、哮喘以及各类呼吸道传染病等的治疗开辟了新途径。目前已有数十种抗体（antibodies,Abs）获得市场批准,而且还有更多的抗体药物正在临床开发中。这些Abs中的大多数是针对哮喘、肺癌、慢性阻塞性肺病、特发性肺纤维化以及呼吸道传染病等疾病。其中,呼吸道传染病的爆发具有传播迅猛、传染性强的特点,常引发全球关注,如当下肆虐全球的新型冠状病毒肺炎。针对呼吸道传染病的多种Abs为其临床治疗提供了新策略。基于此,综述了已获准和正在临床开发的适用于治疗呼吸道传染病的Abs,通过综述抗体治疗的分子机制、优势和发展趋势,以期为呼吸道传染病治疗中抗体药物的研发提供参考。     

The N-terminus of Paenibacillus larvae C3larvinA modulates catalytic efficiency

C3larvinA was recently described as a mono-ADP-ribosyltransferase (mART) toxin from the enterobacterial repetitive intergenic consensus (ERIC) III genotype of the agricultural pathogen, Paenibacillus larvae. It was shown to be the full-length, functional version of the previously described C3larvin_trunc toxin, due to a 33-residue extension of the N-terminus of the protein. In the present study, a series of deletions and substitutions were made to the N-terminus of C3larvinA to assess the contribution of the α₁-helix to toxin structure and function. Catalytic characterization of these variants identified Asp²³ and Ala³¹ residues as supportive to enzymatic function. A third residue, Lys³⁶, was also found to contribute to the catalytic activity of the enzyme. Analysis of the C3larvinA homology model revealed that these three residues were participating in a series of interactions to properly orient both the Q-X-E and S-T-S motifs. Ala³¹ and Lys³⁶ were found to associate with a structural network of residues previously identified in silico, whereas Asp²³ forms novel interactions not previously described. At last, the membrane translocation activity into host target cells of each variant was assessed, highlighting a possible relationship between protein dipole and target cell entry.     

Innate lymphoid cells and gastrointestinal disease

Innate lymphoid cells (ILCs) are a group of innate immune cells, which constitute the first line of defense in the immune system, together with skin and mucous membrane. ILCs also play an important role in maintaining the homeostasis of the body, particularly in the complex and diverse environment of the intestine. ILCs respond to different microenvironments, maintaining homeostasis directly or indirectly through cytokines. As a result, ILCs, with complex and pleiotropic characteristics, are associated with many gastrointestinal diseases. Their ability of transition among those subgroups makes them function as both promoting and inhibiting cells, thus affecting homeostasis and disease progressing to either alleviation or deterioration. With these special characteristics, ILCs theoretically can be used in the new generation of immunotherapy as an alternative and supplement to current tumor therapy. Our review summarizes the characteristics of ILCs with respect to category, function, and the relationship with intestinal homeostasis and gastrointestinal diseases. In addition, potential tumor immunotherapies involving ILCs are also discussed to shed light on the perspectives of immunotherapy.     

Knowledge and attitudes regarding genetic testing among Jordanians: An approach towards genomic medicine

BackgroundThe twenty first century can be called the genomic era referring to the rapid development of genetics, and the beginning of genomic medicine. An initial step towards genomic medicine is to evaluate the knowledge and attitude towards genetic testing among different populations. The aims of this study were to assess the genetic knowledge and attitude towards genetic testing among the Jordanian population and patients with immune diseases. In addition, we evaluated the association between knowledge, attitude and several demographic factors of the population.MethodsThis study was performed using an online questionnaire that was distributed to respondents from different regions of Jordan.ResultsA total of 1149 participants were recruited from the Jordanian population. Overall factual genetic knowledge of the participants was good (65.4%), with education level, working or studying in a health-related field and household average monthly income being significant predictors of factual knowledge scores (P = 0.03, P < 0.001 and P < 0.001, respectively). However, factual knowledge results revealed that scores of questions related to diseases were significantly higher than scores of gene-related scientific facts (P < 0.01). Participants of our study reported to have low perceived knowledge on medical uses (39.5%) and social consequences (23.9%) of genetic testing. Regarding the participants’ attitudes, favorable attitudes towards genetic testing were prevailing (91.5%). Favorable attitudes were more prominent among higher educated participants, and participants with higher scores of factual knowledge.ConclusionDespite the fact that our Jordanian-based study revealed a good level of genetic knowledge as well as a favorable attitude towards genetic testing, we realized an imbalance of knowledge between gene-related scientific facts and disease-related concepts as well as between factual and perceived genetic knowledge, which indicates the necessity of increasing the awareness about genetic testing in order to ensure that individuals can take informed decisions that help in the employment of personalized medicine.     

Noncommunicable disease outcomes and the effects of vertical and horizontal health aid

Foreign health aid forms a substantial portion of health spending in many low- and middle-income countries (LMICs). It can be either vertical (funds earmarked for specific diseases) or horizontal (funds used for broad health sector strengthening). Historically, most health aid has been disbursed vertically toward key infectious diseases, with minimal allocations to noncommunicable diseases (NCDs). High NCD burden in LMICs underscores a need for increased assistance toward NCD objectives, but evidence on the outcomes of health aid for NCDs is sparse. We obtained annual data on cause-specific deaths and disability-adjusted life years (DALYs) for four leading NCDs across 116 countries, 2000–2016, and evaluated the relationship between these indicators and vertical and horizontal health aid using country fixed-effects models with 1-to-5-year lagged effects. After adjusting for fixed and time-variant country heterogeneity, vertical assistance for NCDs was significantly associated with subsequent reductions in NCD morbidity and mortality, particularly for persons under age 70 and for cardiovascular and chronic respiratory diseases. An additional dollar in per-capita NCD vertical assistance corresponded to reductions in the average annual NCD burden of 7,459 DALYs/281 deaths after one year, 7,728 DALYs/319 deaths after two years, and 8,957 DALYs/346 deaths after three years. The findings suggest that vertical assistance for NCD programs may be an appropriate mechanism for addressing short-term NCD needs in LMICs, where it may help to fill health sector gaps in NCD care, but longer-term evaluation is needed for assessing the role of horizontal assistance.     

Research and effectiveness of anti-viral drugs against COVID-19; global public intervention to prevent coronavirus and to improve human health

Since the first case report on COVID-19, its transmission took place rapidly across the globe. Currently, it is reported to be spread into a total of 216 countries and territories. The suppression on industrial and gasoline burning activities accompanied after COVID-19 lock down favorably boosted the nature to restore its deteriorated sections such as in air with the improved Air quality index and in water bodies with the natural tone of purity. Increased use of anti-viral drugs along with herbal therapies has been observed at mass scale as global intervention to prevent the disease. The use of personal protective equipment and disinfection strategies for the control of pandemic has dramatically increased the pollution of plastic and medical waste. This article aims to forecast and highlight the evidence-based impact/changes (+ive and -ive) of coronavirus on the environment, global interventions to prevent the disease along with the levels of effectiveness of personal used protective equipment to stop the spread of coronavirus.     

Ageing Effect Evaluation on HD-sEMG Signals Using CCA Approach

ObjectivesThe objective of the proposed study is to exploit the technology of high-density surface electromyography (HD-sEMG), in order to evaluate the muscle activation in young and elderly subjects during a daily life gesture, namely, Sit To Stand (STS), using wireless connected ambulatory equipment (TMSi©) and Blind Source Separation (BSS) approach with Canonical Correlation Analysis (CCA).Materials and methodsSixteen subjects participated (50% females) divided into two categories (‘H1’: young (30.62 yrs ±5.92, 23.95 kg/m² ±3.08), versus ‘H2’: old (61.87 yrs ±7.98, 23.4 kg/m² ±3.38)), in the recording of HD-sEMG signals, using 32-electrodes square grids (4×8), during Sit To Stand (STS) motion, three times at spontaneous speed. The studied muscle is the Rectus Femoris (RF) muscle. The recorded HD-sEMG signals were analyzed with CCA approach to extract correlation coefficient sets according to two age categories (young versus old), in order to evaluate its discriminating power with ageing. Statistical tests (t-test) were used to evaluate the discrimination for these two categories.ResultsThe calculation of CCA correlation coefficients showed a significant difference between young and old category concerning the mean CCA correlation coefficient (P<0.001***) and also the standard deviation of the CCA correlation coefficients (P<0.0001****).ConclusionThe obtained results are promising and indicate a clear difference between the obtained source variability using CCA method between the young and the old tested subjects during daily life motion. Furthermore, these estimated sources seem to be impacted by both anatomical and functional modifications with ageing.