Broad-spectrum Strategy Research Articles

Predicting the evolution from first-episode psychosis to mood or psychotic disorder: A systematic review of biological markers.

The development of paraclinical tools to assist clinical assessment is already widespread in nearly all other medical specialties. In psychiatry, many efforts are being made to improve management strategies using these new techniques. The first episode psychosis (FEP) is a clinical entity whose evolution after onset is difficult to predict in the current state of our practices. Our main objective was to identify from the literature the most promising biological markers for early prediction of thymic or psychotic trajectories following FEP. We performed a systematic literature review on 4 databases: PubMed, Scopus, PsycINFO, and Web of Science following PRISMA guidelines and using search terms related to FEP and biomarkers. Eight studies were included in our final analysis. Several biomarkers showed promising discriminatory capacities for predicting post-FEP evolution: the interleukins IL-6, IL-12p40, IL-1β, and the mRNA expression levels of the DICER-1 and AKT-1 genes. Other studies that opted for broad-spectrum strategies also highlighted new leads for the discovery of additional biomarkers. Overall, our results indicate the value of replicating studies targeting the analysis of the predictive capacities of several biological markers. It also appears important to homogenize methodologies and favor the construction of predictive models on several of these markers to reinforce their statistical significance.

H2S scavenger as a broad-spectrum strategy to deplete bacteria-derived H2S for antibacterial sensitization

Bacteria-derived H2S plays multifunctional protective roles against antibiotics insult, and the H2S biogenesis pathway is emerging as a viable target for the antibacterial adjuvant design. However, the development of a pan-inhibitor against H2S-synthesizing enzymes is challenging and underdeveloped. Herein, we propose an alternative strategy to downregulate the H2S levels in H2S-producing bacteria, which depletes the bacteria-derived H2S chemically by H2S scavengers without acting on the synthesizing enzymes. After the screening of chemically diversified scaffolds and a structural optimization campaign, a potent and specific H2S scavenger is successfully identified, which displays efficient H2S depletion in several H2S-producing bacteria, potentiates both bactericidal agents and photodynamic therapy, enhances the bacterial clearance of macrophages and polymorphonuclear neutrophils, disrupts the formation of bacterial biofilm and increases the sensitivity of bacterial persister cells to antibiotics. Most importantly, such an H2S scavenger exhibits sensitizing effects with gentamicin in Pseudomonas aeruginosa -infected pneumonia and skin wound female mouse models. In aggregate, our results not only provide an effective strategy to deplete bacteria-derived H2S and establish the H2S biogenesis pathway as a viable target for persisters and drug-resistant bacteria, but also deliver a promising antibacterial adjuvant for potential clinical translation.

Activation of retinoid X receptors protects retinal neurons and pigment epithelial cells from BMAA-induced death

Exposure to the non-protein amino acid cyanotoxin β–N-methylamino-L-alanine (BMAA), released by cyanobacteria found in many water reservoirs has been associated with neurodegenerative diseases. We previously demonstrated that BMAA induced cell death in both retina photoreceptors (PHRs) and amacrine neurons by triggering different molecular pathways, as activation of NMDA receptors and formation of carbamate-adducts was only observed in amacrine cell death. We established that activation of Retinoid X Receptors (RXR) protects retinal cells, including retina pigment epithelial (RPE) cells from oxidative stress-induced apoptosis. We now investigated the mechanisms underlying BMAA toxicity in these cells and those involved in RXR protection.BMAA addition to rat retinal neurons during early development in vitro increased reactive oxygen species (ROS) generation and polyADP ribose polymers (PAR) formation, while pre-treatment with serine (Ser) before BMAA addition decreased PHR death. Notably, RXR activation with the HX630 agonist prevented BMAA-induced death in both neuronal types, reducing ROS generation, preserving mitochondrial potential, and decreasing TUNEL-positive cells and PAR formation. This suggests that BMAA promoted PHR death by substituting Ser in polypeptide chains and by inducing polyADP ribose polymerase activation. BMAA induced cell death in ARPE-19 cells, a human epithelial cell line; RXR activation prevented this death, decreasing ROS generation and caspase 3/7 activity.These findings suggest that RXR activation prevents BMAA harmful effects on retinal neurons and RPE cells, supporting this activation as a broad-spectrum strategy for treating retina degenerations.

Macrophage-Inspired marine antifouling coating with dynamic surfaces based on regulation of dynamic covalent bonds

Macrophages can kill bacteria and viruses by releasing free radicals, which provides a possible approach to construct antifouling coatings with dynamic surfaces that release free radicals if the breaking of dynamic covalent bonds is precisely regulated. Herein, inspired by the defensive behavior of macrophages of releasing free radicals to kill bacteria and viruses, a marine antifouling coating composed of polyurethane incorporating dimethylglyoxime (PUx-DMG) is prepared by precise regulation of dynamic oxime-urethane covalent bonds. The obtained alkyl radical (R·) derived from the cleavage of the oxime-urethane bonds manages to effectively suppress the attachment of marine biofouling. Moreover, the intrinsic dynamic surface makes it difficult for biofouling to adhere and ultimately achieves sustainable antifouling property. Notably, the PU50-DMG coating not only presents efficient antibacterial and antialgae properties, but also prevents macroorganisms from settling in the sea for up to 4 months. This provides a pioneer broad-spectrum strategy to explore the marine antifouling coatings.

C-Jun N-terminal Kinase (JNK), p38, and Caspases: Promising Therapeutic Targets for the Regulation of Apoptosis in Cancer Cells by Phytochemicals

Abstract: Carcinogenesis is a process in which uncontrolled cell proliferation forms preneoplastic nodules which precede the appearance of cancer. In normal cells, growth and proliferation are regulated by certain growth and hormonal stimulation, while mutational alterations in these signals render the cells independent and resistant to these signals. In cancer, the critical homeostatic balance between cell growth and apoptosis is lost and the cells continue to survive beyond their normal life span. The activation of c-Jun N-terminal kinase (JNK), p38 and caspases are involved in potential proapoptotic signaling pathways. JNK, p38 MAPK pathway and caspases play a crucial role in the control of apoptosis in response to stress. The most recent and up-to-date literature was evaluated in this study, which describes the role of JNK, p38 MAPK pathway and caspases as therapeutic target in cancer. Chemotherapy uses drugs that are cytotoxic to highly proliferating tumor cells but also kills the non-tumor rapidly proliferating cells in the hair, skin and gastrointestinal tract epithelium, thereby accounting the side effects of these types of treatments. Recently, chemopreventive modalities derived from phytoconstituents present in plants provide a broad-spectrum strategy to overcome the incidence of cancer. Non-toxic, safe and affordable bioavailabilities of chemopreventive agents provide credence support in the field of cancer research compared to conventional therapies that cause serious consequences. Chemoprevention envisages the basic mechanisms like modulating the activity of xenobiotic-metabolizing enzymes, induction of apoptosis, immune system activation, suppressing angiogenesis and the formation of metastasis, antioxidant and anti-inflammatory properties. The present review highlighted the role of phytoconstituents derived from food, vegetables and medicinal plants in the induction of apoptosis in cancer cells, which in turn is mediated by the activation of JNK, p38 MAPK pathways, and caspases.

Strategy and performance of audiovisual streaming platforms

Purpose: This work aims to analyze and classify the competitive strategies of 37 streaming platforms and identify which strategic groups perform better globally. Design/methodology/approach: This study is based on the structure-conduct-performance paradigm and uses Porter's typology to reach its goal. It classified the 37 platforms into their respective strategic groups based on eight strategic variables using k-means cluster analysis. Then, group performances were compared using ANOVA to test the mean differences of two performance variables. Originality/relevance: The audiovisual industry is experiencing a radical change in content consumption, distribution, and production. Streaming technology, which delivers content over the internet without downloads, increased flexibility and sparked a wave of adoption of audiovisual streaming platforms that destabilized other sectors, such as home video. Consequently, this phenomenon left a gap in studies about the strategy and performance of the industry, which this paper intends to fill. Main findings: As a result, 14% of the platforms studied were allocated to the Differentiation strategic group, 30% to Cost Leadership, 19% to Differentiation Focus, 8% to Cost Focus, and 30% were considered Stuck-In-The-Middle. We identified that the strategic groups present significant differences in performance, validating the applicability of Porter's typology. Theoretical contributions: The study found that broad-spectrum strategies such as Cost Leadership and Differentiation promote better performance than focus strategies at this industry stage. Surprisingly, Stuck-In-The-Middle companies also perform well, similar to companies with broad-spectrum strategies.

Nanobodies against porcine CD163 as PRRSV broad inhibitor

PRRSV (Porcine Reproductive and Respiratory Syndrome Virus) is a major swine pathogen causing economic losses. To the date, effective broad PRRSV inhibitory strategies have not been available in practice yet. Targeting the key viral receptor CD163 to block PRRSV entry has emerged as an alternative approach beside vaccines for PRRSV inhibition. As an effective therapeutic tool, nanoantibodies (Nbs) have been widely used in antiviral research. In this study, a phage display VHH library was constructed for the selection of Nbs against porcine CD163 scavenger receptor cysteine-rich 5–9 domain (SRCR5–9). After five rounds of bio-panning and indirect ELISA, seven CD163-specific Nbs (Nb1-Nb7) were identified. All obtained Nbs displayed strong affinity to CD163 receptor and excellent antiviral activity. In particular, Nb2 exhibited significant broad inhibitory effects on variable PRRSV lineages and downregulated virus-related NF-κB signaling. Further studies suggested that Nbs mainly exerted antiviral functions by interfering with virus attachment stage, and also decreased the transcription of CD163. The conformational epitopes recognized by Nbs were localized in the SRCR5 domain of CD163, a crucial region in PRRSV infection. Overall, our findings provide a novel insight into the biofunction of CD163 in antiviral infection and the development of broad-spectrum strategies against PRRSV.

An inhaled bioadhesive hydrogel to shield non-human primates from SARS-CoV-2 infection.

The surge of fast-spreading SARS-CoV-2 mutated variants highlights the need for fast, broad-spectrum strategies to counteract viral infections. In this work, we report a physical barrier against SARS-CoV-2 infection based on an inhalable bioadhesive hydrogel, named spherical hydrogel inhalation for enhanced lung defence (SHIELD). Conveniently delivered via a dry powder inhaler, SHIELD particles form a dense hydrogel network that coats the airway, enhancing the diffusional barrier properties and restricting virus penetration. SHIELD's protective effect is first demonstrated in mice against two SARS-CoV-2 pseudo-viruses with different mutated spike proteins. Strikingly, in African green monkeys, a single SHIELD inhalation provides protection for up to 8 hours, efficiently reducing infection by the SARS-CoV-2 WA1 and B.1.617.2 (Delta) variants. Notably, SHIELD is made with food-grade materials and does not affect normal respiratory functions. This approach could offer additional protection to the population against SARS-CoV-2 and other respiratory pathogens.

Virus-host protein-protein interactions as molecular drug targets for arboviral infections

Arboviruses have the potential to spread quickly and cause a global health emergency. These are RNA viruses that use RNA-dependent RNA polymerase (RdRp) for their replication. RdRp lacks proofreading activity, leading to high error rates, low replicative fidelity, and more genetic variability. In addition, shorter generation time and faster evolutionary rate of these viruses lead to re-emergence and recurrence of arboviral infections due to the emergence of new variants and the development of antiviral resistance. During the replication inside the host cell through protein-protein interactions (PPIs), these viruses interact with several host factors and utilize the host cellular machinery for their benefit. Besides this, viruses employ several transmission strategies to combat host innate and adaptive immune responses by manipulating the signaling and metabolic pathways of the hosts. Hence, antiviral therapies targeting host-virus PPIs can provide an alternative broad-spectrum strategy against RNA viruses. The approach of targeting virus-specific proteins for developing antivirals is expected to solve the problem of antiviral drug resistance and combat emerging new variants of these viruses. This review focuses on host-virus PPIs of arboviral infections that directly affect the host immune signaling and metabolic pathways. Better understanding of these mechanisms will develop new therapeutic tools to treat viral infections.

Variable Susceptibility to Gallium Compounds of Major Cystic Fibrosis Pathogens.

The decreasing efficacy of existing antibiotics against pulmonary pathogens that affect cystic fibrosis (CF) patients calls for the development of novel antimicrobials. Iron uptake and metabolism are vital processes for bacteria, hence potential therapeutic targets. Gallium [Ga(III)] is a ferric iron-mimetic that inhibits bacterial growth by disrupting iron uptake and metabolism. In this work we evaluate the efficacy of three Ga(III) compounds, namely, Ga(NO3)3, (GaN), Ga(III)-maltolate (GaM), and Ga(III)-protoporphyrin IX (GaPPIX), against a collection of CF pathogens using both reference media and media mimicking biological fluids. All CF pathogens, except Streptococcus pneumoniae, were susceptible to at least one Ga(III) compound. Notably, Mycobacterium abscessus and Stenotrophomonas maltophilia were susceptible to all Ga(III) compounds. Achromobacter xylosoxidans, Burkholderia cepacia complex, and Pseudomonas aeruginosa were more susceptible to GaN and GaM, whereas Staphylococcus aureus and Haemophilus influenzae were more sensitive to GaPPIX. The results of this study support the development of Ga(III)-based therapy as a broad-spectrum strategy to treat CF lung infections.

Efficacious antibacterial potency of novel bacteriophages against ESBL-producing Klebsiella pneumoniae isolated from burn wound infections.

Background and Objectives:Prevalence of extended spectrum β-lactamase (ESBL) leads to the development of antibiotic resistance and mortality in burn patients. One of the alternative strategies for controlling ESBL bacterial infections is clinical trials of bacteriophage therapy. The aim of this study was to isolate and characterize specific bacteriophages against ESBL-producing Klebsiella pneumoniae in patients with burn ulcers.Materials and Methods:Clinical samples were isolated from the hospitalized patient in burn medical centers, Iran. Biochemical screenings and 16S rRNA gene sequencing were determined. The phages were isolated from municipal sewerage treatment plants, Isfahan, Iran. TEM and FESEM, adsorption velocity, growth curve, host range, and the viability of the phage particles as well as proteomics and enzyme digestion patterns were examined.Results:The results showed that Klebsiella pneumoniae Iaufa_lad2 (GenBank accession number: MW836954) was confirmed as an ESBL-producing strain using combined disk method. This bacterium showed significant sensitivity to three phages including PɸBw-Kp1, PɸBw-Kp2, and PɸBw-Kp3. Morphological characterization demonstrated that the phage PɸBw-Kp3 to the Siphoviridae family (lambda-like phages) and both phages PɸBw-Kp1 and ɸBw-Kp2 to the Podoviridae family (T1-like phages). The isolated bacteriophages had a large burst size, thermal and pH viability and efficient adsorption rate to the host cells.Conclusion:In present study, the efficacy of bacteriophages against ESBL pathogenic bacterium promises a remarkable achievement for phage therapy. It seems that, these isolated bacteriophages, in the form of phage cocktails, had a strong antibacterial impacts and a broad-spectrum strategy against ESBL-producing Klebsiella pneumoniae isolated from burn ulcers.

Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part II: strategies for therapeutics development

ABSTRACT Introduction: The cellular prion protein (PrPC), some of its derivatives (especially PrP N-terminal N1 peptide and shed PrP), and PrPC-containing exosomes have strong neuroprotective activities, which have been reviewed in the companion article (Part I) and are briefly summarized here. Areas covered: We propose that elevating the extracellular levels of a protective PrP form using gene therapy and other approaches is a very promising novel avenue for prophylactic and therapeutic treatments against prion disease, Alzheimer’s disease, and several other neurodegenerative diseases. We will dissect the pros and cons of various potential PrP-based treatment options and propose a few strategies that are more likely to succeed. The cited references were obtained from extensive PubMed searches of recent literature, including peer-reviewed original articles and review articles. Expert opinion: Concurrent knockdown of celllular PrP expression and elevation of the extracellular levels of a neuroprotective PrP N-terminal peptide via optimized gene therapy vectors is a highly promising broad-spectrum prophylactic and therapeutic strategy against several neurodegenerative diseases, including prion diseases, Alzheimer’s disease and Parkinson’s disease.

Prodrug Nanomedicine Inhibits Chemotherapy-Induced Proliferative Burst by Altering the Deleterious Intercellular Communication.

Chemotherapy is one of the most commonly used clinical antitumor strategies. However, the therapy-induced proliferative burst, which always accompanies drug resistance and metastasis, has become a major obstacle during treatment. Except for some endogenous cellular or genetic mechanisms and some microenvironmental selection pressures, the intercellular connections in the tumor microenvironment (TME) are also thought to be the driving force for the acquired drug resistance and proliferative burst. Even though some pathway inhibitors or cell exempting strategies could be applied to partially avoid these unwanted communications, the complexity of the TME and the limited knowledge about those unknown detrimental connections might greatly compromise the efforts. Therefore, a more broad-spectrum strategy is urgently needed to relieve the drug-induced burst proliferation during various treatments. In this article, based on the possible discrepancies in metabolic activity between cells with different growth rates, several ester-bond-based prodrugs were synthesized. After screening, 7-ethyl-10-hyodroxycamptothecin-based prodrug nanoparticles were found to efficiently overcome the paclitaxel resistance, to selectively act on the malignantly proliferated drug-resistant cells and, furthermore, to greatly diminish the proliferative effect of common cytotoxic agents by blocking the detrimental intercellular connections. With the discriminating ability against malignant proliferating cells, the as-prepared prodrug nanomedicine exhibited significant anticancer efficacy against both drug-sensitive and drug-resistant tumor models, either by itself or by combining with highly potent nonselective chemotherapeutics. This work provides a different perspective and a possible solution for the treatment of therapy-induced burst proliferation.

BIKE regulates dengue virus infection and is a cellular target for broad-spectrum antivirals

Global health is threatened by emerging viruses, many of which lack approved therapies and effective vaccines, including dengue, Ebola, and Venezuelan equine encephalitis. We previously reported that AAK1 and GAK, two of the four members of the understudied Numb-associated kinases (NAK) family, control intracellular trafficking of RNA viruses. Nevertheless, the role of BIKE and STK16 in viral infection remained unknown. Here, we reveal a requirement for BIKE, but not STK-16, in dengue virus (DENV) infection. BIKE mediates both early (postinternalization) and late (assembly/egress) stages in the DENV life cycle, and this effect is mediated in part by phosphorylation of a threonine 156 (T156) residue in the μ subunit of the adaptor protein (AP) 2 complex. Pharmacological compounds with potent anti-BIKE activity, including the investigational anticancer drug 5Z-7-oxozeaenol and more selective inhibitors, suppress DENV infection both in vitro and ex vivo. BIKE overexpression reverses the antiviral activity, validating that the mechanism of antiviral action is, at least in part, mediated by BIKE. Lastly, 5Z-7-oxozeaenol exhibits antiviral activity against viruses from three unrelated RNA viral families with a high genetic barrier to resistance. These findings reveal regulation of poorly understood stages of the DENV life cycle via BIKE signaling and establish a proof-of-principle that pharmacological inhibition of BIKE can be potentially used as a broad-spectrum strategy against acute emerging viral infections.

Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor.

The recent outbreak of COVID-19 caused by SARS-CoV-2 brought a great global public health and economic concern. SARS-CoV-2 is an enveloped RNA virus, from the genus Betacoronavirus. Although few molecules have been tested and shown some efficacy against SARS-CoV-2 in humans but a safe and cost-effective attachment inhibitors are still required for the treatment of COVID-19. Natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Therefore, this study was planned to screen natural products from Ayurveda that have the potential to modulate host immune system as well as block the virus entry in host cells by interfering its interaction with cellular receptor and may be used to develop an effective and broad-spectrum strategy for the management of COVID-19 as well as other coronavirus infections in coming future. To decipher the antiviral activity of the selected natural products, molecular docking was performed. Further, the drug-likeness, pharmacokinetics and toxicity parameters of the selected natural products were determined. Docking results suggest that curcumin and nimbin exhibits highest interaction with spike glycoprotein (MolDock score − 141.36 and − 148.621 kcal/mole) and ACE2 receptor (MolDock score − 142.647 and − 140.108 kcal/mole) as compared with other selected natural products/drugs and controls. Also, the pharmacokinetics data illustrated that all selected natural products have better pharmacological properties (low molecular weight; no violation of Lipinski rule of five, good absorption profiles, oral bioavailability, good blood–brain barrier penetration, and low toxicity risk). Our study exhibited that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine, and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting viral attachment to the host cells. However, few other natural products like resveratrol, quercetin, luteolin, naringenin, zingiberene, and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may be used for ACE2-mediated attachment inhibition of SARS-CoV-2.

From normal to competo-allosteric regulation: insights into the binding pattern dynamics of DSPI protein of Pseudomonas aeruginosa

DSPI, a putative enoyl-coenzyme A (CoA) hydratase/isomerase, is anticipated to be involved in the synthesis of cis-2-decenoic acid (CDA), a quorum sensing (QS) signal molecule present in the superbug Pseudomonas aeruginosa. The current study not only adapts a broad-spectrum strategy for the lucid design of small molecule modulators but also provides novel allosteric inhibitors for DSPI, to investigate its function and potential as a therapeutic target. Docking analysis revealed that the compound 10252273, bound to the specific allosteric site, interacted with Glu118, unique amino acid residue of the active binding pocket, hence indicates the presence of a competitive allosteric site. The current study thus identifies and characterizes inhibitors by targeting the normal binding site and also reports the presence of the competo-allosteric site in the same binding tunnel as the normal site. Molecular docking studies proposed two chemical compounds that share a benzamide-benzimidazole (BB) backbone as potent inhibitors that can obstruct the mechanism of DSPI by targeting both the normal and proposed allosteric binding sites. MD simulations further revealed the disruption of the normal binding site due to the displacement of critical residues Cys146 and Glu118. The rearrangement of H-bond pattern, pi-pi interactions, and strong hydrophobic interactions were observed at both the binding sites. The allosteric pocket inhibitor exhibited improved binding energy than the normal site inhibitor based on MMGBSA and MMPBSA analysis. With subsequent characterization, the current study reveals the allosteric binding site and provides insights into the drug binding mechanism of DSPI.Communicated by Ramaswamy H. Sarma

Self-Interactions of a Virus Glycan Shield

Viruses are able to infect cells because they possess a cell-surface component which enables them to bind on host cells, escape the surveillance of the immune system, and survive harsh environments. These physical properties on virus surface come from a coat or shield of carbohydrates present on it. These carbohydrates are attached to proteins embedded within the virus envelope or membrane. Current research in this field focuses on the chemical recognition of the sugars or proteins on the virus coat by receptors on host cells. Our goal is to interrogate the physical interactions of the virus coat in order to research broad-spectrum strategies that will disrupt the protection afforded by carbohydrate shield. The specific aim of the presented research is to test the propensity of sugar residues constituting the virus glycan shield to self-interact. The pseudovirus HIV pol- env- / VSV-G has a glycan shield that composed of mannose, galactose, sialic acid, and glucosamine. We synthesized gold nanoparticles coated with these sugars and tested the interaction with the pseudovirus. UV-VIS spectrophotometer results show that the plasmon resonance peak of the sugar-coated nanoparticles shifted in the presence of several of these sugars, but not in the presence of the control citrate-coated nanoparticles. The shift in colors is consistent with the coating on the nanoparticles being modified, possibly by binding to viruses. The UV studies were complemented by Dynamic Light Scattering studies which show a larger aggregate virus+nanoparticle species developing when there is a plasmon shift. AFM imaging was performed to deconstruct the structure of the aggregates. Preliminary results indicate that the sialic acid and mannobiose residues on the surface of a virus have a greater propensity for self-interactions, and may play a role in host-virus interaction since host cells are also abundant in these residues.

Viral Manipulation of the Host Metabolic Network.

Viruses are intracellular parasites that rely on host machinery to replicate and achieve a successful infection. Viruses have evolved to retain a broad range of strategies to manipulate host cell metabolism and metabolic resources, channeling them toward the production of virion components leading to viral production. Although several viruses share similar strategies for manipulating host cell metabolism, these processes depend on several factors, namely, the viral life cycle and the metabolic and energetic status of the infected cell. Based on this knowledge, the development of new therapeutic approaches that circumvent viral spread through the target of altered metabolic pathways is an opportunity to tackle the infection. However, finding effective broad-spectrum strategies that aim at restoring to homeostasis the metabolic alterations induced upon virus infection is still a Holy Grail quest for antiviral therapies. Here, we review the strategies by which viruses manipulate host metabolism for their own benefit, with a particular emphasis on carbohydrate, glutamine, and lipid metabolism.

Micro-remains, ENSO, and environmental reconstruction of El Paraíso, Peru, a late preceramic site

The transition from the Middle Preceramic (8000–4500calBP) to the Late Preceramic Period (4450–3800calBP) in coastal Perú witnessed a dramatic change in both resource management and subsistence practices: lomas environments were abandoned in favor of riparian and littoral ecozones, while hunting and gathering was increasingly replaced by agriculture. The reason behind this transition remains a subject of debate; it has been attributed to population pressure, the development of domesticates, especially maize, environmental degradation or climate change. A recent regional study (Beresford-Jones et al., 2015) supports the 1960s Edward Lanning hypothesis that a combination of environmental and climate change forced Middle Preceramic occupants to move toward the river estuaries on the South Coast. Here, microbotanical data from the Late Preceramic site of El Paraíso on the Central Coast of Peru tests the Lanning hypothesis at the site-scale. The data demonstrate that inhabitants practiced a seasonal, Broad-Spectrum strategy by taking advantage of an ENSO-related florescence. Meanwhile, a trend toward increased salinity of nearby marshlands impacted the continued occupation of the site.

Diet reconstructed from an analysis of plant microfossils in human dental calculus from the Bronze Age site of Shilinggang, southwestern China

The extracted microfossils from the dental calculus of ancient teeth are a new form of archaeological evidence which can provide direct information on the plant diet of a population. Here, we present the results of analyses of starch grains and phytoliths trapped in the dental calculus of humans who occupied the Bronze Age site of Shilinggang (∼2500 cal yr BP) in Yunnan Province, southwestern China. The results demonstrate that the inhabitants consumed a wide range of plants, including rice, millet, and palms, together with other food plants which have not previously been detected in Yunnan. The discovery of various underground storage organs (USOs; tubers, roots, bulbs, and rhizomes) and acorns complements the application of conventional macrofossil and isotope studies to understand the diet of the Bronze Age human population of Yunnan. The wide variety of plant foods consumed suggests that the inhabitants adopted a broad-spectrum strategy of gathering food and cultivating crops in northwest Yunnan Province in the late Bronze Age at a time when agricultural societies were developed in the central plains of China.