Backbone resonance assignments for the SET domain of the human methyltransferase NSD2

Aberrant NSD2 methyltransferase activity is implicated as the oncogenic driver in multiple myeloma, suggesting opportunities for novel therapeutic intervention. The methyltransferase activity of NSD2 resides in its catalytic SET domain, which is conserved among most lysine methyltransferases. Here we report the backbone \(\hbox {H}^{\mathrm{N}}\), N, C\(^{\prime }\), \(\hbox {C}^\alpha\) and side-chain \(\hbox {C}^\beta\) assignments of a 25 kDa NSD2 SET domain construct, spanning residues 991–1203. A chemical shift analysis of C\(^{\prime }\), \(\hbox {C}^\alpha\) and \(\hbox {C}^\beta\) resonances predicts a secondary structural pattern that is in agreement with homology models.     

Cellular mechanosensitivity to substrate stiffness decreases with increasing dissimilarity to cell stiffness

Computational modelling has received increasing attention to investigate multi-scale coupled problems in micro-heterogeneous biological structures such as cells. In the current study, we investigated for a single cell the effects of (1) different cell-substrate attachment (2) and different substrate modulus \(\textit{E}_\mathrm{s}\) on intracellular deformations. A fibroblast was geometrically reconstructed from confocal micrographs. Finite element models of the cell on a planar substrate were developed. Intracellular deformations due to substrate stretch of \(\lambda =1.1\), were assessed for: (1) cell-substrate attachment implemented as full basal contact (FC) and 124 focal adhesions (FA), respectively, and \(\textit{E}_\mathrm{s}\,=\,\)140 KPa and (2) \(\textit{E}_\mathrm{s}\,=\,10\), 140, 1000, and 10,000 KPa, respectively, and FA attachment. The largest strains in cytosol, nucleus and cell membrane were higher for FC (1.35\(\text {e}^{-2}\), 0.235\(\text {e}^{-2}\) and 0.6\(\text {e}^{-2}\)) than for FA attachment (0.0952\(\text {e}^{-2}\), 0.0472\(\text {e}^{-2}\) and 0.05\(\text {e}^{-2}\)). For increasing \(\textit{E}_\mathrm{s}\), the largest maximum principal strain was 4.4\(\text {e}^{-4}\), 5\(\text {e}^{-4}\), 5.3\(\text {e}^{-4}\) and 5.3\(\text {e}^{-4}\) in the membrane, 9.5\(\text {e}^{-4}\), 1.1\(\text {e}^{-4}\), 1.2\(\text {e}^{-3}\) and 1.2\(\text {e}^{-3}\) in the cytosol, and 4.5\(\text {e}^{-4}\), 5.3\(\text {e}^{-4}\), 5.7\(\text {e}^{-4}\) and 5.7\(\text {e}^{-4}\) in the nucleus. The results show (1) the importance of representing FA in cell models and (2) higher cellular mechanical sensitivity for substrate stiffness changes in the range of cell stiffness. The latter indicates that matching substrate stiffness to cell stiffness, and moderate variation of the former is very effective for controlled variation of cell deformation. The developed methodology is useful for parametric studies on cellular mechanics to obtain quantitative data of subcellular strains and stresses that cannot easily be measured experimentally.     

Plausibility and parameter sensitivity of micro-finite element-based joint load prediction at the proximal femur

A micro-finite element-based method to estimate the bone loading history based on bone architecture was recently presented in the literature. However, a thorough investigation of the parameter sensitivity and plausibility of this method to predict joint loads is still missing. The goals of this study were (1) to analyse the parameter sensitivity of the joint load predictions at one proximal femur and (2) to assess the plausibility of the results by comparing load predictions of ten proximal femora to in vivo hip joint forces measured with instrumented prostheses (available from www.orthoload.com). Joint loads were predicted by optimally scaling the magnitude of four unit loads (inclined \(-20^{\circ }\) to \(100^{\circ }\) with respect to the vertical axis) applied to micro-finite element models created from high-resolution computed tomography scans (\(30.3~\upmu \)m voxel size). Parameter sensitivity analysis was performed by varying a total of nine parameters and showed that predictions of the peak load directions (range 10\(^{\circ }\)–\(30^{\circ }\)) are more robust than the predicted peak load magnitudes (range 2344.8–4689.5 N). Comparing the results of all ten femora with the in vivo loading data of ten subjects showed that peak loads are plausible both in terms of the load direction (in vivo: \(18.2\pm 2.0^{\circ }\), predicted: \(20.0^{\circ }\)) and magnitude (in vivo: \(2707.6\pm 443.3~\hbox {N}\), predicted: \(3372.2\pm 597.9~\hbox {N}\)). Overall, this study suggests that micro-finite element-based joint load predictions are both plausible and robust in terms of the predicted peak load direction, but predicted load magnitudes should be interpreted with caution.     

Simulated bone remodeling around tilted dental implants in the anterior maxilla

Dental implants have to be placed with the long axis in different angulations due to the change in bone morphology. The objective of this study was to investigate the different bone remodeling response induced by the tilted dental implants and to assess whether it could lead to bone loss and implant failure. In this study, bone remodeling due to palato-labially inclined dental implants placed in the anterior maxillary incisor region was simulated. CT-based finite element models of a maxillary bone with dental implants were created herein. Five dental implants were placed at \(+10^{\circ }\), \(+5^{\circ }\), \(0^{\circ }\), \(-5^{\circ }\) and \(-10^{\circ }\), respectively. The remodeling progression was recorded and compared. Model \(-10^{\circ }\) (palatal side) shows the highest bone density values, but the inclined implant at \(+10^{\circ }\) (labial side) leads to significant bone loss. From a biomechanical perspective, it is speculated that a palatally inclined implant is more likely to enhance the bone density in the maxillary anterior region, but labial inclination of implant could jeopardize its stability.     

Cell Volume Regulation in the Proximal Tubule of Rat Kidney

We developed a dynamic model of a rat proximal convoluted tubule cell in order to investigate cell volume regulation mechanisms in this nephron segment. We examined whether regulatory volume decrease (RVD), which follows exposure to a hyposmotic peritubular solution, can be achieved solely via stimulation of basolateral K\(^+\) and \(\hbox {Cl}^-\) channels and \(\hbox {Na}^+\)–\(\hbox {HCO}_3^-\) cotransporters. We also determined whether regulatory volume increase (RVI), which follows exposure to a hyperosmotic peritubular solution under certain conditions, may be accomplished by activating basolateral \(\hbox {Na}^+\)/H\(^+\) exchangers. Model predictions were in good agreement with experimental observations in mouse proximal tubule cells assuming that a 10% increase in cell volume induces a fourfold increase in the expression of basolateral K\(^+\) and \(\hbox {Cl}^-\) channels and \(\hbox {Na}^+\)–\(\hbox {HCO}_3^-\) cotransporters. Our results also suggest that in response to a hyposmotic challenge and subsequent cell swelling, \(\hbox {Na}^+\)–\(\hbox {HCO}^-_3\) cotransporters are more efficient than basolateral K\(^+\) and \(\hbox {Cl}^-\) channels at lowering intracellular osmolality and reducing cell volume. Moreover, both RVD and RVI are predicted to stabilize net transcellular \(\hbox {Na}^+\) reabsorption, that is, to limit the net \(\hbox {Na}^+\) flux decrease during a hyposmotic challenge or the net \(\hbox {Na}^+\) flux increase during a hyperosmotic challenge.     

Trend analysis of variations in carbon stock using stock big data

Changes in land use affect the terrestrial carbon stock through changes in the land cover. Research on land use and analysis of variations in carbon stock have practical applications in the optimization of land use and the mitigation of climate change effects. This study was conducted in Baixiang and Julu counties in the Taihang Piedmont by employing the trend analysis method to characterize the variation in county land use and carbon stock. The findings show that in both counties, agricultural and unused land areas decreased while built-up land area increased, and the reduction in cropland was the main reason behind the agricultural land reduction. An inflection point appeared on the cropland curves of Julu, because the cropland area decreased by 1576.97 hm\(^{2}\) from 2004 to 2006. Cropland area in Baixiang decreased from 1996 to 1998 by a total of 129.89 hm\(^{2}\) and then remained relatively stable after 1998. The total carbon storage and variation in land use in the two counties displayed similar trends. Total carbon reserves in Julu increased by 2.76 \(\times \) 10\(^{4}\) tC (carbon equivalent), while those in Baixiang decreased by 0.63 \(\times \) 10\(^{4}\) tC. Carbon stock of built-up land in Julu and Baixiang increased by 2.44 \(\times \) 10\(^{4}\) and 1.22 \(\times \) 10\(^{4}\) tC, respectively.     

Failure properties of vena cava tissue due to deep penetration during filter insertion

In this work, we use an in-vitro mechanical test to explore the resistance of biaxially stretched vena cava tissue against deep perforation and a methodology which integrates experimental and numerical modeling to identify constitutive fracture properties of the vena cava. Six sheep vena cava were harvested just after killing, and cyclic uniaxial tension tests in longitudinal and circumferential directions and biaxial deep penetration tests were performed. After that, we use a nonlinear finite element model to simulate in vitro penetration of the cava tissue in order to fit the fracture properties under penetration of the vena cava by defining a cohesive fracture zone. An iterative process was developed in order to fit the fracture properties of the vena cava using the previously obtained experimental results. The proposed solutions were obtained with fracture energy of 0.22 or 0.33 N/mm. In comparison with the experimental data, the simulation using \(\delta _{0}=0.01\,\hbox {mm}\), \(\delta _{r}=0.35\,\hbox {mm}\), and \(K=220\, \hbox {N}/\hbox {mm}^{3}\) parameters (\(F_{\hbox {max}}=0.92\)) is in good agreement with results from penetration experiments of cava tissue. It is noticeable that the parameter estimation process of the fracture behavior is more accurate than the estimation process of the elastic behavior for the toe region of the curve.     

Performance and kinetics of ANAMMOX granular sludge with pH shock in a sequencing batch reactor

As an efficient and cost-effective nitrogen removal process, anaerobic ammonium oxidation (ANAMMOX) could be well operated at suitable pH condition. However, pH shock occurred in different kinds of wastewater and affected ANANNOX process greatly. The present research aimed at studying the performance and kinetics of ANAMMOX granular sludge with pH shock. When influent pH was below 7.5, effluent \({\text{NH}}_{4}^{ + }\)–N and \({\text{NO}}_{2}^{ - }\)–N increased with decreasing pH. At Ph 6.0, effluent \({\text{NO}}_{2}^{ - }\)–N approached 100 mg/L, and the ratios of \(\Delta {\text{NO}}_{2}^{ - } - {\text{N}}:\Delta {\text{NH}}_{4}^{ + } - {\text{N and }}\Delta {\text{NO}}_{3}^{ - } - {\text{N}}:\Delta {\text{NH}}_{4}^{ + } - {\text{N}}\) approached 2.2 and 1.3, respectively. Both greatly deviated from theoretical values. When influent pH was above 7.5, effluent \({\text{NH}}_{4}^{ + }\)–N and \({\text{NO}}_{2}^{ - }\)–N increased with increasing pH. At pH 9.0, ammonium removal rate (ARR) and nitrite removal rate (NRR) decreased to 0.011 ± 0.004 and 0.035 ± 0.004 kg/(m³·d), respectively. Besides, \(\Delta {\text{NO}}_{2}^{ - }\)–N:\(\Delta {\text{NH}}_{4}^{ + }\)–N deviated from theoretical value. Longer recovery time from pH 9.0 than from pH 6.0 indicated that alkaline surroundings inhibited anaerobic ammonium oxidizing bacteria (AAOB) greater. The sludge settling velocity was 2.15 cm/s at pH 7.5. However, it decreased to 2.02 cm/s when pH was 9.0. Acidic pH had little effect on sludge size, but disintegration of ANAMMOX granule was achieved with pH of 9.0. The Bell-shaped (A) model and the Ratkowsky model were more applicable to simulate the effect resulting from pH shock on ANAMMOX activity (R² > 0.95), and both could describe ANAMMOX activity well with pH shock. They indicated that q_max was 0.37 kg \(\Delta {\text{NH}}_{4}^{ + }\)–N/(kgMLSS·d) at the optimum pH value (7.47) in present study. The minimum pH during which ANAMMOX occurred was 5.68 while the maximum pH for ANAMMOX reaction was 9.26. Based on nitrogen removal performance with different pH, strongly acidic (pH ≤ 6.5) or alkaline (pH ≥ 8.5) inhibited ANAMMOX process. Besides, ANAMMOX appeared to be more susceptible to alkaline wastewater. Compared to extremely acidic condition (low pH), extremely alkaline condition (high pH) affected ANAMMOX granules much more.     

Comparison of the Functional Activities of Xanthine Oxidases Isolated from Microorganisms and from Cow’s Milk

The characteristics of the formation of the superoxide radical anion (\(\rm{O}_2^{\bullet-}\)) and hydrogen peroxide by xanthine oxidases isolated from microorganisms and from cow’s milk were investigated. The increase in pH led to an increase in the rate of xanthine oxidation with oxygen by both xanthine oxidases. The functioning of xanthine oxidase from milk along with the two-electron reduction of O₂ to H₂O₂ carries through the one-electron reduction of O₂ to \(\rm{O}_2^{\bullet-}\), and the rate and the fraction of generation of \(\rm{O}_2^{\bullet-}\) increased with increasing pH. Under operation of the microbial xanthine oxidase, the \(\rm{O}_2^{\bullet-}\) radical was not detected in the medium. The results suggest a difference in the operation of active centers of enzyme from different sources.     

<Superscript>1</Superscript>H, <Superscript>13</Superscript>C, <Superscript>15</Superscript>N resonance assignments of the extracellular loop 1 domain (ECL1) of <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis> D39 FtsX,an essential cell division protein

FtsX is an integral membrane protein from Streptococcus pneumoniae (pneumococcus) that harbors an extracellular loop 1 domain (\({\text{FtsX}}^{\text{ECL1}}_{Spn}\)) that interacts with PcsB, an peptidoglycan hydrolase that is essential for cell growth and division. Here, we report nearly complete backbone and side chain resonance assignments and a secondary structural analysis of \({\text{FtsX}}^{\text{ECL1}}_{Spn}\) (residues 47–168 of FtsX) as first steps toward structure determination of \({\text{FtsX}}^{\text{ECL1}}_{Spn}\).     

A finite-element model of mechanosensation by a Pacinian corpuscle cluster in human skin

The Pacinian corpuscle (PC) is the cutaneous mechanoreceptor responsible for sensation of high-frequency (20–1000 Hz) vibrations. PCs lie deep within the skin, often in multicorpuscle clusters with overlapping receptive fields. We developed a finite-element mechanical model of one or two PCs embedded within human skin, coupled to a multiphysics PC model to simulate action potentials elicited by each PC. A vibration was applied to the skin surface, and the resulting mechanical signal was analyzed using two metrics: the deformation amplitude ratio (\({\rho }_{\mathrm{1S}} \), \({\rho }_{\mathrm{2S}} )\) and the phase shift of the vibration (\({\delta }_{\mathrm{S}1}^{\mathrm{mech}} \), \({\delta }_{\mathrm{S}2}^{\mathrm{mech}} )\) between the stimulus and the PC. Our results showed that the amplitude attenuation and phase shift at a PC increased with distance from the stimulus to the PC. Differences in amplitude (\(\rho _{12} )\) and phase shift (\({\delta }_{12}^{\mathrm{mech}} )\) between the two PCs in simulated clusters directly affected the interspike interval between the action potentials elicited by each PC (\({\delta }_{12}^{\mathrm{spike}} )\). While \({\delta }_{12}^{\mathrm{mech}} \) had a linear relationship with \({\delta }_{12}^{\mathrm{spike}} \), \(\rho _{12} \)’s effect on \({\delta }_{12}^{\mathrm{spike}} \) was greater for lower values of \(\rho _{12} \). In our simulations, the separation between PCs and the distance of each PC from the stimulus location resulted in differences in amplitude and phase shift at each PC that caused \({\delta }_{12}^{\mathrm{spike}} \) to vary with PC location. Our results suggest that PCs within a cluster receive different mechanical stimuli which may enhance source localization of vibrotactile stimuli, drawing parallels to sound localization in binaural hearing.     

Measuring the signs of the methyl <Superscript>1</Superscript>H chemical shift differences between major and ‘invisible’ minor protein conformational states using methyl <Superscript>1</Superscript>H multi-quantum spectroscopy

Carr–Purcell–Meiboom–Gill (CPMG) type relaxation dispersion experiments are now routinely used to characterise protein conformational dynamics that occurs on the μs to millisecond (ms) timescale between a visible major state and ‘invisible’ minor states. The exchange rate(s) (\( k_{{{\text{ex}}}} \)), population(s) of the minor state(s) and the absolute value of the chemical shift difference \(|{\Delta \varpi }|\) (ppm) between different exchanging states can be extracted from the CPMG data. However the sign of \({\Delta \varpi }\) that is required to reconstruct the spectrum of the ‘invisible’ minor state(s) cannot be obtained from CPMG data alone. Building upon the recently developed triple quantum (TQ) methyl \( ^{1} {\text{H}} \) CPMG experiment (Yuwen in Angew Chem 55:11490–11494, 2016) we have developed pulse sequences that use carbon detection to generate and evolve single quantum (SQ), double quantum (DQ) and TQ coherences from methyl protons in the indirect dimension to measure the chemical exchange-induced shifts of the SQ, DQ and TQ coherences from which the sign of \({\Delta \varpi }\) is readily obtained for two state exchange. Further a combined analysis of the CPMG data and the difference in exchange induced shifts between the SQ and DQ resonances and between the SQ and TQ resonances improves the estimates of exchange parameters like the population of the minor state. We demonstrate the use of these experiments on two proteins undergoing exchange: (1) the ~ 18 kDa cavity mutant of T4 Lysozyme (\( k_{{{\text{ex}}}} \sim\,3500{\text{ s}}^{{ - 1}} \)) and (2) the \(\sim\,4.7\) kDa Peripheral Sub-unit Binding Domain (PSBD) from the acetyl transferase of Bacillus stearothermophilus (\(k_{ex} \sim\,13,000\hbox { s}^{-1}\)).     

Analysis of two susceptibility SNPs in HLA region and evidence of interaction between rs6457617 in <Emphasis Type="BoldItalic">HLA-DQB1</Emphasis> and <Emphasis Type="BoldItalic">HLA-DRB1</Emphasis>*04 locus on Tunisian rheumatoid arthritis

Previous genomewide association studies (GWAS) and meta-analyses have enumerated several genes/loci in major histocompatibility complex region, which are consistently associated with rheumatoid arthritis (RA) in different ethnic populations. Given the genetic heterogeneity of the disease, it is necessary to replicate these susceptibility loci in other populations. In this case, we investigate the analysis of two SNPs, rs13192471 and rs6457617, from the human leukocyte antigen (HLA) region with the risk of RA in Tunisian population. These SNPs were previously identified to have a strong RA association signal in several GWAS studies. A case–control sample composed of 142 RA patients and 123 healthy controls was analysed. Genotyping of rs13192471 and rs6457617 was carried out using real-time PCR methods by TaqMan allelic discrimination assay. A trend of significant association was found in rs6457617 TT genotype with susceptibility to RA (\(P = 0.04\), \(p_{c} = 0.08\), \(\hbox {OR} = 1.73\)). Moreover, using multivariable analysis, the combination of rs6457617*TT–HLA-DRB1*\(04^{+}\) increased risk of RA (\(\hbox {OR} = 2.38\)), which suggest a gene–gene interaction event between rs6457617 located within the HLA-DQB1 and HLA-DRB1. Additionally, haplotypic analysis highlighted a significant association of rs6457617*T–HLA-DRB1*\(04^{+}\) haplotype with susceptibility to RA (\(P = 0.018\), \(p_{c} = 0.036\), \(\hbox {OR} = 1.72\)). An evidence of association was shown subsequently in \(\hbox {antiCCP}^{+}\) subgroup with rs6457617 both in T allele and TT genotype (\(P = 0.01\), \(p_{c} = 0.03\), \(\hbox {OR} = 1.66\) and \(P = 0.008\), \(p_{c} = 0.024\), \(\hbox {OR} = 1.28\), respectively). However, no association was shown for rs13192471 polymorphism with susceptibility and severity to RA. This study suggests the involvement of rs6457617 locus as risk variant for susceptibility/severity to RA in Tunisian population. Secondly, it highlights the gene–gene interaction between HLA-DQB1 and HLA-DRB1.     

Towards the prediction of flow-induced shear stress distributions experienced by breast cancer cells in the lymphatics

Tumour metastasis in the lymphatics is a crucial step in the progression of breast cancer. The dynamics by which breast cancer cells (BCCs) travel in the lymphatics remains poorly understood. The goal of this work is to develop a model capable of predicting the shear stresses metastasising BCCs experience using numerical and experimental techniques. This paper models the fluidic transport of large particles (\(\eta =d_{\mathrm{p}}/W=0.1-0.4\) where \(d_{\mathrm{p}}\) is the particle diameter and W is the channel width) subjected to lymphatic flow conditions (\({ Re}=0.04\)), in a \(100\times 100\,\upmu \hbox {m}\) microchannel. The feasibility of using the dynamic fluid body interaction (DFBI) method to predict particle motion was assessed, and particle tracking experiments were performed. The experiments found that particle translational velocity decreased from the undisturbed fluid velocity with increasing particle size (5–14% velocity lag for \(\eta =0.1-0.3\)). DFBI simulations were found to better predict particle behaviour than theoretical predictions; however, mesh restrictions in the near-wall region (\(0.2\,\mathrm{W}>y>0.8\,\mathrm{W}\)) result in computationally expensive models. The simulations were in good agreement with the experiments (\(<12\%\) difference) across the channel (\(0.2\,\mathrm{W}\le y\le 0.8\,\mathrm{W}\)), with differences up to 25% in the near-wall region. Particles experience a range of shear stresses (0.002–0.12 Pa) and spatial shear gradients (\(0.004-0.137\,\hbox {Pa}/\upmu \hbox {m}\)) depending on their size and radial position. The predicted shear gradients are far in excess of values associated with BCC apoptosis (\(0.004-0.023\,\hbox {Pa}/\upmu \hbox {m}\)). Increasing our understanding of the shear stress magnitudes and gradients experienced by BCCs could be leveraged to elucidate whether a particular BCC size or location exists that encourages metastasis within the lymphatics.     

Potential use of sulfite as a supplemental electron donor for wastewater denitrification

Biological denitrification typically requires the addition of a supplemental electron donor, which can add a significant operating expense to wastewater treatment facilities. Most common electron donors are organic, but reduced inorganic sulfur compounds (RISCs), such as sulfide (HS^?) and elemental sulfur (S⁰), may be more cost-effective. S⁰ is an inexpensive and well characterized electron donor, but it provides slow denitrification rates due to its low solubility. A lesser-known RISC is sulfite (\({\text{SO}}_{3}^{2 - }\)), which can be easily produced from S⁰ by a simple combustion process. Unlike S⁰, \({\text{SO}}_{3}^{2 - }\) is highly soluble, and therefore may provide higher denitrification rates. However, very little is known about microbial denitrification with \({\text{SO}}_{3}^{2 - }\). Also, \({\text{SO}}_{3}^{2 - }\) is a strong reductant that reacts abiotically with oxygen and has toxic effects on microorganisms. This paper reviews \({\text{SO}}_{3}^{2 - }\) in the environment, \({\text{SO}}_{3}^{2 - }\) chemistry, microbiology, toxicity, and its potential use for denitrification. Since \({\text{SO}}_{3}^{2 - }\) is an intermediate in the sulfur oxidation pathway of most sulfur-oxidizing microorganisms, it is an energetic electron donor and it should select for a \({\text{SO}}_{3}^{2 - }\)-oxidizing community. Our review of the literature, as well as our own lab experience, suggests that \({\text{SO}}_{3}^{2 - }\) can effectively serve as an electron donor for denitrification. Further research is needed to determine the kinetics of \({\text{SO}}_{3}^{2 - }\)-based denitrification, its toxic threshold for sulfur-oxidizing microorganisms, and its potential inhibition of sensitive species such as nitrifying microorganisms and potential formation of nitrous oxide. Its effect on sludge settling efficiency also should be explored.     

Genetic variability and structure of an isolated population of <Emphasis Type="Italic">Ambystoma altamirani</Emphasis>, a mole salamander that lives in the mountains of one of the largest urban areas in the world

Amphibians are globally threatened by habitat loss and fragmentation; species within the order Ambystoma are not the exception, as there are 18 species of mole salamanders in México, of which 16 are endemic and all species are under some national or international status of protection. The mole salamander, Ambystoma altamirani is a microendemic species, which is distributed in central México, within the trans-Mexican volcanic belt, and is one of the most threatened species due to habitat destruction and the introduction of exotic species. Nine microsatellite markers were used to determine the genetic structure, genetic variability, effective population size, presence of bottlenecks and inbreeding coefficient of one population of A. altamirani to generate information which might help to protect and conserve this threatened species. We found two genetic subpopulations with significant level of genetic structure (\(F_{\mathrm{ST}}= 0.005\)) and high levels of genetic variability (\(H_{\mathrm{o}}= 0.883\); \(H_{\mathrm{e}}= 0.621\)); we also found a small population size (\(N_{\mathrm{e}} = 8.8\)), the presence of historical (\(M =\) 0.486) and recent bottlenecks under IAM and TPM models, with a low, but significant coefficient of inbreeding (\(F_{\mathrm{IS}} = -\)0.451). This information will help us to raise conservation strategies of this microendemic mole salamander species.