The cao vit gibbon (Nomascus nasutus) is one of the rarest primates on Earth and now only survives in a single forest patch of less than 5000 ha on the Vietnam-China border. Accurate monitoring of ...the last remaining population is critical to inform ongoing conservation interventions and track conservation success over time. However, traditional methods for monitoring gibbons, involving triangulation of groups from their songs, are inherently subjective and likely subject to considerable measurement errors. To overcome this, we aimed to use 'vocal fingerprinting' to distinguish the different singing males in the population. During the 2021 population survey, we complemented the traditional observations made by survey teams with a concurrent passive acoustic monitoring array. Counts of gibbon group sizes were also assisted with a UAV-mounted thermal camera. After identifying eight family groups in the acoustic data and incorporating long-term data, we estimate that the population was comprised of 74 individuals in 11 family groups, which is 38% smaller than previously thought. We have no evidence that the population has declined-indeed it appears to be growing, with new groups having formed in recent years-and the difference is instead due to double-counting of groups in previous surveys employing the triangulation method. Indeed, using spatially explicit capture-recapture modelling, we uncovered substantial measurement error in the bearings and distances from field teams. We also applied semi- and fully-automatic approaches to clustering the male calls into groups, finding no evidence that we had missed any males with the manual approach. Given the very small size of the population, conservation actions are now even more urgent, in particular habitat restoration to allow the population to expand. Our new population estimate now serves as a more robust basis for informing management actions and tracking conservation success over time.
Abstract
Bioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery and design of bioactive peptides. Yet, suitable experimental approaches are ...required to validate candidates in high throughput and at low cost. Here, we established a cell-free protein synthesis (CFPS) pipeline for the rapid and inexpensive production of antimicrobial peptides (AMPs) directly from DNA templates. To validate our platform, we used deep learning to design thousands of AMPs de novo. Using computational methods, we prioritized 500 candidates that we produced and screened with our CFPS pipeline. We identified 30 functional AMPs, which we characterized further through molecular dynamics simulations, antimicrobial activity and toxicity. Notably, six de novo-AMPs feature broad-spectrum activity against multidrug-resistant pathogens and do not develop bacterial resistance. Our work demonstrates the potential of CFPS for high throughput and low-cost production and testing of bioactive peptides within less than 24 h.
The level of fetal hemoglobin (HbF) is an important disease modifier for β‐thalassemia and sickle cell disease patients. Indeed, genetic tinkering with the HbF repression machinery has demonstrated ...great potential for disease mitigation. Such genetic treatments are costly and the high incidence of β‐hemoglobinopathies in low‐income countries, therefore, calls for the development of affordable, off‐the‐shelf, oral treatments. The use of PROTAC (PRoteolysis TArgeting Chimeras) technology to influence the epigenetic mechanisms involved in HbF suppression may provide a solution. In this minireview, we briefly explain the HbF repression network highlighting the epigenetic factors that could be targeted for degradation by PROTACs. We hope that this review will inspire clinicians, molecular and chemical biologists to collaborate and contribute to this fascinating field, which should ultimately deliver drugs that reactivate HbF expression with high specificity and low toxicity.
Closing the gap! The level of fetal hemoglobin (HbF) is an important disease modifier for β‐thalassemia and sickle cell disease patients. Indeed, genetic tinkering with the HbF repression machinery has demonstrated great potential for disease mitigation. This minireview provides an overview of the epigenetic crosstalk involved in fetal HbF repression, discussing the possibility of using targeted protein degradation for β‐hemoglobinopathy treatments.
Virtual combinatorial libraries are prevalent in drug discovery due to improvements in the prediction of synthetic reactions that can be performed. This has gone hand in hand with the development of ...virtual screening capabilities to effectively screen the large chemical spaces spanned by exhaustive enumeration of reaction products. In this study, we generated a small‐molecule dipeptide mimic library to target proteins binding small peptides. The library was created based on the general idea of peptide synthesis, that is, amino acid mimics were reacted in silico to form the dipeptide mimics, yielding 2,036,819 unique compounds. After docking calculations, two compounds from the library were synthesized and tested against WD repeat‐containing protein 5 (WDR5) and histamine receptors H1–H4 to evaluate whether these molecules are viable in assays. The compounds showed the highest potency at the histamine H3 receptor, with Ki values in the two‐digit micromolar range.
A library of small molecules was created to mimic the action of dipeptides. This was done by performing in silico reactions of amino acid mimics (building blocks) with known robust reactions. The library was validated by synthesizing two compounds and testing them in vitro against different proteins.
Objectives
This work aimed to construct a versatile, effective, and food-grade
Agrobacterium tumefaciens
-mediated transformation (ATMT) system for recombinant expression in the filamentous fungus
...Penicillium rubens
(also known as
Pencillium chrysogenum
).
Results
In this study, the wild-type
P. chrysogenum
VTCC 31172 strain was re-classified as
P. rubens
by a multilocus sequencing analysis. Further, the
pyrG
gene required for uridine/uracil biosynthesis was successfully deleted in the VTCC 31172 strain by homologous recombination to generate a stable uridine/uracil auxotrophic mutant (Δ
pyrG
). The growth of the
P. rubens
Δ
pyrG
strain could be restored by uridine/uracil supplementation, and a new ATMT system based on the uridine/uracil auxotrophic mechanism was established for this strain. The optimal ATMT efficiency could reach 1750 transformants for 10
6
spores (equivalent to 0.18%). In addition, supplementation of uridine/uracil at the concentrations of 0.005–0.02% during the co-cultivation process significantly promoted transformation efficiency. Especially, we demonstrated that the
pyrG
marker and the
amyB
promoter from the
koji
mold
Aspergillus oryzae
were fully functional in
P. rubens
Δ
pyrG
. Expression of the
DsRed
reporter gene under the regulation of the
A. oryzae amyB
promoter lighted up the mycelium of
P. rubens
with a robust red signal under fluorescence microscopy. Furthermore, genomic integration of multiple copies of the
Aspergillus fumigatus phyA
gene under the control of the
amyB
promoter significantly enhanced phytase activity in
P. rubens
.
Conclusions
The ATMT system developed in our work provides a safe genetic platform for producing recombinant products in
P. rubens
without using drug resistance markers.
Epidermolysis bullosa (EB) is a disorder characterized by the appearance of blisters, erosions and wounds in response to minimal trauma. The disease manifests with noticeable symptoms ranging from ...mild to severe, classified into four major types: epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), dystrophic epidermolysis bullosa (DEB) and Kindler syndrome. Preimplantation genetic diagnosis for the disease remains the only available option for families at risk for the recurrence of the disorder without having to terminate an ongoing pregnancy.
A novel
mutation was used to design primers for the polymerase chain reaction (PCR) to amplify the segment spanning the mutation in the family and their in-vitro fertilization (IVF) embryos. Then, the PCR products were sequenced with Sanger sequencing to detect the alteration in the allele, and some embryos would go through NGS-based preimplantation screening for chromosomal abnormalities.
The established protocol for EB detected mutant allele in 6/9 embryos (66.6%), while the remaining 3 embryos (33.4%) appeared to not carry any mutation. Only one among 3 embryos was recommended to be transferred into the mother's uterus.
The established preimplantation genetic diagnosis procedure is helpful to families affected by epidermolysis bullosa caused by
mutations but wish to have healthy children.
Industrial wastewater often consists of toxic chemicals and pollutants, which are extremely harmful to the environment. Heavy metals are toxic chemicals and considered one of the major hazards to the ...aquatic ecosystem. Analytical techniques, such as potentiometric methods, are some of the methods to detect heavy metals in wastewaters. In this work, the quantitative structure-property relationship (QSPR) was applied using a range of machine learning techniques to predict the stability constant (logβ
) and potentiometric sensitivity (PS
) of 200 ligands in complexes with the heavy metal ions Cu
, Cd
, and Pb
. In result, the logβML models developed for four ions showed good performance with square correlation coefficients (R
) ranging from 0.80 to 1.00 for the training and 0.72 to 0.85 for the test sets. Likewise, the PSML displayed acceptable performance with an R
of 0.87 to 1.00 for the training and 0.73 to 0.95 for the test sets. By screening a virtual database of coumarin-like structures, several new ligands bearing the coumarin moiety were identified. Three of them, namely NEW02, NEW03, and NEW07, showed very good sensitivity and stability in the metal complexes. Subsequent quantum-chemical calculations, as well as physicochemical/toxicological profiling were performed to investigate their metal-binding ability and developability of the designed sensors. Finally, synthesis schemes are proposed to obtain these three ligands with major efficiency from simple resources. The three coumarins designed clearly demonstrated capability to be suitable as good florescent chemosensors towards heavy metals. Overall, the computational methods applied in this study showed a very good performance as useful tools for designing novel fluorescent probes and assessing their sensing abilities.
In this study, Cr
3
C
2
-25NiCr cermet coatings were fabricated by atmospheric plasma spraying on 304 stainless steel substrate. Then, the coatings were sealed with a Polytetrafluoroethylene (PTFE) ...emulsion by using two methods: conventional impregnation and ultrasonic vibration. The phase composition, surface morphology, porosity, permeability of PTFE emulsion into the coating, wear and corrosion resistance of the coatings were investigated. The results showed that in the PTFE sealed coatings, besides carbide phases, a PTFE phase with an hexagonal crystal structure was formed. The PTFE covered the surface of the coating. The ultrasonic vibration method increased the permeability of the PTFE emulsion into the coating by more than 2 times that of the conventional impregnation method. The PTFE sealed coating by ultrasonic vibration method had a lower porosity, higher wear and corrosion resistances in 3.5 wt.% NaCl solution than the PTFE coating sealed by conventional impregnation method and PTFE unsealed coating.
Background
Reports of pregnant women infected with avian influenza are rare. Studies showed that A/H5N1 virus can penetrate the placental barrier and infect the fetus. Of six documented cases, four ...died and two survivors had a spontaneous abortion.
Objectives
We report a clinical, outcome and epidemiological characteristics of a 36‐week pregnant woman infected with A/H5N1 and her newborn in Soc Trang province of Vietnam in 2012.
Methods
Epidemiological and laboratory investigations were conducted. Clinical manifestations, progress, treatment and outcome of the case‐patient and her newborn were collected. Human tracheal aspirate, throat swab and serum specimens were tested for influenza A/H5N1, A/H3N1, A/H1N1pdm09 and B by real‐time RT‐PCR and genome sequencing. Poultry throat and rectal swabs were tested by PCR and virus isolation.
Results
Case‐patient hospitalized with high fever and cough, and died after onset 6 days. She continuously slaughtered sick poultry 5 days before illness onset. Clinical manifestation showed rapid progressive severe pneumonia. Her tracheal aspirate sample was positive influenza A/H5N1 virus. Her new‐born was delivered by caesarean section with low birth weight and early onset pneumonia, however fully recovered after 16 days treatment. Neonate's throat swabs and paired serum samples tested negative for influenza A/H5N1. Clade 1.1 A/H5N1 virus was detected in poultry samples, was same clade and highly homogenous with the virus was detected in the mother.
Conclusions
This was the first documented a live birth from a pregnant woman infected with influenza A/H5N1 virus. Intensive studies are needed to better understand mother‐to‐child transmission of influenza A/H5N1 virus.
Ninh Thuan and Binh Thuan are two provinces in South Central Vietnam with two very unique phenomena: (1) Having a uniquely hot and dry climate in the context that Vietnam’s general climate is ...tropical and humid and (2) The red sand plateau has spectacular scenery and a huge volume that is superior to other coastal sand dunes of Vietnam. Quaternary geologists and hydrogeologists have studied many coastal areas of Ninh Thuan—Binh Thuan since 1975, but have not yet been able to answer four very basic questions: (1) arid climate and very poor groundwater storage capacity are related to the very thin Quaternary sediments and uplifting Tertiary geological structure? (2) Where does quartz sand come from with such a huge, magnificent and beautiful red color? (3) When was the sand dune formed and what is the mechanism of formation? (4) Do the sand dunes are a good aquifer? To answer the above questions, the authors have studied sequence stratigraphy on both objects: (1) inner low plains and (2) coastal sand dunes. According to that approach, the sand dunes are divided into 5 sequences as follows: (1) sequence 1 (Sq
1
-
) has an early Pleistocene age (1600–700 ka BP); (2) Sequence 2 (Sq
2
-
) has an early-middle Pleistocene age (700–150 ka BP); (3) Sequence 3 (Sq
3
-
) has late middle Pleistocene age (150–70 ka BP); (4) Sequence 4 (Sq
4
-
) has an early-late Pleistocene age (70–30 ka BP); and (5) Sequence 5 (Sq
5
-
-Q
2
) has from late late Pleistocene to Holocene. These 5 sequences constitute an aquifer of good quality with undivided Quaternary stratigraphy. In the alluvial-lagoon plains, the sequence stratigraphical column has only 4 sequences: (1) Sq
2
:
; (2) Sq
3
:
; (3) Sq
4
:
; and (4) Sq
5
:
-Q
2
. These sequences constitute two aquifers of poor quality: (1) aquifer qp
1
correspond to lowstand alluvial gravelly sand facies complexes of from early middle to early late Pleistocene (S
g
(
-
) LST); and (2) aquifer qp
2
correspond to lowstand late late Pleistocene gravelly sand facies complex (S
g
LST).
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