Elucidating the Preadipocyte and Its Role in Adipocyte Formation: a Comprehensive Review

Adipogenesis is a complex process whereby the multipotent adipose-derived stem cell is converted to a preadipocyte before terminal differentiation into the mature adipocyte. Preadipocytes are present throughout adult life, exhibit adipose fat depot specificity, and differentiate and proliferate from distinct progenitor cells. The mechanisms that promote preadipocyte commitment and maturation involve numerous protein factor regulators, epigenetic factors, and miRNAs. Detailed characterization of this process is currently an area of intense research and understanding the roles of preadipocytes in tissue plasticity may provide insight into novel approaches for tissue engineering, regenerative medicine and treating a host of obesity-related conditions. In the current study, we analyzed the current literature and present a review of the characteristics of transitioning adipocytes and detail how local microenvironments influence their progression towards terminal differentiation and maturation. Specifically, we detail the characterization of preadipocyte via surface markers, examine the signaling cascades and regulation behind adipogenesis and cell maturation, and survey their role in tissue plasticity and health and disease.     

Monoclonal antibodies for prophylactic and therapeutic use against viral infections

Neutralizing antibodies play an essential part in antiviral immunity and are instrumental in preventing or modulating viral diseases. Polyclonal antibody preparations are increasingly being replaced by highly potent monoclonal antibodies (mAbs). Cocktails of mAbs and bispecific constructs can be used to simultaneously target multiple viral epitopes and to overcome issues of neutralization escape. Advances in antibody engineering have led to a large array of novel mAb formats, while deeper insight into the biology of several viruses and increasing knowledge of their neutralizing epitopes has extended the list of potential targets. In addition, progress in developing inexpensive production platforms will make antiviral mAbs more widely available and affordable.     

Rabies virus vaccines: Is there a need for a pan-lyssavirus vaccine?

All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens.     

Ikoma lyssavirus, highly divergent novel lyssavirus in an African civet

Evidence in support of a novel lyssavirus was obtained from brain samples of an African civet in Tanzania. Results of phylogenetic analysis of nucleoprotein gene sequences from representative Lyssavirus species and this novel lyssavirus provided strong empirical evidence that this is a new lyssavirus species, designated Ikoma lyssavirus.     

Screening for incontinence in a secure psychiatric service for women

Incontinence is associated with mental illness and neuroleptic medications but diagnosis and treatment is often poor or non‐existent. Problems of incontinence are compounded in secure psychiatric services for women by poor health, obesity, and a sedentary lifestyle. Addressing the physical health of this group necessitates a more accurate picture of the nature, incidence, and management of incontinence. A point‐in‐time survey of 108 women who agreed to be interviewed (93%) covered presence, frequency, and nature of incontinence, and information on management case note data was used to gather demographic and previous medical history, comparisons were made between patients with and without problems of incontinence. Findings indicate a problem of incontinence in 48% of women with a dominance of problems of stress and urge enuresis. Of modifiable factors that contribute to enuresis, the current study highlighted the contribution of obesity, smoking and clozapine medication. A further finding was the preference for managing rather than treating problems of incontinence. Actions to improve the detection and treatment of this problem are described.     

Serological Detection of Antibodies to Peste des Petits Ruminants Virus in Large Ruminants

Peste des petits ruminants (PPR) is an economically important disease of small ruminants with a rapidly expanding geographical distribution. Peste des petits ruminants virus may manifest in a variety of ways with disease ranging from acute to subclinical. We investigated the exposure of large ruminants to PPRV in areas where the virus is endemic in the small ruminant population by assessing the serological status of groups of animals. This study focused on the Punjab province of Pakistan as an area where the virus is endemic and where mixed farming practices occur enabling close interactions between small and large ruminant populations. An overall PPR seropositivity was detected in 10.0% of cattle and 14.16% of buffaloes. Following an assessment of serological profiles in large ruminants within different age groups, a maximum seroprevalence was observed in cattle (17.5%) and buffaloes (22.5%) over 2 years of age indicating the potential utility of sampling large ruminant populations for PPR serosurveillance. The large ruminants sampled between one and two years of age had similar levels of seropositivity within populations with 11.2% and 16.2% of animals being seropositive, respectively. Current PPR vaccination strategies do not enable the differentiation between infected and vaccinated small ruminants, and as such, the serological surveillance of sheep and goats is of little value. When considering eradication programmes for PPRV, this factor is of great significance. However, where large and small ruminants are farmed together, serological surveillance of large ruminants may provide a snapshot of virus infection within populations where mild disease is present or where small ruminants are regularly vaccinated.     

Molecular Evolution of Peste des Petits Ruminants Virus

Despite safe and efficacious vaccines against peste des petits ruminants virus (PPRV), this virus has emerged as the cause of a highly contagious disease with serious economic consequences for small ruminant agriculture across Asia, the Middle East, and Africa. We used complete and partial genome sequences of all 4 lineages of the virus to investigate evolutionary and epidemiologic dynamics of PPRV. A Bayesian phylogenetic analysis of all PPRV lineages mapped the time to most recent common ancestor and initial divergence of PPRV to a lineage III isolate at the beginning of 20th century. A phylogeographic approach estimated the probability for root location of an ancestral PPRV and individual lineages as being Nigeria for PPRV, Senegal for lineage I, Nigeria/Ghana for lineage II, Sudan for lineage III, and India for lineage IV. Substitution rates are critical parameters for understanding virus evolution because restrictions in genetic variation can lead to lower adaptability and pathogenicity.     

Lyssaviruses and Bats: Emergence and Zoonotic Threat

The continued detection of zoonotic viral infections in bats has led to the microbial fauna of these mammals being studied at a greater level than ever before. Whilst numerous pathogens have been discovered in bat species, infection with lyssaviruses is of particular significance from a zoonotic perspective as, where human infection has been reported, it is invariably fatal. Here we review the detection of lyssaviruses within different bat species and overview what is understood regarding their maintenance and transmission following both experimental and natural infection. We discuss the relevance of these pathogens as zoonotic agents and the threat of newly discovered viruses to human populations.     

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus,Respiratory Syncytial Virus and Influenza A Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca²⁺ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.